Doug Campos-Outcalt, MD, MPA

Keeping up with the ever-changing immunization schedules recommended by the Centers for Disease Control and Prevention (CDC)’s Advisory Committee on Immunization Practices (ACIP) can be difficult. The most recent changes are the interim recommendations from the February 2011 ACIP meeting pertaining to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine immunization and postexposure prophylaxis (PEP) for health care personnel. Updated schedules for routine immunization of children and adults that incorporate additions and changes made in the preceding year were published by the CDC in February.^1,2

ACIP widens the scope of pertussis prevention

The past decade has seen an increase in pertussis cases, including an increase in the number of cases among infants and adolescents (FIGURE). In 2010, California reported 8383 cases, including 10 infant deaths. This was the highest number and rate of cases reported in more than 50 years.³ Other states have also experienced recent increases.

This evolving epidemiology of pertussis has prompted ACIP to recommend a routine single Tdap dose for adolescents between the ages of 11 and 18 years who have completed the recommended DTP/DTaP (diphtheria and tetanus toxoids and pertussis/diphtheria and tetanus toxoids and acellular pertussis) vaccination series and for adults ages 19 to 64 years. ACIP also recommends a single dose for children ages 7 to 10 if they are not fully vaccinated against pertussis and for adults 65 and older who have not previously received Tdap and who are in close contact with infants. The last 2 are off-label recommendations. ACIP has also eliminated any recommended interval between the time of vaccination with tetanus or diphtheriatoxoid (Td) containing vaccine and the administration of Tdap.⁴

FIGURE
Reported pertussis incidence by age group, 1990-2009

Source: Centers for Disease Control and Prevention. Pertussis (whooping cough): surveillance and reporting. Available at: www.cdc.gov/pertussis/surv-reporting.html. Accessed March 21, 2011.

2 new recommendations for clinician postexposure prophylaxis

Interim recommendations from the most recent ACIP meeting in February 2011⁵ re-emphasize that health care personnel should receive Tdap and recommend that health care facilities take steps to increase adherence, including providing the vaccine at no cost.⁵

Since health care personnel are at increased risk of exposure to pertussis, ACIP also made 2 recommendations for PEP.

1. All health care personnel (vaccinated or not) in close contact with a pertussis patient (as defined in TABLE 1) who are likely to expose patients at high risk for complications from pertussis (infants <1 year of age and those with certain immunodeficiency conditions, chronic lung disease, respiratory insufficiency, or cystic fibrosis) should receive PEP.
2. Exposed personnel who do not work with high-risk patients should receive PEP or be monitored daily for 21 days, treated at first signs of infection, and excluded from patient contact for 5 days if symptoms develop. The antimicrobials and doses for treatment and prevention of pertussis have been published in the Morbidity and Mortality Weekly Report.⁶ Options for PEP include azithromycin, clarithromycin, erythromycin, and trimethoprim-sulfamethoxazole.⁶

TABLE 1
Definition of close contact with a pertussis patient

Face-to-face exposure within 3 feet of a symptomatic patient Direct contact with respiratory, oral, or nasal secretions from a symptomatic patient, via coughing, sneezing, shared food and eating utensils, mouth-to-mouth resuscitation, or examination of the mouth, nose, and throat Close proximity with a symptomatic patient for ≥1 hour in a confined space
Source: Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2005.6

Coming soon: Complete vaccine recommendations for health care workers
Recent experience with pertussis (and influenza) has highlighted the need for health care personnel to be vaccinated against infectious diseases to protect themselves, their patients, and their families. To that end, ACIP plans to publish a compendium later this year that brings together all recommendations regarding immunizations for health care personnel. When it becomes available, family physicians will be able to refer to this document to ensure that they and their staff are immunized in line with CDC recommendations.

The latest on influenza vaccine, PCV13, MCV4, hepatitis B, and HPV

The most notable additions to the routine schedules ACIP announced during the past year are universal, yearly influenza immunization from the age of 6 months on and the replacement of the 7-valent pneumococcal conjugate vaccine (PCV7) with a 13-valent product (PCV13) for infants and children. Details of these recommendations, including how to transition from PCV7 to PCV13, were published late last year by the CDC and described in another Practice Alert.^7-9

In addition, changes were made in the schedules for meningococcal conjugate vaccine. A 2-dose primary series, instead of a single dose, of MCV4 is now recommended for those with compromised immunity. A booster of MCV4 is now recommended at age 16 for those vaccinated at 11 or 12 years, and at age 16 to 18 for those vaccinated at 13 to 15 years.¹⁰ The MCV4 recommendations are summarized in TABLE 2.

 

More schedule details in the footnotes. The new schedules contain a number of clarifications in the footnotes that:^1,11

• explain the spacing of the 3-dose primary series for hepatitis B vaccine (HepB) for infants if they do not receive a dose immediately after birth
• clarify the circumstances in which children younger than age 9 need 2 doses of influenza vaccine
• describe the availability of both a quadrivalent human papillomavirus vaccine (HPV4) and a bivalent vaccine (HPV2) to prevent precancerous cervical lesions and cancer
• list the option for using HPV4 for males for the prevention of genital warts.

TABLE 2
Meningococcal conjugate vaccine recommendations by risk group, ACIP 2010

Risk group	Primary series	Booster dose
Individuals ages 11-18 years	1 dose, preferably at age 11 or 12 years	Age 16 years, if primary dose given at age 11 or 12 years Age 16-18 years, if primary dose given at age 13-15 years No booster needed if primary dose given at ≥16 years
HIV-infected individuals ages 11-18 years	2 doses, 2 months apart	Age 16 years, if primary series given at age 11 or 12 years Age 16-18 years, if primary series given at age 13-15 years No booster needed if primary series given at ≥16 years
Individuals ages 2-55 years with persistent complement component deficiency such as C5-C9, properdin, or factor D, or functional or anatomic asplenia	2 doses, 2 months apart	Every 5 years At the earliest opportunity if primary series was 1 dose, then every 5 years thereafter
Individuals ages 2-55 years with prolonged increased risk of exposure, such as microbiologists routinely working with Neisseria meningitidis and travelers to, or residents of, countries where meningococcal disease is hyperendemic or epidemic	1 dose	After 3 years for individuals ages 2-6 years After 5 years for individuals ≥7 years if still at increased risk
Source: Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2011.10

Keeping up with the ever-changing immunization schedules recommended by the Centers for Disease Control and Prevention (CDC)’s Advisory Committee on Immunization Practices (ACIP) can be difficult. The most recent changes are the interim recommendations from the February 2011 ACIP meeting pertaining to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine immunization and postexposure prophylaxis (PEP) for health care personnel. Updated schedules for routine immunization of children and adults that incorporate additions and changes made in the preceding year were published by the CDC in February.^1,2

ACIP widens the scope of pertussis prevention

The past decade has seen an increase in pertussis cases, including an increase in the number of cases among infants and adolescents (FIGURE). In 2010, California reported 8383 cases, including 10 infant deaths. This was the highest number and rate of cases reported in more than 50 years.³ Other states have also experienced recent increases.

This evolving epidemiology of pertussis has prompted ACIP to recommend a routine single Tdap dose for adolescents between the ages of 11 and 18 years who have completed the recommended DTP/DTaP (diphtheria and tetanus toxoids and pertussis/diphtheria and tetanus toxoids and acellular pertussis) vaccination series and for adults ages 19 to 64 years. ACIP also recommends a single dose for children ages 7 to 10 if they are not fully vaccinated against pertussis and for adults 65 and older who have not previously received Tdap and who are in close contact with infants. The last 2 are off-label recommendations. ACIP has also eliminated any recommended interval between the time of vaccination with tetanus or diphtheriatoxoid (Td) containing vaccine and the administration of Tdap.⁴

FIGURE
Reported pertussis incidence by age group, 1990-2009

Source: Centers for Disease Control and Prevention. Pertussis (whooping cough): surveillance and reporting. Available at: www.cdc.gov/pertussis/surv-reporting.html. Accessed March 21, 2011.

2 new recommendations for clinician postexposure prophylaxis

Interim recommendations from the most recent ACIP meeting in February 2011⁵ re-emphasize that health care personnel should receive Tdap and recommend that health care facilities take steps to increase adherence, including providing the vaccine at no cost.⁵

Since health care personnel are at increased risk of exposure to pertussis, ACIP also made 2 recommendations for PEP.

1. All health care personnel (vaccinated or not) in close contact with a pertussis patient (as defined in TABLE 1) who are likely to expose patients at high risk for complications from pertussis (infants <1 year of age and those with certain immunodeficiency conditions, chronic lung disease, respiratory insufficiency, or cystic fibrosis) should receive PEP.
2. Exposed personnel who do not work with high-risk patients should receive PEP or be monitored daily for 21 days, treated at first signs of infection, and excluded from patient contact for 5 days if symptoms develop. The antimicrobials and doses for treatment and prevention of pertussis have been published in the Morbidity and Mortality Weekly Report.⁶ Options for PEP include azithromycin, clarithromycin, erythromycin, and trimethoprim-sulfamethoxazole.⁶

TABLE 1
Definition of close contact with a pertussis patient

Face-to-face exposure within 3 feet of a symptomatic patient Direct contact with respiratory, oral, or nasal secretions from a symptomatic patient, via coughing, sneezing, shared food and eating utensils, mouth-to-mouth resuscitation, or examination of the mouth, nose, and throat Close proximity with a symptomatic patient for ≥1 hour in a confined space
Source: Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2005.6

Coming soon: Complete vaccine recommendations for health care workers
Recent experience with pertussis (and influenza) has highlighted the need for health care personnel to be vaccinated against infectious diseases to protect themselves, their patients, and their families. To that end, ACIP plans to publish a compendium later this year that brings together all recommendations regarding immunizations for health care personnel. When it becomes available, family physicians will be able to refer to this document to ensure that they and their staff are immunized in line with CDC recommendations.

The latest on influenza vaccine, PCV13, MCV4, hepatitis B, and HPV

The most notable additions to the routine schedules ACIP announced during the past year are universal, yearly influenza immunization from the age of 6 months on and the replacement of the 7-valent pneumococcal conjugate vaccine (PCV7) with a 13-valent product (PCV13) for infants and children. Details of these recommendations, including how to transition from PCV7 to PCV13, were published late last year by the CDC and described in another Practice Alert.^7-9

In addition, changes were made in the schedules for meningococcal conjugate vaccine. A 2-dose primary series, instead of a single dose, of MCV4 is now recommended for those with compromised immunity. A booster of MCV4 is now recommended at age 16 for those vaccinated at 11 or 12 years, and at age 16 to 18 for those vaccinated at 13 to 15 years.¹⁰ The MCV4 recommendations are summarized in TABLE 2.

 

More schedule details in the footnotes. The new schedules contain a number of clarifications in the footnotes that:^1,11

• explain the spacing of the 3-dose primary series for hepatitis B vaccine (HepB) for infants if they do not receive a dose immediately after birth
• clarify the circumstances in which children younger than age 9 need 2 doses of influenza vaccine
• describe the availability of both a quadrivalent human papillomavirus vaccine (HPV4) and a bivalent vaccine (HPV2) to prevent precancerous cervical lesions and cancer
• list the option for using HPV4 for males for the prevention of genital warts.

TABLE 2
Meningococcal conjugate vaccine recommendations by risk group, ACIP 2010

Risk group	Primary series	Booster dose
Individuals ages 11-18 years	1 dose, preferably at age 11 or 12 years	Age 16 years, if primary dose given at age 11 or 12 years Age 16-18 years, if primary dose given at age 13-15 years No booster needed if primary dose given at ≥16 years
HIV-infected individuals ages 11-18 years	2 doses, 2 months apart	Age 16 years, if primary series given at age 11 or 12 years Age 16-18 years, if primary series given at age 13-15 years No booster needed if primary series given at ≥16 years
Individuals ages 2-55 years with persistent complement component deficiency such as C5-C9, properdin, or factor D, or functional or anatomic asplenia	2 doses, 2 months apart	Every 5 years At the earliest opportunity if primary series was 1 dose, then every 5 years thereafter
Individuals ages 2-55 years with prolonged increased risk of exposure, such as microbiologists routinely working with Neisseria meningitidis and travelers to, or residents of, countries where meningococcal disease is hyperendemic or epidemic	1 dose	After 3 years for individuals ages 2-6 years After 5 years for individuals ≥7 years if still at increased risk
Source: Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2011.10

Keeping up with the ever-changing immunization schedules recommended by the Centers for Disease Control and Prevention (CDC)’s Advisory Committee on Immunization Practices (ACIP) can be difficult. The most recent changes are the interim recommendations from the February 2011 ACIP meeting pertaining to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine immunization and postexposure prophylaxis (PEP) for health care personnel. Updated schedules for routine immunization of children and adults that incorporate additions and changes made in the preceding year were published by the CDC in February.^1,2

ACIP widens the scope of pertussis prevention

The past decade has seen an increase in pertussis cases, including an increase in the number of cases among infants and adolescents (FIGURE). In 2010, California reported 8383 cases, including 10 infant deaths. This was the highest number and rate of cases reported in more than 50 years.³ Other states have also experienced recent increases.

This evolving epidemiology of pertussis has prompted ACIP to recommend a routine single Tdap dose for adolescents between the ages of 11 and 18 years who have completed the recommended DTP/DTaP (diphtheria and tetanus toxoids and pertussis/diphtheria and tetanus toxoids and acellular pertussis) vaccination series and for adults ages 19 to 64 years. ACIP also recommends a single dose for children ages 7 to 10 if they are not fully vaccinated against pertussis and for adults 65 and older who have not previously received Tdap and who are in close contact with infants. The last 2 are off-label recommendations. ACIP has also eliminated any recommended interval between the time of vaccination with tetanus or diphtheriatoxoid (Td) containing vaccine and the administration of Tdap.⁴

FIGURE
Reported pertussis incidence by age group, 1990-2009

Source: Centers for Disease Control and Prevention. Pertussis (whooping cough): surveillance and reporting. Available at: www.cdc.gov/pertussis/surv-reporting.html. Accessed March 21, 2011.

2 new recommendations for clinician postexposure prophylaxis

Interim recommendations from the most recent ACIP meeting in February 2011⁵ re-emphasize that health care personnel should receive Tdap and recommend that health care facilities take steps to increase adherence, including providing the vaccine at no cost.⁵

Since health care personnel are at increased risk of exposure to pertussis, ACIP also made 2 recommendations for PEP.

1. All health care personnel (vaccinated or not) in close contact with a pertussis patient (as defined in TABLE 1) who are likely to expose patients at high risk for complications from pertussis (infants <1 year of age and those with certain immunodeficiency conditions, chronic lung disease, respiratory insufficiency, or cystic fibrosis) should receive PEP.
2. Exposed personnel who do not work with high-risk patients should receive PEP or be monitored daily for 21 days, treated at first signs of infection, and excluded from patient contact for 5 days if symptoms develop. The antimicrobials and doses for treatment and prevention of pertussis have been published in the Morbidity and Mortality Weekly Report.⁶ Options for PEP include azithromycin, clarithromycin, erythromycin, and trimethoprim-sulfamethoxazole.⁶

TABLE 1
Definition of close contact with a pertussis patient

Face-to-face exposure within 3 feet of a symptomatic patient Direct contact with respiratory, oral, or nasal secretions from a symptomatic patient, via coughing, sneezing, shared food and eating utensils, mouth-to-mouth resuscitation, or examination of the mouth, nose, and throat Close proximity with a symptomatic patient for ≥1 hour in a confined space
Source: Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2005.6

Coming soon: Complete vaccine recommendations for health care workers
Recent experience with pertussis (and influenza) has highlighted the need for health care personnel to be vaccinated against infectious diseases to protect themselves, their patients, and their families. To that end, ACIP plans to publish a compendium later this year that brings together all recommendations regarding immunizations for health care personnel. When it becomes available, family physicians will be able to refer to this document to ensure that they and their staff are immunized in line with CDC recommendations.

The latest on influenza vaccine, PCV13, MCV4, hepatitis B, and HPV

The most notable additions to the routine schedules ACIP announced during the past year are universal, yearly influenza immunization from the age of 6 months on and the replacement of the 7-valent pneumococcal conjugate vaccine (PCV7) with a 13-valent product (PCV13) for infants and children. Details of these recommendations, including how to transition from PCV7 to PCV13, were published late last year by the CDC and described in another Practice Alert.^7-9

In addition, changes were made in the schedules for meningococcal conjugate vaccine. A 2-dose primary series, instead of a single dose, of MCV4 is now recommended for those with compromised immunity. A booster of MCV4 is now recommended at age 16 for those vaccinated at 11 or 12 years, and at age 16 to 18 for those vaccinated at 13 to 15 years.¹⁰ The MCV4 recommendations are summarized in TABLE 2.

 

More schedule details in the footnotes. The new schedules contain a number of clarifications in the footnotes that:^1,11

• explain the spacing of the 3-dose primary series for hepatitis B vaccine (HepB) for infants if they do not receive a dose immediately after birth
• clarify the circumstances in which children younger than age 9 need 2 doses of influenza vaccine
• describe the availability of both a quadrivalent human papillomavirus vaccine (HPV4) and a bivalent vaccine (HPV2) to prevent precancerous cervical lesions and cancer
• list the option for using HPV4 for males for the prevention of genital warts.

TABLE 2
Meningococcal conjugate vaccine recommendations by risk group, ACIP 2010

Risk group	Primary series	Booster dose
Individuals ages 11-18 years	1 dose, preferably at age 11 or 12 years	Age 16 years, if primary dose given at age 11 or 12 years Age 16-18 years, if primary dose given at age 13-15 years No booster needed if primary dose given at ≥16 years
HIV-infected individuals ages 11-18 years	2 doses, 2 months apart	Age 16 years, if primary series given at age 11 or 12 years Age 16-18 years, if primary series given at age 13-15 years No booster needed if primary series given at ≥16 years
Individuals ages 2-55 years with persistent complement component deficiency such as C5-C9, properdin, or factor D, or functional or anatomic asplenia	2 doses, 2 months apart	Every 5 years At the earliest opportunity if primary series was 1 dose, then every 5 years thereafter
Individuals ages 2-55 years with prolonged increased risk of exposure, such as microbiologists routinely working with Neisseria meningitidis and travelers to, or residents of, countries where meningococcal disease is hyperendemic or epidemic	1 dose	After 3 years for individuals ages 2-6 years After 5 years for individuals ≥7 years if still at increased risk
Source: Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2011.10

In 2010, the CDC released an update of its Sexually Transmitted Diseases (STD) Treatment Guidelines,¹ which were last updated in 2006. The guidelines are widely viewed as the most authoritative source of information on the diagnosis, treatment, and follow-up of STDs, and they are the standard for publicly and privately funded clinics focusing on sexual health.

What’s new

Some of the notable changes made since the last update in 2006 appear in TABLE 1.^1,2

Uncomplicated gonorrhea. Cephalosporins are the only class of antibiotic recommended as first-line treatment for gonorrhea. (In a 2007 recommendation revision, the CDC opted to no longer recommend quinolone antibiotics for the treatment of gonorrhea, because of widespread bacterial resistance.³) Preference is now given to ceftriaxone because of its proven effectiveness against pharyngeal infection, which is often asymptomatic, difficult to detect, and difficult to eradicate. Additionally, the 2010 update has increased the recommended dose of ceftriazone from 125 to 250 mg intramuscularly. The larger dose is more effective against pharyngeal infection; it is also a safeguard against decreased bacterial susceptibility to cephalosporins, which, although still very low, has been reported in more cases recently.

The guidelines still recommend that azithromycin, 1 g orally in a single dose, be given with ceftriaxone because of the relatively high rate of co-infection with Chlamydia trachomatis and the potential for azithromycin to assist with eradicating any gonorrhea with decreased susceptibility to ceftriaxone.

Pelvic inflammatory disease. Quinolones have also been removed from the list of options for outpatient treatment of pelvic inflammatory disease. All recommended regimens now specify a parenteral cephalosporin as a single injection with doxycycline 100 mg PO twice a day for 14 days, with or without metronidazole 500 mg PO twice a day for 14 days.

Bacterial vaginosis. Tinidazole, 2 g orally once a day for 2 days or 1 g orally once a day for 5 days, is now an alternative agent for bacterial vaginosis. However, preferred treatments remain metronidazole 500 mg orally twice a day for 7 days, metronidazole gel intravaginally once a day for 5 days, or clindamycin cream intravaginally at bedtime for 7 days.

Newborn gonococcal eye infection. A relatively minor change is the elimination of tetracycline as prophylaxis for newborn gonococcal eye infections, leaving only erythromycin ointment to prevent the condition.

TABLE 1
2010 vs 2006: How have the CDC recommendations for STD treatment changed?^1,2

Uncomplicated gonococcal infections of the cervix, urethra, rectum, and pharynx Ceftriaxone IM dose increased from 125 to 250 mg Quinolones no longer recommended
Pelvic inflammatory disease Parenteral regimens Quinolones no longer recommended Outpatient regimens Quinolones no longer recommended Completely oral regimens no longer recommended; all include an injectable cephalosporin
Bacterial vaginosis Tinidazole now an alternative agent; however, Metronidazole orally, metronidazole intravaginally, or clindamycin intravaginally still preferred
Prophylaxis for gonococcal eye infection in a newborn Tetracycline ointment no longer recommended Erythromycin ointment the only recommended regimen

Single-dose therapy preferred among equivalent options

Single-dose therapy (TABLE 2), while often more expensive than other options, increases compliance and helps ensure treatment completion. Single-dose therapy administered in your office is essentially directly observed treatment, an intervention that has become the standard of care for other diseases such as tuberculosis. If the single-dose agent is as effective as alternative medications, directly observed on-site administration is the preferred option for treating STDs.

TABLE 2
Single-dose therapies for specific STDs¹

Infection or condition	Single-dose therapy
Candida	Miconazole 1200 mg vaginal suppository   or Tioconazole 6.5% ointment 5 g intravaginally   or Butoconazole 2% cream 5 g intravaginally   or Fluconazole 150 mg PO
Cervicitis	Azithromycin 1 g PO
Chancroid	Azithromycin 1 g PO   or Ceftriaxone 250 mg IM
Chlamydia urogenital infection	Azithromycin 1 g PO
Gonorrhea: conjunctivitis	Ceftriaxone 1 g IM
Gonorrhea: uncomplicated infection of the cervix, urethra, rectum	Ceftriaxone 250 mg IM (preferred)   or Cefixime 400 mg PO   or Single-dose injectable cephalosporin plus Azithromycin 1 g PO
Gonorrhea: uncomplicated infection of the pharynx	Ceftriaxone 250 mg IM   plus Azithromycin 1 g PO
Nongonococcal urethritis	Azithromycin 1 g PO
Post-sexual assault prophylaxis	Ceftriaxone 250 mg IM   or Cefixime 400 mg PO   plus Metronidazole 2 g PO   plus Azithromycin 1 g PO
Recurrent, persistent nongonococcal urethritis	Metronidazole 2 g PO   or Tinidazole 2 g PO   plus Azithromycin 1 g PO (if not used for initial episode)
Syphilis: primary, secondary, and early latent	Benzathine penicillin G 2.4 million units IM
Trichomoniasis	Metronidazole 2 g PO   or Tinidazole 2 g PO

Other guideline recommendations
The CDC’s STD treatment guidelines contain a wealth of useful information beyond treatment advice: recommended methods of confirming diagnoses, analyses of the usefulness of various diagnostic tests, recommendations on how to manage sex partners of those infected, guidance on STD prevention counseling, and considerations for special populations and circumstances.

 

Additionally, there is a section on screening for STDs reflecting recommendations of the US Preventive Services Task Force (USPSTF); it also includes recommendations from the American College of Obstetricians and Gynecologists. In at least one instance, though, the USPSTF recommendation on screening for HIV infection contradicts other CDC sources.^4,5 Also included is guidance on using vaccines to prevent hepatitis A, hepatitis B, and human papillomavirus (HPV), which follows the recommendations of the Advisory Committee on Immunization Practices. When to use DNA testing to detect HPV is described briefly.

A shortcoming of the CDC guidelines
Although the CDC’s STD guidelines remain the most authoritative source of information on the diagnosis and treatment of STDs, they do not seem to use a consistent method for assessing and describing the strength of the evidence behind the recommendations, which family physicians have come to expect. (However, it is sometimes possible to discern the type and strength of evidence for a particular recommendation from the written discussion.)

The new guidelines state that a series of papers to be published in Clinical Infectious Diseases will describe more fully the evidence behind some of the recommendations and include evidence tables. However, in future guideline updates, it would be helpful if the CDC were to include a brief description of the quantity and strength of evidence alongside each recommended treatment option in the tables.

How best to keep up to date
Although the new guidelines summarize the current status of recommendations on the diagnosis, treatment, and prevention of STDs and are a useful resource for family physicians, we cannot stay current simply by referring to them alone over the next 4 to 5 years until a new edition is published. As new evidence develops, changes in recommendations will be published in the Morbidity and Mortality Weekly Report.

Case in point: new interim HIV recommendations. Interim recommendations were recently released on pre-exposure prophylaxis for men who have sex with men.⁶ (For more on these recommendations, check out this month’s audiocast at jfponline.com.) Final recommendations are expected later this year. Recommendations for post-exposure prophylaxis to prevent HIV infection are also expected soon.

In 2010, the CDC released an update of its Sexually Transmitted Diseases (STD) Treatment Guidelines,¹ which were last updated in 2006. The guidelines are widely viewed as the most authoritative source of information on the diagnosis, treatment, and follow-up of STDs, and they are the standard for publicly and privately funded clinics focusing on sexual health.

What’s new

Some of the notable changes made since the last update in 2006 appear in TABLE 1.^1,2

Uncomplicated gonorrhea. Cephalosporins are the only class of antibiotic recommended as first-line treatment for gonorrhea. (In a 2007 recommendation revision, the CDC opted to no longer recommend quinolone antibiotics for the treatment of gonorrhea, because of widespread bacterial resistance.³) Preference is now given to ceftriaxone because of its proven effectiveness against pharyngeal infection, which is often asymptomatic, difficult to detect, and difficult to eradicate. Additionally, the 2010 update has increased the recommended dose of ceftriazone from 125 to 250 mg intramuscularly. The larger dose is more effective against pharyngeal infection; it is also a safeguard against decreased bacterial susceptibility to cephalosporins, which, although still very low, has been reported in more cases recently.

The guidelines still recommend that azithromycin, 1 g orally in a single dose, be given with ceftriaxone because of the relatively high rate of co-infection with Chlamydia trachomatis and the potential for azithromycin to assist with eradicating any gonorrhea with decreased susceptibility to ceftriaxone.

Pelvic inflammatory disease. Quinolones have also been removed from the list of options for outpatient treatment of pelvic inflammatory disease. All recommended regimens now specify a parenteral cephalosporin as a single injection with doxycycline 100 mg PO twice a day for 14 days, with or without metronidazole 500 mg PO twice a day for 14 days.

Bacterial vaginosis. Tinidazole, 2 g orally once a day for 2 days or 1 g orally once a day for 5 days, is now an alternative agent for bacterial vaginosis. However, preferred treatments remain metronidazole 500 mg orally twice a day for 7 days, metronidazole gel intravaginally once a day for 5 days, or clindamycin cream intravaginally at bedtime for 7 days.

Newborn gonococcal eye infection. A relatively minor change is the elimination of tetracycline as prophylaxis for newborn gonococcal eye infections, leaving only erythromycin ointment to prevent the condition.

TABLE 1
2010 vs 2006: How have the CDC recommendations for STD treatment changed?^1,2

Uncomplicated gonococcal infections of the cervix, urethra, rectum, and pharynx Ceftriaxone IM dose increased from 125 to 250 mg Quinolones no longer recommended
Pelvic inflammatory disease Parenteral regimens Quinolones no longer recommended Outpatient regimens Quinolones no longer recommended Completely oral regimens no longer recommended; all include an injectable cephalosporin
Bacterial vaginosis Tinidazole now an alternative agent; however, Metronidazole orally, metronidazole intravaginally, or clindamycin intravaginally still preferred
Prophylaxis for gonococcal eye infection in a newborn Tetracycline ointment no longer recommended Erythromycin ointment the only recommended regimen

Single-dose therapy preferred among equivalent options

Single-dose therapy (TABLE 2), while often more expensive than other options, increases compliance and helps ensure treatment completion. Single-dose therapy administered in your office is essentially directly observed treatment, an intervention that has become the standard of care for other diseases such as tuberculosis. If the single-dose agent is as effective as alternative medications, directly observed on-site administration is the preferred option for treating STDs.

TABLE 2
Single-dose therapies for specific STDs¹

Infection or condition	Single-dose therapy
Candida	Miconazole 1200 mg vaginal suppository   or Tioconazole 6.5% ointment 5 g intravaginally   or Butoconazole 2% cream 5 g intravaginally   or Fluconazole 150 mg PO
Cervicitis	Azithromycin 1 g PO
Chancroid	Azithromycin 1 g PO   or Ceftriaxone 250 mg IM
Chlamydia urogenital infection	Azithromycin 1 g PO
Gonorrhea: conjunctivitis	Ceftriaxone 1 g IM
Gonorrhea: uncomplicated infection of the cervix, urethra, rectum	Ceftriaxone 250 mg IM (preferred)   or Cefixime 400 mg PO   or Single-dose injectable cephalosporin plus Azithromycin 1 g PO
Gonorrhea: uncomplicated infection of the pharynx	Ceftriaxone 250 mg IM   plus Azithromycin 1 g PO
Nongonococcal urethritis	Azithromycin 1 g PO
Post-sexual assault prophylaxis	Ceftriaxone 250 mg IM   or Cefixime 400 mg PO   plus Metronidazole 2 g PO   plus Azithromycin 1 g PO
Recurrent, persistent nongonococcal urethritis	Metronidazole 2 g PO   or Tinidazole 2 g PO   plus Azithromycin 1 g PO (if not used for initial episode)
Syphilis: primary, secondary, and early latent	Benzathine penicillin G 2.4 million units IM
Trichomoniasis	Metronidazole 2 g PO   or Tinidazole 2 g PO

Other guideline recommendations
The CDC’s STD treatment guidelines contain a wealth of useful information beyond treatment advice: recommended methods of confirming diagnoses, analyses of the usefulness of various diagnostic tests, recommendations on how to manage sex partners of those infected, guidance on STD prevention counseling, and considerations for special populations and circumstances.

 

Additionally, there is a section on screening for STDs reflecting recommendations of the US Preventive Services Task Force (USPSTF); it also includes recommendations from the American College of Obstetricians and Gynecologists. In at least one instance, though, the USPSTF recommendation on screening for HIV infection contradicts other CDC sources.^4,5 Also included is guidance on using vaccines to prevent hepatitis A, hepatitis B, and human papillomavirus (HPV), which follows the recommendations of the Advisory Committee on Immunization Practices. When to use DNA testing to detect HPV is described briefly.

A shortcoming of the CDC guidelines
Although the CDC’s STD guidelines remain the most authoritative source of information on the diagnosis and treatment of STDs, they do not seem to use a consistent method for assessing and describing the strength of the evidence behind the recommendations, which family physicians have come to expect. (However, it is sometimes possible to discern the type and strength of evidence for a particular recommendation from the written discussion.)

The new guidelines state that a series of papers to be published in Clinical Infectious Diseases will describe more fully the evidence behind some of the recommendations and include evidence tables. However, in future guideline updates, it would be helpful if the CDC were to include a brief description of the quantity and strength of evidence alongside each recommended treatment option in the tables.

How best to keep up to date
Although the new guidelines summarize the current status of recommendations on the diagnosis, treatment, and prevention of STDs and are a useful resource for family physicians, we cannot stay current simply by referring to them alone over the next 4 to 5 years until a new edition is published. As new evidence develops, changes in recommendations will be published in the Morbidity and Mortality Weekly Report.

Case in point: new interim HIV recommendations. Interim recommendations were recently released on pre-exposure prophylaxis for men who have sex with men.⁶ (For more on these recommendations, check out this month’s audiocast at jfponline.com.) Final recommendations are expected later this year. Recommendations for post-exposure prophylaxis to prevent HIV infection are also expected soon.

In 2010, the CDC released an update of its Sexually Transmitted Diseases (STD) Treatment Guidelines,¹ which were last updated in 2006. The guidelines are widely viewed as the most authoritative source of information on the diagnosis, treatment, and follow-up of STDs, and they are the standard for publicly and privately funded clinics focusing on sexual health.

What’s new

Some of the notable changes made since the last update in 2006 appear in TABLE 1.^1,2

Uncomplicated gonorrhea. Cephalosporins are the only class of antibiotic recommended as first-line treatment for gonorrhea. (In a 2007 recommendation revision, the CDC opted to no longer recommend quinolone antibiotics for the treatment of gonorrhea, because of widespread bacterial resistance.³) Preference is now given to ceftriaxone because of its proven effectiveness against pharyngeal infection, which is often asymptomatic, difficult to detect, and difficult to eradicate. Additionally, the 2010 update has increased the recommended dose of ceftriazone from 125 to 250 mg intramuscularly. The larger dose is more effective against pharyngeal infection; it is also a safeguard against decreased bacterial susceptibility to cephalosporins, which, although still very low, has been reported in more cases recently.

The guidelines still recommend that azithromycin, 1 g orally in a single dose, be given with ceftriaxone because of the relatively high rate of co-infection with Chlamydia trachomatis and the potential for azithromycin to assist with eradicating any gonorrhea with decreased susceptibility to ceftriaxone.

Pelvic inflammatory disease. Quinolones have also been removed from the list of options for outpatient treatment of pelvic inflammatory disease. All recommended regimens now specify a parenteral cephalosporin as a single injection with doxycycline 100 mg PO twice a day for 14 days, with or without metronidazole 500 mg PO twice a day for 14 days.

Bacterial vaginosis. Tinidazole, 2 g orally once a day for 2 days or 1 g orally once a day for 5 days, is now an alternative agent for bacterial vaginosis. However, preferred treatments remain metronidazole 500 mg orally twice a day for 7 days, metronidazole gel intravaginally once a day for 5 days, or clindamycin cream intravaginally at bedtime for 7 days.

Newborn gonococcal eye infection. A relatively minor change is the elimination of tetracycline as prophylaxis for newborn gonococcal eye infections, leaving only erythromycin ointment to prevent the condition.

TABLE 1
2010 vs 2006: How have the CDC recommendations for STD treatment changed?^1,2

Uncomplicated gonococcal infections of the cervix, urethra, rectum, and pharynx Ceftriaxone IM dose increased from 125 to 250 mg Quinolones no longer recommended
Pelvic inflammatory disease Parenteral regimens Quinolones no longer recommended Outpatient regimens Quinolones no longer recommended Completely oral regimens no longer recommended; all include an injectable cephalosporin
Bacterial vaginosis Tinidazole now an alternative agent; however, Metronidazole orally, metronidazole intravaginally, or clindamycin intravaginally still preferred
Prophylaxis for gonococcal eye infection in a newborn Tetracycline ointment no longer recommended Erythromycin ointment the only recommended regimen

Single-dose therapy preferred among equivalent options

Single-dose therapy (TABLE 2), while often more expensive than other options, increases compliance and helps ensure treatment completion. Single-dose therapy administered in your office is essentially directly observed treatment, an intervention that has become the standard of care for other diseases such as tuberculosis. If the single-dose agent is as effective as alternative medications, directly observed on-site administration is the preferred option for treating STDs.

TABLE 2
Single-dose therapies for specific STDs¹

Infection or condition	Single-dose therapy
Candida	Miconazole 1200 mg vaginal suppository   or Tioconazole 6.5% ointment 5 g intravaginally   or Butoconazole 2% cream 5 g intravaginally   or Fluconazole 150 mg PO
Cervicitis	Azithromycin 1 g PO
Chancroid	Azithromycin 1 g PO   or Ceftriaxone 250 mg IM
Chlamydia urogenital infection	Azithromycin 1 g PO
Gonorrhea: conjunctivitis	Ceftriaxone 1 g IM
Gonorrhea: uncomplicated infection of the cervix, urethra, rectum	Ceftriaxone 250 mg IM (preferred)   or Cefixime 400 mg PO   or Single-dose injectable cephalosporin plus Azithromycin 1 g PO
Gonorrhea: uncomplicated infection of the pharynx	Ceftriaxone 250 mg IM   plus Azithromycin 1 g PO
Nongonococcal urethritis	Azithromycin 1 g PO
Post-sexual assault prophylaxis	Ceftriaxone 250 mg IM   or Cefixime 400 mg PO   plus Metronidazole 2 g PO   plus Azithromycin 1 g PO
Recurrent, persistent nongonococcal urethritis	Metronidazole 2 g PO   or Tinidazole 2 g PO   plus Azithromycin 1 g PO (if not used for initial episode)
Syphilis: primary, secondary, and early latent	Benzathine penicillin G 2.4 million units IM
Trichomoniasis	Metronidazole 2 g PO   or Tinidazole 2 g PO

Other guideline recommendations
The CDC’s STD treatment guidelines contain a wealth of useful information beyond treatment advice: recommended methods of confirming diagnoses, analyses of the usefulness of various diagnostic tests, recommendations on how to manage sex partners of those infected, guidance on STD prevention counseling, and considerations for special populations and circumstances.

 

Additionally, there is a section on screening for STDs reflecting recommendations of the US Preventive Services Task Force (USPSTF); it also includes recommendations from the American College of Obstetricians and Gynecologists. In at least one instance, though, the USPSTF recommendation on screening for HIV infection contradicts other CDC sources.^4,5 Also included is guidance on using vaccines to prevent hepatitis A, hepatitis B, and human papillomavirus (HPV), which follows the recommendations of the Advisory Committee on Immunization Practices. When to use DNA testing to detect HPV is described briefly.

A shortcoming of the CDC guidelines
Although the CDC’s STD guidelines remain the most authoritative source of information on the diagnosis and treatment of STDs, they do not seem to use a consistent method for assessing and describing the strength of the evidence behind the recommendations, which family physicians have come to expect. (However, it is sometimes possible to discern the type and strength of evidence for a particular recommendation from the written discussion.)

The new guidelines state that a series of papers to be published in Clinical Infectious Diseases will describe more fully the evidence behind some of the recommendations and include evidence tables. However, in future guideline updates, it would be helpful if the CDC were to include a brief description of the quantity and strength of evidence alongside each recommended treatment option in the tables.

How best to keep up to date
Although the new guidelines summarize the current status of recommendations on the diagnosis, treatment, and prevention of STDs and are a useful resource for family physicians, we cannot stay current simply by referring to them alone over the next 4 to 5 years until a new edition is published. As new evidence develops, changes in recommendations will be published in the Morbidity and Mortality Weekly Report.

Case in point: new interim HIV recommendations. Interim recommendations were recently released on pre-exposure prophylaxis for men who have sex with men.⁶ (For more on these recommendations, check out this month’s audiocast at jfponline.com.) Final recommendations are expected later this year. Recommendations for post-exposure prophylaxis to prevent HIV infection are also expected soon.

At its October 2010 meeting, the Advisory Committee on Immunization Practices (ACIP) made 2 additions to its recommendations for quadrivalent meningococcal conjugate vaccine (MCV4), based on evolving knowledge of the vaccine and its duration of protection.

• A booster dose at age 16 has been added to the routine schedule for those vaccinated at ages 11 to 12 years. A booster dose has also been added for those vaccinated at ages 13 to 15 years, although the recommended timing of this booster had not been finalized at press time.
• A 2-dose primary series, 2 months apart, is now recommended for patients at higher risk of meningococcal disease. The high-risk category includes those with persistent complement component deficiency, asplenia, or human immunodeficiency virus (HIV). High-risk patients who were previously vaccinated should receive a booster dose at the earliest opportunity and continue to receive boosters at the appropriate interval (3-5 years).

Meningitis is rare but serious
Meningococcal meningitis is a potentially devastating disease in adolescents and young adults. It has a case fatality rate of about 20%, and the sequelae for survivors can be severe: 3.1% require limb amputations and another 10.9% suffer neurological deficits.¹ Thankfully, meningococcal disease is rare, occurring at rates below 1 in 200,000 in the 11- to 15-year-old age group and less than 1 in 100,000 in the 16- to 21-year-old age group.²

Routine immunization with MCV4 is recommended for adolescents
In 2007, ACIP recommended routine use of MCV4 for adolescents between the ages of 11 and 18 years. The recommendation gave preference to immunization at ages 11 to 12 years, along with the other adolescent vaccines given at that time.³ Updated recommendations in effect in 2010 state that those at highest risk for meningococcal infection (those with functional or anatomic asplenia, C3 complement deficiency, or HIV infection) should be vaccinated with MCV4 starting at age 2 and revaccinated every 3 years if last vaccinated at 2 to 6 years, and every 5 years if last vaccinated at or after age 7.^4,5 TABLE 1 lists the recommendations for MCV4 in place prior to the October 2010 ACIP meeting.

Two MCV4 products are licensed for use in the United States: Menactra (Sanofi Pasteur) and Menveo (Novartis). Both contain antigens against 4 serotypes, A, C, Y, and W-135. Neither protects against type B, which causes a majority of the disease in infants.⁶ In recent years, serotype A disease has become extremely rare in the United States.⁶ MCV4 coverage for adolescents ages 13 to 17 years is increasing, going from 41.8% in 2008 to 53.6% in 2009.⁷

TABLE 1
Recommendations for MCV4 prior to October 2010^3-5

Immunize all adolescents between the ages of 11 and 18. Immunization at the 11- to 12-year visit is preferred.
Immunize all individuals between the ages of 2 and 55 who are at increased risk for meningococcal disease: college freshmen living in dormitories, microbiologists routinely exposed to isolates of Neisseria meningitidis, military recruits, travelers to (or residents of) countries in which N meningitidis meningitis is hyperendemic or epidemic, individuals with terminal complement component deficiencies, and individuals with anatomic or functional asplenia.
Administer a booster dose for those at continued high risk 3 years after a first dose given between ages 2 and 6, and 5 years after a first dose given at age 7 or older. Revaccinate those in increased risk groups at 5-year intervals indefinitely. The recommendation for a second dose does not apply to college freshmen living in dorms.
MCV4, meningococcal conjugate vaccine.

The new recommendations: One is more controversial than the other

The recommendation for a 2-dose primary series in high-risk groups was not controversial. The same conditions that place individuals at highest risk for meningococcal infection also result in a less robust response to a single dose of the vaccine, and a 2-dose series is needed to achieve protective antibody levels in a high proportion of those vaccine recipients.⁸ This recommendation will affect relatively few patients.

The recommendation for booster doses in the general adolescent population generated a lot more debate. Studies performed since the licensure of MCV4 have shown that levels of protective antibodies decline over time. Five years after vaccination, 50% of vaccine recipients have levels below that considered fully protective.² One small case-control study of 107 cases suggested that the number of years from receipt of the vaccine was a risk factor for meningococcal disease.²

However, rates of meningococcal meningitis in adolescents have been declining over the past few years (TABLE 2), and there are no surveillance data to support the conclusion that teens vaccinated at ages 11 to 12 years are at increased risk as they age. In addition, the number of cases is very low (TABLE 3) and the cost benefit analysis of a booster dose of MCV4 is very unfavorable.^1,2

 

TABLE 2
Rates* of serogroup C, Y, and W-135 meningococcal disease^†

	Age group (y)
Year	11-19	≥20
2004-2005	0.23	0.16
2006-2007	0.27	0.22
2008-2009	0.14	0.21
*Annual rate per 100,000. †Serogroup A disease is too rare for inclusion here. Source: Cohn A. Advisory Committee on Immunization Practices Meeting; October 27, 2010.2

TABLE 3
Average annual number of cases of C, Y, and W-135 meningococcal disease

Age group (y)	2000-2004	2005-2009	Change
11-14	46	12	-74%
15-18	106	77	-27%
19-22	62	52	-16%
Total (11-22)	214	141	-34%
Source: Cohn A. Advisory Committee on Immunization Practices Meeting; October 27, 2010.2

ACIP weighed the options for a booster dose
Three options were presented at the October 2010 ACIP meeting:

• Option 1: No change to the current recommendation for vaccination of 11- to 12-year-olds. Wait and see what happens to disease incidence over several more years.
• Option 2: Move the age of vaccination to 15 years with no booster. This would allow protection to persist through the years of highest risk (16-21 years).
• Option 3: Keep the recommendation for vaccination at ages 11 to 12 years, and add a booster dose at age 16.

The first option was the least cost effective: $281,000/quality-adjusted life year (QALY). The second option was the most cost effective at $121,000/QALY. The last option came out in the middle: $157,000/QALY, but it would save the most lives—9 more per year compared with Option 2.¹ There is, however, a caveat with regard to the cost-effectiveness estimates. The numbers were obtained using incidence data from the year 2000; incidence has declined since then, and cost-effectiveness estimates would be much less favorable using today’s rates.

These issues were discussed at length, and the decision to add a booster dose at age 16 was made on a close vote. This decision illustrates how difficult vaccine policy-making has become in recent years, when choices must be made about recommending safe, effective, and expensive vaccines to prevent illnesses that are both rare and serious.

The new MCV4 recommendations will be added to the child immunization schedule for 2011.

The take-home message for family physicians is to strive to increase the proportion of 11- to 12-year-olds who are fully vaccinated and in 2011 to begin to advise those who are between the ages of 16 and 20 years of the recommendation for a booster dose of MCV4.

At its October 2010 meeting, the Advisory Committee on Immunization Practices (ACIP) made 2 additions to its recommendations for quadrivalent meningococcal conjugate vaccine (MCV4), based on evolving knowledge of the vaccine and its duration of protection.

• A booster dose at age 16 has been added to the routine schedule for those vaccinated at ages 11 to 12 years. A booster dose has also been added for those vaccinated at ages 13 to 15 years, although the recommended timing of this booster had not been finalized at press time.
• A 2-dose primary series, 2 months apart, is now recommended for patients at higher risk of meningococcal disease. The high-risk category includes those with persistent complement component deficiency, asplenia, or human immunodeficiency virus (HIV). High-risk patients who were previously vaccinated should receive a booster dose at the earliest opportunity and continue to receive boosters at the appropriate interval (3-5 years).

Meningitis is rare but serious
Meningococcal meningitis is a potentially devastating disease in adolescents and young adults. It has a case fatality rate of about 20%, and the sequelae for survivors can be severe: 3.1% require limb amputations and another 10.9% suffer neurological deficits.¹ Thankfully, meningococcal disease is rare, occurring at rates below 1 in 200,000 in the 11- to 15-year-old age group and less than 1 in 100,000 in the 16- to 21-year-old age group.²

Routine immunization with MCV4 is recommended for adolescents
In 2007, ACIP recommended routine use of MCV4 for adolescents between the ages of 11 and 18 years. The recommendation gave preference to immunization at ages 11 to 12 years, along with the other adolescent vaccines given at that time.³ Updated recommendations in effect in 2010 state that those at highest risk for meningococcal infection (those with functional or anatomic asplenia, C3 complement deficiency, or HIV infection) should be vaccinated with MCV4 starting at age 2 and revaccinated every 3 years if last vaccinated at 2 to 6 years, and every 5 years if last vaccinated at or after age 7.^4,5 TABLE 1 lists the recommendations for MCV4 in place prior to the October 2010 ACIP meeting.

Two MCV4 products are licensed for use in the United States: Menactra (Sanofi Pasteur) and Menveo (Novartis). Both contain antigens against 4 serotypes, A, C, Y, and W-135. Neither protects against type B, which causes a majority of the disease in infants.⁶ In recent years, serotype A disease has become extremely rare in the United States.⁶ MCV4 coverage for adolescents ages 13 to 17 years is increasing, going from 41.8% in 2008 to 53.6% in 2009.⁷

TABLE 1
Recommendations for MCV4 prior to October 2010^3-5

Immunize all adolescents between the ages of 11 and 18. Immunization at the 11- to 12-year visit is preferred.
Immunize all individuals between the ages of 2 and 55 who are at increased risk for meningococcal disease: college freshmen living in dormitories, microbiologists routinely exposed to isolates of Neisseria meningitidis, military recruits, travelers to (or residents of) countries in which N meningitidis meningitis is hyperendemic or epidemic, individuals with terminal complement component deficiencies, and individuals with anatomic or functional asplenia.
Administer a booster dose for those at continued high risk 3 years after a first dose given between ages 2 and 6, and 5 years after a first dose given at age 7 or older. Revaccinate those in increased risk groups at 5-year intervals indefinitely. The recommendation for a second dose does not apply to college freshmen living in dorms.
MCV4, meningococcal conjugate vaccine.

The new recommendations: One is more controversial than the other

The recommendation for a 2-dose primary series in high-risk groups was not controversial. The same conditions that place individuals at highest risk for meningococcal infection also result in a less robust response to a single dose of the vaccine, and a 2-dose series is needed to achieve protective antibody levels in a high proportion of those vaccine recipients.⁸ This recommendation will affect relatively few patients.

The recommendation for booster doses in the general adolescent population generated a lot more debate. Studies performed since the licensure of MCV4 have shown that levels of protective antibodies decline over time. Five years after vaccination, 50% of vaccine recipients have levels below that considered fully protective.² One small case-control study of 107 cases suggested that the number of years from receipt of the vaccine was a risk factor for meningococcal disease.²

However, rates of meningococcal meningitis in adolescents have been declining over the past few years (TABLE 2), and there are no surveillance data to support the conclusion that teens vaccinated at ages 11 to 12 years are at increased risk as they age. In addition, the number of cases is very low (TABLE 3) and the cost benefit analysis of a booster dose of MCV4 is very unfavorable.^1,2

 

TABLE 2
Rates* of serogroup C, Y, and W-135 meningococcal disease^†

	Age group (y)
Year	11-19	≥20
2004-2005	0.23	0.16
2006-2007	0.27	0.22
2008-2009	0.14	0.21
*Annual rate per 100,000. †Serogroup A disease is too rare for inclusion here. Source: Cohn A. Advisory Committee on Immunization Practices Meeting; October 27, 2010.2

TABLE 3
Average annual number of cases of C, Y, and W-135 meningococcal disease

Age group (y)	2000-2004	2005-2009	Change
11-14	46	12	-74%
15-18	106	77	-27%
19-22	62	52	-16%
Total (11-22)	214	141	-34%
Source: Cohn A. Advisory Committee on Immunization Practices Meeting; October 27, 2010.2

ACIP weighed the options for a booster dose
Three options were presented at the October 2010 ACIP meeting:

• Option 1: No change to the current recommendation for vaccination of 11- to 12-year-olds. Wait and see what happens to disease incidence over several more years.
• Option 2: Move the age of vaccination to 15 years with no booster. This would allow protection to persist through the years of highest risk (16-21 years).
• Option 3: Keep the recommendation for vaccination at ages 11 to 12 years, and add a booster dose at age 16.

The first option was the least cost effective: $281,000/quality-adjusted life year (QALY). The second option was the most cost effective at $121,000/QALY. The last option came out in the middle: $157,000/QALY, but it would save the most lives—9 more per year compared with Option 2.¹ There is, however, a caveat with regard to the cost-effectiveness estimates. The numbers were obtained using incidence data from the year 2000; incidence has declined since then, and cost-effectiveness estimates would be much less favorable using today’s rates.

These issues were discussed at length, and the decision to add a booster dose at age 16 was made on a close vote. This decision illustrates how difficult vaccine policy-making has become in recent years, when choices must be made about recommending safe, effective, and expensive vaccines to prevent illnesses that are both rare and serious.

The new MCV4 recommendations will be added to the child immunization schedule for 2011.

The take-home message for family physicians is to strive to increase the proportion of 11- to 12-year-olds who are fully vaccinated and in 2011 to begin to advise those who are between the ages of 16 and 20 years of the recommendation for a booster dose of MCV4.

At its October 2010 meeting, the Advisory Committee on Immunization Practices (ACIP) made 2 additions to its recommendations for quadrivalent meningococcal conjugate vaccine (MCV4), based on evolving knowledge of the vaccine and its duration of protection.

• A booster dose at age 16 has been added to the routine schedule for those vaccinated at ages 11 to 12 years. A booster dose has also been added for those vaccinated at ages 13 to 15 years, although the recommended timing of this booster had not been finalized at press time.
• A 2-dose primary series, 2 months apart, is now recommended for patients at higher risk of meningococcal disease. The high-risk category includes those with persistent complement component deficiency, asplenia, or human immunodeficiency virus (HIV). High-risk patients who were previously vaccinated should receive a booster dose at the earliest opportunity and continue to receive boosters at the appropriate interval (3-5 years).

Meningitis is rare but serious
Meningococcal meningitis is a potentially devastating disease in adolescents and young adults. It has a case fatality rate of about 20%, and the sequelae for survivors can be severe: 3.1% require limb amputations and another 10.9% suffer neurological deficits.¹ Thankfully, meningococcal disease is rare, occurring at rates below 1 in 200,000 in the 11- to 15-year-old age group and less than 1 in 100,000 in the 16- to 21-year-old age group.²

Routine immunization with MCV4 is recommended for adolescents
In 2007, ACIP recommended routine use of MCV4 for adolescents between the ages of 11 and 18 years. The recommendation gave preference to immunization at ages 11 to 12 years, along with the other adolescent vaccines given at that time.³ Updated recommendations in effect in 2010 state that those at highest risk for meningococcal infection (those with functional or anatomic asplenia, C3 complement deficiency, or HIV infection) should be vaccinated with MCV4 starting at age 2 and revaccinated every 3 years if last vaccinated at 2 to 6 years, and every 5 years if last vaccinated at or after age 7.^4,5 TABLE 1 lists the recommendations for MCV4 in place prior to the October 2010 ACIP meeting.

Two MCV4 products are licensed for use in the United States: Menactra (Sanofi Pasteur) and Menveo (Novartis). Both contain antigens against 4 serotypes, A, C, Y, and W-135. Neither protects against type B, which causes a majority of the disease in infants.⁶ In recent years, serotype A disease has become extremely rare in the United States.⁶ MCV4 coverage for adolescents ages 13 to 17 years is increasing, going from 41.8% in 2008 to 53.6% in 2009.⁷

TABLE 1
Recommendations for MCV4 prior to October 2010^3-5

Immunize all adolescents between the ages of 11 and 18. Immunization at the 11- to 12-year visit is preferred.
Immunize all individuals between the ages of 2 and 55 who are at increased risk for meningococcal disease: college freshmen living in dormitories, microbiologists routinely exposed to isolates of Neisseria meningitidis, military recruits, travelers to (or residents of) countries in which N meningitidis meningitis is hyperendemic or epidemic, individuals with terminal complement component deficiencies, and individuals with anatomic or functional asplenia.
Administer a booster dose for those at continued high risk 3 years after a first dose given between ages 2 and 6, and 5 years after a first dose given at age 7 or older. Revaccinate those in increased risk groups at 5-year intervals indefinitely. The recommendation for a second dose does not apply to college freshmen living in dorms.
MCV4, meningococcal conjugate vaccine.

The new recommendations: One is more controversial than the other

The recommendation for a 2-dose primary series in high-risk groups was not controversial. The same conditions that place individuals at highest risk for meningococcal infection also result in a less robust response to a single dose of the vaccine, and a 2-dose series is needed to achieve protective antibody levels in a high proportion of those vaccine recipients.⁸ This recommendation will affect relatively few patients.

The recommendation for booster doses in the general adolescent population generated a lot more debate. Studies performed since the licensure of MCV4 have shown that levels of protective antibodies decline over time. Five years after vaccination, 50% of vaccine recipients have levels below that considered fully protective.² One small case-control study of 107 cases suggested that the number of years from receipt of the vaccine was a risk factor for meningococcal disease.²

However, rates of meningococcal meningitis in adolescents have been declining over the past few years (TABLE 2), and there are no surveillance data to support the conclusion that teens vaccinated at ages 11 to 12 years are at increased risk as they age. In addition, the number of cases is very low (TABLE 3) and the cost benefit analysis of a booster dose of MCV4 is very unfavorable.^1,2

 

TABLE 2
Rates* of serogroup C, Y, and W-135 meningococcal disease^†

	Age group (y)
Year	11-19	≥20
2004-2005	0.23	0.16
2006-2007	0.27	0.22
2008-2009	0.14	0.21
*Annual rate per 100,000. †Serogroup A disease is too rare for inclusion here. Source: Cohn A. Advisory Committee on Immunization Practices Meeting; October 27, 2010.2

TABLE 3
Average annual number of cases of C, Y, and W-135 meningococcal disease

Age group (y)	2000-2004	2005-2009	Change
11-14	46	12	-74%
15-18	106	77	-27%
19-22	62	52	-16%
Total (11-22)	214	141	-34%
Source: Cohn A. Advisory Committee on Immunization Practices Meeting; October 27, 2010.2

ACIP weighed the options for a booster dose
Three options were presented at the October 2010 ACIP meeting:

• Option 1: No change to the current recommendation for vaccination of 11- to 12-year-olds. Wait and see what happens to disease incidence over several more years.
• Option 2: Move the age of vaccination to 15 years with no booster. This would allow protection to persist through the years of highest risk (16-21 years).
• Option 3: Keep the recommendation for vaccination at ages 11 to 12 years, and add a booster dose at age 16.

The first option was the least cost effective: $281,000/quality-adjusted life year (QALY). The second option was the most cost effective at $121,000/QALY. The last option came out in the middle: $157,000/QALY, but it would save the most lives—9 more per year compared with Option 2.¹ There is, however, a caveat with regard to the cost-effectiveness estimates. The numbers were obtained using incidence data from the year 2000; incidence has declined since then, and cost-effectiveness estimates would be much less favorable using today’s rates.

These issues were discussed at length, and the decision to add a booster dose at age 16 was made on a close vote. This decision illustrates how difficult vaccine policy-making has become in recent years, when choices must be made about recommending safe, effective, and expensive vaccines to prevent illnesses that are both rare and serious.

The new MCV4 recommendations will be added to the child immunization schedule for 2011.

The take-home message for family physicians is to strive to increase the proportion of 11- to 12-year-olds who are fully vaccinated and in 2011 to begin to advise those who are between the ages of 16 and 20 years of the recommendation for a booster dose of MCV4.

Influenza pandemics like the one we had last year are uncommon, and mounting an effective response was a difficult challenge. The pandemic hit early and hard. Physicians and the public health system responded well, administering a seasonal flu vaccine as well as a new H1N1 vaccine that was approved, produced, and distributed in record time. Before the end of the season, approximately 30% of the population had received an H1N1 vaccine and 40% a seasonal vaccine.¹

What happened last year

The influenza attack rate in 2009-2010 exceeded that of a normal influenza season and the age groups most affected were also different, with those over the age of 65 largely spared.² Virtually all the influenza last year was caused by the pandemic H1N1 strain.² Fortuitously, the virus was not especially virulent and the death rates were below what was initially expected. TABLE 1 lists the population death rates that occurred for different age groups.² Most of the more than 2000 deaths were among those with high-risk conditions.³ Those conditions are listed in TABLE 2.

There were, however, 269 deaths by late March among children, which far exceeded the number of deaths in this age group for the previous 3 influenza seasons.² For the most part, these higher mortality rates were due to higher attack rates, rather than higher case fatality rates. This is evident from hospitalization rates for children younger than age 5, which exceeded those of other age groups, as shown in FIGURE 1.

TABLE 1
2009-2010 Influenza death rates by age

Age group, years	Death rate/100,000
0-4	0.43
5-18	0.36
19-24	0.54
25-49	0.87
50-64	1.56
≥65	0.95
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.2

TABLE 2
Individuals at higher risk for influenza complications (or who may spread infection to those at higher risk)

Children <5 years Adults ≥50 years Individuals with the following conditions: chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, neurological, hematologic, or metabolic disorders (including diabetes mellitus) Individuals with immunosuppression, including that caused by medications or by HIV infection Women who are pregnant, or who may be pregnant during the influenza season Individuals <19 years who are receiving long-term aspirin therapy Residents of nursing homes and other chronic-care facilities American Indians and Alaskan natives Individuals who are morbidly obese (body mass index ≥40 kg/m2) Health care professionals Household contacts and caregivers of children <5 years and adults ≥50 years Household contacts and caregivers of individuals who are at higher risk for severe complications of influenza

Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.4

FIGURE 1
Cumulative lab-confirmed hospitalization rate by age group, 2009 H1N1, April 2009-February 13, 2010*

*Based on 35 states reporting (n=49,516).
Source: Finelli L, et al. Available at http://www.cdc.gov/vaccines/recs/acip/downloads/mtg-slides-feb10/05-2-flu-vac.pdf. 2010.³

The task will be simpler this year
While it’s not possible to predict what will happen in the upcoming season, 2 developments should simplify the family physician’s task of adhering to official recommendations:

• Only 1 vaccine formulation will be available, and
• For the first time, the recommendation is to vaccinate everyone who does not have a contraindication.⁴

The vaccine for the 2010-2011 season will contain 3 antigens: the pandemic H1N1 virus, an H3N2 A strain (A/Perth/16/2009), and a B virus (B/Brisbane/60/2008).² The decision on which antigens to include is made 6 months in advance of the start of the next flu season and is based on information about the most common influenza antigens circulating worldwide at that time.

Immunization for all

This year’s recommendation to immunize everyone who does not have a contraindication is a major change from the age- and risk-based recommendations of past years. The universal recommendation is the culmination of the incremental expansions of recommendation categories that occurred over the past decade, which resulted in suboptimal immunization rates.¹ In 2009, only 40% to 50% of adults for whom the seasonal vaccine was recommended received it.⁵ While the annual influenza vaccine recommendation is now universal, those who should be specially targeted include those in TABLE 2. Most public health authorities believe children should also receive special emphasis because of the high transmission rate among school-age children and their home contacts. Next, of course, come health care workers, who should be vaccinated to protect ourselves, our families, and our patients.^4,6

Antivirals for treatment and prevention

There are 2 uses for antivirals to combat influenza: treatment of those infected and chemoprevention for those exposed to someone infected. Treatment is recommended for those with confirmed or suspected influenza who have severe, complicated, or progressive illness or who are hospitalized.⁷ Treatment should be strongly considered for anyone at higher risk for complications and death from influenza.⁷

 

Chemoprevention is now being deemphasized because of a concern for possible development of antiviral resistance. It should be considered for those in the high-risk categories (TABLE 2) with a documented exposure.⁷

Which antiviral to use will depend on which influenza strains are circulating and their resistance patterns. So far, H1N1 has remained largely sensitive to both neuraminidase inhibitors: oseltamivir and zanamivir. However, oseltamivir resistance has been documented in a few cases and will be monitored carefully.

Family physicians will need to stay informed by state and local health departments about circulating strains and resistance patterns. The latest Centers for Disease Control and Prevention (CDC) guidance on antiviral therapy can be consulted for dosage and other details on the 4 antiviral drugs licensed in the United States.⁷

What you must know about vaccine safety

Because of increasing public awareness of safety issues, family physicians will frequently need to address patients’ questions about the safety of this year’s vaccine. Last year, multiple reporting systems including the Vaccine Adverse Event Reporting System (VAERS), Vaccine Safety Datalink (VSD) Project, the Defense Medical Surveillance System (DMSS), and others, extensively monitored adverse events that could potentially be linked to the H1N1 vaccine.⁸ Three so-called weak signals—indications of a possible link to a rare, but statistically significant adverse event—were received.

The 3 signals were for Guillain-Barré syndrome (GBS), Bell’s palsy, and thrombocytopenia/idiopathic thrombocytopenic purpura. The status of the investigation of each potential link to the vaccine can be found on the National Vaccine Advisory Committee (NVAC) safety Web site at http://www.hhs.gov/nvpo/nvac/reports/index.html.

The GBS signal has been investigated the most aggressively because this adverse reaction has been linked to the so-called swine flu vaccine of 1976. One analysis has been published in the Morbidity and Mortality Weekly Report.⁹ Whether GBS has a causal link to the H1N1 vaccine remains in doubt. In the worst-case scenario, if causation is determined, it appears that the vaccine would account for no more than 1 excess case of GBS per million doses.⁹

In Western Australia, there has been a recent report of an excess of fever and febrile seizures in children 6 months to 5 years of age, and fever in children 5 to 9 years of age who received seasonal influenza vaccine. The rate of febrile seizures in children younger than age 3 was 7 per 1000, which is 7 times the rate normally expected. These adverse reactions were associated with only 1 vaccine product, Fluvax, and Fluvax Junior, manufactured by CSL Biotherapies.¹⁰ The CSL product is marketed in the United States by Merck & Co. under the brand name Afluria.

The Advisory Committee on Immunization Practices (ACIP) has issued the following recommendations:¹¹

• Afluria should not be used in children ages 6 months through 8 years. The exception: children who are ages 5 through 8 years who are considered to be at high risk for influenza complications and for whom no other trivalent inactivated vaccine is available.
• Other age-appropriate, licensed seasonal influenza vaccine formulations should be used for prevention of influenza in children ages 6 months through 8 years.

High-dose vaccine for elderly patients

A new seasonal influenza vaccine (Fluzone High-Dose, manufactured by Sanofi Pasteur) is now available for use in people who are 65 years of age and older.¹² Fluzone High-Dose contains 4 times the amount of influenza antigen as other inactivated seasonal influenza vaccines. Fluzone High-Dose vaccine produces higher antibody levels in the elderly but also a higher frequency of local reactions. Studies are being conducted to see if the vaccine results in better patient outcomes. ACIP does not state a preference for any of the available influenza vaccines for those who are 65 years of age and older.¹²

Children younger than age 9: One dose or two?

The new recommendations for deciding if a child under the age of 9 years should receive 1 or 2 doses of the vaccine run counter to the trend for simplification in influenza vaccine recommendations. The decision depends on the child’s past immunization history for both seasonal and H1N1 vaccines. To be fully vaccinated with only 1 dose this year, a child must have previously received at least 1 dose of H1N1 vaccine and 2 doses of seasonal vaccine. FIGURE 2 illustrates the process you need to go through to make the dosage choice. When the child’s immunization history is unknown or uncertain, give 2 doses, separated by 4 weeks.⁴

FIGURE 2
Children younger than 9: Ask 4 questions

Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.⁴

Influenza pandemics like the one we had last year are uncommon, and mounting an effective response was a difficult challenge. The pandemic hit early and hard. Physicians and the public health system responded well, administering a seasonal flu vaccine as well as a new H1N1 vaccine that was approved, produced, and distributed in record time. Before the end of the season, approximately 30% of the population had received an H1N1 vaccine and 40% a seasonal vaccine.¹

What happened last year

The influenza attack rate in 2009-2010 exceeded that of a normal influenza season and the age groups most affected were also different, with those over the age of 65 largely spared.² Virtually all the influenza last year was caused by the pandemic H1N1 strain.² Fortuitously, the virus was not especially virulent and the death rates were below what was initially expected. TABLE 1 lists the population death rates that occurred for different age groups.² Most of the more than 2000 deaths were among those with high-risk conditions.³ Those conditions are listed in TABLE 2.

There were, however, 269 deaths by late March among children, which far exceeded the number of deaths in this age group for the previous 3 influenza seasons.² For the most part, these higher mortality rates were due to higher attack rates, rather than higher case fatality rates. This is evident from hospitalization rates for children younger than age 5, which exceeded those of other age groups, as shown in FIGURE 1.

TABLE 1
2009-2010 Influenza death rates by age

Age group, years	Death rate/100,000
0-4	0.43
5-18	0.36
19-24	0.54
25-49	0.87
50-64	1.56
≥65	0.95
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.2

TABLE 2
Individuals at higher risk for influenza complications (or who may spread infection to those at higher risk)

Children <5 years Adults ≥50 years Individuals with the following conditions: chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, neurological, hematologic, or metabolic disorders (including diabetes mellitus) Individuals with immunosuppression, including that caused by medications or by HIV infection Women who are pregnant, or who may be pregnant during the influenza season Individuals <19 years who are receiving long-term aspirin therapy Residents of nursing homes and other chronic-care facilities American Indians and Alaskan natives Individuals who are morbidly obese (body mass index ≥40 kg/m2) Health care professionals Household contacts and caregivers of children <5 years and adults ≥50 years Household contacts and caregivers of individuals who are at higher risk for severe complications of influenza

Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.4

FIGURE 1
Cumulative lab-confirmed hospitalization rate by age group, 2009 H1N1, April 2009-February 13, 2010*

*Based on 35 states reporting (n=49,516).
Source: Finelli L, et al. Available at http://www.cdc.gov/vaccines/recs/acip/downloads/mtg-slides-feb10/05-2-flu-vac.pdf. 2010.³

The task will be simpler this year
While it’s not possible to predict what will happen in the upcoming season, 2 developments should simplify the family physician’s task of adhering to official recommendations:

• Only 1 vaccine formulation will be available, and
• For the first time, the recommendation is to vaccinate everyone who does not have a contraindication.⁴

The vaccine for the 2010-2011 season will contain 3 antigens: the pandemic H1N1 virus, an H3N2 A strain (A/Perth/16/2009), and a B virus (B/Brisbane/60/2008).² The decision on which antigens to include is made 6 months in advance of the start of the next flu season and is based on information about the most common influenza antigens circulating worldwide at that time.

Immunization for all

This year’s recommendation to immunize everyone who does not have a contraindication is a major change from the age- and risk-based recommendations of past years. The universal recommendation is the culmination of the incremental expansions of recommendation categories that occurred over the past decade, which resulted in suboptimal immunization rates.¹ In 2009, only 40% to 50% of adults for whom the seasonal vaccine was recommended received it.⁵ While the annual influenza vaccine recommendation is now universal, those who should be specially targeted include those in TABLE 2. Most public health authorities believe children should also receive special emphasis because of the high transmission rate among school-age children and their home contacts. Next, of course, come health care workers, who should be vaccinated to protect ourselves, our families, and our patients.^4,6

Antivirals for treatment and prevention

There are 2 uses for antivirals to combat influenza: treatment of those infected and chemoprevention for those exposed to someone infected. Treatment is recommended for those with confirmed or suspected influenza who have severe, complicated, or progressive illness or who are hospitalized.⁷ Treatment should be strongly considered for anyone at higher risk for complications and death from influenza.⁷

 

Chemoprevention is now being deemphasized because of a concern for possible development of antiviral resistance. It should be considered for those in the high-risk categories (TABLE 2) with a documented exposure.⁷

Which antiviral to use will depend on which influenza strains are circulating and their resistance patterns. So far, H1N1 has remained largely sensitive to both neuraminidase inhibitors: oseltamivir and zanamivir. However, oseltamivir resistance has been documented in a few cases and will be monitored carefully.

Family physicians will need to stay informed by state and local health departments about circulating strains and resistance patterns. The latest Centers for Disease Control and Prevention (CDC) guidance on antiviral therapy can be consulted for dosage and other details on the 4 antiviral drugs licensed in the United States.⁷

What you must know about vaccine safety

Because of increasing public awareness of safety issues, family physicians will frequently need to address patients’ questions about the safety of this year’s vaccine. Last year, multiple reporting systems including the Vaccine Adverse Event Reporting System (VAERS), Vaccine Safety Datalink (VSD) Project, the Defense Medical Surveillance System (DMSS), and others, extensively monitored adverse events that could potentially be linked to the H1N1 vaccine.⁸ Three so-called weak signals—indications of a possible link to a rare, but statistically significant adverse event—were received.

The 3 signals were for Guillain-Barré syndrome (GBS), Bell’s palsy, and thrombocytopenia/idiopathic thrombocytopenic purpura. The status of the investigation of each potential link to the vaccine can be found on the National Vaccine Advisory Committee (NVAC) safety Web site at http://www.hhs.gov/nvpo/nvac/reports/index.html.

The GBS signal has been investigated the most aggressively because this adverse reaction has been linked to the so-called swine flu vaccine of 1976. One analysis has been published in the Morbidity and Mortality Weekly Report.⁹ Whether GBS has a causal link to the H1N1 vaccine remains in doubt. In the worst-case scenario, if causation is determined, it appears that the vaccine would account for no more than 1 excess case of GBS per million doses.⁹

In Western Australia, there has been a recent report of an excess of fever and febrile seizures in children 6 months to 5 years of age, and fever in children 5 to 9 years of age who received seasonal influenza vaccine. The rate of febrile seizures in children younger than age 3 was 7 per 1000, which is 7 times the rate normally expected. These adverse reactions were associated with only 1 vaccine product, Fluvax, and Fluvax Junior, manufactured by CSL Biotherapies.¹⁰ The CSL product is marketed in the United States by Merck & Co. under the brand name Afluria.

The Advisory Committee on Immunization Practices (ACIP) has issued the following recommendations:¹¹

• Afluria should not be used in children ages 6 months through 8 years. The exception: children who are ages 5 through 8 years who are considered to be at high risk for influenza complications and for whom no other trivalent inactivated vaccine is available.
• Other age-appropriate, licensed seasonal influenza vaccine formulations should be used for prevention of influenza in children ages 6 months through 8 years.

High-dose vaccine for elderly patients

A new seasonal influenza vaccine (Fluzone High-Dose, manufactured by Sanofi Pasteur) is now available for use in people who are 65 years of age and older.¹² Fluzone High-Dose contains 4 times the amount of influenza antigen as other inactivated seasonal influenza vaccines. Fluzone High-Dose vaccine produces higher antibody levels in the elderly but also a higher frequency of local reactions. Studies are being conducted to see if the vaccine results in better patient outcomes. ACIP does not state a preference for any of the available influenza vaccines for those who are 65 years of age and older.¹²

Children younger than age 9: One dose or two?

The new recommendations for deciding if a child under the age of 9 years should receive 1 or 2 doses of the vaccine run counter to the trend for simplification in influenza vaccine recommendations. The decision depends on the child’s past immunization history for both seasonal and H1N1 vaccines. To be fully vaccinated with only 1 dose this year, a child must have previously received at least 1 dose of H1N1 vaccine and 2 doses of seasonal vaccine. FIGURE 2 illustrates the process you need to go through to make the dosage choice. When the child’s immunization history is unknown or uncertain, give 2 doses, separated by 4 weeks.⁴

FIGURE 2
Children younger than 9: Ask 4 questions

Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.⁴

Influenza pandemics like the one we had last year are uncommon, and mounting an effective response was a difficult challenge. The pandemic hit early and hard. Physicians and the public health system responded well, administering a seasonal flu vaccine as well as a new H1N1 vaccine that was approved, produced, and distributed in record time. Before the end of the season, approximately 30% of the population had received an H1N1 vaccine and 40% a seasonal vaccine.¹

What happened last year

The influenza attack rate in 2009-2010 exceeded that of a normal influenza season and the age groups most affected were also different, with those over the age of 65 largely spared.² Virtually all the influenza last year was caused by the pandemic H1N1 strain.² Fortuitously, the virus was not especially virulent and the death rates were below what was initially expected. TABLE 1 lists the population death rates that occurred for different age groups.² Most of the more than 2000 deaths were among those with high-risk conditions.³ Those conditions are listed in TABLE 2.

There were, however, 269 deaths by late March among children, which far exceeded the number of deaths in this age group for the previous 3 influenza seasons.² For the most part, these higher mortality rates were due to higher attack rates, rather than higher case fatality rates. This is evident from hospitalization rates for children younger than age 5, which exceeded those of other age groups, as shown in FIGURE 1.

TABLE 1
2009-2010 Influenza death rates by age

Age group, years	Death rate/100,000
0-4	0.43
5-18	0.36
19-24	0.54
25-49	0.87
50-64	1.56
≥65	0.95
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.2

TABLE 2
Individuals at higher risk for influenza complications (or who may spread infection to those at higher risk)

Children <5 years Adults ≥50 years Individuals with the following conditions: chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, neurological, hematologic, or metabolic disorders (including diabetes mellitus) Individuals with immunosuppression, including that caused by medications or by HIV infection Women who are pregnant, or who may be pregnant during the influenza season Individuals <19 years who are receiving long-term aspirin therapy Residents of nursing homes and other chronic-care facilities American Indians and Alaskan natives Individuals who are morbidly obese (body mass index ≥40 kg/m2) Health care professionals Household contacts and caregivers of children <5 years and adults ≥50 years Household contacts and caregivers of individuals who are at higher risk for severe complications of influenza

Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.4

FIGURE 1
Cumulative lab-confirmed hospitalization rate by age group, 2009 H1N1, April 2009-February 13, 2010*

*Based on 35 states reporting (n=49,516).
Source: Finelli L, et al. Available at http://www.cdc.gov/vaccines/recs/acip/downloads/mtg-slides-feb10/05-2-flu-vac.pdf. 2010.³

The task will be simpler this year
While it’s not possible to predict what will happen in the upcoming season, 2 developments should simplify the family physician’s task of adhering to official recommendations:

• Only 1 vaccine formulation will be available, and
• For the first time, the recommendation is to vaccinate everyone who does not have a contraindication.⁴

The vaccine for the 2010-2011 season will contain 3 antigens: the pandemic H1N1 virus, an H3N2 A strain (A/Perth/16/2009), and a B virus (B/Brisbane/60/2008).² The decision on which antigens to include is made 6 months in advance of the start of the next flu season and is based on information about the most common influenza antigens circulating worldwide at that time.

Immunization for all

This year’s recommendation to immunize everyone who does not have a contraindication is a major change from the age- and risk-based recommendations of past years. The universal recommendation is the culmination of the incremental expansions of recommendation categories that occurred over the past decade, which resulted in suboptimal immunization rates.¹ In 2009, only 40% to 50% of adults for whom the seasonal vaccine was recommended received it.⁵ While the annual influenza vaccine recommendation is now universal, those who should be specially targeted include those in TABLE 2. Most public health authorities believe children should also receive special emphasis because of the high transmission rate among school-age children and their home contacts. Next, of course, come health care workers, who should be vaccinated to protect ourselves, our families, and our patients.^4,6

Antivirals for treatment and prevention

There are 2 uses for antivirals to combat influenza: treatment of those infected and chemoprevention for those exposed to someone infected. Treatment is recommended for those with confirmed or suspected influenza who have severe, complicated, or progressive illness or who are hospitalized.⁷ Treatment should be strongly considered for anyone at higher risk for complications and death from influenza.⁷

 

Chemoprevention is now being deemphasized because of a concern for possible development of antiviral resistance. It should be considered for those in the high-risk categories (TABLE 2) with a documented exposure.⁷

Which antiviral to use will depend on which influenza strains are circulating and their resistance patterns. So far, H1N1 has remained largely sensitive to both neuraminidase inhibitors: oseltamivir and zanamivir. However, oseltamivir resistance has been documented in a few cases and will be monitored carefully.

Family physicians will need to stay informed by state and local health departments about circulating strains and resistance patterns. The latest Centers for Disease Control and Prevention (CDC) guidance on antiviral therapy can be consulted for dosage and other details on the 4 antiviral drugs licensed in the United States.⁷

What you must know about vaccine safety

Because of increasing public awareness of safety issues, family physicians will frequently need to address patients’ questions about the safety of this year’s vaccine. Last year, multiple reporting systems including the Vaccine Adverse Event Reporting System (VAERS), Vaccine Safety Datalink (VSD) Project, the Defense Medical Surveillance System (DMSS), and others, extensively monitored adverse events that could potentially be linked to the H1N1 vaccine.⁸ Three so-called weak signals—indications of a possible link to a rare, but statistically significant adverse event—were received.

The 3 signals were for Guillain-Barré syndrome (GBS), Bell’s palsy, and thrombocytopenia/idiopathic thrombocytopenic purpura. The status of the investigation of each potential link to the vaccine can be found on the National Vaccine Advisory Committee (NVAC) safety Web site at http://www.hhs.gov/nvpo/nvac/reports/index.html.

The GBS signal has been investigated the most aggressively because this adverse reaction has been linked to the so-called swine flu vaccine of 1976. One analysis has been published in the Morbidity and Mortality Weekly Report.⁹ Whether GBS has a causal link to the H1N1 vaccine remains in doubt. In the worst-case scenario, if causation is determined, it appears that the vaccine would account for no more than 1 excess case of GBS per million doses.⁹

In Western Australia, there has been a recent report of an excess of fever and febrile seizures in children 6 months to 5 years of age, and fever in children 5 to 9 years of age who received seasonal influenza vaccine. The rate of febrile seizures in children younger than age 3 was 7 per 1000, which is 7 times the rate normally expected. These adverse reactions were associated with only 1 vaccine product, Fluvax, and Fluvax Junior, manufactured by CSL Biotherapies.¹⁰ The CSL product is marketed in the United States by Merck & Co. under the brand name Afluria.

The Advisory Committee on Immunization Practices (ACIP) has issued the following recommendations:¹¹

• Afluria should not be used in children ages 6 months through 8 years. The exception: children who are ages 5 through 8 years who are considered to be at high risk for influenza complications and for whom no other trivalent inactivated vaccine is available.
• Other age-appropriate, licensed seasonal influenza vaccine formulations should be used for prevention of influenza in children ages 6 months through 8 years.

High-dose vaccine for elderly patients

A new seasonal influenza vaccine (Fluzone High-Dose, manufactured by Sanofi Pasteur) is now available for use in people who are 65 years of age and older.¹² Fluzone High-Dose contains 4 times the amount of influenza antigen as other inactivated seasonal influenza vaccines. Fluzone High-Dose vaccine produces higher antibody levels in the elderly but also a higher frequency of local reactions. Studies are being conducted to see if the vaccine results in better patient outcomes. ACIP does not state a preference for any of the available influenza vaccines for those who are 65 years of age and older.¹²

Children younger than age 9: One dose or two?

The new recommendations for deciding if a child under the age of 9 years should receive 1 or 2 doses of the vaccine run counter to the trend for simplification in influenza vaccine recommendations. The decision depends on the child’s past immunization history for both seasonal and H1N1 vaccines. To be fully vaccinated with only 1 dose this year, a child must have previously received at least 1 dose of H1N1 vaccine and 2 doses of seasonal vaccine. FIGURE 2 illustrates the process you need to go through to make the dosage choice. When the child’s immunization history is unknown or uncertain, give 2 doses, separated by 4 weeks.⁴

FIGURE 2
Children younger than 9: Ask 4 questions

Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.⁴

A new, 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13), from Wyeth Pharmaceuticals was licensed by the US Food and Drug Administration (FDA) in February for use in all children ages 6 weeks to 59 months. The new vaccine was licensed for the prevention of invasive pneumococcal disease (pneumonia, meningitis, and bacteremia) and otitis media.¹ PCV13 is meant to replace the 7-valent PCV7 (Prevnar), and will offer protection against a wider array of pneumococcal serotypes.¹

Invasive pneumococcal disease in kids has diminished substantially

Soon after PCV7 was included in the routine child immunization schedule, the incidence of invasive pneumococcal disease (IPD) began to decline.^2-5 In 1 study, the annual rate of IPD among children younger than 5 years of age decreased from 98.7 cases/100,000 in 1998–1999 to 22.6 cases/100,000 in 2006-2007.³ This decline was due to a decrease in the rate of disease caused by the 7 vaccine serotypes, from 81.9 cases/100,000 to 0.4 cases/100,000.

However, during that same time period, the rate of IPD caused by nonvaccine serotypes increased from 16.8 cases/100,000 population to 22.1 cases/100,000.³ The percentage of IPD caused by nonvaccine serotypes rose from 20% to 90% among children younger than 5 years of age during that time period.³

Fewer cases in adults, as well
In addition to the decline of IPD in children, there has also been a decline in adults. In those older than age 65, the rate of IPD decreased from 60.1/100,000 to 38.2/100,000 between 1998 and 2007—most likely because routine use of the PCV7 vaccine in children has resulted in decreased carriage and transmission of infection from children to adults.³ As in children, the decline was due to a decreasing incidence of infection from PCV7 vaccine serotypes, from 33.7 cases/100,000 to 3.3 cases/100,000. At the same time, the rate of disease caused by nonvaccine serotypes increased from 26.4 cases/100,000 to 34.9 cases/100,000.³

Nonvaccine serotypes still cause concern
While the overall decline in IPD has been a public health success, the increase in incidence of disease caused by nonvaccine serotypes has been cause for concern. According to an analysis of 2007 data from the Centers for Disease Control and Prevention (CDC)’s Active Bacterial Core surveillance, 64% of IPD cases in children younger than 5 years of age in 2006-2007 were caused by serotypes 1, 3, 5, 6A, 7F, and 19A.⁶ Several of these replacement serotypes have high levels of resistance to penicillin and erythromycin. This trend is what led to the development of the PCV13, which adds these 6 to the 7 serotypes covered by Prevnar.

The dosing schedule is complicated

The recommended schedule for the older PCV7 vaccine has always been a challenge, because the number of doses depends on the age of the child when first vaccinated.^7,8 The introduction of PCV13 adds to the complexity, because many children will be in the midst of a PCV7 series when they make the transition to PCV13.

The Advisory Committee on Immunization Practices (ACIP) recommendations on how many doses of PCV13 a child should receive depend now on the age at which the first PCV vaccine was received (either PCV7 or PCV13), the number of doses of each received, and the presence or absence of high-risk medical conditions. These recommendations are summarized below and illustrated in TABLE 1 and TABLE 2.

TABLE 1
PCV13: Routine vaccination schedule

Age at first dose	Primary series*	Booster dose†
2-6 months	3 doses	1 dose, 12-15 months
7-11 months	2 doses	1 dose, 12-15 months
12-23 months	2 doses	None
24-59 months, healthy children	1 dose	None
24-71 months for children with certain chronic diseases or immunocompromising conditions (see TABLE 3)	2 doses	None
*Minimum interval between doses is 8 weeks, except for children vaccinated at <12 months for whom the minimum interval is 4 weeks. Minimum age for first dose is 6 weeks.
†Given at least 8 weeks after previous dose.
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.1

TABLE 2
In transition: From PCV7 to PCV13

Infant series			Booster dose	Supplemental PCV13 dose
2 months	4 months	6 months	≥12 months*	14-59 months†
PCV7	PCV13	PCV13	PCV13	None
PCV7	PCV7	PCV13	PCV13	None
PCV7	PCV7	PCV7	PCV13	None
PCV7	PCV7	PCV7	PCV7	PCV13
*No additional PCV13 doses are indicated for children ages 12-23 months who have received 2 or 3 doses of PCV before age 12 months and at least 1 dose of PCV13 at ≥12 months.
†For children with underlying medical conditions (see TABLE 3), a single supplemental PCV13 dose is recommended through age 71 months.
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.1

For a child who started PCV7 on time and is in mid series, the recommendation is to simply finish the series with PCV13.

If a child has completed a series of PCV7, the recommendation is to give him or her 1 dose of PCV13 up to age 59 months. (If the child has a chronic underlying medical condition, this age is extended to 71 months.¹)

 

Infants between the ages of 1 and 6 months who have never received any PCV product should complete a series of PCV13 at 2, 4, 6, and 12 to 15 months—the same time line as the PCV7 series.

Children ages 7 to 59 months who have not been vaccinated with PCV7 or PCV13 previously should receive 1 to 3 doses of PCV13, depending on their age at the time when vaccination begins and whether underlying medical conditions are present (TABLE 3).

Healthy children ages 24 to 59 months without previous PCV vaccine should receive 1 dose of PCV13.

Children ages 24 to 71 months without previous PCV vaccine who have a chronic medical condition that increases their risk for pneumococcal disease should receive 2 doses of PCV13, 8 weeks apart.¹

TABLE 3
Underlying conditions that place kids at risk for pneumococcal disease

Risk group	Condition
Immunocompetent children	Chronic heart disease*
	Chronic lung disease†
	Diabetes mellitus
	Cerebrospinal fluid leaks
	Cochlear implant
Children with functional or anatomic asplenia	Sickle cell disease and other hemoglobulinopathies
	Congenital or acquired asplenia or splenic dysfunction
Children with immunocompromising conditions	HIV infection
	Chronic renal failure and nephrotic syndrome
	Diseases associated with immunosuppressive drugs or radiation therapy, including malignant neoplasms, leukemias, lymphomas, and Hodgkin’s disease; or solid organ transplantation
	Congenital immunodeficiency‡
*Particularly cyanotic congenital heart disease and cardiac failure.
†Including asthma if treated with prolonged high-dose oral corticosteroids.
‡Includes B- (humoral) or T-lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phagocytic disorders (excluding chronic granulomatous disease).
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.1

Recommendations for children at higher risk

Provisional recommendations from ACIP advise that children 2 through 18 years of age at increased risk for invasive pneumococcal disease should also receive 23-valent pneumococcal polysaccharide vaccine (PPSV23). Ideally, the child should have received all of the recommended doses of PCV13 before the physician administers PPSV23, with a minimum interval of at least 8 weeks after the last dose of PCV13.

However, some children will have previously received PPSV23. They should also receive the recommended PCV13 doses. A second dose of PPSV23 is recommended 5 years after the first dose of PPSV23 for children who have sickle cell disease, or functional or anatomic asplenia, human immunodeficiency virus (HIV) infection, or other immunocompromising conditions. No more than 2 PPSV23 doses are recommended.⁹

The ACIP provisional recommendations also say that a single dose of PCV13 may be administered to children ages 6 to 18 years who are at increased risk for IPD because of sickle cell disease, HIV infection or other immunocompromising condition, cochlear implant, or cerebrospinal fluid leaks, regardless of whether they have previously received PCV7 or PPSV23.⁹ This, however, is an off-label recommendation.

The usual contraindications
PCV13 is contraindicated among individuals known to have a severe allergic reaction to any component of PCV13 or PCV7 or to any diphtheria toxoid-containing vaccine, because the pneumococcal antigens are conjugated to a diphtheria carrier protein.¹

A useful vaccine, with its share of challenges

The pneumococcal conjugate vaccine combats infections such as pneumococcal pneumonia and meningitis, which are potentially serious—even though their incidence is relatively low.

The vaccine’s high private-sector cost—reported by the manufacturer to the CDC as $435 for the full, 4-dose series of PCV13—can be a drawback for the family physician trying to keep a full array of vaccine products on hand.¹⁰ Eligible low-income and uninsured children can receive free vaccine under the federal Vaccines for Children Program, and providers who choose to enroll in the program can access free vaccines and may charge for the expense of administering them.¹¹

With this hurdle overcome, the remaining challenge for physicians will be to stay on top of the complicated dosing schedule.

A new, 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13), from Wyeth Pharmaceuticals was licensed by the US Food and Drug Administration (FDA) in February for use in all children ages 6 weeks to 59 months. The new vaccine was licensed for the prevention of invasive pneumococcal disease (pneumonia, meningitis, and bacteremia) and otitis media.¹ PCV13 is meant to replace the 7-valent PCV7 (Prevnar), and will offer protection against a wider array of pneumococcal serotypes.¹

Invasive pneumococcal disease in kids has diminished substantially

Soon after PCV7 was included in the routine child immunization schedule, the incidence of invasive pneumococcal disease (IPD) began to decline.^2-5 In 1 study, the annual rate of IPD among children younger than 5 years of age decreased from 98.7 cases/100,000 in 1998–1999 to 22.6 cases/100,000 in 2006-2007.³ This decline was due to a decrease in the rate of disease caused by the 7 vaccine serotypes, from 81.9 cases/100,000 to 0.4 cases/100,000.

However, during that same time period, the rate of IPD caused by nonvaccine serotypes increased from 16.8 cases/100,000 population to 22.1 cases/100,000.³ The percentage of IPD caused by nonvaccine serotypes rose from 20% to 90% among children younger than 5 years of age during that time period.³

Fewer cases in adults, as well
In addition to the decline of IPD in children, there has also been a decline in adults. In those older than age 65, the rate of IPD decreased from 60.1/100,000 to 38.2/100,000 between 1998 and 2007—most likely because routine use of the PCV7 vaccine in children has resulted in decreased carriage and transmission of infection from children to adults.³ As in children, the decline was due to a decreasing incidence of infection from PCV7 vaccine serotypes, from 33.7 cases/100,000 to 3.3 cases/100,000. At the same time, the rate of disease caused by nonvaccine serotypes increased from 26.4 cases/100,000 to 34.9 cases/100,000.³

Nonvaccine serotypes still cause concern
While the overall decline in IPD has been a public health success, the increase in incidence of disease caused by nonvaccine serotypes has been cause for concern. According to an analysis of 2007 data from the Centers for Disease Control and Prevention (CDC)’s Active Bacterial Core surveillance, 64% of IPD cases in children younger than 5 years of age in 2006-2007 were caused by serotypes 1, 3, 5, 6A, 7F, and 19A.⁶ Several of these replacement serotypes have high levels of resistance to penicillin and erythromycin. This trend is what led to the development of the PCV13, which adds these 6 to the 7 serotypes covered by Prevnar.

The dosing schedule is complicated

The recommended schedule for the older PCV7 vaccine has always been a challenge, because the number of doses depends on the age of the child when first vaccinated.^7,8 The introduction of PCV13 adds to the complexity, because many children will be in the midst of a PCV7 series when they make the transition to PCV13.

The Advisory Committee on Immunization Practices (ACIP) recommendations on how many doses of PCV13 a child should receive depend now on the age at which the first PCV vaccine was received (either PCV7 or PCV13), the number of doses of each received, and the presence or absence of high-risk medical conditions. These recommendations are summarized below and illustrated in TABLE 1 and TABLE 2.

TABLE 1
PCV13: Routine vaccination schedule

Age at first dose	Primary series*	Booster dose†
2-6 months	3 doses	1 dose, 12-15 months
7-11 months	2 doses	1 dose, 12-15 months
12-23 months	2 doses	None
24-59 months, healthy children	1 dose	None
24-71 months for children with certain chronic diseases or immunocompromising conditions (see TABLE 3)	2 doses	None
*Minimum interval between doses is 8 weeks, except for children vaccinated at <12 months for whom the minimum interval is 4 weeks. Minimum age for first dose is 6 weeks.
†Given at least 8 weeks after previous dose.
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.1

TABLE 2
In transition: From PCV7 to PCV13

Infant series			Booster dose	Supplemental PCV13 dose
2 months	4 months	6 months	≥12 months*	14-59 months†
PCV7	PCV13	PCV13	PCV13	None
PCV7	PCV7	PCV13	PCV13	None
PCV7	PCV7	PCV7	PCV13	None
PCV7	PCV7	PCV7	PCV7	PCV13
*No additional PCV13 doses are indicated for children ages 12-23 months who have received 2 or 3 doses of PCV before age 12 months and at least 1 dose of PCV13 at ≥12 months.
†For children with underlying medical conditions (see TABLE 3), a single supplemental PCV13 dose is recommended through age 71 months.
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.1

For a child who started PCV7 on time and is in mid series, the recommendation is to simply finish the series with PCV13.

If a child has completed a series of PCV7, the recommendation is to give him or her 1 dose of PCV13 up to age 59 months. (If the child has a chronic underlying medical condition, this age is extended to 71 months.¹)

 

Infants between the ages of 1 and 6 months who have never received any PCV product should complete a series of PCV13 at 2, 4, 6, and 12 to 15 months—the same time line as the PCV7 series.

Children ages 7 to 59 months who have not been vaccinated with PCV7 or PCV13 previously should receive 1 to 3 doses of PCV13, depending on their age at the time when vaccination begins and whether underlying medical conditions are present (TABLE 3).

Healthy children ages 24 to 59 months without previous PCV vaccine should receive 1 dose of PCV13.

Children ages 24 to 71 months without previous PCV vaccine who have a chronic medical condition that increases their risk for pneumococcal disease should receive 2 doses of PCV13, 8 weeks apart.¹

TABLE 3
Underlying conditions that place kids at risk for pneumococcal disease

Risk group	Condition
Immunocompetent children	Chronic heart disease*
	Chronic lung disease†
	Diabetes mellitus
	Cerebrospinal fluid leaks
	Cochlear implant
Children with functional or anatomic asplenia	Sickle cell disease and other hemoglobulinopathies
	Congenital or acquired asplenia or splenic dysfunction
Children with immunocompromising conditions	HIV infection
	Chronic renal failure and nephrotic syndrome
	Diseases associated with immunosuppressive drugs or radiation therapy, including malignant neoplasms, leukemias, lymphomas, and Hodgkin’s disease; or solid organ transplantation
	Congenital immunodeficiency‡
*Particularly cyanotic congenital heart disease and cardiac failure.
†Including asthma if treated with prolonged high-dose oral corticosteroids.
‡Includes B- (humoral) or T-lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phagocytic disorders (excluding chronic granulomatous disease).
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.1

Recommendations for children at higher risk

Provisional recommendations from ACIP advise that children 2 through 18 years of age at increased risk for invasive pneumococcal disease should also receive 23-valent pneumococcal polysaccharide vaccine (PPSV23). Ideally, the child should have received all of the recommended doses of PCV13 before the physician administers PPSV23, with a minimum interval of at least 8 weeks after the last dose of PCV13.

However, some children will have previously received PPSV23. They should also receive the recommended PCV13 doses. A second dose of PPSV23 is recommended 5 years after the first dose of PPSV23 for children who have sickle cell disease, or functional or anatomic asplenia, human immunodeficiency virus (HIV) infection, or other immunocompromising conditions. No more than 2 PPSV23 doses are recommended.⁹

The ACIP provisional recommendations also say that a single dose of PCV13 may be administered to children ages 6 to 18 years who are at increased risk for IPD because of sickle cell disease, HIV infection or other immunocompromising condition, cochlear implant, or cerebrospinal fluid leaks, regardless of whether they have previously received PCV7 or PPSV23.⁹ This, however, is an off-label recommendation.

The usual contraindications
PCV13 is contraindicated among individuals known to have a severe allergic reaction to any component of PCV13 or PCV7 or to any diphtheria toxoid-containing vaccine, because the pneumococcal antigens are conjugated to a diphtheria carrier protein.¹

A useful vaccine, with its share of challenges

The pneumococcal conjugate vaccine combats infections such as pneumococcal pneumonia and meningitis, which are potentially serious—even though their incidence is relatively low.

The vaccine’s high private-sector cost—reported by the manufacturer to the CDC as $435 for the full, 4-dose series of PCV13—can be a drawback for the family physician trying to keep a full array of vaccine products on hand.¹⁰ Eligible low-income and uninsured children can receive free vaccine under the federal Vaccines for Children Program, and providers who choose to enroll in the program can access free vaccines and may charge for the expense of administering them.¹¹

With this hurdle overcome, the remaining challenge for physicians will be to stay on top of the complicated dosing schedule.

A new, 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13), from Wyeth Pharmaceuticals was licensed by the US Food and Drug Administration (FDA) in February for use in all children ages 6 weeks to 59 months. The new vaccine was licensed for the prevention of invasive pneumococcal disease (pneumonia, meningitis, and bacteremia) and otitis media.¹ PCV13 is meant to replace the 7-valent PCV7 (Prevnar), and will offer protection against a wider array of pneumococcal serotypes.¹

Invasive pneumococcal disease in kids has diminished substantially

Soon after PCV7 was included in the routine child immunization schedule, the incidence of invasive pneumococcal disease (IPD) began to decline.^2-5 In 1 study, the annual rate of IPD among children younger than 5 years of age decreased from 98.7 cases/100,000 in 1998–1999 to 22.6 cases/100,000 in 2006-2007.³ This decline was due to a decrease in the rate of disease caused by the 7 vaccine serotypes, from 81.9 cases/100,000 to 0.4 cases/100,000.

However, during that same time period, the rate of IPD caused by nonvaccine serotypes increased from 16.8 cases/100,000 population to 22.1 cases/100,000.³ The percentage of IPD caused by nonvaccine serotypes rose from 20% to 90% among children younger than 5 years of age during that time period.³

Fewer cases in adults, as well
In addition to the decline of IPD in children, there has also been a decline in adults. In those older than age 65, the rate of IPD decreased from 60.1/100,000 to 38.2/100,000 between 1998 and 2007—most likely because routine use of the PCV7 vaccine in children has resulted in decreased carriage and transmission of infection from children to adults.³ As in children, the decline was due to a decreasing incidence of infection from PCV7 vaccine serotypes, from 33.7 cases/100,000 to 3.3 cases/100,000. At the same time, the rate of disease caused by nonvaccine serotypes increased from 26.4 cases/100,000 to 34.9 cases/100,000.³

Nonvaccine serotypes still cause concern
While the overall decline in IPD has been a public health success, the increase in incidence of disease caused by nonvaccine serotypes has been cause for concern. According to an analysis of 2007 data from the Centers for Disease Control and Prevention (CDC)’s Active Bacterial Core surveillance, 64% of IPD cases in children younger than 5 years of age in 2006-2007 were caused by serotypes 1, 3, 5, 6A, 7F, and 19A.⁶ Several of these replacement serotypes have high levels of resistance to penicillin and erythromycin. This trend is what led to the development of the PCV13, which adds these 6 to the 7 serotypes covered by Prevnar.

The dosing schedule is complicated

The recommended schedule for the older PCV7 vaccine has always been a challenge, because the number of doses depends on the age of the child when first vaccinated.^7,8 The introduction of PCV13 adds to the complexity, because many children will be in the midst of a PCV7 series when they make the transition to PCV13.

The Advisory Committee on Immunization Practices (ACIP) recommendations on how many doses of PCV13 a child should receive depend now on the age at which the first PCV vaccine was received (either PCV7 or PCV13), the number of doses of each received, and the presence or absence of high-risk medical conditions. These recommendations are summarized below and illustrated in TABLE 1 and TABLE 2.

TABLE 1
PCV13: Routine vaccination schedule

Age at first dose	Primary series*	Booster dose†
2-6 months	3 doses	1 dose, 12-15 months
7-11 months	2 doses	1 dose, 12-15 months
12-23 months	2 doses	None
24-59 months, healthy children	1 dose	None
24-71 months for children with certain chronic diseases or immunocompromising conditions (see TABLE 3)	2 doses	None
*Minimum interval between doses is 8 weeks, except for children vaccinated at <12 months for whom the minimum interval is 4 weeks. Minimum age for first dose is 6 weeks.
†Given at least 8 weeks after previous dose.
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.1

TABLE 2
In transition: From PCV7 to PCV13

Infant series			Booster dose	Supplemental PCV13 dose
2 months	4 months	6 months	≥12 months*	14-59 months†
PCV7	PCV13	PCV13	PCV13	None
PCV7	PCV7	PCV13	PCV13	None
PCV7	PCV7	PCV7	PCV13	None
PCV7	PCV7	PCV7	PCV7	PCV13
*No additional PCV13 doses are indicated for children ages 12-23 months who have received 2 or 3 doses of PCV before age 12 months and at least 1 dose of PCV13 at ≥12 months.
†For children with underlying medical conditions (see TABLE 3), a single supplemental PCV13 dose is recommended through age 71 months.
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.1

For a child who started PCV7 on time and is in mid series, the recommendation is to simply finish the series with PCV13.

If a child has completed a series of PCV7, the recommendation is to give him or her 1 dose of PCV13 up to age 59 months. (If the child has a chronic underlying medical condition, this age is extended to 71 months.¹)

 

Infants between the ages of 1 and 6 months who have never received any PCV product should complete a series of PCV13 at 2, 4, 6, and 12 to 15 months—the same time line as the PCV7 series.

Children ages 7 to 59 months who have not been vaccinated with PCV7 or PCV13 previously should receive 1 to 3 doses of PCV13, depending on their age at the time when vaccination begins and whether underlying medical conditions are present (TABLE 3).

Healthy children ages 24 to 59 months without previous PCV vaccine should receive 1 dose of PCV13.

Children ages 24 to 71 months without previous PCV vaccine who have a chronic medical condition that increases their risk for pneumococcal disease should receive 2 doses of PCV13, 8 weeks apart.¹

TABLE 3
Underlying conditions that place kids at risk for pneumococcal disease

Risk group	Condition
Immunocompetent children	Chronic heart disease*
	Chronic lung disease†
	Diabetes mellitus
	Cerebrospinal fluid leaks
	Cochlear implant
Children with functional or anatomic asplenia	Sickle cell disease and other hemoglobulinopathies
	Congenital or acquired asplenia or splenic dysfunction
Children with immunocompromising conditions	HIV infection
	Chronic renal failure and nephrotic syndrome
	Diseases associated with immunosuppressive drugs or radiation therapy, including malignant neoplasms, leukemias, lymphomas, and Hodgkin’s disease; or solid organ transplantation
	Congenital immunodeficiency‡
*Particularly cyanotic congenital heart disease and cardiac failure.
†Including asthma if treated with prolonged high-dose oral corticosteroids.
‡Includes B- (humoral) or T-lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phagocytic disorders (excluding chronic granulomatous disease).
Source: CDC. MMWR Morb Mortal Wkly Rep. 2010.1

Recommendations for children at higher risk

Provisional recommendations from ACIP advise that children 2 through 18 years of age at increased risk for invasive pneumococcal disease should also receive 23-valent pneumococcal polysaccharide vaccine (PPSV23). Ideally, the child should have received all of the recommended doses of PCV13 before the physician administers PPSV23, with a minimum interval of at least 8 weeks after the last dose of PCV13.

However, some children will have previously received PPSV23. They should also receive the recommended PCV13 doses. A second dose of PPSV23 is recommended 5 years after the first dose of PPSV23 for children who have sickle cell disease, or functional or anatomic asplenia, human immunodeficiency virus (HIV) infection, or other immunocompromising conditions. No more than 2 PPSV23 doses are recommended.⁹

The ACIP provisional recommendations also say that a single dose of PCV13 may be administered to children ages 6 to 18 years who are at increased risk for IPD because of sickle cell disease, HIV infection or other immunocompromising condition, cochlear implant, or cerebrospinal fluid leaks, regardless of whether they have previously received PCV7 or PPSV23.⁹ This, however, is an off-label recommendation.

The usual contraindications
PCV13 is contraindicated among individuals known to have a severe allergic reaction to any component of PCV13 or PCV7 or to any diphtheria toxoid-containing vaccine, because the pneumococcal antigens are conjugated to a diphtheria carrier protein.¹

A useful vaccine, with its share of challenges

The pneumococcal conjugate vaccine combats infections such as pneumococcal pneumonia and meningitis, which are potentially serious—even though their incidence is relatively low.

The vaccine’s high private-sector cost—reported by the manufacturer to the CDC as $435 for the full, 4-dose series of PCV13—can be a drawback for the family physician trying to keep a full array of vaccine products on hand.¹⁰ Eligible low-income and uninsured children can receive free vaccine under the federal Vaccines for Children Program, and providers who choose to enroll in the program can access free vaccines and may charge for the expense of administering them.¹¹

With this hurdle overcome, the remaining challenge for physicians will be to stay on top of the complicated dosing schedule.

Late in 2009, a change in the recommendations of the US Preventive Services Task Force (USPSTF) brought more public attention to this panel than it had ever experienced before. This publicity centered on revised recommendations on breast cancer screening that pointed out that mammograms benefit a few women under 50, but are also associated with some harms. The Task Force recommended that patients and physicians discuss these potential benefits and harms and make an individual decision about whether to have a mammogram.¹

Even though the criticism was loud—and harsh—from some sectors, many professional organizations, including the American Academy of Family Physicians, the American College of Physicians, and the American College of Preventive Medicine, came to the defense of the Task Force and its rigorous, evidence-based methodology.^2-4 Both the Journal of the American Medical Association and the Annals of Internal Medicine have since published a series of articles and opinions on the controversy, most of them favorable to the Task Force and its methods.^2-9

Lost in all the brouhaha were a number of other, less controversial recommendations that the Task Force made in 2009 (and early 2010). You can find them at www.ahrq.gov/clinic/uspstfix.htm. They are categorized by strength of recommendation (TABLE 1) and listed in TABLES 2 and 3. Family physicians should review the A and B recommendations and try to incorporate those into practice. At the same time, we should avoid services in the D category, as the evidence is strong that they are not effective or cause more harm than benefit. The C and I recommendations leave more discretion for physicians and patients to decide on these interventions based on personal values and risks. A C recommendation means the service can benefit some individuals, but the totality of benefit is small. An I recommendation means that evidence is insufficient to evaluate benefits vs harms.

TABLE 1
US Preventive Services Task Force recommendation categories

Grade	Definition
A	The USPSTF recommends the service. There is high certainty that the net benefit is substantial.
B	The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.
C	The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.
D	The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.
I	The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.
Source: Agency for Healthcare Research and Quality. US Preventive Services Task Force (USPSTF) ratings. Available at: http://www.uspreventiveservicestaskforce.org/uspstf07/ratingsv2.htm. Accessed September 5, 2013.

TABLE 2
USPSTF recommends FOR

CARDIOVASCULAR DISEASE PREVENTION
Using aspirin for men 45 to 79 years of age, when the potential benefit due to a reduction in myocardial infarctions (MIs) outweighs the potential harm due to an increase in gastrointestinal (GI) hemorrhage (A). Using aspirin for women 55 to 79 years of age when the potential benefit of a reduction in ischemic strokes outweighs the potential harm of an increase in GI hemorrhage (A). Asking all adults about tobacco use and providing tobacco cessation interventions for those who use tobacco products (A).
PREGNANCY
Asking all pregnant women about tobacco use and providing augmented, pregnancy-tailored counseling for those who smoke (A). Using a daily supplement containing 0.4 to 0.8 mg (400-800 mcg) folic acid for all women planning or capable of pregnancy (A). Screening pregnant women for hepatitis B virus (HBV) infection at their first prenatal visit (A). Screening all pregnant women for syphilis infection (A).
CANCER SCREENING
Using biennial screening mammography for women who are 50 to 74 years of age (B).
DEPRESSION
Screening adults for depression when staff-assisted depression care supports are in place to assure accurate diagnosis, effective treatment, and follow-up (B). Screening adolescents (12-18 years of age) for major depressive disorder when systems are in place to ensure accurate diagnosis, psychotherapy (cognitive-behavioral or interpersonal), and follow-up (B).
OBESITY
Screening children who are ≥6 years for obesity and offering or referring for comprehensive, intensive behavioral interventions to promote improvement in weight status (B).

TABLE 3
USPSTF recommends AGAINST routinely

Screening women <50 years with biennial mammography. This should be an individual decision that takes patient context into account, including the patient’s values regarding specific benefits and harms. Screening adults for depression when staff-assisted depression care supports are not in place. There may be considerations that support screening for depression in an individual patient.
USPSTF recommends AGAINST
Using aspirin for stroke prevention in women <55 years and for MI prevention in men <45 years. Teaching women breast self-examination.
USPSTF indicates the evidence is INSUFFICIENT to assess the balance of benefits and harms of
Screening asymptomatic men and women with no history of coronary heart disease (CHD) using nontraditional risk factors to prevent CHD events. Nontraditional risk factors are high-sensitivity C-reactive protein, ankle–brachial index, leukocyte count, fasting blood glucose level, periodontal disease, carotid intima–media thickness, coronary artery calcification score on electron-beam computed tomography, homocysteine level, and lipoprotein(a) level. Using aspirin for cardiovascular disease prevention in men and women who are ≥80 years. Using screening mammography in women ≥75 years. Performing clinical breast examination in addition to screening mammography in women ≥40 years. Using either digital mammography or magnetic resonance imaging instead of film mammography as screening modalities for breast cancer. Screening children (7-11 years of age) for depression. Screening infants for hyperbilirubinemia to prevent chronic bilirubin encephalopathy. Screening for visual acuity for the improvement of functional outcomes in older adults. Using whole-body skin examination by a primary care clinician, or patient skin self-examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer in the adult general population.
Source: Agency for Healthcare Research and Quality. Available at: www.ahrq.gov/clinic/uspstfix.htm. Accessed April 2, 2010.

 

The A and B recommendations you may have missed

The major additions to the A and B recommendations pertained to the use of aspirin to prevent cardiovascular disease, routine screening for depression in adults and adolescents, and screening for obesity in children ages 6 and older. The other recommendations in these categories were reaffirmations of previous recommendations (asking about smoking and providing smoking cessation guidance to adults and pregnant women, advising folic acid supplementation for women planning or capable of pregnancy, and screening pregnant women for syphilis and hepatitis B virus) and the more controversial recommendation for biennial rather than annual mammography for women ages 50 to 74.

The use of aspirin to prevent myocardial infarction in men ages 45 to 79 and ischemic strokes in women ages 55 to 79 was endorsed if a patient’s risk of these cardiovascular events exceeds the risk of bleeding from regular aspirin use. The Task Force recommendation statement is available athttp://www.ahrq.gov/clinic/uspstf09/aspirincvd/aspcvdrs.htmand provides links to tools for calculating the risk of a myocardial infarction (MI) and ischemic stroke, as well as 2 tables to compare the risks and benefits of aspirin therapy for prevention.

Screening adults for depression is endorsed if “staff-assisted depression care supports” are in place to assure accurate diagnosis, effective treatment, and follow-up. Such support includes the presence of clinical staff members who can assist the primary care provider with care support or coordination, case management, or mental health treatment. The definition can be accessed athttp://www.ahrq.gov/clinic/uspstf09/adultdepression/addeprrs.htm.

One example in the statement describes “a successful study designed for practices without ready access to mental health specialty care, (in which) office staff recruited, screened, and enrolled participants who screened positive for depression before a clinic visit. If the physician confirmed the depression diagnosis, the participant was scheduled for a return visit with the physician and to meet with the nurse specialist in 1 week. The nurse specialist reassessed the patient’s level of depression, discussed treatment options and preferences, and asked the participant to complete a homework assignment. Participants completed up to 8 additional sessions that followed the same pattern, either by phone or in person.”

Screening for major depressive disorder (MDD) in adolescents 12 to 18 years of age is recommended when systems are in place to ensure accurate diagnosis, psychotherapy (cognitive-behavioral or interpersonal), and follow-up. The Task Force addressed screening for MDD only—not for less severe depression. The instruments the group recommended using included the Patient Health Questionnaire for Adolescents (PHQ-A) and the Beck Depression Inventory-Primary Care Version (BDI-PC).

The recommendation for screening for obesity in children ages 6 and older reflects the difficulty in achieving long-term, sustainable weight loss in this group. Effective comprehensive weight-management programs include counseling and other interventions that target both diet and physical activity. Behavioral interventions and parental involvement are also encouraged. Moderate- to high-intensity programs include more than 25 hours of contact with the child and/or the family over a 6-month period; less than this does not result in sustained improvement.

What about the D and I categories?

Two interventions received a D recommendation: Use of aspirin for stroke prevention in women <55 years and for MI prevention in men <45 years, and teaching breast self-examination (BSE) to women. The BSE recommendation has been misinterpreted as recommending against women performing self-breast exams. The recommendation is against formalized teaching of the procedure by physicians, as this leads to increased false positives and no improvement in outcomes when compared to women performing exams on their own.

The list of interventions receiving an I recommendation include some services that are commonly offered in the belief that they are effective. The Task Force is attempting to develop methodologies to decrease the number of interventions that receive an I recommendation. Currently, about 40% of all recommendations end up in this category, and physicians and patients alike could use more guidance on them. This plethora of recommendations made with insufficient evidence reflects the “ready, shoot, aim” philosophy of American medicine. We tend to accept and adopt new interventions before they are proven effective. The I recommendations are valuable reminders that, while many interventions are in common use, we often do not know as much as we should about their benefits and harms.

Late in 2009, a change in the recommendations of the US Preventive Services Task Force (USPSTF) brought more public attention to this panel than it had ever experienced before. This publicity centered on revised recommendations on breast cancer screening that pointed out that mammograms benefit a few women under 50, but are also associated with some harms. The Task Force recommended that patients and physicians discuss these potential benefits and harms and make an individual decision about whether to have a mammogram.¹

Even though the criticism was loud—and harsh—from some sectors, many professional organizations, including the American Academy of Family Physicians, the American College of Physicians, and the American College of Preventive Medicine, came to the defense of the Task Force and its rigorous, evidence-based methodology.^2-4 Both the Journal of the American Medical Association and the Annals of Internal Medicine have since published a series of articles and opinions on the controversy, most of them favorable to the Task Force and its methods.^2-9

Lost in all the brouhaha were a number of other, less controversial recommendations that the Task Force made in 2009 (and early 2010). You can find them at www.ahrq.gov/clinic/uspstfix.htm. They are categorized by strength of recommendation (TABLE 1) and listed in TABLES 2 and 3. Family physicians should review the A and B recommendations and try to incorporate those into practice. At the same time, we should avoid services in the D category, as the evidence is strong that they are not effective or cause more harm than benefit. The C and I recommendations leave more discretion for physicians and patients to decide on these interventions based on personal values and risks. A C recommendation means the service can benefit some individuals, but the totality of benefit is small. An I recommendation means that evidence is insufficient to evaluate benefits vs harms.

TABLE 1
US Preventive Services Task Force recommendation categories

Grade	Definition
A	The USPSTF recommends the service. There is high certainty that the net benefit is substantial.
B	The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.
C	The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.
D	The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.
I	The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.
Source: Agency for Healthcare Research and Quality. US Preventive Services Task Force (USPSTF) ratings. Available at: http://www.uspreventiveservicestaskforce.org/uspstf07/ratingsv2.htm. Accessed September 5, 2013.

TABLE 2
USPSTF recommends FOR

CARDIOVASCULAR DISEASE PREVENTION
Using aspirin for men 45 to 79 years of age, when the potential benefit due to a reduction in myocardial infarctions (MIs) outweighs the potential harm due to an increase in gastrointestinal (GI) hemorrhage (A). Using aspirin for women 55 to 79 years of age when the potential benefit of a reduction in ischemic strokes outweighs the potential harm of an increase in GI hemorrhage (A). Asking all adults about tobacco use and providing tobacco cessation interventions for those who use tobacco products (A).
PREGNANCY
Asking all pregnant women about tobacco use and providing augmented, pregnancy-tailored counseling for those who smoke (A). Using a daily supplement containing 0.4 to 0.8 mg (400-800 mcg) folic acid for all women planning or capable of pregnancy (A). Screening pregnant women for hepatitis B virus (HBV) infection at their first prenatal visit (A). Screening all pregnant women for syphilis infection (A).
CANCER SCREENING
Using biennial screening mammography for women who are 50 to 74 years of age (B).
DEPRESSION
Screening adults for depression when staff-assisted depression care supports are in place to assure accurate diagnosis, effective treatment, and follow-up (B). Screening adolescents (12-18 years of age) for major depressive disorder when systems are in place to ensure accurate diagnosis, psychotherapy (cognitive-behavioral or interpersonal), and follow-up (B).
OBESITY
Screening children who are ≥6 years for obesity and offering or referring for comprehensive, intensive behavioral interventions to promote improvement in weight status (B).

TABLE 3
USPSTF recommends AGAINST routinely

Screening women <50 years with biennial mammography. This should be an individual decision that takes patient context into account, including the patient’s values regarding specific benefits and harms. Screening adults for depression when staff-assisted depression care supports are not in place. There may be considerations that support screening for depression in an individual patient.
USPSTF recommends AGAINST
Using aspirin for stroke prevention in women <55 years and for MI prevention in men <45 years. Teaching women breast self-examination.
USPSTF indicates the evidence is INSUFFICIENT to assess the balance of benefits and harms of
Screening asymptomatic men and women with no history of coronary heart disease (CHD) using nontraditional risk factors to prevent CHD events. Nontraditional risk factors are high-sensitivity C-reactive protein, ankle–brachial index, leukocyte count, fasting blood glucose level, periodontal disease, carotid intima–media thickness, coronary artery calcification score on electron-beam computed tomography, homocysteine level, and lipoprotein(a) level. Using aspirin for cardiovascular disease prevention in men and women who are ≥80 years. Using screening mammography in women ≥75 years. Performing clinical breast examination in addition to screening mammography in women ≥40 years. Using either digital mammography or magnetic resonance imaging instead of film mammography as screening modalities for breast cancer. Screening children (7-11 years of age) for depression. Screening infants for hyperbilirubinemia to prevent chronic bilirubin encephalopathy. Screening for visual acuity for the improvement of functional outcomes in older adults. Using whole-body skin examination by a primary care clinician, or patient skin self-examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer in the adult general population.
Source: Agency for Healthcare Research and Quality. Available at: www.ahrq.gov/clinic/uspstfix.htm. Accessed April 2, 2010.

 

The A and B recommendations you may have missed

The major additions to the A and B recommendations pertained to the use of aspirin to prevent cardiovascular disease, routine screening for depression in adults and adolescents, and screening for obesity in children ages 6 and older. The other recommendations in these categories were reaffirmations of previous recommendations (asking about smoking and providing smoking cessation guidance to adults and pregnant women, advising folic acid supplementation for women planning or capable of pregnancy, and screening pregnant women for syphilis and hepatitis B virus) and the more controversial recommendation for biennial rather than annual mammography for women ages 50 to 74.

The use of aspirin to prevent myocardial infarction in men ages 45 to 79 and ischemic strokes in women ages 55 to 79 was endorsed if a patient’s risk of these cardiovascular events exceeds the risk of bleeding from regular aspirin use. The Task Force recommendation statement is available athttp://www.ahrq.gov/clinic/uspstf09/aspirincvd/aspcvdrs.htmand provides links to tools for calculating the risk of a myocardial infarction (MI) and ischemic stroke, as well as 2 tables to compare the risks and benefits of aspirin therapy for prevention.

Screening adults for depression is endorsed if “staff-assisted depression care supports” are in place to assure accurate diagnosis, effective treatment, and follow-up. Such support includes the presence of clinical staff members who can assist the primary care provider with care support or coordination, case management, or mental health treatment. The definition can be accessed athttp://www.ahrq.gov/clinic/uspstf09/adultdepression/addeprrs.htm.

One example in the statement describes “a successful study designed for practices without ready access to mental health specialty care, (in which) office staff recruited, screened, and enrolled participants who screened positive for depression before a clinic visit. If the physician confirmed the depression diagnosis, the participant was scheduled for a return visit with the physician and to meet with the nurse specialist in 1 week. The nurse specialist reassessed the patient’s level of depression, discussed treatment options and preferences, and asked the participant to complete a homework assignment. Participants completed up to 8 additional sessions that followed the same pattern, either by phone or in person.”

Screening for major depressive disorder (MDD) in adolescents 12 to 18 years of age is recommended when systems are in place to ensure accurate diagnosis, psychotherapy (cognitive-behavioral or interpersonal), and follow-up. The Task Force addressed screening for MDD only—not for less severe depression. The instruments the group recommended using included the Patient Health Questionnaire for Adolescents (PHQ-A) and the Beck Depression Inventory-Primary Care Version (BDI-PC).

The recommendation for screening for obesity in children ages 6 and older reflects the difficulty in achieving long-term, sustainable weight loss in this group. Effective comprehensive weight-management programs include counseling and other interventions that target both diet and physical activity. Behavioral interventions and parental involvement are also encouraged. Moderate- to high-intensity programs include more than 25 hours of contact with the child and/or the family over a 6-month period; less than this does not result in sustained improvement.

What about the D and I categories?

Two interventions received a D recommendation: Use of aspirin for stroke prevention in women <55 years and for MI prevention in men <45 years, and teaching breast self-examination (BSE) to women. The BSE recommendation has been misinterpreted as recommending against women performing self-breast exams. The recommendation is against formalized teaching of the procedure by physicians, as this leads to increased false positives and no improvement in outcomes when compared to women performing exams on their own.

The list of interventions receiving an I recommendation include some services that are commonly offered in the belief that they are effective. The Task Force is attempting to develop methodologies to decrease the number of interventions that receive an I recommendation. Currently, about 40% of all recommendations end up in this category, and physicians and patients alike could use more guidance on them. This plethora of recommendations made with insufficient evidence reflects the “ready, shoot, aim” philosophy of American medicine. We tend to accept and adopt new interventions before they are proven effective. The I recommendations are valuable reminders that, while many interventions are in common use, we often do not know as much as we should about their benefits and harms.

Late in 2009, a change in the recommendations of the US Preventive Services Task Force (USPSTF) brought more public attention to this panel than it had ever experienced before. This publicity centered on revised recommendations on breast cancer screening that pointed out that mammograms benefit a few women under 50, but are also associated with some harms. The Task Force recommended that patients and physicians discuss these potential benefits and harms and make an individual decision about whether to have a mammogram.¹

Even though the criticism was loud—and harsh—from some sectors, many professional organizations, including the American Academy of Family Physicians, the American College of Physicians, and the American College of Preventive Medicine, came to the defense of the Task Force and its rigorous, evidence-based methodology.^2-4 Both the Journal of the American Medical Association and the Annals of Internal Medicine have since published a series of articles and opinions on the controversy, most of them favorable to the Task Force and its methods.^2-9

Lost in all the brouhaha were a number of other, less controversial recommendations that the Task Force made in 2009 (and early 2010). You can find them at www.ahrq.gov/clinic/uspstfix.htm. They are categorized by strength of recommendation (TABLE 1) and listed in TABLES 2 and 3. Family physicians should review the A and B recommendations and try to incorporate those into practice. At the same time, we should avoid services in the D category, as the evidence is strong that they are not effective or cause more harm than benefit. The C and I recommendations leave more discretion for physicians and patients to decide on these interventions based on personal values and risks. A C recommendation means the service can benefit some individuals, but the totality of benefit is small. An I recommendation means that evidence is insufficient to evaluate benefits vs harms.

TABLE 1
US Preventive Services Task Force recommendation categories

Grade	Definition
A	The USPSTF recommends the service. There is high certainty that the net benefit is substantial.
B	The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.
C	The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.
D	The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.
I	The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.
Source: Agency for Healthcare Research and Quality. US Preventive Services Task Force (USPSTF) ratings. Available at: http://www.uspreventiveservicestaskforce.org/uspstf07/ratingsv2.htm. Accessed September 5, 2013.

TABLE 2
USPSTF recommends FOR

CARDIOVASCULAR DISEASE PREVENTION
Using aspirin for men 45 to 79 years of age, when the potential benefit due to a reduction in myocardial infarctions (MIs) outweighs the potential harm due to an increase in gastrointestinal (GI) hemorrhage (A). Using aspirin for women 55 to 79 years of age when the potential benefit of a reduction in ischemic strokes outweighs the potential harm of an increase in GI hemorrhage (A). Asking all adults about tobacco use and providing tobacco cessation interventions for those who use tobacco products (A).
PREGNANCY
Asking all pregnant women about tobacco use and providing augmented, pregnancy-tailored counseling for those who smoke (A). Using a daily supplement containing 0.4 to 0.8 mg (400-800 mcg) folic acid for all women planning or capable of pregnancy (A). Screening pregnant women for hepatitis B virus (HBV) infection at their first prenatal visit (A). Screening all pregnant women for syphilis infection (A).
CANCER SCREENING
Using biennial screening mammography for women who are 50 to 74 years of age (B).
DEPRESSION
Screening adults for depression when staff-assisted depression care supports are in place to assure accurate diagnosis, effective treatment, and follow-up (B). Screening adolescents (12-18 years of age) for major depressive disorder when systems are in place to ensure accurate diagnosis, psychotherapy (cognitive-behavioral or interpersonal), and follow-up (B).
OBESITY
Screening children who are ≥6 years for obesity and offering or referring for comprehensive, intensive behavioral interventions to promote improvement in weight status (B).

TABLE 3
USPSTF recommends AGAINST routinely

Screening women <50 years with biennial mammography. This should be an individual decision that takes patient context into account, including the patient’s values regarding specific benefits and harms. Screening adults for depression when staff-assisted depression care supports are not in place. There may be considerations that support screening for depression in an individual patient.
USPSTF recommends AGAINST
Using aspirin for stroke prevention in women <55 years and for MI prevention in men <45 years. Teaching women breast self-examination.
USPSTF indicates the evidence is INSUFFICIENT to assess the balance of benefits and harms of
Screening asymptomatic men and women with no history of coronary heart disease (CHD) using nontraditional risk factors to prevent CHD events. Nontraditional risk factors are high-sensitivity C-reactive protein, ankle–brachial index, leukocyte count, fasting blood glucose level, periodontal disease, carotid intima–media thickness, coronary artery calcification score on electron-beam computed tomography, homocysteine level, and lipoprotein(a) level. Using aspirin for cardiovascular disease prevention in men and women who are ≥80 years. Using screening mammography in women ≥75 years. Performing clinical breast examination in addition to screening mammography in women ≥40 years. Using either digital mammography or magnetic resonance imaging instead of film mammography as screening modalities for breast cancer. Screening children (7-11 years of age) for depression. Screening infants for hyperbilirubinemia to prevent chronic bilirubin encephalopathy. Screening for visual acuity for the improvement of functional outcomes in older adults. Using whole-body skin examination by a primary care clinician, or patient skin self-examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer in the adult general population.
Source: Agency for Healthcare Research and Quality. Available at: www.ahrq.gov/clinic/uspstfix.htm. Accessed April 2, 2010.

 

The A and B recommendations you may have missed

The major additions to the A and B recommendations pertained to the use of aspirin to prevent cardiovascular disease, routine screening for depression in adults and adolescents, and screening for obesity in children ages 6 and older. The other recommendations in these categories were reaffirmations of previous recommendations (asking about smoking and providing smoking cessation guidance to adults and pregnant women, advising folic acid supplementation for women planning or capable of pregnancy, and screening pregnant women for syphilis and hepatitis B virus) and the more controversial recommendation for biennial rather than annual mammography for women ages 50 to 74.

The use of aspirin to prevent myocardial infarction in men ages 45 to 79 and ischemic strokes in women ages 55 to 79 was endorsed if a patient’s risk of these cardiovascular events exceeds the risk of bleeding from regular aspirin use. The Task Force recommendation statement is available athttp://www.ahrq.gov/clinic/uspstf09/aspirincvd/aspcvdrs.htmand provides links to tools for calculating the risk of a myocardial infarction (MI) and ischemic stroke, as well as 2 tables to compare the risks and benefits of aspirin therapy for prevention.

Screening adults for depression is endorsed if “staff-assisted depression care supports” are in place to assure accurate diagnosis, effective treatment, and follow-up. Such support includes the presence of clinical staff members who can assist the primary care provider with care support or coordination, case management, or mental health treatment. The definition can be accessed athttp://www.ahrq.gov/clinic/uspstf09/adultdepression/addeprrs.htm.

One example in the statement describes “a successful study designed for practices without ready access to mental health specialty care, (in which) office staff recruited, screened, and enrolled participants who screened positive for depression before a clinic visit. If the physician confirmed the depression diagnosis, the participant was scheduled for a return visit with the physician and to meet with the nurse specialist in 1 week. The nurse specialist reassessed the patient’s level of depression, discussed treatment options and preferences, and asked the participant to complete a homework assignment. Participants completed up to 8 additional sessions that followed the same pattern, either by phone or in person.”

Screening for major depressive disorder (MDD) in adolescents 12 to 18 years of age is recommended when systems are in place to ensure accurate diagnosis, psychotherapy (cognitive-behavioral or interpersonal), and follow-up. The Task Force addressed screening for MDD only—not for less severe depression. The instruments the group recommended using included the Patient Health Questionnaire for Adolescents (PHQ-A) and the Beck Depression Inventory-Primary Care Version (BDI-PC).

The recommendation for screening for obesity in children ages 6 and older reflects the difficulty in achieving long-term, sustainable weight loss in this group. Effective comprehensive weight-management programs include counseling and other interventions that target both diet and physical activity. Behavioral interventions and parental involvement are also encouraged. Moderate- to high-intensity programs include more than 25 hours of contact with the child and/or the family over a 6-month period; less than this does not result in sustained improvement.

What about the D and I categories?

Two interventions received a D recommendation: Use of aspirin for stroke prevention in women <55 years and for MI prevention in men <45 years, and teaching breast self-examination (BSE) to women. The BSE recommendation has been misinterpreted as recommending against women performing self-breast exams. The recommendation is against formalized teaching of the procedure by physicians, as this leads to increased false positives and no improvement in outcomes when compared to women performing exams on their own.

The list of interventions receiving an I recommendation include some services that are commonly offered in the belief that they are effective. The Task Force is attempting to develop methodologies to decrease the number of interventions that receive an I recommendation. Currently, about 40% of all recommendations end up in this category, and physicians and patients alike could use more guidance on them. This plethora of recommendations made with insufficient evidence reflects the “ready, shoot, aim” philosophy of American medicine. We tend to accept and adopt new interventions before they are proven effective. The I recommendations are valuable reminders that, while many interventions are in common use, we often do not know as much as we should about their benefits and harms.

The past 10 years have seen marked advances in vaccine research, resulting in more products being available. In 1983 the childhood vaccination schedule included protection against seven diseases: polio, tetanus, diphtheria, pertussis, measles, mumps, and rubella. The schedule in 2010 includes protection against organisms that cause seven more: Haemophilus influenzae, hepatitis A, hepatitis B, influenza, meningococcus, pneumococcus, and varicella.¹ In addition, new vaccine products are available for adolescents, offering protection against meningococcus, seasonal influenza, and human papillomavirus (HPV) and extending the length of protection against pertussis. For adults, a vaccine now protects against shingles, and several products offer boosting of pertussis immunity.

This rapid growth in the number of recommended vaccine products has made it challenging for practicing physicians to stay current on and to implement the ever-changing recommendations. The purpose of this article is to summarize the additions and changes over the past 3 years to the schedules of recommended vaccines for children, adolescents, and adults.

VACCINE UPDATE FOR CHILDREN

The recent changes to the childhood immunization schedule have added protection against rotavirus and seasonal influenza and have expanded the protection against hepatitis A and varicella.

Rotavirus vaccination for infants

Rotavirus is the leading cause of infectious gastroenteritis in infants. It causes significant morbidity and expense, accounting for 2.7 million episodes per year in the United States, 410,000 outpatient or office visits, 201,000 to 272,000 emergency department visits, 55,000 to 70,000 hospitalizations, and 20 to 60 deaths.² Although the number of deaths in the United States is not large, rotavirus is a leading cause of infant deaths around the world.

A rotavirus vaccine was first introduced in the United States in 1998 but was withdrawn from the market in less than a year due to risk of intussusception, which occurred in 1 per 10,000 infants vaccinated.² Two different rotavirus vaccines have recently been approved by the US Food and Drug Administration: a five-antigen vaccine (RV5; RotaTeq) in 2006 and a single-antigen vaccine (RV1; Rotarix) in 2008. Both are modified live-virus vaccines, given orally. They contain different antigens and have different schedules of administration— RV5 requires three doses, while RV1 requires two doses. Table 1 summarizes the characteristics of each product.

Rotavirus vaccination is challenging because of the time frame in which the series needs to be given. The first dose has to be given after 6 weeks of age but before 15 weeks of age, and the last dose should be given before 8 months of age, with a minimum of 4 weeks between doses. It is preferable to use the same product to finish the series. They can be used interchangeably, but this then requires three total doses.

The effectiveness of the vaccine in preventing rotavirus gastroenteritis in the first year after vaccination was greater than 80% in most studies and approached 100% in preventing serious gastroenteritis.²

Those vaccinated appear to have a slightly higher rate of diarrhea and vomiting in the first 42 days after vaccination. Safety monitoring after the products were licensed has not shown an increased rate of intussusception with either product.

The only contraindication to the vaccines is a serious allergic reaction to them or to one of their components. They should be used with caution in patients who have suppressed immunity, acute gastroenteritis, preexisting gastrointestinal disease, or previous intussusception.

 

 

Seasonal influenza vaccine extended to ages 5–18

Gradually, we seem to be moving toward vaccinating everyone every year against seasonal influenza. Previously, vaccination was recommended for children age 6 months through 4 years; in 2008, the Advisory Committee on Immunization Practices (ACIP) extended the recommendation to the age group 5 through 18 years.³

Two types of seasonal influenza vaccine are available: trivalent influenza vaccine (TIV), which contains killed virus and is given by injection, and live-attenuated seasonal influenza vaccine (LAIV), which is given by nasal spray. Both contain the same three seasonal influenza antigens, selected each year by a team of experts. TIV is licensed for those age 6 months and older, and LAIV is licensed for ages 2 through 49 years.⁴

Since LAIV contains a live-attenuated virus, it should not be used in anyone who has a chronic illness (including those under the age of 5 with recurrent wheezing, those with suppressed immunity, and those with a history of Guillain-Barré syndrome); in pregnant women; or those who have close contact with anyone who is immune-suppressed. The injection is contraindicated for those who have had a serious allergic reaction to eggs.

Children younger than 9 years should receive two doses of either type of vaccine the first year they are vaccinated. Those who receive only one dose the first year they are vaccinated should receive two doses the next year. If they fail to receive two doses in the next year, only a single dose is recommended after that. This is a slight modification of the previous recommendation that only one dose be given the second year if only one dose was given the first year.⁵

Hepatitis A vaccine at age 12–23 months

An inactivated hepatitis A vaccine (HepA) was first licensed in 1995; another was licensed in 1996. Recommendations for their use have been revised periodically, and their widespread use has resulted in a marked reduction in the incidence of hepatitis A virus infection.

The current recommendation is that all children be vaccinated at age 12 to 23 months. In addition, in areas of high prevalence, vaccine is recommended for older children who have not been vaccinated. Other target groups are those at higher risk of hepatitis A, including travelers to endemic areas, users of illicit drugs, and men who have sex with men.⁶ Indications for vaccination before travel, after exposure to hepatitis A infection, and in families of international adoptees are covered later in this paper in a discussion about vaccinations in adults.

Varicella at 12–15 months and 4–6 years, with catch-up for others

Before varicella vaccine was licensed in 1995, 4 million cases of varicella infection (chickenpox) were reported in the United States each year, resulting in thousands of hospitalizations and more than 100 deaths. The vaccine is now widely used, with a coverage rate of 88%, and it has proven to be 85% effective.⁷ The result was a marked decrease in the incidence of varicella and in varicella-related hospitalizations and deaths.

In spite of this success, the number of varicella cases has remained constant over the past few years, and sporadic outbreaks continue to occur, predominantly in schools, even schools in which a high percentage of the children are vaccinated.^7,8 These outbreaks have involved infections in unvaccinated children and also “breakthrough disease” in children who have been vaccinated. If someone who has received one dose of vaccine is exposed to varicella, the risk of a breakthrough infection is about 15%.⁹ A two-dose series of varicella vaccine reduces the risk by about 75%.⁷ Breakthrough disease is usually milder than infection in the unvaccinated, with fewer skin lesions, milder symptoms, and fewer complications, but those affected are still infectious to others.

In 2005 and 2006, this ongoing risk of varicella prompted the ACIP to consider and recommend several new control measures:

• Two doses of varicella vaccine for all children, the first dose at age 12 to 15 months and the second at age 4 to 6 years—the same schedule as for immunization against measles, mumps, and rubella
• Two doses of varicella vaccine, the second given 4 to 8 weeks after the first, for all adolescents and adults who have no evidence of immunity
• A catch-up second dose for everyone who received one dose previously
• Screening for varicella immunity in pregnant women and postpartum vaccination with two doses for those who are not immune, the first dose given before discharge and the second dose 4 to 8 weeks later.

 

VACCINE UPDATE FOR ADOLESCENTS

A number of vaccines are now available and recommended for routine use in adolescents.⁹ These include HPV vaccine for girls, quadrivalent meningococcal conjugate vaccine (MCV4), and combined tetanus toxoid, reduced-dose diphtheria toxoid, and acellular pertussis (Tdap). All these are now recommended routinely at age 11 or 12. Seasonal influenza vaccine is recommended annually through age 18.

For the next decade, a catch-up varicella booster will also be recommended for adolescents because of waning varicella immunity from a single dose. Adolescents should also receive some catch-up vaccines if they did not receive them in childhood and should be considered for some vaccines that are recommended on the basis of risk. Table 2 lists the vaccines that should be considered during a clinical visit for those age 11 through 18 years.

Meningococcal conjugate vaccine for all at age 11–18

In 2007, the ACIP recommended MCV4 for all at age 11 through 18 at the earliest opportunity. ¹⁰ For those who remain at high risk (Table 3) and who were vaccinated with either MCV4 or the meningococcal polysaccharide vaccine (MPSV4), a booster is recommended after 3 years (if vaccinated before age 7), and after 5 years if vaccinated age 7 and up. College freshman who were vaccinated with MCV4 do not need a booster dose.

There is some evidence that MCV4 may be linked to a small risk of Guillain-Barré syndrome. Although this link has not been conclusively proven, a history of Guillain-Barré syndrome calls for caution in using MCV4. For those who have a history of this syndrome but need protection against meningococcal infection, the MPSV4 is an alternative.¹¹

Pertussis: A Tdap booster at age 11–18

From Broder KR, et al; ACIP. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the ACIP. MMWR Recomm Rep 2006; 55(RR–3):1–34

The incidence of pertussis in the United States declined dramatically after pertussis vaccine was introduced in the 1940s. Before then, the disease caused an average of 160,000 cases (150 per 100,000 population) and 5,000 deaths each year. Figure 1¹² shows how pertussis incidence declined steadily over 3 decades to reach a low of 1,010 cases in 1976. However, while other vaccine-preventable diseases such as polio, measles, rubella, diphtheria, and tetanus have declined to only a few cases each year or have been totally eliminated, pertussis has made a slight comeback. The number of cases began to increase in the 1980s and reached 7,000 to 8,000 per year between 1996 and 2000. There were 11,647 cases in 2003.

In addition, a greater percentage of cases now occurs in adolescents and young adults. Half of reported cases are now in those age 10 years and older. Most nonimmunized or incompletely immunized infants who develop pertussis were exposed to the disease by older household members, not by same-age cohorts. Since the disease presents as nonspecific cough in adolescents, it is often not diagnosed, and the incidence is probably much higher than the reported number of cases would indicate.

These trends were cause for public health concern and led to the development of pertussis-containing vaccine products for adolescents and adults. Two Tdap products are available: one is licensed for those ages 10 to 64 (Boostrix), the other for ages 11 to 64 (Adacel). Since 2005, the ACIP has recommended a single dose of Tdap for those age 11 to 18, preferably at 11 or 12 years.¹² The optimal interval from the last tetanus-diphtheria shot is 5 years, but a shorter interval is acceptable. Thereafter, boosters with the tetanus toxoid and reduced-dose diphtheria toxoid (Td) vaccine are recommended every 10 years. If an adolescent has not previously received a complete series of a tetanus-diphtheria product, he or she should be given the recommended number of doses, only one of which should be Tdap, the others Td. The number and timing of doses can be found at www.cdc.gov/mmwr/preview/mmwrhtml/rr55e223a5.htm.

 

 

Human papillomavirus vaccination for girls age 11–12

HPV is sexually transmitted and causes genital warts, cervical cancer, and other oral, anal, and genital cancers.

HPV is the most common sexually transmitted infection in the United States, with over 6 million new cases each year.¹³ A study in 2003 to 2004 using HPV DNA typing of cervicovaginal swab specimens in a sample of women between the ages of 14 and 59 found an overall point prevalence of 26.8% of any HPV type.¹⁴ Those between 20 and 24 years had the highest prevalence at 44.8%. Those ages 14 to 19 had a prevalence of 24.5%. Several studies have reported a similar age-related increase in HPV prevalence.^15,16

One survey found that nearly 25% of girls in the United States are sexually active by age 15, 40% by age 16, and 70% by age 18.¹⁷ The 2005 Behavioral Risk Survey found that nearly 4% of girls were sexually active before age 13, and by the ninth grade 5.7% of those who were sexually active had had four or more partners.¹⁸ To receive the full benefit from the HPV vaccine, it should be given before this risk of acquiring HPV occurs.

A quadrivalent HPV vaccine (HPV4) was first licensed in the United States in 2006 for use in girls and women 9 to 26 years old to prevent cervical, vulvar, and vaginal precancerous lesions and cancer, and for prevention of anogenital warts. It contains viral proteins from HPV types 6, 11, 16, and 18, the types currently responsible for 70% of cervical cancers and 90% of anogenital warts. The vaccine is prepared in a yeast substrate and contains an aluminum-based adjuvant.

HPV4 has proven highly effective in women ages 16 to 26 not previously exposed to the four HPV types in the vaccine. The end points used in these studies were cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, anogenital warts, and vulvar and vaginal intraepithelial neoplasms.^13,19,20 The vaccine’s effectiveness has been 98% to 100% after 3 to 5 years. These trials are ongoing.

The vaccine’s efficacy in women with current or past HPV infection is less certain. Studies of this question have included only small numbers, and the confidence intervals are large and include 0. In intention-to-treat studies, its efficacy has been 39% to 46% for prevention of cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ caused by HPV-16 or HPV-18, 69% for prevention of HPV-16- or HPV-18-related vaginal intraepithelial neoplasia, and 68.5% for vaccine-type-related warts.¹³

The most common adverse effects of HPV4 have included redness, pain, and swelling at the injection site, which occur in about 20% of recipients.¹³ There is an increased risk of syncope immediately after the vaccine is given, and observation for 15 minutes after injection is recommended. A recent study suggested a link between the vaccine and venous thromboembolism. ²¹ The rate was 2 per million doses, and because many of the recipients also were taking oral contraceptives, their venous thromboembolism has not yet been definitively proven to be caused by the vaccine.

HPV4 is contraindicated in those who have experienced a severe allergic reaction to a previous dose or who have an allergy to a vaccine component. Vaccination should be deferred in those with moderate or severe acute illnesses.

In June 2006, the ACIP¹³ made the following recommendations for HPV4:

• Girls ages 11 to 12 years should be routinely vaccinated with three doses
• The series can start as early as age 9 years
• Women and girls age 13 to 26 who have not been previously vaccinated should receive catch-up vaccination
• Neither Papanicolaou (Pap) testing nor HPV screening is necessary before vaccination
• HPV4 can be given with other age-appropriate vaccines
• Vaccination does not change the recommendations for cervical cancer screening
• The recommendations remain the same regardless of abnormal Pap tests, positive HPV DNA tests, or warts.

There have been two very recent developments regarding HPV vaccines.

A bivalent vaccine (HPV2) has been licensed in the United States and approved for use in girls and women ages 10 to 25 for prevention of cervical cancer and precancerous lesions. It contains antigens against HPV-16 and HPV-18 but does not provide protection against genital warts. The ACIP has stated no preference for the bivalent or the quadrivalent vaccine for the prevention of cervical cancer and precancerous lesions.

HPV4 has also gained licensure for use in boys and men age 9 to 26 for the prevention of genital warts. The ACIP has not recommended it for routine use, leaving the decision to patients and physicians after weighing the potential benefits and costs.

 

VACCINE UPDATE FOR ADULTS

Four vaccines are now routinely recommended for adults:

• Seasonal influenza vaccine starting at age 50
• Pneumococcal polysaccharide vaccine (PPSV23) starting at age 65
• Herpes zoster vaccine starting at age 60
• A diphtheria and tetanus toxoid product every 10 years, with Tdap given once.²²

The rest of the adult schedule is based on catch-up (measles, mumps, rubella, varicella) or risk (hepatitis A and B and meningococccal disease). Seasonal influenza and pneumococcal vaccinations are also recommended before ages 50 and 65, respectively, for those with certain risk conditions. The complete adult immunization schedule can be found on the US Centers for Disease Control and Prevention (CDC) Web site.²²

One dose of Tdap instead of the next Td booster

The CDC now recommends that a single dose of Tdap should replace the next dose of Td for adults ages 19 to 64 as part of the every-10-year tetanus-diphtheria boosting recommendation and if indicated for wound management. ²³ In addition, a single dose of Tdap should be given to adults who have close contact with infants less than 6 months of age. The optimal interval between this Tdap shot and the last Td booster is 2 years or greater, but shorter intervals are acceptable. Women of childbearing age should receive Tdap preconception or postpartum if they have not previously received it. Tdap is not approved for use during pregnancy. Health care workers should also receive a dose of Tdap if they have never received it previously and if their last Td booster was more than 2 years ago, although less than 2 years is acceptable.

Contraindications to Tdap include anaphylaxis to a vaccine component and encephalopathy occurring within 7 days of previously receiving a pertussis vaccine.

Herpes zoster vaccine for those age 60 and older

Shingles causes considerable morbidity in older adults. The lifetime risk is 25%, and onefourth of those with shingles develop postherpetic neuralgia.

Herpes zoster vaccine is a live-attenuated vaccine that requires only a single injection. It is licensed for use in those ages 60 and older, and the ACIP recommends its routine use.²⁴ Its effectiveness is approximately 50% and is inversely related to age. The number of patients who need to be vaccinated to prevent one lifetime case of shingles is 17.

Contraindications to this vaccine include a prior anaphylactic reaction to gelatin or neomycin, compromised immunity due to disease or to immune-suppressive therapy including high-dose corticosteroids, and active tuberculosis.

Payment for this vaccine by Medicare is through Part D, creating some administrative difficulties for physicians’ offices.

Pneumococcal vaccination extended to smokers and people with asthma

The ACIP recently added two new groups for whom PPSV23 is recommended: smokers and those with asthma.²⁵ Smoking poses as much of a risk for pneumococcal pneumonia as do diabetes and other chronic illnesses that are currently indications for the vaccine. The number needed to vaccinate to prevent one case of pneumonia among smokers is 10,000 in people ages 18 to 44, and 4,000 in those ages 45 to 64.²⁶

The ACIP also clarified the recommendation for a second dose of PPSV23.²⁵ A second dose 5 years after the first is recommended for those who have immune suppression, sickle cell disease, or asplenia. People over age 65 should receive a second dose if they were vaccinated more than 5 years previously and before age 65.

New uses for hepatitis A vaccine

A combined hepatitis A and hepatitis B vaccine (Twinrix) has received approval for an alternate, four-dose schedule at 0, 7, 21 days, and 12 months.²⁷ It has previously only been approved for a three-dose schedule at 0, 1, and 6 months. The new alternative schedule allows greater protection for travelers who need to depart within less than 1 month.

For unvaccinated people who are acutely exposed to hepatitis A virus and for those traveling to areas of high prevalence who do not have time to complete the two doses of hepatitis A vaccine, the only prevention available until recently has been immune globulin. This has changed: hepatitis A vaccine can now be used in both groups. The new recommendations for postexposure prophylaxis is that either a single dose of hepatitis A vaccine or use of immune globulin is acceptable.²⁸ In ages 12 months to 40 years, vaccine is preferred. For those over age 40, immune globulin is preferred, but vaccine is acceptable. For children younger than 12 months, the immune-suppressed, and those with chronic liver disease, immune globulin should be used.

Those traveling or working in countries with high rates of hepatitis A can be protected with either hepatitis A vaccine or immune globulin. A single dose of the vaccine is sufficient for healthy people, with a second dose at the recommended interval to complete the series. Those younger than 12 months and those who choose not to receive the vaccine, including those who are allergic to it, should be offered immune globulin. Both immune globulin and hepatitis A vaccine should be considered for certain patients who plan to travel within 2 weeks of the first vaccine dose, ie, those over age 40, those with compromised immunity, and those with chronic liver disease or other chronic conditions.

Hepatitis A vaccine is now also recommended for all unvaccinated people who anticipate close personal contact with an international adoptee during the first 60 days following arrival from countries with high or intermediate hepatitis A endemicity.²⁹ The first dose should be given as soon as the adoption is planned and ideally at least 2 weeks before the child arrives.

The past 10 years have seen marked advances in vaccine research, resulting in more products being available. In 1983 the childhood vaccination schedule included protection against seven diseases: polio, tetanus, diphtheria, pertussis, measles, mumps, and rubella. The schedule in 2010 includes protection against organisms that cause seven more: Haemophilus influenzae, hepatitis A, hepatitis B, influenza, meningococcus, pneumococcus, and varicella.¹ In addition, new vaccine products are available for adolescents, offering protection against meningococcus, seasonal influenza, and human papillomavirus (HPV) and extending the length of protection against pertussis. For adults, a vaccine now protects against shingles, and several products offer boosting of pertussis immunity.

This rapid growth in the number of recommended vaccine products has made it challenging for practicing physicians to stay current on and to implement the ever-changing recommendations. The purpose of this article is to summarize the additions and changes over the past 3 years to the schedules of recommended vaccines for children, adolescents, and adults.

VACCINE UPDATE FOR CHILDREN

The recent changes to the childhood immunization schedule have added protection against rotavirus and seasonal influenza and have expanded the protection against hepatitis A and varicella.

Rotavirus vaccination for infants

Rotavirus is the leading cause of infectious gastroenteritis in infants. It causes significant morbidity and expense, accounting for 2.7 million episodes per year in the United States, 410,000 outpatient or office visits, 201,000 to 272,000 emergency department visits, 55,000 to 70,000 hospitalizations, and 20 to 60 deaths.² Although the number of deaths in the United States is not large, rotavirus is a leading cause of infant deaths around the world.

A rotavirus vaccine was first introduced in the United States in 1998 but was withdrawn from the market in less than a year due to risk of intussusception, which occurred in 1 per 10,000 infants vaccinated.² Two different rotavirus vaccines have recently been approved by the US Food and Drug Administration: a five-antigen vaccine (RV5; RotaTeq) in 2006 and a single-antigen vaccine (RV1; Rotarix) in 2008. Both are modified live-virus vaccines, given orally. They contain different antigens and have different schedules of administration— RV5 requires three doses, while RV1 requires two doses. Table 1 summarizes the characteristics of each product.

Rotavirus vaccination is challenging because of the time frame in which the series needs to be given. The first dose has to be given after 6 weeks of age but before 15 weeks of age, and the last dose should be given before 8 months of age, with a minimum of 4 weeks between doses. It is preferable to use the same product to finish the series. They can be used interchangeably, but this then requires three total doses.

The effectiveness of the vaccine in preventing rotavirus gastroenteritis in the first year after vaccination was greater than 80% in most studies and approached 100% in preventing serious gastroenteritis.²

Those vaccinated appear to have a slightly higher rate of diarrhea and vomiting in the first 42 days after vaccination. Safety monitoring after the products were licensed has not shown an increased rate of intussusception with either product.

The only contraindication to the vaccines is a serious allergic reaction to them or to one of their components. They should be used with caution in patients who have suppressed immunity, acute gastroenteritis, preexisting gastrointestinal disease, or previous intussusception.

 

 

Seasonal influenza vaccine extended to ages 5–18

Gradually, we seem to be moving toward vaccinating everyone every year against seasonal influenza. Previously, vaccination was recommended for children age 6 months through 4 years; in 2008, the Advisory Committee on Immunization Practices (ACIP) extended the recommendation to the age group 5 through 18 years.³

Two types of seasonal influenza vaccine are available: trivalent influenza vaccine (TIV), which contains killed virus and is given by injection, and live-attenuated seasonal influenza vaccine (LAIV), which is given by nasal spray. Both contain the same three seasonal influenza antigens, selected each year by a team of experts. TIV is licensed for those age 6 months and older, and LAIV is licensed for ages 2 through 49 years.⁴

Since LAIV contains a live-attenuated virus, it should not be used in anyone who has a chronic illness (including those under the age of 5 with recurrent wheezing, those with suppressed immunity, and those with a history of Guillain-Barré syndrome); in pregnant women; or those who have close contact with anyone who is immune-suppressed. The injection is contraindicated for those who have had a serious allergic reaction to eggs.

Children younger than 9 years should receive two doses of either type of vaccine the first year they are vaccinated. Those who receive only one dose the first year they are vaccinated should receive two doses the next year. If they fail to receive two doses in the next year, only a single dose is recommended after that. This is a slight modification of the previous recommendation that only one dose be given the second year if only one dose was given the first year.⁵

Hepatitis A vaccine at age 12–23 months

An inactivated hepatitis A vaccine (HepA) was first licensed in 1995; another was licensed in 1996. Recommendations for their use have been revised periodically, and their widespread use has resulted in a marked reduction in the incidence of hepatitis A virus infection.

The current recommendation is that all children be vaccinated at age 12 to 23 months. In addition, in areas of high prevalence, vaccine is recommended for older children who have not been vaccinated. Other target groups are those at higher risk of hepatitis A, including travelers to endemic areas, users of illicit drugs, and men who have sex with men.⁶ Indications for vaccination before travel, after exposure to hepatitis A infection, and in families of international adoptees are covered later in this paper in a discussion about vaccinations in adults.

Varicella at 12–15 months and 4–6 years, with catch-up for others

Before varicella vaccine was licensed in 1995, 4 million cases of varicella infection (chickenpox) were reported in the United States each year, resulting in thousands of hospitalizations and more than 100 deaths. The vaccine is now widely used, with a coverage rate of 88%, and it has proven to be 85% effective.⁷ The result was a marked decrease in the incidence of varicella and in varicella-related hospitalizations and deaths.

In spite of this success, the number of varicella cases has remained constant over the past few years, and sporadic outbreaks continue to occur, predominantly in schools, even schools in which a high percentage of the children are vaccinated.^7,8 These outbreaks have involved infections in unvaccinated children and also “breakthrough disease” in children who have been vaccinated. If someone who has received one dose of vaccine is exposed to varicella, the risk of a breakthrough infection is about 15%.⁹ A two-dose series of varicella vaccine reduces the risk by about 75%.⁷ Breakthrough disease is usually milder than infection in the unvaccinated, with fewer skin lesions, milder symptoms, and fewer complications, but those affected are still infectious to others.

In 2005 and 2006, this ongoing risk of varicella prompted the ACIP to consider and recommend several new control measures:

• Two doses of varicella vaccine for all children, the first dose at age 12 to 15 months and the second at age 4 to 6 years—the same schedule as for immunization against measles, mumps, and rubella
• Two doses of varicella vaccine, the second given 4 to 8 weeks after the first, for all adolescents and adults who have no evidence of immunity
• A catch-up second dose for everyone who received one dose previously
• Screening for varicella immunity in pregnant women and postpartum vaccination with two doses for those who are not immune, the first dose given before discharge and the second dose 4 to 8 weeks later.

 

VACCINE UPDATE FOR ADOLESCENTS

A number of vaccines are now available and recommended for routine use in adolescents.⁹ These include HPV vaccine for girls, quadrivalent meningococcal conjugate vaccine (MCV4), and combined tetanus toxoid, reduced-dose diphtheria toxoid, and acellular pertussis (Tdap). All these are now recommended routinely at age 11 or 12. Seasonal influenza vaccine is recommended annually through age 18.

For the next decade, a catch-up varicella booster will also be recommended for adolescents because of waning varicella immunity from a single dose. Adolescents should also receive some catch-up vaccines if they did not receive them in childhood and should be considered for some vaccines that are recommended on the basis of risk. Table 2 lists the vaccines that should be considered during a clinical visit for those age 11 through 18 years.

Meningococcal conjugate vaccine for all at age 11–18

In 2007, the ACIP recommended MCV4 for all at age 11 through 18 at the earliest opportunity. ¹⁰ For those who remain at high risk (Table 3) and who were vaccinated with either MCV4 or the meningococcal polysaccharide vaccine (MPSV4), a booster is recommended after 3 years (if vaccinated before age 7), and after 5 years if vaccinated age 7 and up. College freshman who were vaccinated with MCV4 do not need a booster dose.

There is some evidence that MCV4 may be linked to a small risk of Guillain-Barré syndrome. Although this link has not been conclusively proven, a history of Guillain-Barré syndrome calls for caution in using MCV4. For those who have a history of this syndrome but need protection against meningococcal infection, the MPSV4 is an alternative.¹¹

Pertussis: A Tdap booster at age 11–18

From Broder KR, et al; ACIP. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the ACIP. MMWR Recomm Rep 2006; 55(RR–3):1–34

The incidence of pertussis in the United States declined dramatically after pertussis vaccine was introduced in the 1940s. Before then, the disease caused an average of 160,000 cases (150 per 100,000 population) and 5,000 deaths each year. Figure 1¹² shows how pertussis incidence declined steadily over 3 decades to reach a low of 1,010 cases in 1976. However, while other vaccine-preventable diseases such as polio, measles, rubella, diphtheria, and tetanus have declined to only a few cases each year or have been totally eliminated, pertussis has made a slight comeback. The number of cases began to increase in the 1980s and reached 7,000 to 8,000 per year between 1996 and 2000. There were 11,647 cases in 2003.

In addition, a greater percentage of cases now occurs in adolescents and young adults. Half of reported cases are now in those age 10 years and older. Most nonimmunized or incompletely immunized infants who develop pertussis were exposed to the disease by older household members, not by same-age cohorts. Since the disease presents as nonspecific cough in adolescents, it is often not diagnosed, and the incidence is probably much higher than the reported number of cases would indicate.

These trends were cause for public health concern and led to the development of pertussis-containing vaccine products for adolescents and adults. Two Tdap products are available: one is licensed for those ages 10 to 64 (Boostrix), the other for ages 11 to 64 (Adacel). Since 2005, the ACIP has recommended a single dose of Tdap for those age 11 to 18, preferably at 11 or 12 years.¹² The optimal interval from the last tetanus-diphtheria shot is 5 years, but a shorter interval is acceptable. Thereafter, boosters with the tetanus toxoid and reduced-dose diphtheria toxoid (Td) vaccine are recommended every 10 years. If an adolescent has not previously received a complete series of a tetanus-diphtheria product, he or she should be given the recommended number of doses, only one of which should be Tdap, the others Td. The number and timing of doses can be found at www.cdc.gov/mmwr/preview/mmwrhtml/rr55e223a5.htm.

 

 

Human papillomavirus vaccination for girls age 11–12

HPV is sexually transmitted and causes genital warts, cervical cancer, and other oral, anal, and genital cancers.

HPV is the most common sexually transmitted infection in the United States, with over 6 million new cases each year.¹³ A study in 2003 to 2004 using HPV DNA typing of cervicovaginal swab specimens in a sample of women between the ages of 14 and 59 found an overall point prevalence of 26.8% of any HPV type.¹⁴ Those between 20 and 24 years had the highest prevalence at 44.8%. Those ages 14 to 19 had a prevalence of 24.5%. Several studies have reported a similar age-related increase in HPV prevalence.^15,16

One survey found that nearly 25% of girls in the United States are sexually active by age 15, 40% by age 16, and 70% by age 18.¹⁷ The 2005 Behavioral Risk Survey found that nearly 4% of girls were sexually active before age 13, and by the ninth grade 5.7% of those who were sexually active had had four or more partners.¹⁸ To receive the full benefit from the HPV vaccine, it should be given before this risk of acquiring HPV occurs.

A quadrivalent HPV vaccine (HPV4) was first licensed in the United States in 2006 for use in girls and women 9 to 26 years old to prevent cervical, vulvar, and vaginal precancerous lesions and cancer, and for prevention of anogenital warts. It contains viral proteins from HPV types 6, 11, 16, and 18, the types currently responsible for 70% of cervical cancers and 90% of anogenital warts. The vaccine is prepared in a yeast substrate and contains an aluminum-based adjuvant.

HPV4 has proven highly effective in women ages 16 to 26 not previously exposed to the four HPV types in the vaccine. The end points used in these studies were cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, anogenital warts, and vulvar and vaginal intraepithelial neoplasms.^13,19,20 The vaccine’s effectiveness has been 98% to 100% after 3 to 5 years. These trials are ongoing.

The vaccine’s efficacy in women with current or past HPV infection is less certain. Studies of this question have included only small numbers, and the confidence intervals are large and include 0. In intention-to-treat studies, its efficacy has been 39% to 46% for prevention of cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ caused by HPV-16 or HPV-18, 69% for prevention of HPV-16- or HPV-18-related vaginal intraepithelial neoplasia, and 68.5% for vaccine-type-related warts.¹³

The most common adverse effects of HPV4 have included redness, pain, and swelling at the injection site, which occur in about 20% of recipients.¹³ There is an increased risk of syncope immediately after the vaccine is given, and observation for 15 minutes after injection is recommended. A recent study suggested a link between the vaccine and venous thromboembolism. ²¹ The rate was 2 per million doses, and because many of the recipients also were taking oral contraceptives, their venous thromboembolism has not yet been definitively proven to be caused by the vaccine.

HPV4 is contraindicated in those who have experienced a severe allergic reaction to a previous dose or who have an allergy to a vaccine component. Vaccination should be deferred in those with moderate or severe acute illnesses.

In June 2006, the ACIP¹³ made the following recommendations for HPV4:

• Girls ages 11 to 12 years should be routinely vaccinated with three doses
• The series can start as early as age 9 years
• Women and girls age 13 to 26 who have not been previously vaccinated should receive catch-up vaccination
• Neither Papanicolaou (Pap) testing nor HPV screening is necessary before vaccination
• HPV4 can be given with other age-appropriate vaccines
• Vaccination does not change the recommendations for cervical cancer screening
• The recommendations remain the same regardless of abnormal Pap tests, positive HPV DNA tests, or warts.

There have been two very recent developments regarding HPV vaccines.

A bivalent vaccine (HPV2) has been licensed in the United States and approved for use in girls and women ages 10 to 25 for prevention of cervical cancer and precancerous lesions. It contains antigens against HPV-16 and HPV-18 but does not provide protection against genital warts. The ACIP has stated no preference for the bivalent or the quadrivalent vaccine for the prevention of cervical cancer and precancerous lesions.

HPV4 has also gained licensure for use in boys and men age 9 to 26 for the prevention of genital warts. The ACIP has not recommended it for routine use, leaving the decision to patients and physicians after weighing the potential benefits and costs.

 

VACCINE UPDATE FOR ADULTS

Four vaccines are now routinely recommended for adults:

• Seasonal influenza vaccine starting at age 50
• Pneumococcal polysaccharide vaccine (PPSV23) starting at age 65
• Herpes zoster vaccine starting at age 60
• A diphtheria and tetanus toxoid product every 10 years, with Tdap given once.²²

The rest of the adult schedule is based on catch-up (measles, mumps, rubella, varicella) or risk (hepatitis A and B and meningococccal disease). Seasonal influenza and pneumococcal vaccinations are also recommended before ages 50 and 65, respectively, for those with certain risk conditions. The complete adult immunization schedule can be found on the US Centers for Disease Control and Prevention (CDC) Web site.²²

One dose of Tdap instead of the next Td booster

The CDC now recommends that a single dose of Tdap should replace the next dose of Td for adults ages 19 to 64 as part of the every-10-year tetanus-diphtheria boosting recommendation and if indicated for wound management. ²³ In addition, a single dose of Tdap should be given to adults who have close contact with infants less than 6 months of age. The optimal interval between this Tdap shot and the last Td booster is 2 years or greater, but shorter intervals are acceptable. Women of childbearing age should receive Tdap preconception or postpartum if they have not previously received it. Tdap is not approved for use during pregnancy. Health care workers should also receive a dose of Tdap if they have never received it previously and if their last Td booster was more than 2 years ago, although less than 2 years is acceptable.

Contraindications to Tdap include anaphylaxis to a vaccine component and encephalopathy occurring within 7 days of previously receiving a pertussis vaccine.

Herpes zoster vaccine for those age 60 and older

Shingles causes considerable morbidity in older adults. The lifetime risk is 25%, and onefourth of those with shingles develop postherpetic neuralgia.

Herpes zoster vaccine is a live-attenuated vaccine that requires only a single injection. It is licensed for use in those ages 60 and older, and the ACIP recommends its routine use.²⁴ Its effectiveness is approximately 50% and is inversely related to age. The number of patients who need to be vaccinated to prevent one lifetime case of shingles is 17.

Contraindications to this vaccine include a prior anaphylactic reaction to gelatin or neomycin, compromised immunity due to disease or to immune-suppressive therapy including high-dose corticosteroids, and active tuberculosis.

Payment for this vaccine by Medicare is through Part D, creating some administrative difficulties for physicians’ offices.

Pneumococcal vaccination extended to smokers and people with asthma

The ACIP recently added two new groups for whom PPSV23 is recommended: smokers and those with asthma.²⁵ Smoking poses as much of a risk for pneumococcal pneumonia as do diabetes and other chronic illnesses that are currently indications for the vaccine. The number needed to vaccinate to prevent one case of pneumonia among smokers is 10,000 in people ages 18 to 44, and 4,000 in those ages 45 to 64.²⁶

The ACIP also clarified the recommendation for a second dose of PPSV23.²⁵ A second dose 5 years after the first is recommended for those who have immune suppression, sickle cell disease, or asplenia. People over age 65 should receive a second dose if they were vaccinated more than 5 years previously and before age 65.

New uses for hepatitis A vaccine

A combined hepatitis A and hepatitis B vaccine (Twinrix) has received approval for an alternate, four-dose schedule at 0, 7, 21 days, and 12 months.²⁷ It has previously only been approved for a three-dose schedule at 0, 1, and 6 months. The new alternative schedule allows greater protection for travelers who need to depart within less than 1 month.

For unvaccinated people who are acutely exposed to hepatitis A virus and for those traveling to areas of high prevalence who do not have time to complete the two doses of hepatitis A vaccine, the only prevention available until recently has been immune globulin. This has changed: hepatitis A vaccine can now be used in both groups. The new recommendations for postexposure prophylaxis is that either a single dose of hepatitis A vaccine or use of immune globulin is acceptable.²⁸ In ages 12 months to 40 years, vaccine is preferred. For those over age 40, immune globulin is preferred, but vaccine is acceptable. For children younger than 12 months, the immune-suppressed, and those with chronic liver disease, immune globulin should be used.

Those traveling or working in countries with high rates of hepatitis A can be protected with either hepatitis A vaccine or immune globulin. A single dose of the vaccine is sufficient for healthy people, with a second dose at the recommended interval to complete the series. Those younger than 12 months and those who choose not to receive the vaccine, including those who are allergic to it, should be offered immune globulin. Both immune globulin and hepatitis A vaccine should be considered for certain patients who plan to travel within 2 weeks of the first vaccine dose, ie, those over age 40, those with compromised immunity, and those with chronic liver disease or other chronic conditions.

Hepatitis A vaccine is now also recommended for all unvaccinated people who anticipate close personal contact with an international adoptee during the first 60 days following arrival from countries with high or intermediate hepatitis A endemicity.²⁹ The first dose should be given as soon as the adoption is planned and ideally at least 2 weeks before the child arrives.

The past 10 years have seen marked advances in vaccine research, resulting in more products being available. In 1983 the childhood vaccination schedule included protection against seven diseases: polio, tetanus, diphtheria, pertussis, measles, mumps, and rubella. The schedule in 2010 includes protection against organisms that cause seven more: Haemophilus influenzae, hepatitis A, hepatitis B, influenza, meningococcus, pneumococcus, and varicella.¹ In addition, new vaccine products are available for adolescents, offering protection against meningococcus, seasonal influenza, and human papillomavirus (HPV) and extending the length of protection against pertussis. For adults, a vaccine now protects against shingles, and several products offer boosting of pertussis immunity.

This rapid growth in the number of recommended vaccine products has made it challenging for practicing physicians to stay current on and to implement the ever-changing recommendations. The purpose of this article is to summarize the additions and changes over the past 3 years to the schedules of recommended vaccines for children, adolescents, and adults.

VACCINE UPDATE FOR CHILDREN

The recent changes to the childhood immunization schedule have added protection against rotavirus and seasonal influenza and have expanded the protection against hepatitis A and varicella.

Rotavirus vaccination for infants

Rotavirus is the leading cause of infectious gastroenteritis in infants. It causes significant morbidity and expense, accounting for 2.7 million episodes per year in the United States, 410,000 outpatient or office visits, 201,000 to 272,000 emergency department visits, 55,000 to 70,000 hospitalizations, and 20 to 60 deaths.² Although the number of deaths in the United States is not large, rotavirus is a leading cause of infant deaths around the world.

A rotavirus vaccine was first introduced in the United States in 1998 but was withdrawn from the market in less than a year due to risk of intussusception, which occurred in 1 per 10,000 infants vaccinated.² Two different rotavirus vaccines have recently been approved by the US Food and Drug Administration: a five-antigen vaccine (RV5; RotaTeq) in 2006 and a single-antigen vaccine (RV1; Rotarix) in 2008. Both are modified live-virus vaccines, given orally. They contain different antigens and have different schedules of administration— RV5 requires three doses, while RV1 requires two doses. Table 1 summarizes the characteristics of each product.

Rotavirus vaccination is challenging because of the time frame in which the series needs to be given. The first dose has to be given after 6 weeks of age but before 15 weeks of age, and the last dose should be given before 8 months of age, with a minimum of 4 weeks between doses. It is preferable to use the same product to finish the series. They can be used interchangeably, but this then requires three total doses.

The effectiveness of the vaccine in preventing rotavirus gastroenteritis in the first year after vaccination was greater than 80% in most studies and approached 100% in preventing serious gastroenteritis.²

Those vaccinated appear to have a slightly higher rate of diarrhea and vomiting in the first 42 days after vaccination. Safety monitoring after the products were licensed has not shown an increased rate of intussusception with either product.

The only contraindication to the vaccines is a serious allergic reaction to them or to one of their components. They should be used with caution in patients who have suppressed immunity, acute gastroenteritis, preexisting gastrointestinal disease, or previous intussusception.

 

 

Seasonal influenza vaccine extended to ages 5–18

Gradually, we seem to be moving toward vaccinating everyone every year against seasonal influenza. Previously, vaccination was recommended for children age 6 months through 4 years; in 2008, the Advisory Committee on Immunization Practices (ACIP) extended the recommendation to the age group 5 through 18 years.³

Two types of seasonal influenza vaccine are available: trivalent influenza vaccine (TIV), which contains killed virus and is given by injection, and live-attenuated seasonal influenza vaccine (LAIV), which is given by nasal spray. Both contain the same three seasonal influenza antigens, selected each year by a team of experts. TIV is licensed for those age 6 months and older, and LAIV is licensed for ages 2 through 49 years.⁴

Since LAIV contains a live-attenuated virus, it should not be used in anyone who has a chronic illness (including those under the age of 5 with recurrent wheezing, those with suppressed immunity, and those with a history of Guillain-Barré syndrome); in pregnant women; or those who have close contact with anyone who is immune-suppressed. The injection is contraindicated for those who have had a serious allergic reaction to eggs.

Children younger than 9 years should receive two doses of either type of vaccine the first year they are vaccinated. Those who receive only one dose the first year they are vaccinated should receive two doses the next year. If they fail to receive two doses in the next year, only a single dose is recommended after that. This is a slight modification of the previous recommendation that only one dose be given the second year if only one dose was given the first year.⁵

Hepatitis A vaccine at age 12–23 months

An inactivated hepatitis A vaccine (HepA) was first licensed in 1995; another was licensed in 1996. Recommendations for their use have been revised periodically, and their widespread use has resulted in a marked reduction in the incidence of hepatitis A virus infection.

The current recommendation is that all children be vaccinated at age 12 to 23 months. In addition, in areas of high prevalence, vaccine is recommended for older children who have not been vaccinated. Other target groups are those at higher risk of hepatitis A, including travelers to endemic areas, users of illicit drugs, and men who have sex with men.⁶ Indications for vaccination before travel, after exposure to hepatitis A infection, and in families of international adoptees are covered later in this paper in a discussion about vaccinations in adults.

Varicella at 12–15 months and 4–6 years, with catch-up for others

Before varicella vaccine was licensed in 1995, 4 million cases of varicella infection (chickenpox) were reported in the United States each year, resulting in thousands of hospitalizations and more than 100 deaths. The vaccine is now widely used, with a coverage rate of 88%, and it has proven to be 85% effective.⁷ The result was a marked decrease in the incidence of varicella and in varicella-related hospitalizations and deaths.

In spite of this success, the number of varicella cases has remained constant over the past few years, and sporadic outbreaks continue to occur, predominantly in schools, even schools in which a high percentage of the children are vaccinated.^7,8 These outbreaks have involved infections in unvaccinated children and also “breakthrough disease” in children who have been vaccinated. If someone who has received one dose of vaccine is exposed to varicella, the risk of a breakthrough infection is about 15%.⁹ A two-dose series of varicella vaccine reduces the risk by about 75%.⁷ Breakthrough disease is usually milder than infection in the unvaccinated, with fewer skin lesions, milder symptoms, and fewer complications, but those affected are still infectious to others.

In 2005 and 2006, this ongoing risk of varicella prompted the ACIP to consider and recommend several new control measures:

• Two doses of varicella vaccine for all children, the first dose at age 12 to 15 months and the second at age 4 to 6 years—the same schedule as for immunization against measles, mumps, and rubella
• Two doses of varicella vaccine, the second given 4 to 8 weeks after the first, for all adolescents and adults who have no evidence of immunity
• A catch-up second dose for everyone who received one dose previously
• Screening for varicella immunity in pregnant women and postpartum vaccination with two doses for those who are not immune, the first dose given before discharge and the second dose 4 to 8 weeks later.

 

VACCINE UPDATE FOR ADOLESCENTS

A number of vaccines are now available and recommended for routine use in adolescents.⁹ These include HPV vaccine for girls, quadrivalent meningococcal conjugate vaccine (MCV4), and combined tetanus toxoid, reduced-dose diphtheria toxoid, and acellular pertussis (Tdap). All these are now recommended routinely at age 11 or 12. Seasonal influenza vaccine is recommended annually through age 18.

For the next decade, a catch-up varicella booster will also be recommended for adolescents because of waning varicella immunity from a single dose. Adolescents should also receive some catch-up vaccines if they did not receive them in childhood and should be considered for some vaccines that are recommended on the basis of risk. Table 2 lists the vaccines that should be considered during a clinical visit for those age 11 through 18 years.

Meningococcal conjugate vaccine for all at age 11–18

In 2007, the ACIP recommended MCV4 for all at age 11 through 18 at the earliest opportunity. ¹⁰ For those who remain at high risk (Table 3) and who were vaccinated with either MCV4 or the meningococcal polysaccharide vaccine (MPSV4), a booster is recommended after 3 years (if vaccinated before age 7), and after 5 years if vaccinated age 7 and up. College freshman who were vaccinated with MCV4 do not need a booster dose.

There is some evidence that MCV4 may be linked to a small risk of Guillain-Barré syndrome. Although this link has not been conclusively proven, a history of Guillain-Barré syndrome calls for caution in using MCV4. For those who have a history of this syndrome but need protection against meningococcal infection, the MPSV4 is an alternative.¹¹

Pertussis: A Tdap booster at age 11–18

From Broder KR, et al; ACIP. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the ACIP. MMWR Recomm Rep 2006; 55(RR–3):1–34

The incidence of pertussis in the United States declined dramatically after pertussis vaccine was introduced in the 1940s. Before then, the disease caused an average of 160,000 cases (150 per 100,000 population) and 5,000 deaths each year. Figure 1¹² shows how pertussis incidence declined steadily over 3 decades to reach a low of 1,010 cases in 1976. However, while other vaccine-preventable diseases such as polio, measles, rubella, diphtheria, and tetanus have declined to only a few cases each year or have been totally eliminated, pertussis has made a slight comeback. The number of cases began to increase in the 1980s and reached 7,000 to 8,000 per year between 1996 and 2000. There were 11,647 cases in 2003.

In addition, a greater percentage of cases now occurs in adolescents and young adults. Half of reported cases are now in those age 10 years and older. Most nonimmunized or incompletely immunized infants who develop pertussis were exposed to the disease by older household members, not by same-age cohorts. Since the disease presents as nonspecific cough in adolescents, it is often not diagnosed, and the incidence is probably much higher than the reported number of cases would indicate.

These trends were cause for public health concern and led to the development of pertussis-containing vaccine products for adolescents and adults. Two Tdap products are available: one is licensed for those ages 10 to 64 (Boostrix), the other for ages 11 to 64 (Adacel). Since 2005, the ACIP has recommended a single dose of Tdap for those age 11 to 18, preferably at 11 or 12 years.¹² The optimal interval from the last tetanus-diphtheria shot is 5 years, but a shorter interval is acceptable. Thereafter, boosters with the tetanus toxoid and reduced-dose diphtheria toxoid (Td) vaccine are recommended every 10 years. If an adolescent has not previously received a complete series of a tetanus-diphtheria product, he or she should be given the recommended number of doses, only one of which should be Tdap, the others Td. The number and timing of doses can be found at www.cdc.gov/mmwr/preview/mmwrhtml/rr55e223a5.htm.

 

 

Human papillomavirus vaccination for girls age 11–12

HPV is sexually transmitted and causes genital warts, cervical cancer, and other oral, anal, and genital cancers.

HPV is the most common sexually transmitted infection in the United States, with over 6 million new cases each year.¹³ A study in 2003 to 2004 using HPV DNA typing of cervicovaginal swab specimens in a sample of women between the ages of 14 and 59 found an overall point prevalence of 26.8% of any HPV type.¹⁴ Those between 20 and 24 years had the highest prevalence at 44.8%. Those ages 14 to 19 had a prevalence of 24.5%. Several studies have reported a similar age-related increase in HPV prevalence.^15,16

One survey found that nearly 25% of girls in the United States are sexually active by age 15, 40% by age 16, and 70% by age 18.¹⁷ The 2005 Behavioral Risk Survey found that nearly 4% of girls were sexually active before age 13, and by the ninth grade 5.7% of those who were sexually active had had four or more partners.¹⁸ To receive the full benefit from the HPV vaccine, it should be given before this risk of acquiring HPV occurs.

A quadrivalent HPV vaccine (HPV4) was first licensed in the United States in 2006 for use in girls and women 9 to 26 years old to prevent cervical, vulvar, and vaginal precancerous lesions and cancer, and for prevention of anogenital warts. It contains viral proteins from HPV types 6, 11, 16, and 18, the types currently responsible for 70% of cervical cancers and 90% of anogenital warts. The vaccine is prepared in a yeast substrate and contains an aluminum-based adjuvant.

HPV4 has proven highly effective in women ages 16 to 26 not previously exposed to the four HPV types in the vaccine. The end points used in these studies were cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, anogenital warts, and vulvar and vaginal intraepithelial neoplasms.^13,19,20 The vaccine’s effectiveness has been 98% to 100% after 3 to 5 years. These trials are ongoing.

The vaccine’s efficacy in women with current or past HPV infection is less certain. Studies of this question have included only small numbers, and the confidence intervals are large and include 0. In intention-to-treat studies, its efficacy has been 39% to 46% for prevention of cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ caused by HPV-16 or HPV-18, 69% for prevention of HPV-16- or HPV-18-related vaginal intraepithelial neoplasia, and 68.5% for vaccine-type-related warts.¹³

The most common adverse effects of HPV4 have included redness, pain, and swelling at the injection site, which occur in about 20% of recipients.¹³ There is an increased risk of syncope immediately after the vaccine is given, and observation for 15 minutes after injection is recommended. A recent study suggested a link between the vaccine and venous thromboembolism. ²¹ The rate was 2 per million doses, and because many of the recipients also were taking oral contraceptives, their venous thromboembolism has not yet been definitively proven to be caused by the vaccine.

HPV4 is contraindicated in those who have experienced a severe allergic reaction to a previous dose or who have an allergy to a vaccine component. Vaccination should be deferred in those with moderate or severe acute illnesses.

In June 2006, the ACIP¹³ made the following recommendations for HPV4:

• Girls ages 11 to 12 years should be routinely vaccinated with three doses
• The series can start as early as age 9 years
• Women and girls age 13 to 26 who have not been previously vaccinated should receive catch-up vaccination
• Neither Papanicolaou (Pap) testing nor HPV screening is necessary before vaccination
• HPV4 can be given with other age-appropriate vaccines
• Vaccination does not change the recommendations for cervical cancer screening
• The recommendations remain the same regardless of abnormal Pap tests, positive HPV DNA tests, or warts.

There have been two very recent developments regarding HPV vaccines.

A bivalent vaccine (HPV2) has been licensed in the United States and approved for use in girls and women ages 10 to 25 for prevention of cervical cancer and precancerous lesions. It contains antigens against HPV-16 and HPV-18 but does not provide protection against genital warts. The ACIP has stated no preference for the bivalent or the quadrivalent vaccine for the prevention of cervical cancer and precancerous lesions.

HPV4 has also gained licensure for use in boys and men age 9 to 26 for the prevention of genital warts. The ACIP has not recommended it for routine use, leaving the decision to patients and physicians after weighing the potential benefits and costs.

 

VACCINE UPDATE FOR ADULTS

Four vaccines are now routinely recommended for adults:

• Seasonal influenza vaccine starting at age 50
• Pneumococcal polysaccharide vaccine (PPSV23) starting at age 65
• Herpes zoster vaccine starting at age 60
• A diphtheria and tetanus toxoid product every 10 years, with Tdap given once.²²

The rest of the adult schedule is based on catch-up (measles, mumps, rubella, varicella) or risk (hepatitis A and B and meningococccal disease). Seasonal influenza and pneumococcal vaccinations are also recommended before ages 50 and 65, respectively, for those with certain risk conditions. The complete adult immunization schedule can be found on the US Centers for Disease Control and Prevention (CDC) Web site.²²

One dose of Tdap instead of the next Td booster

The CDC now recommends that a single dose of Tdap should replace the next dose of Td for adults ages 19 to 64 as part of the every-10-year tetanus-diphtheria boosting recommendation and if indicated for wound management. ²³ In addition, a single dose of Tdap should be given to adults who have close contact with infants less than 6 months of age. The optimal interval between this Tdap shot and the last Td booster is 2 years or greater, but shorter intervals are acceptable. Women of childbearing age should receive Tdap preconception or postpartum if they have not previously received it. Tdap is not approved for use during pregnancy. Health care workers should also receive a dose of Tdap if they have never received it previously and if their last Td booster was more than 2 years ago, although less than 2 years is acceptable.

Contraindications to Tdap include anaphylaxis to a vaccine component and encephalopathy occurring within 7 days of previously receiving a pertussis vaccine.

Herpes zoster vaccine for those age 60 and older

Shingles causes considerable morbidity in older adults. The lifetime risk is 25%, and onefourth of those with shingles develop postherpetic neuralgia.

Herpes zoster vaccine is a live-attenuated vaccine that requires only a single injection. It is licensed for use in those ages 60 and older, and the ACIP recommends its routine use.²⁴ Its effectiveness is approximately 50% and is inversely related to age. The number of patients who need to be vaccinated to prevent one lifetime case of shingles is 17.

Contraindications to this vaccine include a prior anaphylactic reaction to gelatin or neomycin, compromised immunity due to disease or to immune-suppressive therapy including high-dose corticosteroids, and active tuberculosis.

Payment for this vaccine by Medicare is through Part D, creating some administrative difficulties for physicians’ offices.

Pneumococcal vaccination extended to smokers and people with asthma

The ACIP recently added two new groups for whom PPSV23 is recommended: smokers and those with asthma.²⁵ Smoking poses as much of a risk for pneumococcal pneumonia as do diabetes and other chronic illnesses that are currently indications for the vaccine. The number needed to vaccinate to prevent one case of pneumonia among smokers is 10,000 in people ages 18 to 44, and 4,000 in those ages 45 to 64.²⁶

The ACIP also clarified the recommendation for a second dose of PPSV23.²⁵ A second dose 5 years after the first is recommended for those who have immune suppression, sickle cell disease, or asplenia. People over age 65 should receive a second dose if they were vaccinated more than 5 years previously and before age 65.

New uses for hepatitis A vaccine

A combined hepatitis A and hepatitis B vaccine (Twinrix) has received approval for an alternate, four-dose schedule at 0, 7, 21 days, and 12 months.²⁷ It has previously only been approved for a three-dose schedule at 0, 1, and 6 months. The new alternative schedule allows greater protection for travelers who need to depart within less than 1 month.

For unvaccinated people who are acutely exposed to hepatitis A virus and for those traveling to areas of high prevalence who do not have time to complete the two doses of hepatitis A vaccine, the only prevention available until recently has been immune globulin. This has changed: hepatitis A vaccine can now be used in both groups. The new recommendations for postexposure prophylaxis is that either a single dose of hepatitis A vaccine or use of immune globulin is acceptable.²⁸ In ages 12 months to 40 years, vaccine is preferred. For those over age 40, immune globulin is preferred, but vaccine is acceptable. For children younger than 12 months, the immune-suppressed, and those with chronic liver disease, immune globulin should be used.

Those traveling or working in countries with high rates of hepatitis A can be protected with either hepatitis A vaccine or immune globulin. A single dose of the vaccine is sufficient for healthy people, with a second dose at the recommended interval to complete the series. Those younger than 12 months and those who choose not to receive the vaccine, including those who are allergic to it, should be offered immune globulin. Both immune globulin and hepatitis A vaccine should be considered for certain patients who plan to travel within 2 weeks of the first vaccine dose, ie, those over age 40, those with compromised immunity, and those with chronic liver disease or other chronic conditions.

Hepatitis A vaccine is now also recommended for all unvaccinated people who anticipate close personal contact with an international adoptee during the first 60 days following arrival from countries with high or intermediate hepatitis A endemicity.²⁹ The first dose should be given as soon as the adoption is planned and ideally at least 2 weeks before the child arrives.

The Advisory Committee on Immunization Practices (ACIP) made a number of major new recommendations last year. These new recommendations address:

• expanded use of hepatitis A virus (HAV) vaccine
• preferences for combination vaccines
• timing of poliovirus vaccine doses
• resumption of the normal Haemophilus influenzae Type b (Hib) schedule, as shortages have resolved
• the use of a new bivalent human papilloma virus (HPV2) vaccine in women and quadrivalent (HPV4) vaccine in men
• a reduced-dose schedule for rabies postexposure prophylaxis
• proof of immunity against mumps, measles, and rubella for health care workers
• recommendations for meningococcal vaccine boosters.

Adoptive families need more protection against HAV

Each year, approximately 18,000 children are adopted from foreign countries, almost all of them born in countries with high or intermediate rates of HAV, 85% of them under 5 years of age.¹ Identifying adoptees with an acute HAV infection is problematic, because in this age group, fewer than 10% of infected children manifest jaundice.¹ The Centers for Disease Control and Prevention (CDC) has recorded a small number of cases of acute HAV infection traced back to exposure to adoptees, and there is some evidence that 1% to 6% of new international adoptees have acute, and infectious, HAV.¹

In response to these data, the most recent ACIP recommendation expands indications for HAV vaccine to include anyone who will be in close personal contact—living in the same household or providing regular babysitting—with an adoptee from any country with high or intermediate endemic rates of HAV. The vaccine should be given within the first 60 days of the adoptee’s arrival in the United States.¹The first dose of the 2-dose series should be given as soon as the adoption is planned, ideally 2 or more weeks before exposure to the adoptee.

This new recommendation adds to earlier expansions of indications for HAV vaccine, which include universal use in children, use in postexposure prophylaxis, and preexposure protection for travelers.^2,3

ACIP still prefers combination vaccines, with caveats

Increasing numbers of vaccine products with multiple antigens have reduced the number of injections needed to complete the recommended childhood immunization schedule. These new products also create a situation in which parents and physicians have to choose between using the combination products or staying with component vaccines that contain fewer antigens, but necessitate a larger number of injections.

When ACIP considered this dilemma, committee members gave the general preference to combination vaccines. At the same time, the committee acknowledged that many considerations—storage, costs, number of injections, vaccine availability, vaccination status, likelihood of improved coverage, likelihood of return visits, patient preference, and the potential for adverse events—factor into the decision.⁴

MMRV is a special case. One combination product received special attention because of the potential for increased rates of febrile seizures. Combined measles, mumps, rubella, and varicella (MMRV) vaccine is currently in short supply, but when the supply improves it will provide 1 less injection to immunize against 4 childhood viral infections at each of 2 visits. However, there is good evidence that in children 1 to 2 years of age who are receiving the first dose of MMRV, there is an additional incidence of febrile seizures of 1 in every 2300 to 2600, compared with children receiving separate doses of MMR and varicella vaccines.⁵ There is no increased risk for older children or for the second dose.

ACIP considered this risk and recommends discussing the benefits and risks of MMR and varicella separately vs using the MMRV combination vaccine. The committee notes: “Use of MMR and varicella vaccines avoids [the] increased risk for fever and febrile seizures following MMRV vaccine.”⁵

IPV combination dosing is clarified

The inclusion of inactivated poliovirus (IPV) antigen into new combination vaccine products has caused some confusion over the recommended dosing schedule of polio vaccine. ACIP has now clarified that for the recommended 4-dose IPV schedule, the fourth dose should be administered after age 4 and at least 6 months after dose 3. In addition, the minimal intervals (4 weeks) in the first 6 months of life should be used only for those traveling overseas.⁶

Resume normal Hib schedule

With the licensure of a new Hib product (Hiberix, GlaxoSmithKline) for the booster dose of Hib starting at age 15 months, the supply of Hib vaccine has stabilized. Supply is now adequate to resume all 4 doses in the routine schedule and to recall all children who had their booster dose deferred. Children can be vaccinated with Hib through the age of 59 months (prior to their fifth birthday).⁷

 

2 HPV vaccines are now available

With the licensure of an HPV2 vaccine for use in women in the United States (Cervarix, GlaxoSmithKline), 2 HPV vaccine products are now available for use.⁸ An HPV4 vaccine (Gardasil, Merck & Co.) was licensed in 2006. The TABLE compares the composition, dosing schedules, and precaution for these 2 products. Each requires 3 doses, but the age ranges and dosing schedules are slightly different. The HPV4 vaccine contains antigens against HPV types 16 and 18, which cause 70% of cervical cancers and precancerous lesions, and types 6 and 11, which cause 90% of anogenital warts.⁹

The HPV2 vaccine contains antigens for HPV types 16 and 18 only and does not protect against warts. The bivalent product appears to produce a higher level of antibody response and may provide better cross protection against other HPV types. ACIP compared effectiveness studies of both vaccines and decided to show no preference for either vaccine for the prevention of cervical cancer and precancerous lesions.

TABLE
HPV vaccines: A side-by-side comparison

	HPV4	HPV2
Year licensed	2006	2009
Virus-like particle types	6, 11, 16, 18	16,18
Hypersensitivity-related contraindication	Yeast	Latex
Schedule	0, 2, 6 months	0, 1, 6 months
Age range	9-26 years	10-25 years

The recommendation is for routine vaccination with an HPV product for all adolescent girls ages 11 to 12, with catch-up through age 26. If a female wants protection against anogenital warts, HPV4 is recommended. It is preferable to complete a 3-dose series with the same product, but if this is not possible, a series can be completed with the other product. The HPV4 vaccine is made using yeast, and prefilled HPV2 syringes contain latex. Hypersensitivity to these substances is a contraindication to their use. Patients who receive either vaccine should be observed for 15 minutes after the injection to prevent injury from syncope.

HPV4 in men. The HPV4 vaccine has now been licensed in the United States for use in males ages 9 to 26 to prevent anogenital warts. It may also protect against HPV-caused cancers (oral, genital, and anal), but the proof of that is still lacking. ACIP debated whether to recommend HPV4 for boys routinely at age 11 to 12 and decided against this. Instead the group voted for a “permissive” recommendation that states HPV4 may be given to adolescents and young men ages 9 to 26 to prevent warts and that protection is better if it is administered before exposure.¹⁰ This allows vaccine use in young males to be provided in the Vaccines for Children Program, but falls short of including it in the routine vaccine schedules.

The reasons for not recommending HPV4 routinely in young men were the cost and the perception that anogenital warts are primarily a cosmetic problem, although it was acknowledged that they can cause serious psychological morbidity. ACIP acknowledged that using HPV4 in men might lead to more protection for women because viral spread would be reduced, but stated that much more protection for women would be gained from a higher level of vaccination among women. As the evidence of protection against HPV-related cancers in men is gathered, ACIP will probably revisit this recommendation.

For a more detailed discussion of the issues posed by these 2 vaccines, see “The case for HPV immunization” in the Journal of Family Practice, December 2009.¹¹

Rabies vaccine: 4 doses are sufficient

Due to a threatened shortage of rabies vaccine, ACIP commissioned a study to determine if a 4-dose series might be as effective as the licensed 5-dose series. The results showed that a reduced-dose series achieved equivalent antibody levels, so ACIP voted to recommend 4 doses of vaccine at days 0, 3, 7, and 14 postexposure.¹² The vaccine should be part of a 3-pronged approach to prevent rabies after an exposure, along with rabies immune globulin administration and wound cleaning.¹³ The 4-dose schedule differs from the rabies vaccine package inserts and the FDA licensure information.

Tougher immunity criteria for health care personnel

Prior to 2009, criteria for proof of immunity to measles, mumps, or rubella among health care workers included serologic testing, history of 2 vaccines after age 1, physician-diagnosed disease, or being born prior to 1957. The new criteria require laboratory confirmation of a physician diagnosis and add a footnote to the “born before 1957” criterion that states: Institutions with unvaccinated health care workers who lack laboratory evidence of immunity should consider vaccinating them with 2 doses of MMR (for measles and mumps) and 1 dose of MMR (for rubella). In an outbreak, the new standards recommend inoculating unvaccinated health care personnel who do not have serological proof of immunity with 2 doses for outbreaks of measles or mumps and 1 dose during an outbreak of rubella.^14,15

 

Meningococcal booster for those at high risk

ACIP now recommends quadrivalent meningococcal conjugate vaccine (MCV4) for all teens ages 11 to 18 years and for anyone 2 to 55 years of age who is at increased risk for meningococcal disease.¹⁶ MCV4 is licensed as a single dose.

Because of the high risk for meningococcal disease among certain groups of people, as well as limited data on duration of protection, ACIP now recommends that individuals previously vaccinated with either MCV4 or meningococcal polysaccharide vaccine (MPSV4) who are at prolonged increased risk be revaccinated with MCV4.

Those who were previously vaccinated at 7 years of age or older should be revaccinated 5 years after their previous meningococcal vaccine; individuals who were previously vaccinated at ages 2 to 6 years should be revaccinated 3 years after their previous meningococcal vaccine.

Individuals at prolonged risk for meningococcal disease are those with complement component deficiencies or anatomic or functional asplenia, microbiologists who routinely work with Neisseria meningitides, and travelers to countries where meningococcal disease is hyperendemic or epidemic.

College freshmen living in dormitories who were previously vaccinated with MCV4 do not need to be revaccinated. However, college freshmen living in dormitories who were vaccinated with MPSV4 ≥5 years previously should be vaccinated with MCV4.

New pneumococcal vaccine with more coverage
A new pneumococcal conjugate vaccine (PCV13) for infants and children will be licensed soon. It will replace the PCV7 vaccine now recommended routinely. ACIP will make recommendations on how to introduce PCV13 into a schedule for infants and children who are in the middle of a PCV7 series, and for catch-up vaccination for children who have completed a PCV7 series.

The new vaccine will provide added protection against an additional 6 types of pneumococcal bacteria, and will replace the older product immediately after licensure. It is unclear what will become of unused supplies of PCV7. Physicians who need to order PCV7 in this interim period before the new vaccine is licensed will be faced with difficult choices. The options include ordering only small quantities or trying to get an advance commitment from the manufacturers to take back any unused vaccine.

The Advisory Committee on Immunization Practices (ACIP) made a number of major new recommendations last year. These new recommendations address:

• expanded use of hepatitis A virus (HAV) vaccine
• preferences for combination vaccines
• timing of poliovirus vaccine doses
• resumption of the normal Haemophilus influenzae Type b (Hib) schedule, as shortages have resolved
• the use of a new bivalent human papilloma virus (HPV2) vaccine in women and quadrivalent (HPV4) vaccine in men
• a reduced-dose schedule for rabies postexposure prophylaxis
• proof of immunity against mumps, measles, and rubella for health care workers
• recommendations for meningococcal vaccine boosters.

Adoptive families need more protection against HAV

Each year, approximately 18,000 children are adopted from foreign countries, almost all of them born in countries with high or intermediate rates of HAV, 85% of them under 5 years of age.¹ Identifying adoptees with an acute HAV infection is problematic, because in this age group, fewer than 10% of infected children manifest jaundice.¹ The Centers for Disease Control and Prevention (CDC) has recorded a small number of cases of acute HAV infection traced back to exposure to adoptees, and there is some evidence that 1% to 6% of new international adoptees have acute, and infectious, HAV.¹

In response to these data, the most recent ACIP recommendation expands indications for HAV vaccine to include anyone who will be in close personal contact—living in the same household or providing regular babysitting—with an adoptee from any country with high or intermediate endemic rates of HAV. The vaccine should be given within the first 60 days of the adoptee’s arrival in the United States.¹The first dose of the 2-dose series should be given as soon as the adoption is planned, ideally 2 or more weeks before exposure to the adoptee.

This new recommendation adds to earlier expansions of indications for HAV vaccine, which include universal use in children, use in postexposure prophylaxis, and preexposure protection for travelers.^2,3

ACIP still prefers combination vaccines, with caveats

Increasing numbers of vaccine products with multiple antigens have reduced the number of injections needed to complete the recommended childhood immunization schedule. These new products also create a situation in which parents and physicians have to choose between using the combination products or staying with component vaccines that contain fewer antigens, but necessitate a larger number of injections.

When ACIP considered this dilemma, committee members gave the general preference to combination vaccines. At the same time, the committee acknowledged that many considerations—storage, costs, number of injections, vaccine availability, vaccination status, likelihood of improved coverage, likelihood of return visits, patient preference, and the potential for adverse events—factor into the decision.⁴

MMRV is a special case. One combination product received special attention because of the potential for increased rates of febrile seizures. Combined measles, mumps, rubella, and varicella (MMRV) vaccine is currently in short supply, but when the supply improves it will provide 1 less injection to immunize against 4 childhood viral infections at each of 2 visits. However, there is good evidence that in children 1 to 2 years of age who are receiving the first dose of MMRV, there is an additional incidence of febrile seizures of 1 in every 2300 to 2600, compared with children receiving separate doses of MMR and varicella vaccines.⁵ There is no increased risk for older children or for the second dose.

ACIP considered this risk and recommends discussing the benefits and risks of MMR and varicella separately vs using the MMRV combination vaccine. The committee notes: “Use of MMR and varicella vaccines avoids [the] increased risk for fever and febrile seizures following MMRV vaccine.”⁵

IPV combination dosing is clarified

The inclusion of inactivated poliovirus (IPV) antigen into new combination vaccine products has caused some confusion over the recommended dosing schedule of polio vaccine. ACIP has now clarified that for the recommended 4-dose IPV schedule, the fourth dose should be administered after age 4 and at least 6 months after dose 3. In addition, the minimal intervals (4 weeks) in the first 6 months of life should be used only for those traveling overseas.⁶

Resume normal Hib schedule

With the licensure of a new Hib product (Hiberix, GlaxoSmithKline) for the booster dose of Hib starting at age 15 months, the supply of Hib vaccine has stabilized. Supply is now adequate to resume all 4 doses in the routine schedule and to recall all children who had their booster dose deferred. Children can be vaccinated with Hib through the age of 59 months (prior to their fifth birthday).⁷

 

2 HPV vaccines are now available

With the licensure of an HPV2 vaccine for use in women in the United States (Cervarix, GlaxoSmithKline), 2 HPV vaccine products are now available for use.⁸ An HPV4 vaccine (Gardasil, Merck & Co.) was licensed in 2006. The TABLE compares the composition, dosing schedules, and precaution for these 2 products. Each requires 3 doses, but the age ranges and dosing schedules are slightly different. The HPV4 vaccine contains antigens against HPV types 16 and 18, which cause 70% of cervical cancers and precancerous lesions, and types 6 and 11, which cause 90% of anogenital warts.⁹

The HPV2 vaccine contains antigens for HPV types 16 and 18 only and does not protect against warts. The bivalent product appears to produce a higher level of antibody response and may provide better cross protection against other HPV types. ACIP compared effectiveness studies of both vaccines and decided to show no preference for either vaccine for the prevention of cervical cancer and precancerous lesions.

TABLE
HPV vaccines: A side-by-side comparison

	HPV4	HPV2
Year licensed	2006	2009
Virus-like particle types	6, 11, 16, 18	16,18
Hypersensitivity-related contraindication	Yeast	Latex
Schedule	0, 2, 6 months	0, 1, 6 months
Age range	9-26 years	10-25 years

The recommendation is for routine vaccination with an HPV product for all adolescent girls ages 11 to 12, with catch-up through age 26. If a female wants protection against anogenital warts, HPV4 is recommended. It is preferable to complete a 3-dose series with the same product, but if this is not possible, a series can be completed with the other product. The HPV4 vaccine is made using yeast, and prefilled HPV2 syringes contain latex. Hypersensitivity to these substances is a contraindication to their use. Patients who receive either vaccine should be observed for 15 minutes after the injection to prevent injury from syncope.

HPV4 in men. The HPV4 vaccine has now been licensed in the United States for use in males ages 9 to 26 to prevent anogenital warts. It may also protect against HPV-caused cancers (oral, genital, and anal), but the proof of that is still lacking. ACIP debated whether to recommend HPV4 for boys routinely at age 11 to 12 and decided against this. Instead the group voted for a “permissive” recommendation that states HPV4 may be given to adolescents and young men ages 9 to 26 to prevent warts and that protection is better if it is administered before exposure.¹⁰ This allows vaccine use in young males to be provided in the Vaccines for Children Program, but falls short of including it in the routine vaccine schedules.

The reasons for not recommending HPV4 routinely in young men were the cost and the perception that anogenital warts are primarily a cosmetic problem, although it was acknowledged that they can cause serious psychological morbidity. ACIP acknowledged that using HPV4 in men might lead to more protection for women because viral spread would be reduced, but stated that much more protection for women would be gained from a higher level of vaccination among women. As the evidence of protection against HPV-related cancers in men is gathered, ACIP will probably revisit this recommendation.

For a more detailed discussion of the issues posed by these 2 vaccines, see “The case for HPV immunization” in the Journal of Family Practice, December 2009.¹¹

Rabies vaccine: 4 doses are sufficient

Due to a threatened shortage of rabies vaccine, ACIP commissioned a study to determine if a 4-dose series might be as effective as the licensed 5-dose series. The results showed that a reduced-dose series achieved equivalent antibody levels, so ACIP voted to recommend 4 doses of vaccine at days 0, 3, 7, and 14 postexposure.¹² The vaccine should be part of a 3-pronged approach to prevent rabies after an exposure, along with rabies immune globulin administration and wound cleaning.¹³ The 4-dose schedule differs from the rabies vaccine package inserts and the FDA licensure information.

Tougher immunity criteria for health care personnel

Prior to 2009, criteria for proof of immunity to measles, mumps, or rubella among health care workers included serologic testing, history of 2 vaccines after age 1, physician-diagnosed disease, or being born prior to 1957. The new criteria require laboratory confirmation of a physician diagnosis and add a footnote to the “born before 1957” criterion that states: Institutions with unvaccinated health care workers who lack laboratory evidence of immunity should consider vaccinating them with 2 doses of MMR (for measles and mumps) and 1 dose of MMR (for rubella). In an outbreak, the new standards recommend inoculating unvaccinated health care personnel who do not have serological proof of immunity with 2 doses for outbreaks of measles or mumps and 1 dose during an outbreak of rubella.^14,15

 

Meningococcal booster for those at high risk

ACIP now recommends quadrivalent meningococcal conjugate vaccine (MCV4) for all teens ages 11 to 18 years and for anyone 2 to 55 years of age who is at increased risk for meningococcal disease.¹⁶ MCV4 is licensed as a single dose.

Because of the high risk for meningococcal disease among certain groups of people, as well as limited data on duration of protection, ACIP now recommends that individuals previously vaccinated with either MCV4 or meningococcal polysaccharide vaccine (MPSV4) who are at prolonged increased risk be revaccinated with MCV4.

Those who were previously vaccinated at 7 years of age or older should be revaccinated 5 years after their previous meningococcal vaccine; individuals who were previously vaccinated at ages 2 to 6 years should be revaccinated 3 years after their previous meningococcal vaccine.

Individuals at prolonged risk for meningococcal disease are those with complement component deficiencies or anatomic or functional asplenia, microbiologists who routinely work with Neisseria meningitides, and travelers to countries where meningococcal disease is hyperendemic or epidemic.

College freshmen living in dormitories who were previously vaccinated with MCV4 do not need to be revaccinated. However, college freshmen living in dormitories who were vaccinated with MPSV4 ≥5 years previously should be vaccinated with MCV4.

New pneumococcal vaccine with more coverage
A new pneumococcal conjugate vaccine (PCV13) for infants and children will be licensed soon. It will replace the PCV7 vaccine now recommended routinely. ACIP will make recommendations on how to introduce PCV13 into a schedule for infants and children who are in the middle of a PCV7 series, and for catch-up vaccination for children who have completed a PCV7 series.

The new vaccine will provide added protection against an additional 6 types of pneumococcal bacteria, and will replace the older product immediately after licensure. It is unclear what will become of unused supplies of PCV7. Physicians who need to order PCV7 in this interim period before the new vaccine is licensed will be faced with difficult choices. The options include ordering only small quantities or trying to get an advance commitment from the manufacturers to take back any unused vaccine.