ID Consult

Do the right thing: Immunize yourself and your office staff!

With the recent licensure of a new acellular pertussis vaccine for adults, now is a good time to review the immunization status of heath care workers in your setting. We should protect ourselves against vaccine-preventable diseases such as pertussis, influenza, varicella, and hepatitis A so that our patients will be protected as well.

Indeed, the federal government has prioritized immunization of health care workers in its pandemic influenza preparedness plan. Without the personnel to care for affected individuals in the event of a human H5N1 outbreak, we would be risking a greater disaster.

Health care workers who treat children have a particular responsibility to protect themselves. As we know, children less than 6 months of age are vulnerable to a wide variety of infections for which they have not yet been fully immunized. Infants born prematurely—more of whom are surviving today—also remain at high risk for infection during the first year of life.

We also are seeing increasing numbers of older children with chronic diseases such as asthma, as well as more of those left immunosuppressed from formerly fatal diseases such as cancer and HIV. We simply cannot allow ourselves to become the agents for transmission to these vulnerable patients.

I want to touch on four adult vaccines in particular:

Pertussis

Earlier this year, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) recommended that health care workers in hospitals or ambulatory care settings and those who have direct patient contact should receive the recently licensed adult formulation of the tetanus-diphtheria-acellular pertussis vaccine (Adacel, Sanofi Pasteur). Priority should be given to providers who have direct contact with infants who are less than 12 months of age.

Because the efficacy of routine childhood pertussis immunization decays after about 10 years, most adults are currently susceptible to pertussis. Although the disease is rarely fatal in adults (as it can be in infants), it does cause prolonged cough lasting for 3 or more weeks in 80%–100% of adults, and posttussive vomiting in 50%. Missed work for illness or medical care occurs in 78% of adults for a mean of 9.8 days, according to data from the CDC.

Transmission of pertussis is most likely to occur during the early phase of disease (catarrhal stage), when cough and coryza are unlikely to be recognized as anything other than a cold. Now that there's a licensed vaccine that will prevent pertussis transmission—not to mention updating our tetanus and diphtheria immunity—it's in everybody's best interest for health care workers to just get vaccinated.

Influenza

Protection against annual influenza also is essential for health care workers who see children. Both the ACIP and the American Academy of Pediatrics now recommend that all children aged 6–59 months receive an annual influenza vaccination. However, children under 6 months of age remain susceptible. Moreover, any child who has not previously received an influenza vaccine needs two doses over a 6-week period, and remains susceptible for several weeks after receiving the second dose.

Health care workers who are younger than 50 years of age and don't have high-risk chronic conditions have the option of choosing the live attenuated virus influenza vaccine (FluMist, MedImmune Inc.) as an alternative to the inactivated injectable vaccine.

For the vast majority of health care workers, there is no need to refrain from working after receipt of the live virus vaccine.

The only exception is those who have direct contact with severely immunosuppressed patients, such as bone marrow recipients.

Varicella

Although the routine childhood vaccine has dramatically reduced its incidence and severity, varicella still persists in the community. When it does occur in adults, it tends to be far more serious than it is in children.

The importance of immunity to varicella is even more critical now that varicella zoster immune globulin—previously given following a known exposure to varicella—is no longer being manufactured in the United States. It's available as an experimental product from Canada, but even if you were able to obtain a supply, it would not likely be in enough time to avert the full-blown clinical picture. You can still take acyclovir prophylactically, but only if you know you've been exposed.

Most pediatricians practicing today have already had chickenpox and are, therefore, immune.

However, that may not be true much longer. Every year my hospital tests incoming medical students for antibodies to varicella, and this past year we found that 10% of these young adults lacked immunity.

Hepatitis A

Last fall, ACIP recommended that all children at least 1 year of age receive the hepatitis A vaccine. Typically, children with hepatitis A infection are either asymptomatic or have nonspecific symptoms such as fever and gastroenteritis. Jaundice is uncommon. If you are treating a child with hepatitis A, you are at high risk for clinically significant illness, including jaundice.

While there is no specific recommendation for hepatitis A vaccination of health care workers, the CDC does state that the vaccine can be given to “any person wishing to obtain immunity.” For those of us whose job is to protect our patients and ourselves, I think it's a good idea.

For more on adult immunization, go to www.cdc.gov/nip/recs/adult-schedule.htm

Do the right thing: Immunize yourself and your office staff!

With the recent licensure of a new acellular pertussis vaccine for adults, now is a good time to review the immunization status of heath care workers in your setting. We should protect ourselves against vaccine-preventable diseases such as pertussis, influenza, varicella, and hepatitis A so that our patients will be protected as well.

Indeed, the federal government has prioritized immunization of health care workers in its pandemic influenza preparedness plan. Without the personnel to care for affected individuals in the event of a human H5N1 outbreak, we would be risking a greater disaster.

Health care workers who treat children have a particular responsibility to protect themselves. As we know, children less than 6 months of age are vulnerable to a wide variety of infections for which they have not yet been fully immunized. Infants born prematurely—more of whom are surviving today—also remain at high risk for infection during the first year of life.

We also are seeing increasing numbers of older children with chronic diseases such as asthma, as well as more of those left immunosuppressed from formerly fatal diseases such as cancer and HIV. We simply cannot allow ourselves to become the agents for transmission to these vulnerable patients.

I want to touch on four adult vaccines in particular:

Pertussis

Earlier this year, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) recommended that health care workers in hospitals or ambulatory care settings and those who have direct patient contact should receive the recently licensed adult formulation of the tetanus-diphtheria-acellular pertussis vaccine (Adacel, Sanofi Pasteur). Priority should be given to providers who have direct contact with infants who are less than 12 months of age.

Because the efficacy of routine childhood pertussis immunization decays after about 10 years, most adults are currently susceptible to pertussis. Although the disease is rarely fatal in adults (as it can be in infants), it does cause prolonged cough lasting for 3 or more weeks in 80%–100% of adults, and posttussive vomiting in 50%. Missed work for illness or medical care occurs in 78% of adults for a mean of 9.8 days, according to data from the CDC.

Transmission of pertussis is most likely to occur during the early phase of disease (catarrhal stage), when cough and coryza are unlikely to be recognized as anything other than a cold. Now that there's a licensed vaccine that will prevent pertussis transmission—not to mention updating our tetanus and diphtheria immunity—it's in everybody's best interest for health care workers to just get vaccinated.

Influenza

Protection against annual influenza also is essential for health care workers who see children. Both the ACIP and the American Academy of Pediatrics now recommend that all children aged 6–59 months receive an annual influenza vaccination. However, children under 6 months of age remain susceptible. Moreover, any child who has not previously received an influenza vaccine needs two doses over a 6-week period, and remains susceptible for several weeks after receiving the second dose.

Health care workers who are younger than 50 years of age and don't have high-risk chronic conditions have the option of choosing the live attenuated virus influenza vaccine (FluMist, MedImmune Inc.) as an alternative to the inactivated injectable vaccine.

For the vast majority of health care workers, there is no need to refrain from working after receipt of the live virus vaccine.

The only exception is those who have direct contact with severely immunosuppressed patients, such as bone marrow recipients.

Varicella

Although the routine childhood vaccine has dramatically reduced its incidence and severity, varicella still persists in the community. When it does occur in adults, it tends to be far more serious than it is in children.

The importance of immunity to varicella is even more critical now that varicella zoster immune globulin—previously given following a known exposure to varicella—is no longer being manufactured in the United States. It's available as an experimental product from Canada, but even if you were able to obtain a supply, it would not likely be in enough time to avert the full-blown clinical picture. You can still take acyclovir prophylactically, but only if you know you've been exposed.

Most pediatricians practicing today have already had chickenpox and are, therefore, immune.

However, that may not be true much longer. Every year my hospital tests incoming medical students for antibodies to varicella, and this past year we found that 10% of these young adults lacked immunity.

Hepatitis A

Last fall, ACIP recommended that all children at least 1 year of age receive the hepatitis A vaccine. Typically, children with hepatitis A infection are either asymptomatic or have nonspecific symptoms such as fever and gastroenteritis. Jaundice is uncommon. If you are treating a child with hepatitis A, you are at high risk for clinically significant illness, including jaundice.

While there is no specific recommendation for hepatitis A vaccination of health care workers, the CDC does state that the vaccine can be given to “any person wishing to obtain immunity.” For those of us whose job is to protect our patients and ourselves, I think it's a good idea.

For more on adult immunization, go to www.cdc.gov/nip/recs/adult-schedule.htm

Do the right thing: Immunize yourself and your office staff!

With the recent licensure of a new acellular pertussis vaccine for adults, now is a good time to review the immunization status of heath care workers in your setting. We should protect ourselves against vaccine-preventable diseases such as pertussis, influenza, varicella, and hepatitis A so that our patients will be protected as well.

Indeed, the federal government has prioritized immunization of health care workers in its pandemic influenza preparedness plan. Without the personnel to care for affected individuals in the event of a human H5N1 outbreak, we would be risking a greater disaster.

Health care workers who treat children have a particular responsibility to protect themselves. As we know, children less than 6 months of age are vulnerable to a wide variety of infections for which they have not yet been fully immunized. Infants born prematurely—more of whom are surviving today—also remain at high risk for infection during the first year of life.

We also are seeing increasing numbers of older children with chronic diseases such as asthma, as well as more of those left immunosuppressed from formerly fatal diseases such as cancer and HIV. We simply cannot allow ourselves to become the agents for transmission to these vulnerable patients.

I want to touch on four adult vaccines in particular:

Pertussis

Earlier this year, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) recommended that health care workers in hospitals or ambulatory care settings and those who have direct patient contact should receive the recently licensed adult formulation of the tetanus-diphtheria-acellular pertussis vaccine (Adacel, Sanofi Pasteur). Priority should be given to providers who have direct contact with infants who are less than 12 months of age.

Because the efficacy of routine childhood pertussis immunization decays after about 10 years, most adults are currently susceptible to pertussis. Although the disease is rarely fatal in adults (as it can be in infants), it does cause prolonged cough lasting for 3 or more weeks in 80%–100% of adults, and posttussive vomiting in 50%. Missed work for illness or medical care occurs in 78% of adults for a mean of 9.8 days, according to data from the CDC.

Transmission of pertussis is most likely to occur during the early phase of disease (catarrhal stage), when cough and coryza are unlikely to be recognized as anything other than a cold. Now that there's a licensed vaccine that will prevent pertussis transmission—not to mention updating our tetanus and diphtheria immunity—it's in everybody's best interest for health care workers to just get vaccinated.

Influenza

Protection against annual influenza also is essential for health care workers who see children. Both the ACIP and the American Academy of Pediatrics now recommend that all children aged 6–59 months receive an annual influenza vaccination. However, children under 6 months of age remain susceptible. Moreover, any child who has not previously received an influenza vaccine needs two doses over a 6-week period, and remains susceptible for several weeks after receiving the second dose.

Health care workers who are younger than 50 years of age and don't have high-risk chronic conditions have the option of choosing the live attenuated virus influenza vaccine (FluMist, MedImmune Inc.) as an alternative to the inactivated injectable vaccine.

For the vast majority of health care workers, there is no need to refrain from working after receipt of the live virus vaccine.

The only exception is those who have direct contact with severely immunosuppressed patients, such as bone marrow recipients.

Varicella

Although the routine childhood vaccine has dramatically reduced its incidence and severity, varicella still persists in the community. When it does occur in adults, it tends to be far more serious than it is in children.

The importance of immunity to varicella is even more critical now that varicella zoster immune globulin—previously given following a known exposure to varicella—is no longer being manufactured in the United States. It's available as an experimental product from Canada, but even if you were able to obtain a supply, it would not likely be in enough time to avert the full-blown clinical picture. You can still take acyclovir prophylactically, but only if you know you've been exposed.

Most pediatricians practicing today have already had chickenpox and are, therefore, immune.

However, that may not be true much longer. Every year my hospital tests incoming medical students for antibodies to varicella, and this past year we found that 10% of these young adults lacked immunity.

Hepatitis A

Last fall, ACIP recommended that all children at least 1 year of age receive the hepatitis A vaccine. Typically, children with hepatitis A infection are either asymptomatic or have nonspecific symptoms such as fever and gastroenteritis. Jaundice is uncommon. If you are treating a child with hepatitis A, you are at high risk for clinically significant illness, including jaundice.

While there is no specific recommendation for hepatitis A vaccination of health care workers, the CDC does state that the vaccine can be given to “any person wishing to obtain immunity.” For those of us whose job is to protect our patients and ourselves, I think it's a good idea.

For more on adult immunization, go to www.cdc.gov/nip/recs/adult-schedule.htm

You may actually see cases of mumps in the coming year. It's time to get reacquainted with what it looks like, what the complications are, and what the control measures are.

As of the first week of May, a mumps outbreak that began in December 2005 with a few reported cases at a university in eastern Iowa had grown to more than 1,500 confirmed, probable, and suspected cases in Iowa, along with several hundred additional cases reported in Illinois, Indiana, Kansas, Michigan, Minnesota, Missouri, Nebraska, and Wisconsin.

Compare that with an average of just 5 mumps cases per year in Iowa since 1996 and 265 cases annually for the entire country since 2001, and it's obvious we've got a problem that could stay with us for a while.

Mumps is an acute viral illness, first described by Hippocrates in the 5th century. Approximately 40%–50% of patients present with unilateral or bilateral parotitis and fever, while another 20%–30% are asymptomatic.

Before the measles-mumps-rubella (MMR) vaccine entered the U.S. market in 1967, a physician who saw a child with parotitis would automatically think of mumps.

Today, we're more likely to suspect that submaxillary/sublingual swelling is related to lymphadenitis, and a sore throat with fever to strep throat.

Some patients complain of pain in the corner of the jaw and/or an earache, which can be confused with otitis.

For the time being at least, we need to resurrect our clinical suspicion for mumps in order to avoid giving unnecessary antibiotics.

Once you suspect mumps, you can culture the nasopharynx, throat, or urine or do a serology looking for IgM antibodies. Check with your laboratory to make sure that the viral culture they perform will identify mumps because standard shell vial culture could miss it.

Although usually self-limited, mumps can cause complications such as meningitis, encephalitis, inflammation of the testes or ovaries, myocarditis, arthritis, and deafness.

Any of these can occur in the absence of parotitis.

Symptomatic meningitis occurs in up to 15% of cases. In fact, mumps was the most common cause of viral meningitis in the prevaccine era.

Interestingly enough—and this is a clinical pearl—mumps meningitis is associated with a lymphocytic pleocytosis (inflammatory cells in the cerebrospinal fluid) that is typical of viral meningitis, but with a low glucose level.

Most children with typical summertime enterovirus meningitis have normal or low-normal CSF glucose levels, typically around 40%–50% of peripheral glucose.

In contrast, those levels might be somewhere between 10% and 25% with mumps meningitis. A low CSF glucose level might make you think of bacterial meningitis, so again, it's important to rule that out in order to treat appropriately.

In Iowa thus far, the median patient age at onset is 22 years. About one-fifth of all the patients are currently attending college.

Of 1,201 patients for whom vaccine history was investigated, 51% had documentation of receiving two MMR doses, 12% one dose, and 6% no doses. (Information was not available for the other 31%.)

It's not clear why immunized individuals would be contracting mumps. Although waning immunity may be a factor, in highly vaccinated populations a majority of individuals affected by a typical measles outbreak may represent vaccine nonresponders. This observation in the past led to the recommendation for two doses of MMR to be given.

Although a second dose can be given 30 days after the first, we currently give the second dose when a child starts school, potentially leaving the 1- to 5-year-old population vulnerable. Time will tell whether this age group emerges as a high-risk group.

In Iowa, the most common symptoms were parotitis in 60%, sore throat in 50%, submaxillary/maxillary gland swelling in 41%, and fever in 31%. Another 27% had headache, 9% cough, and 6% orchitis; 0.2% (3 patients) had encephalitis. Average duration of symptoms was 5 days.

In the prevaccine era, as many as 50% of postpubertal males with mumps developed testicular inflammation and 5% of postpubertal females developed ovarian inflammation, which may be confused with appendicitis. It's not clear why more cases of those complications haven't been reported in Iowa, although it's possible the information simply hasn't been sought.

Since mumps is self-limited, there's not much we can do as clinicians other than to make sure that our patients—as well as ourselves and our staffs—have received two doses of the MMR vaccine.

One dose of MMR is said to be 97% effective against mumps, but immunogenicity studies vary and some suggest that a single dose may protect 85%. A second dose may bring the protection rate to 90% or more. Vaccine immunity probably doesn't last more than 25 years. Mumps is similar in transmissibility to influenza and rubella, but less so than either measles or varicella.

Individuals born before 1957 are believed to be immune because they were exposed, but we're not sure about the status of those born between 1957 and the time the vaccine came into widespread use, in the mid-1970s.

The CDC has advised that the vaccine be offered to these individuals living in affected areas.

Suspected cases should be reported immediately to local public health officials, and those individuals should be isolated for 9 days after symptom onset. It is possible the CDC will make further recommendations after this column goes to press.

MMR vaccine has a good safety profile, but adult women may develop a transient arthritis/arthralgia following vaccination. Studies show that 12%–26% of adult female vaccine recipients, compared with 0%–3% of children, will have arthralgia; the rate in adolescent girls falls somewhere in between.

The majority of cases are mild and don't interfere with normal activity.

More information and updates are available from the CDC at www.cdc.gov/nip/diseases/mumps/mumps-outbreak.htm

CDC/NIP/Barbara Rice

You may actually see cases of mumps in the coming year. It's time to get reacquainted with what it looks like, what the complications are, and what the control measures are.

As of the first week of May, a mumps outbreak that began in December 2005 with a few reported cases at a university in eastern Iowa had grown to more than 1,500 confirmed, probable, and suspected cases in Iowa, along with several hundred additional cases reported in Illinois, Indiana, Kansas, Michigan, Minnesota, Missouri, Nebraska, and Wisconsin.

Compare that with an average of just 5 mumps cases per year in Iowa since 1996 and 265 cases annually for the entire country since 2001, and it's obvious we've got a problem that could stay with us for a while.

Mumps is an acute viral illness, first described by Hippocrates in the 5th century. Approximately 40%–50% of patients present with unilateral or bilateral parotitis and fever, while another 20%–30% are asymptomatic.

Before the measles-mumps-rubella (MMR) vaccine entered the U.S. market in 1967, a physician who saw a child with parotitis would automatically think of mumps.

Today, we're more likely to suspect that submaxillary/sublingual swelling is related to lymphadenitis, and a sore throat with fever to strep throat.

Some patients complain of pain in the corner of the jaw and/or an earache, which can be confused with otitis.

For the time being at least, we need to resurrect our clinical suspicion for mumps in order to avoid giving unnecessary antibiotics.

Once you suspect mumps, you can culture the nasopharynx, throat, or urine or do a serology looking for IgM antibodies. Check with your laboratory to make sure that the viral culture they perform will identify mumps because standard shell vial culture could miss it.

Although usually self-limited, mumps can cause complications such as meningitis, encephalitis, inflammation of the testes or ovaries, myocarditis, arthritis, and deafness.

Any of these can occur in the absence of parotitis.

Symptomatic meningitis occurs in up to 15% of cases. In fact, mumps was the most common cause of viral meningitis in the prevaccine era.

Interestingly enough—and this is a clinical pearl—mumps meningitis is associated with a lymphocytic pleocytosis (inflammatory cells in the cerebrospinal fluid) that is typical of viral meningitis, but with a low glucose level.

Most children with typical summertime enterovirus meningitis have normal or low-normal CSF glucose levels, typically around 40%–50% of peripheral glucose.

In contrast, those levels might be somewhere between 10% and 25% with mumps meningitis. A low CSF glucose level might make you think of bacterial meningitis, so again, it's important to rule that out in order to treat appropriately.

In Iowa thus far, the median patient age at onset is 22 years. About one-fifth of all the patients are currently attending college.

Of 1,201 patients for whom vaccine history was investigated, 51% had documentation of receiving two MMR doses, 12% one dose, and 6% no doses. (Information was not available for the other 31%.)

It's not clear why immunized individuals would be contracting mumps. Although waning immunity may be a factor, in highly vaccinated populations a majority of individuals affected by a typical measles outbreak may represent vaccine nonresponders. This observation in the past led to the recommendation for two doses of MMR to be given.

Although a second dose can be given 30 days after the first, we currently give the second dose when a child starts school, potentially leaving the 1- to 5-year-old population vulnerable. Time will tell whether this age group emerges as a high-risk group.

In Iowa, the most common symptoms were parotitis in 60%, sore throat in 50%, submaxillary/maxillary gland swelling in 41%, and fever in 31%. Another 27% had headache, 9% cough, and 6% orchitis; 0.2% (3 patients) had encephalitis. Average duration of symptoms was 5 days.

In the prevaccine era, as many as 50% of postpubertal males with mumps developed testicular inflammation and 5% of postpubertal females developed ovarian inflammation, which may be confused with appendicitis. It's not clear why more cases of those complications haven't been reported in Iowa, although it's possible the information simply hasn't been sought.

Since mumps is self-limited, there's not much we can do as clinicians other than to make sure that our patients—as well as ourselves and our staffs—have received two doses of the MMR vaccine.

One dose of MMR is said to be 97% effective against mumps, but immunogenicity studies vary and some suggest that a single dose may protect 85%. A second dose may bring the protection rate to 90% or more. Vaccine immunity probably doesn't last more than 25 years. Mumps is similar in transmissibility to influenza and rubella, but less so than either measles or varicella.

Individuals born before 1957 are believed to be immune because they were exposed, but we're not sure about the status of those born between 1957 and the time the vaccine came into widespread use, in the mid-1970s.

The CDC has advised that the vaccine be offered to these individuals living in affected areas.

Suspected cases should be reported immediately to local public health officials, and those individuals should be isolated for 9 days after symptom onset. It is possible the CDC will make further recommendations after this column goes to press.

MMR vaccine has a good safety profile, but adult women may develop a transient arthritis/arthralgia following vaccination. Studies show that 12%–26% of adult female vaccine recipients, compared with 0%–3% of children, will have arthralgia; the rate in adolescent girls falls somewhere in between.

The majority of cases are mild and don't interfere with normal activity.

More information and updates are available from the CDC at www.cdc.gov/nip/diseases/mumps/mumps-outbreak.htm

CDC/NIP/Barbara Rice

You may actually see cases of mumps in the coming year. It's time to get reacquainted with what it looks like, what the complications are, and what the control measures are.

As of the first week of May, a mumps outbreak that began in December 2005 with a few reported cases at a university in eastern Iowa had grown to more than 1,500 confirmed, probable, and suspected cases in Iowa, along with several hundred additional cases reported in Illinois, Indiana, Kansas, Michigan, Minnesota, Missouri, Nebraska, and Wisconsin.

Compare that with an average of just 5 mumps cases per year in Iowa since 1996 and 265 cases annually for the entire country since 2001, and it's obvious we've got a problem that could stay with us for a while.

Mumps is an acute viral illness, first described by Hippocrates in the 5th century. Approximately 40%–50% of patients present with unilateral or bilateral parotitis and fever, while another 20%–30% are asymptomatic.

Before the measles-mumps-rubella (MMR) vaccine entered the U.S. market in 1967, a physician who saw a child with parotitis would automatically think of mumps.

Today, we're more likely to suspect that submaxillary/sublingual swelling is related to lymphadenitis, and a sore throat with fever to strep throat.

Some patients complain of pain in the corner of the jaw and/or an earache, which can be confused with otitis.

For the time being at least, we need to resurrect our clinical suspicion for mumps in order to avoid giving unnecessary antibiotics.

Once you suspect mumps, you can culture the nasopharynx, throat, or urine or do a serology looking for IgM antibodies. Check with your laboratory to make sure that the viral culture they perform will identify mumps because standard shell vial culture could miss it.

Although usually self-limited, mumps can cause complications such as meningitis, encephalitis, inflammation of the testes or ovaries, myocarditis, arthritis, and deafness.

Any of these can occur in the absence of parotitis.

Symptomatic meningitis occurs in up to 15% of cases. In fact, mumps was the most common cause of viral meningitis in the prevaccine era.

Interestingly enough—and this is a clinical pearl—mumps meningitis is associated with a lymphocytic pleocytosis (inflammatory cells in the cerebrospinal fluid) that is typical of viral meningitis, but with a low glucose level.

Most children with typical summertime enterovirus meningitis have normal or low-normal CSF glucose levels, typically around 40%–50% of peripheral glucose.

In contrast, those levels might be somewhere between 10% and 25% with mumps meningitis. A low CSF glucose level might make you think of bacterial meningitis, so again, it's important to rule that out in order to treat appropriately.

In Iowa thus far, the median patient age at onset is 22 years. About one-fifth of all the patients are currently attending college.

Of 1,201 patients for whom vaccine history was investigated, 51% had documentation of receiving two MMR doses, 12% one dose, and 6% no doses. (Information was not available for the other 31%.)

It's not clear why immunized individuals would be contracting mumps. Although waning immunity may be a factor, in highly vaccinated populations a majority of individuals affected by a typical measles outbreak may represent vaccine nonresponders. This observation in the past led to the recommendation for two doses of MMR to be given.

Although a second dose can be given 30 days after the first, we currently give the second dose when a child starts school, potentially leaving the 1- to 5-year-old population vulnerable. Time will tell whether this age group emerges as a high-risk group.

In Iowa, the most common symptoms were parotitis in 60%, sore throat in 50%, submaxillary/maxillary gland swelling in 41%, and fever in 31%. Another 27% had headache, 9% cough, and 6% orchitis; 0.2% (3 patients) had encephalitis. Average duration of symptoms was 5 days.

In the prevaccine era, as many as 50% of postpubertal males with mumps developed testicular inflammation and 5% of postpubertal females developed ovarian inflammation, which may be confused with appendicitis. It's not clear why more cases of those complications haven't been reported in Iowa, although it's possible the information simply hasn't been sought.

Since mumps is self-limited, there's not much we can do as clinicians other than to make sure that our patients—as well as ourselves and our staffs—have received two doses of the MMR vaccine.

One dose of MMR is said to be 97% effective against mumps, but immunogenicity studies vary and some suggest that a single dose may protect 85%. A second dose may bring the protection rate to 90% or more. Vaccine immunity probably doesn't last more than 25 years. Mumps is similar in transmissibility to influenza and rubella, but less so than either measles or varicella.

Individuals born before 1957 are believed to be immune because they were exposed, but we're not sure about the status of those born between 1957 and the time the vaccine came into widespread use, in the mid-1970s.

The CDC has advised that the vaccine be offered to these individuals living in affected areas.

Suspected cases should be reported immediately to local public health officials, and those individuals should be isolated for 9 days after symptom onset. It is possible the CDC will make further recommendations after this column goes to press.

MMR vaccine has a good safety profile, but adult women may develop a transient arthritis/arthralgia following vaccination. Studies show that 12%–26% of adult female vaccine recipients, compared with 0%–3% of children, will have arthralgia; the rate in adolescent girls falls somewhere in between.

The majority of cases are mild and don't interfere with normal activity.

More information and updates are available from the CDC at www.cdc.gov/nip/diseases/mumps/mumps-outbreak.htm

CDC/NIP/Barbara Rice

Novel approaches are necessary to address the emerging problem of the child who fails conventional therapy for acute otorrhea following tympanostomy tube insertion.

We've seen an increase in the number of children with otorrhea through a tympanostomy tube lasting more than 10 days in the past few years, primarily due to the emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Another contributing factor is the increased use of quinolone ear drops, which are thought to promote the occurrence of fungal infections.

Approximately 30% of children who undergo tube placement develop acute otorrhea. Haemophilus influenzae and Streptococcus pneumoniae are responsible for 40%–45% of these cases, particularly in children under 2 years of age and in those who develop symptoms during the winter months. It's hypothesized that these children have ongoing eustachian tube dysfunction that permits nasopharyngeal pathogens to ascend to the middle ear, resulting in acute otorrhea through the tympanostomy tube.

The other 55%–60% of cases are caused by pathogens from the external canal, most commonly Staphylococcus aureus and Pseudomonas aeruginosa. These patients tend to be older, to develop symptoms during the warmer months, and to have a malodorous discharge (in contrast to the nasopharyngeal pathogens, which are odorless).

There appears to be a contribution from water in the ear, which triggers an inflammatory response.

In the past, standard treatment for ear drainage in children was oral antibiotics aimed at H. influenzae and pneumococcus, such as amoxicillin, amoxicillin-clavulanate, or a cephalosporin.

More recently, there has been a shift to greater use of topical fluoroquinolones—particularly ofloxacin and ciprofloxacin—with the increased recognition that the staphylococcus and pseudomonas pathogens also contribute to the microbiology of this disease.

Even in young children, otic preparations are often considered superior to oral antibiotics because they are active against all four of the main pathogens, safely achieve high concentrations in the middle ear, and are less likely to contribute to the emergence of resistance because they are not given systemically.

And of course, they eliminate the bad taste problem.

Now, however, we're starting to see clinical failures with both oral and topical antibiotics, primarily due to CA-MRSA. Among otherwise healthy children, the risk for the development of otorrhea due to MRSA appears to increase with the number of acute otitis media episodes prior to tube placement, as well as with the number of courses and duration of treatment prior to tube placement (Arch. Otolaryngol. Head Neck Surg. 2005;131:868–73).

For MRSA-associated skin and soft tissue infections, drugs such as trimethoprim-sulfamethoxazole, linezolid, or even intravenous vancomycin are usually effective. However, these agents are often ineffective or associated with relapse as soon as therapy is discontinued when a foreign body such as a tympanostomy tube is involved, because of the lack of blood supply and the formation of biofilm.

What does appear to work, at least in small case reports, is the use of either topical vancomycin or combination topical plus oral treatment.

In one report, a group in Thailand combined a 500-mg vial of vancomycin powder with 20 mL of sterile distilled water to create a 25-mg/mL vancomycin solution. Two 0.8-mg drops were placed into the ear three times daily for 10 days in 35 patients with MRSA otorrhea. A control group of 20 patients was treated with the same regimen of gentamycin 0.3% drops (J. Laryngol. Otol. 2004;118:645–7).

Clinical cure was achieved in 30 (86%) of the vancomycin recipients, compared with 2 (10%) of those treated with gentamycin. Failures occurred in just 2 (6%) patients given vancomycin versus 16 (80%) given gentamycin.

Of course, this is a small study, but it is based on sound biologic principles and there appear to be no adverse effects. We certainly need more long-term data, but I think topical vancomycin may represent a good alternative to removal of the tubes in some patients. If your pharmacy is able to make this formulation, I think it offers an option to tube removal if CA-MRSA is cultured and the child fails initial oral or topical therapy.

In another small study, successful eradication of MRSA was achieved using a combination of oral trimethoprim-sulfamethoxazole plus topical gentamycin sulfate or polymyxin B sulfate-neomycin sulfate-hydrocortisone (Cortisporin) in six children (five with prior tympanostomy tube placement and one with perforation of the tympanic membrane) who had failed either oral antibiotics or fluoroquinolone ear drops alone (Arch. Otolaryngol. Head Neck Surg. 2005;131:782–4). However, I'd be less apt to use this approach because of concerns about potential ototoxicity of the gentamycin/neomycin on the vestibular system.

In addition to CA-MRSA, otorrhea due to fungal organisms is now being seen increasingly in children who have been treated previously for bacterial infections following tube placement.

In a retrospective review conducted at a pediatric otolaryngology clinic, out of a total 1,242 patients who underwent ear culture between 1996 and 2003, 166 patients (119 with otitis media, 41 with otitis externa, and 6 with both) aged 16 days to 18 years (mean 4 years) were found to have fungal organisms. The proportion of fungus-positive cultures increased dramatically in the years following the availability of the fluoroquinolone drops, from just 4.2% of 356 cultures obtained during 1996–1998 to 18.2% of the 457 cultures done during 1999–2001 (Int. J. Pediatr. Otorhinolaryngol. 2005;69:1503–8).

The most common of the fungi were Candida albicans (43% of the 166), Candida parapsilosis (23.5%), and Aspergillus fumigatus (21%). Although reporting of medications was inconsistent, the authors estimated that the patients had previously received an average of 1.7 oral antibiotics and 1.1 ototopical agents before the culture was taken. Infection resolved in all the patients with treatment, which included clotrimazole topical and tolnaftate topical in 27 patients each, fluconazole in 25, acetic acid alone in 14, and topical plus fluconazole in 10. The thinking is that the use of broad-spectrum quinolone drops may be promoting the emergence of fungus by eliminating the colonizers in the external ear canal, thereby allowing the fungus to grow. This doesn't imply we should stop using quinolone-containing otic solutions, but I do think we need to be aware of the possibility and culture the middle ear in a child who still has otorrhea after 5–7 days of treatment.

Of course, we all know that prevention is the best medicine.

A group from Turkey recently published a comparison of 1 mL intraoperative isotonic saline irrigation, postoperative antibiotic treatment (sulbactam/ampicillin 25 mg/kg for 5 days), postoperative ofloxacin drops (twice a day for 5 days), or placebo in 280 children (mean age 5.9 years) undergoing bilateral ventilation tube insertion because of serous otitis media during 2000–2004 (Am. J. Otolaryngol. 2005;26:123–7).

At 2 weeks post surgery, purulent otorrhea was observed in 15.7% of the saline group, 14.2% of those who received prophylactic oral antibiotics, and 8.6% of the topical antibiotic group, all significantly lower than the 30% rate among the controls. It appears that saline irrigation of the middle ear prior to tube placement offers a low-cost intervention for reducing early post-tympanostomy tube otorrhea.

Novel approaches are necessary to address the emerging problem of the child who fails conventional therapy for acute otorrhea following tympanostomy tube insertion.

We've seen an increase in the number of children with otorrhea through a tympanostomy tube lasting more than 10 days in the past few years, primarily due to the emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Another contributing factor is the increased use of quinolone ear drops, which are thought to promote the occurrence of fungal infections.

Approximately 30% of children who undergo tube placement develop acute otorrhea. Haemophilus influenzae and Streptococcus pneumoniae are responsible for 40%–45% of these cases, particularly in children under 2 years of age and in those who develop symptoms during the winter months. It's hypothesized that these children have ongoing eustachian tube dysfunction that permits nasopharyngeal pathogens to ascend to the middle ear, resulting in acute otorrhea through the tympanostomy tube.

The other 55%–60% of cases are caused by pathogens from the external canal, most commonly Staphylococcus aureus and Pseudomonas aeruginosa. These patients tend to be older, to develop symptoms during the warmer months, and to have a malodorous discharge (in contrast to the nasopharyngeal pathogens, which are odorless).

There appears to be a contribution from water in the ear, which triggers an inflammatory response.

In the past, standard treatment for ear drainage in children was oral antibiotics aimed at H. influenzae and pneumococcus, such as amoxicillin, amoxicillin-clavulanate, or a cephalosporin.

More recently, there has been a shift to greater use of topical fluoroquinolones—particularly ofloxacin and ciprofloxacin—with the increased recognition that the staphylococcus and pseudomonas pathogens also contribute to the microbiology of this disease.

Even in young children, otic preparations are often considered superior to oral antibiotics because they are active against all four of the main pathogens, safely achieve high concentrations in the middle ear, and are less likely to contribute to the emergence of resistance because they are not given systemically.

And of course, they eliminate the bad taste problem.

Now, however, we're starting to see clinical failures with both oral and topical antibiotics, primarily due to CA-MRSA. Among otherwise healthy children, the risk for the development of otorrhea due to MRSA appears to increase with the number of acute otitis media episodes prior to tube placement, as well as with the number of courses and duration of treatment prior to tube placement (Arch. Otolaryngol. Head Neck Surg. 2005;131:868–73).

For MRSA-associated skin and soft tissue infections, drugs such as trimethoprim-sulfamethoxazole, linezolid, or even intravenous vancomycin are usually effective. However, these agents are often ineffective or associated with relapse as soon as therapy is discontinued when a foreign body such as a tympanostomy tube is involved, because of the lack of blood supply and the formation of biofilm.

What does appear to work, at least in small case reports, is the use of either topical vancomycin or combination topical plus oral treatment.

In one report, a group in Thailand combined a 500-mg vial of vancomycin powder with 20 mL of sterile distilled water to create a 25-mg/mL vancomycin solution. Two 0.8-mg drops were placed into the ear three times daily for 10 days in 35 patients with MRSA otorrhea. A control group of 20 patients was treated with the same regimen of gentamycin 0.3% drops (J. Laryngol. Otol. 2004;118:645–7).

Clinical cure was achieved in 30 (86%) of the vancomycin recipients, compared with 2 (10%) of those treated with gentamycin. Failures occurred in just 2 (6%) patients given vancomycin versus 16 (80%) given gentamycin.

Of course, this is a small study, but it is based on sound biologic principles and there appear to be no adverse effects. We certainly need more long-term data, but I think topical vancomycin may represent a good alternative to removal of the tubes in some patients. If your pharmacy is able to make this formulation, I think it offers an option to tube removal if CA-MRSA is cultured and the child fails initial oral or topical therapy.

In another small study, successful eradication of MRSA was achieved using a combination of oral trimethoprim-sulfamethoxazole plus topical gentamycin sulfate or polymyxin B sulfate-neomycin sulfate-hydrocortisone (Cortisporin) in six children (five with prior tympanostomy tube placement and one with perforation of the tympanic membrane) who had failed either oral antibiotics or fluoroquinolone ear drops alone (Arch. Otolaryngol. Head Neck Surg. 2005;131:782–4). However, I'd be less apt to use this approach because of concerns about potential ototoxicity of the gentamycin/neomycin on the vestibular system.

In addition to CA-MRSA, otorrhea due to fungal organisms is now being seen increasingly in children who have been treated previously for bacterial infections following tube placement.

In a retrospective review conducted at a pediatric otolaryngology clinic, out of a total 1,242 patients who underwent ear culture between 1996 and 2003, 166 patients (119 with otitis media, 41 with otitis externa, and 6 with both) aged 16 days to 18 years (mean 4 years) were found to have fungal organisms. The proportion of fungus-positive cultures increased dramatically in the years following the availability of the fluoroquinolone drops, from just 4.2% of 356 cultures obtained during 1996–1998 to 18.2% of the 457 cultures done during 1999–2001 (Int. J. Pediatr. Otorhinolaryngol. 2005;69:1503–8).

The most common of the fungi were Candida albicans (43% of the 166), Candida parapsilosis (23.5%), and Aspergillus fumigatus (21%). Although reporting of medications was inconsistent, the authors estimated that the patients had previously received an average of 1.7 oral antibiotics and 1.1 ototopical agents before the culture was taken. Infection resolved in all the patients with treatment, which included clotrimazole topical and tolnaftate topical in 27 patients each, fluconazole in 25, acetic acid alone in 14, and topical plus fluconazole in 10. The thinking is that the use of broad-spectrum quinolone drops may be promoting the emergence of fungus by eliminating the colonizers in the external ear canal, thereby allowing the fungus to grow. This doesn't imply we should stop using quinolone-containing otic solutions, but I do think we need to be aware of the possibility and culture the middle ear in a child who still has otorrhea after 5–7 days of treatment.

Of course, we all know that prevention is the best medicine.

A group from Turkey recently published a comparison of 1 mL intraoperative isotonic saline irrigation, postoperative antibiotic treatment (sulbactam/ampicillin 25 mg/kg for 5 days), postoperative ofloxacin drops (twice a day for 5 days), or placebo in 280 children (mean age 5.9 years) undergoing bilateral ventilation tube insertion because of serous otitis media during 2000–2004 (Am. J. Otolaryngol. 2005;26:123–7).

At 2 weeks post surgery, purulent otorrhea was observed in 15.7% of the saline group, 14.2% of those who received prophylactic oral antibiotics, and 8.6% of the topical antibiotic group, all significantly lower than the 30% rate among the controls. It appears that saline irrigation of the middle ear prior to tube placement offers a low-cost intervention for reducing early post-tympanostomy tube otorrhea.

Novel approaches are necessary to address the emerging problem of the child who fails conventional therapy for acute otorrhea following tympanostomy tube insertion.

We've seen an increase in the number of children with otorrhea through a tympanostomy tube lasting more than 10 days in the past few years, primarily due to the emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Another contributing factor is the increased use of quinolone ear drops, which are thought to promote the occurrence of fungal infections.

Approximately 30% of children who undergo tube placement develop acute otorrhea. Haemophilus influenzae and Streptococcus pneumoniae are responsible for 40%–45% of these cases, particularly in children under 2 years of age and in those who develop symptoms during the winter months. It's hypothesized that these children have ongoing eustachian tube dysfunction that permits nasopharyngeal pathogens to ascend to the middle ear, resulting in acute otorrhea through the tympanostomy tube.

The other 55%–60% of cases are caused by pathogens from the external canal, most commonly Staphylococcus aureus and Pseudomonas aeruginosa. These patients tend to be older, to develop symptoms during the warmer months, and to have a malodorous discharge (in contrast to the nasopharyngeal pathogens, which are odorless).

There appears to be a contribution from water in the ear, which triggers an inflammatory response.

In the past, standard treatment for ear drainage in children was oral antibiotics aimed at H. influenzae and pneumococcus, such as amoxicillin, amoxicillin-clavulanate, or a cephalosporin.

More recently, there has been a shift to greater use of topical fluoroquinolones—particularly ofloxacin and ciprofloxacin—with the increased recognition that the staphylococcus and pseudomonas pathogens also contribute to the microbiology of this disease.

Even in young children, otic preparations are often considered superior to oral antibiotics because they are active against all four of the main pathogens, safely achieve high concentrations in the middle ear, and are less likely to contribute to the emergence of resistance because they are not given systemically.

And of course, they eliminate the bad taste problem.

Now, however, we're starting to see clinical failures with both oral and topical antibiotics, primarily due to CA-MRSA. Among otherwise healthy children, the risk for the development of otorrhea due to MRSA appears to increase with the number of acute otitis media episodes prior to tube placement, as well as with the number of courses and duration of treatment prior to tube placement (Arch. Otolaryngol. Head Neck Surg. 2005;131:868–73).

For MRSA-associated skin and soft tissue infections, drugs such as trimethoprim-sulfamethoxazole, linezolid, or even intravenous vancomycin are usually effective. However, these agents are often ineffective or associated with relapse as soon as therapy is discontinued when a foreign body such as a tympanostomy tube is involved, because of the lack of blood supply and the formation of biofilm.

What does appear to work, at least in small case reports, is the use of either topical vancomycin or combination topical plus oral treatment.

In one report, a group in Thailand combined a 500-mg vial of vancomycin powder with 20 mL of sterile distilled water to create a 25-mg/mL vancomycin solution. Two 0.8-mg drops were placed into the ear three times daily for 10 days in 35 patients with MRSA otorrhea. A control group of 20 patients was treated with the same regimen of gentamycin 0.3% drops (J. Laryngol. Otol. 2004;118:645–7).

Clinical cure was achieved in 30 (86%) of the vancomycin recipients, compared with 2 (10%) of those treated with gentamycin. Failures occurred in just 2 (6%) patients given vancomycin versus 16 (80%) given gentamycin.

Of course, this is a small study, but it is based on sound biologic principles and there appear to be no adverse effects. We certainly need more long-term data, but I think topical vancomycin may represent a good alternative to removal of the tubes in some patients. If your pharmacy is able to make this formulation, I think it offers an option to tube removal if CA-MRSA is cultured and the child fails initial oral or topical therapy.

In another small study, successful eradication of MRSA was achieved using a combination of oral trimethoprim-sulfamethoxazole plus topical gentamycin sulfate or polymyxin B sulfate-neomycin sulfate-hydrocortisone (Cortisporin) in six children (five with prior tympanostomy tube placement and one with perforation of the tympanic membrane) who had failed either oral antibiotics or fluoroquinolone ear drops alone (Arch. Otolaryngol. Head Neck Surg. 2005;131:782–4). However, I'd be less apt to use this approach because of concerns about potential ototoxicity of the gentamycin/neomycin on the vestibular system.

In addition to CA-MRSA, otorrhea due to fungal organisms is now being seen increasingly in children who have been treated previously for bacterial infections following tube placement.

In a retrospective review conducted at a pediatric otolaryngology clinic, out of a total 1,242 patients who underwent ear culture between 1996 and 2003, 166 patients (119 with otitis media, 41 with otitis externa, and 6 with both) aged 16 days to 18 years (mean 4 years) were found to have fungal organisms. The proportion of fungus-positive cultures increased dramatically in the years following the availability of the fluoroquinolone drops, from just 4.2% of 356 cultures obtained during 1996–1998 to 18.2% of the 457 cultures done during 1999–2001 (Int. J. Pediatr. Otorhinolaryngol. 2005;69:1503–8).

The most common of the fungi were Candida albicans (43% of the 166), Candida parapsilosis (23.5%), and Aspergillus fumigatus (21%). Although reporting of medications was inconsistent, the authors estimated that the patients had previously received an average of 1.7 oral antibiotics and 1.1 ototopical agents before the culture was taken. Infection resolved in all the patients with treatment, which included clotrimazole topical and tolnaftate topical in 27 patients each, fluconazole in 25, acetic acid alone in 14, and topical plus fluconazole in 10. The thinking is that the use of broad-spectrum quinolone drops may be promoting the emergence of fungus by eliminating the colonizers in the external ear canal, thereby allowing the fungus to grow. This doesn't imply we should stop using quinolone-containing otic solutions, but I do think we need to be aware of the possibility and culture the middle ear in a child who still has otorrhea after 5–7 days of treatment.

Of course, we all know that prevention is the best medicine.

A group from Turkey recently published a comparison of 1 mL intraoperative isotonic saline irrigation, postoperative antibiotic treatment (sulbactam/ampicillin 25 mg/kg for 5 days), postoperative ofloxacin drops (twice a day for 5 days), or placebo in 280 children (mean age 5.9 years) undergoing bilateral ventilation tube insertion because of serous otitis media during 2000–2004 (Am. J. Otolaryngol. 2005;26:123–7).

At 2 weeks post surgery, purulent otorrhea was observed in 15.7% of the saline group, 14.2% of those who received prophylactic oral antibiotics, and 8.6% of the topical antibiotic group, all significantly lower than the 30% rate among the controls. It appears that saline irrigation of the middle ear prior to tube placement offers a low-cost intervention for reducing early post-tympanostomy tube otorrhea.

We now have one—and will probably soon have a second—new and improved rotavirus vaccine, with which we will be able to prevent much of the winter-spring infant gastroenteritis misery. Further, a lower economic burden will result from fewer lost parental workdays. And there's another bonus: Reactogenicity is lower with the new vaccines, compared with the old RotaShield, which was withdrawn from the market in 1999.

The design of the trials that were submitted for Food and Drug Administration approval of the new vaccines included a very large sample size—with over 60,000 children each for both Merck & Co.'s bovine-derived RotaTeq and GlaxoSmithKline's human-derived Rotarix—and close follow-up. Both vaccines have been highly effective against rotavirus disease in the first year of life, including the most severe forms of illness and hospitalizations, with lower rates of vaccine-associated fever, irritability, and loose stools.

Importantly, neither vaccine appears to increase the risk for intussusception, the adverse event that caused the removal of the previous rhesus-derived RotaShield vaccine from the market. Of course, we can't be absolutely certain until the new vaccines are in widespread use—that's when the problem with RotaShield was detected. However, it's likely that the problem would have revealed itself sooner if the recalled vaccine had been tested in 60,000 subjects prior to approval.

Moreover, it makes clinical sense that if a vaccine causes less systemic response (fever, irritability, and loose stools), it also might lead to lesser reactions in the gut-associated lymphoid tissue, a proposed mechanism for the vaccine-provoked intussusceptions.

About 400,000 rotavirus-associated deaths occur each year in the developing world, but rotavirus disease usually isn't lethal for children in the United States (20–60 deaths per year). In this country, cost effectiveness is the prime issue, particularly with regard to reducing the 50,000 annual rotavirus-associated hospitalizations.

According to one estimate, rotavirus costs the United States more than $1 billion a year, including direct medical costs and parental lost workdays. Compare that with the $770 million a year to immunize the estimated 4.1 million infants in an annual birth cohort with Rotateq, which Merck has just announced will cost $62.50/dose when purchased in 10 single-dose packs. Overall, this looks like we can still come out ahead.

The benefits of a protective rotavirus vaccine also may extend beyond simply preventing gastroenteritis. This winter, an 11-month-old ill-appearing child was transferred to our facility with a sepsis picture. He had a high fever, lethargy, vomiting, and a tense fontanelle. However, he had no diarrhea and had CSF pleocytosis (WBC count of 28, half neutrophils). The next day, he developed green, mucus-laden diarrhea, which tested positive for rotavirus antigen. This was a case of aseptic meningitis due to rotavirus infection.

Such nondiarrheal initial presentations of rotavirus infection during the winter and early spring are not all that rare. Indeed, in active surveillance of 763 children aged 15 days through 4 years and admitted to the hospital between November 1997 and June 1998 with eventual rotavirus diagnosis, 9% presented initially without diarrhea (Pediatr. Infect. Dis. J. 2002;21:221–7). Rotavirus as a cause of aseptic meningitis also has been confirmed using polymerase chain reaction detection of rotavirus RNA in the cerebrospinal fluid of children who present with seizures (J. Clin. Microbiol. 2002;40:4797–9).

Although most children with a nondiarrheal initial presentation develop the classic rotavirus stools within 48 hours, the initial sepsislike picture occurs most often in infants under 1 year of age. If the rotavirus antigen assay comes back positive in such patients, you can sometimes avoid adding to the diarrhea with unnecessary antibiotics.

The caveat, however, is that young infants may have positive stool rotavirus antigen tests in the absence of rotavirus-producing disease (false positive). This is thought to represent a “colonization” that occurs in most younger infants, becomes less common after 6 months, and is present in fewer than 10% of children as they reach 1 year of age. For this reason, some laboratories are reluctant to perform rotavirus antigen assays on children less than 6 months of age. So, even with a positive rotavirus assay in a young infant, antibiotics may need to be continued until bacterial cultures are confirmed negative.

Other studies have shown disseminated rotavirus outside the gastrointestinal tract.

One study found rotavirus antigen in 22 of 33 serum samples of children with rotavirus diarrhea, suggesting that the virus can “escape” the GI tract in children, resulting in viremia (Lancet 2003;362:1445–9). The virus itself has also been found in the liver and kidney in immunodeficient children (J. Pediatr. 1992;120:912–7).

Another presentation that can throw you off the rotavirus track is when the presenting symptoms are heavily respiratory in the first 36 hours. Rotavirus has been found in nasopharyngeal secretions of such patients (Diagn. Microbiol. Infect. Dis. 1986;4:87–8), and it makes sense that the upper respiratory tract could be part of the initial portal of infection.

So, beyond a notable reduction in winter diarrhea in infants, the new rotavirus vaccines may also have the added benefit of preventing some febrile seizures and even an occasional case of aseptic meningitis.

I currently have no financial connections with either the Merck or the GSK rotavirus vaccines, although I participated in early studies involving the Merck product more than 5 years ago.

We now have one—and will probably soon have a second—new and improved rotavirus vaccine, with which we will be able to prevent much of the winter-spring infant gastroenteritis misery. Further, a lower economic burden will result from fewer lost parental workdays. And there's another bonus: Reactogenicity is lower with the new vaccines, compared with the old RotaShield, which was withdrawn from the market in 1999.

The design of the trials that were submitted for Food and Drug Administration approval of the new vaccines included a very large sample size—with over 60,000 children each for both Merck & Co.'s bovine-derived RotaTeq and GlaxoSmithKline's human-derived Rotarix—and close follow-up. Both vaccines have been highly effective against rotavirus disease in the first year of life, including the most severe forms of illness and hospitalizations, with lower rates of vaccine-associated fever, irritability, and loose stools.

Importantly, neither vaccine appears to increase the risk for intussusception, the adverse event that caused the removal of the previous rhesus-derived RotaShield vaccine from the market. Of course, we can't be absolutely certain until the new vaccines are in widespread use—that's when the problem with RotaShield was detected. However, it's likely that the problem would have revealed itself sooner if the recalled vaccine had been tested in 60,000 subjects prior to approval.

Moreover, it makes clinical sense that if a vaccine causes less systemic response (fever, irritability, and loose stools), it also might lead to lesser reactions in the gut-associated lymphoid tissue, a proposed mechanism for the vaccine-provoked intussusceptions.

About 400,000 rotavirus-associated deaths occur each year in the developing world, but rotavirus disease usually isn't lethal for children in the United States (20–60 deaths per year). In this country, cost effectiveness is the prime issue, particularly with regard to reducing the 50,000 annual rotavirus-associated hospitalizations.

According to one estimate, rotavirus costs the United States more than $1 billion a year, including direct medical costs and parental lost workdays. Compare that with the $770 million a year to immunize the estimated 4.1 million infants in an annual birth cohort with Rotateq, which Merck has just announced will cost $62.50/dose when purchased in 10 single-dose packs. Overall, this looks like we can still come out ahead.

The benefits of a protective rotavirus vaccine also may extend beyond simply preventing gastroenteritis. This winter, an 11-month-old ill-appearing child was transferred to our facility with a sepsis picture. He had a high fever, lethargy, vomiting, and a tense fontanelle. However, he had no diarrhea and had CSF pleocytosis (WBC count of 28, half neutrophils). The next day, he developed green, mucus-laden diarrhea, which tested positive for rotavirus antigen. This was a case of aseptic meningitis due to rotavirus infection.

Such nondiarrheal initial presentations of rotavirus infection during the winter and early spring are not all that rare. Indeed, in active surveillance of 763 children aged 15 days through 4 years and admitted to the hospital between November 1997 and June 1998 with eventual rotavirus diagnosis, 9% presented initially without diarrhea (Pediatr. Infect. Dis. J. 2002;21:221–7). Rotavirus as a cause of aseptic meningitis also has been confirmed using polymerase chain reaction detection of rotavirus RNA in the cerebrospinal fluid of children who present with seizures (J. Clin. Microbiol. 2002;40:4797–9).

Although most children with a nondiarrheal initial presentation develop the classic rotavirus stools within 48 hours, the initial sepsislike picture occurs most often in infants under 1 year of age. If the rotavirus antigen assay comes back positive in such patients, you can sometimes avoid adding to the diarrhea with unnecessary antibiotics.

The caveat, however, is that young infants may have positive stool rotavirus antigen tests in the absence of rotavirus-producing disease (false positive). This is thought to represent a “colonization” that occurs in most younger infants, becomes less common after 6 months, and is present in fewer than 10% of children as they reach 1 year of age. For this reason, some laboratories are reluctant to perform rotavirus antigen assays on children less than 6 months of age. So, even with a positive rotavirus assay in a young infant, antibiotics may need to be continued until bacterial cultures are confirmed negative.

Other studies have shown disseminated rotavirus outside the gastrointestinal tract.

One study found rotavirus antigen in 22 of 33 serum samples of children with rotavirus diarrhea, suggesting that the virus can “escape” the GI tract in children, resulting in viremia (Lancet 2003;362:1445–9). The virus itself has also been found in the liver and kidney in immunodeficient children (J. Pediatr. 1992;120:912–7).

Another presentation that can throw you off the rotavirus track is when the presenting symptoms are heavily respiratory in the first 36 hours. Rotavirus has been found in nasopharyngeal secretions of such patients (Diagn. Microbiol. Infect. Dis. 1986;4:87–8), and it makes sense that the upper respiratory tract could be part of the initial portal of infection.

So, beyond a notable reduction in winter diarrhea in infants, the new rotavirus vaccines may also have the added benefit of preventing some febrile seizures and even an occasional case of aseptic meningitis.

I currently have no financial connections with either the Merck or the GSK rotavirus vaccines, although I participated in early studies involving the Merck product more than 5 years ago.

We now have one—and will probably soon have a second—new and improved rotavirus vaccine, with which we will be able to prevent much of the winter-spring infant gastroenteritis misery. Further, a lower economic burden will result from fewer lost parental workdays. And there's another bonus: Reactogenicity is lower with the new vaccines, compared with the old RotaShield, which was withdrawn from the market in 1999.

The design of the trials that were submitted for Food and Drug Administration approval of the new vaccines included a very large sample size—with over 60,000 children each for both Merck & Co.'s bovine-derived RotaTeq and GlaxoSmithKline's human-derived Rotarix—and close follow-up. Both vaccines have been highly effective against rotavirus disease in the first year of life, including the most severe forms of illness and hospitalizations, with lower rates of vaccine-associated fever, irritability, and loose stools.

Importantly, neither vaccine appears to increase the risk for intussusception, the adverse event that caused the removal of the previous rhesus-derived RotaShield vaccine from the market. Of course, we can't be absolutely certain until the new vaccines are in widespread use—that's when the problem with RotaShield was detected. However, it's likely that the problem would have revealed itself sooner if the recalled vaccine had been tested in 60,000 subjects prior to approval.

Moreover, it makes clinical sense that if a vaccine causes less systemic response (fever, irritability, and loose stools), it also might lead to lesser reactions in the gut-associated lymphoid tissue, a proposed mechanism for the vaccine-provoked intussusceptions.

About 400,000 rotavirus-associated deaths occur each year in the developing world, but rotavirus disease usually isn't lethal for children in the United States (20–60 deaths per year). In this country, cost effectiveness is the prime issue, particularly with regard to reducing the 50,000 annual rotavirus-associated hospitalizations.

According to one estimate, rotavirus costs the United States more than $1 billion a year, including direct medical costs and parental lost workdays. Compare that with the $770 million a year to immunize the estimated 4.1 million infants in an annual birth cohort with Rotateq, which Merck has just announced will cost $62.50/dose when purchased in 10 single-dose packs. Overall, this looks like we can still come out ahead.

The benefits of a protective rotavirus vaccine also may extend beyond simply preventing gastroenteritis. This winter, an 11-month-old ill-appearing child was transferred to our facility with a sepsis picture. He had a high fever, lethargy, vomiting, and a tense fontanelle. However, he had no diarrhea and had CSF pleocytosis (WBC count of 28, half neutrophils). The next day, he developed green, mucus-laden diarrhea, which tested positive for rotavirus antigen. This was a case of aseptic meningitis due to rotavirus infection.

Such nondiarrheal initial presentations of rotavirus infection during the winter and early spring are not all that rare. Indeed, in active surveillance of 763 children aged 15 days through 4 years and admitted to the hospital between November 1997 and June 1998 with eventual rotavirus diagnosis, 9% presented initially without diarrhea (Pediatr. Infect. Dis. J. 2002;21:221–7). Rotavirus as a cause of aseptic meningitis also has been confirmed using polymerase chain reaction detection of rotavirus RNA in the cerebrospinal fluid of children who present with seizures (J. Clin. Microbiol. 2002;40:4797–9).

Although most children with a nondiarrheal initial presentation develop the classic rotavirus stools within 48 hours, the initial sepsislike picture occurs most often in infants under 1 year of age. If the rotavirus antigen assay comes back positive in such patients, you can sometimes avoid adding to the diarrhea with unnecessary antibiotics.

The caveat, however, is that young infants may have positive stool rotavirus antigen tests in the absence of rotavirus-producing disease (false positive). This is thought to represent a “colonization” that occurs in most younger infants, becomes less common after 6 months, and is present in fewer than 10% of children as they reach 1 year of age. For this reason, some laboratories are reluctant to perform rotavirus antigen assays on children less than 6 months of age. So, even with a positive rotavirus assay in a young infant, antibiotics may need to be continued until bacterial cultures are confirmed negative.

Other studies have shown disseminated rotavirus outside the gastrointestinal tract.

One study found rotavirus antigen in 22 of 33 serum samples of children with rotavirus diarrhea, suggesting that the virus can “escape” the GI tract in children, resulting in viremia (Lancet 2003;362:1445–9). The virus itself has also been found in the liver and kidney in immunodeficient children (J. Pediatr. 1992;120:912–7).

Another presentation that can throw you off the rotavirus track is when the presenting symptoms are heavily respiratory in the first 36 hours. Rotavirus has been found in nasopharyngeal secretions of such patients (Diagn. Microbiol. Infect. Dis. 1986;4:87–8), and it makes sense that the upper respiratory tract could be part of the initial portal of infection.

So, beyond a notable reduction in winter diarrhea in infants, the new rotavirus vaccines may also have the added benefit of preventing some febrile seizures and even an occasional case of aseptic meningitis.

I currently have no financial connections with either the Merck or the GSK rotavirus vaccines, although I participated in early studies involving the Merck product more than 5 years ago.

Upon returning from the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, I wanted to share my view of what seemed to emerge as a theme from the many papers published on ear infection treatment.

First, consensus exists on the importance of a bulging tympanic membrane in the diagnosis of acute otitis media (AOM) and its differentiation from otitis media with effusion (OME). Most AOM experts appear to agree that antibiotic treatment is warranted and recommended for children with clear-cut AOM as distinguished by a bulging eardrum.

Watchful observation or placebo treatment should involve less ill, older children who are verbal enough to describe their pain accurately.

Second, in children with a bulging tympanic membrane, the chances for bacterial infection are high, probably around 90%–98%. These children are not the ones with an 80% or greater likelihood of “spontaneous resolution” of their ear infections at the same speed as those who receive antibiotics.

Third, the spontaneous resolution rate of bacterial otitis media depends on when you ask the question: 1–2 days into treatment, on days 3–5, on days 10–14, or on day 28.

Most of the symptomatic benefit of antibiotics occurs during the early days of treatment.

The rates of persistent effusion, measured later, will be lower if appropriate antibiotics are used.

Fourth, the effectiveness of antibiotic therapy should be gauged against the likelihood of resolution that would accompany placebo treatment of otitis media.

Research in this area involves ethical, medicolegal, and practical concerns. The patient populations who enroll in trials in which children could be receiving antibiotic, placebo, or possibly one or two tympanocenteses (ear taps) are almost certainly different from each other and different from what we see in everyday practice.

The situation is dynamic in terms of study populations, investigative sites, causative bacteria, and antibiotic resistance.

Thus, comparisons across studies and across time should be made with extreme caution; frankly, I don't think they should be made at all.

Absent new data to the contrary—and I know of none—among children who have AOM of sufficient severity to receive an ear tap, bacterial eradication by natural host defense occurs 3–5 days after the onset of symptoms in 20% of these patients with Streptococcus pneumoniae, in 50% of those with Haemophilus influenzae, and in 70% with Moraxella catarrhalis. These numbers have been confirmed in multiple studies.

The bacterial profile for AOM in the United States has changed significantly because of the conjugate pneumococcal vaccine (Prevnar).

In vaccinated children, the No. 1 bacterial species is now H. influenzae, and more than half of those organisms make β-lactamase, rendering them resistant to the current first-line antibiotic choice, amoxicillin.

In fact, it appears that about 60% of AOM in Prevnar-vaccinated children involve H. influenzae.

But we can't ignore S. pneumoniae, which makes up about 30% of the total bacterial burden.

Although most of those strains are now penicillin susceptible because of the vaccine, the resistant strains are still around. The ratios may change with time, but S. pneumoniae is more worrisome because of its invasiveness and suppurative complications.

Finally, at least for the moment, we see a clearer distinction emerging among antibiotics as “good, better, and best” for anticipated effectiveness and for tolerability in the current U.S. pathogen mix. (See table below.)

Of course, there are caveats to these distinctions.

Measures of efficacy include bacterial cure (by double tympanocentesis study designs) and pharmacokinetic/pharmacodynamic antibiotic measurements of the key pathogens in middle-ear fluids.

Although I'm tempted to add “tolerability to the pocketbook (monetary cost)” and “annoyance cost of phone calls from the managed care policy police” as measures of tolerability and adherence to the prescribed regimen, the tolerability measurements in the table refer to taste, the number of doses per day, the duration of treatment, and the number of office visits involved.

Not included in the table are cefixime and ceftibuten because these agents are not satisfactorily effective against penicillin-nonsusceptible S. pneumoniae. (Combined with high-dose amoxicillin, however, such a combination would be expected to work very well.)

Also not listed are cefaclor and loracarbef because their efficacy, by current standards, has not been tested and they are anticipated not to be that good, although the tolerability is excellent.

Now the debate will continue around what to do in practice: Do we start with a good antibiotic, then go to a better one? Or start with a better one, and then jump to the best? Or start with the best and go to other “bests”—or to ear taps or tubes?

The best antibiotics in efficacy are not the same as the best in tolerability, so which one takes precedence? The most effective antibiotic won't work if it is not taken, and the most tolerable antibiotic won't work if it is not effective.

Stay tuned for the next chapter.

Upon returning from the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, I wanted to share my view of what seemed to emerge as a theme from the many papers published on ear infection treatment.

First, consensus exists on the importance of a bulging tympanic membrane in the diagnosis of acute otitis media (AOM) and its differentiation from otitis media with effusion (OME). Most AOM experts appear to agree that antibiotic treatment is warranted and recommended for children with clear-cut AOM as distinguished by a bulging eardrum.

Watchful observation or placebo treatment should involve less ill, older children who are verbal enough to describe their pain accurately.

Second, in children with a bulging tympanic membrane, the chances for bacterial infection are high, probably around 90%–98%. These children are not the ones with an 80% or greater likelihood of “spontaneous resolution” of their ear infections at the same speed as those who receive antibiotics.

Third, the spontaneous resolution rate of bacterial otitis media depends on when you ask the question: 1–2 days into treatment, on days 3–5, on days 10–14, or on day 28.

Most of the symptomatic benefit of antibiotics occurs during the early days of treatment.

The rates of persistent effusion, measured later, will be lower if appropriate antibiotics are used.

Fourth, the effectiveness of antibiotic therapy should be gauged against the likelihood of resolution that would accompany placebo treatment of otitis media.

Research in this area involves ethical, medicolegal, and practical concerns. The patient populations who enroll in trials in which children could be receiving antibiotic, placebo, or possibly one or two tympanocenteses (ear taps) are almost certainly different from each other and different from what we see in everyday practice.

The situation is dynamic in terms of study populations, investigative sites, causative bacteria, and antibiotic resistance.

Thus, comparisons across studies and across time should be made with extreme caution; frankly, I don't think they should be made at all.

Absent new data to the contrary—and I know of none—among children who have AOM of sufficient severity to receive an ear tap, bacterial eradication by natural host defense occurs 3–5 days after the onset of symptoms in 20% of these patients with Streptococcus pneumoniae, in 50% of those with Haemophilus influenzae, and in 70% with Moraxella catarrhalis. These numbers have been confirmed in multiple studies.

The bacterial profile for AOM in the United States has changed significantly because of the conjugate pneumococcal vaccine (Prevnar).

In vaccinated children, the No. 1 bacterial species is now H. influenzae, and more than half of those organisms make β-lactamase, rendering them resistant to the current first-line antibiotic choice, amoxicillin.

In fact, it appears that about 60% of AOM in Prevnar-vaccinated children involve H. influenzae.

But we can't ignore S. pneumoniae, which makes up about 30% of the total bacterial burden.

Although most of those strains are now penicillin susceptible because of the vaccine, the resistant strains are still around. The ratios may change with time, but S. pneumoniae is more worrisome because of its invasiveness and suppurative complications.

Finally, at least for the moment, we see a clearer distinction emerging among antibiotics as “good, better, and best” for anticipated effectiveness and for tolerability in the current U.S. pathogen mix. (See table below.)

Of course, there are caveats to these distinctions.

Measures of efficacy include bacterial cure (by double tympanocentesis study designs) and pharmacokinetic/pharmacodynamic antibiotic measurements of the key pathogens in middle-ear fluids.

Although I'm tempted to add “tolerability to the pocketbook (monetary cost)” and “annoyance cost of phone calls from the managed care policy police” as measures of tolerability and adherence to the prescribed regimen, the tolerability measurements in the table refer to taste, the number of doses per day, the duration of treatment, and the number of office visits involved.

Not included in the table are cefixime and ceftibuten because these agents are not satisfactorily effective against penicillin-nonsusceptible S. pneumoniae. (Combined with high-dose amoxicillin, however, such a combination would be expected to work very well.)

Also not listed are cefaclor and loracarbef because their efficacy, by current standards, has not been tested and they are anticipated not to be that good, although the tolerability is excellent.

Now the debate will continue around what to do in practice: Do we start with a good antibiotic, then go to a better one? Or start with a better one, and then jump to the best? Or start with the best and go to other “bests”—or to ear taps or tubes?

The best antibiotics in efficacy are not the same as the best in tolerability, so which one takes precedence? The most effective antibiotic won't work if it is not taken, and the most tolerable antibiotic won't work if it is not effective.

Stay tuned for the next chapter.

Upon returning from the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, I wanted to share my view of what seemed to emerge as a theme from the many papers published on ear infection treatment.

First, consensus exists on the importance of a bulging tympanic membrane in the diagnosis of acute otitis media (AOM) and its differentiation from otitis media with effusion (OME). Most AOM experts appear to agree that antibiotic treatment is warranted and recommended for children with clear-cut AOM as distinguished by a bulging eardrum.

Watchful observation or placebo treatment should involve less ill, older children who are verbal enough to describe their pain accurately.

Second, in children with a bulging tympanic membrane, the chances for bacterial infection are high, probably around 90%–98%. These children are not the ones with an 80% or greater likelihood of “spontaneous resolution” of their ear infections at the same speed as those who receive antibiotics.

Third, the spontaneous resolution rate of bacterial otitis media depends on when you ask the question: 1–2 days into treatment, on days 3–5, on days 10–14, or on day 28.

Most of the symptomatic benefit of antibiotics occurs during the early days of treatment.

The rates of persistent effusion, measured later, will be lower if appropriate antibiotics are used.

Fourth, the effectiveness of antibiotic therapy should be gauged against the likelihood of resolution that would accompany placebo treatment of otitis media.

Research in this area involves ethical, medicolegal, and practical concerns. The patient populations who enroll in trials in which children could be receiving antibiotic, placebo, or possibly one or two tympanocenteses (ear taps) are almost certainly different from each other and different from what we see in everyday practice.

The situation is dynamic in terms of study populations, investigative sites, causative bacteria, and antibiotic resistance.

Thus, comparisons across studies and across time should be made with extreme caution; frankly, I don't think they should be made at all.

Absent new data to the contrary—and I know of none—among children who have AOM of sufficient severity to receive an ear tap, bacterial eradication by natural host defense occurs 3–5 days after the onset of symptoms in 20% of these patients with Streptococcus pneumoniae, in 50% of those with Haemophilus influenzae, and in 70% with Moraxella catarrhalis. These numbers have been confirmed in multiple studies.

The bacterial profile for AOM in the United States has changed significantly because of the conjugate pneumococcal vaccine (Prevnar).

In vaccinated children, the No. 1 bacterial species is now H. influenzae, and more than half of those organisms make β-lactamase, rendering them resistant to the current first-line antibiotic choice, amoxicillin.

In fact, it appears that about 60% of AOM in Prevnar-vaccinated children involve H. influenzae.

But we can't ignore S. pneumoniae, which makes up about 30% of the total bacterial burden.

Although most of those strains are now penicillin susceptible because of the vaccine, the resistant strains are still around. The ratios may change with time, but S. pneumoniae is more worrisome because of its invasiveness and suppurative complications.

Finally, at least for the moment, we see a clearer distinction emerging among antibiotics as “good, better, and best” for anticipated effectiveness and for tolerability in the current U.S. pathogen mix. (See table below.)

Of course, there are caveats to these distinctions.

Measures of efficacy include bacterial cure (by double tympanocentesis study designs) and pharmacokinetic/pharmacodynamic antibiotic measurements of the key pathogens in middle-ear fluids.

Although I'm tempted to add “tolerability to the pocketbook (monetary cost)” and “annoyance cost of phone calls from the managed care policy police” as measures of tolerability and adherence to the prescribed regimen, the tolerability measurements in the table refer to taste, the number of doses per day, the duration of treatment, and the number of office visits involved.

Not included in the table are cefixime and ceftibuten because these agents are not satisfactorily effective against penicillin-nonsusceptible S. pneumoniae. (Combined with high-dose amoxicillin, however, such a combination would be expected to work very well.)

Also not listed are cefaclor and loracarbef because their efficacy, by current standards, has not been tested and they are anticipated not to be that good, although the tolerability is excellent.

Now the debate will continue around what to do in practice: Do we start with a good antibiotic, then go to a better one? Or start with a better one, and then jump to the best? Or start with the best and go to other “bests”—or to ear taps or tubes?

The best antibiotics in efficacy are not the same as the best in tolerability, so which one takes precedence? The most effective antibiotic won't work if it is not taken, and the most tolerable antibiotic won't work if it is not effective.

Stay tuned for the next chapter.

Influenza is the big 2005 infectious disease story that will continue into 2006. Here are some other important current ID topics that you may have heard less about:

▸ Empyema. Routine use of the conjugate pneumococcal vaccine does not appear to have decreased the incidence of empyema in children, although it has reduced the number of cases caused by Streptococcus pneumoniae. Now we're seeing increasing numbers due to methicillin-resistant Staphylococcus aureus.

Of 230 children (mean age 4.0 years) diagnosed in Houston between 1993 and 2002 with community-acquired pneumonia and empyema, 32% of the 219 who had pleural fluid cultures performed were positive, while another 27 had a cause identified by blood culture (Pediatrics 2004;113:1735–40).

The number of children admitted for empyema per 10,000 total hospital admissions increased steadily from 5.8 in 1993–1994 to 13 in 1997–1998 to a peak of 23 in 1999–2000. The rate then dropped to 12.6/10,000 in 2001–2002, primarily due to a drop in cases caused by S. pneumoniae, which accounted for 29 of 44 positive isolates (66%) in 1999–2000, compared with just 4 of 15 (27%) in 2001–2002. We may now be seeing more cases due to nonvaccine strains.

Meanwhile, isolation of S. aureus increased from 8 of 44 positive isolates (18%) in 1999–2000 to 9 of 15 (60%) in 2001–2002, of which the majority were in children under 1 year of age.

Half (4/8) of those seen in 1999–2000 were MRSA, versus more than three-fourths (7/9) in 2001–2002.

The authors concluded—and I agree—that if you live in a community in which MRSA now accounts for more than 10% of invasive infections, vancomycin plus ceftriaxone should be the first-line empiric therapy for empyema and pleural effusions associated with community-acquired pneumonia. The use of clindamycin plus ceftriaxone may be acceptable in institutions where MRSA remains susceptible to clindamycin.

Of the 212 patients for whom information on therapeutic intervention was available, 59% underwent video-assisted thoracoscopy (VATS), which is now emerging as the most cost-effective treatment for complicated pleural empyemas at the institutions where physicians have become expert at performing it.

Among the 125 children who underwent VATS, length of hospital stay was significantly shorter (12 vs. 15 days) for the 49 who underwent the procedure within 48 hours of admission, compared with the 76 children in whom VATS was performed beyond 2 days. Length of fever after hospitalization was also significantly shorter in the group who underwent early VATS (7 vs. 9 days).

▸ Oral rehydration therapy. As we anxiously await the availability of new rotavirus vaccines, we will continue to see large numbers of children with dehydration due to viral gastroenteritis during the colder months.

Intravenous fluid therapy (IVF) still is widely used even in children whose dehydration is not severe, despite evidence that oral rehydration therapy (ORT) can be initiated more quickly, is just as effective, and is well-received by patients and their families.

Among data supporting ORT are those from a study in which 73 children aged 8 weeks to 3 years who presented to an urban pediatric emergency department with mild to moderate (5%–10%) dehydration were randomized to receive either IVF or ORT (Pediatrics 2005;115:295–301).

There was no difference between the two groups in the overall proportion achieving successful rehydration at 4 hours (56% ORT vs. 57% IVF), urine output was similar, and no patient in either group had severe emesis.

However, more patients who received IVF had weight gain by the end of the 4 hours (100% IVF vs. 83% ORT). The mean time to initiate therapy was substantially shorter with ORT (19.9 vs. 41.2 minutes), and fewer ORT patients were hospitalized (30% vs. 49%).

Five of the 36 children randomized to ORT were unable to tolerate it and required IV placement. When analyzed by treatment received, overall successful rehydration still did not differ significantly (61% ORT vs. 62% IVF), while hospitalization was required in 23% with ORT versus 50% with IVF.

Of course, ORT isn't for everyone, including patients with hypotension, chronic underlying illness, growth failure, or oral-motor impairments. I also would advise IVF for infants less than 2 months of age and for patients who are severely dehydrated or have been sick for more than 5 days.

The addition in future of a rotavirus vaccine to our child immunization schedule may effectively reduce the need for such hydration therapy in the pediatric population.

▸ Varicella. Rates have declined so dramatically in the decade since the vaccine became available that we may be in danger of forgetting about varicella altogether. Many adolescents remain at high risk because they were born too late to receive the vaccine as part of routine infant immunization, but they are now less likely to have been exposed to the natural virus earlier in childhood.

Of the four current routine adolescent vaccinations, varicella was the one recommended the least often by 210 pediatricians and family physicians who responded to a mailed survey (59% response rate).

Overall, 98% of respndents reported routinely recommending vaccination against tetanus-diphtheria, 90% against hepatitis B, and 84% against measles, mumps, and rubella, compared with just 60% who reported routinely recommending varicella vaccination of susceptible adolescents (J. Am. Board Fam. Pract. 2005;18:13–9).

Only 68% of the respondents reported that it was “very important” to ensure that adolescents were up to date on protection against varicella, whereas 86%–97% reported the same regarding hepatitis B; measles, mumps, rubella; and tetanus-diphtheria.

Among the reasons cited by the authors is the perception that varicella is a benign illness.

In fact, in a high-risk host, the disease can result in severe secondary bacterial infection including necrotizing fasciitis and viral dissemination to the lungs, liver, and central nervous system.

With varicella zoster immune globulin currently in short supply—and possibly for the foreseeable future—intravenous immune globulin is now the primary means of postexposure prophylaxis for susceptible individuals.

We mustn't let down our guard with varicella. It still results in pediatric deaths each year.

Influenza is the big 2005 infectious disease story that will continue into 2006. Here are some other important current ID topics that you may have heard less about:

▸ Empyema. Routine use of the conjugate pneumococcal vaccine does not appear to have decreased the incidence of empyema in children, although it has reduced the number of cases caused by Streptococcus pneumoniae. Now we're seeing increasing numbers due to methicillin-resistant Staphylococcus aureus.

Of 230 children (mean age 4.0 years) diagnosed in Houston between 1993 and 2002 with community-acquired pneumonia and empyema, 32% of the 219 who had pleural fluid cultures performed were positive, while another 27 had a cause identified by blood culture (Pediatrics 2004;113:1735–40).

The number of children admitted for empyema per 10,000 total hospital admissions increased steadily from 5.8 in 1993–1994 to 13 in 1997–1998 to a peak of 23 in 1999–2000. The rate then dropped to 12.6/10,000 in 2001–2002, primarily due to a drop in cases caused by S. pneumoniae, which accounted for 29 of 44 positive isolates (66%) in 1999–2000, compared with just 4 of 15 (27%) in 2001–2002. We may now be seeing more cases due to nonvaccine strains.

Meanwhile, isolation of S. aureus increased from 8 of 44 positive isolates (18%) in 1999–2000 to 9 of 15 (60%) in 2001–2002, of which the majority were in children under 1 year of age.

Half (4/8) of those seen in 1999–2000 were MRSA, versus more than three-fourths (7/9) in 2001–2002.

The authors concluded—and I agree—that if you live in a community in which MRSA now accounts for more than 10% of invasive infections, vancomycin plus ceftriaxone should be the first-line empiric therapy for empyema and pleural effusions associated with community-acquired pneumonia. The use of clindamycin plus ceftriaxone may be acceptable in institutions where MRSA remains susceptible to clindamycin.

Of the 212 patients for whom information on therapeutic intervention was available, 59% underwent video-assisted thoracoscopy (VATS), which is now emerging as the most cost-effective treatment for complicated pleural empyemas at the institutions where physicians have become expert at performing it.

Among the 125 children who underwent VATS, length of hospital stay was significantly shorter (12 vs. 15 days) for the 49 who underwent the procedure within 48 hours of admission, compared with the 76 children in whom VATS was performed beyond 2 days. Length of fever after hospitalization was also significantly shorter in the group who underwent early VATS (7 vs. 9 days).

▸ Oral rehydration therapy. As we anxiously await the availability of new rotavirus vaccines, we will continue to see large numbers of children with dehydration due to viral gastroenteritis during the colder months.

Intravenous fluid therapy (IVF) still is widely used even in children whose dehydration is not severe, despite evidence that oral rehydration therapy (ORT) can be initiated more quickly, is just as effective, and is well-received by patients and their families.

Among data supporting ORT are those from a study in which 73 children aged 8 weeks to 3 years who presented to an urban pediatric emergency department with mild to moderate (5%–10%) dehydration were randomized to receive either IVF or ORT (Pediatrics 2005;115:295–301).

There was no difference between the two groups in the overall proportion achieving successful rehydration at 4 hours (56% ORT vs. 57% IVF), urine output was similar, and no patient in either group had severe emesis.

However, more patients who received IVF had weight gain by the end of the 4 hours (100% IVF vs. 83% ORT). The mean time to initiate therapy was substantially shorter with ORT (19.9 vs. 41.2 minutes), and fewer ORT patients were hospitalized (30% vs. 49%).

Five of the 36 children randomized to ORT were unable to tolerate it and required IV placement. When analyzed by treatment received, overall successful rehydration still did not differ significantly (61% ORT vs. 62% IVF), while hospitalization was required in 23% with ORT versus 50% with IVF.

Of course, ORT isn't for everyone, including patients with hypotension, chronic underlying illness, growth failure, or oral-motor impairments. I also would advise IVF for infants less than 2 months of age and for patients who are severely dehydrated or have been sick for more than 5 days.

The addition in future of a rotavirus vaccine to our child immunization schedule may effectively reduce the need for such hydration therapy in the pediatric population.

▸ Varicella. Rates have declined so dramatically in the decade since the vaccine became available that we may be in danger of forgetting about varicella altogether. Many adolescents remain at high risk because they were born too late to receive the vaccine as part of routine infant immunization, but they are now less likely to have been exposed to the natural virus earlier in childhood.

Of the four current routine adolescent vaccinations, varicella was the one recommended the least often by 210 pediatricians and family physicians who responded to a mailed survey (59% response rate).

Overall, 98% of respndents reported routinely recommending vaccination against tetanus-diphtheria, 90% against hepatitis B, and 84% against measles, mumps, and rubella, compared with just 60% who reported routinely recommending varicella vaccination of susceptible adolescents (J. Am. Board Fam. Pract. 2005;18:13–9).

Only 68% of the respondents reported that it was “very important” to ensure that adolescents were up to date on protection against varicella, whereas 86%–97% reported the same regarding hepatitis B; measles, mumps, rubella; and tetanus-diphtheria.

Among the reasons cited by the authors is the perception that varicella is a benign illness.

In fact, in a high-risk host, the disease can result in severe secondary bacterial infection including necrotizing fasciitis and viral dissemination to the lungs, liver, and central nervous system.

With varicella zoster immune globulin currently in short supply—and possibly for the foreseeable future—intravenous immune globulin is now the primary means of postexposure prophylaxis for susceptible individuals.

We mustn't let down our guard with varicella. It still results in pediatric deaths each year.

Influenza is the big 2005 infectious disease story that will continue into 2006. Here are some other important current ID topics that you may have heard less about:

▸ Empyema. Routine use of the conjugate pneumococcal vaccine does not appear to have decreased the incidence of empyema in children, although it has reduced the number of cases caused by Streptococcus pneumoniae. Now we're seeing increasing numbers due to methicillin-resistant Staphylococcus aureus.

Of 230 children (mean age 4.0 years) diagnosed in Houston between 1993 and 2002 with community-acquired pneumonia and empyema, 32% of the 219 who had pleural fluid cultures performed were positive, while another 27 had a cause identified by blood culture (Pediatrics 2004;113:1735–40).

The number of children admitted for empyema per 10,000 total hospital admissions increased steadily from 5.8 in 1993–1994 to 13 in 1997–1998 to a peak of 23 in 1999–2000. The rate then dropped to 12.6/10,000 in 2001–2002, primarily due to a drop in cases caused by S. pneumoniae, which accounted for 29 of 44 positive isolates (66%) in 1999–2000, compared with just 4 of 15 (27%) in 2001–2002. We may now be seeing more cases due to nonvaccine strains.

Meanwhile, isolation of S. aureus increased from 8 of 44 positive isolates (18%) in 1999–2000 to 9 of 15 (60%) in 2001–2002, of which the majority were in children under 1 year of age.

Half (4/8) of those seen in 1999–2000 were MRSA, versus more than three-fourths (7/9) in 2001–2002.

The authors concluded—and I agree—that if you live in a community in which MRSA now accounts for more than 10% of invasive infections, vancomycin plus ceftriaxone should be the first-line empiric therapy for empyema and pleural effusions associated with community-acquired pneumonia. The use of clindamycin plus ceftriaxone may be acceptable in institutions where MRSA remains susceptible to clindamycin.

Of the 212 patients for whom information on therapeutic intervention was available, 59% underwent video-assisted thoracoscopy (VATS), which is now emerging as the most cost-effective treatment for complicated pleural empyemas at the institutions where physicians have become expert at performing it.

Among the 125 children who underwent VATS, length of hospital stay was significantly shorter (12 vs. 15 days) for the 49 who underwent the procedure within 48 hours of admission, compared with the 76 children in whom VATS was performed beyond 2 days. Length of fever after hospitalization was also significantly shorter in the group who underwent early VATS (7 vs. 9 days).

▸ Oral rehydration therapy. As we anxiously await the availability of new rotavirus vaccines, we will continue to see large numbers of children with dehydration due to viral gastroenteritis during the colder months.

Intravenous fluid therapy (IVF) still is widely used even in children whose dehydration is not severe, despite evidence that oral rehydration therapy (ORT) can be initiated more quickly, is just as effective, and is well-received by patients and their families.

Among data supporting ORT are those from a study in which 73 children aged 8 weeks to 3 years who presented to an urban pediatric emergency department with mild to moderate (5%–10%) dehydration were randomized to receive either IVF or ORT (Pediatrics 2005;115:295–301).

There was no difference between the two groups in the overall proportion achieving successful rehydration at 4 hours (56% ORT vs. 57% IVF), urine output was similar, and no patient in either group had severe emesis.

However, more patients who received IVF had weight gain by the end of the 4 hours (100% IVF vs. 83% ORT). The mean time to initiate therapy was substantially shorter with ORT (19.9 vs. 41.2 minutes), and fewer ORT patients were hospitalized (30% vs. 49%).

Five of the 36 children randomized to ORT were unable to tolerate it and required IV placement. When analyzed by treatment received, overall successful rehydration still did not differ significantly (61% ORT vs. 62% IVF), while hospitalization was required in 23% with ORT versus 50% with IVF.

Of course, ORT isn't for everyone, including patients with hypotension, chronic underlying illness, growth failure, or oral-motor impairments. I also would advise IVF for infants less than 2 months of age and for patients who are severely dehydrated or have been sick for more than 5 days.

The addition in future of a rotavirus vaccine to our child immunization schedule may effectively reduce the need for such hydration therapy in the pediatric population.

▸ Varicella. Rates have declined so dramatically in the decade since the vaccine became available that we may be in danger of forgetting about varicella altogether. Many adolescents remain at high risk because they were born too late to receive the vaccine as part of routine infant immunization, but they are now less likely to have been exposed to the natural virus earlier in childhood.

Of the four current routine adolescent vaccinations, varicella was the one recommended the least often by 210 pediatricians and family physicians who responded to a mailed survey (59% response rate).

Overall, 98% of respndents reported routinely recommending vaccination against tetanus-diphtheria, 90% against hepatitis B, and 84% against measles, mumps, and rubella, compared with just 60% who reported routinely recommending varicella vaccination of susceptible adolescents (J. Am. Board Fam. Pract. 2005;18:13–9).

Only 68% of the respondents reported that it was “very important” to ensure that adolescents were up to date on protection against varicella, whereas 86%–97% reported the same regarding hepatitis B; measles, mumps, rubella; and tetanus-diphtheria.

Among the reasons cited by the authors is the perception that varicella is a benign illness.

In fact, in a high-risk host, the disease can result in severe secondary bacterial infection including necrotizing fasciitis and viral dissemination to the lungs, liver, and central nervous system.

With varicella zoster immune globulin currently in short supply—and possibly for the foreseeable future—intravenous immune globulin is now the primary means of postexposure prophylaxis for susceptible individuals.

We mustn't let down our guard with varicella. It still results in pediatric deaths each year.

We should be concerned but not panicked about avian influenza. As clinicians, we need to reassure families about the small but perhaps increasing potential for pandemic flu and answer their questions, but at the same time focus our immediate efforts on prevention and management of the nonpandemic annual influenza season that is just around the corner.

There appears to be confusion out there—even among some physicians—about the details concerning what avian influenza is and what would need to happen for it to become a pandemic. In fact, avian influenza isn't new—periodic outbreaks have occurred and been reasonably controlled in animals worldwide, including in the United States, for decades.

At least one strain of avian influenza, an H5N1 strain, is now endemic in much of Asia and has recently spread to Europe, killing poultry and other birds in several countries. The H5N1 strain was first recognized in 1997, when it infected 18 people and killed 6 in Hong Kong. Since 2003, it has been diagnosed in more than 100 humans in several countries in Southeast Asia with greater than a 50% mortality.

But this avian H5N1 strain in humans has not become pandemic. A true pandemic requires sustained human-to-human transmission. To date, nearly all of the infected individuals have been in direct contact with infected poultry. For a pandemic to occur, a human influenza strain and an avian influenza strain need to simultaneously infect an intermediate host (usually a pig but perhaps even a cat). Then the strains would need to exchange genes via reassortment, and a reassortment mutant would then need to reemerge and reinfect humans.

This hasn't happened yet, and if we're lucky it never will. Indeed, H5N1 has been circulating among birds in the Far East since 1997 without this reassortment occurring. But humans packed densely into small geographic areas together with avian species and intermediate mammalian hosts—the current situation in parts of Asia—do increase the chance that reassortment might happen.

This theoretical possibility is why many officials are concerned. The U.S. Department of Health and Human Services has now developed a $7.1 billion national strategy to address pandemic influenza (www.pandemicflu.gov

1. Intensifying surveillance and collaborating on containment.

2. Stockpiling antivirals and vaccines.

3. Creating a network of federal, state, and local preparedness agencies.

4. Increasing public education and communication.

Although not perfect or complete, this plan is evolving rapidly.

For this reason, I have recently changed my view about personal stockpiling of antivirals. A few months ago, when there were apparently ample supplies, I believed that families and first responders should keep a neuraminidase inhibitor on hand, anticipating influenza season. I no longer support this practice because demand has risen, and there simply isn't enough antiviral medication to go around.

Now I think it makes more sense to keep these drugs in central locations to be distributed to outbreak sites for pandemic influenza—instead of scattered among individuals around the country.

Of course, if you have a patient with confirmed influenza for less than 48 hours, it still makes sense to treat with oseltamivir or zanamivir if these drugs are available. When the local type is an influenza A, you could also use rimantadine or amantadine, depending on their availability and on the patient's age, if no other contraindications to these two drugs are present.

But for now I strongly believe that our top priority should be immunizing our patients against the nonpandemic annual influenza that we know is coming soon. And I mean all children, not just those aged 6–23 months or those with high-risk medical conditions. Indeed, I support the emerging viewpoint that immunizing school-aged children is also critical to preventing transmission within a community.

Among the many lines of emerging evidence for this approach is a recent report from Japan saying that although both oral oseltamivir and inhaled zanamivir reduce the duration of influenza symptoms in children, they do not significantly shorten the period of viral shedding (Pediatr. Infect. Dis. J. 2005;24:931–2). Another recent study determined that children aged 3–4 years are the first to become infected with influenza each season, and therefore serve as vectors for the rest of the community (Am. J. Epidemiol. 2005;162:686–93).

These findings are of concern because children typically go back to school or day care once their symptoms diminish. I agree with Ram Yogev, M.D., who recently called for the policy-making organizations to consider issuing an evidence-based recommendation for routine vaccination of all healthy children (Pediatrics 2005;116:1214–5). Of course, there are logistics to overcome with such a large undertaking, but I feel the benefits can be huge, too.

The Centers for Disease Control and Prevention advises, “In addition to the groups for which annual influenza vaccination is recommended, physicians should administer influenza vaccine to any person who wishes to reduce the likelihood of becoming ill with influenza or transmitting influenza to others should they become infected (the vaccine can be administered to children [older than] 6 months), depending on vaccine availability” (MMWR 2005;54[RR08]:1–40).

In my mind, that's what we should be doing. Not only will this protect our patients and their contacts, but it will also reduce the chance that garden-variety influenza will be mistaken for H5N1. In fact, the human H5N1 cases seen in Asia have involved more gastrointestinal symptoms in children than does the typical annual flu; the human H5N1 cases have also had leukopenia, thrombocytopenia, and elevated liver enzyme levels, which are not normally seen with the regular flu. Be especially alert for those symptoms, particularly in a child who has traveled overseas where H5N1 has been found.

We should be concerned but not panicked about avian influenza. As clinicians, we need to reassure families about the small but perhaps increasing potential for pandemic flu and answer their questions, but at the same time focus our immediate efforts on prevention and management of the nonpandemic annual influenza season that is just around the corner.

There appears to be confusion out there—even among some physicians—about the details concerning what avian influenza is and what would need to happen for it to become a pandemic. In fact, avian influenza isn't new—periodic outbreaks have occurred and been reasonably controlled in animals worldwide, including in the United States, for decades.

At least one strain of avian influenza, an H5N1 strain, is now endemic in much of Asia and has recently spread to Europe, killing poultry and other birds in several countries. The H5N1 strain was first recognized in 1997, when it infected 18 people and killed 6 in Hong Kong. Since 2003, it has been diagnosed in more than 100 humans in several countries in Southeast Asia with greater than a 50% mortality.

But this avian H5N1 strain in humans has not become pandemic. A true pandemic requires sustained human-to-human transmission. To date, nearly all of the infected individuals have been in direct contact with infected poultry. For a pandemic to occur, a human influenza strain and an avian influenza strain need to simultaneously infect an intermediate host (usually a pig but perhaps even a cat). Then the strains would need to exchange genes via reassortment, and a reassortment mutant would then need to reemerge and reinfect humans.

This hasn't happened yet, and if we're lucky it never will. Indeed, H5N1 has been circulating among birds in the Far East since 1997 without this reassortment occurring. But humans packed densely into small geographic areas together with avian species and intermediate mammalian hosts—the current situation in parts of Asia—do increase the chance that reassortment might happen.

This theoretical possibility is why many officials are concerned. The U.S. Department of Health and Human Services has now developed a $7.1 billion national strategy to address pandemic influenza (www.pandemicflu.gov

1. Intensifying surveillance and collaborating on containment.

2. Stockpiling antivirals and vaccines.

3. Creating a network of federal, state, and local preparedness agencies.

4. Increasing public education and communication.

Although not perfect or complete, this plan is evolving rapidly.

For this reason, I have recently changed my view about personal stockpiling of antivirals. A few months ago, when there were apparently ample supplies, I believed that families and first responders should keep a neuraminidase inhibitor on hand, anticipating influenza season. I no longer support this practice because demand has risen, and there simply isn't enough antiviral medication to go around.

Now I think it makes more sense to keep these drugs in central locations to be distributed to outbreak sites for pandemic influenza—instead of scattered among individuals around the country.

Of course, if you have a patient with confirmed influenza for less than 48 hours, it still makes sense to treat with oseltamivir or zanamivir if these drugs are available. When the local type is an influenza A, you could also use rimantadine or amantadine, depending on their availability and on the patient's age, if no other contraindications to these two drugs are present.

But for now I strongly believe that our top priority should be immunizing our patients against the nonpandemic annual influenza that we know is coming soon. And I mean all children, not just those aged 6–23 months or those with high-risk medical conditions. Indeed, I support the emerging viewpoint that immunizing school-aged children is also critical to preventing transmission within a community.

Among the many lines of emerging evidence for this approach is a recent report from Japan saying that although both oral oseltamivir and inhaled zanamivir reduce the duration of influenza symptoms in children, they do not significantly shorten the period of viral shedding (Pediatr. Infect. Dis. J. 2005;24:931–2). Another recent study determined that children aged 3–4 years are the first to become infected with influenza each season, and therefore serve as vectors for the rest of the community (Am. J. Epidemiol. 2005;162:686–93).

These findings are of concern because children typically go back to school or day care once their symptoms diminish. I agree with Ram Yogev, M.D., who recently called for the policy-making organizations to consider issuing an evidence-based recommendation for routine vaccination of all healthy children (Pediatrics 2005;116:1214–5). Of course, there are logistics to overcome with such a large undertaking, but I feel the benefits can be huge, too.

The Centers for Disease Control and Prevention advises, “In addition to the groups for which annual influenza vaccination is recommended, physicians should administer influenza vaccine to any person who wishes to reduce the likelihood of becoming ill with influenza or transmitting influenza to others should they become infected (the vaccine can be administered to children [older than] 6 months), depending on vaccine availability” (MMWR 2005;54[RR08]:1–40).

In my mind, that's what we should be doing. Not only will this protect our patients and their contacts, but it will also reduce the chance that garden-variety influenza will be mistaken for H5N1. In fact, the human H5N1 cases seen in Asia have involved more gastrointestinal symptoms in children than does the typical annual flu; the human H5N1 cases have also had leukopenia, thrombocytopenia, and elevated liver enzyme levels, which are not normally seen with the regular flu. Be especially alert for those symptoms, particularly in a child who has traveled overseas where H5N1 has been found.

We should be concerned but not panicked about avian influenza. As clinicians, we need to reassure families about the small but perhaps increasing potential for pandemic flu and answer their questions, but at the same time focus our immediate efforts on prevention and management of the nonpandemic annual influenza season that is just around the corner.

There appears to be confusion out there—even among some physicians—about the details concerning what avian influenza is and what would need to happen for it to become a pandemic. In fact, avian influenza isn't new—periodic outbreaks have occurred and been reasonably controlled in animals worldwide, including in the United States, for decades.

At least one strain of avian influenza, an H5N1 strain, is now endemic in much of Asia and has recently spread to Europe, killing poultry and other birds in several countries. The H5N1 strain was first recognized in 1997, when it infected 18 people and killed 6 in Hong Kong. Since 2003, it has been diagnosed in more than 100 humans in several countries in Southeast Asia with greater than a 50% mortality.

But this avian H5N1 strain in humans has not become pandemic. A true pandemic requires sustained human-to-human transmission. To date, nearly all of the infected individuals have been in direct contact with infected poultry. For a pandemic to occur, a human influenza strain and an avian influenza strain need to simultaneously infect an intermediate host (usually a pig but perhaps even a cat). Then the strains would need to exchange genes via reassortment, and a reassortment mutant would then need to reemerge and reinfect humans.

This hasn't happened yet, and if we're lucky it never will. Indeed, H5N1 has been circulating among birds in the Far East since 1997 without this reassortment occurring. But humans packed densely into small geographic areas together with avian species and intermediate mammalian hosts—the current situation in parts of Asia—do increase the chance that reassortment might happen.

This theoretical possibility is why many officials are concerned. The U.S. Department of Health and Human Services has now developed a $7.1 billion national strategy to address pandemic influenza (www.pandemicflu.gov

1. Intensifying surveillance and collaborating on containment.

2. Stockpiling antivirals and vaccines.

3. Creating a network of federal, state, and local preparedness agencies.

4. Increasing public education and communication.

Although not perfect or complete, this plan is evolving rapidly.

For this reason, I have recently changed my view about personal stockpiling of antivirals. A few months ago, when there were apparently ample supplies, I believed that families and first responders should keep a neuraminidase inhibitor on hand, anticipating influenza season. I no longer support this practice because demand has risen, and there simply isn't enough antiviral medication to go around.

Now I think it makes more sense to keep these drugs in central locations to be distributed to outbreak sites for pandemic influenza—instead of scattered among individuals around the country.

Of course, if you have a patient with confirmed influenza for less than 48 hours, it still makes sense to treat with oseltamivir or zanamivir if these drugs are available. When the local type is an influenza A, you could also use rimantadine or amantadine, depending on their availability and on the patient's age, if no other contraindications to these two drugs are present.

But for now I strongly believe that our top priority should be immunizing our patients against the nonpandemic annual influenza that we know is coming soon. And I mean all children, not just those aged 6–23 months or those with high-risk medical conditions. Indeed, I support the emerging viewpoint that immunizing school-aged children is also critical to preventing transmission within a community.

Among the many lines of emerging evidence for this approach is a recent report from Japan saying that although both oral oseltamivir and inhaled zanamivir reduce the duration of influenza symptoms in children, they do not significantly shorten the period of viral shedding (Pediatr. Infect. Dis. J. 2005;24:931–2). Another recent study determined that children aged 3–4 years are the first to become infected with influenza each season, and therefore serve as vectors for the rest of the community (Am. J. Epidemiol. 2005;162:686–93).

These findings are of concern because children typically go back to school or day care once their symptoms diminish. I agree with Ram Yogev, M.D., who recently called for the policy-making organizations to consider issuing an evidence-based recommendation for routine vaccination of all healthy children (Pediatrics 2005;116:1214–5). Of course, there are logistics to overcome with such a large undertaking, but I feel the benefits can be huge, too.

The Centers for Disease Control and Prevention advises, “In addition to the groups for which annual influenza vaccination is recommended, physicians should administer influenza vaccine to any person who wishes to reduce the likelihood of becoming ill with influenza or transmitting influenza to others should they become infected (the vaccine can be administered to children [older than] 6 months), depending on vaccine availability” (MMWR 2005;54[RR08]:1–40).

In my mind, that's what we should be doing. Not only will this protect our patients and their contacts, but it will also reduce the chance that garden-variety influenza will be mistaken for H5N1. In fact, the human H5N1 cases seen in Asia have involved more gastrointestinal symptoms in children than does the typical annual flu; the human H5N1 cases have also had leukopenia, thrombocytopenia, and elevated liver enzyme levels, which are not normally seen with the regular flu. Be especially alert for those symptoms, particularly in a child who has traveled overseas where H5N1 has been found.

November marks the season of two viral respiratory illnesses for which steroids are part of the treatment. But although the role of steroids is now established for croup, their use in bronchiolitis remains controversial.

Croup, otherwise known as laryngotracheal bronchitis, typically begins with an upper respiratory infection and proceeds to a barking cough, hoarseness, and then stridor. Caused mostly by the parainfluenza viruses (1,2, or 3) or respiratory syncytial virus (RSV), it is usually mild and self-limited, although in rare cases, obstruction can occur.

It's important to differentiate croup from bacterial tracheitis, which is characterized by thick, purulent exudate in a child who is highly febrile and toxic with an elevated WBC count, and from the rare case of epiglottitis, in which the child is typically drooling, looks very toxic, has significant airway obstruction, and is air hungry.

Humidified air is the primary treatment for the child with mild croup, despite the lack of clinical trials supporting its use. Anecdotally, using a humidifier or placing the child in hot shower mist results in resolution of croupy symptoms relatively rapidly, whereas respiratory symptoms might progress without treatment. Although there are no controlled trials to support this treatment, such an approach is frequently successful.

Though steroids have been well-established in the treatment of severe croup, in recent years, oral dexamethasone, along with oxygen, has become standard for the child with moderate croup, as well. Recent data have pointed to its benefit, and physicians have become more comfortable using steroids in such children in the context of asthma.

In a recent Cochrane metaanalysis of 31 controlled trials involving a total of 3,736 children with croup, glucocorticoid treatment was associated with significant improvements in the Westley croup score at 6 and 12 hours. The steroid-treated children had half the number of return visits/readmissions and spent a mean of 12 fewer hours in the emergency department and/or hospital (Cochrane Database Syst. Rev. 2004;CD001955).

Epinephrine use was also 10% lower among the steroid-treated children in the Cochrane analysis. When nebulized epinephrine is needed—typically if stridor is moderate, worse, or persistent after initiation of steroids—it's important to observe the child for 3–4 hours after initiation of epinephrine, to make sure stridor does not return, given that the effects of epinephrine do not usually last beyond 2 hours.

For the child with severe croup, the initial treatment is oxygen along with nebulized epinephrine to break the spasm. Steroids are clearly indicated after that; it's just a matter of determining whether the child can tolerate them orally or needs to receive them intravenously.

In contrast to croup, the treatment of bronchiolitis—and indeed its clinical identification—are less well defined. A near-universal illness within the first 2 years of life during the months of November-April, bronchiolitis is usually caused by RSV, although now it appears that human metapneumovirus may account for up to 15% of cases.

Children at greatest risk for serious disease are those younger than 6 months, those born prior to 35 weeks' gestation, and those with chronic lung disease (particularly bronchopulmonary dysplasia), heart disease, or severe immunocompromise, such as bone marrow transplant recipients.

Although the classical presentation of bronchiolitis is coryza, stridor, and mild to moderate respiratory distress, a small proportion of children will present with apnea alone.

Most experts would agree that oxygen and fluids (usually given intravenously) are part of the treatment, though there is some debate about how much fluid is appropriate to prevent dehydration but avoid excess fluid in the lungs. More controversial, however, are the roles of bronchodilators and of steroids.

Results of various studies looking at the response to β-agonist therapy among children with bronchiolitis have been mixed. The problem with these studies appears to be that the results have depended upon the population selected: Studies that have included only children with nasal washings positive for RSV or “pure” bronchiolitis tend to show less benefit, whereas bronchodilators have tended to work better in studies that use a clinical definition for bronchiolitis that includes repeated wheezing, which overlaps with asthma.

Indeed, it's nearly impossible to distinguish RSV bronchiolitis from a first asthma episode in a 6-month-old.

Some of these infants may have more of an atopic illness than a true respiratory viral illness, and we do know that bronchodilators work best in children with atopic disease.

But, it has been hypothesized that RSV may act as a trigger for wheezing in an atopic child, so the presence of RSV certainly doesn't eliminate the potential of allergic bronchospasm.

My approach, then, is to give a trial of inhaled albuterol when the child's symptoms are severe enough to be in the hospital or emergency department and to assess oxygenation, respiratory effort, and respiration rate/retraction after 1–2 hours. If the child has had recurrent episodes or has underlying lung disease, a consideration of steroids is appropriate. Studies to date have found inconsistent results as to the benefit of steroids in first episodes with potential benefit in those with underlying lung pathology or recurrent episodes—the hypothesis being that decreasing bronchiolar inflammation and swelling relieves the airway obstruction. More data support the use of oral than nebulized steroids in children who can take them by mouth. Otherwise, intravenous steroids are required.

Interestingly, recent data have come out suggesting racial differences in response to both glucocorticoids and to inhaled albuterol.

One study, for example, found that black asthmatics required greater concentrations of glucocorticoid in vitro to suppress T-lympocyte activation (Chest 2005;127:571–8), while another found significant differences in bronchodilator response between Puerto Rican and Mexican asthmatic subjects, based on pharmacogenetic differences (Am. J. Respir. Crit. Care. Med. 2005;171:535–6).

More studies are necessary so we can begin to incorporate these avenues of research into clinical practice.

November marks the season of two viral respiratory illnesses for which steroids are part of the treatment. But although the role of steroids is now established for croup, their use in bronchiolitis remains controversial.

Croup, otherwise known as laryngotracheal bronchitis, typically begins with an upper respiratory infection and proceeds to a barking cough, hoarseness, and then stridor. Caused mostly by the parainfluenza viruses (1,2, or 3) or respiratory syncytial virus (RSV), it is usually mild and self-limited, although in rare cases, obstruction can occur.

It's important to differentiate croup from bacterial tracheitis, which is characterized by thick, purulent exudate in a child who is highly febrile and toxic with an elevated WBC count, and from the rare case of epiglottitis, in which the child is typically drooling, looks very toxic, has significant airway obstruction, and is air hungry.

Humidified air is the primary treatment for the child with mild croup, despite the lack of clinical trials supporting its use. Anecdotally, using a humidifier or placing the child in hot shower mist results in resolution of croupy symptoms relatively rapidly, whereas respiratory symptoms might progress without treatment. Although there are no controlled trials to support this treatment, such an approach is frequently successful.

Though steroids have been well-established in the treatment of severe croup, in recent years, oral dexamethasone, along with oxygen, has become standard for the child with moderate croup, as well. Recent data have pointed to its benefit, and physicians have become more comfortable using steroids in such children in the context of asthma.

In a recent Cochrane metaanalysis of 31 controlled trials involving a total of 3,736 children with croup, glucocorticoid treatment was associated with significant improvements in the Westley croup score at 6 and 12 hours. The steroid-treated children had half the number of return visits/readmissions and spent a mean of 12 fewer hours in the emergency department and/or hospital (Cochrane Database Syst. Rev. 2004;CD001955).

Epinephrine use was also 10% lower among the steroid-treated children in the Cochrane analysis. When nebulized epinephrine is needed—typically if stridor is moderate, worse, or persistent after initiation of steroids—it's important to observe the child for 3–4 hours after initiation of epinephrine, to make sure stridor does not return, given that the effects of epinephrine do not usually last beyond 2 hours.

For the child with severe croup, the initial treatment is oxygen along with nebulized epinephrine to break the spasm. Steroids are clearly indicated after that; it's just a matter of determining whether the child can tolerate them orally or needs to receive them intravenously.

In contrast to croup, the treatment of bronchiolitis—and indeed its clinical identification—are less well defined. A near-universal illness within the first 2 years of life during the months of November-April, bronchiolitis is usually caused by RSV, although now it appears that human metapneumovirus may account for up to 15% of cases.

Children at greatest risk for serious disease are those younger than 6 months, those born prior to 35 weeks' gestation, and those with chronic lung disease (particularly bronchopulmonary dysplasia), heart disease, or severe immunocompromise, such as bone marrow transplant recipients.

Although the classical presentation of bronchiolitis is coryza, stridor, and mild to moderate respiratory distress, a small proportion of children will present with apnea alone.

Most experts would agree that oxygen and fluids (usually given intravenously) are part of the treatment, though there is some debate about how much fluid is appropriate to prevent dehydration but avoid excess fluid in the lungs. More controversial, however, are the roles of bronchodilators and of steroids.

Results of various studies looking at the response to β-agonist therapy among children with bronchiolitis have been mixed. The problem with these studies appears to be that the results have depended upon the population selected: Studies that have included only children with nasal washings positive for RSV or “pure” bronchiolitis tend to show less benefit, whereas bronchodilators have tended to work better in studies that use a clinical definition for bronchiolitis that includes repeated wheezing, which overlaps with asthma.

Indeed, it's nearly impossible to distinguish RSV bronchiolitis from a first asthma episode in a 6-month-old.

Some of these infants may have more of an atopic illness than a true respiratory viral illness, and we do know that bronchodilators work best in children with atopic disease.

But, it has been hypothesized that RSV may act as a trigger for wheezing in an atopic child, so the presence of RSV certainly doesn't eliminate the potential of allergic bronchospasm.

My approach, then, is to give a trial of inhaled albuterol when the child's symptoms are severe enough to be in the hospital or emergency department and to assess oxygenation, respiratory effort, and respiration rate/retraction after 1–2 hours. If the child has had recurrent episodes or has underlying lung disease, a consideration of steroids is appropriate. Studies to date have found inconsistent results as to the benefit of steroids in first episodes with potential benefit in those with underlying lung pathology or recurrent episodes—the hypothesis being that decreasing bronchiolar inflammation and swelling relieves the airway obstruction. More data support the use of oral than nebulized steroids in children who can take them by mouth. Otherwise, intravenous steroids are required.

Interestingly, recent data have come out suggesting racial differences in response to both glucocorticoids and to inhaled albuterol.

One study, for example, found that black asthmatics required greater concentrations of glucocorticoid in vitro to suppress T-lympocyte activation (Chest 2005;127:571–8), while another found significant differences in bronchodilator response between Puerto Rican and Mexican asthmatic subjects, based on pharmacogenetic differences (Am. J. Respir. Crit. Care. Med. 2005;171:535–6).

More studies are necessary so we can begin to incorporate these avenues of research into clinical practice.

November marks the season of two viral respiratory illnesses for which steroids are part of the treatment. But although the role of steroids is now established for croup, their use in bronchiolitis remains controversial.

Croup, otherwise known as laryngotracheal bronchitis, typically begins with an upper respiratory infection and proceeds to a barking cough, hoarseness, and then stridor. Caused mostly by the parainfluenza viruses (1,2, or 3) or respiratory syncytial virus (RSV), it is usually mild and self-limited, although in rare cases, obstruction can occur.

It's important to differentiate croup from bacterial tracheitis, which is characterized by thick, purulent exudate in a child who is highly febrile and toxic with an elevated WBC count, and from the rare case of epiglottitis, in which the child is typically drooling, looks very toxic, has significant airway obstruction, and is air hungry.

Humidified air is the primary treatment for the child with mild croup, despite the lack of clinical trials supporting its use. Anecdotally, using a humidifier or placing the child in hot shower mist results in resolution of croupy symptoms relatively rapidly, whereas respiratory symptoms might progress without treatment. Although there are no controlled trials to support this treatment, such an approach is frequently successful.

Though steroids have been well-established in the treatment of severe croup, in recent years, oral dexamethasone, along with oxygen, has become standard for the child with moderate croup, as well. Recent data have pointed to its benefit, and physicians have become more comfortable using steroids in such children in the context of asthma.

In a recent Cochrane metaanalysis of 31 controlled trials involving a total of 3,736 children with croup, glucocorticoid treatment was associated with significant improvements in the Westley croup score at 6 and 12 hours. The steroid-treated children had half the number of return visits/readmissions and spent a mean of 12 fewer hours in the emergency department and/or hospital (Cochrane Database Syst. Rev. 2004;CD001955).

Epinephrine use was also 10% lower among the steroid-treated children in the Cochrane analysis. When nebulized epinephrine is needed—typically if stridor is moderate, worse, or persistent after initiation of steroids—it's important to observe the child for 3–4 hours after initiation of epinephrine, to make sure stridor does not return, given that the effects of epinephrine do not usually last beyond 2 hours.

For the child with severe croup, the initial treatment is oxygen along with nebulized epinephrine to break the spasm. Steroids are clearly indicated after that; it's just a matter of determining whether the child can tolerate them orally or needs to receive them intravenously.

In contrast to croup, the treatment of bronchiolitis—and indeed its clinical identification—are less well defined. A near-universal illness within the first 2 years of life during the months of November-April, bronchiolitis is usually caused by RSV, although now it appears that human metapneumovirus may account for up to 15% of cases.

Children at greatest risk for serious disease are those younger than 6 months, those born prior to 35 weeks' gestation, and those with chronic lung disease (particularly bronchopulmonary dysplasia), heart disease, or severe immunocompromise, such as bone marrow transplant recipients.

Although the classical presentation of bronchiolitis is coryza, stridor, and mild to moderate respiratory distress, a small proportion of children will present with apnea alone.

Most experts would agree that oxygen and fluids (usually given intravenously) are part of the treatment, though there is some debate about how much fluid is appropriate to prevent dehydration but avoid excess fluid in the lungs. More controversial, however, are the roles of bronchodilators and of steroids.

Results of various studies looking at the response to β-agonist therapy among children with bronchiolitis have been mixed. The problem with these studies appears to be that the results have depended upon the population selected: Studies that have included only children with nasal washings positive for RSV or “pure” bronchiolitis tend to show less benefit, whereas bronchodilators have tended to work better in studies that use a clinical definition for bronchiolitis that includes repeated wheezing, which overlaps with asthma.

Indeed, it's nearly impossible to distinguish RSV bronchiolitis from a first asthma episode in a 6-month-old.

Some of these infants may have more of an atopic illness than a true respiratory viral illness, and we do know that bronchodilators work best in children with atopic disease.

But, it has been hypothesized that RSV may act as a trigger for wheezing in an atopic child, so the presence of RSV certainly doesn't eliminate the potential of allergic bronchospasm.

My approach, then, is to give a trial of inhaled albuterol when the child's symptoms are severe enough to be in the hospital or emergency department and to assess oxygenation, respiratory effort, and respiration rate/retraction after 1–2 hours. If the child has had recurrent episodes or has underlying lung disease, a consideration of steroids is appropriate. Studies to date have found inconsistent results as to the benefit of steroids in first episodes with potential benefit in those with underlying lung pathology or recurrent episodes—the hypothesis being that decreasing bronchiolar inflammation and swelling relieves the airway obstruction. More data support the use of oral than nebulized steroids in children who can take them by mouth. Otherwise, intravenous steroids are required.

Interestingly, recent data have come out suggesting racial differences in response to both glucocorticoids and to inhaled albuterol.

One study, for example, found that black asthmatics required greater concentrations of glucocorticoid in vitro to suppress T-lympocyte activation (Chest 2005;127:571–8), while another found significant differences in bronchodilator response between Puerto Rican and Mexican asthmatic subjects, based on pharmacogenetic differences (Am. J. Respir. Crit. Care. Med. 2005;171:535–6).

More studies are necessary so we can begin to incorporate these avenues of research into clinical practice.

We may soon be able to prevent cervical cancer in women by vaccinating preteens against human papillomavirus.

Two candidate HPV vaccines—GlaxoSmithKline's Cervarix and Merck's Gardasil—are expected to be licensed for use in the United States in 2006. Both vaccines are highly effective in preventing infection with both HPV strains 16 and 18, which are responsible for 70%–75% of cervical cancers in women.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention is already working on guidelines for their use, as is the American Academy of Pediatrics. Both groups are likely to recommend that the vaccines be given to girls aged 11–12 as part of the adolescent “vaccine platform,” along with the meningococcal conjugate vaccine and the adolescent and adult DTaP vaccine.

I see this as a new frontier. It's a fabulous opportunity for those of us who work in vaccinology to be able to move from the prevention of infectious disease per se to the prevention of cancer. Cervical cancer affects approximately 12,000 women in the United States. And despite advances in Pap screening and treatment, the disease kills more than 4,000 women annually.

Nearly all (99.7%) of cervical cancer cases are caused by HPV infection. Approximately 15–20 of the 30–40 anogenital types of HPV that have been identified are oncogenic: HPV 16 causes about 54% of cases, and HPV 18 about 13%. Among the nononcogenic types, HPV 6 and 11 are most often associated with external genital warts. The Merck vaccine targets those two strains as well.

We know that acquisition of HPV typically occurs very soon after initiation of sexual intercourse. In a study of 608 U.S. college women who were followed at 6-month intervals, 43% had become infected with HPV by the third year. Indeed, nearly three-fourths of new HPV infections occur in sexually active young adults aged 15–24, and the prevalence of infection in women less than 25 years of age ranges from 28% to 46%.

As more vaccines are being added to the already-crowded childhood and adolescent immunization schedules, payers will be looking to prioritize more than they have with vaccines in the past. Some authorities think it makes sense to hold off for now on vaccinating males against HPV, even though they are, of course, the major source of infection for females. But since the majority of females pick up HPV by the time they reach their late 20s or early 30s and are therefore at risk for cervical cancer, how can we justify not vaccinating every girl in America?

At last year's meeting of the Interscience Conference on Antimicrobials and Chemotherapy, data were presented for a monovalent version of the current Merck vaccine containing only strain 16. In that phase II “proof of principle” study involving 1,533 women aged 16–23 years who were initially negative for HPV 16 DNA and antibodies, the vaccine was 94% effective in preventing persistent HPV infection and 100% effective against cervical intraepithelial neoplasia grades 2 and 3, compared with placebo over 3.5 years.

No cases of cervical intraepithelial neoplasia (CIN) were seen among vaccine recipients, compared with CIN 1 in 12 in the placebo group, CIN 2 in 7, and CIN 3 in 6 in the placebo group (PEDIATRIC NEWS, December 2004, p. 10).

Now, phase III data for the current quadrivalent Merck vaccine from a total of 1,529 male and female subjects aged 10–23 show 100% seroconversion at 6 months for HPV types 16, 6, and 11, and 99.9% seroconversion for serotype 18. Antibody levels for all four serotypes were significantly higher among females and males aged 10–15 years than among those aged 16–23. These data were presented earlier this year at the annual meeting of the European Society of Pediatric Infectious Diseases.

The GlaxoSmithKline vaccine also was found highly effective in a multinational randomized, placebo-controlled study of 1,113 women aged 15–25 years who were followed up to 27 months. Vaccine efficacy overall was 91.6% against incident infection and 100% against persistent infection with HPV 16 and/or 18. In the intention-to-treat analysis, vaccine efficacy was 95.1% against persistent cervical infection and 92.9% against cytologic abnormalities associated with HPV 16 and 18 infection (Lancet 2004;364:1731–2).

Merck and GlaxoSmithKline are now each studying the efficacy and safety of their HPV vaccines in more than 20,000 people aged 9–24 years. The results should tell us whether the vaccines have a therapeutic effect in women who are already infected with HPV, perhaps by inducing antibodies to generate an immune response thereby preventing the progression from simple, transient infection to persistent infection to stage 3 (CIN). However, the first order of business is to target girls before they become sexually active.

About a million women per year have an abnormal Pap smear. What follows is a series of costly and anxiety-provoking steps, including colposcopy, cervical scraping, and if abnormal cells are found, cervical biopsy and possible hysterectomy, all at a cost of approximately $2.8 billion. Widespread vaccination against HPV could substantially reduce this burden.

Although the HPV vaccines will not be the first to prevent cancer—the hepatitis B vaccine reduces the likelihood of developing hepatocellular carcinoma—they are the first to be specifically developed and marketed for cancer prevention. As an infectious disease specialist, I see this concept as novel and very, very exciting.

We may soon be able to prevent cervical cancer in women by vaccinating preteens against human papillomavirus.

Two candidate HPV vaccines—GlaxoSmithKline's Cervarix and Merck's Gardasil—are expected to be licensed for use in the United States in 2006. Both vaccines are highly effective in preventing infection with both HPV strains 16 and 18, which are responsible for 70%–75% of cervical cancers in women.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention is already working on guidelines for their use, as is the American Academy of Pediatrics. Both groups are likely to recommend that the vaccines be given to girls aged 11–12 as part of the adolescent “vaccine platform,” along with the meningococcal conjugate vaccine and the adolescent and adult DTaP vaccine.

I see this as a new frontier. It's a fabulous opportunity for those of us who work in vaccinology to be able to move from the prevention of infectious disease per se to the prevention of cancer. Cervical cancer affects approximately 12,000 women in the United States. And despite advances in Pap screening and treatment, the disease kills more than 4,000 women annually.

Nearly all (99.7%) of cervical cancer cases are caused by HPV infection. Approximately 15–20 of the 30–40 anogenital types of HPV that have been identified are oncogenic: HPV 16 causes about 54% of cases, and HPV 18 about 13%. Among the nononcogenic types, HPV 6 and 11 are most often associated with external genital warts. The Merck vaccine targets those two strains as well.

We know that acquisition of HPV typically occurs very soon after initiation of sexual intercourse. In a study of 608 U.S. college women who were followed at 6-month intervals, 43% had become infected with HPV by the third year. Indeed, nearly three-fourths of new HPV infections occur in sexually active young adults aged 15–24, and the prevalence of infection in women less than 25 years of age ranges from 28% to 46%.

As more vaccines are being added to the already-crowded childhood and adolescent immunization schedules, payers will be looking to prioritize more than they have with vaccines in the past. Some authorities think it makes sense to hold off for now on vaccinating males against HPV, even though they are, of course, the major source of infection for females. But since the majority of females pick up HPV by the time they reach their late 20s or early 30s and are therefore at risk for cervical cancer, how can we justify not vaccinating every girl in America?

At last year's meeting of the Interscience Conference on Antimicrobials and Chemotherapy, data were presented for a monovalent version of the current Merck vaccine containing only strain 16. In that phase II “proof of principle” study involving 1,533 women aged 16–23 years who were initially negative for HPV 16 DNA and antibodies, the vaccine was 94% effective in preventing persistent HPV infection and 100% effective against cervical intraepithelial neoplasia grades 2 and 3, compared with placebo over 3.5 years.

No cases of cervical intraepithelial neoplasia (CIN) were seen among vaccine recipients, compared with CIN 1 in 12 in the placebo group, CIN 2 in 7, and CIN 3 in 6 in the placebo group (PEDIATRIC NEWS, December 2004, p. 10).

Now, phase III data for the current quadrivalent Merck vaccine from a total of 1,529 male and female subjects aged 10–23 show 100% seroconversion at 6 months for HPV types 16, 6, and 11, and 99.9% seroconversion for serotype 18. Antibody levels for all four serotypes were significantly higher among females and males aged 10–15 years than among those aged 16–23. These data were presented earlier this year at the annual meeting of the European Society of Pediatric Infectious Diseases.

The GlaxoSmithKline vaccine also was found highly effective in a multinational randomized, placebo-controlled study of 1,113 women aged 15–25 years who were followed up to 27 months. Vaccine efficacy overall was 91.6% against incident infection and 100% against persistent infection with HPV 16 and/or 18. In the intention-to-treat analysis, vaccine efficacy was 95.1% against persistent cervical infection and 92.9% against cytologic abnormalities associated with HPV 16 and 18 infection (Lancet 2004;364:1731–2).

Merck and GlaxoSmithKline are now each studying the efficacy and safety of their HPV vaccines in more than 20,000 people aged 9–24 years. The results should tell us whether the vaccines have a therapeutic effect in women who are already infected with HPV, perhaps by inducing antibodies to generate an immune response thereby preventing the progression from simple, transient infection to persistent infection to stage 3 (CIN). However, the first order of business is to target girls before they become sexually active.

About a million women per year have an abnormal Pap smear. What follows is a series of costly and anxiety-provoking steps, including colposcopy, cervical scraping, and if abnormal cells are found, cervical biopsy and possible hysterectomy, all at a cost of approximately $2.8 billion. Widespread vaccination against HPV could substantially reduce this burden.

Although the HPV vaccines will not be the first to prevent cancer—the hepatitis B vaccine reduces the likelihood of developing hepatocellular carcinoma—they are the first to be specifically developed and marketed for cancer prevention. As an infectious disease specialist, I see this concept as novel and very, very exciting.

We may soon be able to prevent cervical cancer in women by vaccinating preteens against human papillomavirus.

Two candidate HPV vaccines—GlaxoSmithKline's Cervarix and Merck's Gardasil—are expected to be licensed for use in the United States in 2006. Both vaccines are highly effective in preventing infection with both HPV strains 16 and 18, which are responsible for 70%–75% of cervical cancers in women.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention is already working on guidelines for their use, as is the American Academy of Pediatrics. Both groups are likely to recommend that the vaccines be given to girls aged 11–12 as part of the adolescent “vaccine platform,” along with the meningococcal conjugate vaccine and the adolescent and adult DTaP vaccine.

I see this as a new frontier. It's a fabulous opportunity for those of us who work in vaccinology to be able to move from the prevention of infectious disease per se to the prevention of cancer. Cervical cancer affects approximately 12,000 women in the United States. And despite advances in Pap screening and treatment, the disease kills more than 4,000 women annually.

Nearly all (99.7%) of cervical cancer cases are caused by HPV infection. Approximately 15–20 of the 30–40 anogenital types of HPV that have been identified are oncogenic: HPV 16 causes about 54% of cases, and HPV 18 about 13%. Among the nononcogenic types, HPV 6 and 11 are most often associated with external genital warts. The Merck vaccine targets those two strains as well.

We know that acquisition of HPV typically occurs very soon after initiation of sexual intercourse. In a study of 608 U.S. college women who were followed at 6-month intervals, 43% had become infected with HPV by the third year. Indeed, nearly three-fourths of new HPV infections occur in sexually active young adults aged 15–24, and the prevalence of infection in women less than 25 years of age ranges from 28% to 46%.

As more vaccines are being added to the already-crowded childhood and adolescent immunization schedules, payers will be looking to prioritize more than they have with vaccines in the past. Some authorities think it makes sense to hold off for now on vaccinating males against HPV, even though they are, of course, the major source of infection for females. But since the majority of females pick up HPV by the time they reach their late 20s or early 30s and are therefore at risk for cervical cancer, how can we justify not vaccinating every girl in America?

At last year's meeting of the Interscience Conference on Antimicrobials and Chemotherapy, data were presented for a monovalent version of the current Merck vaccine containing only strain 16. In that phase II “proof of principle” study involving 1,533 women aged 16–23 years who were initially negative for HPV 16 DNA and antibodies, the vaccine was 94% effective in preventing persistent HPV infection and 100% effective against cervical intraepithelial neoplasia grades 2 and 3, compared with placebo over 3.5 years.

No cases of cervical intraepithelial neoplasia (CIN) were seen among vaccine recipients, compared with CIN 1 in 12 in the placebo group, CIN 2 in 7, and CIN 3 in 6 in the placebo group (PEDIATRIC NEWS, December 2004, p. 10).

Now, phase III data for the current quadrivalent Merck vaccine from a total of 1,529 male and female subjects aged 10–23 show 100% seroconversion at 6 months for HPV types 16, 6, and 11, and 99.9% seroconversion for serotype 18. Antibody levels for all four serotypes were significantly higher among females and males aged 10–15 years than among those aged 16–23. These data were presented earlier this year at the annual meeting of the European Society of Pediatric Infectious Diseases.

The GlaxoSmithKline vaccine also was found highly effective in a multinational randomized, placebo-controlled study of 1,113 women aged 15–25 years who were followed up to 27 months. Vaccine efficacy overall was 91.6% against incident infection and 100% against persistent infection with HPV 16 and/or 18. In the intention-to-treat analysis, vaccine efficacy was 95.1% against persistent cervical infection and 92.9% against cytologic abnormalities associated with HPV 16 and 18 infection (Lancet 2004;364:1731–2).

Merck and GlaxoSmithKline are now each studying the efficacy and safety of their HPV vaccines in more than 20,000 people aged 9–24 years. The results should tell us whether the vaccines have a therapeutic effect in women who are already infected with HPV, perhaps by inducing antibodies to generate an immune response thereby preventing the progression from simple, transient infection to persistent infection to stage 3 (CIN). However, the first order of business is to target girls before they become sexually active.

About a million women per year have an abnormal Pap smear. What follows is a series of costly and anxiety-provoking steps, including colposcopy, cervical scraping, and if abnormal cells are found, cervical biopsy and possible hysterectomy, all at a cost of approximately $2.8 billion. Widespread vaccination against HPV could substantially reduce this burden.

Although the HPV vaccines will not be the first to prevent cancer—the hepatitis B vaccine reduces the likelihood of developing hepatocellular carcinoma—they are the first to be specifically developed and marketed for cancer prevention. As an infectious disease specialist, I see this concept as novel and very, very exciting.

Skeletal infection has always been among the top five reasons for inpatient pediatric infectious disease consultations in our institution. Early diagnosis, prompt surgical drainage, and appropriate antimicrobial therapy remain the keys to good outcome. While the clinical manifestations of these infections haven't changed over the years, the microbiologic etiologies have, and this has impacted therapeutic decision making.

Staphylococcal infection remains the most common cause of skeletal infection overall. In recent years, as methicillin-resistant Staphylococcus aureus (MRSA) has emerged, clindamycin has become a common empiric antimicrobial choice for such cases. However, this may not be a good choice for therapy for some children with skeletal infection.

Once considered an unusual cause of pediatric infection, Kingella kingae has emerged as potentially the No. 1 cause of septic arthritis in the child younger than 24 months of age. This fastidious organism, which is often resistant to clindamycin, colonizes the oropharynx of approximately 15% of healthy toddler children. The problem is, it is difficult to grow on culture, requiring an enhanced isolation methodology and a little longer than normal (4.4 days) to grow. Knowing when to think about K. kingae as a potential pathogen should help you provide successful treatment for such children.

Consider the typical case in which a previously healthy and fully immunized child toddler with a recent upper respiratory infection (URI) presents in your office with a high spiking fever and irritability. History reveals no ill contacts, pets, or travel, and you cannot localize a focus for fever or fussiness on examination.

The next day, the child is limping. At this point, further evaluation is warranted and you consider the diagnosis of septic arthritis, keeping in mind that it is a medical and surgical emergency. In the febrile limping toddler with presumed septic arthritis, immediate evaluation by an orthopedic surgeon is necessary. Joint drainage is promptly performed.

What tip-offs might suggest to you that K. kingae should be considered as a potential pathogen, and how might this impact your therapeutic decision making?

For the most part, this organism is an important cause of skeletal infection only in those less than 2 years of age. Other information that may be helpful includes the fact that concomitant URI or stomatitis occurs frequently in such patients (over half in one study), suggesting a respiratory or buccal source for the infection. And this organism has a predilection for ankle involvement in cases of arthritis and calcaneal involvement in bone infection.

Keeping this in mind, since K. kingae is extremely hard to grow on culture, you should alert your surgeon and microbiology laboratory. In addition to routine cultures, ask your orthopedic surgeon to place some of the purulent fluid into a blood culture bottle, in addition to plating for routine culture. Over a decade ago, physicians were alerted to the importance of using BACTEC blood culture bottles to isolate K. kingae in toddlers with skeletal infection (J. Clin. Microbiol.1992;30:1278–81).

The investigators analyzed culture records for the 1988–1991 period and compared the performance of routine culture versus use of blood culture bottle for the recovery of pathogens. A diagnostic joint tap was performed in 216 children. Of those, 63 specimens grew significant organisms. Both methods were comparable for recovery of usual pathogens, but K. kingae isolates were detected by the BACTEC system only, in 13 of 14 specimens.

Just how often K. kingae is the culprit in infant septic arthritis is not completely clear since many centers have not routinely used the above technique to enhance growth.

In a study conducted in Atlanta between 1990 and 1995, where joint aspirates were inoculated into thioglycolate broth, rather than blood culture, gram-positive bacteria were identified in 47 of 60 children (78%) younger than 3 years of age with culture-positive hematogenous septic arthritis and acute or subacute osteomyelitis, while gram-negative organisms were identified in 13 (22%). Of those, K. kingae was cultured in 10 (17%); all such cases occurred in children between the ages of 10.5 and 23.5 months. (J. Pediatr. Orthop. 1998;18:262–7).

Now comes information that implicates K. kingae in a cluster of skeletal infection in one day care center in Minnesota. Three cases occurred among children aged 17–21 months attending the same toddler classroom. Within the same week, all affected children had onset of fever, and antalgic gait. They all had preceding or concurrent upper respiratory illness. K. kingae was isolated from clinical specimens.

For physicians who have been practicing long enough to remember the Haemophilus influenzae type b era, this may seem familiar.

Before the Hib vaccine became widely used, H. influenzae type b was recognized as the etiologic agent in 80% of septic arthritis cases in children less than 2 years of age, and day care center outbreaks were notable.

A colonization study was performed in response to the Minnesota outbreak. Published in Pediatrics in August 2005, the investigators demonstrated that 13% of children at the index day care center (and 45% in the room where the cluster occurred) were colonized in the nasopharynx with K. kingae. Interestingly, no day care center staff or children less than 16 months old were colonized. They compared the nasopharyngeal colonization results with a control day care center. Similarly, 16% of toddler age children were colonized. (Pediatrics 2005;116:e206–13).

In the pre-Hib vaccine era, we routinely used to use rifampin to eradicate Hib carriage among children in day care. Rifampin was used to attempt decolonization of children in the outbreak but proved to be only moderately effective: three of nine children who took rifampin remained positive on reculture 10–14 days later.

As practitioners recognize the importance of recognizing K. kingae as a pathogen in the infant with skeletal infection (and others are noting the emergence of clindamycin-resistant MRSA), clinical decision making in cases of pediatric skeletal infection are becoming increasingly difficult.

A collaborative approach with you, your infectious disease specialist, and orthopedic surgeon that focuses on early diagnosis, pathogen isolation, prompt surgical drainage, and appropriate antimicrobial therapy should allow for the best outcomes.

An example of a typical Gram stain of organisms from a Kingella kingae colony is shown. Courtesy Dr. Pablo Yagupsky

Skeletal infection has always been among the top five reasons for inpatient pediatric infectious disease consultations in our institution. Early diagnosis, prompt surgical drainage, and appropriate antimicrobial therapy remain the keys to good outcome. While the clinical manifestations of these infections haven't changed over the years, the microbiologic etiologies have, and this has impacted therapeutic decision making.

Staphylococcal infection remains the most common cause of skeletal infection overall. In recent years, as methicillin-resistant Staphylococcus aureus (MRSA) has emerged, clindamycin has become a common empiric antimicrobial choice for such cases. However, this may not be a good choice for therapy for some children with skeletal infection.

Once considered an unusual cause of pediatric infection, Kingella kingae has emerged as potentially the No. 1 cause of septic arthritis in the child younger than 24 months of age. This fastidious organism, which is often resistant to clindamycin, colonizes the oropharynx of approximately 15% of healthy toddler children. The problem is, it is difficult to grow on culture, requiring an enhanced isolation methodology and a little longer than normal (4.4 days) to grow. Knowing when to think about K. kingae as a potential pathogen should help you provide successful treatment for such children.

Consider the typical case in which a previously healthy and fully immunized child toddler with a recent upper respiratory infection (URI) presents in your office with a high spiking fever and irritability. History reveals no ill contacts, pets, or travel, and you cannot localize a focus for fever or fussiness on examination.

The next day, the child is limping. At this point, further evaluation is warranted and you consider the diagnosis of septic arthritis, keeping in mind that it is a medical and surgical emergency. In the febrile limping toddler with presumed septic arthritis, immediate evaluation by an orthopedic surgeon is necessary. Joint drainage is promptly performed.

What tip-offs might suggest to you that K. kingae should be considered as a potential pathogen, and how might this impact your therapeutic decision making?

For the most part, this organism is an important cause of skeletal infection only in those less than 2 years of age. Other information that may be helpful includes the fact that concomitant URI or stomatitis occurs frequently in such patients (over half in one study), suggesting a respiratory or buccal source for the infection. And this organism has a predilection for ankle involvement in cases of arthritis and calcaneal involvement in bone infection.

Keeping this in mind, since K. kingae is extremely hard to grow on culture, you should alert your surgeon and microbiology laboratory. In addition to routine cultures, ask your orthopedic surgeon to place some of the purulent fluid into a blood culture bottle, in addition to plating for routine culture. Over a decade ago, physicians were alerted to the importance of using BACTEC blood culture bottles to isolate K. kingae in toddlers with skeletal infection (J. Clin. Microbiol.1992;30:1278–81).

The investigators analyzed culture records for the 1988–1991 period and compared the performance of routine culture versus use of blood culture bottle for the recovery of pathogens. A diagnostic joint tap was performed in 216 children. Of those, 63 specimens grew significant organisms. Both methods were comparable for recovery of usual pathogens, but K. kingae isolates were detected by the BACTEC system only, in 13 of 14 specimens.

Just how often K. kingae is the culprit in infant septic arthritis is not completely clear since many centers have not routinely used the above technique to enhance growth.

In a study conducted in Atlanta between 1990 and 1995, where joint aspirates were inoculated into thioglycolate broth, rather than blood culture, gram-positive bacteria were identified in 47 of 60 children (78%) younger than 3 years of age with culture-positive hematogenous septic arthritis and acute or subacute osteomyelitis, while gram-negative organisms were identified in 13 (22%). Of those, K. kingae was cultured in 10 (17%); all such cases occurred in children between the ages of 10.5 and 23.5 months. (J. Pediatr. Orthop. 1998;18:262–7).

Now comes information that implicates K. kingae in a cluster of skeletal infection in one day care center in Minnesota. Three cases occurred among children aged 17–21 months attending the same toddler classroom. Within the same week, all affected children had onset of fever, and antalgic gait. They all had preceding or concurrent upper respiratory illness. K. kingae was isolated from clinical specimens.

For physicians who have been practicing long enough to remember the Haemophilus influenzae type b era, this may seem familiar.

Before the Hib vaccine became widely used, H. influenzae type b was recognized as the etiologic agent in 80% of septic arthritis cases in children less than 2 years of age, and day care center outbreaks were notable.

A colonization study was performed in response to the Minnesota outbreak. Published in Pediatrics in August 2005, the investigators demonstrated that 13% of children at the index day care center (and 45% in the room where the cluster occurred) were colonized in the nasopharynx with K. kingae. Interestingly, no day care center staff or children less than 16 months old were colonized. They compared the nasopharyngeal colonization results with a control day care center. Similarly, 16% of toddler age children were colonized. (Pediatrics 2005;116:e206–13).

In the pre-Hib vaccine era, we routinely used to use rifampin to eradicate Hib carriage among children in day care. Rifampin was used to attempt decolonization of children in the outbreak but proved to be only moderately effective: three of nine children who took rifampin remained positive on reculture 10–14 days later.

As practitioners recognize the importance of recognizing K. kingae as a pathogen in the infant with skeletal infection (and others are noting the emergence of clindamycin-resistant MRSA), clinical decision making in cases of pediatric skeletal infection are becoming increasingly difficult.

A collaborative approach with you, your infectious disease specialist, and orthopedic surgeon that focuses on early diagnosis, pathogen isolation, prompt surgical drainage, and appropriate antimicrobial therapy should allow for the best outcomes.

An example of a typical Gram stain of organisms from a Kingella kingae colony is shown. Courtesy Dr. Pablo Yagupsky

Skeletal infection has always been among the top five reasons for inpatient pediatric infectious disease consultations in our institution. Early diagnosis, prompt surgical drainage, and appropriate antimicrobial therapy remain the keys to good outcome. While the clinical manifestations of these infections haven't changed over the years, the microbiologic etiologies have, and this has impacted therapeutic decision making.

Staphylococcal infection remains the most common cause of skeletal infection overall. In recent years, as methicillin-resistant Staphylococcus aureus (MRSA) has emerged, clindamycin has become a common empiric antimicrobial choice for such cases. However, this may not be a good choice for therapy for some children with skeletal infection.

Once considered an unusual cause of pediatric infection, Kingella kingae has emerged as potentially the No. 1 cause of septic arthritis in the child younger than 24 months of age. This fastidious organism, which is often resistant to clindamycin, colonizes the oropharynx of approximately 15% of healthy toddler children. The problem is, it is difficult to grow on culture, requiring an enhanced isolation methodology and a little longer than normal (4.4 days) to grow. Knowing when to think about K. kingae as a potential pathogen should help you provide successful treatment for such children.

Consider the typical case in which a previously healthy and fully immunized child toddler with a recent upper respiratory infection (URI) presents in your office with a high spiking fever and irritability. History reveals no ill contacts, pets, or travel, and you cannot localize a focus for fever or fussiness on examination.

The next day, the child is limping. At this point, further evaluation is warranted and you consider the diagnosis of septic arthritis, keeping in mind that it is a medical and surgical emergency. In the febrile limping toddler with presumed septic arthritis, immediate evaluation by an orthopedic surgeon is necessary. Joint drainage is promptly performed.

What tip-offs might suggest to you that K. kingae should be considered as a potential pathogen, and how might this impact your therapeutic decision making?

For the most part, this organism is an important cause of skeletal infection only in those less than 2 years of age. Other information that may be helpful includes the fact that concomitant URI or stomatitis occurs frequently in such patients (over half in one study), suggesting a respiratory or buccal source for the infection. And this organism has a predilection for ankle involvement in cases of arthritis and calcaneal involvement in bone infection.

Keeping this in mind, since K. kingae is extremely hard to grow on culture, you should alert your surgeon and microbiology laboratory. In addition to routine cultures, ask your orthopedic surgeon to place some of the purulent fluid into a blood culture bottle, in addition to plating for routine culture. Over a decade ago, physicians were alerted to the importance of using BACTEC blood culture bottles to isolate K. kingae in toddlers with skeletal infection (J. Clin. Microbiol.1992;30:1278–81).

The investigators analyzed culture records for the 1988–1991 period and compared the performance of routine culture versus use of blood culture bottle for the recovery of pathogens. A diagnostic joint tap was performed in 216 children. Of those, 63 specimens grew significant organisms. Both methods were comparable for recovery of usual pathogens, but K. kingae isolates were detected by the BACTEC system only, in 13 of 14 specimens.

Just how often K. kingae is the culprit in infant septic arthritis is not completely clear since many centers have not routinely used the above technique to enhance growth.

In a study conducted in Atlanta between 1990 and 1995, where joint aspirates were inoculated into thioglycolate broth, rather than blood culture, gram-positive bacteria were identified in 47 of 60 children (78%) younger than 3 years of age with culture-positive hematogenous septic arthritis and acute or subacute osteomyelitis, while gram-negative organisms were identified in 13 (22%). Of those, K. kingae was cultured in 10 (17%); all such cases occurred in children between the ages of 10.5 and 23.5 months. (J. Pediatr. Orthop. 1998;18:262–7).

Now comes information that implicates K. kingae in a cluster of skeletal infection in one day care center in Minnesota. Three cases occurred among children aged 17–21 months attending the same toddler classroom. Within the same week, all affected children had onset of fever, and antalgic gait. They all had preceding or concurrent upper respiratory illness. K. kingae was isolated from clinical specimens.

For physicians who have been practicing long enough to remember the Haemophilus influenzae type b era, this may seem familiar.

Before the Hib vaccine became widely used, H. influenzae type b was recognized as the etiologic agent in 80% of septic arthritis cases in children less than 2 years of age, and day care center outbreaks were notable.

A colonization study was performed in response to the Minnesota outbreak. Published in Pediatrics in August 2005, the investigators demonstrated that 13% of children at the index day care center (and 45% in the room where the cluster occurred) were colonized in the nasopharynx with K. kingae. Interestingly, no day care center staff or children less than 16 months old were colonized. They compared the nasopharyngeal colonization results with a control day care center. Similarly, 16% of toddler age children were colonized. (Pediatrics 2005;116:e206–13).

In the pre-Hib vaccine era, we routinely used to use rifampin to eradicate Hib carriage among children in day care. Rifampin was used to attempt decolonization of children in the outbreak but proved to be only moderately effective: three of nine children who took rifampin remained positive on reculture 10–14 days later.

As practitioners recognize the importance of recognizing K. kingae as a pathogen in the infant with skeletal infection (and others are noting the emergence of clindamycin-resistant MRSA), clinical decision making in cases of pediatric skeletal infection are becoming increasingly difficult.

A collaborative approach with you, your infectious disease specialist, and orthopedic surgeon that focuses on early diagnosis, pathogen isolation, prompt surgical drainage, and appropriate antimicrobial therapy should allow for the best outcomes.

An example of a typical Gram stain of organisms from a Kingella kingae colony is shown. Courtesy Dr. Pablo Yagupsky