Mary Anne Jackson

We're starting to see the first evidence that rotavirus disease rates are going down, perhaps even more than we expected, thanks to the vaccine.

Although rates of both respiratory syncytial virus and influenza were up this past winter, compared with the previous couple of years, it's been very gratifying for the infectious disease community to see, for the first time, a paucity of rotavirus cases.

As every practitioner who treats children knows, rotavirus is the most common cause of severe wintertime gastroenteritis among children younger than 5 years. The numbers have stayed consistent: Every year, approximately 3 million children get rotavirus disease, about 700,000 seek health care for it, 250,000 present to the emergency department, 50,000 are admitted, and a small number (20–60) die. A recent analysis from the Centers for Disease Control and Prevention (CDC) showed that the total annual cost to society from rotavirus in the United States (in 2004 dollars) was $893 million, $319 million of which was to the health care system (Pediatrics 2007;119:684–97).

A previous oral rotavirus vaccine—the tetravalent rhesus vaccine, RotaShield—was removed from the market in 1999 because of a detected increase in intussusception after about a half-million children had received one or more doses. In February 2006, Rotateq—a new live, oral pentavalent human-bovine reassortment rotavirus vaccine (Merck & Co.)—was licensed and recommended. I'm excited about preliminary numbers, which suggest that rotavirus immunization may be more successful than predicted.

Here at Children's Mercy Hospital in Kansas City (317 beds/14,000 annual admissions), we test only the sickest children for rotavirus. During the 2006 rotavirus season, we tested 1,009 and got 514 positives (51%). In 2007, we had 686 positives out of 1,271 tested (54%)—not much different. We wouldn't have expected an impact that soon after the vaccine was licensed.

This year, however, we saw a dramatic change. Only 495 children presented with gastroenteritis who were sick enough to prompt testing, and of those, just 93 (19%) were positive. Even more amazing, only 38 children were admitted to the hospital, which represented a 10-fold decrease, compared with previous years. What happened to all our rotavirus cases?

This finding is even more remarkable when you look at how consistent our rotavirus disease rates have been over time. Last year, we combined our rotavirus data for the years 2000–2005 with those from Children's Hospital of Philadelphia (CHOP) from 2004–2006 and reported that approximately half of children admitted with severe diarrhea were tested for rotavirus (47% of 2,552 children at Mercy and 56% of 779 at CHOP). Of those, 71% of our 1,197 and 55% of CHOP's 438 were positive (Pediatr. Infect. Dis. J. 2007;26:914–9).

We haven't changed anything about our testing or admitting practices since those data were collected, which strongly suggests that our new numbers represent a real drop.

Moreover, if you look at the CDC's rotavirus surveillance data (www.cdc.gov/rotavirus

If nationwide surveillance data continue to bear out what we've seen at my hospital, the vaccine's impact will have far exceeded expectations. In the CDC cost analysis I mentioned earlier, investigators estimated that if vaccine coverage were equivalent to current national estimates for other vaccines such as diphtheria-tetanus-acellular pertussis—which is probably a big overestimate—a routine rotavirus vaccination program would prevent 51% of all cases of rotavirus gastroenteritis and 64% of all serious cases, including rotavirus-related hospitalization and emergency department visits.

Our 86% decrease (93 cases this year vs. 686 in 2007) is far greater than predicted by the CDC's analysis. Although viral shedding of the rotavirus vaccine is nowhere near what we used to see with oral polio vaccine, there is evidence that it occurs. In one study, fecal shedding of vaccine-virus strains was found in 8.9% of 360 recipients after the first dose (Int. J. Infect. Dis. 2007;11[Suppl 2]:S36–42), which raises the question of possible herd immunity.

Now, with the recent approval of Rotarix (GlaxoSmithKline)—another oral rotavirus vaccine that is given in two doses, compared with Rotateq's three—I'm optimistic that there will be more good news in the battle against this common childhood infection. Can you imagine the day when a pediatric resident will not see a hospitalized child who has rotavirus infection during the winter months?

I have no financial relationships with either Merck or GSK.

We're starting to see the first evidence that rotavirus disease rates are going down, perhaps even more than we expected, thanks to the vaccine.

Although rates of both respiratory syncytial virus and influenza were up this past winter, compared with the previous couple of years, it's been very gratifying for the infectious disease community to see, for the first time, a paucity of rotavirus cases.

As every practitioner who treats children knows, rotavirus is the most common cause of severe wintertime gastroenteritis among children younger than 5 years. The numbers have stayed consistent: Every year, approximately 3 million children get rotavirus disease, about 700,000 seek health care for it, 250,000 present to the emergency department, 50,000 are admitted, and a small number (20–60) die. A recent analysis from the Centers for Disease Control and Prevention (CDC) showed that the total annual cost to society from rotavirus in the United States (in 2004 dollars) was $893 million, $319 million of which was to the health care system (Pediatrics 2007;119:684–97).

A previous oral rotavirus vaccine—the tetravalent rhesus vaccine, RotaShield—was removed from the market in 1999 because of a detected increase in intussusception after about a half-million children had received one or more doses. In February 2006, Rotateq—a new live, oral pentavalent human-bovine reassortment rotavirus vaccine (Merck & Co.)—was licensed and recommended. I'm excited about preliminary numbers, which suggest that rotavirus immunization may be more successful than predicted.

Here at Children's Mercy Hospital in Kansas City (317 beds/14,000 annual admissions), we test only the sickest children for rotavirus. During the 2006 rotavirus season, we tested 1,009 and got 514 positives (51%). In 2007, we had 686 positives out of 1,271 tested (54%)—not much different. We wouldn't have expected an impact that soon after the vaccine was licensed.

This year, however, we saw a dramatic change. Only 495 children presented with gastroenteritis who were sick enough to prompt testing, and of those, just 93 (19%) were positive. Even more amazing, only 38 children were admitted to the hospital, which represented a 10-fold decrease, compared with previous years. What happened to all our rotavirus cases?

This finding is even more remarkable when you look at how consistent our rotavirus disease rates have been over time. Last year, we combined our rotavirus data for the years 2000–2005 with those from Children's Hospital of Philadelphia (CHOP) from 2004–2006 and reported that approximately half of children admitted with severe diarrhea were tested for rotavirus (47% of 2,552 children at Mercy and 56% of 779 at CHOP). Of those, 71% of our 1,197 and 55% of CHOP's 438 were positive (Pediatr. Infect. Dis. J. 2007;26:914–9).

We haven't changed anything about our testing or admitting practices since those data were collected, which strongly suggests that our new numbers represent a real drop.

Moreover, if you look at the CDC's rotavirus surveillance data (www.cdc.gov/rotavirus

If nationwide surveillance data continue to bear out what we've seen at my hospital, the vaccine's impact will have far exceeded expectations. In the CDC cost analysis I mentioned earlier, investigators estimated that if vaccine coverage were equivalent to current national estimates for other vaccines such as diphtheria-tetanus-acellular pertussis—which is probably a big overestimate—a routine rotavirus vaccination program would prevent 51% of all cases of rotavirus gastroenteritis and 64% of all serious cases, including rotavirus-related hospitalization and emergency department visits.

Our 86% decrease (93 cases this year vs. 686 in 2007) is far greater than predicted by the CDC's analysis. Although viral shedding of the rotavirus vaccine is nowhere near what we used to see with oral polio vaccine, there is evidence that it occurs. In one study, fecal shedding of vaccine-virus strains was found in 8.9% of 360 recipients after the first dose (Int. J. Infect. Dis. 2007;11[Suppl 2]:S36–42), which raises the question of possible herd immunity.

Now, with the recent approval of Rotarix (GlaxoSmithKline)—another oral rotavirus vaccine that is given in two doses, compared with Rotateq's three—I'm optimistic that there will be more good news in the battle against this common childhood infection. Can you imagine the day when a pediatric resident will not see a hospitalized child who has rotavirus infection during the winter months?

I have no financial relationships with either Merck or GSK.

We're starting to see the first evidence that rotavirus disease rates are going down, perhaps even more than we expected, thanks to the vaccine.

Although rates of both respiratory syncytial virus and influenza were up this past winter, compared with the previous couple of years, it's been very gratifying for the infectious disease community to see, for the first time, a paucity of rotavirus cases.

As every practitioner who treats children knows, rotavirus is the most common cause of severe wintertime gastroenteritis among children younger than 5 years. The numbers have stayed consistent: Every year, approximately 3 million children get rotavirus disease, about 700,000 seek health care for it, 250,000 present to the emergency department, 50,000 are admitted, and a small number (20–60) die. A recent analysis from the Centers for Disease Control and Prevention (CDC) showed that the total annual cost to society from rotavirus in the United States (in 2004 dollars) was $893 million, $319 million of which was to the health care system (Pediatrics 2007;119:684–97).

A previous oral rotavirus vaccine—the tetravalent rhesus vaccine, RotaShield—was removed from the market in 1999 because of a detected increase in intussusception after about a half-million children had received one or more doses. In February 2006, Rotateq—a new live, oral pentavalent human-bovine reassortment rotavirus vaccine (Merck & Co.)—was licensed and recommended. I'm excited about preliminary numbers, which suggest that rotavirus immunization may be more successful than predicted.

Here at Children's Mercy Hospital in Kansas City (317 beds/14,000 annual admissions), we test only the sickest children for rotavirus. During the 2006 rotavirus season, we tested 1,009 and got 514 positives (51%). In 2007, we had 686 positives out of 1,271 tested (54%)—not much different. We wouldn't have expected an impact that soon after the vaccine was licensed.

This year, however, we saw a dramatic change. Only 495 children presented with gastroenteritis who were sick enough to prompt testing, and of those, just 93 (19%) were positive. Even more amazing, only 38 children were admitted to the hospital, which represented a 10-fold decrease, compared with previous years. What happened to all our rotavirus cases?

This finding is even more remarkable when you look at how consistent our rotavirus disease rates have been over time. Last year, we combined our rotavirus data for the years 2000–2005 with those from Children's Hospital of Philadelphia (CHOP) from 2004–2006 and reported that approximately half of children admitted with severe diarrhea were tested for rotavirus (47% of 2,552 children at Mercy and 56% of 779 at CHOP). Of those, 71% of our 1,197 and 55% of CHOP's 438 were positive (Pediatr. Infect. Dis. J. 2007;26:914–9).

We haven't changed anything about our testing or admitting practices since those data were collected, which strongly suggests that our new numbers represent a real drop.

Moreover, if you look at the CDC's rotavirus surveillance data (www.cdc.gov/rotavirus

If nationwide surveillance data continue to bear out what we've seen at my hospital, the vaccine's impact will have far exceeded expectations. In the CDC cost analysis I mentioned earlier, investigators estimated that if vaccine coverage were equivalent to current national estimates for other vaccines such as diphtheria-tetanus-acellular pertussis—which is probably a big overestimate—a routine rotavirus vaccination program would prevent 51% of all cases of rotavirus gastroenteritis and 64% of all serious cases, including rotavirus-related hospitalization and emergency department visits.

Our 86% decrease (93 cases this year vs. 686 in 2007) is far greater than predicted by the CDC's analysis. Although viral shedding of the rotavirus vaccine is nowhere near what we used to see with oral polio vaccine, there is evidence that it occurs. In one study, fecal shedding of vaccine-virus strains was found in 8.9% of 360 recipients after the first dose (Int. J. Infect. Dis. 2007;11[Suppl 2]:S36–42), which raises the question of possible herd immunity.

Now, with the recent approval of Rotarix (GlaxoSmithKline)—another oral rotavirus vaccine that is given in two doses, compared with Rotateq's three—I'm optimistic that there will be more good news in the battle against this common childhood infection. Can you imagine the day when a pediatric resident will not see a hospitalized child who has rotavirus infection during the winter months?

I have no financial relationships with either Merck or GSK.

[email protected]

Happy New Year! It's time again for my annual prognosis of the top 10 infectious disease issues likely to have an impact on our practices in the next 12 months.

▸ 1. Local school-based immunization programs could become a reality. Nationally, it will take increased vaccine production and better organization of school-based infrastructure. Still, I foresee some local initiatives coming to fruition in 2008.

We have evidence that such programs work. In a recent study, Dr. James C. King Jr. and his associates at the University of Maryland, Baltimore, identified 11 demographically similar clusters of elementary schools (24 total) in four states. One school in each cluster served as the “intervention” school, and the others as controls. Healthy children aged 5 years and older in the intervention schools were offered free nasal influenza vaccine before the 2004–2005 influenza season (N. Engl. J. Med. 2006;355:2523–32).

The investigators identified the predicted peak weeks of influenza activity for each state, then evaluated rates of illness and school absence in the respective schools by a survey of parents immediately following the predicted week of peak influenza activity. Of the 5,840 children in the intervention schools, 47% (2,717) received the vaccine.

Compared with the children in the control schools, those in vaccinated schools were significantly less likely to experience any fever or flulike illness (40% vs. 52%) or to visit a clinic or physician's office for any type of care (7 vs. 11 per 100 patients). They also received fewer prescriptions, used fewer over-the-counter medicines, and were less likely to miss school.

While we're waiting for school programs, remember that it's still not too late to have an impact personally on influenza disease by targeting your high-risk patients and offering vaccine to any child in your practice.

▸ 2. Community pneumonia and otitis media may become harder to treat as pneumococcal disease rates plateau and new strains continue to appear. Serotype 19A will emerge as the nemesis and cause more disease associated with multidrug resistance. In the PROTEKT US study, coverage with the 7-valent conjugate pneumococcal vaccine (PCV7) and antimicrobial susceptibility among Streptococcus pneumoniae isolates collected from children aged 0–14 years were examined for the periods 2000–2001, 2002–2003, and 2003–2004. The most common serotypes in year 4 were the nonvaccine serotypes 19A (19% of all isolates), 6A (8%), 3 (8%), 15 (6%), and 35B (6%), along with 19F (13%), which is included in the vaccine (J. Clin. Microbiol. 2007;45:290–3).

Although the proportion of S. pneumoniae isolates from the U.S. pediatric population covered by PCV7 decreased substantially in the 4 years after the vaccine was introduced, there were significant increases in strains that were resistant to commonly used antibiotics, including beta-lactams and macrolides, as well as in multidrug resistant strains, particularly among respiratory tract isolates.

In a separate report, Dr. Michael E. Pichichero and Dr. Janet R. Casey identified serotype 19A pneumococcus as an otopathogen that is resistant to all antibiotics currently approved for the treatment of acute otitis media in children (JAMA 2007;298:1772–8). Will pediatricians need to be trained in tympanocentesis again? My crystal ball says maybe.

▸ 3. Travel-related issues will arise more often in your practice. The number of children traveling overseas continues to increase. While curbside consultations generally target malaria prophylaxis, pediatricians also should offer counseling regarding food- and waterborne disease, other vector-borne diseases, and airborne diseases.

Such counseling should take into account the patient's age, nutritional status, and any underlying illness. All routine immunizations should be updated. The country, accommodations, and length of trip will all dictate which travel vaccines the child will need. Other topics to cover include food and water precautions, planning for symptomatic treatment of traveler's diarrhea, protection against mosquito-borne pathogens and TB where it is endemic, and a plan for evaluation on return for those staying longer than a month. I particularly recommend an article entitled, “Germs on a plane—infectious issues and the pediatric international traveler: What pediatricians should know,” by two Canadian researchers (Pediatr. Ann. 2007;36:344–51).

▸ 4. A new blood test for tuberculosis may supplant intradermal skin testing. Interferon-γ release assays using whole blood may reliably determine if a child has been infected with TB. The tests require just one visit and the results are often available within 1 day. The tests provide greater specificity than tests using purified protein derivatives such as the TB antigen, with similar sensitivity.

▸ 5. The vaccine reimbursement issue will continue to dominate discussions among policy experts, but it's not likely we'll see a solution. In February 2007, the American Academy of Pediatrics and the American Medical Association held a joint congress at which major proposals included setting national standards for minimal reimbursement, standardizing vaccine administration fees, and having vaccine manufacturers work with pediatricians to offset the cost for inventory of new vaccines. It's a start. I hope that working through bureaucratic channels won't take as long as I anticipate.

▸ 6. Infections from exotic pets will continue to rise. Many families with young children continue to own reptiles and other unusual animals, despite AAP recommendations against it. Every well-child evaluation should include a question about pet ownership. There is cause for concern if the family has an animal other than a dog, cat, small rodent, or fish. Here is a question-based mnemonic borrowed from the Black Pine Animal Park, an exotic animal rescue organization in Indiana:

G: How much will this animal Grow?

O: How Old can this animal live to be?

O: Will this animal create Odors I won't like?

D: What kind of Diet does this animal require?

L: Can this animal be Lethal to me and others?

I: Is it Illegal for me to own this animal?

F: Just how much Fun will it really be to own this animal?

E: What are the Environmental requirements for this animal?

▸ 7. Rotavirus cases will decrease. There is high hope that the rotavirus vaccine will have an impact on hospitalization and emergency visit rates for rotavirus disease. Currently 1 in 17 children infected with rotavirus becomes ill enough to visit the emergency department, and 1 in 65 is hospitalized. If, as anticipated, the vaccine eliminates 98% of such severe cases, it will be easy to appreciate its impact.

▸ 8. Vaccination coverage will be high, but still not high enough. Although the 2004 numbers showed the highest rates ever recorded, about 20% of children younger than 2 years are still inadequately immunized. New strategies will be needed for 2008, but they must be designed carefully.

A court in Maryland recently ordered that parents be sent to jail if their children are not immunized. This did not go over well with the public and many physicians questioned the approach.

▸ 9. Methicillin-resistant Staphylococcus aureus cases will continue to rise. Unfortunately, clindamycin-resistance rates will increase in 2008, making empiric treatment of invasive diseases such as osteomyelitis increasingly difficult.

▸ 10. Active surveillance for MRSA will become a reality for the hospitalized patient, at least for children in high-risk settings such as the intensive care unit. Where and how often children will be cultured (nasal/axilla/rectal?weekly/while hospitalized?) will vary from institution to institution. However, all institutions will attempt to identify those patients already colonized with MRSA at the time of hospitalization and will utilize barrier precautions to prevent hospital spread.

[email protected]

Happy New Year! It's time again for my annual prognosis of the top 10 infectious disease issues likely to have an impact on our practices in the next 12 months.

▸ 1. Local school-based immunization programs could become a reality. Nationally, it will take increased vaccine production and better organization of school-based infrastructure. Still, I foresee some local initiatives coming to fruition in 2008.

We have evidence that such programs work. In a recent study, Dr. James C. King Jr. and his associates at the University of Maryland, Baltimore, identified 11 demographically similar clusters of elementary schools (24 total) in four states. One school in each cluster served as the “intervention” school, and the others as controls. Healthy children aged 5 years and older in the intervention schools were offered free nasal influenza vaccine before the 2004–2005 influenza season (N. Engl. J. Med. 2006;355:2523–32).

The investigators identified the predicted peak weeks of influenza activity for each state, then evaluated rates of illness and school absence in the respective schools by a survey of parents immediately following the predicted week of peak influenza activity. Of the 5,840 children in the intervention schools, 47% (2,717) received the vaccine.

Compared with the children in the control schools, those in vaccinated schools were significantly less likely to experience any fever or flulike illness (40% vs. 52%) or to visit a clinic or physician's office for any type of care (7 vs. 11 per 100 patients). They also received fewer prescriptions, used fewer over-the-counter medicines, and were less likely to miss school.

While we're waiting for school programs, remember that it's still not too late to have an impact personally on influenza disease by targeting your high-risk patients and offering vaccine to any child in your practice.

▸ 2. Community pneumonia and otitis media may become harder to treat as pneumococcal disease rates plateau and new strains continue to appear. Serotype 19A will emerge as the nemesis and cause more disease associated with multidrug resistance. In the PROTEKT US study, coverage with the 7-valent conjugate pneumococcal vaccine (PCV7) and antimicrobial susceptibility among Streptococcus pneumoniae isolates collected from children aged 0–14 years were examined for the periods 2000–2001, 2002–2003, and 2003–2004. The most common serotypes in year 4 were the nonvaccine serotypes 19A (19% of all isolates), 6A (8%), 3 (8%), 15 (6%), and 35B (6%), along with 19F (13%), which is included in the vaccine (J. Clin. Microbiol. 2007;45:290–3).

Although the proportion of S. pneumoniae isolates from the U.S. pediatric population covered by PCV7 decreased substantially in the 4 years after the vaccine was introduced, there were significant increases in strains that were resistant to commonly used antibiotics, including beta-lactams and macrolides, as well as in multidrug resistant strains, particularly among respiratory tract isolates.

In a separate report, Dr. Michael E. Pichichero and Dr. Janet R. Casey identified serotype 19A pneumococcus as an otopathogen that is resistant to all antibiotics currently approved for the treatment of acute otitis media in children (JAMA 2007;298:1772–8). Will pediatricians need to be trained in tympanocentesis again? My crystal ball says maybe.

▸ 3. Travel-related issues will arise more often in your practice. The number of children traveling overseas continues to increase. While curbside consultations generally target malaria prophylaxis, pediatricians also should offer counseling regarding food- and waterborne disease, other vector-borne diseases, and airborne diseases.

Such counseling should take into account the patient's age, nutritional status, and any underlying illness. All routine immunizations should be updated. The country, accommodations, and length of trip will all dictate which travel vaccines the child will need. Other topics to cover include food and water precautions, planning for symptomatic treatment of traveler's diarrhea, protection against mosquito-borne pathogens and TB where it is endemic, and a plan for evaluation on return for those staying longer than a month. I particularly recommend an article entitled, “Germs on a plane—infectious issues and the pediatric international traveler: What pediatricians should know,” by two Canadian researchers (Pediatr. Ann. 2007;36:344–51).

▸ 4. A new blood test for tuberculosis may supplant intradermal skin testing. Interferon-γ release assays using whole blood may reliably determine if a child has been infected with TB. The tests require just one visit and the results are often available within 1 day. The tests provide greater specificity than tests using purified protein derivatives such as the TB antigen, with similar sensitivity.

▸ 5. The vaccine reimbursement issue will continue to dominate discussions among policy experts, but it's not likely we'll see a solution. In February 2007, the American Academy of Pediatrics and the American Medical Association held a joint congress at which major proposals included setting national standards for minimal reimbursement, standardizing vaccine administration fees, and having vaccine manufacturers work with pediatricians to offset the cost for inventory of new vaccines. It's a start. I hope that working through bureaucratic channels won't take as long as I anticipate.

▸ 6. Infections from exotic pets will continue to rise. Many families with young children continue to own reptiles and other unusual animals, despite AAP recommendations against it. Every well-child evaluation should include a question about pet ownership. There is cause for concern if the family has an animal other than a dog, cat, small rodent, or fish. Here is a question-based mnemonic borrowed from the Black Pine Animal Park, an exotic animal rescue organization in Indiana:

G: How much will this animal Grow?

O: How Old can this animal live to be?

O: Will this animal create Odors I won't like?

D: What kind of Diet does this animal require?

L: Can this animal be Lethal to me and others?

I: Is it Illegal for me to own this animal?

F: Just how much Fun will it really be to own this animal?

E: What are the Environmental requirements for this animal?

▸ 7. Rotavirus cases will decrease. There is high hope that the rotavirus vaccine will have an impact on hospitalization and emergency visit rates for rotavirus disease. Currently 1 in 17 children infected with rotavirus becomes ill enough to visit the emergency department, and 1 in 65 is hospitalized. If, as anticipated, the vaccine eliminates 98% of such severe cases, it will be easy to appreciate its impact.

▸ 8. Vaccination coverage will be high, but still not high enough. Although the 2004 numbers showed the highest rates ever recorded, about 20% of children younger than 2 years are still inadequately immunized. New strategies will be needed for 2008, but they must be designed carefully.

A court in Maryland recently ordered that parents be sent to jail if their children are not immunized. This did not go over well with the public and many physicians questioned the approach.

▸ 9. Methicillin-resistant Staphylococcus aureus cases will continue to rise. Unfortunately, clindamycin-resistance rates will increase in 2008, making empiric treatment of invasive diseases such as osteomyelitis increasingly difficult.

▸ 10. Active surveillance for MRSA will become a reality for the hospitalized patient, at least for children in high-risk settings such as the intensive care unit. Where and how often children will be cultured (nasal/axilla/rectal?weekly/while hospitalized?) will vary from institution to institution. However, all institutions will attempt to identify those patients already colonized with MRSA at the time of hospitalization and will utilize barrier precautions to prevent hospital spread.

[email protected]

Happy New Year! It's time again for my annual prognosis of the top 10 infectious disease issues likely to have an impact on our practices in the next 12 months.

▸ 1. Local school-based immunization programs could become a reality. Nationally, it will take increased vaccine production and better organization of school-based infrastructure. Still, I foresee some local initiatives coming to fruition in 2008.

We have evidence that such programs work. In a recent study, Dr. James C. King Jr. and his associates at the University of Maryland, Baltimore, identified 11 demographically similar clusters of elementary schools (24 total) in four states. One school in each cluster served as the “intervention” school, and the others as controls. Healthy children aged 5 years and older in the intervention schools were offered free nasal influenza vaccine before the 2004–2005 influenza season (N. Engl. J. Med. 2006;355:2523–32).

The investigators identified the predicted peak weeks of influenza activity for each state, then evaluated rates of illness and school absence in the respective schools by a survey of parents immediately following the predicted week of peak influenza activity. Of the 5,840 children in the intervention schools, 47% (2,717) received the vaccine.

Compared with the children in the control schools, those in vaccinated schools were significantly less likely to experience any fever or flulike illness (40% vs. 52%) or to visit a clinic or physician's office for any type of care (7 vs. 11 per 100 patients). They also received fewer prescriptions, used fewer over-the-counter medicines, and were less likely to miss school.

While we're waiting for school programs, remember that it's still not too late to have an impact personally on influenza disease by targeting your high-risk patients and offering vaccine to any child in your practice.

▸ 2. Community pneumonia and otitis media may become harder to treat as pneumococcal disease rates plateau and new strains continue to appear. Serotype 19A will emerge as the nemesis and cause more disease associated with multidrug resistance. In the PROTEKT US study, coverage with the 7-valent conjugate pneumococcal vaccine (PCV7) and antimicrobial susceptibility among Streptococcus pneumoniae isolates collected from children aged 0–14 years were examined for the periods 2000–2001, 2002–2003, and 2003–2004. The most common serotypes in year 4 were the nonvaccine serotypes 19A (19% of all isolates), 6A (8%), 3 (8%), 15 (6%), and 35B (6%), along with 19F (13%), which is included in the vaccine (J. Clin. Microbiol. 2007;45:290–3).

Although the proportion of S. pneumoniae isolates from the U.S. pediatric population covered by PCV7 decreased substantially in the 4 years after the vaccine was introduced, there were significant increases in strains that were resistant to commonly used antibiotics, including beta-lactams and macrolides, as well as in multidrug resistant strains, particularly among respiratory tract isolates.

In a separate report, Dr. Michael E. Pichichero and Dr. Janet R. Casey identified serotype 19A pneumococcus as an otopathogen that is resistant to all antibiotics currently approved for the treatment of acute otitis media in children (JAMA 2007;298:1772–8). Will pediatricians need to be trained in tympanocentesis again? My crystal ball says maybe.

▸ 3. Travel-related issues will arise more often in your practice. The number of children traveling overseas continues to increase. While curbside consultations generally target malaria prophylaxis, pediatricians also should offer counseling regarding food- and waterborne disease, other vector-borne diseases, and airborne diseases.

Such counseling should take into account the patient's age, nutritional status, and any underlying illness. All routine immunizations should be updated. The country, accommodations, and length of trip will all dictate which travel vaccines the child will need. Other topics to cover include food and water precautions, planning for symptomatic treatment of traveler's diarrhea, protection against mosquito-borne pathogens and TB where it is endemic, and a plan for evaluation on return for those staying longer than a month. I particularly recommend an article entitled, “Germs on a plane—infectious issues and the pediatric international traveler: What pediatricians should know,” by two Canadian researchers (Pediatr. Ann. 2007;36:344–51).

▸ 4. A new blood test for tuberculosis may supplant intradermal skin testing. Interferon-γ release assays using whole blood may reliably determine if a child has been infected with TB. The tests require just one visit and the results are often available within 1 day. The tests provide greater specificity than tests using purified protein derivatives such as the TB antigen, with similar sensitivity.

▸ 5. The vaccine reimbursement issue will continue to dominate discussions among policy experts, but it's not likely we'll see a solution. In February 2007, the American Academy of Pediatrics and the American Medical Association held a joint congress at which major proposals included setting national standards for minimal reimbursement, standardizing vaccine administration fees, and having vaccine manufacturers work with pediatricians to offset the cost for inventory of new vaccines. It's a start. I hope that working through bureaucratic channels won't take as long as I anticipate.

▸ 6. Infections from exotic pets will continue to rise. Many families with young children continue to own reptiles and other unusual animals, despite AAP recommendations against it. Every well-child evaluation should include a question about pet ownership. There is cause for concern if the family has an animal other than a dog, cat, small rodent, or fish. Here is a question-based mnemonic borrowed from the Black Pine Animal Park, an exotic animal rescue organization in Indiana:

G: How much will this animal Grow?

O: How Old can this animal live to be?

O: Will this animal create Odors I won't like?

D: What kind of Diet does this animal require?

L: Can this animal be Lethal to me and others?

I: Is it Illegal for me to own this animal?

F: Just how much Fun will it really be to own this animal?

E: What are the Environmental requirements for this animal?

▸ 7. Rotavirus cases will decrease. There is high hope that the rotavirus vaccine will have an impact on hospitalization and emergency visit rates for rotavirus disease. Currently 1 in 17 children infected with rotavirus becomes ill enough to visit the emergency department, and 1 in 65 is hospitalized. If, as anticipated, the vaccine eliminates 98% of such severe cases, it will be easy to appreciate its impact.

▸ 8. Vaccination coverage will be high, but still not high enough. Although the 2004 numbers showed the highest rates ever recorded, about 20% of children younger than 2 years are still inadequately immunized. New strategies will be needed for 2008, but they must be designed carefully.

A court in Maryland recently ordered that parents be sent to jail if their children are not immunized. This did not go over well with the public and many physicians questioned the approach.

▸ 9. Methicillin-resistant Staphylococcus aureus cases will continue to rise. Unfortunately, clindamycin-resistance rates will increase in 2008, making empiric treatment of invasive diseases such as osteomyelitis increasingly difficult.

▸ 10. Active surveillance for MRSA will become a reality for the hospitalized patient, at least for children in high-risk settings such as the intensive care unit. Where and how often children will be cultured (nasal/axilla/rectal?weekly/while hospitalized?) will vary from institution to institution. However, all institutions will attempt to identify those patients already colonized with MRSA at the time of hospitalization and will utilize barrier precautions to prevent hospital spread.

[email protected]

It's both surprising and humbling to realize that something we've been doing for the last 50 years appears to have been entirely unnecessary and possibly even harmful.

We now know that's exactly the case when it comes to prescribing prophylactic antibiotics before dental and other invasive procedures for the majority of our patients with benign and even most nonbenign heart conditions. Old habits are hard to break, but we now must do just that.

In September, the American Academy of Pediatrics endorsed the new guidelines from the American Heart Association on the prevention of infective endocarditis, published earlier this year (Circulation 2007 April 19 [Epub ahead of print]). In essence, they whittle down the previous long list of moderate and severe cardiac conditions for which antimicrobial prophylaxis is recommended to just these six highest-risk conditions:

▸ Prosthetic cardiac valve.

▸ Previous infective endocarditis.

▸ Unrepaired cyanotic congenital heart disease, including palliative shunts and conduits.

▸ Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure (the time in which endothelialization of prosthetic material occurs).

▸ Repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization).

▸ Cardiac transplantation recipients who develop cardiac valvulopathy.

That's it. No other conditions meet the criteria. In addition, among patients with the conditions listed above, the only procedures that still require prophylaxis are dental procedures that involve manipulation of the gingival tissue or the periapical region of teeth or perforation of the oral mucosa, and respiratory tract procedures for which there is a risk of mucosal perforation. Procedures involving the gastrointestinal and genitourinary tracts are no longer on the list.

The AHA first recommended antibiotics to prevent infective endocarditis back in 1955, and had revised those guidelines frequently thereafter until 1997. The rationale was reasonable enough: Infective endocarditis (IE) is a life-threatening condition. Although rare, there is an increased risk of IE among people with certain underlying heart conditions who developed transient bacteremia as a result of procedures that induce bleeding.

Animal data had suggested that antibiotics could prevent such infections, and it was presumed that the same would be true in humans. There was never any human data, although there were case reports of endocarditis cases that were temporally associated with dental procedures. It just seemed to make sense that “premedication” with antibiotics was the way to safely and effectively prevent IE.

Dentists in particular have felt such a strong sense of responsibility about this, both professionally and legally, that many have refused to perform procedures on any child with even the most benign of heart murmurs without the “protection” of antibiotics.

The development of IE is thought to be a result of turbulent blood flow produced by congenital or acquired heart disease, creating a predisposition for deposition of platelets and fibrin on the endothelial surface, resulting in nonbacterial thrombotic endocarditis. This could lead to subsequent invasion of the bloodstream with certain microbial species—most commonly viridans group streptococci, staphylococci, or enterococci—that have the potential to colonize the site, which then could result in IE.

We know that transient bacteremia is common when you manipulate the teeth in periodontal tissues. It is estimated to occur approximately 10%–100% of the time during tooth extraction, 36%–88% with peridontal surgery, and up to 40% with simple teeth cleaning. But—and here's the kicker—transient bacteremia also occurs at least as often in routine daily activities such as tooth brushing and flossing (20%–68%), use of wooden toothpicks (20%–40%), use of water irrigation devices (7%–50%), and even chewing food (7%–51%)!

When you consider that these activities are performed daily, whereas dental visits occur just once or twice a year, the idea that we can prevent IE by simply giving antibiotics prior to dental procedures seems short-sighted at best.

In fact, one author found that the cumulative risk to a child of transient bacteremia from tooth brushing twice daily for a 1 year was 154,000 times greater than from a single tooth extraction, the dental procedure believed most likely to cause bacteremia. And, the cumulative risk from ALL daily activities may be as high as 5.6 MILLION times greater than that of a single tooth extraction (Pediatr. Cardiol. 1999;20:317-25)!

Even if antimicrobial prophylaxis were 100% effective, and assuming that dental procedures are responsible for 1% of all IE cases, you could only prevent about 1 case for every 14 million dental procedures performed. And of course, we need to consider the risks of antibiotic overuse as well as the cost. No matter how you look at it, there's no bang for your buck in any patients other than those with the most severe cardiac conditions.

Now is the time to begin educating families that antimicrobial prophylaxis for dental procedures is no longer necessary. Admitting we've been wrong all along won't be easy, but I believe patients will understand if we take the time to carefully explain the rationales then and now. With the increasing emphasis on an evidence base for everything we do, this may not be the last time we'll have to revise our thinking.

[email protected]

It's both surprising and humbling to realize that something we've been doing for the last 50 years appears to have been entirely unnecessary and possibly even harmful.

We now know that's exactly the case when it comes to prescribing prophylactic antibiotics before dental and other invasive procedures for the majority of our patients with benign and even most nonbenign heart conditions. Old habits are hard to break, but we now must do just that.

In September, the American Academy of Pediatrics endorsed the new guidelines from the American Heart Association on the prevention of infective endocarditis, published earlier this year (Circulation 2007 April 19 [Epub ahead of print]). In essence, they whittle down the previous long list of moderate and severe cardiac conditions for which antimicrobial prophylaxis is recommended to just these six highest-risk conditions:

▸ Prosthetic cardiac valve.

▸ Previous infective endocarditis.

▸ Unrepaired cyanotic congenital heart disease, including palliative shunts and conduits.

▸ Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure (the time in which endothelialization of prosthetic material occurs).

▸ Repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization).

▸ Cardiac transplantation recipients who develop cardiac valvulopathy.

That's it. No other conditions meet the criteria. In addition, among patients with the conditions listed above, the only procedures that still require prophylaxis are dental procedures that involve manipulation of the gingival tissue or the periapical region of teeth or perforation of the oral mucosa, and respiratory tract procedures for which there is a risk of mucosal perforation. Procedures involving the gastrointestinal and genitourinary tracts are no longer on the list.

The AHA first recommended antibiotics to prevent infective endocarditis back in 1955, and had revised those guidelines frequently thereafter until 1997. The rationale was reasonable enough: Infective endocarditis (IE) is a life-threatening condition. Although rare, there is an increased risk of IE among people with certain underlying heart conditions who developed transient bacteremia as a result of procedures that induce bleeding.

Animal data had suggested that antibiotics could prevent such infections, and it was presumed that the same would be true in humans. There was never any human data, although there were case reports of endocarditis cases that were temporally associated with dental procedures. It just seemed to make sense that “premedication” with antibiotics was the way to safely and effectively prevent IE.

Dentists in particular have felt such a strong sense of responsibility about this, both professionally and legally, that many have refused to perform procedures on any child with even the most benign of heart murmurs without the “protection” of antibiotics.

The development of IE is thought to be a result of turbulent blood flow produced by congenital or acquired heart disease, creating a predisposition for deposition of platelets and fibrin on the endothelial surface, resulting in nonbacterial thrombotic endocarditis. This could lead to subsequent invasion of the bloodstream with certain microbial species—most commonly viridans group streptococci, staphylococci, or enterococci—that have the potential to colonize the site, which then could result in IE.

We know that transient bacteremia is common when you manipulate the teeth in periodontal tissues. It is estimated to occur approximately 10%–100% of the time during tooth extraction, 36%–88% with peridontal surgery, and up to 40% with simple teeth cleaning. But—and here's the kicker—transient bacteremia also occurs at least as often in routine daily activities such as tooth brushing and flossing (20%–68%), use of wooden toothpicks (20%–40%), use of water irrigation devices (7%–50%), and even chewing food (7%–51%)!

When you consider that these activities are performed daily, whereas dental visits occur just once or twice a year, the idea that we can prevent IE by simply giving antibiotics prior to dental procedures seems short-sighted at best.

In fact, one author found that the cumulative risk to a child of transient bacteremia from tooth brushing twice daily for a 1 year was 154,000 times greater than from a single tooth extraction, the dental procedure believed most likely to cause bacteremia. And, the cumulative risk from ALL daily activities may be as high as 5.6 MILLION times greater than that of a single tooth extraction (Pediatr. Cardiol. 1999;20:317-25)!

Even if antimicrobial prophylaxis were 100% effective, and assuming that dental procedures are responsible for 1% of all IE cases, you could only prevent about 1 case for every 14 million dental procedures performed. And of course, we need to consider the risks of antibiotic overuse as well as the cost. No matter how you look at it, there's no bang for your buck in any patients other than those with the most severe cardiac conditions.

Now is the time to begin educating families that antimicrobial prophylaxis for dental procedures is no longer necessary. Admitting we've been wrong all along won't be easy, but I believe patients will understand if we take the time to carefully explain the rationales then and now. With the increasing emphasis on an evidence base for everything we do, this may not be the last time we'll have to revise our thinking.

[email protected]

It's both surprising and humbling to realize that something we've been doing for the last 50 years appears to have been entirely unnecessary and possibly even harmful.

We now know that's exactly the case when it comes to prescribing prophylactic antibiotics before dental and other invasive procedures for the majority of our patients with benign and even most nonbenign heart conditions. Old habits are hard to break, but we now must do just that.

In September, the American Academy of Pediatrics endorsed the new guidelines from the American Heart Association on the prevention of infective endocarditis, published earlier this year (Circulation 2007 April 19 [Epub ahead of print]). In essence, they whittle down the previous long list of moderate and severe cardiac conditions for which antimicrobial prophylaxis is recommended to just these six highest-risk conditions:

▸ Prosthetic cardiac valve.

▸ Previous infective endocarditis.

▸ Unrepaired cyanotic congenital heart disease, including palliative shunts and conduits.

▸ Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure (the time in which endothelialization of prosthetic material occurs).

▸ Repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization).

▸ Cardiac transplantation recipients who develop cardiac valvulopathy.

That's it. No other conditions meet the criteria. In addition, among patients with the conditions listed above, the only procedures that still require prophylaxis are dental procedures that involve manipulation of the gingival tissue or the periapical region of teeth or perforation of the oral mucosa, and respiratory tract procedures for which there is a risk of mucosal perforation. Procedures involving the gastrointestinal and genitourinary tracts are no longer on the list.

The AHA first recommended antibiotics to prevent infective endocarditis back in 1955, and had revised those guidelines frequently thereafter until 1997. The rationale was reasonable enough: Infective endocarditis (IE) is a life-threatening condition. Although rare, there is an increased risk of IE among people with certain underlying heart conditions who developed transient bacteremia as a result of procedures that induce bleeding.

Animal data had suggested that antibiotics could prevent such infections, and it was presumed that the same would be true in humans. There was never any human data, although there were case reports of endocarditis cases that were temporally associated with dental procedures. It just seemed to make sense that “premedication” with antibiotics was the way to safely and effectively prevent IE.

Dentists in particular have felt such a strong sense of responsibility about this, both professionally and legally, that many have refused to perform procedures on any child with even the most benign of heart murmurs without the “protection” of antibiotics.

The development of IE is thought to be a result of turbulent blood flow produced by congenital or acquired heart disease, creating a predisposition for deposition of platelets and fibrin on the endothelial surface, resulting in nonbacterial thrombotic endocarditis. This could lead to subsequent invasion of the bloodstream with certain microbial species—most commonly viridans group streptococci, staphylococci, or enterococci—that have the potential to colonize the site, which then could result in IE.

We know that transient bacteremia is common when you manipulate the teeth in periodontal tissues. It is estimated to occur approximately 10%–100% of the time during tooth extraction, 36%–88% with peridontal surgery, and up to 40% with simple teeth cleaning. But—and here's the kicker—transient bacteremia also occurs at least as often in routine daily activities such as tooth brushing and flossing (20%–68%), use of wooden toothpicks (20%–40%), use of water irrigation devices (7%–50%), and even chewing food (7%–51%)!

When you consider that these activities are performed daily, whereas dental visits occur just once or twice a year, the idea that we can prevent IE by simply giving antibiotics prior to dental procedures seems short-sighted at best.

In fact, one author found that the cumulative risk to a child of transient bacteremia from tooth brushing twice daily for a 1 year was 154,000 times greater than from a single tooth extraction, the dental procedure believed most likely to cause bacteremia. And, the cumulative risk from ALL daily activities may be as high as 5.6 MILLION times greater than that of a single tooth extraction (Pediatr. Cardiol. 1999;20:317-25)!

Even if antimicrobial prophylaxis were 100% effective, and assuming that dental procedures are responsible for 1% of all IE cases, you could only prevent about 1 case for every 14 million dental procedures performed. And of course, we need to consider the risks of antibiotic overuse as well as the cost. No matter how you look at it, there's no bang for your buck in any patients other than those with the most severe cardiac conditions.

Now is the time to begin educating families that antimicrobial prophylaxis for dental procedures is no longer necessary. Admitting we've been wrong all along won't be easy, but I believe patients will understand if we take the time to carefully explain the rationales then and now. With the increasing emphasis on an evidence base for everything we do, this may not be the last time we'll have to revise our thinking.

We should not let the declining rate of tuberculosis in the United States lull us into missing opportunities for identifying and treating children who have latent infection or are at risk for the disease.

Happily, the tuberculosis rate in 2006 was the lowest recorded since national reporting began in 1953. The 13,767 reported cases last year, or 4.6 per 100,000 population, represents a 3.2% decline from the rate in 2005. However, the rate of decline in TB has slowed since 2000. From 1993 through 2000, the average annual percentage decline in TB incidence was 7.3% per year. Since 2000, that rate has been just 3.8% per year, according to the latest data from the Centers for Disease Control and Prevention (MMWR 2007;56:245–50).

Trends among children have been similar. In 2005, the latest year for which age-specific data are available, there were 863 cases among children aged 0–14 years, a rate of 1.4 per 100,000. Among those aged 15–24 years, the 1,542 cases represented a rate of 3.7 per 100,000. Both rates were slightly lower than in 2004 (1.6 and 3.8 per 100,000, respectively), and significantly less than the 2.9 and 5.0 rates seen in 1993. But, as with the entire population, the decline has slowed among children, too.

Although the highest rates of TB in the United States are still among ethnic minorities in large urban areas, the disease is not limited to those populations. The proportion of TB cases among foreign-born individuals has increased each year since 1993; such cases now account for about one-fourth of all TB cases. In 2006, 56% of those were from five countries: Mexico, the Philippines, Vietnam, India, and China. Most of the foreign-born individuals in the United States who progress from latent TB infection to TB disease became infected while abroad. These cases represent immigrants, internationally adopted children from countries with high TB rates, and children exposed during foreign travel.

For physicians in the United States who provide primary care for children, identifying children who are at risk for TB is critical. In 2004, the American Academy of Pediatrics (AAP), the American Thoracic Society (ATS), and the CDC issued a comprehensive set of guidelines we all should follow, entitled “Targeted Tuberculin Skin Testing and Treatment of Latent Tuberculosis Infection in Children and Adolescents” (Pediatrics 2004;114:1175).

The three organizations' Pediatric Tuberculosis Collaborative Group recommended four questions to be asked about every patient:

▸ Was the child born outside the United States? (If yes, ask in which country. If the child was born in Africa, Asia, Latin America, or Eastern Europe, place a tuberculin skin test [TST]).

▸ Has the child traveled outside the United States? (If yes, ask where. If the child stayed with friends or family in any of the above-mentioned areas for a week or longer, place a TST test.)

▸ Has the child been exposed to anyone with TB disease? (If yes, a series of questions should follow to determine if the person had TB or latent disease, when the exposure occurred, and the nature of the contact. If exposure is confirmed, place a TST test. If the child has been in contact with someone who has TB disease, notify local health authorities and consult with an infectious disease specialist.)

▸ Does the child have close contact with a person who has a positive TB skin test? (Ask the same follow-up questions as in the preceding.)

The only TB test now recommended is the intradermal injection of 5 tuberculin units of purified protein derivative from Mycobacterium tuberculosis administered by the Mantoux technique.

The AAP/ATC/CDC guidelines define positive TST results in children and adolescents using three cutoff levels for the transverse diameter of the reaction: less than or equal to 5 mm, 10 mm, and 15 mm.

The 5-mm cutoff is used for children at high risk, including those in close contact with TB cases, those with positive findings on chest radiograph, or those with clinical evidence of TB disease.

The 10-mm cutoff is for those at moderate risk, including children less than 4 years of age, those with concomitant medical conditions, or those who were born in a country with a high TB prevalence.

The highest cutoff, 15 mm, is reserved for children aged 4 and older with no known risk factors.

Most physicians are familiar with the correct technique for TB testing, but fewer have had experience in interpreting the results. Guidelines suggest that the reaction must be read by a trained health care provider at 48–72 hours after placement. Interpretation should not be left to the parents. In fact, your office practice personnel may not be experienced either and, therefore, it may not be appropriate to place and read TST in the practice setting.

Evidence suggests that interpretation of TST even by health care providers may be fraught with error. In one study of 107 health care providers including 52 practicing pediatricians, 33 pediatric house officers, and 10 pediatric academicians, 93% identified a known tuberculin converter as tuberculin negative, based on their interpretation of the degree of induration. When presented with an induration of 15 mm, the group's median reading of its size was only 10 mm (Chest 1998;113:1175–7).

Live virus vaccines—measles, mumps, rubella, and varicella—can suppress the TST response. Also be aware that in patients treated with systemic corticosteroids or inpatients who have been treated with the newer tumor necrosis factor antagonists, a false-negative test result can occur, while prior receipt of the BCG vaccine—given at birth in many TB-endemic countries—can produce a false-positive result. However, most children with a history of the BCG vaccine and a positive skin test result have latent tuberculosis. In these instances, consultation with your local infectious disease specialist will be helpful.

Perhaps most important, the identification of children with latent TB infection (LTBI) or tuberculosis disease (who rarely if ever are at risk to transmit TB when less than 10 years of age) is a sentinel event that should provoke an aggressive investigation targeting adult close contacts.

Here in Kansas City, we recently had a TB outbreak in a day care center, mostly among children born in the United States, which was related to their exposure to a foreign-born adult residing in the day care home. Epidemiologic details are being investigated; a combination of problems caused by language barrier, difficulty tracing contacts, and poor record keeping in an unlicensed facility complicate the process.

The guidelines also address treatment for latent TB infection. Daily isoniazid for 9 months is the standard treatment regimen for children and adolescents without a known source case, or those with a source case known to be infected with a susceptible strain. Intermittent regimens are acceptable if given within a directly observed therapy program. Daily rifampin for 6 months is a suitable alternative for those with isoniazid-resistant/rifampin-susceptible strains, or those who can't tolerate isoniazid.

Treatment of LTBI and tuberculosis disease generally should involve the help of your local TB expert. While the proportion of TB cases resistant to both isoniazid and rifampin remained at 1.2% from 2004 to 2005, and isoniazid remains the standard drug for LTBI treatment, we can't be complacent. In 2005, foreign-born individuals accounted for 81.5% of the 124 multidrug-resistant TB cases, and, according to the CDC, that percentage continues to grow. Treatment in such cases is more complicated, involving several drugs that are not generally used in the treatment of TB, and follow-up is important.

We should not let the declining rate of tuberculosis in the United States lull us into missing opportunities for identifying and treating children who have latent infection or are at risk for the disease.

Happily, the tuberculosis rate in 2006 was the lowest recorded since national reporting began in 1953. The 13,767 reported cases last year, or 4.6 per 100,000 population, represents a 3.2% decline from the rate in 2005. However, the rate of decline in TB has slowed since 2000. From 1993 through 2000, the average annual percentage decline in TB incidence was 7.3% per year. Since 2000, that rate has been just 3.8% per year, according to the latest data from the Centers for Disease Control and Prevention (MMWR 2007;56:245–50).

Trends among children have been similar. In 2005, the latest year for which age-specific data are available, there were 863 cases among children aged 0–14 years, a rate of 1.4 per 100,000. Among those aged 15–24 years, the 1,542 cases represented a rate of 3.7 per 100,000. Both rates were slightly lower than in 2004 (1.6 and 3.8 per 100,000, respectively), and significantly less than the 2.9 and 5.0 rates seen in 1993. But, as with the entire population, the decline has slowed among children, too.

Although the highest rates of TB in the United States are still among ethnic minorities in large urban areas, the disease is not limited to those populations. The proportion of TB cases among foreign-born individuals has increased each year since 1993; such cases now account for about one-fourth of all TB cases. In 2006, 56% of those were from five countries: Mexico, the Philippines, Vietnam, India, and China. Most of the foreign-born individuals in the United States who progress from latent TB infection to TB disease became infected while abroad. These cases represent immigrants, internationally adopted children from countries with high TB rates, and children exposed during foreign travel.

For physicians in the United States who provide primary care for children, identifying children who are at risk for TB is critical. In 2004, the American Academy of Pediatrics (AAP), the American Thoracic Society (ATS), and the CDC issued a comprehensive set of guidelines we all should follow, entitled “Targeted Tuberculin Skin Testing and Treatment of Latent Tuberculosis Infection in Children and Adolescents” (Pediatrics 2004;114:1175).

The three organizations' Pediatric Tuberculosis Collaborative Group recommended four questions to be asked about every patient:

▸ Was the child born outside the United States? (If yes, ask in which country. If the child was born in Africa, Asia, Latin America, or Eastern Europe, place a tuberculin skin test [TST]).

▸ Has the child traveled outside the United States? (If yes, ask where. If the child stayed with friends or family in any of the above-mentioned areas for a week or longer, place a TST test.)

▸ Has the child been exposed to anyone with TB disease? (If yes, a series of questions should follow to determine if the person had TB or latent disease, when the exposure occurred, and the nature of the contact. If exposure is confirmed, place a TST test. If the child has been in contact with someone who has TB disease, notify local health authorities and consult with an infectious disease specialist.)

▸ Does the child have close contact with a person who has a positive TB skin test? (Ask the same follow-up questions as in the preceding.)

The only TB test now recommended is the intradermal injection of 5 tuberculin units of purified protein derivative from Mycobacterium tuberculosis administered by the Mantoux technique.

The AAP/ATC/CDC guidelines define positive TST results in children and adolescents using three cutoff levels for the transverse diameter of the reaction: less than or equal to 5 mm, 10 mm, and 15 mm.

The 5-mm cutoff is used for children at high risk, including those in close contact with TB cases, those with positive findings on chest radiograph, or those with clinical evidence of TB disease.

The 10-mm cutoff is for those at moderate risk, including children less than 4 years of age, those with concomitant medical conditions, or those who were born in a country with a high TB prevalence.

The highest cutoff, 15 mm, is reserved for children aged 4 and older with no known risk factors.

Most physicians are familiar with the correct technique for TB testing, but fewer have had experience in interpreting the results. Guidelines suggest that the reaction must be read by a trained health care provider at 48–72 hours after placement. Interpretation should not be left to the parents. In fact, your office practice personnel may not be experienced either and, therefore, it may not be appropriate to place and read TST in the practice setting.

Evidence suggests that interpretation of TST even by health care providers may be fraught with error. In one study of 107 health care providers including 52 practicing pediatricians, 33 pediatric house officers, and 10 pediatric academicians, 93% identified a known tuberculin converter as tuberculin negative, based on their interpretation of the degree of induration. When presented with an induration of 15 mm, the group's median reading of its size was only 10 mm (Chest 1998;113:1175–7).

Live virus vaccines—measles, mumps, rubella, and varicella—can suppress the TST response. Also be aware that in patients treated with systemic corticosteroids or inpatients who have been treated with the newer tumor necrosis factor antagonists, a false-negative test result can occur, while prior receipt of the BCG vaccine—given at birth in many TB-endemic countries—can produce a false-positive result. However, most children with a history of the BCG vaccine and a positive skin test result have latent tuberculosis. In these instances, consultation with your local infectious disease specialist will be helpful.

Perhaps most important, the identification of children with latent TB infection (LTBI) or tuberculosis disease (who rarely if ever are at risk to transmit TB when less than 10 years of age) is a sentinel event that should provoke an aggressive investigation targeting adult close contacts.

Here in Kansas City, we recently had a TB outbreak in a day care center, mostly among children born in the United States, which was related to their exposure to a foreign-born adult residing in the day care home. Epidemiologic details are being investigated; a combination of problems caused by language barrier, difficulty tracing contacts, and poor record keeping in an unlicensed facility complicate the process.

The guidelines also address treatment for latent TB infection. Daily isoniazid for 9 months is the standard treatment regimen for children and adolescents without a known source case, or those with a source case known to be infected with a susceptible strain. Intermittent regimens are acceptable if given within a directly observed therapy program. Daily rifampin for 6 months is a suitable alternative for those with isoniazid-resistant/rifampin-susceptible strains, or those who can't tolerate isoniazid.

Treatment of LTBI and tuberculosis disease generally should involve the help of your local TB expert. While the proportion of TB cases resistant to both isoniazid and rifampin remained at 1.2% from 2004 to 2005, and isoniazid remains the standard drug for LTBI treatment, we can't be complacent. In 2005, foreign-born individuals accounted for 81.5% of the 124 multidrug-resistant TB cases, and, according to the CDC, that percentage continues to grow. Treatment in such cases is more complicated, involving several drugs that are not generally used in the treatment of TB, and follow-up is important.

We should not let the declining rate of tuberculosis in the United States lull us into missing opportunities for identifying and treating children who have latent infection or are at risk for the disease.

Happily, the tuberculosis rate in 2006 was the lowest recorded since national reporting began in 1953. The 13,767 reported cases last year, or 4.6 per 100,000 population, represents a 3.2% decline from the rate in 2005. However, the rate of decline in TB has slowed since 2000. From 1993 through 2000, the average annual percentage decline in TB incidence was 7.3% per year. Since 2000, that rate has been just 3.8% per year, according to the latest data from the Centers for Disease Control and Prevention (MMWR 2007;56:245–50).

Trends among children have been similar. In 2005, the latest year for which age-specific data are available, there were 863 cases among children aged 0–14 years, a rate of 1.4 per 100,000. Among those aged 15–24 years, the 1,542 cases represented a rate of 3.7 per 100,000. Both rates were slightly lower than in 2004 (1.6 and 3.8 per 100,000, respectively), and significantly less than the 2.9 and 5.0 rates seen in 1993. But, as with the entire population, the decline has slowed among children, too.

Although the highest rates of TB in the United States are still among ethnic minorities in large urban areas, the disease is not limited to those populations. The proportion of TB cases among foreign-born individuals has increased each year since 1993; such cases now account for about one-fourth of all TB cases. In 2006, 56% of those were from five countries: Mexico, the Philippines, Vietnam, India, and China. Most of the foreign-born individuals in the United States who progress from latent TB infection to TB disease became infected while abroad. These cases represent immigrants, internationally adopted children from countries with high TB rates, and children exposed during foreign travel.

For physicians in the United States who provide primary care for children, identifying children who are at risk for TB is critical. In 2004, the American Academy of Pediatrics (AAP), the American Thoracic Society (ATS), and the CDC issued a comprehensive set of guidelines we all should follow, entitled “Targeted Tuberculin Skin Testing and Treatment of Latent Tuberculosis Infection in Children and Adolescents” (Pediatrics 2004;114:1175).

The three organizations' Pediatric Tuberculosis Collaborative Group recommended four questions to be asked about every patient:

▸ Was the child born outside the United States? (If yes, ask in which country. If the child was born in Africa, Asia, Latin America, or Eastern Europe, place a tuberculin skin test [TST]).

▸ Has the child traveled outside the United States? (If yes, ask where. If the child stayed with friends or family in any of the above-mentioned areas for a week or longer, place a TST test.)

▸ Has the child been exposed to anyone with TB disease? (If yes, a series of questions should follow to determine if the person had TB or latent disease, when the exposure occurred, and the nature of the contact. If exposure is confirmed, place a TST test. If the child has been in contact with someone who has TB disease, notify local health authorities and consult with an infectious disease specialist.)

▸ Does the child have close contact with a person who has a positive TB skin test? (Ask the same follow-up questions as in the preceding.)

The only TB test now recommended is the intradermal injection of 5 tuberculin units of purified protein derivative from Mycobacterium tuberculosis administered by the Mantoux technique.

The AAP/ATC/CDC guidelines define positive TST results in children and adolescents using three cutoff levels for the transverse diameter of the reaction: less than or equal to 5 mm, 10 mm, and 15 mm.

The 5-mm cutoff is used for children at high risk, including those in close contact with TB cases, those with positive findings on chest radiograph, or those with clinical evidence of TB disease.

The 10-mm cutoff is for those at moderate risk, including children less than 4 years of age, those with concomitant medical conditions, or those who were born in a country with a high TB prevalence.

The highest cutoff, 15 mm, is reserved for children aged 4 and older with no known risk factors.

Most physicians are familiar with the correct technique for TB testing, but fewer have had experience in interpreting the results. Guidelines suggest that the reaction must be read by a trained health care provider at 48–72 hours after placement. Interpretation should not be left to the parents. In fact, your office practice personnel may not be experienced either and, therefore, it may not be appropriate to place and read TST in the practice setting.

Evidence suggests that interpretation of TST even by health care providers may be fraught with error. In one study of 107 health care providers including 52 practicing pediatricians, 33 pediatric house officers, and 10 pediatric academicians, 93% identified a known tuberculin converter as tuberculin negative, based on their interpretation of the degree of induration. When presented with an induration of 15 mm, the group's median reading of its size was only 10 mm (Chest 1998;113:1175–7).

Live virus vaccines—measles, mumps, rubella, and varicella—can suppress the TST response. Also be aware that in patients treated with systemic corticosteroids or inpatients who have been treated with the newer tumor necrosis factor antagonists, a false-negative test result can occur, while prior receipt of the BCG vaccine—given at birth in many TB-endemic countries—can produce a false-positive result. However, most children with a history of the BCG vaccine and a positive skin test result have latent tuberculosis. In these instances, consultation with your local infectious disease specialist will be helpful.

Perhaps most important, the identification of children with latent TB infection (LTBI) or tuberculosis disease (who rarely if ever are at risk to transmit TB when less than 10 years of age) is a sentinel event that should provoke an aggressive investigation targeting adult close contacts.

Here in Kansas City, we recently had a TB outbreak in a day care center, mostly among children born in the United States, which was related to their exposure to a foreign-born adult residing in the day care home. Epidemiologic details are being investigated; a combination of problems caused by language barrier, difficulty tracing contacts, and poor record keeping in an unlicensed facility complicate the process.

The guidelines also address treatment for latent TB infection. Daily isoniazid for 9 months is the standard treatment regimen for children and adolescents without a known source case, or those with a source case known to be infected with a susceptible strain. Intermittent regimens are acceptable if given within a directly observed therapy program. Daily rifampin for 6 months is a suitable alternative for those with isoniazid-resistant/rifampin-susceptible strains, or those who can't tolerate isoniazid.

Treatment of LTBI and tuberculosis disease generally should involve the help of your local TB expert. While the proportion of TB cases resistant to both isoniazid and rifampin remained at 1.2% from 2004 to 2005, and isoniazid remains the standard drug for LTBI treatment, we can't be complacent. In 2005, foreign-born individuals accounted for 81.5% of the 124 multidrug-resistant TB cases, and, according to the CDC, that percentage continues to grow. Treatment in such cases is more complicated, involving several drugs that are not generally used in the treatment of TB, and follow-up is important.

The future is here. It's just not widely distributed yet.

—William Gibson

To answer the question of what's going to be hot in 2007, we need only look at the important advances in 2006.

Listed below are my top infectious disease developments from the prior year, which may have an impact on our practice in the coming year:

▸ Should we still be concerned about meningitis in the infant aged 2–24 months who has fever without a source? The good news is that overall rates of pneumococcal invasive disease are reduced compared to the pre-pneumococcal vaccine era, with the most significant reduction in the number of cases of occult bacteremia. However, we saw more cases of pneumococcal meningitis last year than in any other year in the last decade in our institution, almost all caused by nonvaccine serotypes. Continue to be vigilant in assessing the febrile infant without localizing findings, and carefully document immunization status to identify the underimmunized.

▸ Have we come to a new era in evaluation and management of pediatric urinary tract infection? For about 25 years, the recommendation has been that a voiding cystourethrogram be done after the first febrile UTI, but this has not been substantiated by current studies. Who should have imaging? Those who fail to respond after 72 hours of effective antibiotics, those infected with an unusual organism, those in whom close follow-up of the patient is not possible, those with abnormal urine stream or abdominal mass, and those with recurrence of a febrile UTI. The utility of prophylactic antibiotics to prevent recurrence of a febrile UTI or renal scarring is not known; some data suggest prophylaxis is not necessary. The knowledge that the risk of urosepsis is highest in youngest infants and recurrence is highest in the first 6 months after a UTI should be factored in when making the decision concerning prophylaxis. Look for the upcoming American Academy of Pediatrics policy, which will fully delineate these guidelines.

▸ Will rotavirus epidemiology change, now that the new vaccine has been implemented? Virtually every child is infected with rotavirus by 24 months of age; two-thirds of children are infected more than once. It is estimated that approximately 1 in 17 children will require an emergency department visit and approximately 1 in 65 children will require hospitalization. If the vaccine successfully eliminates 98% of severe cases, the impact on hospitalizations should be dramatic. The vaccine is given orally, with the first dose given between 6 and 12 weeks of age and two additional doses administered at 4- to 10-week intervals. All three doses should be completed before a child reaches 32 weeks of age. This restrictive timing of the immunization schedule has proved problematic, however, and full implementation may take another year or more.

▸ Should we remove a vaccine-preventable infection from the eradicated list? The resurgence of mumps in 2006 was unexpected. Approximately 5,000 cases were reported starting in December 2005, many occurring in individuals with a history of two doses of vaccine. This would not be unexpected in a highly immunized population, but the percentage of such cases still seems high to me and is not totally explained. The Advisory Committee on Immunization Practices now has redefined evidence of mumps immunity. Practitioners should ensure that preschool children and adults not at high risk have had one dose of a live mumps virus vaccine, and that two doses have been given for children in grades K-12 and adults at high risk (for example, persons who work in health care facilities, international travelers, and students at post-high school educational institutions). Immunity can be assumed for those who were born before 1957, have documentation of physician-diagnosed mumps, or laboratory evidence of immunity.

▸ What's new in influenza immunization? Those of you in practice who have struggled with obtaining influenza vaccine for your at-risk pediatric patients are probably wondering how we will ever improve the current distribution system and whether school-based immunization programs will be feasible in the future. A recent New England Journal of Medicine article sheds some light on the matter. (See story, page 4.) Investigators at the University of Maryland in Baltimore used intranasal live attenuated virus vaccine in a school-based immunization strategy to see if it reduced outcomes related to influenzalike illness (ILI). Vaccinated children were less likely to become ill, and ILI in adults in the same household also was reduced. There were lower absentee rates for flulike illness among the children, fewer lost workdays among parents, and a reduced rate of use of health care. Sounds good, but we may still be some years away from a universal program targeting flu in school-age children.

▸ Have we forgotten chickenpox? The average pediatric resident (as well as many young attendings) has never seen clinical varicella. Cases have steadily declined 80%–85% in surveillance sites since licensure of the vaccine. From 1995 to 2001, varicella hospitalizations declined by 72%, and deaths among those 50 years old and younger decreased by 75% or more. A second dose of varicella vaccine is recommended at 4–6 years of age since we learned that 15%–24% of children who have received one dose are not fully protected. Additionally, one dose of the vaccine may not provide immunity into adulthood, when chickenpox is more severe. The Advisory Committee on Immunization Practices also recommends that children, adolescents, and adults who previously received one dose receive a second. The future epidemiologic impact of this disease is not entirely clear.

▸ How is the new vaccine to prevent cervical cancer being received? The licensure and implementation of the human papillomavirus vaccine has challenged pediatricians to educate themselves and their families about the importance of adolescent immunization programs. The Infectious Diseases Society of America is working on a document delineating the working principles and actions needed to strengthen U.S. adult and adolescent immunization coverage. Pediatricians are encouraged to offer immunization at all encounters with teens, and financial structures to ensure opportunities for immunization in nontraditional settings (school-based clinics) are being discussed. Getting public and private payers to provide coverage for vaccines is key, and is a current barrier for some physicians to providing immunizations.

▸ Speaking of adolescent immunization, is eradication of whooping cough achievable now that the adolescent/adult formulation of tetanus-diphtheria-acellular pertussis vaccine (Tdap) has been licensed? Although the incidence of pertussis in North America declined by more than 90% during the last half century as a result of universal childhood pertussis immunization, there has been a steady increase in cases during the last decade, particularly among adolescents and adults. One study found that universal immunization of adolescents 10–19 years old would be expected to prevent between 400,000 and 1.8 million cases and would save between $1.3 billion and 1.6 billion. Pediatricians should also encourage the use of Tdap vaccine for adults (including themselves) who will have close contact with an infant less than 12 months old, ideally at least 1 month before beginning such contact.

▸ What is the risk of Guillain-Barré syndrome in adolescents who receive meningococcal conjugate vaccine? As of September 2006, 17 cases of GBS had been confirmed within 1 month of vaccination. Based on current data, the number of excess cases of GBS for every 1 million doses distributed to persons aged 11–19 years is approximately 1.25 (CI = 0.058–5.99). Although a surge of cases following vaccine licensure has not been noted, the timing issue is interesting in that most cases occurred 2 weeks after the patient received the vaccine.

The future is here. It's just not widely distributed yet.

—William Gibson

To answer the question of what's going to be hot in 2007, we need only look at the important advances in 2006.

Listed below are my top infectious disease developments from the prior year, which may have an impact on our practice in the coming year:

▸ Should we still be concerned about meningitis in the infant aged 2–24 months who has fever without a source? The good news is that overall rates of pneumococcal invasive disease are reduced compared to the pre-pneumococcal vaccine era, with the most significant reduction in the number of cases of occult bacteremia. However, we saw more cases of pneumococcal meningitis last year than in any other year in the last decade in our institution, almost all caused by nonvaccine serotypes. Continue to be vigilant in assessing the febrile infant without localizing findings, and carefully document immunization status to identify the underimmunized.

▸ Have we come to a new era in evaluation and management of pediatric urinary tract infection? For about 25 years, the recommendation has been that a voiding cystourethrogram be done after the first febrile UTI, but this has not been substantiated by current studies. Who should have imaging? Those who fail to respond after 72 hours of effective antibiotics, those infected with an unusual organism, those in whom close follow-up of the patient is not possible, those with abnormal urine stream or abdominal mass, and those with recurrence of a febrile UTI. The utility of prophylactic antibiotics to prevent recurrence of a febrile UTI or renal scarring is not known; some data suggest prophylaxis is not necessary. The knowledge that the risk of urosepsis is highest in youngest infants and recurrence is highest in the first 6 months after a UTI should be factored in when making the decision concerning prophylaxis. Look for the upcoming American Academy of Pediatrics policy, which will fully delineate these guidelines.

▸ Will rotavirus epidemiology change, now that the new vaccine has been implemented? Virtually every child is infected with rotavirus by 24 months of age; two-thirds of children are infected more than once. It is estimated that approximately 1 in 17 children will require an emergency department visit and approximately 1 in 65 children will require hospitalization. If the vaccine successfully eliminates 98% of severe cases, the impact on hospitalizations should be dramatic. The vaccine is given orally, with the first dose given between 6 and 12 weeks of age and two additional doses administered at 4- to 10-week intervals. All three doses should be completed before a child reaches 32 weeks of age. This restrictive timing of the immunization schedule has proved problematic, however, and full implementation may take another year or more.

▸ Should we remove a vaccine-preventable infection from the eradicated list? The resurgence of mumps in 2006 was unexpected. Approximately 5,000 cases were reported starting in December 2005, many occurring in individuals with a history of two doses of vaccine. This would not be unexpected in a highly immunized population, but the percentage of such cases still seems high to me and is not totally explained. The Advisory Committee on Immunization Practices now has redefined evidence of mumps immunity. Practitioners should ensure that preschool children and adults not at high risk have had one dose of a live mumps virus vaccine, and that two doses have been given for children in grades K-12 and adults at high risk (for example, persons who work in health care facilities, international travelers, and students at post-high school educational institutions). Immunity can be assumed for those who were born before 1957, have documentation of physician-diagnosed mumps, or laboratory evidence of immunity.

▸ What's new in influenza immunization? Those of you in practice who have struggled with obtaining influenza vaccine for your at-risk pediatric patients are probably wondering how we will ever improve the current distribution system and whether school-based immunization programs will be feasible in the future. A recent New England Journal of Medicine article sheds some light on the matter. (See story, page 4.) Investigators at the University of Maryland in Baltimore used intranasal live attenuated virus vaccine in a school-based immunization strategy to see if it reduced outcomes related to influenzalike illness (ILI). Vaccinated children were less likely to become ill, and ILI in adults in the same household also was reduced. There were lower absentee rates for flulike illness among the children, fewer lost workdays among parents, and a reduced rate of use of health care. Sounds good, but we may still be some years away from a universal program targeting flu in school-age children.

▸ Have we forgotten chickenpox? The average pediatric resident (as well as many young attendings) has never seen clinical varicella. Cases have steadily declined 80%–85% in surveillance sites since licensure of the vaccine. From 1995 to 2001, varicella hospitalizations declined by 72%, and deaths among those 50 years old and younger decreased by 75% or more. A second dose of varicella vaccine is recommended at 4–6 years of age since we learned that 15%–24% of children who have received one dose are not fully protected. Additionally, one dose of the vaccine may not provide immunity into adulthood, when chickenpox is more severe. The Advisory Committee on Immunization Practices also recommends that children, adolescents, and adults who previously received one dose receive a second. The future epidemiologic impact of this disease is not entirely clear.

▸ How is the new vaccine to prevent cervical cancer being received? The licensure and implementation of the human papillomavirus vaccine has challenged pediatricians to educate themselves and their families about the importance of adolescent immunization programs. The Infectious Diseases Society of America is working on a document delineating the working principles and actions needed to strengthen U.S. adult and adolescent immunization coverage. Pediatricians are encouraged to offer immunization at all encounters with teens, and financial structures to ensure opportunities for immunization in nontraditional settings (school-based clinics) are being discussed. Getting public and private payers to provide coverage for vaccines is key, and is a current barrier for some physicians to providing immunizations.

▸ Speaking of adolescent immunization, is eradication of whooping cough achievable now that the adolescent/adult formulation of tetanus-diphtheria-acellular pertussis vaccine (Tdap) has been licensed? Although the incidence of pertussis in North America declined by more than 90% during the last half century as a result of universal childhood pertussis immunization, there has been a steady increase in cases during the last decade, particularly among adolescents and adults. One study found that universal immunization of adolescents 10–19 years old would be expected to prevent between 400,000 and 1.8 million cases and would save between $1.3 billion and 1.6 billion. Pediatricians should also encourage the use of Tdap vaccine for adults (including themselves) who will have close contact with an infant less than 12 months old, ideally at least 1 month before beginning such contact.

▸ What is the risk of Guillain-Barré syndrome in adolescents who receive meningococcal conjugate vaccine? As of September 2006, 17 cases of GBS had been confirmed within 1 month of vaccination. Based on current data, the number of excess cases of GBS for every 1 million doses distributed to persons aged 11–19 years is approximately 1.25 (CI = 0.058–5.99). Although a surge of cases following vaccine licensure has not been noted, the timing issue is interesting in that most cases occurred 2 weeks after the patient received the vaccine.

The future is here. It's just not widely distributed yet.

—William Gibson

To answer the question of what's going to be hot in 2007, we need only look at the important advances in 2006.

Listed below are my top infectious disease developments from the prior year, which may have an impact on our practice in the coming year:

▸ Should we still be concerned about meningitis in the infant aged 2–24 months who has fever without a source? The good news is that overall rates of pneumococcal invasive disease are reduced compared to the pre-pneumococcal vaccine era, with the most significant reduction in the number of cases of occult bacteremia. However, we saw more cases of pneumococcal meningitis last year than in any other year in the last decade in our institution, almost all caused by nonvaccine serotypes. Continue to be vigilant in assessing the febrile infant without localizing findings, and carefully document immunization status to identify the underimmunized.

▸ Have we come to a new era in evaluation and management of pediatric urinary tract infection? For about 25 years, the recommendation has been that a voiding cystourethrogram be done after the first febrile UTI, but this has not been substantiated by current studies. Who should have imaging? Those who fail to respond after 72 hours of effective antibiotics, those infected with an unusual organism, those in whom close follow-up of the patient is not possible, those with abnormal urine stream or abdominal mass, and those with recurrence of a febrile UTI. The utility of prophylactic antibiotics to prevent recurrence of a febrile UTI or renal scarring is not known; some data suggest prophylaxis is not necessary. The knowledge that the risk of urosepsis is highest in youngest infants and recurrence is highest in the first 6 months after a UTI should be factored in when making the decision concerning prophylaxis. Look for the upcoming American Academy of Pediatrics policy, which will fully delineate these guidelines.

▸ Will rotavirus epidemiology change, now that the new vaccine has been implemented? Virtually every child is infected with rotavirus by 24 months of age; two-thirds of children are infected more than once. It is estimated that approximately 1 in 17 children will require an emergency department visit and approximately 1 in 65 children will require hospitalization. If the vaccine successfully eliminates 98% of severe cases, the impact on hospitalizations should be dramatic. The vaccine is given orally, with the first dose given between 6 and 12 weeks of age and two additional doses administered at 4- to 10-week intervals. All three doses should be completed before a child reaches 32 weeks of age. This restrictive timing of the immunization schedule has proved problematic, however, and full implementation may take another year or more.

▸ Should we remove a vaccine-preventable infection from the eradicated list? The resurgence of mumps in 2006 was unexpected. Approximately 5,000 cases were reported starting in December 2005, many occurring in individuals with a history of two doses of vaccine. This would not be unexpected in a highly immunized population, but the percentage of such cases still seems high to me and is not totally explained. The Advisory Committee on Immunization Practices now has redefined evidence of mumps immunity. Practitioners should ensure that preschool children and adults not at high risk have had one dose of a live mumps virus vaccine, and that two doses have been given for children in grades K-12 and adults at high risk (for example, persons who work in health care facilities, international travelers, and students at post-high school educational institutions). Immunity can be assumed for those who were born before 1957, have documentation of physician-diagnosed mumps, or laboratory evidence of immunity.

▸ What's new in influenza immunization? Those of you in practice who have struggled with obtaining influenza vaccine for your at-risk pediatric patients are probably wondering how we will ever improve the current distribution system and whether school-based immunization programs will be feasible in the future. A recent New England Journal of Medicine article sheds some light on the matter. (See story, page 4.) Investigators at the University of Maryland in Baltimore used intranasal live attenuated virus vaccine in a school-based immunization strategy to see if it reduced outcomes related to influenzalike illness (ILI). Vaccinated children were less likely to become ill, and ILI in adults in the same household also was reduced. There were lower absentee rates for flulike illness among the children, fewer lost workdays among parents, and a reduced rate of use of health care. Sounds good, but we may still be some years away from a universal program targeting flu in school-age children.

▸ Have we forgotten chickenpox? The average pediatric resident (as well as many young attendings) has never seen clinical varicella. Cases have steadily declined 80%–85% in surveillance sites since licensure of the vaccine. From 1995 to 2001, varicella hospitalizations declined by 72%, and deaths among those 50 years old and younger decreased by 75% or more. A second dose of varicella vaccine is recommended at 4–6 years of age since we learned that 15%–24% of children who have received one dose are not fully protected. Additionally, one dose of the vaccine may not provide immunity into adulthood, when chickenpox is more severe. The Advisory Committee on Immunization Practices also recommends that children, adolescents, and adults who previously received one dose receive a second. The future epidemiologic impact of this disease is not entirely clear.

▸ How is the new vaccine to prevent cervical cancer being received? The licensure and implementation of the human papillomavirus vaccine has challenged pediatricians to educate themselves and their families about the importance of adolescent immunization programs. The Infectious Diseases Society of America is working on a document delineating the working principles and actions needed to strengthen U.S. adult and adolescent immunization coverage. Pediatricians are encouraged to offer immunization at all encounters with teens, and financial structures to ensure opportunities for immunization in nontraditional settings (school-based clinics) are being discussed. Getting public and private payers to provide coverage for vaccines is key, and is a current barrier for some physicians to providing immunizations.

▸ Speaking of adolescent immunization, is eradication of whooping cough achievable now that the adolescent/adult formulation of tetanus-diphtheria-acellular pertussis vaccine (Tdap) has been licensed? Although the incidence of pertussis in North America declined by more than 90% during the last half century as a result of universal childhood pertussis immunization, there has been a steady increase in cases during the last decade, particularly among adolescents and adults. One study found that universal immunization of adolescents 10–19 years old would be expected to prevent between 400,000 and 1.8 million cases and would save between $1.3 billion and 1.6 billion. Pediatricians should also encourage the use of Tdap vaccine for adults (including themselves) who will have close contact with an infant less than 12 months old, ideally at least 1 month before beginning such contact.

▸ What is the risk of Guillain-Barré syndrome in adolescents who receive meningococcal conjugate vaccine? As of September 2006, 17 cases of GBS had been confirmed within 1 month of vaccination. Based on current data, the number of excess cases of GBS for every 1 million doses distributed to persons aged 11–19 years is approximately 1.25 (CI = 0.058–5.99). Although a surge of cases following vaccine licensure has not been noted, the timing issue is interesting in that most cases occurred 2 weeks after the patient received the vaccine.

When the 7-valent pneumococcal conjugate vaccine was first introduced in 2000, many of us had high hopes that it would bring with it a new era in which we could leave invasive pneumococcal disease out of the equation and not have to worry that we might be missing a case of meningitis.

Indeed, the vaccine has resulted in an impressive overall reduction in pediatric invasive pneumococcal infection.

Unfortunately, emerging data now suggest that rates of invasive disease caused by nonvaccine serotypes are rising and that the overall disease reduction seen in the first 5 years since licensure of the vaccine may have leveled off.

With Haemophilus influenzae type b (Hib), all invasive disease was caused by a single strain. Following the universal implementation of the Hib vaccine in the 1990s, invasive Hib disease has virtually disappeared.

In contrast, pneumococcal infection involves multiple serotypes. This alone inherently limits the success that the 7-valent pneumococcal conjugate vaccine (PCV7) may have and explains part of the changing epidemiology.

Ongoing surveillance is extremely important now, and will continue to be as we move forward with new vaccines containing additional serotypes.

Here at Children's Mercy Hospital, my colleagues Dr. Douglas S. Swanson and Dr. Christopher J. Harrison compared data from patients with invasive pneumococcal disease in the pre-PCV7 era of 1998–2000 with data from 2001 through March 2006. They found that the total number of invasive pneumococcal infections in Kansas City children has decreased from prevaccine years, with the average annual number of invasive pneumococcal disease cases declining by about 50%, from 43 cases/year during 1998–2000 to 21 cases/year from 2001 through March 2006. This is remarkable and consistent with data from other pediatric hospitals.

Steenhoff et al. recently compared data on pneumococcal bacteremia from the pre-PCV7 era in Philadelphia with data from 2001 through May 2005, and found that the incidence decreased by 57% (CID 2006;42:907–14).

Schutze et al. similarly noted a decrease in disease incidence of invasive disease in Arkansas from a high of 5.78/100,000 population to 3.02/100,000 population in the postvaccine era (Pediatr. Infect. Dis. J. 2004;23:1125–9).

Occult pneumococcal bacteremia has been by far the most common of the invasive infections that pediatricians have encountered in the past and appears to be the most common invasive infection impacted by PCV7. This entity, which traditionally occurs in infants from 6 to 36 months of age with high fever and no localizing findings, generally has a benign outcome. Complications, including meningitis, occur rarely.

Reduction of more virulent diseases like empyema and meningitis with PCV7 has been clearly demonstrated. However, data suggest that pneumococcus continues to play an important role in complicated pneumonia with empyema.

In a study from the United Kingdom published earlier this summer, locally presenting pleural empyema cases in children increased threefold during 2003–2004. Antigen analysis of empyema fluid identified Streptococcus pneumoniae in 27 of 29 cases for whom samples were available, and capsular polysaccharide type 1 was confirmed in 18 of those (Pediatr. Infect. Dis. J. 2006;25:559–60).

The authors, Fletcher et al. of the South West of England Invasive Community Acquired Infection Study Group, concluded that “use of a conjugate vaccine without serotype 1 antigen would have had limited impact on this morbidity in our region.”

Postvaccine licensure studies have shown a decline in incidence of pneumococcal meningitis cases. In our review, this was less remarkable, with an average of 6.7 cases/year in 1998–2000 and 4.8 cases/year from 2001 through March 2006. This year alone we have treated eight patients with pneumococcal meningitis.

Serotype replacement is a major issue. In our institution since 2001, only 2 of the 20 isolates that have been serotyped are vaccine-specific serotypes. The apparent failure of the vaccine to impact 19A disease is notable, because it was hoped that cross-protection with vaccine serotype 19F would occur.

Kaplan et al. of the U.S. Pediatric Multicenter Pneumococcal Surveillance Group recently examined this issue. Investigators from eight children's hospitals have been prospectively identifying children in their centers with invasive infections caused by S. pneumoniae for the last 9 years. They found that serotypes 15, 19A, and 33 were the most common nonvaccine serotypes and accounted for almost half of nonvaccine isolates recovered from vaccinated patients in the postvaccine era (Pediatrics 2004;113:443–9).

The vaccine's impact on antimicrobial resistance is less clear. Schutze et al. noted that 44% of isolates were nonsusceptible to penicillin in 1998–2000, not significantly different from the 46% seen in the postvaccine era of 2001–2003.

In our institution, 34% of the invasive isolates in 1998–2000 were penicillin nonsusceptible, compared with 42% in 2001 through March 2006. The latter finding was not statistically significant, but it does support data from other studies suggesting that the vaccine's impact on cases of invasive disease caused by penicillin nonsusceptible pneumococcal strains warrants continued monitoring.

In a study that was funded in part by Wyeth et al. of Kaiser Permanente, Oakland, Calif., found that the herd immunity conferred by individuals vaccinated with PCV7 resulted in significant savings in cost per life-year saved during the first 5 years following introduction of the vaccine.

However, they acknowledged, “if serotype replacement increases over time, it is possible that the efficacy of the vaccine—both for the vaccinated and nonvaccinated populations—could decline in the future” (Pediatr. Infect. Dis. J. 2006;25:494–501).

Current efforts to develop new multivalent pneumococcal conjugate vaccines will pay off in the long run. As we turn our attention to the next phase of development, we also must keep in mind and prioritize the needs in the developing world.

According to the World Health Organization, as many as 1 million children under 5 years of age die every year of pneumococcal pneumonia, meningitis, and sepsis. In populations with high child mortality rates, pneumonia is the leading infectious cause of mortality, accounting for about 20%–25% of all deaths in children.

Clinical trials now underway in Africa and elsewhere are utilizing conjugate pneumococcal vaccines containing between 7 and 13 serotypes. While serotype replacement could eventually occur in the developing world as well, the immediate impact in reducing disease and death would be enormous and undeniably worthwhile.

Phase III studies are ongoing with one prototype that contains 13 serotypes including 19A, 1, 3, 5, 6A, and 7V. Investigators estimate that in the United States, the 13-valent vaccine will cover around 60% of the remaining disease in children and expand coverage for strains prevalent in developing countries.

Despite the success of conjugate pneumococcal vaccine, it is clear that it will not be associated with the type of triumph we achieved with the Hib vaccine.

For the near future at least, we will need to remain vigilant when evaluating febrile children, understanding the clinical setting in which pneumococcal infection may occur. As the epidemiology of pneumococcal infection evolves, it is important for clinicians to continue to stay abreast of data regarding disease incidence, emerging serotypes, bacterial resistance, and future advances.

When the 7-valent pneumococcal conjugate vaccine was first introduced in 2000, many of us had high hopes that it would bring with it a new era in which we could leave invasive pneumococcal disease out of the equation and not have to worry that we might be missing a case of meningitis.

Indeed, the vaccine has resulted in an impressive overall reduction in pediatric invasive pneumococcal infection.

Unfortunately, emerging data now suggest that rates of invasive disease caused by nonvaccine serotypes are rising and that the overall disease reduction seen in the first 5 years since licensure of the vaccine may have leveled off.

With Haemophilus influenzae type b (Hib), all invasive disease was caused by a single strain. Following the universal implementation of the Hib vaccine in the 1990s, invasive Hib disease has virtually disappeared.

In contrast, pneumococcal infection involves multiple serotypes. This alone inherently limits the success that the 7-valent pneumococcal conjugate vaccine (PCV7) may have and explains part of the changing epidemiology.

Ongoing surveillance is extremely important now, and will continue to be as we move forward with new vaccines containing additional serotypes.

Here at Children's Mercy Hospital, my colleagues Dr. Douglas S. Swanson and Dr. Christopher J. Harrison compared data from patients with invasive pneumococcal disease in the pre-PCV7 era of 1998–2000 with data from 2001 through March 2006. They found that the total number of invasive pneumococcal infections in Kansas City children has decreased from prevaccine years, with the average annual number of invasive pneumococcal disease cases declining by about 50%, from 43 cases/year during 1998–2000 to 21 cases/year from 2001 through March 2006. This is remarkable and consistent with data from other pediatric hospitals.

Steenhoff et al. recently compared data on pneumococcal bacteremia from the pre-PCV7 era in Philadelphia with data from 2001 through May 2005, and found that the incidence decreased by 57% (CID 2006;42:907–14).

Schutze et al. similarly noted a decrease in disease incidence of invasive disease in Arkansas from a high of 5.78/100,000 population to 3.02/100,000 population in the postvaccine era (Pediatr. Infect. Dis. J. 2004;23:1125–9).

Occult pneumococcal bacteremia has been by far the most common of the invasive infections that pediatricians have encountered in the past and appears to be the most common invasive infection impacted by PCV7. This entity, which traditionally occurs in infants from 6 to 36 months of age with high fever and no localizing findings, generally has a benign outcome. Complications, including meningitis, occur rarely.

Reduction of more virulent diseases like empyema and meningitis with PCV7 has been clearly demonstrated. However, data suggest that pneumococcus continues to play an important role in complicated pneumonia with empyema.

In a study from the United Kingdom published earlier this summer, locally presenting pleural empyema cases in children increased threefold during 2003–2004. Antigen analysis of empyema fluid identified Streptococcus pneumoniae in 27 of 29 cases for whom samples were available, and capsular polysaccharide type 1 was confirmed in 18 of those (Pediatr. Infect. Dis. J. 2006;25:559–60).

The authors, Fletcher et al. of the South West of England Invasive Community Acquired Infection Study Group, concluded that “use of a conjugate vaccine without serotype 1 antigen would have had limited impact on this morbidity in our region.”

Postvaccine licensure studies have shown a decline in incidence of pneumococcal meningitis cases. In our review, this was less remarkable, with an average of 6.7 cases/year in 1998–2000 and 4.8 cases/year from 2001 through March 2006. This year alone we have treated eight patients with pneumococcal meningitis.

Serotype replacement is a major issue. In our institution since 2001, only 2 of the 20 isolates that have been serotyped are vaccine-specific serotypes. The apparent failure of the vaccine to impact 19A disease is notable, because it was hoped that cross-protection with vaccine serotype 19F would occur.

Kaplan et al. of the U.S. Pediatric Multicenter Pneumococcal Surveillance Group recently examined this issue. Investigators from eight children's hospitals have been prospectively identifying children in their centers with invasive infections caused by S. pneumoniae for the last 9 years. They found that serotypes 15, 19A, and 33 were the most common nonvaccine serotypes and accounted for almost half of nonvaccine isolates recovered from vaccinated patients in the postvaccine era (Pediatrics 2004;113:443–9).

The vaccine's impact on antimicrobial resistance is less clear. Schutze et al. noted that 44% of isolates were nonsusceptible to penicillin in 1998–2000, not significantly different from the 46% seen in the postvaccine era of 2001–2003.

In our institution, 34% of the invasive isolates in 1998–2000 were penicillin nonsusceptible, compared with 42% in 2001 through March 2006. The latter finding was not statistically significant, but it does support data from other studies suggesting that the vaccine's impact on cases of invasive disease caused by penicillin nonsusceptible pneumococcal strains warrants continued monitoring.

In a study that was funded in part by Wyeth et al. of Kaiser Permanente, Oakland, Calif., found that the herd immunity conferred by individuals vaccinated with PCV7 resulted in significant savings in cost per life-year saved during the first 5 years following introduction of the vaccine.

However, they acknowledged, “if serotype replacement increases over time, it is possible that the efficacy of the vaccine—both for the vaccinated and nonvaccinated populations—could decline in the future” (Pediatr. Infect. Dis. J. 2006;25:494–501).

Current efforts to develop new multivalent pneumococcal conjugate vaccines will pay off in the long run. As we turn our attention to the next phase of development, we also must keep in mind and prioritize the needs in the developing world.

According to the World Health Organization, as many as 1 million children under 5 years of age die every year of pneumococcal pneumonia, meningitis, and sepsis. In populations with high child mortality rates, pneumonia is the leading infectious cause of mortality, accounting for about 20%–25% of all deaths in children.

Clinical trials now underway in Africa and elsewhere are utilizing conjugate pneumococcal vaccines containing between 7 and 13 serotypes. While serotype replacement could eventually occur in the developing world as well, the immediate impact in reducing disease and death would be enormous and undeniably worthwhile.

Phase III studies are ongoing with one prototype that contains 13 serotypes including 19A, 1, 3, 5, 6A, and 7V. Investigators estimate that in the United States, the 13-valent vaccine will cover around 60% of the remaining disease in children and expand coverage for strains prevalent in developing countries.

Despite the success of conjugate pneumococcal vaccine, it is clear that it will not be associated with the type of triumph we achieved with the Hib vaccine.

For the near future at least, we will need to remain vigilant when evaluating febrile children, understanding the clinical setting in which pneumococcal infection may occur. As the epidemiology of pneumococcal infection evolves, it is important for clinicians to continue to stay abreast of data regarding disease incidence, emerging serotypes, bacterial resistance, and future advances.

When the 7-valent pneumococcal conjugate vaccine was first introduced in 2000, many of us had high hopes that it would bring with it a new era in which we could leave invasive pneumococcal disease out of the equation and not have to worry that we might be missing a case of meningitis.

Indeed, the vaccine has resulted in an impressive overall reduction in pediatric invasive pneumococcal infection.

Unfortunately, emerging data now suggest that rates of invasive disease caused by nonvaccine serotypes are rising and that the overall disease reduction seen in the first 5 years since licensure of the vaccine may have leveled off.

With Haemophilus influenzae type b (Hib), all invasive disease was caused by a single strain. Following the universal implementation of the Hib vaccine in the 1990s, invasive Hib disease has virtually disappeared.

In contrast, pneumococcal infection involves multiple serotypes. This alone inherently limits the success that the 7-valent pneumococcal conjugate vaccine (PCV7) may have and explains part of the changing epidemiology.

Ongoing surveillance is extremely important now, and will continue to be as we move forward with new vaccines containing additional serotypes.

Here at Children's Mercy Hospital, my colleagues Dr. Douglas S. Swanson and Dr. Christopher J. Harrison compared data from patients with invasive pneumococcal disease in the pre-PCV7 era of 1998–2000 with data from 2001 through March 2006. They found that the total number of invasive pneumococcal infections in Kansas City children has decreased from prevaccine years, with the average annual number of invasive pneumococcal disease cases declining by about 50%, from 43 cases/year during 1998–2000 to 21 cases/year from 2001 through March 2006. This is remarkable and consistent with data from other pediatric hospitals.

Steenhoff et al. recently compared data on pneumococcal bacteremia from the pre-PCV7 era in Philadelphia with data from 2001 through May 2005, and found that the incidence decreased by 57% (CID 2006;42:907–14).

Schutze et al. similarly noted a decrease in disease incidence of invasive disease in Arkansas from a high of 5.78/100,000 population to 3.02/100,000 population in the postvaccine era (Pediatr. Infect. Dis. J. 2004;23:1125–9).

Occult pneumococcal bacteremia has been by far the most common of the invasive infections that pediatricians have encountered in the past and appears to be the most common invasive infection impacted by PCV7. This entity, which traditionally occurs in infants from 6 to 36 months of age with high fever and no localizing findings, generally has a benign outcome. Complications, including meningitis, occur rarely.

Reduction of more virulent diseases like empyema and meningitis with PCV7 has been clearly demonstrated. However, data suggest that pneumococcus continues to play an important role in complicated pneumonia with empyema.

In a study from the United Kingdom published earlier this summer, locally presenting pleural empyema cases in children increased threefold during 2003–2004. Antigen analysis of empyema fluid identified Streptococcus pneumoniae in 27 of 29 cases for whom samples were available, and capsular polysaccharide type 1 was confirmed in 18 of those (Pediatr. Infect. Dis. J. 2006;25:559–60).

The authors, Fletcher et al. of the South West of England Invasive Community Acquired Infection Study Group, concluded that “use of a conjugate vaccine without serotype 1 antigen would have had limited impact on this morbidity in our region.”

Postvaccine licensure studies have shown a decline in incidence of pneumococcal meningitis cases. In our review, this was less remarkable, with an average of 6.7 cases/year in 1998–2000 and 4.8 cases/year from 2001 through March 2006. This year alone we have treated eight patients with pneumococcal meningitis.

Serotype replacement is a major issue. In our institution since 2001, only 2 of the 20 isolates that have been serotyped are vaccine-specific serotypes. The apparent failure of the vaccine to impact 19A disease is notable, because it was hoped that cross-protection with vaccine serotype 19F would occur.

Kaplan et al. of the U.S. Pediatric Multicenter Pneumococcal Surveillance Group recently examined this issue. Investigators from eight children's hospitals have been prospectively identifying children in their centers with invasive infections caused by S. pneumoniae for the last 9 years. They found that serotypes 15, 19A, and 33 were the most common nonvaccine serotypes and accounted for almost half of nonvaccine isolates recovered from vaccinated patients in the postvaccine era (Pediatrics 2004;113:443–9).

The vaccine's impact on antimicrobial resistance is less clear. Schutze et al. noted that 44% of isolates were nonsusceptible to penicillin in 1998–2000, not significantly different from the 46% seen in the postvaccine era of 2001–2003.

In our institution, 34% of the invasive isolates in 1998–2000 were penicillin nonsusceptible, compared with 42% in 2001 through March 2006. The latter finding was not statistically significant, but it does support data from other studies suggesting that the vaccine's impact on cases of invasive disease caused by penicillin nonsusceptible pneumococcal strains warrants continued monitoring.

In a study that was funded in part by Wyeth et al. of Kaiser Permanente, Oakland, Calif., found that the herd immunity conferred by individuals vaccinated with PCV7 resulted in significant savings in cost per life-year saved during the first 5 years following introduction of the vaccine.

However, they acknowledged, “if serotype replacement increases over time, it is possible that the efficacy of the vaccine—both for the vaccinated and nonvaccinated populations—could decline in the future” (Pediatr. Infect. Dis. J. 2006;25:494–501).

Current efforts to develop new multivalent pneumococcal conjugate vaccines will pay off in the long run. As we turn our attention to the next phase of development, we also must keep in mind and prioritize the needs in the developing world.

According to the World Health Organization, as many as 1 million children under 5 years of age die every year of pneumococcal pneumonia, meningitis, and sepsis. In populations with high child mortality rates, pneumonia is the leading infectious cause of mortality, accounting for about 20%–25% of all deaths in children.

Clinical trials now underway in Africa and elsewhere are utilizing conjugate pneumococcal vaccines containing between 7 and 13 serotypes. While serotype replacement could eventually occur in the developing world as well, the immediate impact in reducing disease and death would be enormous and undeniably worthwhile.

Phase III studies are ongoing with one prototype that contains 13 serotypes including 19A, 1, 3, 5, 6A, and 7V. Investigators estimate that in the United States, the 13-valent vaccine will cover around 60% of the remaining disease in children and expand coverage for strains prevalent in developing countries.

Despite the success of conjugate pneumococcal vaccine, it is clear that it will not be associated with the type of triumph we achieved with the Hib vaccine.

For the near future at least, we will need to remain vigilant when evaluating febrile children, understanding the clinical setting in which pneumococcal infection may occur. As the epidemiology of pneumococcal infection evolves, it is important for clinicians to continue to stay abreast of data regarding disease incidence, emerging serotypes, bacterial resistance, and future advances.

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

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.

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