ID Consult

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 And there's another bonus: Reactogenicity is lower with the new vaccines, compared with the old RotaShield, which was withdrawn from the market in 1999.

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

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

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

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

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

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

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

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

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

Other studies have shown disseminated rotavirus outside the gastrointestinal tract.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Other studies have shown disseminated rotavirus outside the gastrointestinal tract.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Other studies have shown disseminated rotavirus outside the gastrointestinal tract.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Of course, there are caveats to these distinctions.

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

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

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

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

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

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

Stay tuned for the next chapter.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Of course, there are caveats to these distinctions.

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

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

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

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

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

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

Stay tuned for the next chapter.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Of course, there are caveats to these distinctions.

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

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

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

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

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

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

Stay tuned for the next chapter.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

1. Intensifying surveillance and collaborating on containment.

2. Stockpiling antivirals and vaccines.

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

4. Increasing public education and communication.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

1. Intensifying surveillance and collaborating on containment.

2. Stockpiling antivirals and vaccines.

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

4. Increasing public education and communication.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

1. Intensifying surveillance and collaborating on containment.

2. Stockpiling antivirals and vaccines.

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

4. Increasing public education and communication.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Quinolone otic drops may represent a better choice for treating swimmer's ear in children than are the generics that we're accustomed to using.

Both Floxin (ofloxacin otic solution 0.3%) and Ciprodex (ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension) have recently been approved for the treatment of acute otitis externa in children as young as age 6 months. Otolaryngologists are using these drugs extensively in children, but so far, the pediatric community has not embraced them. This lag is due in part to the way these products have been marketed. But I believe that inappropriate concern about fluoroquinolone-associated arthropathy has also impeded use of what appear to be products with greater efficacy and convenience, and possibly even lower cost, in the case of Floxin.

Overall, the data suggest that efficacy of Floxin and Ciprodex drops in treating acute otitis externa in children is greater than 90%, compared with about 80% for the generics such as Cortisporin (neomycin, polymyxin B sulfates, and hydrocortisone otic solution), and about 70% for astringents such as acetic acid, isopropyl alcohol, or hydrogen peroxide.

In an open-label, phase III trial involving 439 children with acute otitis externa in Latin America, a 7-day course of Floxin given once daily—5 drops for children aged 6 months to 12 years, 10 drops for those 13 years and older—produced eradication rates of 96% overall (Clin. Ther. 2004;26:1046–54).

Similar efficacy for Ciprodex was seen in a recent randomized, blinded multicenter trial in 396 otitis externa patients older than 1 year. Clinical cure rates at day 18 were 90.9% after 7 days of Ciprodex (3–4 drops twice daily), compared with 83.9% after 7 days of Cortisporin (3–4 drops three times daily), while microbiologic eradication rates were 94.7% and 86%, respectively (Curr. Med. Res. Opin. 2004;20:1175–83).

Antimicrobial resistance to the older topicals might be one reason for the quinolones' superior efficacy. Data from two multicenter trials conducted by Floxin manufacturer Daiichi Pharmaceuticals Inc. suggested that the two most common organisms associated with otitis externa—Pseudomonas aeruginosa and Staphylococcus aureus—appear to be developing resistance to Cortisporin but not to Floxin (South. Med. J. 2004; 97:465–71).

The quinolones are also more convenient to administer. Floxin is available in 5-mL and 10-mL plastic dropper bottles and as “singles” containing individual once-daily doses (one packet for ages 6 months to 12 years and two for children aged 13 years and older, given for 7 days). The dropper bottles also allow for once-daily dosing (5 drops for ages 6 months to 13 years and 10 drops for ages 13 and older). Ciprodex dosing for patients 6 months and older is four drops twice daily for 7 days.

In contrast, 3 drops of Cortisporin must be administered three or four times daily to children with acute otitis externa.

There is some disagreement about whether a corticosteroid—contained in Ciprodex and Cortisporin but not Floxin—adds significant benefit. While the anti-inflammatory effect does produce greater symptomatic relief, it also may dampen the immune response. Because the data suggest Floxin is just as effective as Ciprodex, and more effective than Cortisporin, the steroid may not be much of an advantage.

Floxin can be slightly cheaper than the generic Cortisporin on a per-treatment basis: Computed with the average wholesale price for a 5-mL bottle, the cost of 5 drops of Floxin daily for 7 days is $17.60, compared with $18.34 for a 10-day treatment of Cortisporin, 4 drops daily. The cost of Ciprodex is somewhat higher than for the generic.

In addition to being more effective and convenient without costing more, quinolone drops are also quite safe. Systemic absorption of these topicals is essentially zero. And even with oral administration, combined data from studies involving approximately 16,000 children and adolescents have not revealed a single case of arthropathy, which has been seen in juvenile animals only. Safety data such as these led to the recent approval of ciprofloxacin for children 1 year and older with complicated urinary tract infections or pyelonephritis.

In four Bristol-Meyers Squibb-sponsored trials analyzed by my group and others, there was no evidence of arthrotoxicity among 867 children with recurrent or acute otitis media who were treated with gatifloxacin. Our results will be published in the August issue of Clinical Infectious Diseases.

Of course, as physicians we should also try to help our patients avoid swimmer's ear in the first place, and especially to prevent recurrence in those who've had the problem in the past. Swimming is the No. 1 cause of otitis externa, with lakes and rivers being the culprit more often than chlorinated swimming pools. Patients who regularly swim in natural bodies of water might be advised to place a couple drops of rubbing alcohol or hydrogen peroxide in each ear after emerging from the water.

In swimmer's ear, the child complains of ear pain, but often you can't see the eardrum because the ear is so swollen.

The second-most frequent cause of otitis externa in children occurs among those with drainage from tympanostomy tubes or a perforated eardrum.

The third is trauma. Children—or their parents—may stick cotton swabs or bobby pins in the child's ear, perhaps in an attempt to remove wax, and end up abrading the canal. This kind of trauma can introduce bacterial contamination. Such practices should be discouraged.

I served as a one-time consultant to Floxin manufacturer Daiichi. I have no affiliation with Bayer Pharmaceuticals Corp. or its subsidiary Alcon Laboratories Inc., the makers of Ciprodex.

Quinolone otic drops may represent a better choice for treating swimmer's ear in children than are the generics that we're accustomed to using.

Both Floxin (ofloxacin otic solution 0.3%) and Ciprodex (ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension) have recently been approved for the treatment of acute otitis externa in children as young as age 6 months. Otolaryngologists are using these drugs extensively in children, but so far, the pediatric community has not embraced them. This lag is due in part to the way these products have been marketed. But I believe that inappropriate concern about fluoroquinolone-associated arthropathy has also impeded use of what appear to be products with greater efficacy and convenience, and possibly even lower cost, in the case of Floxin.

Overall, the data suggest that efficacy of Floxin and Ciprodex drops in treating acute otitis externa in children is greater than 90%, compared with about 80% for the generics such as Cortisporin (neomycin, polymyxin B sulfates, and hydrocortisone otic solution), and about 70% for astringents such as acetic acid, isopropyl alcohol, or hydrogen peroxide.

In an open-label, phase III trial involving 439 children with acute otitis externa in Latin America, a 7-day course of Floxin given once daily—5 drops for children aged 6 months to 12 years, 10 drops for those 13 years and older—produced eradication rates of 96% overall (Clin. Ther. 2004;26:1046–54).

Similar efficacy for Ciprodex was seen in a recent randomized, blinded multicenter trial in 396 otitis externa patients older than 1 year. Clinical cure rates at day 18 were 90.9% after 7 days of Ciprodex (3–4 drops twice daily), compared with 83.9% after 7 days of Cortisporin (3–4 drops three times daily), while microbiologic eradication rates were 94.7% and 86%, respectively (Curr. Med. Res. Opin. 2004;20:1175–83).

Antimicrobial resistance to the older topicals might be one reason for the quinolones' superior efficacy. Data from two multicenter trials conducted by Floxin manufacturer Daiichi Pharmaceuticals Inc. suggested that the two most common organisms associated with otitis externa—Pseudomonas aeruginosa and Staphylococcus aureus—appear to be developing resistance to Cortisporin but not to Floxin (South. Med. J. 2004; 97:465–71).

The quinolones are also more convenient to administer. Floxin is available in 5-mL and 10-mL plastic dropper bottles and as “singles” containing individual once-daily doses (one packet for ages 6 months to 12 years and two for children aged 13 years and older, given for 7 days). The dropper bottles also allow for once-daily dosing (5 drops for ages 6 months to 13 years and 10 drops for ages 13 and older). Ciprodex dosing for patients 6 months and older is four drops twice daily for 7 days.

In contrast, 3 drops of Cortisporin must be administered three or four times daily to children with acute otitis externa.

There is some disagreement about whether a corticosteroid—contained in Ciprodex and Cortisporin but not Floxin—adds significant benefit. While the anti-inflammatory effect does produce greater symptomatic relief, it also may dampen the immune response. Because the data suggest Floxin is just as effective as Ciprodex, and more effective than Cortisporin, the steroid may not be much of an advantage.

Floxin can be slightly cheaper than the generic Cortisporin on a per-treatment basis: Computed with the average wholesale price for a 5-mL bottle, the cost of 5 drops of Floxin daily for 7 days is $17.60, compared with $18.34 for a 10-day treatment of Cortisporin, 4 drops daily. The cost of Ciprodex is somewhat higher than for the generic.

In addition to being more effective and convenient without costing more, quinolone drops are also quite safe. Systemic absorption of these topicals is essentially zero. And even with oral administration, combined data from studies involving approximately 16,000 children and adolescents have not revealed a single case of arthropathy, which has been seen in juvenile animals only. Safety data such as these led to the recent approval of ciprofloxacin for children 1 year and older with complicated urinary tract infections or pyelonephritis.

In four Bristol-Meyers Squibb-sponsored trials analyzed by my group and others, there was no evidence of arthrotoxicity among 867 children with recurrent or acute otitis media who were treated with gatifloxacin. Our results will be published in the August issue of Clinical Infectious Diseases.

Of course, as physicians we should also try to help our patients avoid swimmer's ear in the first place, and especially to prevent recurrence in those who've had the problem in the past. Swimming is the No. 1 cause of otitis externa, with lakes and rivers being the culprit more often than chlorinated swimming pools. Patients who regularly swim in natural bodies of water might be advised to place a couple drops of rubbing alcohol or hydrogen peroxide in each ear after emerging from the water.

In swimmer's ear, the child complains of ear pain, but often you can't see the eardrum because the ear is so swollen.

The second-most frequent cause of otitis externa in children occurs among those with drainage from tympanostomy tubes or a perforated eardrum.

The third is trauma. Children—or their parents—may stick cotton swabs or bobby pins in the child's ear, perhaps in an attempt to remove wax, and end up abrading the canal. This kind of trauma can introduce bacterial contamination. Such practices should be discouraged.

I served as a one-time consultant to Floxin manufacturer Daiichi. I have no affiliation with Bayer Pharmaceuticals Corp. or its subsidiary Alcon Laboratories Inc., the makers of Ciprodex.

Quinolone otic drops may represent a better choice for treating swimmer's ear in children than are the generics that we're accustomed to using.

Both Floxin (ofloxacin otic solution 0.3%) and Ciprodex (ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension) have recently been approved for the treatment of acute otitis externa in children as young as age 6 months. Otolaryngologists are using these drugs extensively in children, but so far, the pediatric community has not embraced them. This lag is due in part to the way these products have been marketed. But I believe that inappropriate concern about fluoroquinolone-associated arthropathy has also impeded use of what appear to be products with greater efficacy and convenience, and possibly even lower cost, in the case of Floxin.

Overall, the data suggest that efficacy of Floxin and Ciprodex drops in treating acute otitis externa in children is greater than 90%, compared with about 80% for the generics such as Cortisporin (neomycin, polymyxin B sulfates, and hydrocortisone otic solution), and about 70% for astringents such as acetic acid, isopropyl alcohol, or hydrogen peroxide.

In an open-label, phase III trial involving 439 children with acute otitis externa in Latin America, a 7-day course of Floxin given once daily—5 drops for children aged 6 months to 12 years, 10 drops for those 13 years and older—produced eradication rates of 96% overall (Clin. Ther. 2004;26:1046–54).

Similar efficacy for Ciprodex was seen in a recent randomized, blinded multicenter trial in 396 otitis externa patients older than 1 year. Clinical cure rates at day 18 were 90.9% after 7 days of Ciprodex (3–4 drops twice daily), compared with 83.9% after 7 days of Cortisporin (3–4 drops three times daily), while microbiologic eradication rates were 94.7% and 86%, respectively (Curr. Med. Res. Opin. 2004;20:1175–83).

Antimicrobial resistance to the older topicals might be one reason for the quinolones' superior efficacy. Data from two multicenter trials conducted by Floxin manufacturer Daiichi Pharmaceuticals Inc. suggested that the two most common organisms associated with otitis externa—Pseudomonas aeruginosa and Staphylococcus aureus—appear to be developing resistance to Cortisporin but not to Floxin (South. Med. J. 2004; 97:465–71).

The quinolones are also more convenient to administer. Floxin is available in 5-mL and 10-mL plastic dropper bottles and as “singles” containing individual once-daily doses (one packet for ages 6 months to 12 years and two for children aged 13 years and older, given for 7 days). The dropper bottles also allow for once-daily dosing (5 drops for ages 6 months to 13 years and 10 drops for ages 13 and older). Ciprodex dosing for patients 6 months and older is four drops twice daily for 7 days.

In contrast, 3 drops of Cortisporin must be administered three or four times daily to children with acute otitis externa.

There is some disagreement about whether a corticosteroid—contained in Ciprodex and Cortisporin but not Floxin—adds significant benefit. While the anti-inflammatory effect does produce greater symptomatic relief, it also may dampen the immune response. Because the data suggest Floxin is just as effective as Ciprodex, and more effective than Cortisporin, the steroid may not be much of an advantage.

Floxin can be slightly cheaper than the generic Cortisporin on a per-treatment basis: Computed with the average wholesale price for a 5-mL bottle, the cost of 5 drops of Floxin daily for 7 days is $17.60, compared with $18.34 for a 10-day treatment of Cortisporin, 4 drops daily. The cost of Ciprodex is somewhat higher than for the generic.

In addition to being more effective and convenient without costing more, quinolone drops are also quite safe. Systemic absorption of these topicals is essentially zero. And even with oral administration, combined data from studies involving approximately 16,000 children and adolescents have not revealed a single case of arthropathy, which has been seen in juvenile animals only. Safety data such as these led to the recent approval of ciprofloxacin for children 1 year and older with complicated urinary tract infections or pyelonephritis.

In four Bristol-Meyers Squibb-sponsored trials analyzed by my group and others, there was no evidence of arthrotoxicity among 867 children with recurrent or acute otitis media who were treated with gatifloxacin. Our results will be published in the August issue of Clinical Infectious Diseases.

Of course, as physicians we should also try to help our patients avoid swimmer's ear in the first place, and especially to prevent recurrence in those who've had the problem in the past. Swimming is the No. 1 cause of otitis externa, with lakes and rivers being the culprit more often than chlorinated swimming pools. Patients who regularly swim in natural bodies of water might be advised to place a couple drops of rubbing alcohol or hydrogen peroxide in each ear after emerging from the water.

In swimmer's ear, the child complains of ear pain, but often you can't see the eardrum because the ear is so swollen.

The second-most frequent cause of otitis externa in children occurs among those with drainage from tympanostomy tubes or a perforated eardrum.

The third is trauma. Children—or their parents—may stick cotton swabs or bobby pins in the child's ear, perhaps in an attempt to remove wax, and end up abrading the canal. This kind of trauma can introduce bacterial contamination. Such practices should be discouraged.

I served as a one-time consultant to Floxin manufacturer Daiichi. I have no affiliation with Bayer Pharmaceuticals Corp. or its subsidiary Alcon Laboratories Inc., the makers of Ciprodex.

Soon we will be routinely vaccinating our adolescent patients against pertussis. This will certainly go a long way toward reversing the disease's recent upward trend, but there's still more we need to do.

Specifically, physicians must not only consider the diagnosis in every patient with persistent cough, regardless of age, but should begin treatment presumptively in those who meet the clinical case definition—and their close contacts—without waiting for culture results to come back. Indeed, until physicians begin recognizing that pertussis is widely circulating and is serious, we're not going to be able to reverse the increase that has been occurring since the mid-1970s.

There's an odd paradox to pertussis. It's the only vaccine-preventable disease for which rates are rising instead of falling. Provisional data from the Centers for Disease Control and Prevention for 2004 show a record 18,957 confirmed cases of pertussis, a huge jump from the 11,647 in 2003 and the highest number of cases reported in the United States since 1959. Prior to last year, there had been 9,771 cases in 2002; 7,580 in 2001; and 7,867 in 2000. Compare those numbers with the 4,570 reported in 1990 and 1,730 in 1980. The nadir occurred in 1976, with just 1,010 cases.

Yet, this rise has coincided with the proportion of children aged 19–35 months who received all four doses of DTaP vaccine reaching a record high of 85.6%, according to the CDC's June 2003 to June 2004 National Immunization Survey.

Of course, that still leaves about 15% of unimmunized and underimmunized children—many of whom come from pockets in communities where immunization rates lag significantly behind—with the rest having received a vaccine that's only about 85% effective to begin with. Acellular pertussis vaccine efficacy is hard to determine; the best studies suggest that most vaccines are around 85%, which may be slightly less than the old whole-cell formulations, some of which were estimated to be 90% effective.

Part of the problem is that pertussis continues to be underrecognized and underappreciated as a major public health threat, even though it kills 2 in every 1,000 infants. There were 16 pertussis-related deaths in the 2004 provisional data, 18 in 2003, 22 in 2002, and 15 in 2001. Nearly all were in children under 6 months of age, who had not yet completed the primary immunization series and contracted the disease from undiagnosed adolescents or adults.

Indeed, pertussis is rarely considered by our adult medicine colleagues, even though numerous studies have suggested that pertussis comprises 20%–30% of all cases of persistent cough among adults lasting 2 weeks or longer.

At my center in Kansas City, we had a dramatic increase in confirmed cases of pertussis in children during 2004: 79 cases, compared with an average of 30 per year during 2000–2003, and 20 per year between 1984 and 1999. We diagnosed 26 pertussis cases in the month of December alone, more than the number seen in every previous entire year since 1984. While the proportion of cases in children less than 6 months of age didn't change over time, we did see a statistically significant increase in the proportion among children older than 10 years: 14% in 2004 versus just 1% in prior years.

Hispanic children represented 15% of our cases in 2004, twice as many as in the previous 4 years combined. (Hispanics make up 7% of the population.) Data suggest that foreign-born children may be at particularly high risk for being underimmunized. The percentage of cases receiving state-supported health coverage increased from 50% to 68%, even though studies suggest that children who receive state-funded vaccine tend to be just as well immunized as are privately insured patients. Lastly, children in 2004 were seen in urgent care and emergency department settings more frequently.

Angela L. Myers, M.D., a fellow in pediatric infectious diseases at our institution, conducted an analysis of the medical records of all 79 patients, and compared them with all patients with confirmed pertussis in 2000–2003, with some very interesting results. Although clinical case presentations of pertussis were consistent with previous years, with paroxysmal cough and posttussive vomiting most commonly recorded, the diagnosis had not been considered on initial presentation in 29%.

These findings, which are similar to other U.S. data, illustrate several important points. Many of these children presented at urgent care settings, in which staff are trained to look for the ill child. But children (and adults) with pertussis typically look and feel fine when they're not coughing. The key is ascertaining a detailed history, including whether the cough is paroxysmal, its duration, and an association with other symptoms including posttussive emesis or whoop.

It's also important to document vaccine status and to identify coughing family members. In most cases an adult, often the mother, is the vector for infection in a young infant.

Vaccine status had not been recorded for 48% of patients aged 2 months or older. Specific information regarding the number of pertussis-containing vaccine doses received was infrequently recorded. Contact isolation was discussed in just 8% of cases, despite the fact that restriction from school attendance is very important in school-aged children. Household chemoprophylaxis had been provided in just 51%, and of those diagnosed where vaccine status could be ascertained, just 10% were appropriate for age.

Attempts to document vaccine status are notoriously difficult as many parents do not carry an immunization card, and obtaining details from a public health department or primary care office after hours is nearly impossible. A check of the box “vaccines up to date” relies on simply asking the parent who may or may not know for sure the child's vaccine status.

Among those who had been tested for pertussis, correct treatment was prescribed in just 62%. In many cases, therapy was not optimal: In some cases, amoxicillin was prescribed when otitis was concurrently diagnosed, while in others a macrolide was given but in the wrong dose. For pertussis, a correct regimen would be 10–12 mg/kg per day of azithromycin for each of 5 days, as opposed to 10 mg/kg per day on day 1 followed by 5 mg/kg per day for days 2–5 for otitis media.

And we know that pediatricians are often reluctant to write prescriptions for adults, even though pertussis is highly transmissible and the sooner chemoprophylaxis is given, the better the chance to interrupt transmission. An adult with the disease presents a threat to a young infant living in the same household. (The adult dose is 500 mg/day azithromycin for 5 days.)

Indeed, after educating our local pediatricians about treating pertussis presumptively, we have seen a drop in cases thus far in 2005.

Pertussis Case Definition

Clinical Case Definition

▸ A cough illness lasting at least 2 weeks with one of the following: paroxysms of coughing, inspiratory “whoop,” or posttussive vomiting, and without other apparent cause (as reported by a health professional).

Laboratory Criteria for Diagnosis

▸ Isolation of Bordetella pertussis from a clinical specimen or positive polymerase chain reaction (PCR) assay for B. pertussis.

Case Classification

▸ Confirmed: an acute cough illness of any duration associated with B. pertussis isolation; or a case that meets the clinical case definition and is confirmed by PCR; or a case that meets the clinical case definition and is epidemiologically linked directly to a case confirmed by either culture or PCR.

▸ Probable: meets the clinical case definition, is not laboratory confirmed, and is not epidemiologically linked to a laboratory confirmed case.

Both probable and confirmed cases should be reported to the local health department.

Source: Centers for Disease Control and Prevention and the Council of State and Territorial Epidemiologists

Soon we will be routinely vaccinating our adolescent patients against pertussis. This will certainly go a long way toward reversing the disease's recent upward trend, but there's still more we need to do.

Specifically, physicians must not only consider the diagnosis in every patient with persistent cough, regardless of age, but should begin treatment presumptively in those who meet the clinical case definition—and their close contacts—without waiting for culture results to come back. Indeed, until physicians begin recognizing that pertussis is widely circulating and is serious, we're not going to be able to reverse the increase that has been occurring since the mid-1970s.

There's an odd paradox to pertussis. It's the only vaccine-preventable disease for which rates are rising instead of falling. Provisional data from the Centers for Disease Control and Prevention for 2004 show a record 18,957 confirmed cases of pertussis, a huge jump from the 11,647 in 2003 and the highest number of cases reported in the United States since 1959. Prior to last year, there had been 9,771 cases in 2002; 7,580 in 2001; and 7,867 in 2000. Compare those numbers with the 4,570 reported in 1990 and 1,730 in 1980. The nadir occurred in 1976, with just 1,010 cases.

Yet, this rise has coincided with the proportion of children aged 19–35 months who received all four doses of DTaP vaccine reaching a record high of 85.6%, according to the CDC's June 2003 to June 2004 National Immunization Survey.

Of course, that still leaves about 15% of unimmunized and underimmunized children—many of whom come from pockets in communities where immunization rates lag significantly behind—with the rest having received a vaccine that's only about 85% effective to begin with. Acellular pertussis vaccine efficacy is hard to determine; the best studies suggest that most vaccines are around 85%, which may be slightly less than the old whole-cell formulations, some of which were estimated to be 90% effective.

Part of the problem is that pertussis continues to be underrecognized and underappreciated as a major public health threat, even though it kills 2 in every 1,000 infants. There were 16 pertussis-related deaths in the 2004 provisional data, 18 in 2003, 22 in 2002, and 15 in 2001. Nearly all were in children under 6 months of age, who had not yet completed the primary immunization series and contracted the disease from undiagnosed adolescents or adults.

Indeed, pertussis is rarely considered by our adult medicine colleagues, even though numerous studies have suggested that pertussis comprises 20%–30% of all cases of persistent cough among adults lasting 2 weeks or longer.

At my center in Kansas City, we had a dramatic increase in confirmed cases of pertussis in children during 2004: 79 cases, compared with an average of 30 per year during 2000–2003, and 20 per year between 1984 and 1999. We diagnosed 26 pertussis cases in the month of December alone, more than the number seen in every previous entire year since 1984. While the proportion of cases in children less than 6 months of age didn't change over time, we did see a statistically significant increase in the proportion among children older than 10 years: 14% in 2004 versus just 1% in prior years.

Hispanic children represented 15% of our cases in 2004, twice as many as in the previous 4 years combined. (Hispanics make up 7% of the population.) Data suggest that foreign-born children may be at particularly high risk for being underimmunized. The percentage of cases receiving state-supported health coverage increased from 50% to 68%, even though studies suggest that children who receive state-funded vaccine tend to be just as well immunized as are privately insured patients. Lastly, children in 2004 were seen in urgent care and emergency department settings more frequently.

Angela L. Myers, M.D., a fellow in pediatric infectious diseases at our institution, conducted an analysis of the medical records of all 79 patients, and compared them with all patients with confirmed pertussis in 2000–2003, with some very interesting results. Although clinical case presentations of pertussis were consistent with previous years, with paroxysmal cough and posttussive vomiting most commonly recorded, the diagnosis had not been considered on initial presentation in 29%.

These findings, which are similar to other U.S. data, illustrate several important points. Many of these children presented at urgent care settings, in which staff are trained to look for the ill child. But children (and adults) with pertussis typically look and feel fine when they're not coughing. The key is ascertaining a detailed history, including whether the cough is paroxysmal, its duration, and an association with other symptoms including posttussive emesis or whoop.

It's also important to document vaccine status and to identify coughing family members. In most cases an adult, often the mother, is the vector for infection in a young infant.

Vaccine status had not been recorded for 48% of patients aged 2 months or older. Specific information regarding the number of pertussis-containing vaccine doses received was infrequently recorded. Contact isolation was discussed in just 8% of cases, despite the fact that restriction from school attendance is very important in school-aged children. Household chemoprophylaxis had been provided in just 51%, and of those diagnosed where vaccine status could be ascertained, just 10% were appropriate for age.

Attempts to document vaccine status are notoriously difficult as many parents do not carry an immunization card, and obtaining details from a public health department or primary care office after hours is nearly impossible. A check of the box “vaccines up to date” relies on simply asking the parent who may or may not know for sure the child's vaccine status.

Among those who had been tested for pertussis, correct treatment was prescribed in just 62%. In many cases, therapy was not optimal: In some cases, amoxicillin was prescribed when otitis was concurrently diagnosed, while in others a macrolide was given but in the wrong dose. For pertussis, a correct regimen would be 10–12 mg/kg per day of azithromycin for each of 5 days, as opposed to 10 mg/kg per day on day 1 followed by 5 mg/kg per day for days 2–5 for otitis media.

And we know that pediatricians are often reluctant to write prescriptions for adults, even though pertussis is highly transmissible and the sooner chemoprophylaxis is given, the better the chance to interrupt transmission. An adult with the disease presents a threat to a young infant living in the same household. (The adult dose is 500 mg/day azithromycin for 5 days.)

Indeed, after educating our local pediatricians about treating pertussis presumptively, we have seen a drop in cases thus far in 2005.

Pertussis Case Definition

Clinical Case Definition

▸ A cough illness lasting at least 2 weeks with one of the following: paroxysms of coughing, inspiratory “whoop,” or posttussive vomiting, and without other apparent cause (as reported by a health professional).

Laboratory Criteria for Diagnosis

▸ Isolation of Bordetella pertussis from a clinical specimen or positive polymerase chain reaction (PCR) assay for B. pertussis.

Case Classification

▸ Confirmed: an acute cough illness of any duration associated with B. pertussis isolation; or a case that meets the clinical case definition and is confirmed by PCR; or a case that meets the clinical case definition and is epidemiologically linked directly to a case confirmed by either culture or PCR.

▸ Probable: meets the clinical case definition, is not laboratory confirmed, and is not epidemiologically linked to a laboratory confirmed case.

Both probable and confirmed cases should be reported to the local health department.

Source: Centers for Disease Control and Prevention and the Council of State and Territorial Epidemiologists

Soon we will be routinely vaccinating our adolescent patients against pertussis. This will certainly go a long way toward reversing the disease's recent upward trend, but there's still more we need to do.

Specifically, physicians must not only consider the diagnosis in every patient with persistent cough, regardless of age, but should begin treatment presumptively in those who meet the clinical case definition—and their close contacts—without waiting for culture results to come back. Indeed, until physicians begin recognizing that pertussis is widely circulating and is serious, we're not going to be able to reverse the increase that has been occurring since the mid-1970s.

There's an odd paradox to pertussis. It's the only vaccine-preventable disease for which rates are rising instead of falling. Provisional data from the Centers for Disease Control and Prevention for 2004 show a record 18,957 confirmed cases of pertussis, a huge jump from the 11,647 in 2003 and the highest number of cases reported in the United States since 1959. Prior to last year, there had been 9,771 cases in 2002; 7,580 in 2001; and 7,867 in 2000. Compare those numbers with the 4,570 reported in 1990 and 1,730 in 1980. The nadir occurred in 1976, with just 1,010 cases.

Yet, this rise has coincided with the proportion of children aged 19–35 months who received all four doses of DTaP vaccine reaching a record high of 85.6%, according to the CDC's June 2003 to June 2004 National Immunization Survey.

Of course, that still leaves about 15% of unimmunized and underimmunized children—many of whom come from pockets in communities where immunization rates lag significantly behind—with the rest having received a vaccine that's only about 85% effective to begin with. Acellular pertussis vaccine efficacy is hard to determine; the best studies suggest that most vaccines are around 85%, which may be slightly less than the old whole-cell formulations, some of which were estimated to be 90% effective.

Part of the problem is that pertussis continues to be underrecognized and underappreciated as a major public health threat, even though it kills 2 in every 1,000 infants. There were 16 pertussis-related deaths in the 2004 provisional data, 18 in 2003, 22 in 2002, and 15 in 2001. Nearly all were in children under 6 months of age, who had not yet completed the primary immunization series and contracted the disease from undiagnosed adolescents or adults.

Indeed, pertussis is rarely considered by our adult medicine colleagues, even though numerous studies have suggested that pertussis comprises 20%–30% of all cases of persistent cough among adults lasting 2 weeks or longer.

At my center in Kansas City, we had a dramatic increase in confirmed cases of pertussis in children during 2004: 79 cases, compared with an average of 30 per year during 2000–2003, and 20 per year between 1984 and 1999. We diagnosed 26 pertussis cases in the month of December alone, more than the number seen in every previous entire year since 1984. While the proportion of cases in children less than 6 months of age didn't change over time, we did see a statistically significant increase in the proportion among children older than 10 years: 14% in 2004 versus just 1% in prior years.

Hispanic children represented 15% of our cases in 2004, twice as many as in the previous 4 years combined. (Hispanics make up 7% of the population.) Data suggest that foreign-born children may be at particularly high risk for being underimmunized. The percentage of cases receiving state-supported health coverage increased from 50% to 68%, even though studies suggest that children who receive state-funded vaccine tend to be just as well immunized as are privately insured patients. Lastly, children in 2004 were seen in urgent care and emergency department settings more frequently.

Angela L. Myers, M.D., a fellow in pediatric infectious diseases at our institution, conducted an analysis of the medical records of all 79 patients, and compared them with all patients with confirmed pertussis in 2000–2003, with some very interesting results. Although clinical case presentations of pertussis were consistent with previous years, with paroxysmal cough and posttussive vomiting most commonly recorded, the diagnosis had not been considered on initial presentation in 29%.

These findings, which are similar to other U.S. data, illustrate several important points. Many of these children presented at urgent care settings, in which staff are trained to look for the ill child. But children (and adults) with pertussis typically look and feel fine when they're not coughing. The key is ascertaining a detailed history, including whether the cough is paroxysmal, its duration, and an association with other symptoms including posttussive emesis or whoop.

It's also important to document vaccine status and to identify coughing family members. In most cases an adult, often the mother, is the vector for infection in a young infant.

Vaccine status had not been recorded for 48% of patients aged 2 months or older. Specific information regarding the number of pertussis-containing vaccine doses received was infrequently recorded. Contact isolation was discussed in just 8% of cases, despite the fact that restriction from school attendance is very important in school-aged children. Household chemoprophylaxis had been provided in just 51%, and of those diagnosed where vaccine status could be ascertained, just 10% were appropriate for age.

Attempts to document vaccine status are notoriously difficult as many parents do not carry an immunization card, and obtaining details from a public health department or primary care office after hours is nearly impossible. A check of the box “vaccines up to date” relies on simply asking the parent who may or may not know for sure the child's vaccine status.

Among those who had been tested for pertussis, correct treatment was prescribed in just 62%. In many cases, therapy was not optimal: In some cases, amoxicillin was prescribed when otitis was concurrently diagnosed, while in others a macrolide was given but in the wrong dose. For pertussis, a correct regimen would be 10–12 mg/kg per day of azithromycin for each of 5 days, as opposed to 10 mg/kg per day on day 1 followed by 5 mg/kg per day for days 2–5 for otitis media.

And we know that pediatricians are often reluctant to write prescriptions for adults, even though pertussis is highly transmissible and the sooner chemoprophylaxis is given, the better the chance to interrupt transmission. An adult with the disease presents a threat to a young infant living in the same household. (The adult dose is 500 mg/day azithromycin for 5 days.)

Indeed, after educating our local pediatricians about treating pertussis presumptively, we have seen a drop in cases thus far in 2005.

Pertussis Case Definition

Clinical Case Definition

▸ A cough illness lasting at least 2 weeks with one of the following: paroxysms of coughing, inspiratory “whoop,” or posttussive vomiting, and without other apparent cause (as reported by a health professional).

Laboratory Criteria for Diagnosis

▸ Isolation of Bordetella pertussis from a clinical specimen or positive polymerase chain reaction (PCR) assay for B. pertussis.

Case Classification

▸ Confirmed: an acute cough illness of any duration associated with B. pertussis isolation; or a case that meets the clinical case definition and is confirmed by PCR; or a case that meets the clinical case definition and is epidemiologically linked directly to a case confirmed by either culture or PCR.

▸ Probable: meets the clinical case definition, is not laboratory confirmed, and is not epidemiologically linked to a laboratory confirmed case.

Both probable and confirmed cases should be reported to the local health department.

Source: Centers for Disease Control and Prevention and the Council of State and Territorial Epidemiologists

Just in time for summer, I thought I'd offer some pointers on parasites.

Of course, parasites exist year round. But as the weather gets warmer and our patients head outside to play in the dirt or splash around in the toddler pool, the possibility that they'll pick up one of the following five organisms increases.

Here they are in approximate order of the frequency that we see them in central Kentucky:

▸ Pinworms. By far the most common parasite seen in preschool children, the diagnosis is usually made by a parent who finds a little wriggling rice-sized creature in the child's diaper, underwear, or bedding. Treatment—liquid mebendazole or chewable pyrantel pamoate—is given once, then repeated about 10–14 days later.

Families should be advised to wash all bed linens in hot water to get rid of any residual eggs and to prevent reinfestation.

If the problem recurs, retreat the child and consider treating the whole family and the child's playmates. If the parent reports a third sighting after two rounds of treatment, I will ask that they actually bring the worm in.

Some parents become so excessively concerned that they misinterpret many things as pinworms. It's been quite interesting—I've seen husks of corn, pea shells, and little bits of mucus that aren't even organisms.

Once, we got back a housefly larvae from a child's stool. I'm not sure how it got there.

We've also seen the proglottid of a tapeworm—these often fold up on themselves, and can almost look like a pinworm. That child had been treated several times for pinworms before referral.

Another pinworm-related problem is that the child may continue to experience perianal or vulvar itching and continue to scratch even after the pinworms are eradicated. Sitz baths may be helpful in easing the irritation. If itching continues, applying 1% hydrocortisone cream to the area for no more than 1 week can often break the itch-scratch cycle.

Pinworms are often an emotional issue for families. It's important to convince parents that it's not because they or their child is dirty, but, rather, that they picked up pinworms from their friends. To diffuse the worry, I often tell parents that the upside of pinworms is that their child likely has good social skills.

▸ Giardia. Toddler pools are a frequent yet underrecognized source of giardia, which are more familiarly associated with food-borne outbreaks or with transmission via fresh water, such as mountain springs.

But “kiddy pools” in the backyard or even at professionally maintained pool complexes are a particularly likely source of giardia transmission. Because they're shallow, sunlight can degrade the chlorine to below the giardia-inhibiting levels, which are higher than needed for coliforms.

If you see more than one giardia patient from the same swim club or backyard pool, advise the swim club pool staff or pool owners to make sure the chlorine level is being monitored more often. We had a giardia outbreak in an upscale country club's pool, and the parents were mortified. Acquisition of giardia in the pool is likely due to other toddlers using the pool in diapers.

Giardia typically presents with diarrhea, cramps, an extreme amount of flatulence, and stools with a characteristic green bubbly appearance. Once you've seen a giardia stool, you will know it again. The diagnosis is made with a routine laboratory ova and parasite screen.

Furazolidone is the treatment of choice, but metronidazole also works. Of course, these are two of the worst-tasting medicines around. You might advise parents to try chasing it with a spoonful of Hershey's syrup. In older kids, a Hershey's Kiss works. No, I receive no funding from Hershey's.

▸ Ascaris. In a typical scenario with ascaris, the parent reports finding a 2- to 4-inch long “fishing worm” in the child's diaper. This is the easy diagnosis.

However, we had a case last year of a 4-year-old who had been diagnosed with asthma and who continued wheezing over an 8-month period despite all the usual asthma medications including a couple rounds of steroids. He had eosinophilia, which had been attributed to allergies.

As it turned out, this child did not have asthma at all, but rather a classic case of Loeffler's pneumonia, in which the ascaris larvae had migrated to his lungs, triggering eosinophilia and an asthma-like picture. We treated the child with mebendazole twice a day for 3 days, and both the wheezing and the eosinophilia disappeared. The child didn't wheeze thereafter.

Ascaris was far more common in years past. These days we've become such a clean society we just don't see it as much as we used to and it's dropped off the radar screen. Yet, in addition to the pulmonary case, we've actually had two more classical ascaris cases just in the last month—one was spotted by the mother in the child's diaper, the other in the toilet.

Ascaris can produce abdominal pain and discomfort, and may lead to malabsorption syndrome, weight loss, or vitamin deficiency. Very large infestations can sometimes lead to intestinal obstruction—I saw a case of this a few years ago, when I was working in Omaha, Neb. The parasite also can migrate to the bile duct and obstruct the liver.

With lower-level infestations, however, the nonspecific epigastric and diffuse abdominal discomfort may be indistinguishable from functional abdominal pain.

However, if the problem persists—or if the child has wheezing or pneumonia symptoms, get a complete blood count. If you see eosinophilia, order an ova and parasite stool exam.

▸ Dientamoeba fragilis. If you trained prior to the 1990s, you probably were taught that D. fragilis is merely a harmless commensal and doesn't need to be treated. However, it has become apparent in the last decade or so that this parasite can cause symptoms, including chronic loose stools, cramps, and flatulence. The child usually doesn't look especially ill but complains of abdominal upset and may have up to three to four loose, mucus-containing stools per day.

And D. fragilis hangs on—after the second week or so, you can be fairly certain it's not rotavirus or another acute gastrointestinal virus. Along with giardia, also think of D. fragilis.

Interestingly, D. fragilis will often piggyback with pinworms, literally sticking itself to the pinworm eggs. Therefore, if you've already treated the child for pinworms and the GI symptoms continue, you might want to order another ova and parasite stool exam. This time, however, special procedures are required. Because this organism is so fragile—hence the name—it deteriorates rapidly at room temperature. Parents should be instructed to collect a fresh stool sample and immediately place it in a preservative-containing pack (we use ParaPak). For the greatest sensitivity, three samples must be collected on separate days. Sensitivity of the test is about 85%–90% for three samples taken on consecutive days, and up to 95% if collected on alternate days.

The order to the lab should request a microscopic exam, not just an antigen screen. Microscopy will pick up not only D. fragilis, but other less common parasitic creatures that you don't want to miss, such as Entamoeba histolytica. Parents must also be told to stop any over-the-counter antidiarrheals such as Kaopectate or Pepto-Bismol 24–48 hours prior to the first stool collection, as these agents will make it difficult to visualize the parasites.

If D. fragilis is identified, treatment is metronidazole three times a day for 10 days. Because of fecal-oral transmission, consider asking the parents if they're experiencing loose stools as well. Symptoms tend not to be as dramatic in adults as in kids, but if they've got D. fragilis and you treat them, they often feel better.

▸ Blastocystis hominis. Although similar to D. fragilis in structure, B. hominis is still considered a commensal and not pathogenic. However, if present in high enough quantities, it can still cause nonspecific abdominal symptoms, loose stools, flatulence, and mucus in the stool. If you do a work-up and find no other explanation for the symptoms, it's not unreasonable to treat using the 10-day metronidazole regimen. Here, too, a microscopic exam is necessary to visualize the cysts in the stool.

Although not known to produce any toxins or direct irritants to the colon, it's possible that B. hominis just has not been investigated closely enough to prove its pathogenicity. New data suggest this may be the case.

We've been seeing more lab reports of both D. fragilis and B. hominis in the last few years. It's not clear whether that's because of increased use of preservative packs or actual increased prevalence.

But we definitely seem to get more calls from parents and physicians about parasites as the weather gets warmer.

Just in time for summer, I thought I'd offer some pointers on parasites.

Of course, parasites exist year round. But as the weather gets warmer and our patients head outside to play in the dirt or splash around in the toddler pool, the possibility that they'll pick up one of the following five organisms increases.

Here they are in approximate order of the frequency that we see them in central Kentucky:

▸ Pinworms. By far the most common parasite seen in preschool children, the diagnosis is usually made by a parent who finds a little wriggling rice-sized creature in the child's diaper, underwear, or bedding. Treatment—liquid mebendazole or chewable pyrantel pamoate—is given once, then repeated about 10–14 days later.

Families should be advised to wash all bed linens in hot water to get rid of any residual eggs and to prevent reinfestation.

If the problem recurs, retreat the child and consider treating the whole family and the child's playmates. If the parent reports a third sighting after two rounds of treatment, I will ask that they actually bring the worm in.

Some parents become so excessively concerned that they misinterpret many things as pinworms. It's been quite interesting—I've seen husks of corn, pea shells, and little bits of mucus that aren't even organisms.

Once, we got back a housefly larvae from a child's stool. I'm not sure how it got there.

We've also seen the proglottid of a tapeworm—these often fold up on themselves, and can almost look like a pinworm. That child had been treated several times for pinworms before referral.

Another pinworm-related problem is that the child may continue to experience perianal or vulvar itching and continue to scratch even after the pinworms are eradicated. Sitz baths may be helpful in easing the irritation. If itching continues, applying 1% hydrocortisone cream to the area for no more than 1 week can often break the itch-scratch cycle.

Pinworms are often an emotional issue for families. It's important to convince parents that it's not because they or their child is dirty, but, rather, that they picked up pinworms from their friends. To diffuse the worry, I often tell parents that the upside of pinworms is that their child likely has good social skills.

▸ Giardia. Toddler pools are a frequent yet underrecognized source of giardia, which are more familiarly associated with food-borne outbreaks or with transmission via fresh water, such as mountain springs.

But “kiddy pools” in the backyard or even at professionally maintained pool complexes are a particularly likely source of giardia transmission. Because they're shallow, sunlight can degrade the chlorine to below the giardia-inhibiting levels, which are higher than needed for coliforms.

If you see more than one giardia patient from the same swim club or backyard pool, advise the swim club pool staff or pool owners to make sure the chlorine level is being monitored more often. We had a giardia outbreak in an upscale country club's pool, and the parents were mortified. Acquisition of giardia in the pool is likely due to other toddlers using the pool in diapers.

Giardia typically presents with diarrhea, cramps, an extreme amount of flatulence, and stools with a characteristic green bubbly appearance. Once you've seen a giardia stool, you will know it again. The diagnosis is made with a routine laboratory ova and parasite screen.

Furazolidone is the treatment of choice, but metronidazole also works. Of course, these are two of the worst-tasting medicines around. You might advise parents to try chasing it with a spoonful of Hershey's syrup. In older kids, a Hershey's Kiss works. No, I receive no funding from Hershey's.

▸ Ascaris. In a typical scenario with ascaris, the parent reports finding a 2- to 4-inch long “fishing worm” in the child's diaper. This is the easy diagnosis.

However, we had a case last year of a 4-year-old who had been diagnosed with asthma and who continued wheezing over an 8-month period despite all the usual asthma medications including a couple rounds of steroids. He had eosinophilia, which had been attributed to allergies.

As it turned out, this child did not have asthma at all, but rather a classic case of Loeffler's pneumonia, in which the ascaris larvae had migrated to his lungs, triggering eosinophilia and an asthma-like picture. We treated the child with mebendazole twice a day for 3 days, and both the wheezing and the eosinophilia disappeared. The child didn't wheeze thereafter.

Ascaris was far more common in years past. These days we've become such a clean society we just don't see it as much as we used to and it's dropped off the radar screen. Yet, in addition to the pulmonary case, we've actually had two more classical ascaris cases just in the last month—one was spotted by the mother in the child's diaper, the other in the toilet.

Ascaris can produce abdominal pain and discomfort, and may lead to malabsorption syndrome, weight loss, or vitamin deficiency. Very large infestations can sometimes lead to intestinal obstruction—I saw a case of this a few years ago, when I was working in Omaha, Neb. The parasite also can migrate to the bile duct and obstruct the liver.

With lower-level infestations, however, the nonspecific epigastric and diffuse abdominal discomfort may be indistinguishable from functional abdominal pain.

However, if the problem persists—or if the child has wheezing or pneumonia symptoms, get a complete blood count. If you see eosinophilia, order an ova and parasite stool exam.

▸ Dientamoeba fragilis. If you trained prior to the 1990s, you probably were taught that D. fragilis is merely a harmless commensal and doesn't need to be treated. However, it has become apparent in the last decade or so that this parasite can cause symptoms, including chronic loose stools, cramps, and flatulence. The child usually doesn't look especially ill but complains of abdominal upset and may have up to three to four loose, mucus-containing stools per day.

And D. fragilis hangs on—after the second week or so, you can be fairly certain it's not rotavirus or another acute gastrointestinal virus. Along with giardia, also think of D. fragilis.

Interestingly, D. fragilis will often piggyback with pinworms, literally sticking itself to the pinworm eggs. Therefore, if you've already treated the child for pinworms and the GI symptoms continue, you might want to order another ova and parasite stool exam. This time, however, special procedures are required. Because this organism is so fragile—hence the name—it deteriorates rapidly at room temperature. Parents should be instructed to collect a fresh stool sample and immediately place it in a preservative-containing pack (we use ParaPak). For the greatest sensitivity, three samples must be collected on separate days. Sensitivity of the test is about 85%–90% for three samples taken on consecutive days, and up to 95% if collected on alternate days.

The order to the lab should request a microscopic exam, not just an antigen screen. Microscopy will pick up not only D. fragilis, but other less common parasitic creatures that you don't want to miss, such as Entamoeba histolytica. Parents must also be told to stop any over-the-counter antidiarrheals such as Kaopectate or Pepto-Bismol 24–48 hours prior to the first stool collection, as these agents will make it difficult to visualize the parasites.

If D. fragilis is identified, treatment is metronidazole three times a day for 10 days. Because of fecal-oral transmission, consider asking the parents if they're experiencing loose stools as well. Symptoms tend not to be as dramatic in adults as in kids, but if they've got D. fragilis and you treat them, they often feel better.

▸ Blastocystis hominis. Although similar to D. fragilis in structure, B. hominis is still considered a commensal and not pathogenic. However, if present in high enough quantities, it can still cause nonspecific abdominal symptoms, loose stools, flatulence, and mucus in the stool. If you do a work-up and find no other explanation for the symptoms, it's not unreasonable to treat using the 10-day metronidazole regimen. Here, too, a microscopic exam is necessary to visualize the cysts in the stool.

Although not known to produce any toxins or direct irritants to the colon, it's possible that B. hominis just has not been investigated closely enough to prove its pathogenicity. New data suggest this may be the case.

We've been seeing more lab reports of both D. fragilis and B. hominis in the last few years. It's not clear whether that's because of increased use of preservative packs or actual increased prevalence.

But we definitely seem to get more calls from parents and physicians about parasites as the weather gets warmer.

Just in time for summer, I thought I'd offer some pointers on parasites.

Of course, parasites exist year round. But as the weather gets warmer and our patients head outside to play in the dirt or splash around in the toddler pool, the possibility that they'll pick up one of the following five organisms increases.

Here they are in approximate order of the frequency that we see them in central Kentucky:

▸ Pinworms. By far the most common parasite seen in preschool children, the diagnosis is usually made by a parent who finds a little wriggling rice-sized creature in the child's diaper, underwear, or bedding. Treatment—liquid mebendazole or chewable pyrantel pamoate—is given once, then repeated about 10–14 days later.

Families should be advised to wash all bed linens in hot water to get rid of any residual eggs and to prevent reinfestation.

If the problem recurs, retreat the child and consider treating the whole family and the child's playmates. If the parent reports a third sighting after two rounds of treatment, I will ask that they actually bring the worm in.

Some parents become so excessively concerned that they misinterpret many things as pinworms. It's been quite interesting—I've seen husks of corn, pea shells, and little bits of mucus that aren't even organisms.

Once, we got back a housefly larvae from a child's stool. I'm not sure how it got there.

We've also seen the proglottid of a tapeworm—these often fold up on themselves, and can almost look like a pinworm. That child had been treated several times for pinworms before referral.

Another pinworm-related problem is that the child may continue to experience perianal or vulvar itching and continue to scratch even after the pinworms are eradicated. Sitz baths may be helpful in easing the irritation. If itching continues, applying 1% hydrocortisone cream to the area for no more than 1 week can often break the itch-scratch cycle.

Pinworms are often an emotional issue for families. It's important to convince parents that it's not because they or their child is dirty, but, rather, that they picked up pinworms from their friends. To diffuse the worry, I often tell parents that the upside of pinworms is that their child likely has good social skills.

▸ Giardia. Toddler pools are a frequent yet underrecognized source of giardia, which are more familiarly associated with food-borne outbreaks or with transmission via fresh water, such as mountain springs.

But “kiddy pools” in the backyard or even at professionally maintained pool complexes are a particularly likely source of giardia transmission. Because they're shallow, sunlight can degrade the chlorine to below the giardia-inhibiting levels, which are higher than needed for coliforms.

If you see more than one giardia patient from the same swim club or backyard pool, advise the swim club pool staff or pool owners to make sure the chlorine level is being monitored more often. We had a giardia outbreak in an upscale country club's pool, and the parents were mortified. Acquisition of giardia in the pool is likely due to other toddlers using the pool in diapers.

Giardia typically presents with diarrhea, cramps, an extreme amount of flatulence, and stools with a characteristic green bubbly appearance. Once you've seen a giardia stool, you will know it again. The diagnosis is made with a routine laboratory ova and parasite screen.

Furazolidone is the treatment of choice, but metronidazole also works. Of course, these are two of the worst-tasting medicines around. You might advise parents to try chasing it with a spoonful of Hershey's syrup. In older kids, a Hershey's Kiss works. No, I receive no funding from Hershey's.

▸ Ascaris. In a typical scenario with ascaris, the parent reports finding a 2- to 4-inch long “fishing worm” in the child's diaper. This is the easy diagnosis.

However, we had a case last year of a 4-year-old who had been diagnosed with asthma and who continued wheezing over an 8-month period despite all the usual asthma medications including a couple rounds of steroids. He had eosinophilia, which had been attributed to allergies.

As it turned out, this child did not have asthma at all, but rather a classic case of Loeffler's pneumonia, in which the ascaris larvae had migrated to his lungs, triggering eosinophilia and an asthma-like picture. We treated the child with mebendazole twice a day for 3 days, and both the wheezing and the eosinophilia disappeared. The child didn't wheeze thereafter.

Ascaris was far more common in years past. These days we've become such a clean society we just don't see it as much as we used to and it's dropped off the radar screen. Yet, in addition to the pulmonary case, we've actually had two more classical ascaris cases just in the last month—one was spotted by the mother in the child's diaper, the other in the toilet.

Ascaris can produce abdominal pain and discomfort, and may lead to malabsorption syndrome, weight loss, or vitamin deficiency. Very large infestations can sometimes lead to intestinal obstruction—I saw a case of this a few years ago, when I was working in Omaha, Neb. The parasite also can migrate to the bile duct and obstruct the liver.

With lower-level infestations, however, the nonspecific epigastric and diffuse abdominal discomfort may be indistinguishable from functional abdominal pain.

However, if the problem persists—or if the child has wheezing or pneumonia symptoms, get a complete blood count. If you see eosinophilia, order an ova and parasite stool exam.

▸ Dientamoeba fragilis. If you trained prior to the 1990s, you probably were taught that D. fragilis is merely a harmless commensal and doesn't need to be treated. However, it has become apparent in the last decade or so that this parasite can cause symptoms, including chronic loose stools, cramps, and flatulence. The child usually doesn't look especially ill but complains of abdominal upset and may have up to three to four loose, mucus-containing stools per day.

And D. fragilis hangs on—after the second week or so, you can be fairly certain it's not rotavirus or another acute gastrointestinal virus. Along with giardia, also think of D. fragilis.

Interestingly, D. fragilis will often piggyback with pinworms, literally sticking itself to the pinworm eggs. Therefore, if you've already treated the child for pinworms and the GI symptoms continue, you might want to order another ova and parasite stool exam. This time, however, special procedures are required. Because this organism is so fragile—hence the name—it deteriorates rapidly at room temperature. Parents should be instructed to collect a fresh stool sample and immediately place it in a preservative-containing pack (we use ParaPak). For the greatest sensitivity, three samples must be collected on separate days. Sensitivity of the test is about 85%–90% for three samples taken on consecutive days, and up to 95% if collected on alternate days.

The order to the lab should request a microscopic exam, not just an antigen screen. Microscopy will pick up not only D. fragilis, but other less common parasitic creatures that you don't want to miss, such as Entamoeba histolytica. Parents must also be told to stop any over-the-counter antidiarrheals such as Kaopectate or Pepto-Bismol 24–48 hours prior to the first stool collection, as these agents will make it difficult to visualize the parasites.

If D. fragilis is identified, treatment is metronidazole three times a day for 10 days. Because of fecal-oral transmission, consider asking the parents if they're experiencing loose stools as well. Symptoms tend not to be as dramatic in adults as in kids, but if they've got D. fragilis and you treat them, they often feel better.

▸ Blastocystis hominis. Although similar to D. fragilis in structure, B. hominis is still considered a commensal and not pathogenic. However, if present in high enough quantities, it can still cause nonspecific abdominal symptoms, loose stools, flatulence, and mucus in the stool. If you do a work-up and find no other explanation for the symptoms, it's not unreasonable to treat using the 10-day metronidazole regimen. Here, too, a microscopic exam is necessary to visualize the cysts in the stool.

Although not known to produce any toxins or direct irritants to the colon, it's possible that B. hominis just has not been investigated closely enough to prove its pathogenicity. New data suggest this may be the case.

We've been seeing more lab reports of both D. fragilis and B. hominis in the last few years. It's not clear whether that's because of increased use of preservative packs or actual increased prevalence.

But we definitely seem to get more calls from parents and physicians about parasites as the weather gets warmer.