ID Consult

Recent guidelines for the treatment of acute bacterial sinusitis and otitis media advise physicians to do something that most of us were taught never to do: Use a cephalosporin in a penicillin-allergic patient. Unfortunately, those documents neglected to explain why this once-taboo practice is now the standard of care.

The American Academy of Pediatrics' clinical practice guidelines for the management of sinusitis endorse the use of cefuroxime, cefpodoxime, ceftriaxone, and cefdinir for penicillin-allergic patients in whom the previous penicillin reaction was not severe (Pediatrics 2001;108:798-808), while the guidelines for the diagnosis and management of acute otitis media support the use of the same three oral cephalosporins in patients with “non-type-1 allergy” and ceftriaxone for type 1 allergy (Pediatrics 2004;113:1451-65).

Although the two documents are evidence based and have been endorsed by several other professional groups including the American Academy of Family Physicians, many clinicians have not embraced the recommendation because of the often-cited yet inaccurate statistic that there is a 10% rate of cross-sensitivity to cephalosporins among penicillin-allergic patients.

In fact, the risk that a patient with a history of penicillin allergy will experience a reaction to a first-generation cephalosporin is not more than 0.5%, to a second-generation cephalosporin, not more than 0.2%, and to a third-generation cephalosporin, practically nil. In at least 25 studies, cephalosporins were actually given to penicillin-allergic patients with reaction rates not greater than in non-allergic patients. I have reviewed this literature in the April issue of Pediatrics (2005;115:1048-57).

The misconception arose out of the belief that the cross-reactivity is to the shared β-lactam ring.

Now, however, we know that the β-lactam ring of cephalosporins—unlike that of penicillin and ampicillin—becomes rapidly degraded, so that antibodies are instead targeted to side chain structures. Therefore, cross-reactivity is only possible with the cephalosporins that share penicillin side chains. (See chart.) And even then, the likelihood of a reaction is still far less than 10%.

Many of the older studies suggesting greater rates of cross-reactivity were conducted with penicillin and/or amoxicillin that had been made with Cephalosporium mold, which of course would have caused cross-contamination. Yet, the caution remains in the package label for most cephalosporins.

Patients and physicians alike tend to use the term “allergy” very loosely. But unless the patient experienced a generalized pruritic skin reaction, hives, or anaphylaxis, it was not an IgE-mediated (type 1) reaction.

For patients who do report a true allergic history—or who have had a positive skin test—it would be prudent to avoid the four cephalosporins with side chains similar to amoxicillin—namely cefaclor, cefprozil, cephalexin, and cefadroxil. All other cephalosporins are acceptable, including the four endorsed in the sinusitis/otitis guidelines.

Consider that a major reason for the new guidelines is the increasing rates of macrolide-resistant Streptococcus pneumoniae. The rate was 35% in 2002, and it has been rising since. Therefore, the old paradigm of simply putting a penicillin-allergic patient on azithromycin or clarithromycin is no longer good medicine—in doing so, you are substantially compromising the anticipated efficacy of the drug.

There has never been a case of fatal anaphylaxis with a cephalosporin reported in a child. From a medicolegal standpoint, if the AAP/AAFP guideline says you can use a cephalosporin in a penicillin-allergic patient—as does my evidence-based peer reviewed article in AAP's journal, Pediatrics—rest assured you can do it.

Cross-Reactivity Between Penicillins and Cephalosporins

Contrary to long-held belief, the risk of cross-reactivity between penicillins and cephalosporins is based on the similarities of their side-chain structures, not of the b-lactam ring they all share. The three lists below are grouped by side-chain similarity (or lack thereof in the third group). However, even within groups with related side chains, the risk that a patient with a history of sensitivity to one drug will have a reaction to another is still no more than 0.5%.

Recent guidelines for the treatment of acute bacterial sinusitis and otitis media advise physicians to do something that most of us were taught never to do: Use a cephalosporin in a penicillin-allergic patient. Unfortunately, those documents neglected to explain why this once-taboo practice is now the standard of care.

The American Academy of Pediatrics' clinical practice guidelines for the management of sinusitis endorse the use of cefuroxime, cefpodoxime, ceftriaxone, and cefdinir for penicillin-allergic patients in whom the previous penicillin reaction was not severe (Pediatrics 2001;108:798-808), while the guidelines for the diagnosis and management of acute otitis media support the use of the same three oral cephalosporins in patients with “non-type-1 allergy” and ceftriaxone for type 1 allergy (Pediatrics 2004;113:1451-65).

Although the two documents are evidence based and have been endorsed by several other professional groups including the American Academy of Family Physicians, many clinicians have not embraced the recommendation because of the often-cited yet inaccurate statistic that there is a 10% rate of cross-sensitivity to cephalosporins among penicillin-allergic patients.

In fact, the risk that a patient with a history of penicillin allergy will experience a reaction to a first-generation cephalosporin is not more than 0.5%, to a second-generation cephalosporin, not more than 0.2%, and to a third-generation cephalosporin, practically nil. In at least 25 studies, cephalosporins were actually given to penicillin-allergic patients with reaction rates not greater than in non-allergic patients. I have reviewed this literature in the April issue of Pediatrics (2005;115:1048-57).

The misconception arose out of the belief that the cross-reactivity is to the shared β-lactam ring.

Now, however, we know that the β-lactam ring of cephalosporins—unlike that of penicillin and ampicillin—becomes rapidly degraded, so that antibodies are instead targeted to side chain structures. Therefore, cross-reactivity is only possible with the cephalosporins that share penicillin side chains. (See chart.) And even then, the likelihood of a reaction is still far less than 10%.

Many of the older studies suggesting greater rates of cross-reactivity were conducted with penicillin and/or amoxicillin that had been made with Cephalosporium mold, which of course would have caused cross-contamination. Yet, the caution remains in the package label for most cephalosporins.

Patients and physicians alike tend to use the term “allergy” very loosely. But unless the patient experienced a generalized pruritic skin reaction, hives, or anaphylaxis, it was not an IgE-mediated (type 1) reaction.

For patients who do report a true allergic history—or who have had a positive skin test—it would be prudent to avoid the four cephalosporins with side chains similar to amoxicillin—namely cefaclor, cefprozil, cephalexin, and cefadroxil. All other cephalosporins are acceptable, including the four endorsed in the sinusitis/otitis guidelines.

Consider that a major reason for the new guidelines is the increasing rates of macrolide-resistant Streptococcus pneumoniae. The rate was 35% in 2002, and it has been rising since. Therefore, the old paradigm of simply putting a penicillin-allergic patient on azithromycin or clarithromycin is no longer good medicine—in doing so, you are substantially compromising the anticipated efficacy of the drug.

There has never been a case of fatal anaphylaxis with a cephalosporin reported in a child. From a medicolegal standpoint, if the AAP/AAFP guideline says you can use a cephalosporin in a penicillin-allergic patient—as does my evidence-based peer reviewed article in AAP's journal, Pediatrics—rest assured you can do it.

Cross-Reactivity Between Penicillins and Cephalosporins

Contrary to long-held belief, the risk of cross-reactivity between penicillins and cephalosporins is based on the similarities of their side-chain structures, not of the b-lactam ring they all share. The three lists below are grouped by side-chain similarity (or lack thereof in the third group). However, even within groups with related side chains, the risk that a patient with a history of sensitivity to one drug will have a reaction to another is still no more than 0.5%.

Recent guidelines for the treatment of acute bacterial sinusitis and otitis media advise physicians to do something that most of us were taught never to do: Use a cephalosporin in a penicillin-allergic patient. Unfortunately, those documents neglected to explain why this once-taboo practice is now the standard of care.

The American Academy of Pediatrics' clinical practice guidelines for the management of sinusitis endorse the use of cefuroxime, cefpodoxime, ceftriaxone, and cefdinir for penicillin-allergic patients in whom the previous penicillin reaction was not severe (Pediatrics 2001;108:798-808), while the guidelines for the diagnosis and management of acute otitis media support the use of the same three oral cephalosporins in patients with “non-type-1 allergy” and ceftriaxone for type 1 allergy (Pediatrics 2004;113:1451-65).

Although the two documents are evidence based and have been endorsed by several other professional groups including the American Academy of Family Physicians, many clinicians have not embraced the recommendation because of the often-cited yet inaccurate statistic that there is a 10% rate of cross-sensitivity to cephalosporins among penicillin-allergic patients.

In fact, the risk that a patient with a history of penicillin allergy will experience a reaction to a first-generation cephalosporin is not more than 0.5%, to a second-generation cephalosporin, not more than 0.2%, and to a third-generation cephalosporin, practically nil. In at least 25 studies, cephalosporins were actually given to penicillin-allergic patients with reaction rates not greater than in non-allergic patients. I have reviewed this literature in the April issue of Pediatrics (2005;115:1048-57).

The misconception arose out of the belief that the cross-reactivity is to the shared β-lactam ring.

Now, however, we know that the β-lactam ring of cephalosporins—unlike that of penicillin and ampicillin—becomes rapidly degraded, so that antibodies are instead targeted to side chain structures. Therefore, cross-reactivity is only possible with the cephalosporins that share penicillin side chains. (See chart.) And even then, the likelihood of a reaction is still far less than 10%.

Many of the older studies suggesting greater rates of cross-reactivity were conducted with penicillin and/or amoxicillin that had been made with Cephalosporium mold, which of course would have caused cross-contamination. Yet, the caution remains in the package label for most cephalosporins.

Patients and physicians alike tend to use the term “allergy” very loosely. But unless the patient experienced a generalized pruritic skin reaction, hives, or anaphylaxis, it was not an IgE-mediated (type 1) reaction.

For patients who do report a true allergic history—or who have had a positive skin test—it would be prudent to avoid the four cephalosporins with side chains similar to amoxicillin—namely cefaclor, cefprozil, cephalexin, and cefadroxil. All other cephalosporins are acceptable, including the four endorsed in the sinusitis/otitis guidelines.

Consider that a major reason for the new guidelines is the increasing rates of macrolide-resistant Streptococcus pneumoniae. The rate was 35% in 2002, and it has been rising since. Therefore, the old paradigm of simply putting a penicillin-allergic patient on azithromycin or clarithromycin is no longer good medicine—in doing so, you are substantially compromising the anticipated efficacy of the drug.

There has never been a case of fatal anaphylaxis with a cephalosporin reported in a child. From a medicolegal standpoint, if the AAP/AAFP guideline says you can use a cephalosporin in a penicillin-allergic patient—as does my evidence-based peer reviewed article in AAP's journal, Pediatrics—rest assured you can do it.

Cross-Reactivity Between Penicillins and Cephalosporins

Contrary to long-held belief, the risk of cross-reactivity between penicillins and cephalosporins is based on the similarities of their side-chain structures, not of the b-lactam ring they all share. The three lists below are grouped by side-chain similarity (or lack thereof in the third group). However, even within groups with related side chains, the risk that a patient with a history of sensitivity to one drug will have a reaction to another is still no more than 0.5%.

We've made great strides in combating pediatric HIV/AIDS in the last few years, but children living with HIV still face enormous difficulties.

Indeed, the number of new cases of vertical transmission has dropped to an all-time low, from about 1,000 in the early 1990's to less than 50 in 2003. The obstetric community is now doing a far better job of identifying women with HIV; delivering medical care to them; and, thereby, reducing the rate of vertical transmission to just 1%-2%, from 25%-30% in the 1990's.

Unfortunately, this great success in reducing vertical transmission and the effectiveness of highly active antiretroviral treatment (HAART) in maintaining immune function in HIV-infected children has created a public perception that pediatric HIV/AIDS is no longer an issue.

In fact, there are approximately 5,000 children currently living with HIV/AIDS in the United States, with 250 of them here in Massachusetts. These children have substantial, ongoing problems that place them at increasing risk as they get older. Ongoing services will be required to meet their needs, as will innovative research to ensure that our current approach is safe and effective over a prolonged time period.

Yet, as a result of a shift in public focus to HIV in Africa, there has been a dramatic decrease in both federal and private funds for HIV here in the United States. In Massachusetts, for example, money for HIV programs has declined about 40% in the last 5 years, from about $50 million to about $30 million, without any decline in the number of patients needing services.

Although the numbers of vertically infected newborns have dropped dramatically in the United States, a small number of cases still occur when a woman is tested early in pregnancy and is found to be uninfected, but then acquires the infection later during pregnancy, prior to delivery. We've had a couple of cases in the last year or 2, in which the infant has presented with advanced HIV in the first 6 months of life.

Moreover, increasing numbers of HIV-infected pregnant women and children are coming to the United States from other countries. We currently have two new patients—one is an HIV-infected child from Haiti who was adopted by a New Hampshire couple, the other the child of a mother who had recently come from Cape Verde.

But by far, the greatest number of new cases of pediatric HIV in the United States is now among adolescents who acquire the infection through risky behavior. We see a newly infected adolescent every few months.

Once adolescents become infected with HIV, it can be a challenge to engage them, to convince them that they must take their medications regularly even though they're feeling fine, and to be responsible with regard to their sexual behavior. We've had several of our teenage HIV-infected girls become pregnant, and some of our boys have fathered babies.

Regardless of how children acquire HIV, they face significant health challenges despite the dramatic increase in lifespan that has come with the success of HAART.

Resistance is a major problem. About 50% of all HIV-infected children have some degree of resistance to at least one of the currently licensed antiretroviral agents, while about 10%-15% are completely out of treatment options. The latter scenario, which arises after long-term treatment with multiple agents from multiple classes, will likely only get worse with time.

Unfortunately, there have been no major breakthroughs in terms of new drug classes introduced for the treatment of pediatric HIV in the last 3-4 years. The problem is particularly bad for younger children who can't take large capsules and are relegated to taking liquids or suspensions. The best of these are poor tasting, and the worst ones are foul tasting. Many children simply refuse to take them and end up with inadequate dosing, which increases their risk for developing resistance.

Among the 10%-15% of children whose viruses have mutated to the point that they are 100-fold less susceptible than are wild-type viruses, the only options are to try using five or six different medications, often in combination with a relatively new agent called T20. But T20 can only be given by injection, which is a problem in children. We have one patient on the drug, a very slender boy who now has exquisitely sensitive nodules all over his arms.

The metabolic and cardiovascular changes we're seeing in adults on long-term HAART therapy are also a major cause for concern among children. Although we haven't seen coronary artery disease yet in children, some do have quite high cholesterol and triglyceride levels. I have one child right now with a cholesterol level of more than 700 mg/dL, with visible deposits in his elbows and knees.

My expectation is that our adult medicine colleagues are the ones who will see serious heart disease in these patients, probably in their 20s or 30s, just as the adults are now getting coronary artery disease in their 30s, 40s, and 50s. Currently there is disagreement about how aggressively to treat cardiovascular risk factors in these children. Some argue that these kids have HIV and we should simply leave them alone. My attitude is that because these children have HIV and may live into their 50s, 60s, or 70s, we can't afford to leave them alone.

Body changes—typically increased weight and fat deposition in the trunk—are also a major problem, especially for the teenagers. Girls often have enlarged breasts, big abdomens, a “buffalo hump,” and very large shoulders. Boys tend to develop barrel chests and gynecomastia. As you can imagine, these changes are quite disturbing to teenagers, and may lead them to stop taking their medications. While this syndrome, lipodystrophy, is being extensively studied in adults, little progress has been made in understanding its pathogenesis in children and adolescents.

Disclosure may be yet another problem for many HIV-infected teenagers. We've had several young adolescent patients who don't know their diagnosis. The parents often think they're protecting their kids by not telling them, but we believe that the more the children know, the more likely they are to take an active part in their own care as they mature. We begin discussing disclosure with families when their child reaches 8-10 years of age, depending on individual maturity and intellectual capacity.

A fourth cause for concern—and possibly the greatest—comes from a recent study published by the Pediatric AIDS Clinical Trials Group, in which I participate. We found that neuropsychological function was significantly poorer among HIV-infected children, and was worse with higher viral loads. Moreover, only one measure of neuropsychological functioning improved after effective viral suppression with combination protease inhibitor therapy, and that improvement was relatively minor (Pediatrics 2005;115:380-7).

While it had been previously recognized that HIV-infected children have cognitive and behavioral difficulties, this is the first time it has been looked at with regard to response to HAART therapy. Although the correlation with viral load suggests the problem is disease related, we have not yet determined the relative contributions of disease, treatment, and the often adverse socioeconomic environments these children live in.

We must continue to search for better and safer approaches to preventing vertical transmission. Currently, we give antiretrovirals as early as the second trimester, continue them through labor and delivery, and in the newborn for up to 6 weeks. With all the new drugs that are being introduced, we must be certain that the therapies we're delivering are safe. Now that 98%-99% of these children won't have HIV, we have to make sure they don't have toxicity from the medications, either.

We need to find safer regimens without losing what we've accomplished in preventing vertical transmission, which is in my mind the biggest accomplishment in the prevention of HIV to date.

We've made great strides in combating pediatric HIV/AIDS in the last few years, but children living with HIV still face enormous difficulties.

Indeed, the number of new cases of vertical transmission has dropped to an all-time low, from about 1,000 in the early 1990's to less than 50 in 2003. The obstetric community is now doing a far better job of identifying women with HIV; delivering medical care to them; and, thereby, reducing the rate of vertical transmission to just 1%-2%, from 25%-30% in the 1990's.

Unfortunately, this great success in reducing vertical transmission and the effectiveness of highly active antiretroviral treatment (HAART) in maintaining immune function in HIV-infected children has created a public perception that pediatric HIV/AIDS is no longer an issue.

In fact, there are approximately 5,000 children currently living with HIV/AIDS in the United States, with 250 of them here in Massachusetts. These children have substantial, ongoing problems that place them at increasing risk as they get older. Ongoing services will be required to meet their needs, as will innovative research to ensure that our current approach is safe and effective over a prolonged time period.

Yet, as a result of a shift in public focus to HIV in Africa, there has been a dramatic decrease in both federal and private funds for HIV here in the United States. In Massachusetts, for example, money for HIV programs has declined about 40% in the last 5 years, from about $50 million to about $30 million, without any decline in the number of patients needing services.

Although the numbers of vertically infected newborns have dropped dramatically in the United States, a small number of cases still occur when a woman is tested early in pregnancy and is found to be uninfected, but then acquires the infection later during pregnancy, prior to delivery. We've had a couple of cases in the last year or 2, in which the infant has presented with advanced HIV in the first 6 months of life.

Moreover, increasing numbers of HIV-infected pregnant women and children are coming to the United States from other countries. We currently have two new patients—one is an HIV-infected child from Haiti who was adopted by a New Hampshire couple, the other the child of a mother who had recently come from Cape Verde.

But by far, the greatest number of new cases of pediatric HIV in the United States is now among adolescents who acquire the infection through risky behavior. We see a newly infected adolescent every few months.

Once adolescents become infected with HIV, it can be a challenge to engage them, to convince them that they must take their medications regularly even though they're feeling fine, and to be responsible with regard to their sexual behavior. We've had several of our teenage HIV-infected girls become pregnant, and some of our boys have fathered babies.

Regardless of how children acquire HIV, they face significant health challenges despite the dramatic increase in lifespan that has come with the success of HAART.

Resistance is a major problem. About 50% of all HIV-infected children have some degree of resistance to at least one of the currently licensed antiretroviral agents, while about 10%-15% are completely out of treatment options. The latter scenario, which arises after long-term treatment with multiple agents from multiple classes, will likely only get worse with time.

Unfortunately, there have been no major breakthroughs in terms of new drug classes introduced for the treatment of pediatric HIV in the last 3-4 years. The problem is particularly bad for younger children who can't take large capsules and are relegated to taking liquids or suspensions. The best of these are poor tasting, and the worst ones are foul tasting. Many children simply refuse to take them and end up with inadequate dosing, which increases their risk for developing resistance.

Among the 10%-15% of children whose viruses have mutated to the point that they are 100-fold less susceptible than are wild-type viruses, the only options are to try using five or six different medications, often in combination with a relatively new agent called T20. But T20 can only be given by injection, which is a problem in children. We have one patient on the drug, a very slender boy who now has exquisitely sensitive nodules all over his arms.

The metabolic and cardiovascular changes we're seeing in adults on long-term HAART therapy are also a major cause for concern among children. Although we haven't seen coronary artery disease yet in children, some do have quite high cholesterol and triglyceride levels. I have one child right now with a cholesterol level of more than 700 mg/dL, with visible deposits in his elbows and knees.

My expectation is that our adult medicine colleagues are the ones who will see serious heart disease in these patients, probably in their 20s or 30s, just as the adults are now getting coronary artery disease in their 30s, 40s, and 50s. Currently there is disagreement about how aggressively to treat cardiovascular risk factors in these children. Some argue that these kids have HIV and we should simply leave them alone. My attitude is that because these children have HIV and may live into their 50s, 60s, or 70s, we can't afford to leave them alone.

Body changes—typically increased weight and fat deposition in the trunk—are also a major problem, especially for the teenagers. Girls often have enlarged breasts, big abdomens, a “buffalo hump,” and very large shoulders. Boys tend to develop barrel chests and gynecomastia. As you can imagine, these changes are quite disturbing to teenagers, and may lead them to stop taking their medications. While this syndrome, lipodystrophy, is being extensively studied in adults, little progress has been made in understanding its pathogenesis in children and adolescents.

Disclosure may be yet another problem for many HIV-infected teenagers. We've had several young adolescent patients who don't know their diagnosis. The parents often think they're protecting their kids by not telling them, but we believe that the more the children know, the more likely they are to take an active part in their own care as they mature. We begin discussing disclosure with families when their child reaches 8-10 years of age, depending on individual maturity and intellectual capacity.

A fourth cause for concern—and possibly the greatest—comes from a recent study published by the Pediatric AIDS Clinical Trials Group, in which I participate. We found that neuropsychological function was significantly poorer among HIV-infected children, and was worse with higher viral loads. Moreover, only one measure of neuropsychological functioning improved after effective viral suppression with combination protease inhibitor therapy, and that improvement was relatively minor (Pediatrics 2005;115:380-7).

While it had been previously recognized that HIV-infected children have cognitive and behavioral difficulties, this is the first time it has been looked at with regard to response to HAART therapy. Although the correlation with viral load suggests the problem is disease related, we have not yet determined the relative contributions of disease, treatment, and the often adverse socioeconomic environments these children live in.

We must continue to search for better and safer approaches to preventing vertical transmission. Currently, we give antiretrovirals as early as the second trimester, continue them through labor and delivery, and in the newborn for up to 6 weeks. With all the new drugs that are being introduced, we must be certain that the therapies we're delivering are safe. Now that 98%-99% of these children won't have HIV, we have to make sure they don't have toxicity from the medications, either.

We need to find safer regimens without losing what we've accomplished in preventing vertical transmission, which is in my mind the biggest accomplishment in the prevention of HIV to date.

We've made great strides in combating pediatric HIV/AIDS in the last few years, but children living with HIV still face enormous difficulties.

Indeed, the number of new cases of vertical transmission has dropped to an all-time low, from about 1,000 in the early 1990's to less than 50 in 2003. The obstetric community is now doing a far better job of identifying women with HIV; delivering medical care to them; and, thereby, reducing the rate of vertical transmission to just 1%-2%, from 25%-30% in the 1990's.

Unfortunately, this great success in reducing vertical transmission and the effectiveness of highly active antiretroviral treatment (HAART) in maintaining immune function in HIV-infected children has created a public perception that pediatric HIV/AIDS is no longer an issue.

In fact, there are approximately 5,000 children currently living with HIV/AIDS in the United States, with 250 of them here in Massachusetts. These children have substantial, ongoing problems that place them at increasing risk as they get older. Ongoing services will be required to meet their needs, as will innovative research to ensure that our current approach is safe and effective over a prolonged time period.

Yet, as a result of a shift in public focus to HIV in Africa, there has been a dramatic decrease in both federal and private funds for HIV here in the United States. In Massachusetts, for example, money for HIV programs has declined about 40% in the last 5 years, from about $50 million to about $30 million, without any decline in the number of patients needing services.

Although the numbers of vertically infected newborns have dropped dramatically in the United States, a small number of cases still occur when a woman is tested early in pregnancy and is found to be uninfected, but then acquires the infection later during pregnancy, prior to delivery. We've had a couple of cases in the last year or 2, in which the infant has presented with advanced HIV in the first 6 months of life.

Moreover, increasing numbers of HIV-infected pregnant women and children are coming to the United States from other countries. We currently have two new patients—one is an HIV-infected child from Haiti who was adopted by a New Hampshire couple, the other the child of a mother who had recently come from Cape Verde.

But by far, the greatest number of new cases of pediatric HIV in the United States is now among adolescents who acquire the infection through risky behavior. We see a newly infected adolescent every few months.

Once adolescents become infected with HIV, it can be a challenge to engage them, to convince them that they must take their medications regularly even though they're feeling fine, and to be responsible with regard to their sexual behavior. We've had several of our teenage HIV-infected girls become pregnant, and some of our boys have fathered babies.

Regardless of how children acquire HIV, they face significant health challenges despite the dramatic increase in lifespan that has come with the success of HAART.

Resistance is a major problem. About 50% of all HIV-infected children have some degree of resistance to at least one of the currently licensed antiretroviral agents, while about 10%-15% are completely out of treatment options. The latter scenario, which arises after long-term treatment with multiple agents from multiple classes, will likely only get worse with time.

Unfortunately, there have been no major breakthroughs in terms of new drug classes introduced for the treatment of pediatric HIV in the last 3-4 years. The problem is particularly bad for younger children who can't take large capsules and are relegated to taking liquids or suspensions. The best of these are poor tasting, and the worst ones are foul tasting. Many children simply refuse to take them and end up with inadequate dosing, which increases their risk for developing resistance.

Among the 10%-15% of children whose viruses have mutated to the point that they are 100-fold less susceptible than are wild-type viruses, the only options are to try using five or six different medications, often in combination with a relatively new agent called T20. But T20 can only be given by injection, which is a problem in children. We have one patient on the drug, a very slender boy who now has exquisitely sensitive nodules all over his arms.

The metabolic and cardiovascular changes we're seeing in adults on long-term HAART therapy are also a major cause for concern among children. Although we haven't seen coronary artery disease yet in children, some do have quite high cholesterol and triglyceride levels. I have one child right now with a cholesterol level of more than 700 mg/dL, with visible deposits in his elbows and knees.

My expectation is that our adult medicine colleagues are the ones who will see serious heart disease in these patients, probably in their 20s or 30s, just as the adults are now getting coronary artery disease in their 30s, 40s, and 50s. Currently there is disagreement about how aggressively to treat cardiovascular risk factors in these children. Some argue that these kids have HIV and we should simply leave them alone. My attitude is that because these children have HIV and may live into their 50s, 60s, or 70s, we can't afford to leave them alone.

Body changes—typically increased weight and fat deposition in the trunk—are also a major problem, especially for the teenagers. Girls often have enlarged breasts, big abdomens, a “buffalo hump,” and very large shoulders. Boys tend to develop barrel chests and gynecomastia. As you can imagine, these changes are quite disturbing to teenagers, and may lead them to stop taking their medications. While this syndrome, lipodystrophy, is being extensively studied in adults, little progress has been made in understanding its pathogenesis in children and adolescents.

Disclosure may be yet another problem for many HIV-infected teenagers. We've had several young adolescent patients who don't know their diagnosis. The parents often think they're protecting their kids by not telling them, but we believe that the more the children know, the more likely they are to take an active part in their own care as they mature. We begin discussing disclosure with families when their child reaches 8-10 years of age, depending on individual maturity and intellectual capacity.

A fourth cause for concern—and possibly the greatest—comes from a recent study published by the Pediatric AIDS Clinical Trials Group, in which I participate. We found that neuropsychological function was significantly poorer among HIV-infected children, and was worse with higher viral loads. Moreover, only one measure of neuropsychological functioning improved after effective viral suppression with combination protease inhibitor therapy, and that improvement was relatively minor (Pediatrics 2005;115:380-7).

While it had been previously recognized that HIV-infected children have cognitive and behavioral difficulties, this is the first time it has been looked at with regard to response to HAART therapy. Although the correlation with viral load suggests the problem is disease related, we have not yet determined the relative contributions of disease, treatment, and the often adverse socioeconomic environments these children live in.

We must continue to search for better and safer approaches to preventing vertical transmission. Currently, we give antiretrovirals as early as the second trimester, continue them through labor and delivery, and in the newborn for up to 6 weeks. With all the new drugs that are being introduced, we must be certain that the therapies we're delivering are safe. Now that 98%-99% of these children won't have HIV, we have to make sure they don't have toxicity from the medications, either.

We need to find safer regimens without losing what we've accomplished in preventing vertical transmission, which is in my mind the biggest accomplishment in the prevention of HIV to date.

When it comes to imaging studies for suspected infections in children, sometimes you have to pull out bigger guns. CT and MRI are expensive, stressful to the child, and may require sedation, so we don't use them as first-line tools. But three recent cases illustrate that these modalities may be needed when your suspicions are not borne out by routine imaging.

Case 1: An 8-year-old girl with 3 days of abdominal pain was initially diagnosed via ultrasound (US) at an outlying hospital as having constipation and was treated with an enema. Her pain resolved, but she then returned 5 days later with more intensity, low grade fever, and flank tenderness.

Complete blood count showed 18,300 white blood cells/μL with 70% neutrophils and 412,000 platelets/μL. In the prior year, she'd had three culture-confirmed urinary tract infections due to Escherichia coli that was susceptible to trimethoprim/sulfamethoxazole and cephalexin, with normal renal US and vesicoureterogram. Pyelonephritis was considered, but this time the only urinalysis abnormality was 11 WBC. The urine culture was negative, as was a second US.

She was referred to our hospital. Because US has a nearly 40% false-negative rate for renal abscesses, we obtained an abdominal CT scan. In many cases, abscesses are too small (2 cm or less) to be seen on US. In this child, however, the abscess was large (most of the upper half of her kidney).

The success of US depends upon differences in density creating an echo. Because the uniform consistency of this abscess closely matched that of the kidney, it didn't reflect echoes needed to “see” the abscess.

Ultrasound can be ideal when screening for renal abscesses because of ease of performance: When it's positive, you're done. But if it's negative and you remain suspicious, you need a CT scan with contrast (> 90% sensitive) because US can't definitively rule out a renal or perinephric abscess.

Case 2: Neither routine radiographs (which were normal) nor bone scan (with questionable signal in knee joint area) revealed the cause for a swollen knee and failure to bear weight in a 13-month-old boy.

Joint fluid glucose was normal, and his cell count was 3,800 WBC/μL, less than you'd expect with pyarthrosis. Culture of knee joint fluid was negative. He was diagnosed as having tenosynovitis and treated with ibuprofen.

The swelling was reduced after the tap, but the boy returned 5 days later with a limp. Another plain x-ray was read as normal. Vancomycin was started for “culture-negative” pyarthrosis, fearing methicillin-resistant Staphylococcus aureus. The swelling only marginally improved in the next 4 days, so he was referred to us.

We obtained an MRI. Sure enough, his bone marrow lit up, and there was a defect in his distal femur. He had osteomyelitis with a sympathetic effusion in the knee joint, explaining the negative joint fluid culture.

Plain x-rays often miss early bone infection because prepubertal children have uncalcified areas in their distal long bones. An x-ray “sees” infection as changes in calcium density via defects in already calcified bone or new reactive bone formation around infected but previously uncalcified areas.

Thus, children with incompletely calcified long bones can have osteomyelitis for 10–14 days without visible bony changes on x-ray.

Bone scan findings also had been falsely negative, possibly because the technetium used to localize the infection couldn't enter the infected area due to the expanding pressure of the infection, thus limiting local blood supply.

Plain x-ray and bone scan for osteomyelitis are indeed easier and cheaper than MRI, and in most cases, they are sufficient. However, in this case there were signals that could have triggered an MRI sooner, including a negative joint fluid culture (but this may be true in 30% of septic arthritis cases, so it's only a partial clue) and the relatively normal joint fluid findings. While acute tenosynovitis may be a logical initial diagnosis, the ibuprofen failure points in another direction, i.e., MRI to rule out bone or other soft tissue focus.

An MRI also will pinpoint the focus to allow culture by bone aspiration. Cultures before or early in the antibiotic course can direct antibiotics based on susceptibilities, thereby allowing for intravenous therapy for 5–7 days and then use of oral drug with the same activity to finish the 4- to 6-week regimen.

An early MRI, although expensive, can end up being cost effective by showing where to culture and potentially reducing overall antibiotic costs. Without a cultured pathogen, patients “responding” to broad antibiotics such as vancomycin are necessarily kept on this intravenous drug for the whole course.

Case 3: Our third case was a 13-month-old boy with 2 days of abdominal pain and fever, plus elevated WBC count, sedimentation rate, and C-reactive protein. The child lay rigidly in bed, not allowing anyone to roll him over, move his right leg, or touch his lower right abdomen. His examination initially suggested appendicitis. However, both abdominal x-ray and CT scans were normal.

Our differential diagnosis expanded to include pelvic osteomyelitis, diskitis, or an iliopsoas abscess with referred pain to the hip and abdomen.

A bone scan revealed no abnormality of the iliopsoas area, the sacroiliac joint, or the disks. But we were surprised to see an enhanced signal in the soft tissues near the right side of the pelvis.

An MRI (pelvis to thighs) clearly showed a large abscess in his adductor muscle group. The CT, it turned out, had cut off just above the abscess. He dramatically improved within 48 hours after incision and drainage followed by intravenous antibiotics.

Infections of the lower pelvis (pubis or ischium) or nearby soft tissues are difficult to diagnose in children, who have a hard time localizing the pain. In this child's case, the bone scan, which can image the whole body, helped us locate an area of increased vascularity, so we could confidently order the MRI of the correct part of the abscess.

Probably less than 5% of osteomyelitis or soft tissue abscesses are located in the lower pelvis area. With our patient, a key finding was his refusal to allow lateral movement of his right leg. We assumed that meant a problem was in his sacroiliac joint or muscle groups in his back. We didn't think about the muscles right there in his thigh. This was a reminder to us to think outside the “box,” including the lower pelvic bones and the muscles that attach to those bones.

Abdominal CT of an 8-year-old girl shows a large, uniform abscess filling most of the upper half of her kidney. Because its density was so uniform and similar to kidney tissue, ultrasound had missed it.

An MRI reveals osteomyelitis in the distal femur of a 13-month-old limping boy with sympathetic effusion in his knee joint, which had confused the clinical picture.

In a 13-month-old boy with abdominal pain, lower-body MRI captured what a bone scan had helped localize: A large abscess in the adductor muscle group, below the point where a prior abdominal CT scan had cut off. Photo Courtesy Dr. Christopher J. Harrison

When it comes to imaging studies for suspected infections in children, sometimes you have to pull out bigger guns. CT and MRI are expensive, stressful to the child, and may require sedation, so we don't use them as first-line tools. But three recent cases illustrate that these modalities may be needed when your suspicions are not borne out by routine imaging.

Case 1: An 8-year-old girl with 3 days of abdominal pain was initially diagnosed via ultrasound (US) at an outlying hospital as having constipation and was treated with an enema. Her pain resolved, but she then returned 5 days later with more intensity, low grade fever, and flank tenderness.

Complete blood count showed 18,300 white blood cells/μL with 70% neutrophils and 412,000 platelets/μL. In the prior year, she'd had three culture-confirmed urinary tract infections due to Escherichia coli that was susceptible to trimethoprim/sulfamethoxazole and cephalexin, with normal renal US and vesicoureterogram. Pyelonephritis was considered, but this time the only urinalysis abnormality was 11 WBC. The urine culture was negative, as was a second US.

She was referred to our hospital. Because US has a nearly 40% false-negative rate for renal abscesses, we obtained an abdominal CT scan. In many cases, abscesses are too small (2 cm or less) to be seen on US. In this child, however, the abscess was large (most of the upper half of her kidney).

The success of US depends upon differences in density creating an echo. Because the uniform consistency of this abscess closely matched that of the kidney, it didn't reflect echoes needed to “see” the abscess.

Ultrasound can be ideal when screening for renal abscesses because of ease of performance: When it's positive, you're done. But if it's negative and you remain suspicious, you need a CT scan with contrast (> 90% sensitive) because US can't definitively rule out a renal or perinephric abscess.

Case 2: Neither routine radiographs (which were normal) nor bone scan (with questionable signal in knee joint area) revealed the cause for a swollen knee and failure to bear weight in a 13-month-old boy.

Joint fluid glucose was normal, and his cell count was 3,800 WBC/μL, less than you'd expect with pyarthrosis. Culture of knee joint fluid was negative. He was diagnosed as having tenosynovitis and treated with ibuprofen.

The swelling was reduced after the tap, but the boy returned 5 days later with a limp. Another plain x-ray was read as normal. Vancomycin was started for “culture-negative” pyarthrosis, fearing methicillin-resistant Staphylococcus aureus. The swelling only marginally improved in the next 4 days, so he was referred to us.

We obtained an MRI. Sure enough, his bone marrow lit up, and there was a defect in his distal femur. He had osteomyelitis with a sympathetic effusion in the knee joint, explaining the negative joint fluid culture.

Plain x-rays often miss early bone infection because prepubertal children have uncalcified areas in their distal long bones. An x-ray “sees” infection as changes in calcium density via defects in already calcified bone or new reactive bone formation around infected but previously uncalcified areas.

Thus, children with incompletely calcified long bones can have osteomyelitis for 10–14 days without visible bony changes on x-ray.

Bone scan findings also had been falsely negative, possibly because the technetium used to localize the infection couldn't enter the infected area due to the expanding pressure of the infection, thus limiting local blood supply.

Plain x-ray and bone scan for osteomyelitis are indeed easier and cheaper than MRI, and in most cases, they are sufficient. However, in this case there were signals that could have triggered an MRI sooner, including a negative joint fluid culture (but this may be true in 30% of septic arthritis cases, so it's only a partial clue) and the relatively normal joint fluid findings. While acute tenosynovitis may be a logical initial diagnosis, the ibuprofen failure points in another direction, i.e., MRI to rule out bone or other soft tissue focus.

An MRI also will pinpoint the focus to allow culture by bone aspiration. Cultures before or early in the antibiotic course can direct antibiotics based on susceptibilities, thereby allowing for intravenous therapy for 5–7 days and then use of oral drug with the same activity to finish the 4- to 6-week regimen.

An early MRI, although expensive, can end up being cost effective by showing where to culture and potentially reducing overall antibiotic costs. Without a cultured pathogen, patients “responding” to broad antibiotics such as vancomycin are necessarily kept on this intravenous drug for the whole course.

Case 3: Our third case was a 13-month-old boy with 2 days of abdominal pain and fever, plus elevated WBC count, sedimentation rate, and C-reactive protein. The child lay rigidly in bed, not allowing anyone to roll him over, move his right leg, or touch his lower right abdomen. His examination initially suggested appendicitis. However, both abdominal x-ray and CT scans were normal.

Our differential diagnosis expanded to include pelvic osteomyelitis, diskitis, or an iliopsoas abscess with referred pain to the hip and abdomen.

A bone scan revealed no abnormality of the iliopsoas area, the sacroiliac joint, or the disks. But we were surprised to see an enhanced signal in the soft tissues near the right side of the pelvis.

An MRI (pelvis to thighs) clearly showed a large abscess in his adductor muscle group. The CT, it turned out, had cut off just above the abscess. He dramatically improved within 48 hours after incision and drainage followed by intravenous antibiotics.

Infections of the lower pelvis (pubis or ischium) or nearby soft tissues are difficult to diagnose in children, who have a hard time localizing the pain. In this child's case, the bone scan, which can image the whole body, helped us locate an area of increased vascularity, so we could confidently order the MRI of the correct part of the abscess.

Probably less than 5% of osteomyelitis or soft tissue abscesses are located in the lower pelvis area. With our patient, a key finding was his refusal to allow lateral movement of his right leg. We assumed that meant a problem was in his sacroiliac joint or muscle groups in his back. We didn't think about the muscles right there in his thigh. This was a reminder to us to think outside the “box,” including the lower pelvic bones and the muscles that attach to those bones.

Abdominal CT of an 8-year-old girl shows a large, uniform abscess filling most of the upper half of her kidney. Because its density was so uniform and similar to kidney tissue, ultrasound had missed it.

An MRI reveals osteomyelitis in the distal femur of a 13-month-old limping boy with sympathetic effusion in his knee joint, which had confused the clinical picture.

In a 13-month-old boy with abdominal pain, lower-body MRI captured what a bone scan had helped localize: A large abscess in the adductor muscle group, below the point where a prior abdominal CT scan had cut off. Photo Courtesy Dr. Christopher J. Harrison

When it comes to imaging studies for suspected infections in children, sometimes you have to pull out bigger guns. CT and MRI are expensive, stressful to the child, and may require sedation, so we don't use them as first-line tools. But three recent cases illustrate that these modalities may be needed when your suspicions are not borne out by routine imaging.

Case 1: An 8-year-old girl with 3 days of abdominal pain was initially diagnosed via ultrasound (US) at an outlying hospital as having constipation and was treated with an enema. Her pain resolved, but she then returned 5 days later with more intensity, low grade fever, and flank tenderness.

Complete blood count showed 18,300 white blood cells/μL with 70% neutrophils and 412,000 platelets/μL. In the prior year, she'd had three culture-confirmed urinary tract infections due to Escherichia coli that was susceptible to trimethoprim/sulfamethoxazole and cephalexin, with normal renal US and vesicoureterogram. Pyelonephritis was considered, but this time the only urinalysis abnormality was 11 WBC. The urine culture was negative, as was a second US.

She was referred to our hospital. Because US has a nearly 40% false-negative rate for renal abscesses, we obtained an abdominal CT scan. In many cases, abscesses are too small (2 cm or less) to be seen on US. In this child, however, the abscess was large (most of the upper half of her kidney).

The success of US depends upon differences in density creating an echo. Because the uniform consistency of this abscess closely matched that of the kidney, it didn't reflect echoes needed to “see” the abscess.

Ultrasound can be ideal when screening for renal abscesses because of ease of performance: When it's positive, you're done. But if it's negative and you remain suspicious, you need a CT scan with contrast (> 90% sensitive) because US can't definitively rule out a renal or perinephric abscess.

Case 2: Neither routine radiographs (which were normal) nor bone scan (with questionable signal in knee joint area) revealed the cause for a swollen knee and failure to bear weight in a 13-month-old boy.

Joint fluid glucose was normal, and his cell count was 3,800 WBC/μL, less than you'd expect with pyarthrosis. Culture of knee joint fluid was negative. He was diagnosed as having tenosynovitis and treated with ibuprofen.

The swelling was reduced after the tap, but the boy returned 5 days later with a limp. Another plain x-ray was read as normal. Vancomycin was started for “culture-negative” pyarthrosis, fearing methicillin-resistant Staphylococcus aureus. The swelling only marginally improved in the next 4 days, so he was referred to us.

We obtained an MRI. Sure enough, his bone marrow lit up, and there was a defect in his distal femur. He had osteomyelitis with a sympathetic effusion in the knee joint, explaining the negative joint fluid culture.

Plain x-rays often miss early bone infection because prepubertal children have uncalcified areas in their distal long bones. An x-ray “sees” infection as changes in calcium density via defects in already calcified bone or new reactive bone formation around infected but previously uncalcified areas.

Thus, children with incompletely calcified long bones can have osteomyelitis for 10–14 days without visible bony changes on x-ray.

Bone scan findings also had been falsely negative, possibly because the technetium used to localize the infection couldn't enter the infected area due to the expanding pressure of the infection, thus limiting local blood supply.

Plain x-ray and bone scan for osteomyelitis are indeed easier and cheaper than MRI, and in most cases, they are sufficient. However, in this case there were signals that could have triggered an MRI sooner, including a negative joint fluid culture (but this may be true in 30% of septic arthritis cases, so it's only a partial clue) and the relatively normal joint fluid findings. While acute tenosynovitis may be a logical initial diagnosis, the ibuprofen failure points in another direction, i.e., MRI to rule out bone or other soft tissue focus.

An MRI also will pinpoint the focus to allow culture by bone aspiration. Cultures before or early in the antibiotic course can direct antibiotics based on susceptibilities, thereby allowing for intravenous therapy for 5–7 days and then use of oral drug with the same activity to finish the 4- to 6-week regimen.

An early MRI, although expensive, can end up being cost effective by showing where to culture and potentially reducing overall antibiotic costs. Without a cultured pathogen, patients “responding” to broad antibiotics such as vancomycin are necessarily kept on this intravenous drug for the whole course.

Case 3: Our third case was a 13-month-old boy with 2 days of abdominal pain and fever, plus elevated WBC count, sedimentation rate, and C-reactive protein. The child lay rigidly in bed, not allowing anyone to roll him over, move his right leg, or touch his lower right abdomen. His examination initially suggested appendicitis. However, both abdominal x-ray and CT scans were normal.

Our differential diagnosis expanded to include pelvic osteomyelitis, diskitis, or an iliopsoas abscess with referred pain to the hip and abdomen.

A bone scan revealed no abnormality of the iliopsoas area, the sacroiliac joint, or the disks. But we were surprised to see an enhanced signal in the soft tissues near the right side of the pelvis.

An MRI (pelvis to thighs) clearly showed a large abscess in his adductor muscle group. The CT, it turned out, had cut off just above the abscess. He dramatically improved within 48 hours after incision and drainage followed by intravenous antibiotics.

Infections of the lower pelvis (pubis or ischium) or nearby soft tissues are difficult to diagnose in children, who have a hard time localizing the pain. In this child's case, the bone scan, which can image the whole body, helped us locate an area of increased vascularity, so we could confidently order the MRI of the correct part of the abscess.

Probably less than 5% of osteomyelitis or soft tissue abscesses are located in the lower pelvis area. With our patient, a key finding was his refusal to allow lateral movement of his right leg. We assumed that meant a problem was in his sacroiliac joint or muscle groups in his back. We didn't think about the muscles right there in his thigh. This was a reminder to us to think outside the “box,” including the lower pelvic bones and the muscles that attach to those bones.

Abdominal CT of an 8-year-old girl shows a large, uniform abscess filling most of the upper half of her kidney. Because its density was so uniform and similar to kidney tissue, ultrasound had missed it.

An MRI reveals osteomyelitis in the distal femur of a 13-month-old limping boy with sympathetic effusion in his knee joint, which had confused the clinical picture.

In a 13-month-old boy with abdominal pain, lower-body MRI captured what a bone scan had helped localize: A large abscess in the adductor muscle group, below the point where a prior abdominal CT scan had cut off. Photo Courtesy Dr. Christopher J. Harrison

Yogi Berra once said, “It's tough to make predictions, particularly about the future.” With that said, here are my top predictions for pediatric infectious disease developments in 2005:

▸ Changes in the U.S. vaccine development infrastructure will allow for the distribution of 125 million doses of trivalent inactivated influenza vaccine for the 2005-2006 season. But despite the increase in demand for vaccine fostered by the 2004-2005 shortage, a relatively mild influenza season this winter will lead to relative apathy next season, and 25 million of the 125 million doses manufactured doses will not be utilized.

▸ A vaccine containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) will be licensed and implemented for use in the 11- to 13-year-old population, probably by June 2005. Although pertussis cases will decrease from the peak year of 2004 (partly as a reflection of the normal 2- to 3-year cycle of infection), mortality from pertussis in those younger than 4 months of age will not decrease during 2005.

At our pediatric center, we had a 300% increase in confirmed pertussis cases in 2004, compared with the average annual number of cases seen over the last 30 years. And in contrast to past years where diagnoses were made mostly in infants who required hospitalization, many of last year's cases have been linked to school outbreaks.

▸ Methicillin-resistant Staphylococcus aureus (MRSA) infection in the healthy child will reach epidemic numbers. (One pediatrician in our area who has been in practice for over 30 years says he has never seen so many children with boils!) The importance of draining abscesses will once again be brought to light, and novel antibiotic regimens will be utilized more commonly by the pediatric practitioner.

▸ World AIDS day was observed Dec. 1 and brought to attention the enormous global impact of this infection, particularly focusing on the impact in women. Early in the epidemic, men outnumbered women among HIV-infected individuals, but current figures show more than 50% of adults living with HIV/AIDS in the United States are women, with heterosexual intercourse being the major vector of transmission.

Data from the Centers for Disease Control and Prevention show that HIV infection rates have more than tripled among American teens and adult women since 1986. New cases will continue to occur and minority teenagers will be the hardest group to identify and treat.

▸ A diagnostic test for Kawasaki disease is close, thanks to Anne Rowley, M.D., of Northwestern University, Chicago, but will not be available for 2 more years.

▸ Vancomycin-resistant enterococcal (VRE) colonization in the hospitalized high-risk pediatric patient will become increasingly important and will challenge many more children's hospitals to provide special VRE wards.

▸ Rates of invasive pneumococcal infection in children will plateau as new serogroups of pneumococcus emerge, but cases of meningitis and empyema will continue to occur.

▸ Reports of breakthrough varicella will continue to be reported, while a second dose of varicella vaccine will be recommended by the end of 2005.

▸ The ambitious goal of the World Health Assembly to interrupt wild polio transmission globally by early 2005 will be difficult to achieve. The WHA notes that success depends on “sufficient political will, oversight, and accountability.” Accessing all children, particularly those who live in areas of armed conflict, remains the greatest challenge.

While the number of polio cases worldwide has decreased from 350,000 in 1988 to fewer than 800 cases in 2003, six countries globally are still polio endemic: Nigeria, India, Pakistan, Niger, Afghanistan, and Egypt.

▸ The scariest prediction of all: Human avian influenza cases will emerge beyond the borders of Asia. All known subtypes of influenza A circulate among wild birds. While most demonstrate low pathogenicity, mutation to highly lethal forms has occurred. Strains have jumped the species barrier, resulting in human avian influenza cases which have now been confirmed in Hong Kong, Vietnam, and Thailand, with case fatality rates of up to 70%.

Now, experts fear that reassortment between human and avian subtypes could generate viruses of pandemic potential. Would antiviral therapy be beneficial? (These viruses are typically resistant to amantadine and rimantadine but susceptible to oseltamivir and zanamivir.) Do newer classes of antivirals such as short-interfering RNAs (siRNAs) hold promise for prevention and treatment of influenza A infection? Will the vaccine technology known as “reverse genetics,” which allows the generation of an influenza virus entirely from cloned cDNAs, provide a tool for more efficient vaccine production and development? We can hope, but on this one I'd rather not try to predict.

Yogi Berra once said, “It's tough to make predictions, particularly about the future.” With that said, here are my top predictions for pediatric infectious disease developments in 2005:

▸ Changes in the U.S. vaccine development infrastructure will allow for the distribution of 125 million doses of trivalent inactivated influenza vaccine for the 2005-2006 season. But despite the increase in demand for vaccine fostered by the 2004-2005 shortage, a relatively mild influenza season this winter will lead to relative apathy next season, and 25 million of the 125 million doses manufactured doses will not be utilized.

▸ A vaccine containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) will be licensed and implemented for use in the 11- to 13-year-old population, probably by June 2005. Although pertussis cases will decrease from the peak year of 2004 (partly as a reflection of the normal 2- to 3-year cycle of infection), mortality from pertussis in those younger than 4 months of age will not decrease during 2005.

At our pediatric center, we had a 300% increase in confirmed pertussis cases in 2004, compared with the average annual number of cases seen over the last 30 years. And in contrast to past years where diagnoses were made mostly in infants who required hospitalization, many of last year's cases have been linked to school outbreaks.

▸ Methicillin-resistant Staphylococcus aureus (MRSA) infection in the healthy child will reach epidemic numbers. (One pediatrician in our area who has been in practice for over 30 years says he has never seen so many children with boils!) The importance of draining abscesses will once again be brought to light, and novel antibiotic regimens will be utilized more commonly by the pediatric practitioner.

▸ World AIDS day was observed Dec. 1 and brought to attention the enormous global impact of this infection, particularly focusing on the impact in women. Early in the epidemic, men outnumbered women among HIV-infected individuals, but current figures show more than 50% of adults living with HIV/AIDS in the United States are women, with heterosexual intercourse being the major vector of transmission.

Data from the Centers for Disease Control and Prevention show that HIV infection rates have more than tripled among American teens and adult women since 1986. New cases will continue to occur and minority teenagers will be the hardest group to identify and treat.

▸ A diagnostic test for Kawasaki disease is close, thanks to Anne Rowley, M.D., of Northwestern University, Chicago, but will not be available for 2 more years.

▸ Vancomycin-resistant enterococcal (VRE) colonization in the hospitalized high-risk pediatric patient will become increasingly important and will challenge many more children's hospitals to provide special VRE wards.

▸ Rates of invasive pneumococcal infection in children will plateau as new serogroups of pneumococcus emerge, but cases of meningitis and empyema will continue to occur.

▸ Reports of breakthrough varicella will continue to be reported, while a second dose of varicella vaccine will be recommended by the end of 2005.

▸ The ambitious goal of the World Health Assembly to interrupt wild polio transmission globally by early 2005 will be difficult to achieve. The WHA notes that success depends on “sufficient political will, oversight, and accountability.” Accessing all children, particularly those who live in areas of armed conflict, remains the greatest challenge.

While the number of polio cases worldwide has decreased from 350,000 in 1988 to fewer than 800 cases in 2003, six countries globally are still polio endemic: Nigeria, India, Pakistan, Niger, Afghanistan, and Egypt.

▸ The scariest prediction of all: Human avian influenza cases will emerge beyond the borders of Asia. All known subtypes of influenza A circulate among wild birds. While most demonstrate low pathogenicity, mutation to highly lethal forms has occurred. Strains have jumped the species barrier, resulting in human avian influenza cases which have now been confirmed in Hong Kong, Vietnam, and Thailand, with case fatality rates of up to 70%.

Now, experts fear that reassortment between human and avian subtypes could generate viruses of pandemic potential. Would antiviral therapy be beneficial? (These viruses are typically resistant to amantadine and rimantadine but susceptible to oseltamivir and zanamivir.) Do newer classes of antivirals such as short-interfering RNAs (siRNAs) hold promise for prevention and treatment of influenza A infection? Will the vaccine technology known as “reverse genetics,” which allows the generation of an influenza virus entirely from cloned cDNAs, provide a tool for more efficient vaccine production and development? We can hope, but on this one I'd rather not try to predict.

Yogi Berra once said, “It's tough to make predictions, particularly about the future.” With that said, here are my top predictions for pediatric infectious disease developments in 2005:

▸ Changes in the U.S. vaccine development infrastructure will allow for the distribution of 125 million doses of trivalent inactivated influenza vaccine for the 2005-2006 season. But despite the increase in demand for vaccine fostered by the 2004-2005 shortage, a relatively mild influenza season this winter will lead to relative apathy next season, and 25 million of the 125 million doses manufactured doses will not be utilized.

▸ A vaccine containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) will be licensed and implemented for use in the 11- to 13-year-old population, probably by June 2005. Although pertussis cases will decrease from the peak year of 2004 (partly as a reflection of the normal 2- to 3-year cycle of infection), mortality from pertussis in those younger than 4 months of age will not decrease during 2005.

At our pediatric center, we had a 300% increase in confirmed pertussis cases in 2004, compared with the average annual number of cases seen over the last 30 years. And in contrast to past years where diagnoses were made mostly in infants who required hospitalization, many of last year's cases have been linked to school outbreaks.

▸ Methicillin-resistant Staphylococcus aureus (MRSA) infection in the healthy child will reach epidemic numbers. (One pediatrician in our area who has been in practice for over 30 years says he has never seen so many children with boils!) The importance of draining abscesses will once again be brought to light, and novel antibiotic regimens will be utilized more commonly by the pediatric practitioner.

▸ World AIDS day was observed Dec. 1 and brought to attention the enormous global impact of this infection, particularly focusing on the impact in women. Early in the epidemic, men outnumbered women among HIV-infected individuals, but current figures show more than 50% of adults living with HIV/AIDS in the United States are women, with heterosexual intercourse being the major vector of transmission.

Data from the Centers for Disease Control and Prevention show that HIV infection rates have more than tripled among American teens and adult women since 1986. New cases will continue to occur and minority teenagers will be the hardest group to identify and treat.

▸ A diagnostic test for Kawasaki disease is close, thanks to Anne Rowley, M.D., of Northwestern University, Chicago, but will not be available for 2 more years.

▸ Vancomycin-resistant enterococcal (VRE) colonization in the hospitalized high-risk pediatric patient will become increasingly important and will challenge many more children's hospitals to provide special VRE wards.

▸ Rates of invasive pneumococcal infection in children will plateau as new serogroups of pneumococcus emerge, but cases of meningitis and empyema will continue to occur.

▸ Reports of breakthrough varicella will continue to be reported, while a second dose of varicella vaccine will be recommended by the end of 2005.

▸ The ambitious goal of the World Health Assembly to interrupt wild polio transmission globally by early 2005 will be difficult to achieve. The WHA notes that success depends on “sufficient political will, oversight, and accountability.” Accessing all children, particularly those who live in areas of armed conflict, remains the greatest challenge.

While the number of polio cases worldwide has decreased from 350,000 in 1988 to fewer than 800 cases in 2003, six countries globally are still polio endemic: Nigeria, India, Pakistan, Niger, Afghanistan, and Egypt.

▸ The scariest prediction of all: Human avian influenza cases will emerge beyond the borders of Asia. All known subtypes of influenza A circulate among wild birds. While most demonstrate low pathogenicity, mutation to highly lethal forms has occurred. Strains have jumped the species barrier, resulting in human avian influenza cases which have now been confirmed in Hong Kong, Vietnam, and Thailand, with case fatality rates of up to 70%.

Now, experts fear that reassortment between human and avian subtypes could generate viruses of pandemic potential. Would antiviral therapy be beneficial? (These viruses are typically resistant to amantadine and rimantadine but susceptible to oseltamivir and zanamivir.) Do newer classes of antivirals such as short-interfering RNAs (siRNAs) hold promise for prevention and treatment of influenza A infection? Will the vaccine technology known as “reverse genetics,” which allows the generation of an influenza virus entirely from cloned cDNAs, provide a tool for more efficient vaccine production and development? We can hope, but on this one I'd rather not try to predict.