Stephen I. Pelton, MD

The recent Escherichia coli outbreak in Germany reminds us yet again about the threat of foodborne illness and the need for awareness about the clinical manifestations, the treatment, and the public health implications.

On June 14, a 2-year-old boy became the first child and the 37th person to die in Germany’s ongoing E. coli outbreak. Here in the United States, the Centers for Disease Control and Prevention estimates 48 million people – one in every six Americans – become ill, 128,000 are hospitalized, and 3,000 die of foodborne illness annually. About half of all foodborne illness occurs in children, who are particularly vulnerable due to their immature immune systems, lower body weight, and reduced stomach acid production.

Norovirus has become the most common recognized foodborne pathogen, causing about 5 million illnesses a year, followed by nontyphoidal Salmonella, with just over 1 million annual cases, and Clostridium perfringens, at just under 1 million, according to the CDC. Norovirus illness is usually mild, but it did cause an estimated 149 annual deaths. Nontyphoidal Salmonella is the most common serious cause of foodborne illness with an estimated 378 annual deaths, followed by Toxoplasma gondii (327 deaths) and Listeria monocytogenes (255 deaths). More information on the epidemiology and incidence of foodborne disease in 2011 can be found on the CDC website.

The following foodborne illnesses are frequent causes of morbidity in children. Information on the possible foodborne sources and the effects of infection are from a report compiled by the Pew Health Group in collaboration with the Center for Foodborne Illness Research and Prevention.

• Salmonella. These infections occur in approximately 75 children/100,000 under age 4 years, according to the CDC. It is commonly associated with foods of animal origin, including beef, poultry, milk, and eggs, or cross-contamination from these with other foods. Typical symptoms include diarrhea, fever, and abdominal cramps. More serious short-term manifestations can include colitis, meningitis, septicemia, and death. Treatment involves rehydration as needed.

In general, antibiotic therapy is not warranted, but in immunocompromised hosts and children younger than age 6 months, antimicrobial therapy may be beneficial. In such settings, ceftriaxone is effective when susceptible, specifically in high-risk populations.

• Shigella. This infection occurs in about 28/100,000 children under age 4 years and 26/100,000 for those aged 4-11 years, according to the CDC. It is often associated with vegetables harvested in fields contaminated with sewage; flies that breed in infected feces and contaminate the food; and drinking, swimming, or playing in contaminated water. Short-term effects include high fever, diarrhea that is often bloody, stomach cramps, and seizures in children less than age 2 years. Reactive or chronic arthritis can be a postinfectious sequelae.

Treatment includes rehydration as necessary, and antibiotics for severe disease or dysentery, particularly in those with underlying immunosuppression. Ceftriaxone and ciprofloxacin are effective, although the latter is not licensed for use in young children. Resistance to amoxicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) is common. Treatment of mild cases may be indicated to shorten the duration of excretion.

• Campylobacter. This infection affects 29/100,000 children under age 4 years, similar in incidence to Shigella. Foodborne sources included raw or undercooked poultry or foods cross-contaminated by poultry, unpasteurized milk, and contaminated water. Symptoms include diarrhea (sometimes bloody), cramping, abdominal pain, urinary tract infection, fever, and meningitis. Campylobacter is also associated with Guillain-Barré syndrome or reactive/chronic arthritis.

Again, treatment involves rehydration as necessary. Macrolides (azithromycin or erythromycin) can shorten duration of illness and prevent relapse. These are most effective when given early in the course of infection.

• E. coli or other shiga toxin–producing strains. This foodborne infection has been in the headlines lately, affects about 4/100,000 children between 4 and 11 years of age. Typical food sources include ground beef and other meats, green leafy vegetables, unpasteurized juices or raw milk, or soft cheeses made from raw milk. Symptoms include severe stomach cramps, diarrhea (often bloody), and vomiting. Hemolytic-uremic syndrome occurs in about 15% of children with E. coli 0157:H7 infection. This can result in long-term kidney damage as well as death.

In general, antibiotics have not been shown to benefit patients. Early reports of increased risk of hemolytic-uremic syndrome with antibiotic treatment have not been confirmed. As with the others, rehydration and supportive therapy are the mainstays of treatment.

• Listeria. This infection occurs in about 0.76/100,000 children under age 4 years, according to the CDC. About one-third of all cases involve pregnant women. Common food sources include uncooked meats, particularly cold cuts and hot dogs, as well as smoked seafood, raw milk, soft cheeses made from raw milk, and vegetables grown in contaminated soil or fertilizer. Symptoms include fever, muscle aches, nausea, and diarrhea. Headaches, stiff neck, confusion, loss of balance, and seizures can result if infection spreads to the nervous system.

For invasive disease, ampicillin plus an aminoglycoside is recommended. For penicillin-allergic patients, TMP-SMZ or high-dose vancomycin can be used. Cephalosporins are generally inactive. In the majority of patients with febrile gastroenteritis, the illness is self-limited (typical duration, 2 days or less) and therefore, generally no antibiotic treatment is necessary.

In pregnant women, listerial febrile gastroenteritis can lead to fetal death, premature birth, or infected newborns. Oral ampicillin or TMP-SMZ can be given for several days in immunocompromised or pregnant patients with listerial febrile gastroenteritis, particularly if they are still symptomatic once the culture result is known.

Dr. Pelton is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures. E-mail Dr. Pelton at [email protected].

This column, ID Consult, appears regularly in Pediatric News, a publication of Elsevier.

The recent Escherichia coli outbreak in Germany reminds us yet again about the threat of foodborne illness and the need for awareness about the clinical manifestations, the treatment, and the public health implications.

On June 14, a 2-year-old boy became the first child and the 37th person to die in Germany’s ongoing E. coli outbreak. Here in the United States, the Centers for Disease Control and Prevention estimates 48 million people – one in every six Americans – become ill, 128,000 are hospitalized, and 3,000 die of foodborne illness annually. About half of all foodborne illness occurs in children, who are particularly vulnerable due to their immature immune systems, lower body weight, and reduced stomach acid production.

Norovirus has become the most common recognized foodborne pathogen, causing about 5 million illnesses a year, followed by nontyphoidal Salmonella, with just over 1 million annual cases, and Clostridium perfringens, at just under 1 million, according to the CDC. Norovirus illness is usually mild, but it did cause an estimated 149 annual deaths. Nontyphoidal Salmonella is the most common serious cause of foodborne illness with an estimated 378 annual deaths, followed by Toxoplasma gondii (327 deaths) and Listeria monocytogenes (255 deaths). More information on the epidemiology and incidence of foodborne disease in 2011 can be found on the CDC website.

The following foodborne illnesses are frequent causes of morbidity in children. Information on the possible foodborne sources and the effects of infection are from a report compiled by the Pew Health Group in collaboration with the Center for Foodborne Illness Research and Prevention.

• Salmonella. These infections occur in approximately 75 children/100,000 under age 4 years, according to the CDC. It is commonly associated with foods of animal origin, including beef, poultry, milk, and eggs, or cross-contamination from these with other foods. Typical symptoms include diarrhea, fever, and abdominal cramps. More serious short-term manifestations can include colitis, meningitis, septicemia, and death. Treatment involves rehydration as needed.

In general, antibiotic therapy is not warranted, but in immunocompromised hosts and children younger than age 6 months, antimicrobial therapy may be beneficial. In such settings, ceftriaxone is effective when susceptible, specifically in high-risk populations.

• Shigella. This infection occurs in about 28/100,000 children under age 4 years and 26/100,000 for those aged 4-11 years, according to the CDC. It is often associated with vegetables harvested in fields contaminated with sewage; flies that breed in infected feces and contaminate the food; and drinking, swimming, or playing in contaminated water. Short-term effects include high fever, diarrhea that is often bloody, stomach cramps, and seizures in children less than age 2 years. Reactive or chronic arthritis can be a postinfectious sequelae.

Treatment includes rehydration as necessary, and antibiotics for severe disease or dysentery, particularly in those with underlying immunosuppression. Ceftriaxone and ciprofloxacin are effective, although the latter is not licensed for use in young children. Resistance to amoxicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) is common. Treatment of mild cases may be indicated to shorten the duration of excretion.

• Campylobacter. This infection affects 29/100,000 children under age 4 years, similar in incidence to Shigella. Foodborne sources included raw or undercooked poultry or foods cross-contaminated by poultry, unpasteurized milk, and contaminated water. Symptoms include diarrhea (sometimes bloody), cramping, abdominal pain, urinary tract infection, fever, and meningitis. Campylobacter is also associated with Guillain-Barré syndrome or reactive/chronic arthritis.

Again, treatment involves rehydration as necessary. Macrolides (azithromycin or erythromycin) can shorten duration of illness and prevent relapse. These are most effective when given early in the course of infection.

• E. coli or other shiga toxin–producing strains. This foodborne infection has been in the headlines lately, affects about 4/100,000 children between 4 and 11 years of age. Typical food sources include ground beef and other meats, green leafy vegetables, unpasteurized juices or raw milk, or soft cheeses made from raw milk. Symptoms include severe stomach cramps, diarrhea (often bloody), and vomiting. Hemolytic-uremic syndrome occurs in about 15% of children with E. coli 0157:H7 infection. This can result in long-term kidney damage as well as death.

In general, antibiotics have not been shown to benefit patients. Early reports of increased risk of hemolytic-uremic syndrome with antibiotic treatment have not been confirmed. As with the others, rehydration and supportive therapy are the mainstays of treatment.

• Listeria. This infection occurs in about 0.76/100,000 children under age 4 years, according to the CDC. About one-third of all cases involve pregnant women. Common food sources include uncooked meats, particularly cold cuts and hot dogs, as well as smoked seafood, raw milk, soft cheeses made from raw milk, and vegetables grown in contaminated soil or fertilizer. Symptoms include fever, muscle aches, nausea, and diarrhea. Headaches, stiff neck, confusion, loss of balance, and seizures can result if infection spreads to the nervous system.

For invasive disease, ampicillin plus an aminoglycoside is recommended. For penicillin-allergic patients, TMP-SMZ or high-dose vancomycin can be used. Cephalosporins are generally inactive. In the majority of patients with febrile gastroenteritis, the illness is self-limited (typical duration, 2 days or less) and therefore, generally no antibiotic treatment is necessary.

In pregnant women, listerial febrile gastroenteritis can lead to fetal death, premature birth, or infected newborns. Oral ampicillin or TMP-SMZ can be given for several days in immunocompromised or pregnant patients with listerial febrile gastroenteritis, particularly if they are still symptomatic once the culture result is known.

Dr. Pelton is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures. E-mail Dr. Pelton at [email protected].

This column, ID Consult, appears regularly in Pediatric News, a publication of Elsevier.

The recent Escherichia coli outbreak in Germany reminds us yet again about the threat of foodborne illness and the need for awareness about the clinical manifestations, the treatment, and the public health implications.

On June 14, a 2-year-old boy became the first child and the 37th person to die in Germany’s ongoing E. coli outbreak. Here in the United States, the Centers for Disease Control and Prevention estimates 48 million people – one in every six Americans – become ill, 128,000 are hospitalized, and 3,000 die of foodborne illness annually. About half of all foodborne illness occurs in children, who are particularly vulnerable due to their immature immune systems, lower body weight, and reduced stomach acid production.

Norovirus has become the most common recognized foodborne pathogen, causing about 5 million illnesses a year, followed by nontyphoidal Salmonella, with just over 1 million annual cases, and Clostridium perfringens, at just under 1 million, according to the CDC. Norovirus illness is usually mild, but it did cause an estimated 149 annual deaths. Nontyphoidal Salmonella is the most common serious cause of foodborne illness with an estimated 378 annual deaths, followed by Toxoplasma gondii (327 deaths) and Listeria monocytogenes (255 deaths). More information on the epidemiology and incidence of foodborne disease in 2011 can be found on the CDC website.

The following foodborne illnesses are frequent causes of morbidity in children. Information on the possible foodborne sources and the effects of infection are from a report compiled by the Pew Health Group in collaboration with the Center for Foodborne Illness Research and Prevention.

• Salmonella. These infections occur in approximately 75 children/100,000 under age 4 years, according to the CDC. It is commonly associated with foods of animal origin, including beef, poultry, milk, and eggs, or cross-contamination from these with other foods. Typical symptoms include diarrhea, fever, and abdominal cramps. More serious short-term manifestations can include colitis, meningitis, septicemia, and death. Treatment involves rehydration as needed.

In general, antibiotic therapy is not warranted, but in immunocompromised hosts and children younger than age 6 months, antimicrobial therapy may be beneficial. In such settings, ceftriaxone is effective when susceptible, specifically in high-risk populations.

• Shigella. This infection occurs in about 28/100,000 children under age 4 years and 26/100,000 for those aged 4-11 years, according to the CDC. It is often associated with vegetables harvested in fields contaminated with sewage; flies that breed in infected feces and contaminate the food; and drinking, swimming, or playing in contaminated water. Short-term effects include high fever, diarrhea that is often bloody, stomach cramps, and seizures in children less than age 2 years. Reactive or chronic arthritis can be a postinfectious sequelae.

Treatment includes rehydration as necessary, and antibiotics for severe disease or dysentery, particularly in those with underlying immunosuppression. Ceftriaxone and ciprofloxacin are effective, although the latter is not licensed for use in young children. Resistance to amoxicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) is common. Treatment of mild cases may be indicated to shorten the duration of excretion.

• Campylobacter. This infection affects 29/100,000 children under age 4 years, similar in incidence to Shigella. Foodborne sources included raw or undercooked poultry or foods cross-contaminated by poultry, unpasteurized milk, and contaminated water. Symptoms include diarrhea (sometimes bloody), cramping, abdominal pain, urinary tract infection, fever, and meningitis. Campylobacter is also associated with Guillain-Barré syndrome or reactive/chronic arthritis.

Again, treatment involves rehydration as necessary. Macrolides (azithromycin or erythromycin) can shorten duration of illness and prevent relapse. These are most effective when given early in the course of infection.

• E. coli or other shiga toxin–producing strains. This foodborne infection has been in the headlines lately, affects about 4/100,000 children between 4 and 11 years of age. Typical food sources include ground beef and other meats, green leafy vegetables, unpasteurized juices or raw milk, or soft cheeses made from raw milk. Symptoms include severe stomach cramps, diarrhea (often bloody), and vomiting. Hemolytic-uremic syndrome occurs in about 15% of children with E. coli 0157:H7 infection. This can result in long-term kidney damage as well as death.

In general, antibiotics have not been shown to benefit patients. Early reports of increased risk of hemolytic-uremic syndrome with antibiotic treatment have not been confirmed. As with the others, rehydration and supportive therapy are the mainstays of treatment.

• Listeria. This infection occurs in about 0.76/100,000 children under age 4 years, according to the CDC. About one-third of all cases involve pregnant women. Common food sources include uncooked meats, particularly cold cuts and hot dogs, as well as smoked seafood, raw milk, soft cheeses made from raw milk, and vegetables grown in contaminated soil or fertilizer. Symptoms include fever, muscle aches, nausea, and diarrhea. Headaches, stiff neck, confusion, loss of balance, and seizures can result if infection spreads to the nervous system.

For invasive disease, ampicillin plus an aminoglycoside is recommended. For penicillin-allergic patients, TMP-SMZ or high-dose vancomycin can be used. Cephalosporins are generally inactive. In the majority of patients with febrile gastroenteritis, the illness is self-limited (typical duration, 2 days or less) and therefore, generally no antibiotic treatment is necessary.

In pregnant women, listerial febrile gastroenteritis can lead to fetal death, premature birth, or infected newborns. Oral ampicillin or TMP-SMZ can be given for several days in immunocompromised or pregnant patients with listerial febrile gastroenteritis, particularly if they are still symptomatic once the culture result is known.

Dr. Pelton is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures. E-mail Dr. Pelton at [email protected].

This column, ID Consult, appears regularly in Pediatric News, a publication of Elsevier.

It’s important to keep an open mind when a parent informs you that his or her child has experienced an adverse event following vaccination.

Determining which adverse events are caused by a vaccine and which are mere coincidental associations can be very difficult. As physicians who administer vaccines to children, one of the most important contributions we can make is to report all postimmunization adverse events to the Vaccine Adverse Events Reporting System. Though passive and unable to prove causation, VAERS helps authorities spot events that require follow-up with appropriate studies to determine causality. In general, the Centers for Disease Control and Prevention requires an event to occur within 42 days following immunization to be considered biologically plausible.

The best information we have comes from studies that compare population-based rates of a specific event with the postimmunization rates to see if there is a significant difference. Alternatively, case-control studies can identify whether the odds ratio for receipt of a vaccine is increased among cases. Unfortunately, such studies have been done for only a fraction of all reported postvaccination adverse events.

I’d like to highlight a few prominent adverse events that have been reported following immunization. Some, although unusual, have been causally linked to vaccines. Others, particularly certain severe neurologic outcomes, do not appear to be linked although monitoring continues.

• Thigh swelling and the DTaP vaccine. This one is fairly well established. Often confused with cellulitis, swelling of the entire arm or leg following receipt of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is reported in nearly 2% of all children following the fourth dose, with rates and severity increasing with each successive DTaP dose (Pediatr. Infect. Dis. J. 2008;27[5]:464-5).

However, unlike cellulitis, it is rarely associated with fever or other systemic symptoms, is localized to the vaccinated limb, and usually resolves completely within 48 hours. Although the swelling is likely to occur again with subsequent doses, both the CDC’s Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics recommend that the child receive all recommended DTaP doses following appropriate counseling of the parents.

• Hair loss and the hepatitis B (and other) vaccines. There have been 60 case reports of hair loss (alopecia) following receipt of vaccines, 46 of them associated with the hepatitis B vaccine. These included 16 in which the hair grew back but then fell out again after re-vaccination. Nine of the patients reported previous medication allergy (JAMA 1997;278[14]:1176-8).

This appears to be a true causal effect, although quite rare considering the tens of millions of hepatitis B doses given over the last decades. But in a small number of genetically predisposed children – most of them female – there does appear to be biological plausibility because hair loss has recurred with second dose and is further supported by the several case reports of alopecia in patients with chronic active hepatitis B viral infection.

• Idiopathic thrombocytopenic purpura and MMR vaccine. This link is probably also causal. One study utilizing immunization and hospital admission records demonstrated an absolute risk of one case in every 22,300 doses within 6 weeks of MMR vaccination (Arch. Dis. Child. 2001;84[3]:227-9).

Another study, which attempted to control for the effect of viral infections, found a similar idiopathic thrombocytopenic purpura (ITP) risk of about 1 in 30,000 MMR immunizations. That population-based analysis of 506 consecutive pediatric ITP patients also found that the thrombocytopenia disappeared within a month in 74% of patients and lasted longer than 6 months in only 10% (Vaccine 2007;25[10]:1838-40).

• Myocarditis after vaccination. Inflammatory myocarditis was reported in 10 of approximately 240,000 military recipients of the smallpox vaccine and in 2 additional civilian cases during the widespread pre-event immunization program in 2001. Although it was not definitively linked to the vaccine, ACIP nonetheless recommended that those with heart disease or at risk for it should not receive the vaccine (MMWR 2003;52[13]:282-4).

In children, there have been two reported cases of myocarditis following immunization, one following the hepatitis B vaccine in a previously healthy 12-year-old girl, the other after receipt of meningococcal C conjugate vaccine in a 14-year-old boy. Both showed eosinophilic infiltrates on myocardial biopsies, consistent with an allergic reaction to the vaccine (Pediatr. Infect. Dis J. 2008;27[9]:831-5).

I think the jury is still out on this one. Certainly if you see a case, be sure to report it to VAERS.

• Acute disseminated encephalomyelitis and vaccination: These reports have been coming in since the 1970s, for a variety of different vaccines. Examples include Guillain-Barr? syndrome (GBS) following the Haemophilus influenzae B conjugate vaccine (Eur. J. Pediatr. 1993;152:613-4), central nervous system inflammatory demyelination following hepatitis B vaccination (Neurology. 2009;72[23]:2053), and transverse myelitis with oral polio vaccine (J. Paediatr. Child Health 2006;42[4]:155-9).

Without knowing the background rates of these neurologic complications among unvaccinated individuals, it is impossible to ascertain causality. An excellent data analysis conducted by Dr. Steven Black and colleagues provided very helpful estimates of the numbers of specific severe adverse events that would be expected following receipt of the 2009 H1N1 influenza vaccine.

Based on background rates, they determined that within 6 weeks of vaccination there would be 21.5 coincident cases of GBS per 10 million vaccine recipients, and 86.3 cases of optic neuritis per 10 million female vaccinees. Spontaneous abortions would occur in 16,684 of every 1 million vaccinated pregnant women, and sudden death within 1 hour of any symptom onset in 5.75 of every 10 million people vaccinated (Lancet 2009;374[9707]:2115-22).

Another important analysis was conducted by the CDC to determine whether 33 reported cases of GBS in 11- to 19-year olds within 42 days of receipt of meningococcal conjugate vaccine were causally linked. Background data from the 2000-2004 Healthcare Cost and Utilization project projected that there would be a very close 36 cases for the entire age cohort, suggesting there was no causal link. However, just 20 cases would be expected among 15- to 19-year olds, but the actual number was 26.

Although not statistically significant, this difference was enough to merit continued monitoring by the CDC, which advised that children with prior GBS not receive the vaccine (MMWR 2006;55[13]:364-6).

Finally, a population-based case-control study from France investigated cases of acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis in children younger than 16 years of age between 1994 and 2003, using 12 controls per case matched for age, sex, and geographic location. Rates of hepatitis B vaccination were 24% in cases and 27% in controls, for an adjusted odds ratio of 0.74 (Neurology. 2009;73[17]:1426-7).

One might conclude from this that hepatitis B vaccine is actually protective, but the result was not statistically significant.

Dr. Pelton writes the column, "ID Consult," which regularly appears in Pediatric News, an Elsevier publication. He is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He disclosed that he has received investigator-initiated research grants from Pfizer Inc., Novartis Vaccine and Diagnostics, GlaxoSmithKline, and Intercell. He has served on advisory boards for Pfizer, Novartis, and GSK. To respond to this column, write to [email protected].

It’s important to keep an open mind when a parent informs you that his or her child has experienced an adverse event following vaccination.

Determining which adverse events are caused by a vaccine and which are mere coincidental associations can be very difficult. As physicians who administer vaccines to children, one of the most important contributions we can make is to report all postimmunization adverse events to the Vaccine Adverse Events Reporting System. Though passive and unable to prove causation, VAERS helps authorities spot events that require follow-up with appropriate studies to determine causality. In general, the Centers for Disease Control and Prevention requires an event to occur within 42 days following immunization to be considered biologically plausible.

The best information we have comes from studies that compare population-based rates of a specific event with the postimmunization rates to see if there is a significant difference. Alternatively, case-control studies can identify whether the odds ratio for receipt of a vaccine is increased among cases. Unfortunately, such studies have been done for only a fraction of all reported postvaccination adverse events.

I’d like to highlight a few prominent adverse events that have been reported following immunization. Some, although unusual, have been causally linked to vaccines. Others, particularly certain severe neurologic outcomes, do not appear to be linked although monitoring continues.

• Thigh swelling and the DTaP vaccine. This one is fairly well established. Often confused with cellulitis, swelling of the entire arm or leg following receipt of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is reported in nearly 2% of all children following the fourth dose, with rates and severity increasing with each successive DTaP dose (Pediatr. Infect. Dis. J. 2008;27[5]:464-5).

However, unlike cellulitis, it is rarely associated with fever or other systemic symptoms, is localized to the vaccinated limb, and usually resolves completely within 48 hours. Although the swelling is likely to occur again with subsequent doses, both the CDC’s Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics recommend that the child receive all recommended DTaP doses following appropriate counseling of the parents.

• Hair loss and the hepatitis B (and other) vaccines. There have been 60 case reports of hair loss (alopecia) following receipt of vaccines, 46 of them associated with the hepatitis B vaccine. These included 16 in which the hair grew back but then fell out again after re-vaccination. Nine of the patients reported previous medication allergy (JAMA 1997;278[14]:1176-8).

This appears to be a true causal effect, although quite rare considering the tens of millions of hepatitis B doses given over the last decades. But in a small number of genetically predisposed children – most of them female – there does appear to be biological plausibility because hair loss has recurred with second dose and is further supported by the several case reports of alopecia in patients with chronic active hepatitis B viral infection.

• Idiopathic thrombocytopenic purpura and MMR vaccine. This link is probably also causal. One study utilizing immunization and hospital admission records demonstrated an absolute risk of one case in every 22,300 doses within 6 weeks of MMR vaccination (Arch. Dis. Child. 2001;84[3]:227-9).

Another study, which attempted to control for the effect of viral infections, found a similar idiopathic thrombocytopenic purpura (ITP) risk of about 1 in 30,000 MMR immunizations. That population-based analysis of 506 consecutive pediatric ITP patients also found that the thrombocytopenia disappeared within a month in 74% of patients and lasted longer than 6 months in only 10% (Vaccine 2007;25[10]:1838-40).

• Myocarditis after vaccination. Inflammatory myocarditis was reported in 10 of approximately 240,000 military recipients of the smallpox vaccine and in 2 additional civilian cases during the widespread pre-event immunization program in 2001. Although it was not definitively linked to the vaccine, ACIP nonetheless recommended that those with heart disease or at risk for it should not receive the vaccine (MMWR 2003;52[13]:282-4).

In children, there have been two reported cases of myocarditis following immunization, one following the hepatitis B vaccine in a previously healthy 12-year-old girl, the other after receipt of meningococcal C conjugate vaccine in a 14-year-old boy. Both showed eosinophilic infiltrates on myocardial biopsies, consistent with an allergic reaction to the vaccine (Pediatr. Infect. Dis J. 2008;27[9]:831-5).

I think the jury is still out on this one. Certainly if you see a case, be sure to report it to VAERS.

• Acute disseminated encephalomyelitis and vaccination: These reports have been coming in since the 1970s, for a variety of different vaccines. Examples include Guillain-Barr? syndrome (GBS) following the Haemophilus influenzae B conjugate vaccine (Eur. J. Pediatr. 1993;152:613-4), central nervous system inflammatory demyelination following hepatitis B vaccination (Neurology. 2009;72[23]:2053), and transverse myelitis with oral polio vaccine (J. Paediatr. Child Health 2006;42[4]:155-9).

Without knowing the background rates of these neurologic complications among unvaccinated individuals, it is impossible to ascertain causality. An excellent data analysis conducted by Dr. Steven Black and colleagues provided very helpful estimates of the numbers of specific severe adverse events that would be expected following receipt of the 2009 H1N1 influenza vaccine.

Based on background rates, they determined that within 6 weeks of vaccination there would be 21.5 coincident cases of GBS per 10 million vaccine recipients, and 86.3 cases of optic neuritis per 10 million female vaccinees. Spontaneous abortions would occur in 16,684 of every 1 million vaccinated pregnant women, and sudden death within 1 hour of any symptom onset in 5.75 of every 10 million people vaccinated (Lancet 2009;374[9707]:2115-22).

Another important analysis was conducted by the CDC to determine whether 33 reported cases of GBS in 11- to 19-year olds within 42 days of receipt of meningococcal conjugate vaccine were causally linked. Background data from the 2000-2004 Healthcare Cost and Utilization project projected that there would be a very close 36 cases for the entire age cohort, suggesting there was no causal link. However, just 20 cases would be expected among 15- to 19-year olds, but the actual number was 26.

Although not statistically significant, this difference was enough to merit continued monitoring by the CDC, which advised that children with prior GBS not receive the vaccine (MMWR 2006;55[13]:364-6).

Finally, a population-based case-control study from France investigated cases of acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis in children younger than 16 years of age between 1994 and 2003, using 12 controls per case matched for age, sex, and geographic location. Rates of hepatitis B vaccination were 24% in cases and 27% in controls, for an adjusted odds ratio of 0.74 (Neurology. 2009;73[17]:1426-7).

One might conclude from this that hepatitis B vaccine is actually protective, but the result was not statistically significant.

Dr. Pelton writes the column, "ID Consult," which regularly appears in Pediatric News, an Elsevier publication. He is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He disclosed that he has received investigator-initiated research grants from Pfizer Inc., Novartis Vaccine and Diagnostics, GlaxoSmithKline, and Intercell. He has served on advisory boards for Pfizer, Novartis, and GSK. To respond to this column, write to [email protected].

It’s important to keep an open mind when a parent informs you that his or her child has experienced an adverse event following vaccination.

Determining which adverse events are caused by a vaccine and which are mere coincidental associations can be very difficult. As physicians who administer vaccines to children, one of the most important contributions we can make is to report all postimmunization adverse events to the Vaccine Adverse Events Reporting System. Though passive and unable to prove causation, VAERS helps authorities spot events that require follow-up with appropriate studies to determine causality. In general, the Centers for Disease Control and Prevention requires an event to occur within 42 days following immunization to be considered biologically plausible.

The best information we have comes from studies that compare population-based rates of a specific event with the postimmunization rates to see if there is a significant difference. Alternatively, case-control studies can identify whether the odds ratio for receipt of a vaccine is increased among cases. Unfortunately, such studies have been done for only a fraction of all reported postvaccination adverse events.

I’d like to highlight a few prominent adverse events that have been reported following immunization. Some, although unusual, have been causally linked to vaccines. Others, particularly certain severe neurologic outcomes, do not appear to be linked although monitoring continues.

• Thigh swelling and the DTaP vaccine. This one is fairly well established. Often confused with cellulitis, swelling of the entire arm or leg following receipt of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is reported in nearly 2% of all children following the fourth dose, with rates and severity increasing with each successive DTaP dose (Pediatr. Infect. Dis. J. 2008;27[5]:464-5).

However, unlike cellulitis, it is rarely associated with fever or other systemic symptoms, is localized to the vaccinated limb, and usually resolves completely within 48 hours. Although the swelling is likely to occur again with subsequent doses, both the CDC’s Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics recommend that the child receive all recommended DTaP doses following appropriate counseling of the parents.

• Hair loss and the hepatitis B (and other) vaccines. There have been 60 case reports of hair loss (alopecia) following receipt of vaccines, 46 of them associated with the hepatitis B vaccine. These included 16 in which the hair grew back but then fell out again after re-vaccination. Nine of the patients reported previous medication allergy (JAMA 1997;278[14]:1176-8).

This appears to be a true causal effect, although quite rare considering the tens of millions of hepatitis B doses given over the last decades. But in a small number of genetically predisposed children – most of them female – there does appear to be biological plausibility because hair loss has recurred with second dose and is further supported by the several case reports of alopecia in patients with chronic active hepatitis B viral infection.

• Idiopathic thrombocytopenic purpura and MMR vaccine. This link is probably also causal. One study utilizing immunization and hospital admission records demonstrated an absolute risk of one case in every 22,300 doses within 6 weeks of MMR vaccination (Arch. Dis. Child. 2001;84[3]:227-9).

Another study, which attempted to control for the effect of viral infections, found a similar idiopathic thrombocytopenic purpura (ITP) risk of about 1 in 30,000 MMR immunizations. That population-based analysis of 506 consecutive pediatric ITP patients also found that the thrombocytopenia disappeared within a month in 74% of patients and lasted longer than 6 months in only 10% (Vaccine 2007;25[10]:1838-40).

• Myocarditis after vaccination. Inflammatory myocarditis was reported in 10 of approximately 240,000 military recipients of the smallpox vaccine and in 2 additional civilian cases during the widespread pre-event immunization program in 2001. Although it was not definitively linked to the vaccine, ACIP nonetheless recommended that those with heart disease or at risk for it should not receive the vaccine (MMWR 2003;52[13]:282-4).

In children, there have been two reported cases of myocarditis following immunization, one following the hepatitis B vaccine in a previously healthy 12-year-old girl, the other after receipt of meningococcal C conjugate vaccine in a 14-year-old boy. Both showed eosinophilic infiltrates on myocardial biopsies, consistent with an allergic reaction to the vaccine (Pediatr. Infect. Dis J. 2008;27[9]:831-5).

I think the jury is still out on this one. Certainly if you see a case, be sure to report it to VAERS.

• Acute disseminated encephalomyelitis and vaccination: These reports have been coming in since the 1970s, for a variety of different vaccines. Examples include Guillain-Barr? syndrome (GBS) following the Haemophilus influenzae B conjugate vaccine (Eur. J. Pediatr. 1993;152:613-4), central nervous system inflammatory demyelination following hepatitis B vaccination (Neurology. 2009;72[23]:2053), and transverse myelitis with oral polio vaccine (J. Paediatr. Child Health 2006;42[4]:155-9).

Without knowing the background rates of these neurologic complications among unvaccinated individuals, it is impossible to ascertain causality. An excellent data analysis conducted by Dr. Steven Black and colleagues provided very helpful estimates of the numbers of specific severe adverse events that would be expected following receipt of the 2009 H1N1 influenza vaccine.

Based on background rates, they determined that within 6 weeks of vaccination there would be 21.5 coincident cases of GBS per 10 million vaccine recipients, and 86.3 cases of optic neuritis per 10 million female vaccinees. Spontaneous abortions would occur in 16,684 of every 1 million vaccinated pregnant women, and sudden death within 1 hour of any symptom onset in 5.75 of every 10 million people vaccinated (Lancet 2009;374[9707]:2115-22).

Another important analysis was conducted by the CDC to determine whether 33 reported cases of GBS in 11- to 19-year olds within 42 days of receipt of meningococcal conjugate vaccine were causally linked. Background data from the 2000-2004 Healthcare Cost and Utilization project projected that there would be a very close 36 cases for the entire age cohort, suggesting there was no causal link. However, just 20 cases would be expected among 15- to 19-year olds, but the actual number was 26.

Although not statistically significant, this difference was enough to merit continued monitoring by the CDC, which advised that children with prior GBS not receive the vaccine (MMWR 2006;55[13]:364-6).

Finally, a population-based case-control study from France investigated cases of acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis in children younger than 16 years of age between 1994 and 2003, using 12 controls per case matched for age, sex, and geographic location. Rates of hepatitis B vaccination were 24% in cases and 27% in controls, for an adjusted odds ratio of 0.74 (Neurology. 2009;73[17]:1426-7).

One might conclude from this that hepatitis B vaccine is actually protective, but the result was not statistically significant.

Dr. Pelton writes the column, "ID Consult," which regularly appears in Pediatric News, an Elsevier publication. He is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He disclosed that he has received investigator-initiated research grants from Pfizer Inc., Novartis Vaccine and Diagnostics, GlaxoSmithKline, and Intercell. He has served on advisory boards for Pfizer, Novartis, and GSK. To respond to this column, write to [email protected].

It’s important to keep an open mind when a parent informs you that his or her child has experienced an adverse event following vaccination.

Determining which adverse events are caused by a vaccine and which are mere coincidental associations can be very difficult. As physicians who administer vaccines to children, one of the most important contributions we can make is to report all postimmunization adverse events to the Vaccine Adverse Events Reporting System. Though passive and unable to prove causation, VAERS helps authorities spot events that require follow-up with appropriate studies to determine causality. In general, the Centers for Disease Control and Prevention requires an event to occur within 42 days following immunization to be considered biologically plausible.

The best information we have comes from studies that compare population-based rates of a specific event with the postimmunization rates to see if there is a significant difference. Alternatively, case-control studies can identify whether the odds ratio for receipt of a vaccine is increased among cases. Unfortunately, such studies have been done for only a fraction of all reported postvaccination adverse events.

I’d like to highlight a few prominent adverse events that have been reported following immunization. Some, although unusual, have been causally linked to vaccines. Others, particularly certain severe neurologic outcomes, do not appear to be linked although monitoring continues.

• Thigh swelling and the DTaP vaccine. This one is fairly well established. Often confused with cellulitis, swelling of the entire arm or leg following receipt of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is reported in nearly 2% of all children following the fourth dose, with rates and severity increasing with each successive DTaP dose (Pediatr. Infect. Dis. J. 2008;27[5]:464-5).

However, unlike cellulitis, it is rarely associated with fever or other systemic symptoms, is localized to the vaccinated limb, and usually resolves completely within 48 hours. Although the swelling is likely to occur again with subsequent doses, both the CDC’s Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics recommend that the child receive all recommended DTaP doses following appropriate counseling of the parents.

• Hair loss and the hepatitis B (and other) vaccines. There have been 60 case reports of hair loss (alopecia) following receipt of vaccines, 46 of them associated with the hepatitis B vaccine. These included 16 in which the hair grew back but then fell out again after re-vaccination. Nine of the patients reported previous medication allergy (JAMA 1997;278[14]:1176-8).

This appears to be a true causal effect, although quite rare considering the tens of millions of hepatitis B doses given over the last decades. But in a small number of genetically predisposed children – most of them female – there does appear to be biological plausibility because hair loss has recurred with second dose and is further supported by the several case reports of alopecia in patients with chronic active hepatitis B viral infection.

• Idiopathic thrombocytopenic purpura and MMR vaccine. This link is probably also causal. One study utilizing immunization and hospital admission records demonstrated an absolute risk of one case in every 22,300 doses within 6 weeks of MMR vaccination (Arch. Dis. Child. 2001;84[3]:227-9).

Another study, which attempted to control for the effect of viral infections, found a similar idiopathic thrombocytopenic purpura (ITP) risk of about 1 in 30,000 MMR immunizations. That population-based analysis of 506 consecutive pediatric ITP patients also found that the thrombocytopenia disappeared within a month in 74% of patients and lasted longer than 6 months in only 10% (Vaccine 2007;25[10]:1838-40).

• Myocarditis after vaccination. Inflammatory myocarditis was reported in 10 of approximately 240,000 military recipients of the smallpox vaccine and in 2 additional civilian cases during the widespread pre-event immunization program in 2001. Although it was not definitively linked to the vaccine, ACIP nonetheless recommended that those with heart disease or at risk for it should not receive the vaccine (MMWR 2003;52[13]:282-4).

In children, there have been two reported cases of myocarditis following immunization, one following the hepatitis B vaccine in a previously healthy 12-year-old girl, the other after receipt of meningococcal C conjugate vaccine in a 14-year-old boy. Both showed eosinophilic infiltrates on myocardial biopsies, consistent with an allergic reaction to the vaccine (Pediatr. Infect. Dis J. 2008;27[9]:831-5).

I think the jury is still out on this one. Certainly if you see a case, be sure to report it to VAERS.

• Acute disseminated encephalomyelitis and vaccination: These reports have been coming in since the 1970s, for a variety of different vaccines. Examples include Guillain-Barr? syndrome (GBS) following the Haemophilus influenzae B conjugate vaccine (Eur. J. Pediatr. 1993;152:613-4), central nervous system inflammatory demyelination following hepatitis B vaccination (Neurology. 2009;72[23]:2053), and transverse myelitis with oral polio vaccine (J. Paediatr. Child Health 2006;42[4]:155-9).

Without knowing the background rates of these neurologic complications among unvaccinated individuals, it is impossible to ascertain causality. An excellent data analysis conducted by Dr. Steven Black and colleagues provided very helpful estimates of the numbers of specific severe adverse events that would be expected following receipt of the 2009 H1N1 influenza vaccine.

Based on background rates, they determined that within 6 weeks of vaccination there would be 21.5 coincident cases of GBS per 10 million vaccine recipients, and 86.3 cases of optic neuritis per 10 million female vaccinees. Spontaneous abortions would occur in 16,684 of every 1 million vaccinated pregnant women, and sudden death within 1 hour of any symptom onset in 5.75 of every 10 million people vaccinated (Lancet 2009;374[9707]:2115-22).

Another important analysis was conducted by the CDC to determine whether 33 reported cases of GBS in 11- to 19-year olds within 42 days of receipt of meningococcal conjugate vaccine were causally linked. Background data from the 2000-2004 Healthcare Cost and Utilization project projected that there would be a very close 36 cases for the entire age cohort, suggesting there was no causal link. However, just 20 cases would be expected among 15- to 19-year olds, but the actual number was 26.

Although not statistically significant, this difference was enough to merit continued monitoring by the CDC, which advised that children with prior GBS not receive the vaccine (MMWR 2006;55[13]:364-6).

Finally, a population-based case-control study from France investigated cases of acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis in children younger than 16 years of age between 1994 and 2003, using 12 controls per case matched for age, sex, and geographic location. Rates of hepatitis B vaccination were 24% in cases and 27% in controls, for an adjusted odds ratio of 0.74 (Neurology. 2009;73[17]:1426-7).

One might conclude from this that hepatitis B vaccine is actually protective, but the result was not statistically significant.

Dr. Pelton writes the column, "ID Consult," which regularly appears in Pediatric News, an Elsevier publication. He is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He disclosed that he has received investigator-initiated research grants from Pfizer Inc., Novartis Vaccine and Diagnostics, GlaxoSmithKline, and Intercell. He has served on advisory boards for Pfizer, Novartis, and GSK. To respond to this column, write to [email protected].

It’s important to keep an open mind when a parent informs you that his or her child has experienced an adverse event following vaccination.

Determining which adverse events are caused by a vaccine and which are mere coincidental associations can be very difficult. As physicians who administer vaccines to children, one of the most important contributions we can make is to report all postimmunization adverse events to the Vaccine Adverse Events Reporting System. Though passive and unable to prove causation, VAERS helps authorities spot events that require follow-up with appropriate studies to determine causality. In general, the Centers for Disease Control and Prevention requires an event to occur within 42 days following immunization to be considered biologically plausible.

The best information we have comes from studies that compare population-based rates of a specific event with the postimmunization rates to see if there is a significant difference. Alternatively, case-control studies can identify whether the odds ratio for receipt of a vaccine is increased among cases. Unfortunately, such studies have been done for only a fraction of all reported postvaccination adverse events.

I’d like to highlight a few prominent adverse events that have been reported following immunization. Some, although unusual, have been causally linked to vaccines. Others, particularly certain severe neurologic outcomes, do not appear to be linked although monitoring continues.

• Thigh swelling and the DTaP vaccine. This one is fairly well established. Often confused with cellulitis, swelling of the entire arm or leg following receipt of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is reported in nearly 2% of all children following the fourth dose, with rates and severity increasing with each successive DTaP dose (Pediatr. Infect. Dis. J. 2008;27[5]:464-5).

However, unlike cellulitis, it is rarely associated with fever or other systemic symptoms, is localized to the vaccinated limb, and usually resolves completely within 48 hours. Although the swelling is likely to occur again with subsequent doses, both the CDC’s Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics recommend that the child receive all recommended DTaP doses following appropriate counseling of the parents.

• Hair loss and the hepatitis B (and other) vaccines. There have been 60 case reports of hair loss (alopecia) following receipt of vaccines, 46 of them associated with the hepatitis B vaccine. These included 16 in which the hair grew back but then fell out again after re-vaccination. Nine of the patients reported previous medication allergy (JAMA 1997;278[14]:1176-8).

This appears to be a true causal effect, although quite rare considering the tens of millions of hepatitis B doses given over the last decades. But in a small number of genetically predisposed children – most of them female – there does appear to be biological plausibility because hair loss has recurred with second dose and is further supported by the several case reports of alopecia in patients with chronic active hepatitis B viral infection.

• Idiopathic thrombocytopenic purpura and MMR vaccine. This link is probably also causal. One study utilizing immunization and hospital admission records demonstrated an absolute risk of one case in every 22,300 doses within 6 weeks of MMR vaccination (Arch. Dis. Child. 2001;84[3]:227-9).

Another study, which attempted to control for the effect of viral infections, found a similar idiopathic thrombocytopenic purpura (ITP) risk of about 1 in 30,000 MMR immunizations. That population-based analysis of 506 consecutive pediatric ITP patients also found that the thrombocytopenia disappeared within a month in 74% of patients and lasted longer than 6 months in only 10% (Vaccine 2007;25[10]:1838-40).

• Myocarditis after vaccination. Inflammatory myocarditis was reported in 10 of approximately 240,000 military recipients of the smallpox vaccine and in 2 additional civilian cases during the widespread pre-event immunization program in 2001. Although it was not definitively linked to the vaccine, ACIP nonetheless recommended that those with heart disease or at risk for it should not receive the vaccine (MMWR 2003;52[13]:282-4).

In children, there have been two reported cases of myocarditis following immunization, one following the hepatitis B vaccine in a previously healthy 12-year-old girl, the other after receipt of meningococcal C conjugate vaccine in a 14-year-old boy. Both showed eosinophilic infiltrates on myocardial biopsies, consistent with an allergic reaction to the vaccine (Pediatr. Infect. Dis J. 2008;27[9]:831-5).

I think the jury is still out on this one. Certainly if you see a case, be sure to report it to VAERS.

• Acute disseminated encephalomyelitis and vaccination: These reports have been coming in since the 1970s, for a variety of different vaccines. Examples include Guillain-Barr? syndrome (GBS) following the Haemophilus influenzae B conjugate vaccine (Eur. J. Pediatr. 1993;152:613-4), central nervous system inflammatory demyelination following hepatitis B vaccination (Neurology. 2009;72[23]:2053), and transverse myelitis with oral polio vaccine (J. Paediatr. Child Health 2006;42[4]:155-9).

Without knowing the background rates of these neurologic complications among unvaccinated individuals, it is impossible to ascertain causality. An excellent data analysis conducted by Dr. Steven Black and colleagues provided very helpful estimates of the numbers of specific severe adverse events that would be expected following receipt of the 2009 H1N1 influenza vaccine.

Based on background rates, they determined that within 6 weeks of vaccination there would be 21.5 coincident cases of GBS per 10 million vaccine recipients, and 86.3 cases of optic neuritis per 10 million female vaccinees. Spontaneous abortions would occur in 16,684 of every 1 million vaccinated pregnant women, and sudden death within 1 hour of any symptom onset in 5.75 of every 10 million people vaccinated (Lancet 2009;374[9707]:2115-22).

Another important analysis was conducted by the CDC to determine whether 33 reported cases of GBS in 11- to 19-year olds within 42 days of receipt of meningococcal conjugate vaccine were causally linked. Background data from the 2000-2004 Healthcare Cost and Utilization project projected that there would be a very close 36 cases for the entire age cohort, suggesting there was no causal link. However, just 20 cases would be expected among 15- to 19-year olds, but the actual number was 26.

Although not statistically significant, this difference was enough to merit continued monitoring by the CDC, which advised that children with prior GBS not receive the vaccine (MMWR 2006;55[13]:364-6).

Finally, a population-based case-control study from France investigated cases of acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis in children younger than 16 years of age between 1994 and 2003, using 12 controls per case matched for age, sex, and geographic location. Rates of hepatitis B vaccination were 24% in cases and 27% in controls, for an adjusted odds ratio of 0.74 (Neurology. 2009;73[17]:1426-7).

One might conclude from this that hepatitis B vaccine is actually protective, but the result was not statistically significant.

Dr. Pelton writes the column, "ID Consult," which regularly appears in Pediatric News, an Elsevier publication. He is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He disclosed that he has received investigator-initiated research grants from Pfizer Inc., Novartis Vaccine and Diagnostics, GlaxoSmithKline, and Intercell. He has served on advisory boards for Pfizer, Novartis, and GSK. To respond to this column, write to [email protected].

It’s important to keep an open mind when a parent informs you that his or her child has experienced an adverse event following vaccination.

Determining which adverse events are caused by a vaccine and which are mere coincidental associations can be very difficult. As physicians who administer vaccines to children, one of the most important contributions we can make is to report all postimmunization adverse events to the Vaccine Adverse Events Reporting System. Though passive and unable to prove causation, VAERS helps authorities spot events that require follow-up with appropriate studies to determine causality. In general, the Centers for Disease Control and Prevention requires an event to occur within 42 days following immunization to be considered biologically plausible.

The best information we have comes from studies that compare population-based rates of a specific event with the postimmunization rates to see if there is a significant difference. Alternatively, case-control studies can identify whether the odds ratio for receipt of a vaccine is increased among cases. Unfortunately, such studies have been done for only a fraction of all reported postvaccination adverse events.

I’d like to highlight a few prominent adverse events that have been reported following immunization. Some, although unusual, have been causally linked to vaccines. Others, particularly certain severe neurologic outcomes, do not appear to be linked although monitoring continues.

• Thigh swelling and the DTaP vaccine. This one is fairly well established. Often confused with cellulitis, swelling of the entire arm or leg following receipt of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is reported in nearly 2% of all children following the fourth dose, with rates and severity increasing with each successive DTaP dose (Pediatr. Infect. Dis. J. 2008;27[5]:464-5).

However, unlike cellulitis, it is rarely associated with fever or other systemic symptoms, is localized to the vaccinated limb, and usually resolves completely within 48 hours. Although the swelling is likely to occur again with subsequent doses, both the CDC’s Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics recommend that the child receive all recommended DTaP doses following appropriate counseling of the parents.

• Hair loss and the hepatitis B (and other) vaccines. There have been 60 case reports of hair loss (alopecia) following receipt of vaccines, 46 of them associated with the hepatitis B vaccine. These included 16 in which the hair grew back but then fell out again after re-vaccination. Nine of the patients reported previous medication allergy (JAMA 1997;278[14]:1176-8).

This appears to be a true causal effect, although quite rare considering the tens of millions of hepatitis B doses given over the last decades. But in a small number of genetically predisposed children – most of them female – there does appear to be biological plausibility because hair loss has recurred with second dose and is further supported by the several case reports of alopecia in patients with chronic active hepatitis B viral infection.

• Idiopathic thrombocytopenic purpura and MMR vaccine. This link is probably also causal. One study utilizing immunization and hospital admission records demonstrated an absolute risk of one case in every 22,300 doses within 6 weeks of MMR vaccination (Arch. Dis. Child. 2001;84[3]:227-9).

Another study, which attempted to control for the effect of viral infections, found a similar idiopathic thrombocytopenic purpura (ITP) risk of about 1 in 30,000 MMR immunizations. That population-based analysis of 506 consecutive pediatric ITP patients also found that the thrombocytopenia disappeared within a month in 74% of patients and lasted longer than 6 months in only 10% (Vaccine 2007;25[10]:1838-40).

• Myocarditis after vaccination. Inflammatory myocarditis was reported in 10 of approximately 240,000 military recipients of the smallpox vaccine and in 2 additional civilian cases during the widespread pre-event immunization program in 2001. Although it was not definitively linked to the vaccine, ACIP nonetheless recommended that those with heart disease or at risk for it should not receive the vaccine (MMWR 2003;52[13]:282-4).

In children, there have been two reported cases of myocarditis following immunization, one following the hepatitis B vaccine in a previously healthy 12-year-old girl, the other after receipt of meningococcal C conjugate vaccine in a 14-year-old boy. Both showed eosinophilic infiltrates on myocardial biopsies, consistent with an allergic reaction to the vaccine (Pediatr. Infect. Dis J. 2008;27[9]:831-5).

I think the jury is still out on this one. Certainly if you see a case, be sure to report it to VAERS.

• Acute disseminated encephalomyelitis and vaccination: These reports have been coming in since the 1970s, for a variety of different vaccines. Examples include Guillain-Barr? syndrome (GBS) following the Haemophilus influenzae B conjugate vaccine (Eur. J. Pediatr. 1993;152:613-4), central nervous system inflammatory demyelination following hepatitis B vaccination (Neurology. 2009;72[23]:2053), and transverse myelitis with oral polio vaccine (J. Paediatr. Child Health 2006;42[4]:155-9).

Without knowing the background rates of these neurologic complications among unvaccinated individuals, it is impossible to ascertain causality. An excellent data analysis conducted by Dr. Steven Black and colleagues provided very helpful estimates of the numbers of specific severe adverse events that would be expected following receipt of the 2009 H1N1 influenza vaccine.

Based on background rates, they determined that within 6 weeks of vaccination there would be 21.5 coincident cases of GBS per 10 million vaccine recipients, and 86.3 cases of optic neuritis per 10 million female vaccinees. Spontaneous abortions would occur in 16,684 of every 1 million vaccinated pregnant women, and sudden death within 1 hour of any symptom onset in 5.75 of every 10 million people vaccinated (Lancet 2009;374[9707]:2115-22).

Another important analysis was conducted by the CDC to determine whether 33 reported cases of GBS in 11- to 19-year olds within 42 days of receipt of meningococcal conjugate vaccine were causally linked. Background data from the 2000-2004 Healthcare Cost and Utilization project projected that there would be a very close 36 cases for the entire age cohort, suggesting there was no causal link. However, just 20 cases would be expected among 15- to 19-year olds, but the actual number was 26.

Although not statistically significant, this difference was enough to merit continued monitoring by the CDC, which advised that children with prior GBS not receive the vaccine (MMWR 2006;55[13]:364-6).

Finally, a population-based case-control study from France investigated cases of acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis in children younger than 16 years of age between 1994 and 2003, using 12 controls per case matched for age, sex, and geographic location. Rates of hepatitis B vaccination were 24% in cases and 27% in controls, for an adjusted odds ratio of 0.74 (Neurology. 2009;73[17]:1426-7).

One might conclude from this that hepatitis B vaccine is actually protective, but the result was not statistically significant.

Dr. Pelton writes the column, "ID Consult," which regularly appears in Pediatric News, an Elsevier publication. He is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. He disclosed that he has received investigator-initiated research grants from Pfizer Inc., Novartis Vaccine and Diagnostics, GlaxoSmithKline, and Intercell. He has served on advisory boards for Pfizer, Novartis, and GSK. To respond to this column, write to [email protected].

The conventional wisdom about urinary tract infections has changed over the years, but we still don’t have consensus regarding many of its management issues.

When I was an intern in 1972, it was relatively simple. We would admit a child with a UTI to the hospital, start antimicrobial therapy, do an intravenous pyelogram after a negative urine culture, and keep the child on antibiotics for a month until the follow-up vesicoureterogram (VCUG). But in the 1980s, people began to question the evidence for spending resources on imaging and for promoting antimicrobial resistance when it may not be necessary. We have more evidence today, but still no global consensus on the issues.

We do know that UTIs are common in children of all ages, but the main concern is for those in the under-2-year age group, where there is the greatest risk for renal damage that can result from treatment delayed beyond 72 hours of fever. Vesicoureteral reflux is far more common in this age group and tends to remit with increasing age. There is also agreement that evaluation for UTI is essential for any child in that age range who has had unexplained fever for more than 24 hours. Approximately 5% will be positive.

We have data to guide our decisions regarding who is at greatest risk for UTI. It is higher in females than males, with a 2-to-1 ratio in the first year of life and 4:1 in the second. But among boys, those who are uncircumcised have a 15- to 20-fold higher UTI rate than among those who are circumcised (Pediatrics 1989;83:1011-5).

Since the advent of the 7-valent pneumococcal conjugate vaccine (PCV7), we have seen Escherichia coli increase proportionally as a cause of bacteremia as a result of the decline in pneumococcal disease (Arch. Dis. Child. 2009;94:144-7). However, the overall rate of positive urine culture among children aged 3-36 months presenting to the emergency room with fever has not changed with PCV7, remaining at approximately 7%.

There’s controversy regarding UTI screening. Urine culture is the gold standard, with identification of 10 white blood cells per high-powered field in unspun urine on gram stain. However, this is time consuming and requires an expertise that many practitioners have lost since their training.

The presence of leukocyte esterase and nitrites on dipstick has become a widely used screen for children at risk for UTI. They are highly specific for gram-negative UTIs, but not as good for detecting gram-positive organisms. Dipstick testing works best in ruling out a UTI: If both leukocyte esterase and nitrite tests are negative, the likelihood of a UTI is extremely low. If both are positive in a symptomatic at-risk child, it’s an indication to initiate therapy and obtain a culture to confirm the infection, identify the pathogen, and determine its antimicrobial susceptibility.

While use of the two measures is considered an acceptable, rapid way to screen for UTI, there is a tradeoff. For every 1,000 children with compatible UTI signs and symptoms, these tests will identify greater than 90% of the children with culture-confirmed infection. However, as many as 20% of the children will be treated unnecessarily with antibiotics. This is a significant concern, given the potential for development of resistance.

Collecting the urine specimen is another area that lacks consensus. Urine collected in a bag is unreliable in children less than 2 years of age, and it’s not certain whether bag collection can be used in older children. Three culture collection strategies are recommended by the American Academy of Pediatrics (AAP) guideline committee report: suprapubic aspiration, catheterized specimen for girls/midstream stream in circumcised boys, or midstream clean void in girls or uncircumcised boys.

Suprapubic aspiration is the gold standard, but it’s more time consuming, difficult, and is associated with more discomfort. It is typically reserved for children less than 6 months of age. On the other hand, a single midstream clean void is just 80%-90% reproducible so some recommend a second specimen, especially in asymptomatic or minimally symptomatic children, to achieve greater (95%) reproducibility.

One area in which I do think the data are clear concerns the duration of therapy. Since approximately 50%-60% of children aged 2 months to 2 years with UTIs also have upper tract infection, there is a far better chance of cure and less chance of recurrence with 7-10 days of antibiotics vs. 3 days or fewer (Pediatr. Infect. Dis. J. 1988;7:316-9).

The most controversial areas in UTI management concern imaging and antimicrobial prophylaxis. Imaging, via sonogram plus either VCUG or radionuclide scan, accomplishes four goals: It localizes the infection (upper vs. lower tract), identifies the presence of reflux, identifies structural abnormalities, and detects renal scarring. But most structural abnormalities are already identified with prenatal ultrasound, and it’s not clear whether progression of renal scarring can be prevented with prophylactic antibiotics in children with reflux. Still, localizing the infection might help guide the duration of therapy, with longer courses used for those with upper tract disease.

There is recent conflicting evidence regarding the benefit of antimicrobial prophylaxis. In a meta-analysis of eight randomized controlled trials that included 677 children who had recovered from a symptomatic UTI and in whom vesicoureteral reflux had been identified independent of acute infection, there was no difference between those who did and did not receive antimicrobial prophylaxis in recurrence of symptomatic UTI or in the incidence of new or progressive renal scarring (Acta Paediatr. 2009;98:1781-6)

But the 20-center Swedish Reflux Trial did find benefit. In that study, reflux status was compared in 203 children (128 girls/75 boys) with grade III-IV dilating vesicoureteral reflux who were treated in one of three groups, either with low dose antibiotic prophylaxis, endoscopic therapy, or with surveillance and antibiotic treatment only for febrile UTI. At 2 years, reflux had improved in all treatment arms, with reflux resolution or downgrading to grades I or II occurring in 39% of the prophylaxis group, 71% with endoscopic treatment, and 47% with surveillance (J. Urol. 2010;184:280-5).

Of concern, however, dilating reflux reappeared after initially being downgraded in 20% of the children who had received endoscopic treatment.

Both antimicrobial treatment and endoscopic therapy reduced the infection recurrence rate among the girls, occurring in 8 of 43 (19%) on prophylaxis and 10 of 43 (23%) with endoscopic therapy, compared with 24 of 42 (57%) on surveillance. In girls, the recurrence rate was associated with persistent reflux after 2 years. However, reflux severity (grade III or IV) at study entry did not predict recurrence (J. Urol. 2010;184:286-91).

Given the conflicting data, it’s no surprise that guidelines also differ. The AAP advises ultrasound and VCUG for all children aged 2 months to 2 years, and antimicrobial prophylaxis for all in whom reflux is identified (Pediatrics 1999;103:843-52). In contrast, guidelines from the United Kingdom advise ultrasound only for recurrent or "atypical" UTI, and do not recommend prophylaxis after a first UTI, but only after a recurrence.

Also not surprising, practitioners differ in what they do. In an analysis of Washington State Medicaid data for 780 children diagnosed with UTI during their first year of life, less than half received either timely anatomic imaging (44%) or imaging for reflux (39.5%). Of those who had imaging for reflux, only 51% had adequate antibiotics to maintain antimicrobial prophylaxis between diagnosis and imaging for reflux (Pediatrics 2005;115:1474-8).

I believe there is certainly a role for prophylaxis in a child with recurrent UTI, especially recurrent symptomatic/febrile UTI. But whether there’s a role after the first UTI remains uncertain, with conflicting evidence. We might get some answers from an ongoing randomized, placebo-controlled intervention sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases examining whether prophylactic antibiotics prevent UTIs and renal scarring in children with reflux in which results are expected in June 2011.

Dr. Pelton is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton said he has received research grants and served as a consultant to GlaxoSmithKline, Pfizer, Novartis, and Intercell.

The conventional wisdom about urinary tract infections has changed over the years, but we still don’t have consensus regarding many of its management issues.

When I was an intern in 1972, it was relatively simple. We would admit a child with a UTI to the hospital, start antimicrobial therapy, do an intravenous pyelogram after a negative urine culture, and keep the child on antibiotics for a month until the follow-up vesicoureterogram (VCUG). But in the 1980s, people began to question the evidence for spending resources on imaging and for promoting antimicrobial resistance when it may not be necessary. We have more evidence today, but still no global consensus on the issues.

We do know that UTIs are common in children of all ages, but the main concern is for those in the under-2-year age group, where there is the greatest risk for renal damage that can result from treatment delayed beyond 72 hours of fever. Vesicoureteral reflux is far more common in this age group and tends to remit with increasing age. There is also agreement that evaluation for UTI is essential for any child in that age range who has had unexplained fever for more than 24 hours. Approximately 5% will be positive.

We have data to guide our decisions regarding who is at greatest risk for UTI. It is higher in females than males, with a 2-to-1 ratio in the first year of life and 4:1 in the second. But among boys, those who are uncircumcised have a 15- to 20-fold higher UTI rate than among those who are circumcised (Pediatrics 1989;83:1011-5).

Since the advent of the 7-valent pneumococcal conjugate vaccine (PCV7), we have seen Escherichia coli increase proportionally as a cause of bacteremia as a result of the decline in pneumococcal disease (Arch. Dis. Child. 2009;94:144-7). However, the overall rate of positive urine culture among children aged 3-36 months presenting to the emergency room with fever has not changed with PCV7, remaining at approximately 7%.

There’s controversy regarding UTI screening. Urine culture is the gold standard, with identification of 10 white blood cells per high-powered field in unspun urine on gram stain. However, this is time consuming and requires an expertise that many practitioners have lost since their training.

The presence of leukocyte esterase and nitrites on dipstick has become a widely used screen for children at risk for UTI. They are highly specific for gram-negative UTIs, but not as good for detecting gram-positive organisms. Dipstick testing works best in ruling out a UTI: If both leukocyte esterase and nitrite tests are negative, the likelihood of a UTI is extremely low. If both are positive in a symptomatic at-risk child, it’s an indication to initiate therapy and obtain a culture to confirm the infection, identify the pathogen, and determine its antimicrobial susceptibility.

While use of the two measures is considered an acceptable, rapid way to screen for UTI, there is a tradeoff. For every 1,000 children with compatible UTI signs and symptoms, these tests will identify greater than 90% of the children with culture-confirmed infection. However, as many as 20% of the children will be treated unnecessarily with antibiotics. This is a significant concern, given the potential for development of resistance.

Collecting the urine specimen is another area that lacks consensus. Urine collected in a bag is unreliable in children less than 2 years of age, and it’s not certain whether bag collection can be used in older children. Three culture collection strategies are recommended by the American Academy of Pediatrics (AAP) guideline committee report: suprapubic aspiration, catheterized specimen for girls/midstream stream in circumcised boys, or midstream clean void in girls or uncircumcised boys.

Suprapubic aspiration is the gold standard, but it’s more time consuming, difficult, and is associated with more discomfort. It is typically reserved for children less than 6 months of age. On the other hand, a single midstream clean void is just 80%-90% reproducible so some recommend a second specimen, especially in asymptomatic or minimally symptomatic children, to achieve greater (95%) reproducibility.

One area in which I do think the data are clear concerns the duration of therapy. Since approximately 50%-60% of children aged 2 months to 2 years with UTIs also have upper tract infection, there is a far better chance of cure and less chance of recurrence with 7-10 days of antibiotics vs. 3 days or fewer (Pediatr. Infect. Dis. J. 1988;7:316-9).

The most controversial areas in UTI management concern imaging and antimicrobial prophylaxis. Imaging, via sonogram plus either VCUG or radionuclide scan, accomplishes four goals: It localizes the infection (upper vs. lower tract), identifies the presence of reflux, identifies structural abnormalities, and detects renal scarring. But most structural abnormalities are already identified with prenatal ultrasound, and it’s not clear whether progression of renal scarring can be prevented with prophylactic antibiotics in children with reflux. Still, localizing the infection might help guide the duration of therapy, with longer courses used for those with upper tract disease.

There is recent conflicting evidence regarding the benefit of antimicrobial prophylaxis. In a meta-analysis of eight randomized controlled trials that included 677 children who had recovered from a symptomatic UTI and in whom vesicoureteral reflux had been identified independent of acute infection, there was no difference between those who did and did not receive antimicrobial prophylaxis in recurrence of symptomatic UTI or in the incidence of new or progressive renal scarring (Acta Paediatr. 2009;98:1781-6)

But the 20-center Swedish Reflux Trial did find benefit. In that study, reflux status was compared in 203 children (128 girls/75 boys) with grade III-IV dilating vesicoureteral reflux who were treated in one of three groups, either with low dose antibiotic prophylaxis, endoscopic therapy, or with surveillance and antibiotic treatment only for febrile UTI. At 2 years, reflux had improved in all treatment arms, with reflux resolution or downgrading to grades I or II occurring in 39% of the prophylaxis group, 71% with endoscopic treatment, and 47% with surveillance (J. Urol. 2010;184:280-5).

Of concern, however, dilating reflux reappeared after initially being downgraded in 20% of the children who had received endoscopic treatment.

Both antimicrobial treatment and endoscopic therapy reduced the infection recurrence rate among the girls, occurring in 8 of 43 (19%) on prophylaxis and 10 of 43 (23%) with endoscopic therapy, compared with 24 of 42 (57%) on surveillance. In girls, the recurrence rate was associated with persistent reflux after 2 years. However, reflux severity (grade III or IV) at study entry did not predict recurrence (J. Urol. 2010;184:286-91).

Given the conflicting data, it’s no surprise that guidelines also differ. The AAP advises ultrasound and VCUG for all children aged 2 months to 2 years, and antimicrobial prophylaxis for all in whom reflux is identified (Pediatrics 1999;103:843-52). In contrast, guidelines from the United Kingdom advise ultrasound only for recurrent or "atypical" UTI, and do not recommend prophylaxis after a first UTI, but only after a recurrence.

Also not surprising, practitioners differ in what they do. In an analysis of Washington State Medicaid data for 780 children diagnosed with UTI during their first year of life, less than half received either timely anatomic imaging (44%) or imaging for reflux (39.5%). Of those who had imaging for reflux, only 51% had adequate antibiotics to maintain antimicrobial prophylaxis between diagnosis and imaging for reflux (Pediatrics 2005;115:1474-8).

I believe there is certainly a role for prophylaxis in a child with recurrent UTI, especially recurrent symptomatic/febrile UTI. But whether there’s a role after the first UTI remains uncertain, with conflicting evidence. We might get some answers from an ongoing randomized, placebo-controlled intervention sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases examining whether prophylactic antibiotics prevent UTIs and renal scarring in children with reflux in which results are expected in June 2011.

Dr. Pelton is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton said he has received research grants and served as a consultant to GlaxoSmithKline, Pfizer, Novartis, and Intercell.

The conventional wisdom about urinary tract infections has changed over the years, but we still don’t have consensus regarding many of its management issues.

When I was an intern in 1972, it was relatively simple. We would admit a child with a UTI to the hospital, start antimicrobial therapy, do an intravenous pyelogram after a negative urine culture, and keep the child on antibiotics for a month until the follow-up vesicoureterogram (VCUG). But in the 1980s, people began to question the evidence for spending resources on imaging and for promoting antimicrobial resistance when it may not be necessary. We have more evidence today, but still no global consensus on the issues.

We do know that UTIs are common in children of all ages, but the main concern is for those in the under-2-year age group, where there is the greatest risk for renal damage that can result from treatment delayed beyond 72 hours of fever. Vesicoureteral reflux is far more common in this age group and tends to remit with increasing age. There is also agreement that evaluation for UTI is essential for any child in that age range who has had unexplained fever for more than 24 hours. Approximately 5% will be positive.

We have data to guide our decisions regarding who is at greatest risk for UTI. It is higher in females than males, with a 2-to-1 ratio in the first year of life and 4:1 in the second. But among boys, those who are uncircumcised have a 15- to 20-fold higher UTI rate than among those who are circumcised (Pediatrics 1989;83:1011-5).

Since the advent of the 7-valent pneumococcal conjugate vaccine (PCV7), we have seen Escherichia coli increase proportionally as a cause of bacteremia as a result of the decline in pneumococcal disease (Arch. Dis. Child. 2009;94:144-7). However, the overall rate of positive urine culture among children aged 3-36 months presenting to the emergency room with fever has not changed with PCV7, remaining at approximately 7%.

There’s controversy regarding UTI screening. Urine culture is the gold standard, with identification of 10 white blood cells per high-powered field in unspun urine on gram stain. However, this is time consuming and requires an expertise that many practitioners have lost since their training.

The presence of leukocyte esterase and nitrites on dipstick has become a widely used screen for children at risk for UTI. They are highly specific for gram-negative UTIs, but not as good for detecting gram-positive organisms. Dipstick testing works best in ruling out a UTI: If both leukocyte esterase and nitrite tests are negative, the likelihood of a UTI is extremely low. If both are positive in a symptomatic at-risk child, it’s an indication to initiate therapy and obtain a culture to confirm the infection, identify the pathogen, and determine its antimicrobial susceptibility.

While use of the two measures is considered an acceptable, rapid way to screen for UTI, there is a tradeoff. For every 1,000 children with compatible UTI signs and symptoms, these tests will identify greater than 90% of the children with culture-confirmed infection. However, as many as 20% of the children will be treated unnecessarily with antibiotics. This is a significant concern, given the potential for development of resistance.

Collecting the urine specimen is another area that lacks consensus. Urine collected in a bag is unreliable in children less than 2 years of age, and it’s not certain whether bag collection can be used in older children. Three culture collection strategies are recommended by the American Academy of Pediatrics (AAP) guideline committee report: suprapubic aspiration, catheterized specimen for girls/midstream stream in circumcised boys, or midstream clean void in girls or uncircumcised boys.

Suprapubic aspiration is the gold standard, but it’s more time consuming, difficult, and is associated with more discomfort. It is typically reserved for children less than 6 months of age. On the other hand, a single midstream clean void is just 80%-90% reproducible so some recommend a second specimen, especially in asymptomatic or minimally symptomatic children, to achieve greater (95%) reproducibility.

One area in which I do think the data are clear concerns the duration of therapy. Since approximately 50%-60% of children aged 2 months to 2 years with UTIs also have upper tract infection, there is a far better chance of cure and less chance of recurrence with 7-10 days of antibiotics vs. 3 days or fewer (Pediatr. Infect. Dis. J. 1988;7:316-9).

The most controversial areas in UTI management concern imaging and antimicrobial prophylaxis. Imaging, via sonogram plus either VCUG or radionuclide scan, accomplishes four goals: It localizes the infection (upper vs. lower tract), identifies the presence of reflux, identifies structural abnormalities, and detects renal scarring. But most structural abnormalities are already identified with prenatal ultrasound, and it’s not clear whether progression of renal scarring can be prevented with prophylactic antibiotics in children with reflux. Still, localizing the infection might help guide the duration of therapy, with longer courses used for those with upper tract disease.

There is recent conflicting evidence regarding the benefit of antimicrobial prophylaxis. In a meta-analysis of eight randomized controlled trials that included 677 children who had recovered from a symptomatic UTI and in whom vesicoureteral reflux had been identified independent of acute infection, there was no difference between those who did and did not receive antimicrobial prophylaxis in recurrence of symptomatic UTI or in the incidence of new or progressive renal scarring (Acta Paediatr. 2009;98:1781-6)

But the 20-center Swedish Reflux Trial did find benefit. In that study, reflux status was compared in 203 children (128 girls/75 boys) with grade III-IV dilating vesicoureteral reflux who were treated in one of three groups, either with low dose antibiotic prophylaxis, endoscopic therapy, or with surveillance and antibiotic treatment only for febrile UTI. At 2 years, reflux had improved in all treatment arms, with reflux resolution or downgrading to grades I or II occurring in 39% of the prophylaxis group, 71% with endoscopic treatment, and 47% with surveillance (J. Urol. 2010;184:280-5).

Of concern, however, dilating reflux reappeared after initially being downgraded in 20% of the children who had received endoscopic treatment.

Both antimicrobial treatment and endoscopic therapy reduced the infection recurrence rate among the girls, occurring in 8 of 43 (19%) on prophylaxis and 10 of 43 (23%) with endoscopic therapy, compared with 24 of 42 (57%) on surveillance. In girls, the recurrence rate was associated with persistent reflux after 2 years. However, reflux severity (grade III or IV) at study entry did not predict recurrence (J. Urol. 2010;184:286-91).

Given the conflicting data, it’s no surprise that guidelines also differ. The AAP advises ultrasound and VCUG for all children aged 2 months to 2 years, and antimicrobial prophylaxis for all in whom reflux is identified (Pediatrics 1999;103:843-52). In contrast, guidelines from the United Kingdom advise ultrasound only for recurrent or "atypical" UTI, and do not recommend prophylaxis after a first UTI, but only after a recurrence.

Also not surprising, practitioners differ in what they do. In an analysis of Washington State Medicaid data for 780 children diagnosed with UTI during their first year of life, less than half received either timely anatomic imaging (44%) or imaging for reflux (39.5%). Of those who had imaging for reflux, only 51% had adequate antibiotics to maintain antimicrobial prophylaxis between diagnosis and imaging for reflux (Pediatrics 2005;115:1474-8).

I believe there is certainly a role for prophylaxis in a child with recurrent UTI, especially recurrent symptomatic/febrile UTI. But whether there’s a role after the first UTI remains uncertain, with conflicting evidence. We might get some answers from an ongoing randomized, placebo-controlled intervention sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases examining whether prophylactic antibiotics prevent UTIs and renal scarring in children with reflux in which results are expected in June 2011.

Dr. Pelton is chief of pediatric infectious disease and also is the coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton said he has received research grants and served as a consultant to GlaxoSmithKline, Pfizer, Novartis, and Intercell.