Stephen I. Pelton

At the Conference on Retroviruses and Opportunistic Infection in March, investigators presented the case of a child born to an HIV-infected mother who received highly active antiretroviral therapy (HAART) beginning at 30 hours of age. The child was demonstrated to have plasma viremia on day 2 of life and a positive qualitative DNA polymerase chain reaction. The child received triple-drug therapy and declining plasma viremia was documented on three additional occasions during the first month of life. The child was treated with three drugs for approximately 18 months and was lost to follow-up; no HAART was administered beyond that time. At age 26 months, after months without antiretroviral therapy, HIV DNA was detected at 4 copies/million peripheral blood mononuclear cell (PBMC). Plasma viral load, PBMC DNA, and HIV-specific antibodies remained undetectable with standard clinical assays. Does this child represent a functional cure as the investigators suggest? Will early, multidrug therapy cure HIV in infants with intrauterine or perinatal acquisition of HIV?

The functional cure of HIV in this newborn builds on the already successful experiences in prevention of HIV transmission by administration of antiretroviral therapy within the first 48 hours of life or after exposure, most often in health care workers after needle stick. Since the 1990s, postexposure prophylaxis against HIV infection has been used after occupational exposures, most often after needle sticks. A case-control study supported the efficacy of this approach in that health care workers who received zidovudine after needle stick exposures were 81% less likely to develop HIV infection (N. Eng. J. Med. 1997;337:1485-90). The success of postexposure prophylaxis appears to be related to the inoculum of virus as represented by visible blood and large bore needles being more often associated with transmission. This evidence suggests that when administered early enough after a challenge dose, infection can be prevented.

Similarly, New York State’s mandatory HIV testing for all newborns has identified that when administration of zidovudine was initiated within the first 48 hours after birth to neonate whose mothers did not receive prior antiretroviral treatment, the rate of HIV infection was reduced from about 18% to about 9%. (N. Engl. J. Med. 1998;339:1409-14) A large study furthered these observations demonstrating that ART administered within 48 hours of birth reduces rates of infection in infants born to HIV infected women who did not receive prior treatment during pregnancy (N. Engl. J. Med. 2012;366:2368-79). Evidence has also accumulated that concurrent administration of ART to breast feeding infants of HIV infected mothers (N. Engl. J. Med. 2008;359:119-29) or to HIV uninfected sexually partners of HIV infected men decreases virus transmission substantially (MMWR 2011;60:65-8).

What is different in our newborn is the documentation of increasing plasma viral replication in the first month of life, signifying infection, not simply exposure. First, most newborn infection arises from exposure shortly before or at the time of birth. Studies demonstrating a lower transmission rate in twin B, compared with twin A, are thought to relate to the time in the birth canal and exposure in to genital tract secretions or blood. Once the infant is exposed, the immune system will respond with an array of immune cellular mechanisms hoping to prevent replication, dissemination, and development of latency [infection of primarily resting-memory T lymphocytes in which the virus is "silent"]. Current concepts suggest that this battle between the virus and the immune system occurs over several days, and the virus is either cleared or infection is established. In this infant, viremia was documented at 30 hours of age, which makes it less certain when infection occurred (intrauterine vs. perinatal) and therefore at what sequence in the pathogenesis antiretroviral therapies were initiated. The outcome, however, suggests that it was before latency was established, permitting a long term functional cure as evidenced by the fact that replicating virus could not be detected some 8 months off treatment.

Is this a one-of-a-kind event, where infection and functional cure was exquisitely demonstrated? Is this more common than we have documented and explains some of the success of strategies that initiate prophylaxis within the first 48 hours?

Did this child fail to develop latent infection because triple-drug therapy was initiated at less than 30 hours of age? It would perhaps be more puzzling if this child were infected in utero as suggested by the early detection of viremia. If intrauterine infection occurred, then why wasn’t latent infection established prior to initiation of therapy? What conclusion can we draw from this experience? First, there is still a significant amount of biology about newborn transmission that requires further study. While our approach to prevention of mother to child transmission incorporating maternal, peripartum, and postpartum prophylaxis has been hugely successful, now we have further evidence that early initiation of ARTs to infants born to HIV-infected women who had not received prophylaxis/treatment can still be effective in either prevention or possible cure.

Recent data of functional cure in adults when HAART is initiated in the early stages of infection raises new hope that current ART may be sufficiently powerful to rapidly clear viremia and prevent infection of a complete array of resting cells that perpetuate infection. I think it is premature to conclude we understand the time sequence of exposure to infection well enough to predict in whom we might achieve a cure, but it is not premature to imagine that we are moving the football down the field.

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

At the Conference on Retroviruses and Opportunistic Infection in March, investigators presented the case of a child born to an HIV-infected mother who received highly active antiretroviral therapy (HAART) beginning at 30 hours of age. The child was demonstrated to have plasma viremia on day 2 of life and a positive qualitative DNA polymerase chain reaction. The child received triple-drug therapy and declining plasma viremia was documented on three additional occasions during the first month of life. The child was treated with three drugs for approximately 18 months and was lost to follow-up; no HAART was administered beyond that time. At age 26 months, after months without antiretroviral therapy, HIV DNA was detected at 4 copies/million peripheral blood mononuclear cell (PBMC). Plasma viral load, PBMC DNA, and HIV-specific antibodies remained undetectable with standard clinical assays. Does this child represent a functional cure as the investigators suggest? Will early, multidrug therapy cure HIV in infants with intrauterine or perinatal acquisition of HIV?

The functional cure of HIV in this newborn builds on the already successful experiences in prevention of HIV transmission by administration of antiretroviral therapy within the first 48 hours of life or after exposure, most often in health care workers after needle stick. Since the 1990s, postexposure prophylaxis against HIV infection has been used after occupational exposures, most often after needle sticks. A case-control study supported the efficacy of this approach in that health care workers who received zidovudine after needle stick exposures were 81% less likely to develop HIV infection (N. Eng. J. Med. 1997;337:1485-90). The success of postexposure prophylaxis appears to be related to the inoculum of virus as represented by visible blood and large bore needles being more often associated with transmission. This evidence suggests that when administered early enough after a challenge dose, infection can be prevented.

Similarly, New York State’s mandatory HIV testing for all newborns has identified that when administration of zidovudine was initiated within the first 48 hours after birth to neonate whose mothers did not receive prior antiretroviral treatment, the rate of HIV infection was reduced from about 18% to about 9%. (N. Engl. J. Med. 1998;339:1409-14) A large study furthered these observations demonstrating that ART administered within 48 hours of birth reduces rates of infection in infants born to HIV infected women who did not receive prior treatment during pregnancy (N. Engl. J. Med. 2012;366:2368-79). Evidence has also accumulated that concurrent administration of ART to breast feeding infants of HIV infected mothers (N. Engl. J. Med. 2008;359:119-29) or to HIV uninfected sexually partners of HIV infected men decreases virus transmission substantially (MMWR 2011;60:65-8).

What is different in our newborn is the documentation of increasing plasma viral replication in the first month of life, signifying infection, not simply exposure. First, most newborn infection arises from exposure shortly before or at the time of birth. Studies demonstrating a lower transmission rate in twin B, compared with twin A, are thought to relate to the time in the birth canal and exposure in to genital tract secretions or blood. Once the infant is exposed, the immune system will respond with an array of immune cellular mechanisms hoping to prevent replication, dissemination, and development of latency [infection of primarily resting-memory T lymphocytes in which the virus is "silent"]. Current concepts suggest that this battle between the virus and the immune system occurs over several days, and the virus is either cleared or infection is established. In this infant, viremia was documented at 30 hours of age, which makes it less certain when infection occurred (intrauterine vs. perinatal) and therefore at what sequence in the pathogenesis antiretroviral therapies were initiated. The outcome, however, suggests that it was before latency was established, permitting a long term functional cure as evidenced by the fact that replicating virus could not be detected some 8 months off treatment.

Is this a one-of-a-kind event, where infection and functional cure was exquisitely demonstrated? Is this more common than we have documented and explains some of the success of strategies that initiate prophylaxis within the first 48 hours?

Did this child fail to develop latent infection because triple-drug therapy was initiated at less than 30 hours of age? It would perhaps be more puzzling if this child were infected in utero as suggested by the early detection of viremia. If intrauterine infection occurred, then why wasn’t latent infection established prior to initiation of therapy? What conclusion can we draw from this experience? First, there is still a significant amount of biology about newborn transmission that requires further study. While our approach to prevention of mother to child transmission incorporating maternal, peripartum, and postpartum prophylaxis has been hugely successful, now we have further evidence that early initiation of ARTs to infants born to HIV-infected women who had not received prophylaxis/treatment can still be effective in either prevention or possible cure.

Recent data of functional cure in adults when HAART is initiated in the early stages of infection raises new hope that current ART may be sufficiently powerful to rapidly clear viremia and prevent infection of a complete array of resting cells that perpetuate infection. I think it is premature to conclude we understand the time sequence of exposure to infection well enough to predict in whom we might achieve a cure, but it is not premature to imagine that we are moving the football down the field.

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

At the Conference on Retroviruses and Opportunistic Infection in March, investigators presented the case of a child born to an HIV-infected mother who received highly active antiretroviral therapy (HAART) beginning at 30 hours of age. The child was demonstrated to have plasma viremia on day 2 of life and a positive qualitative DNA polymerase chain reaction. The child received triple-drug therapy and declining plasma viremia was documented on three additional occasions during the first month of life. The child was treated with three drugs for approximately 18 months and was lost to follow-up; no HAART was administered beyond that time. At age 26 months, after months without antiretroviral therapy, HIV DNA was detected at 4 copies/million peripheral blood mononuclear cell (PBMC). Plasma viral load, PBMC DNA, and HIV-specific antibodies remained undetectable with standard clinical assays. Does this child represent a functional cure as the investigators suggest? Will early, multidrug therapy cure HIV in infants with intrauterine or perinatal acquisition of HIV?

The functional cure of HIV in this newborn builds on the already successful experiences in prevention of HIV transmission by administration of antiretroviral therapy within the first 48 hours of life or after exposure, most often in health care workers after needle stick. Since the 1990s, postexposure prophylaxis against HIV infection has been used after occupational exposures, most often after needle sticks. A case-control study supported the efficacy of this approach in that health care workers who received zidovudine after needle stick exposures were 81% less likely to develop HIV infection (N. Eng. J. Med. 1997;337:1485-90). The success of postexposure prophylaxis appears to be related to the inoculum of virus as represented by visible blood and large bore needles being more often associated with transmission. This evidence suggests that when administered early enough after a challenge dose, infection can be prevented.

Similarly, New York State’s mandatory HIV testing for all newborns has identified that when administration of zidovudine was initiated within the first 48 hours after birth to neonate whose mothers did not receive prior antiretroviral treatment, the rate of HIV infection was reduced from about 18% to about 9%. (N. Engl. J. Med. 1998;339:1409-14) A large study furthered these observations demonstrating that ART administered within 48 hours of birth reduces rates of infection in infants born to HIV infected women who did not receive prior treatment during pregnancy (N. Engl. J. Med. 2012;366:2368-79). Evidence has also accumulated that concurrent administration of ART to breast feeding infants of HIV infected mothers (N. Engl. J. Med. 2008;359:119-29) or to HIV uninfected sexually partners of HIV infected men decreases virus transmission substantially (MMWR 2011;60:65-8).

What is different in our newborn is the documentation of increasing plasma viral replication in the first month of life, signifying infection, not simply exposure. First, most newborn infection arises from exposure shortly before or at the time of birth. Studies demonstrating a lower transmission rate in twin B, compared with twin A, are thought to relate to the time in the birth canal and exposure in to genital tract secretions or blood. Once the infant is exposed, the immune system will respond with an array of immune cellular mechanisms hoping to prevent replication, dissemination, and development of latency [infection of primarily resting-memory T lymphocytes in which the virus is "silent"]. Current concepts suggest that this battle between the virus and the immune system occurs over several days, and the virus is either cleared or infection is established. In this infant, viremia was documented at 30 hours of age, which makes it less certain when infection occurred (intrauterine vs. perinatal) and therefore at what sequence in the pathogenesis antiretroviral therapies were initiated. The outcome, however, suggests that it was before latency was established, permitting a long term functional cure as evidenced by the fact that replicating virus could not be detected some 8 months off treatment.

Is this a one-of-a-kind event, where infection and functional cure was exquisitely demonstrated? Is this more common than we have documented and explains some of the success of strategies that initiate prophylaxis within the first 48 hours?

Did this child fail to develop latent infection because triple-drug therapy was initiated at less than 30 hours of age? It would perhaps be more puzzling if this child were infected in utero as suggested by the early detection of viremia. If intrauterine infection occurred, then why wasn’t latent infection established prior to initiation of therapy? What conclusion can we draw from this experience? First, there is still a significant amount of biology about newborn transmission that requires further study. While our approach to prevention of mother to child transmission incorporating maternal, peripartum, and postpartum prophylaxis has been hugely successful, now we have further evidence that early initiation of ARTs to infants born to HIV-infected women who had not received prophylaxis/treatment can still be effective in either prevention or possible cure.

Recent data of functional cure in adults when HAART is initiated in the early stages of infection raises new hope that current ART may be sufficiently powerful to rapidly clear viremia and prevent infection of a complete array of resting cells that perpetuate infection. I think it is premature to conclude we understand the time sequence of exposure to infection well enough to predict in whom we might achieve a cure, but it is not premature to imagine that we are moving the football down the field.

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

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 – 1 in every 6 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 because of 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).

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.

▸ E. coli or other shiga toxin–producing strains. This foodborne infection has been in the headlines lately, and 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.

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 – 1 in every 6 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 because of 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).

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.

▸ E. coli or other shiga toxin–producing strains. This foodborne infection has been in the headlines lately, and 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.

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 – 1 in every 6 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 because of 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).

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.

▸ E. coli or other shiga toxin–producing strains. This foodborne infection has been in the headlines lately, and 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.

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 (http://vaers.hhs.gov/index

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;27:464-5).

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;278:1176-8). This appears to be a true causal effect, although 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 chronic active hepatitis B viral infection patients.

▸ 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;84:227-9). 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;25:1838-40).

▸ 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;52:282-4).

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;27:831-5). 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-Barré 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;72:2053), and transverse myelitis with oral polio vaccine (J. Paediatr. Child Health 2006;42:155-9).

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;374:2115-22).

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 estimated that there would be very close to 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;55:364-6).

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;73:1426-7). One might conclude from this that hepatitis B vaccine is actually protective, but the result was not statistically significant.

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 (http://vaers.hhs.gov/index

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;27:464-5).

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;278:1176-8). This appears to be a true causal effect, although 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 chronic active hepatitis B viral infection patients.

▸ 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;84:227-9). 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;25:1838-40).

▸ 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;52:282-4).

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;27:831-5). 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-Barré 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;72:2053), and transverse myelitis with oral polio vaccine (J. Paediatr. Child Health 2006;42:155-9).

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;374:2115-22).

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 estimated that there would be very close to 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;55:364-6).

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;73:1426-7). One might conclude from this that hepatitis B vaccine is actually protective, but the result was not statistically significant.

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 (http://vaers.hhs.gov/index

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;27:464-5).

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;278:1176-8). This appears to be a true causal effect, although 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 chronic active hepatitis B viral infection patients.

▸ 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;84:227-9). 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;25:1838-40).

▸ 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;52:282-4).

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;27:831-5). 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-Barré 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;72:2053), and transverse myelitis with oral polio vaccine (J. Paediatr. Child Health 2006;42:155-9).

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;374:2115-22).

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 estimated that there would be very close to 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;55:364-6).

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;73:1426-7). One might conclude from this that hepatitis B vaccine is actually protective, but the result was not statistically significant.

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.

Today we 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.

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 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.

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 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 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.

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 103;1999:843-52). 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 (clinicaltrials.gov

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.

Today we 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.

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 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.

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 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 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.

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 103;1999:843-52). 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 (clinicaltrials.gov

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.

Today we 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.

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 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.

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 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 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.

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 103;1999:843-52). 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 (clinicaltrials.gov

The new 13-valent pneumococcal conjugate vaccine (Prevnar 13) is picking up right where the 7-valent version left off.

It has been 10 years since the introduction of the 7-valent pneumococcal conjugate vaccine (Prevnar). Overall in the United States, the program has had significant success, with an approximate 65%-70% reduction in invasive disease due to Streptococcus pneumoniae. We've also seen substantial reductions in acute otitis media (AOM) and community-acquired pneumonia (CAP).

Nonetheless, in the last few years we've started to see a small but real increase in invasive disease due to nonvaccine serotypes, documented by the Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) system.

At the same time, there has also been documentation of an increase in AOM and a presumption of increases in CAP due to nonvaccine serotypes. These are harder to document, because data are typically obtained from hospital admissions or insurance claims and not from microbiological testing as is done with the ABCs. However, small studies using tympanocentesis have shown high proportions of nonvaccine S. pneumoniae serotypes in children with middle ear disease (Pediatr. Infect. Dis. J. 2007;26:S12–6).

Although we can't determine exactly what proportion of CAP and AOM is due to S. pneumoniae at any given time – and the longitudinal data are complicated by the secular changes in AOM definition – we do know that for every 1 case of invasive disease there are about 10 cases of CAP and 100 of AOM. So, we're looking at very clinically significant numbers.

In addition to the shift in serotypes, we've seen the emergence of multidrug-resistant pneumococci, particularly strain 19A. While these strains are usually sensitive to vancomycin, linezolid, and fluoroquinolones, they are resistant to the usual first-line antimicrobials, including amoxicillin, clindamycin, and trimethoprim-sulfamethoxazole, as well as ceftriaxone and other cephalosporins. Thus, both CAP and AOM have become more difficult to treat in children who don't respond to initial therapy.

Licensed earlier this year, PCV13 (Prevnar 13) contains all seven of the PCV7 strains (4, 6B, 9V, 14, 18C, 19F, and 23F), plus six more (1, 3, 5, 6A, 7F, and 19A). The serotypes represent either those that have been increasing in some countries using PCV7 (19A, 7F, 3) or that are globally important (1 and 5).

The vaccine was licensed on the basis of immunogenicity for the new serotypes as well as comparability to PCV7 for the seven “old” serotypes and a comparable safety profile.

The 13-valent vaccine is being introduced somewhat differently than was PCV7. The recommendation from the CDC Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians is to administer PCV13 routinely to all children aged 2, 4, 6, and 12–15 months.

For children who previously received one or more doses of PCV7, the series should be completed with PCV13. And for children 15 months through 5 years of age who received only PCV7 (or no vaccine), a single dose of PCV13 is recommended.

In contrast, when PCV7 was licensed, the recommended catchup immunization was through 2 years of age and only high-risk children aged 2–5 years. That's because, in general, the risk for invasive pneumococcal disease begins to decline after 3 years of age.

However, the data on multidrug-resistant strain 19A suggest that it has been producing substantial disease in previously healthy children up through 5 years of age.

In addition, nasopharyngeal carriage of 19A has been seen frequently in children up to age 5. It is hoped that preventing that carriage will reduce the spread to unvaccinated children less than 4–5 months of age, immunocompromised children who don't respond sufficiently to the vaccine, and adults.

Adding indirect protection to a large part of the population should help to reduce the incidence of disease due to the new vaccine serotypes.

Finally, I'd like to address a question that often arises. With new conjugate pneumococcal vaccines, are we simply shifting the serotypes that produce disease and not actually preventing it? I would say no. With each new expansion of the vaccine, not only do we add broader coverage, but we expect to see a further reduction in disease.

It is anticipated that the six new strains of PCV13 will add another 10%-15% reduction in pneumococcal disease beyond the 65%-70% we've already seen with PCV7, so that we will now achieve an approximate 80%-90% disease reduction compared with rates in 1998–1999.

However, I don't think we will entirely eliminate pneumococcal disease. A few other important nonvaccine serotypes, including 22F, 33F, and 15B/C, are likely to continue and possibly increase slightly following the introduction of PCV13. Nonetheless, it will help us to reduce the burden of pneumococcal disease on child health.

The new 13-valent pneumococcal conjugate vaccine (Prevnar 13) is picking up right where the 7-valent version left off.

It has been 10 years since the introduction of the 7-valent pneumococcal conjugate vaccine (Prevnar). Overall in the United States, the program has had significant success, with an approximate 65%-70% reduction in invasive disease due to Streptococcus pneumoniae. We've also seen substantial reductions in acute otitis media (AOM) and community-acquired pneumonia (CAP).

Nonetheless, in the last few years we've started to see a small but real increase in invasive disease due to nonvaccine serotypes, documented by the Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) system.

At the same time, there has also been documentation of an increase in AOM and a presumption of increases in CAP due to nonvaccine serotypes. These are harder to document, because data are typically obtained from hospital admissions or insurance claims and not from microbiological testing as is done with the ABCs. However, small studies using tympanocentesis have shown high proportions of nonvaccine S. pneumoniae serotypes in children with middle ear disease (Pediatr. Infect. Dis. J. 2007;26:S12–6).

Although we can't determine exactly what proportion of CAP and AOM is due to S. pneumoniae at any given time – and the longitudinal data are complicated by the secular changes in AOM definition – we do know that for every 1 case of invasive disease there are about 10 cases of CAP and 100 of AOM. So, we're looking at very clinically significant numbers.

In addition to the shift in serotypes, we've seen the emergence of multidrug-resistant pneumococci, particularly strain 19A. While these strains are usually sensitive to vancomycin, linezolid, and fluoroquinolones, they are resistant to the usual first-line antimicrobials, including amoxicillin, clindamycin, and trimethoprim-sulfamethoxazole, as well as ceftriaxone and other cephalosporins. Thus, both CAP and AOM have become more difficult to treat in children who don't respond to initial therapy.

Licensed earlier this year, PCV13 (Prevnar 13) contains all seven of the PCV7 strains (4, 6B, 9V, 14, 18C, 19F, and 23F), plus six more (1, 3, 5, 6A, 7F, and 19A). The serotypes represent either those that have been increasing in some countries using PCV7 (19A, 7F, 3) or that are globally important (1 and 5).

The vaccine was licensed on the basis of immunogenicity for the new serotypes as well as comparability to PCV7 for the seven “old” serotypes and a comparable safety profile.

The 13-valent vaccine is being introduced somewhat differently than was PCV7. The recommendation from the CDC Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians is to administer PCV13 routinely to all children aged 2, 4, 6, and 12–15 months.

For children who previously received one or more doses of PCV7, the series should be completed with PCV13. And for children 15 months through 5 years of age who received only PCV7 (or no vaccine), a single dose of PCV13 is recommended.

In contrast, when PCV7 was licensed, the recommended catchup immunization was through 2 years of age and only high-risk children aged 2–5 years. That's because, in general, the risk for invasive pneumococcal disease begins to decline after 3 years of age.

However, the data on multidrug-resistant strain 19A suggest that it has been producing substantial disease in previously healthy children up through 5 years of age.

In addition, nasopharyngeal carriage of 19A has been seen frequently in children up to age 5. It is hoped that preventing that carriage will reduce the spread to unvaccinated children less than 4–5 months of age, immunocompromised children who don't respond sufficiently to the vaccine, and adults.

Adding indirect protection to a large part of the population should help to reduce the incidence of disease due to the new vaccine serotypes.

Finally, I'd like to address a question that often arises. With new conjugate pneumococcal vaccines, are we simply shifting the serotypes that produce disease and not actually preventing it? I would say no. With each new expansion of the vaccine, not only do we add broader coverage, but we expect to see a further reduction in disease.

It is anticipated that the six new strains of PCV13 will add another 10%-15% reduction in pneumococcal disease beyond the 65%-70% we've already seen with PCV7, so that we will now achieve an approximate 80%-90% disease reduction compared with rates in 1998–1999.

However, I don't think we will entirely eliminate pneumococcal disease. A few other important nonvaccine serotypes, including 22F, 33F, and 15B/C, are likely to continue and possibly increase slightly following the introduction of PCV13. Nonetheless, it will help us to reduce the burden of pneumococcal disease on child health.

The new 13-valent pneumococcal conjugate vaccine (Prevnar 13) is picking up right where the 7-valent version left off.

It has been 10 years since the introduction of the 7-valent pneumococcal conjugate vaccine (Prevnar). Overall in the United States, the program has had significant success, with an approximate 65%-70% reduction in invasive disease due to Streptococcus pneumoniae. We've also seen substantial reductions in acute otitis media (AOM) and community-acquired pneumonia (CAP).

Nonetheless, in the last few years we've started to see a small but real increase in invasive disease due to nonvaccine serotypes, documented by the Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) system.

At the same time, there has also been documentation of an increase in AOM and a presumption of increases in CAP due to nonvaccine serotypes. These are harder to document, because data are typically obtained from hospital admissions or insurance claims and not from microbiological testing as is done with the ABCs. However, small studies using tympanocentesis have shown high proportions of nonvaccine S. pneumoniae serotypes in children with middle ear disease (Pediatr. Infect. Dis. J. 2007;26:S12–6).

Although we can't determine exactly what proportion of CAP and AOM is due to S. pneumoniae at any given time – and the longitudinal data are complicated by the secular changes in AOM definition – we do know that for every 1 case of invasive disease there are about 10 cases of CAP and 100 of AOM. So, we're looking at very clinically significant numbers.

In addition to the shift in serotypes, we've seen the emergence of multidrug-resistant pneumococci, particularly strain 19A. While these strains are usually sensitive to vancomycin, linezolid, and fluoroquinolones, they are resistant to the usual first-line antimicrobials, including amoxicillin, clindamycin, and trimethoprim-sulfamethoxazole, as well as ceftriaxone and other cephalosporins. Thus, both CAP and AOM have become more difficult to treat in children who don't respond to initial therapy.

Licensed earlier this year, PCV13 (Prevnar 13) contains all seven of the PCV7 strains (4, 6B, 9V, 14, 18C, 19F, and 23F), plus six more (1, 3, 5, 6A, 7F, and 19A). The serotypes represent either those that have been increasing in some countries using PCV7 (19A, 7F, 3) or that are globally important (1 and 5).

The vaccine was licensed on the basis of immunogenicity for the new serotypes as well as comparability to PCV7 for the seven “old” serotypes and a comparable safety profile.

The 13-valent vaccine is being introduced somewhat differently than was PCV7. The recommendation from the CDC Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians is to administer PCV13 routinely to all children aged 2, 4, 6, and 12–15 months.

For children who previously received one or more doses of PCV7, the series should be completed with PCV13. And for children 15 months through 5 years of age who received only PCV7 (or no vaccine), a single dose of PCV13 is recommended.

In contrast, when PCV7 was licensed, the recommended catchup immunization was through 2 years of age and only high-risk children aged 2–5 years. That's because, in general, the risk for invasive pneumococcal disease begins to decline after 3 years of age.

However, the data on multidrug-resistant strain 19A suggest that it has been producing substantial disease in previously healthy children up through 5 years of age.

In addition, nasopharyngeal carriage of 19A has been seen frequently in children up to age 5. It is hoped that preventing that carriage will reduce the spread to unvaccinated children less than 4–5 months of age, immunocompromised children who don't respond sufficiently to the vaccine, and adults.

Adding indirect protection to a large part of the population should help to reduce the incidence of disease due to the new vaccine serotypes.

Finally, I'd like to address a question that often arises. With new conjugate pneumococcal vaccines, are we simply shifting the serotypes that produce disease and not actually preventing it? I would say no. With each new expansion of the vaccine, not only do we add broader coverage, but we expect to see a further reduction in disease.

It is anticipated that the six new strains of PCV13 will add another 10%-15% reduction in pneumococcal disease beyond the 65%-70% we've already seen with PCV7, so that we will now achieve an approximate 80%-90% disease reduction compared with rates in 1998–1999.

However, I don't think we will entirely eliminate pneumococcal disease. A few other important nonvaccine serotypes, including 22F, 33F, and 15B/C, are likely to continue and possibly increase slightly following the introduction of PCV13. Nonetheless, it will help us to reduce the burden of pneumococcal disease on child health.

I'm very glad that the Lancet finally retracted the 1998 paper by Andrew J. Wakefield et al. that incorrectly suggested a link between the measles-mumps-rubella combined vaccine and autism. In my opinion, as well as others, the data did not warrant publication in 1998.

Following the judgment of the U.K. General Medical Council's Fitness to Practise Panel on Jan. 28, 2010, the Lancet editors said in a Feb. 2 statement, “it has become clear that several elements of the 1998 paper by Wakefield et al. are incorrect, contrary to the findings of an earlier investigation. In particular, the claims in the original paper that children were 'consecutively referred' and that investigations were 'approved' by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published record” (Lancet 2010 Feb. 2 [doi: 10.1016/S0140-6736(10)60175-4

Indeed, the authors never established what they claimed to demonstrate: a link between the MMR vaccine and a phenomenon they called “autistic enterocolitis.” The study was small—just 12 children—there was no control group, and the children had been specifically selected from among those referred to a pediatric gastroenterology clinic with both bowel symptoms and pervasive developmental disorder (Lancet 1998;351:637-41).

The study relied on parental report—8 of the 12 said that the onset of developmental delay symptoms was within 2 weeks of MMR receipt and the authors made no apparent attempt to confirm the reports. The study also relied on very sophisticated technology (in-situ hybridization, in-cell reverse transcriptase, and real-time quantitative TaqMan PCR) to demonstrate measles virus in the gut but failed to include a basic concept—a control population. Research by other investigators including a recent study of children with gastrointestinal syndromes with and without “autistic behavior” have failed to confirm Wakefield's findings.

At most, Wakefield and his colleagues showed a potential association. However, their final paragraph emphasizes the potential linkage (“In most cases, onset of symptoms was after measles, mumps, and rubella immunization”) and in subsequent statements warned against the use of combined MMR vaccines. As a result, use of MMR vaccine plummeted in the United Kingdom, measles cases rose, and overall public confidence in immunization was severely damaged.

Unfortunately the fallout continues today, despite the accumulation of a vast literature contradicting Wakefield's conclusions, including an Institute of Medicine report (“Immunization Safety Review: Vaccines and Autism 2004”) rejecting a causal relationship. One study particularly relevant to Wakefield's advocacy for using single dosing of measles vaccine is the unique situation in Japan, where, due to a problem with the mumps component, use of the MMR vaccine ceased completely in April 1993 and only monovalent vaccines were used thereafter (which, as it happens, is what Wakefield's group had recommended as a solution).

Despite the removal of the combination MMR vaccine from Japan's immunization program, the cumulative incidence of autism spectrum disorder (ASD) increased significantly up to age 7 among children born in Kohoku Ward (population approximately 300,000) in the years 1988-1996, with the most notable rise beginning with the birth cohort of 1993 (J. Child Psychol. Psychiatry 2005;46:572-9). “The significance of this finding is that MMR vaccination is most unlikely to be a cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD,” Dr. Hideo Honda and associates concluded.

Numerous additional studies from the United States, Scandinavia, and elsewhere have also conclusively shown a lack of any link between the vaccine, autism, and/or this supposed gastrointestinal syndrome. There's a good summary of all these data in Wikipedia, under “MMR Vaccine Controversy” (http://en.wikipedia.org/wiki/MMR_vaccine_controversywww.briandeer.com/mmr/lancet-greenhalgh.htm

What are the lessons we learn from this 20-year episode? We all have biases that have the potential to color our view of scientific data. Recently, concern about undue influence from the pharmaceutical industry has become a hot topic, hopefully addressed by full transparency of potential conflicts of interest by authors. It is equally imperative for journal editors to be aware of their biases and to advocate for scientific rigor as the criterion for publication and not a political agenda.

I do not have the insight to claim knowledge of what went awry in the case of the Wakefield paper. I do know that I have heard colleagues say, “How could you believe the results of such and such study; it was sponsored by industry.” This episode should remind us that scientific rigor should be the gold standard that investigators, reviewers, and editors rely on.

The Lancet and this newspaper are both published by Elsevier.

I'm very glad that the Lancet finally retracted the 1998 paper by Andrew J. Wakefield et al. that incorrectly suggested a link between the measles-mumps-rubella combined vaccine and autism. In my opinion, as well as others, the data did not warrant publication in 1998.

Following the judgment of the U.K. General Medical Council's Fitness to Practise Panel on Jan. 28, 2010, the Lancet editors said in a Feb. 2 statement, “it has become clear that several elements of the 1998 paper by Wakefield et al. are incorrect, contrary to the findings of an earlier investigation. In particular, the claims in the original paper that children were 'consecutively referred' and that investigations were 'approved' by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published record” (Lancet 2010 Feb. 2 [doi: 10.1016/S0140-6736(10)60175-4

Indeed, the authors never established what they claimed to demonstrate: a link between the MMR vaccine and a phenomenon they called “autistic enterocolitis.” The study was small—just 12 children—there was no control group, and the children had been specifically selected from among those referred to a pediatric gastroenterology clinic with both bowel symptoms and pervasive developmental disorder (Lancet 1998;351:637-41).

The study relied on parental report—8 of the 12 said that the onset of developmental delay symptoms was within 2 weeks of MMR receipt and the authors made no apparent attempt to confirm the reports. The study also relied on very sophisticated technology (in-situ hybridization, in-cell reverse transcriptase, and real-time quantitative TaqMan PCR) to demonstrate measles virus in the gut but failed to include a basic concept—a control population. Research by other investigators including a recent study of children with gastrointestinal syndromes with and without “autistic behavior” have failed to confirm Wakefield's findings.

At most, Wakefield and his colleagues showed a potential association. However, their final paragraph emphasizes the potential linkage (“In most cases, onset of symptoms was after measles, mumps, and rubella immunization”) and in subsequent statements warned against the use of combined MMR vaccines. As a result, use of MMR vaccine plummeted in the United Kingdom, measles cases rose, and overall public confidence in immunization was severely damaged.

Unfortunately the fallout continues today, despite the accumulation of a vast literature contradicting Wakefield's conclusions, including an Institute of Medicine report (“Immunization Safety Review: Vaccines and Autism 2004”) rejecting a causal relationship. One study particularly relevant to Wakefield's advocacy for using single dosing of measles vaccine is the unique situation in Japan, where, due to a problem with the mumps component, use of the MMR vaccine ceased completely in April 1993 and only monovalent vaccines were used thereafter (which, as it happens, is what Wakefield's group had recommended as a solution).

Despite the removal of the combination MMR vaccine from Japan's immunization program, the cumulative incidence of autism spectrum disorder (ASD) increased significantly up to age 7 among children born in Kohoku Ward (population approximately 300,000) in the years 1988-1996, with the most notable rise beginning with the birth cohort of 1993 (J. Child Psychol. Psychiatry 2005;46:572-9). “The significance of this finding is that MMR vaccination is most unlikely to be a cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD,” Dr. Hideo Honda and associates concluded.

Numerous additional studies from the United States, Scandinavia, and elsewhere have also conclusively shown a lack of any link between the vaccine, autism, and/or this supposed gastrointestinal syndrome. There's a good summary of all these data in Wikipedia, under “MMR Vaccine Controversy” (http://en.wikipedia.org/wiki/MMR_vaccine_controversywww.briandeer.com/mmr/lancet-greenhalgh.htm

What are the lessons we learn from this 20-year episode? We all have biases that have the potential to color our view of scientific data. Recently, concern about undue influence from the pharmaceutical industry has become a hot topic, hopefully addressed by full transparency of potential conflicts of interest by authors. It is equally imperative for journal editors to be aware of their biases and to advocate for scientific rigor as the criterion for publication and not a political agenda.

I do not have the insight to claim knowledge of what went awry in the case of the Wakefield paper. I do know that I have heard colleagues say, “How could you believe the results of such and such study; it was sponsored by industry.” This episode should remind us that scientific rigor should be the gold standard that investigators, reviewers, and editors rely on.

The Lancet and this newspaper are both published by Elsevier.

I'm very glad that the Lancet finally retracted the 1998 paper by Andrew J. Wakefield et al. that incorrectly suggested a link between the measles-mumps-rubella combined vaccine and autism. In my opinion, as well as others, the data did not warrant publication in 1998.

Following the judgment of the U.K. General Medical Council's Fitness to Practise Panel on Jan. 28, 2010, the Lancet editors said in a Feb. 2 statement, “it has become clear that several elements of the 1998 paper by Wakefield et al. are incorrect, contrary to the findings of an earlier investigation. In particular, the claims in the original paper that children were 'consecutively referred' and that investigations were 'approved' by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published record” (Lancet 2010 Feb. 2 [doi: 10.1016/S0140-6736(10)60175-4

Indeed, the authors never established what they claimed to demonstrate: a link between the MMR vaccine and a phenomenon they called “autistic enterocolitis.” The study was small—just 12 children—there was no control group, and the children had been specifically selected from among those referred to a pediatric gastroenterology clinic with both bowel symptoms and pervasive developmental disorder (Lancet 1998;351:637-41).

The study relied on parental report—8 of the 12 said that the onset of developmental delay symptoms was within 2 weeks of MMR receipt and the authors made no apparent attempt to confirm the reports. The study also relied on very sophisticated technology (in-situ hybridization, in-cell reverse transcriptase, and real-time quantitative TaqMan PCR) to demonstrate measles virus in the gut but failed to include a basic concept—a control population. Research by other investigators including a recent study of children with gastrointestinal syndromes with and without “autistic behavior” have failed to confirm Wakefield's findings.

At most, Wakefield and his colleagues showed a potential association. However, their final paragraph emphasizes the potential linkage (“In most cases, onset of symptoms was after measles, mumps, and rubella immunization”) and in subsequent statements warned against the use of combined MMR vaccines. As a result, use of MMR vaccine plummeted in the United Kingdom, measles cases rose, and overall public confidence in immunization was severely damaged.

Unfortunately the fallout continues today, despite the accumulation of a vast literature contradicting Wakefield's conclusions, including an Institute of Medicine report (“Immunization Safety Review: Vaccines and Autism 2004”) rejecting a causal relationship. One study particularly relevant to Wakefield's advocacy for using single dosing of measles vaccine is the unique situation in Japan, where, due to a problem with the mumps component, use of the MMR vaccine ceased completely in April 1993 and only monovalent vaccines were used thereafter (which, as it happens, is what Wakefield's group had recommended as a solution).

Despite the removal of the combination MMR vaccine from Japan's immunization program, the cumulative incidence of autism spectrum disorder (ASD) increased significantly up to age 7 among children born in Kohoku Ward (population approximately 300,000) in the years 1988-1996, with the most notable rise beginning with the birth cohort of 1993 (J. Child Psychol. Psychiatry 2005;46:572-9). “The significance of this finding is that MMR vaccination is most unlikely to be a cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD,” Dr. Hideo Honda and associates concluded.

Numerous additional studies from the United States, Scandinavia, and elsewhere have also conclusively shown a lack of any link between the vaccine, autism, and/or this supposed gastrointestinal syndrome. There's a good summary of all these data in Wikipedia, under “MMR Vaccine Controversy” (http://en.wikipedia.org/wiki/MMR_vaccine_controversywww.briandeer.com/mmr/lancet-greenhalgh.htm

What are the lessons we learn from this 20-year episode? We all have biases that have the potential to color our view of scientific data. Recently, concern about undue influence from the pharmaceutical industry has become a hot topic, hopefully addressed by full transparency of potential conflicts of interest by authors. It is equally imperative for journal editors to be aware of their biases and to advocate for scientific rigor as the criterion for publication and not a political agenda.

I do not have the insight to claim knowledge of what went awry in the case of the Wakefield paper. I do know that I have heard colleagues say, “How could you believe the results of such and such study; it was sponsored by industry.” This episode should remind us that scientific rigor should be the gold standard that investigators, reviewers, and editors rely on.

The Lancet and this newspaper are both published by Elsevier.

[email protected]

Pustular infections due to Staphylococcus aureus in the newborn nursery are preventable.

Approximately 4% of all newborns develop an infection in the first 30 days of life. Of these, pustulosis is the second-most common (after nonpneumonia respiratory tract infections), occurring in about 1 in every 100-200 newborns with a peak onset at 10-15 days of life. Most of these infections are due to S. aureus, and increasingly, methicillin-resistant S. aureus (MRSA).

Indeed, outbreaks of neonatal pustular disease should prompt concern about MRSA in the community. Colonization with S. aureus requires very little exposure. The problem can often be traced to crowding and failures of standard infection control practices in the newborn nursery, along with two other specific recently identified risk factors: circumcision and the use of multidose lidocaine vials.

A case-control study investigated 11 newborns who had onset of MRSA skin and soft-tissue infection within 21 days after discharge from a well-infant nursery at a community hospital over an 8-month period. All were term male infants with pustular-vesicular lesions in the groin, Dr. Dao Nguyen and associates at the Centers for Disease Control and Prevention reported (Infect. Control Hosp. Epidemiol. 2007;28:406-11).

Risk factors associated with the MRSA infections were length of stay, circumcision in the nursery, and receipt of lidocaine injections used to anesthetize for the circumcision procedure. Inspection revealed uncovered circumcision equipment, multiple-dose lidocaine vials, and inadequate hand hygiene practices.

Nineteen cases of MRSA infection were reported in neonates born at Beth Israel Deaconess Medical Center in Boston. Of the 19 infants who have become ill with the drug-resistant staphylococcal infection, 15 have been boys, the Boston Public Health Commission reported. Violations of standard infection control practices related to circumcision and postprocedure care were identified as contributing factors.

A literature review of 10 articles reporting on staphylococcal colonization and infection in the newborn period revealed that male infants have a greater risk than do female infants, and that the male to female ratio is even higher in studies where most of the boys are circumcised as infants (Clin. Pediatr. 2007;46:356-8).

But the answer to the neonatal staphylococcal problem is not to stop circumcising babies. Policies and attitudes toward circumcision are currently being revisited. After a decade or so in which a large body of evidence indicating the procedure reduces the risk for the development of a variety of sexually transmitted diseases was largely ignored, the American Academy of Pediatrics is reviewing its policy on the medical benefits of the procedure.

What's needed is better attention to surgical technique and hygiene during circumcision procedures, along with the use of single-dose lidocaine vials.

For newborns who do develop pustular disease in the diaper area, lower abdomen, or any other area, the approach to management varies considerably. Some infants are hospitalized and treated systemically while others are managed with local or topical therapy. An individualized approach would appear necessary as the spectrum of clinical disease is broad. First, the child should be evaluated for other possible etiologies.

If staphylococcal disease is suspected, the presence or absence of systemic signs, abscess, or local cellulitis will help determine whether systemic therapy is needed or if initial local management is appropriate. In all cases, close follow-up is needed to ensure that resolution occurs.

[email protected]

Pustular infections due to Staphylococcus aureus in the newborn nursery are preventable.

Approximately 4% of all newborns develop an infection in the first 30 days of life. Of these, pustulosis is the second-most common (after nonpneumonia respiratory tract infections), occurring in about 1 in every 100-200 newborns with a peak onset at 10-15 days of life. Most of these infections are due to S. aureus, and increasingly, methicillin-resistant S. aureus (MRSA).

Indeed, outbreaks of neonatal pustular disease should prompt concern about MRSA in the community. Colonization with S. aureus requires very little exposure. The problem can often be traced to crowding and failures of standard infection control practices in the newborn nursery, along with two other specific recently identified risk factors: circumcision and the use of multidose lidocaine vials.

A case-control study investigated 11 newborns who had onset of MRSA skin and soft-tissue infection within 21 days after discharge from a well-infant nursery at a community hospital over an 8-month period. All were term male infants with pustular-vesicular lesions in the groin, Dr. Dao Nguyen and associates at the Centers for Disease Control and Prevention reported (Infect. Control Hosp. Epidemiol. 2007;28:406-11).

Risk factors associated with the MRSA infections were length of stay, circumcision in the nursery, and receipt of lidocaine injections used to anesthetize for the circumcision procedure. Inspection revealed uncovered circumcision equipment, multiple-dose lidocaine vials, and inadequate hand hygiene practices.

Nineteen cases of MRSA infection were reported in neonates born at Beth Israel Deaconess Medical Center in Boston. Of the 19 infants who have become ill with the drug-resistant staphylococcal infection, 15 have been boys, the Boston Public Health Commission reported. Violations of standard infection control practices related to circumcision and postprocedure care were identified as contributing factors.

A literature review of 10 articles reporting on staphylococcal colonization and infection in the newborn period revealed that male infants have a greater risk than do female infants, and that the male to female ratio is even higher in studies where most of the boys are circumcised as infants (Clin. Pediatr. 2007;46:356-8).

But the answer to the neonatal staphylococcal problem is not to stop circumcising babies. Policies and attitudes toward circumcision are currently being revisited. After a decade or so in which a large body of evidence indicating the procedure reduces the risk for the development of a variety of sexually transmitted diseases was largely ignored, the American Academy of Pediatrics is reviewing its policy on the medical benefits of the procedure.

What's needed is better attention to surgical technique and hygiene during circumcision procedures, along with the use of single-dose lidocaine vials.

For newborns who do develop pustular disease in the diaper area, lower abdomen, or any other area, the approach to management varies considerably. Some infants are hospitalized and treated systemically while others are managed with local or topical therapy. An individualized approach would appear necessary as the spectrum of clinical disease is broad. First, the child should be evaluated for other possible etiologies.

If staphylococcal disease is suspected, the presence or absence of systemic signs, abscess, or local cellulitis will help determine whether systemic therapy is needed or if initial local management is appropriate. In all cases, close follow-up is needed to ensure that resolution occurs.

[email protected]

Pustular infections due to Staphylococcus aureus in the newborn nursery are preventable.

Approximately 4% of all newborns develop an infection in the first 30 days of life. Of these, pustulosis is the second-most common (after nonpneumonia respiratory tract infections), occurring in about 1 in every 100-200 newborns with a peak onset at 10-15 days of life. Most of these infections are due to S. aureus, and increasingly, methicillin-resistant S. aureus (MRSA).

Indeed, outbreaks of neonatal pustular disease should prompt concern about MRSA in the community. Colonization with S. aureus requires very little exposure. The problem can often be traced to crowding and failures of standard infection control practices in the newborn nursery, along with two other specific recently identified risk factors: circumcision and the use of multidose lidocaine vials.

A case-control study investigated 11 newborns who had onset of MRSA skin and soft-tissue infection within 21 days after discharge from a well-infant nursery at a community hospital over an 8-month period. All were term male infants with pustular-vesicular lesions in the groin, Dr. Dao Nguyen and associates at the Centers for Disease Control and Prevention reported (Infect. Control Hosp. Epidemiol. 2007;28:406-11).

Risk factors associated with the MRSA infections were length of stay, circumcision in the nursery, and receipt of lidocaine injections used to anesthetize for the circumcision procedure. Inspection revealed uncovered circumcision equipment, multiple-dose lidocaine vials, and inadequate hand hygiene practices.

Nineteen cases of MRSA infection were reported in neonates born at Beth Israel Deaconess Medical Center in Boston. Of the 19 infants who have become ill with the drug-resistant staphylococcal infection, 15 have been boys, the Boston Public Health Commission reported. Violations of standard infection control practices related to circumcision and postprocedure care were identified as contributing factors.

A literature review of 10 articles reporting on staphylococcal colonization and infection in the newborn period revealed that male infants have a greater risk than do female infants, and that the male to female ratio is even higher in studies where most of the boys are circumcised as infants (Clin. Pediatr. 2007;46:356-8).

But the answer to the neonatal staphylococcal problem is not to stop circumcising babies. Policies and attitudes toward circumcision are currently being revisited. After a decade or so in which a large body of evidence indicating the procedure reduces the risk for the development of a variety of sexually transmitted diseases was largely ignored, the American Academy of Pediatrics is reviewing its policy on the medical benefits of the procedure.

What's needed is better attention to surgical technique and hygiene during circumcision procedures, along with the use of single-dose lidocaine vials.

For newborns who do develop pustular disease in the diaper area, lower abdomen, or any other area, the approach to management varies considerably. Some infants are hospitalized and treated systemically while others are managed with local or topical therapy. An individualized approach would appear necessary as the spectrum of clinical disease is broad. First, the child should be evaluated for other possible etiologies.

If staphylococcal disease is suspected, the presence or absence of systemic signs, abscess, or local cellulitis will help determine whether systemic therapy is needed or if initial local management is appropriate. In all cases, close follow-up is needed to ensure that resolution occurs.

Pustular infections due to Staphylococcus aureus in the newborn nursery are preventable. Approximately 4% of all newborns develop an infection in the first 30 days of life. Of these, pustulosis is the second most common (after nonpneumonia respiratory tract infections), occurring in about 1 in every 100-200 newborns with a peak onset at 10-15 days of life. Most of these infections are due to S. aureus, and increasingly, methicillin-resistant S. aureus (MRSA).

Indeed, outbreaks of neonatal pustular disease should prompt concern about MRSA in the community. Colonization with S. aureus requires very little exposure—just a few colonies of bacteria can initiate colonization in newborns. The problem can often be traced to crowding and failures of standard infection control practices in the newborn nursery, along with two other specific recently identified risk factors: circumcision and the use of multidose lidocaine vials.

A case-control study investigated 11 newborns who had onset of MRSA skin and soft-tissue infection within 21 days after discharge from a well-infant nursery at a community hospital over an 8-month period. All were term male infants with pustular-vesicular lesions in the groin, Dr. Dao Nguyen and associates at the Centers for Disease Control and Prevention reported (Infect. Control Hosp. Epidemiol. 2007;28:406-11).

Risk factors associated with the MRSA infections were length of stay, circumcision in the nursery, and receipt of lidocaine injections used to anesthetize for the circumcision procedure. Inspection revealed uncovered circumcision equipment, multiple-dose lidocaine vials, and inadequate hand hygiene practices.

A literature review of 10 articles reporting on staphylococcal colonization and infection in the newborn period revealed that male infants have a greater risk than do female infants, and that the male to female ratio is even higher in studies performed where most of the boys are circumcised as infants (Clin. Pediatr. 2007;46:356-8).

But the answer to the neonatal staphylococcal problem is not to stop circumcising baby boys. Policies and attitudes toward circumcision are currently being revisited. After a decade or so in which a large body of evidence indicating that the procedure reduces the risk for the development of a variety of sexually transmitted diseases including human immunodeficiency virus, herpes simplex virus type 2, and human papillomavirus, as well as urinary tract infections, was largely ignored, the American Academy of Pediatrics is reviewing its policy on the medical benefits of the procedure.

What's needed is better attention to surgical technique and hygiene during circumcision procedures, along with the use of single-dose lidocaine vials. The benefits of circumcision have been established and in certain populations outweigh the risks when done properly.

For newborns who do develop pustular disease in the diaper area, lower abdomen, or any other area, the approach to management varies considerably. Some infants are hospitalized and treated systemically while others are managed with local or topical therapy. An individualized approach would appear necessary as the spectrum of clinical disease is broad.

First, the child should be evaluated for other possible etiologies such as herpetic lesions, erythema toxicum neonatorum, and infection with Malassezia species.

If staphylococcal disease is suspected, the presence or absence of systemic signs, abscess, or local cellulitis will help determine whether systemic therapy is needed or if initial local management is appropriate. In all cases, close follow-up is needed to ensure that resolution occurs.

Pustular infections due to Staphylococcus aureus in the newborn nursery are preventable. Approximately 4% of all newborns develop an infection in the first 30 days of life. Of these, pustulosis is the second most common (after nonpneumonia respiratory tract infections), occurring in about 1 in every 100-200 newborns with a peak onset at 10-15 days of life. Most of these infections are due to S. aureus, and increasingly, methicillin-resistant S. aureus (MRSA).

Indeed, outbreaks of neonatal pustular disease should prompt concern about MRSA in the community. Colonization with S. aureus requires very little exposure—just a few colonies of bacteria can initiate colonization in newborns. The problem can often be traced to crowding and failures of standard infection control practices in the newborn nursery, along with two other specific recently identified risk factors: circumcision and the use of multidose lidocaine vials.

A case-control study investigated 11 newborns who had onset of MRSA skin and soft-tissue infection within 21 days after discharge from a well-infant nursery at a community hospital over an 8-month period. All were term male infants with pustular-vesicular lesions in the groin, Dr. Dao Nguyen and associates at the Centers for Disease Control and Prevention reported (Infect. Control Hosp. Epidemiol. 2007;28:406-11).

Risk factors associated with the MRSA infections were length of stay, circumcision in the nursery, and receipt of lidocaine injections used to anesthetize for the circumcision procedure. Inspection revealed uncovered circumcision equipment, multiple-dose lidocaine vials, and inadequate hand hygiene practices.

A literature review of 10 articles reporting on staphylococcal colonization and infection in the newborn period revealed that male infants have a greater risk than do female infants, and that the male to female ratio is even higher in studies performed where most of the boys are circumcised as infants (Clin. Pediatr. 2007;46:356-8).

But the answer to the neonatal staphylococcal problem is not to stop circumcising baby boys. Policies and attitudes toward circumcision are currently being revisited. After a decade or so in which a large body of evidence indicating that the procedure reduces the risk for the development of a variety of sexually transmitted diseases including human immunodeficiency virus, herpes simplex virus type 2, and human papillomavirus, as well as urinary tract infections, was largely ignored, the American Academy of Pediatrics is reviewing its policy on the medical benefits of the procedure.

What's needed is better attention to surgical technique and hygiene during circumcision procedures, along with the use of single-dose lidocaine vials. The benefits of circumcision have been established and in certain populations outweigh the risks when done properly.

For newborns who do develop pustular disease in the diaper area, lower abdomen, or any other area, the approach to management varies considerably. Some infants are hospitalized and treated systemically while others are managed with local or topical therapy. An individualized approach would appear necessary as the spectrum of clinical disease is broad.

First, the child should be evaluated for other possible etiologies such as herpetic lesions, erythema toxicum neonatorum, and infection with Malassezia species.

If staphylococcal disease is suspected, the presence or absence of systemic signs, abscess, or local cellulitis will help determine whether systemic therapy is needed or if initial local management is appropriate. In all cases, close follow-up is needed to ensure that resolution occurs.

Pustular infections due to Staphylococcus aureus in the newborn nursery are preventable. Approximately 4% of all newborns develop an infection in the first 30 days of life. Of these, pustulosis is the second most common (after nonpneumonia respiratory tract infections), occurring in about 1 in every 100-200 newborns with a peak onset at 10-15 days of life. Most of these infections are due to S. aureus, and increasingly, methicillin-resistant S. aureus (MRSA).

Indeed, outbreaks of neonatal pustular disease should prompt concern about MRSA in the community. Colonization with S. aureus requires very little exposure—just a few colonies of bacteria can initiate colonization in newborns. The problem can often be traced to crowding and failures of standard infection control practices in the newborn nursery, along with two other specific recently identified risk factors: circumcision and the use of multidose lidocaine vials.

A case-control study investigated 11 newborns who had onset of MRSA skin and soft-tissue infection within 21 days after discharge from a well-infant nursery at a community hospital over an 8-month period. All were term male infants with pustular-vesicular lesions in the groin, Dr. Dao Nguyen and associates at the Centers for Disease Control and Prevention reported (Infect. Control Hosp. Epidemiol. 2007;28:406-11).

Risk factors associated with the MRSA infections were length of stay, circumcision in the nursery, and receipt of lidocaine injections used to anesthetize for the circumcision procedure. Inspection revealed uncovered circumcision equipment, multiple-dose lidocaine vials, and inadequate hand hygiene practices.

A literature review of 10 articles reporting on staphylococcal colonization and infection in the newborn period revealed that male infants have a greater risk than do female infants, and that the male to female ratio is even higher in studies performed where most of the boys are circumcised as infants (Clin. Pediatr. 2007;46:356-8).

But the answer to the neonatal staphylococcal problem is not to stop circumcising baby boys. Policies and attitudes toward circumcision are currently being revisited. After a decade or so in which a large body of evidence indicating that the procedure reduces the risk for the development of a variety of sexually transmitted diseases including human immunodeficiency virus, herpes simplex virus type 2, and human papillomavirus, as well as urinary tract infections, was largely ignored, the American Academy of Pediatrics is reviewing its policy on the medical benefits of the procedure.

What's needed is better attention to surgical technique and hygiene during circumcision procedures, along with the use of single-dose lidocaine vials. The benefits of circumcision have been established and in certain populations outweigh the risks when done properly.

For newborns who do develop pustular disease in the diaper area, lower abdomen, or any other area, the approach to management varies considerably. Some infants are hospitalized and treated systemically while others are managed with local or topical therapy. An individualized approach would appear necessary as the spectrum of clinical disease is broad.

First, the child should be evaluated for other possible etiologies such as herpetic lesions, erythema toxicum neonatorum, and infection with Malassezia species.

If staphylococcal disease is suspected, the presence or absence of systemic signs, abscess, or local cellulitis will help determine whether systemic therapy is needed or if initial local management is appropriate. In all cases, close follow-up is needed to ensure that resolution occurs.

[email protected]

Here's an important message for the vaccine-hesitant parents in your practice: Delaying immunizations places your infant at risk for serious infection.

Physicians who care for children have been increasingly encountering parents who are fearful about vaccines and reluctant to allow their children to be vaccinated. A new, worrisome concept circulating on the Internet and elsewhere is that instead of skipping vaccines altogether, children can be vaccinated on “selective” or “alternative” schedules that either eliminate some vaccines or spread the schedule out over a longer period of time. To many parents and perhaps even some physicians, these schedules may sound attractive, but they are not, because they leave young infants unprotected at the very time they are most vulnerable to vaccine-preventable diseases and their complications.

The idea that the currently recommended childhood immunization schedule can be successfully altered is being fostered by a pediatrician named Robert W. Sears—aka “Dr. Bob”—who has written a book entitled, “The Vaccine Book: Making the Right Decision for Your Child.” In it, he presents two immunization schedules that differ substantially from the one recommended by the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American Academy of Family Physicians. He promotes these schedules as acceptable alternatives for the vaccine-adverse family.

Both Dr. Bob's selective and alternative schedules involve spreading out fewer vaccines over a period of six visits in the first 7 months of life (at 2, 3, 4, 5, 6, and 7 months), an inconvenience that in and of itself may further challenge the administration of timely immunizations. Both of his schedules delay the first pneumococcal conjugate vaccine dose until 3 months. Influenza vaccination isn't included at all in his selective schedule, and doesn't appear until 21 months of age on the alternative schedule.

But perhaps even more disturbing than selective or alternative schedules that fail to incorporate age-related epidemiology and risk for complications is Dr. Sears's perspective on parents who choose to delay all vaccinations until their child is 6 months or older. Although he states in his book that he doesn't advise this, he also tells parents that if they choose to postpone immunizations until the child is 2 years old, “it doesn't make sense to then go ahead and catch up with all the shots,” thus giving parents the idea that skipping early immunizations altogether is an acceptable and perhaps even sensible option.

He also recommends certain “precautions to take if you don't vaccinate,” including “ensuring a healthy immune system” through omega-3 oil supplements and other vitamins.

In my opinion, immunizing young infants is very important, and age-related epidemiology and risk for complications support early vaccination. This is particularly true for the following four vaccine-preventable diseases for which there is still significant risk of exposure and evidence that severity is greater in the first year of life:

▸ Pertussis. A single dose of pertussis vaccine does not appear to offer significant protection. Infants with pertussis who received fewer diphtheria-tetanus-pertussis doses were significantly more likely to be hospitalized, demonstrating that underimmunized infants have more serious disease (JAMA 2003;290:2968-75).

In the United States, there were approximately 140 pertussis deaths in infants less than 3 months old between 2000 and 2006 and approximately 100 times as many hospitalizations, often requiring intensive care. We see sharp declines in disease morbidity after 4 months of age, most likely because that's when children receive a second dose of pertussis-containing vaccine. Thus, prevention of early disease is critical and vaccination is part of that strategy, in conjunction with the adolescent/adult vaccine formulation (Tdap) for parents and teenagers.

▸ Invasive pneumococcal disease. Here again, we have data showing that a single dose of pneumococcal conjugate vaccine does not offer significant disease protection (Vaccine 2006;24:2514-20). In Massachusetts, where we have been tracking invasive pneumococcal disease (IPD) in children younger than 18 years old, mortality from IPD in children less than 1 year of age is approximately 10 times higher than for those aged 1-10 years—about 3% of those who develop IPD (Hsu, K., et al., submitted for publication).

▸ Influenza. Children less than 2 years of age are at greater risk for influenza than are older children and are hospitalized with it more often (MMWR 2008;57[RR07]:1-60). Children younger than 2 years also may have higher concentrations of virus in the nasopharynx as well as longer durations of shedding, thus frequently rendering them sources of contagion to household and day care contacts.

Because there is no influenza vaccine for children less than 6 months of age, vaccinating their siblings and all adults around them—a process known as “cocooning”—is the only current strategy for reducing exposure among the most vulnerable children in the community. Starting influenza immunization at 6 months of age, with a second dose 1 month later, provides protection against influenza disease and potentially against bacterial pathogens that tend to take advantage of weakened host defenses during influenza infection.

▸ Varicella. It's a widespread misconception that varicella is serious only in adults. In fact, prior to the licensure of the vaccine, the case-fatality rate from pneumonia, encephalitis, and secondary bacterial sepsis among children less than 1 year of age with chicken pox was 7 times higher than that of those aged 1-10 years, at 6.23 versus 0.75 cases per 100,000 children (MMWR 1996;45[RR-11]:1-36). During the 1990's, the combination of varicella and group A streptococcus was a deadly one, often leading to extensive necrotizing infection or sepsis, hospitalization, and death. Currently, there is concern that methicillin-resistant Staphylococcus aureus (MRSA) also may be an opportunistic pathogen any time there is a break in the skin.

According to the alternative schedule, it's okay to delay varicella vaccine until 18 months; the selective schedule advises waiting until the child is 10 years old, ordering antibody titers, and immunizing only if the child is found susceptible. Clearly, these approaches do not provide early protection from disease. Fortunately, there is little wild-type varicella currently circulating in the community, and the cases that do break through in vaccinated children are usually mild, with small numbers of lesions. However, if immunization rates fall and wild-type varicella becomes more common, more cases complicated by MRSA are likely to occur.

That is one reason why I am particularly concerned with the recent trend of parents organizing “chicken pox parties” to deliberately expose their children to varicella, under the mistaken belief that this is a good way to achieve protection without immunization.

Because there is still no chicken pox vaccine available for children less than 1 year of age, the only way to prevent disease in this high-risk group is to prevent exposure by immunizing their siblings, day care contacts, babysitters, and anyone else with whom they come into regular contact. Not only do the chicken pox parties demonstrate a lack of understanding of the potential seriousness of varicella, but they completely ignore the potential for secondary cases within a household in susceptible adults or infants. Please do your best to educate parents in your practice about the risks of wild-type varicella in young infants and the potential for MRSA suprainfection.

While delaying immunization may make some people feel good, it leaves the most vulnerable of our patients at great risk. It will take time to explain to parents that the currently recommended vaccine schedule incorporates our knowledge about age-related susceptibility, morbidity, and mortality. Delay is not in their child's interest.

[email protected]

Here's an important message for the vaccine-hesitant parents in your practice: Delaying immunizations places your infant at risk for serious infection.

Physicians who care for children have been increasingly encountering parents who are fearful about vaccines and reluctant to allow their children to be vaccinated. A new, worrisome concept circulating on the Internet and elsewhere is that instead of skipping vaccines altogether, children can be vaccinated on “selective” or “alternative” schedules that either eliminate some vaccines or spread the schedule out over a longer period of time. To many parents and perhaps even some physicians, these schedules may sound attractive, but they are not, because they leave young infants unprotected at the very time they are most vulnerable to vaccine-preventable diseases and their complications.

The idea that the currently recommended childhood immunization schedule can be successfully altered is being fostered by a pediatrician named Robert W. Sears—aka “Dr. Bob”—who has written a book entitled, “The Vaccine Book: Making the Right Decision for Your Child.” In it, he presents two immunization schedules that differ substantially from the one recommended by the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American Academy of Family Physicians. He promotes these schedules as acceptable alternatives for the vaccine-adverse family.

Both Dr. Bob's selective and alternative schedules involve spreading out fewer vaccines over a period of six visits in the first 7 months of life (at 2, 3, 4, 5, 6, and 7 months), an inconvenience that in and of itself may further challenge the administration of timely immunizations. Both of his schedules delay the first pneumococcal conjugate vaccine dose until 3 months. Influenza vaccination isn't included at all in his selective schedule, and doesn't appear until 21 months of age on the alternative schedule.

But perhaps even more disturbing than selective or alternative schedules that fail to incorporate age-related epidemiology and risk for complications is Dr. Sears's perspective on parents who choose to delay all vaccinations until their child is 6 months or older. Although he states in his book that he doesn't advise this, he also tells parents that if they choose to postpone immunizations until the child is 2 years old, “it doesn't make sense to then go ahead and catch up with all the shots,” thus giving parents the idea that skipping early immunizations altogether is an acceptable and perhaps even sensible option.

He also recommends certain “precautions to take if you don't vaccinate,” including “ensuring a healthy immune system” through omega-3 oil supplements and other vitamins.

In my opinion, immunizing young infants is very important, and age-related epidemiology and risk for complications support early vaccination. This is particularly true for the following four vaccine-preventable diseases for which there is still significant risk of exposure and evidence that severity is greater in the first year of life:

▸ Pertussis. A single dose of pertussis vaccine does not appear to offer significant protection. Infants with pertussis who received fewer diphtheria-tetanus-pertussis doses were significantly more likely to be hospitalized, demonstrating that underimmunized infants have more serious disease (JAMA 2003;290:2968-75).

In the United States, there were approximately 140 pertussis deaths in infants less than 3 months old between 2000 and 2006 and approximately 100 times as many hospitalizations, often requiring intensive care. We see sharp declines in disease morbidity after 4 months of age, most likely because that's when children receive a second dose of pertussis-containing vaccine. Thus, prevention of early disease is critical and vaccination is part of that strategy, in conjunction with the adolescent/adult vaccine formulation (Tdap) for parents and teenagers.

▸ Invasive pneumococcal disease. Here again, we have data showing that a single dose of pneumococcal conjugate vaccine does not offer significant disease protection (Vaccine 2006;24:2514-20). In Massachusetts, where we have been tracking invasive pneumococcal disease (IPD) in children younger than 18 years old, mortality from IPD in children less than 1 year of age is approximately 10 times higher than for those aged 1-10 years—about 3% of those who develop IPD (Hsu, K., et al., submitted for publication).

▸ Influenza. Children less than 2 years of age are at greater risk for influenza than are older children and are hospitalized with it more often (MMWR 2008;57[RR07]:1-60). Children younger than 2 years also may have higher concentrations of virus in the nasopharynx as well as longer durations of shedding, thus frequently rendering them sources of contagion to household and day care contacts.

Because there is no influenza vaccine for children less than 6 months of age, vaccinating their siblings and all adults around them—a process known as “cocooning”—is the only current strategy for reducing exposure among the most vulnerable children in the community. Starting influenza immunization at 6 months of age, with a second dose 1 month later, provides protection against influenza disease and potentially against bacterial pathogens that tend to take advantage of weakened host defenses during influenza infection.

▸ Varicella. It's a widespread misconception that varicella is serious only in adults. In fact, prior to the licensure of the vaccine, the case-fatality rate from pneumonia, encephalitis, and secondary bacterial sepsis among children less than 1 year of age with chicken pox was 7 times higher than that of those aged 1-10 years, at 6.23 versus 0.75 cases per 100,000 children (MMWR 1996;45[RR-11]:1-36). During the 1990's, the combination of varicella and group A streptococcus was a deadly one, often leading to extensive necrotizing infection or sepsis, hospitalization, and death. Currently, there is concern that methicillin-resistant Staphylococcus aureus (MRSA) also may be an opportunistic pathogen any time there is a break in the skin.

According to the alternative schedule, it's okay to delay varicella vaccine until 18 months; the selective schedule advises waiting until the child is 10 years old, ordering antibody titers, and immunizing only if the child is found susceptible. Clearly, these approaches do not provide early protection from disease. Fortunately, there is little wild-type varicella currently circulating in the community, and the cases that do break through in vaccinated children are usually mild, with small numbers of lesions. However, if immunization rates fall and wild-type varicella becomes more common, more cases complicated by MRSA are likely to occur.

That is one reason why I am particularly concerned with the recent trend of parents organizing “chicken pox parties” to deliberately expose their children to varicella, under the mistaken belief that this is a good way to achieve protection without immunization.

Because there is still no chicken pox vaccine available for children less than 1 year of age, the only way to prevent disease in this high-risk group is to prevent exposure by immunizing their siblings, day care contacts, babysitters, and anyone else with whom they come into regular contact. Not only do the chicken pox parties demonstrate a lack of understanding of the potential seriousness of varicella, but they completely ignore the potential for secondary cases within a household in susceptible adults or infants. Please do your best to educate parents in your practice about the risks of wild-type varicella in young infants and the potential for MRSA suprainfection.

While delaying immunization may make some people feel good, it leaves the most vulnerable of our patients at great risk. It will take time to explain to parents that the currently recommended vaccine schedule incorporates our knowledge about age-related susceptibility, morbidity, and mortality. Delay is not in their child's interest.

[email protected]

Here's an important message for the vaccine-hesitant parents in your practice: Delaying immunizations places your infant at risk for serious infection.

Physicians who care for children have been increasingly encountering parents who are fearful about vaccines and reluctant to allow their children to be vaccinated. A new, worrisome concept circulating on the Internet and elsewhere is that instead of skipping vaccines altogether, children can be vaccinated on “selective” or “alternative” schedules that either eliminate some vaccines or spread the schedule out over a longer period of time. To many parents and perhaps even some physicians, these schedules may sound attractive, but they are not, because they leave young infants unprotected at the very time they are most vulnerable to vaccine-preventable diseases and their complications.

The idea that the currently recommended childhood immunization schedule can be successfully altered is being fostered by a pediatrician named Robert W. Sears—aka “Dr. Bob”—who has written a book entitled, “The Vaccine Book: Making the Right Decision for Your Child.” In it, he presents two immunization schedules that differ substantially from the one recommended by the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American Academy of Family Physicians. He promotes these schedules as acceptable alternatives for the vaccine-adverse family.

Both Dr. Bob's selective and alternative schedules involve spreading out fewer vaccines over a period of six visits in the first 7 months of life (at 2, 3, 4, 5, 6, and 7 months), an inconvenience that in and of itself may further challenge the administration of timely immunizations. Both of his schedules delay the first pneumococcal conjugate vaccine dose until 3 months. Influenza vaccination isn't included at all in his selective schedule, and doesn't appear until 21 months of age on the alternative schedule.

But perhaps even more disturbing than selective or alternative schedules that fail to incorporate age-related epidemiology and risk for complications is Dr. Sears's perspective on parents who choose to delay all vaccinations until their child is 6 months or older. Although he states in his book that he doesn't advise this, he also tells parents that if they choose to postpone immunizations until the child is 2 years old, “it doesn't make sense to then go ahead and catch up with all the shots,” thus giving parents the idea that skipping early immunizations altogether is an acceptable and perhaps even sensible option.

He also recommends certain “precautions to take if you don't vaccinate,” including “ensuring a healthy immune system” through omega-3 oil supplements and other vitamins.

In my opinion, immunizing young infants is very important, and age-related epidemiology and risk for complications support early vaccination. This is particularly true for the following four vaccine-preventable diseases for which there is still significant risk of exposure and evidence that severity is greater in the first year of life:

▸ Pertussis. A single dose of pertussis vaccine does not appear to offer significant protection. Infants with pertussis who received fewer diphtheria-tetanus-pertussis doses were significantly more likely to be hospitalized, demonstrating that underimmunized infants have more serious disease (JAMA 2003;290:2968-75).

In the United States, there were approximately 140 pertussis deaths in infants less than 3 months old between 2000 and 2006 and approximately 100 times as many hospitalizations, often requiring intensive care. We see sharp declines in disease morbidity after 4 months of age, most likely because that's when children receive a second dose of pertussis-containing vaccine. Thus, prevention of early disease is critical and vaccination is part of that strategy, in conjunction with the adolescent/adult vaccine formulation (Tdap) for parents and teenagers.

▸ Invasive pneumococcal disease. Here again, we have data showing that a single dose of pneumococcal conjugate vaccine does not offer significant disease protection (Vaccine 2006;24:2514-20). In Massachusetts, where we have been tracking invasive pneumococcal disease (IPD) in children younger than 18 years old, mortality from IPD in children less than 1 year of age is approximately 10 times higher than for those aged 1-10 years—about 3% of those who develop IPD (Hsu, K., et al., submitted for publication).

▸ Influenza. Children less than 2 years of age are at greater risk for influenza than are older children and are hospitalized with it more often (MMWR 2008;57[RR07]:1-60). Children younger than 2 years also may have higher concentrations of virus in the nasopharynx as well as longer durations of shedding, thus frequently rendering them sources of contagion to household and day care contacts.

Because there is no influenza vaccine for children less than 6 months of age, vaccinating their siblings and all adults around them—a process known as “cocooning”—is the only current strategy for reducing exposure among the most vulnerable children in the community. Starting influenza immunization at 6 months of age, with a second dose 1 month later, provides protection against influenza disease and potentially against bacterial pathogens that tend to take advantage of weakened host defenses during influenza infection.

▸ Varicella. It's a widespread misconception that varicella is serious only in adults. In fact, prior to the licensure of the vaccine, the case-fatality rate from pneumonia, encephalitis, and secondary bacterial sepsis among children less than 1 year of age with chicken pox was 7 times higher than that of those aged 1-10 years, at 6.23 versus 0.75 cases per 100,000 children (MMWR 1996;45[RR-11]:1-36). During the 1990's, the combination of varicella and group A streptococcus was a deadly one, often leading to extensive necrotizing infection or sepsis, hospitalization, and death. Currently, there is concern that methicillin-resistant Staphylococcus aureus (MRSA) also may be an opportunistic pathogen any time there is a break in the skin.

According to the alternative schedule, it's okay to delay varicella vaccine until 18 months; the selective schedule advises waiting until the child is 10 years old, ordering antibody titers, and immunizing only if the child is found susceptible. Clearly, these approaches do not provide early protection from disease. Fortunately, there is little wild-type varicella currently circulating in the community, and the cases that do break through in vaccinated children are usually mild, with small numbers of lesions. However, if immunization rates fall and wild-type varicella becomes more common, more cases complicated by MRSA are likely to occur.

That is one reason why I am particularly concerned with the recent trend of parents organizing “chicken pox parties” to deliberately expose their children to varicella, under the mistaken belief that this is a good way to achieve protection without immunization.

Because there is still no chicken pox vaccine available for children less than 1 year of age, the only way to prevent disease in this high-risk group is to prevent exposure by immunizing their siblings, day care contacts, babysitters, and anyone else with whom they come into regular contact. Not only do the chicken pox parties demonstrate a lack of understanding of the potential seriousness of varicella, but they completely ignore the potential for secondary cases within a household in susceptible adults or infants. Please do your best to educate parents in your practice about the risks of wild-type varicella in young infants and the potential for MRSA suprainfection.

While delaying immunization may make some people feel good, it leaves the most vulnerable of our patients at great risk. It will take time to explain to parents that the currently recommended vaccine schedule incorporates our knowledge about age-related susceptibility, morbidity, and mortality. Delay is not in their child's interest.

[email protected]

Since July 22nd, you have no doubt received phone calls from anxious parents who heard the news report about adverse events associated with the human papillomavirus vaccine, Gardasil. As usual, the media did a good job of creating anxiety both among parents and prescribing physicians. I've heard how much time clinicians now are spending discussing vaccine safety with their patients, and that some have begun administering the HPV vaccine separately from other recommended adolescent vaccines and others have just stopped giving it altogether.

I'd like to review what we know so that you can be prepared to answer questions and, I hope, alleviate fears about Gardasil and other recommended childhood and adolescent vaccines. A statement, issued jointly by the Centers for Disease Control and Prevention and the Food and Drug Administration, summarized all reports concerning Gardasil that were filed with the Vaccine Adverse Events Reporting System (VAERS) from the time the vaccine was licensed on June 8, 2006, through June 30, 2008.

A total of 9,749 adverse events were reported to VAERS in association with administration of Gardasil, of which 94% were classified as nonserious events, and 6% as serious events. It's important to keep in mind the denominator: At the time the statement was issued, Merck & Co. had distributed over 16 million doses of Gardasil in the United States.

Also remember that VAERS is a passive reporting system that receives unconfirmed reports of possible side effects following the use of all vaccines licensed in the United States.

Data from the system are reviewed on an ongoing basis to look for possible signals that require further investigation. Data from VAERS cannot and should not be viewed as implying causation.

The 9,164 nonserious reports included syncope, injection site pain, headache, nausea, and fever. Indeed, fainting after receipt of any vaccine is common among teenagers. Providers are reminded to keep patients seated for at least 15 minutes after vaccination to avoid injury from a possible fall.

The 585 serious adverse events included 20 deaths. There was no common pattern to these deaths that would suggest they were caused by the vaccine. Where autopsy results were available, the cause of death was unrelated to vaccine.

Other serious adverse event reports following receipt of Gardasil were attributable to Guillain-Barre Syndrome, a rare neurologic disorder for which the typical attack rate is highest during adolescence. Further investigation by FDA and CDC found no increase in GBS cases beyond the expected number among Gardasil recipients.

Thromboembolic disorders also were reported following vaccination with Gardasil, most of which occurred in individuals with risk factors for clotting, such as oral contraceptive use.

In addition to VAERS, there also is a safety monitoring system called the Vaccine Safety Datalink Project, a collaboration between CDC and eight managed care organizations that is set up to investigate any possible safety signals arising from VAERS. Gardasil and all other vaccines are monitored with these systems on an ongoing basis. In the meantime, the CDC has not made any changes to its recommendations for the use of Gardasil based on the available information, nor has the FDA revised its prescribing information.

Gardasil, the first HPV vaccine to be licensed, was approved for use in girls and women aged 9-26 years. It was recommended by the CDC's Advisory Committee on Immunization Practices (ACIP) as a three-dose series for routine vaccination of girls aged 11-12 years, and for catch-up in girls and women aged 13-26 years.

The vaccine is made from noninfectious particles, not live or attenuated virus. It contains no thimerosal. It protects against HPV strains 16 and 18, which cause 70% of all cervical cancers, and strains 6 and 11, responsible for 90% of all genital warts in the United States. Data show that the vaccine is most effective when given prior to onset of sexual activity.

When speaking with a worried parent, I think it's critical to explain that association does not imply causation. I also would review the rationale behind giving the HPV vaccine and reiterate that maximum benefit is achieved by immunization before sexual debut.

Every year, about 12,000 women in the United States are diagnosed with cervical cancer and almost 4,000 die from it. Worldwide, cervical cancer is the second most common cancer in women, causing an estimated 470,000 new cases and 233,000 deaths per year. I don't think you can put a price on the value of saving lives by administering a vaccine, although of course plenty of health economists have tried to do just that.

Going forward, I think it behooves physicians who administer vaccines to stay abreast of the news. When you see a headline about any vaccine, check out the Web sites of the CDC (www.cdc.govwww.aap.org

As we're seeing from the recent measles outbreaks across the country, the majority of cases are not the result of vaccine failure but of failure to vaccinate. Our role is to help parents make the right decision. We must be armed with data to prevent associations between daily events from being interpreted as causation.

I am a member of global advisory boards on vaccine for Novartis, Wyeth, and GlaxoSmithKline, for which I receive honoraria.

[email protected]

Since July 22nd, you have no doubt received phone calls from anxious parents who heard the news report about adverse events associated with the human papillomavirus vaccine, Gardasil. As usual, the media did a good job of creating anxiety both among parents and prescribing physicians. I've heard how much time clinicians now are spending discussing vaccine safety with their patients, and that some have begun administering the HPV vaccine separately from other recommended adolescent vaccines and others have just stopped giving it altogether.

I'd like to review what we know so that you can be prepared to answer questions and, I hope, alleviate fears about Gardasil and other recommended childhood and adolescent vaccines. A statement, issued jointly by the Centers for Disease Control and Prevention and the Food and Drug Administration, summarized all reports concerning Gardasil that were filed with the Vaccine Adverse Events Reporting System (VAERS) from the time the vaccine was licensed on June 8, 2006, through June 30, 2008.

A total of 9,749 adverse events were reported to VAERS in association with administration of Gardasil, of which 94% were classified as nonserious events, and 6% as serious events. It's important to keep in mind the denominator: At the time the statement was issued, Merck & Co. had distributed over 16 million doses of Gardasil in the United States.

Also remember that VAERS is a passive reporting system that receives unconfirmed reports of possible side effects following the use of all vaccines licensed in the United States.

Data from the system are reviewed on an ongoing basis to look for possible signals that require further investigation. Data from VAERS cannot and should not be viewed as implying causation.

The 9,164 nonserious reports included syncope, injection site pain, headache, nausea, and fever. Indeed, fainting after receipt of any vaccine is common among teenagers. Providers are reminded to keep patients seated for at least 15 minutes after vaccination to avoid injury from a possible fall.

The 585 serious adverse events included 20 deaths. There was no common pattern to these deaths that would suggest they were caused by the vaccine. Where autopsy results were available, the cause of death was unrelated to vaccine.

Other serious adverse event reports following receipt of Gardasil were attributable to Guillain-Barre Syndrome, a rare neurologic disorder for which the typical attack rate is highest during adolescence. Further investigation by FDA and CDC found no increase in GBS cases beyond the expected number among Gardasil recipients.

Thromboembolic disorders also were reported following vaccination with Gardasil, most of which occurred in individuals with risk factors for clotting, such as oral contraceptive use.

In addition to VAERS, there also is a safety monitoring system called the Vaccine Safety Datalink Project, a collaboration between CDC and eight managed care organizations that is set up to investigate any possible safety signals arising from VAERS. Gardasil and all other vaccines are monitored with these systems on an ongoing basis. In the meantime, the CDC has not made any changes to its recommendations for the use of Gardasil based on the available information, nor has the FDA revised its prescribing information.

Gardasil, the first HPV vaccine to be licensed, was approved for use in girls and women aged 9-26 years. It was recommended by the CDC's Advisory Committee on Immunization Practices (ACIP) as a three-dose series for routine vaccination of girls aged 11-12 years, and for catch-up in girls and women aged 13-26 years.

The vaccine is made from noninfectious particles, not live or attenuated virus. It contains no thimerosal. It protects against HPV strains 16 and 18, which cause 70% of all cervical cancers, and strains 6 and 11, responsible for 90% of all genital warts in the United States. Data show that the vaccine is most effective when given prior to onset of sexual activity.

When speaking with a worried parent, I think it's critical to explain that association does not imply causation. I also would review the rationale behind giving the HPV vaccine and reiterate that maximum benefit is achieved by immunization before sexual debut.

Every year, about 12,000 women in the United States are diagnosed with cervical cancer and almost 4,000 die from it. Worldwide, cervical cancer is the second most common cancer in women, causing an estimated 470,000 new cases and 233,000 deaths per year. I don't think you can put a price on the value of saving lives by administering a vaccine, although of course plenty of health economists have tried to do just that.

Going forward, I think it behooves physicians who administer vaccines to stay abreast of the news. When you see a headline about any vaccine, check out the Web sites of the CDC (www.cdc.govwww.aap.org

As we're seeing from the recent measles outbreaks across the country, the majority of cases are not the result of vaccine failure but of failure to vaccinate. Our role is to help parents make the right decision. We must be armed with data to prevent associations between daily events from being interpreted as causation.

I am a member of global advisory boards on vaccine for Novartis, Wyeth, and GlaxoSmithKline, for which I receive honoraria.

[email protected]

Since July 22nd, you have no doubt received phone calls from anxious parents who heard the news report about adverse events associated with the human papillomavirus vaccine, Gardasil. As usual, the media did a good job of creating anxiety both among parents and prescribing physicians. I've heard how much time clinicians now are spending discussing vaccine safety with their patients, and that some have begun administering the HPV vaccine separately from other recommended adolescent vaccines and others have just stopped giving it altogether.

I'd like to review what we know so that you can be prepared to answer questions and, I hope, alleviate fears about Gardasil and other recommended childhood and adolescent vaccines. A statement, issued jointly by the Centers for Disease Control and Prevention and the Food and Drug Administration, summarized all reports concerning Gardasil that were filed with the Vaccine Adverse Events Reporting System (VAERS) from the time the vaccine was licensed on June 8, 2006, through June 30, 2008.

A total of 9,749 adverse events were reported to VAERS in association with administration of Gardasil, of which 94% were classified as nonserious events, and 6% as serious events. It's important to keep in mind the denominator: At the time the statement was issued, Merck & Co. had distributed over 16 million doses of Gardasil in the United States.

Also remember that VAERS is a passive reporting system that receives unconfirmed reports of possible side effects following the use of all vaccines licensed in the United States.

Data from the system are reviewed on an ongoing basis to look for possible signals that require further investigation. Data from VAERS cannot and should not be viewed as implying causation.

The 9,164 nonserious reports included syncope, injection site pain, headache, nausea, and fever. Indeed, fainting after receipt of any vaccine is common among teenagers. Providers are reminded to keep patients seated for at least 15 minutes after vaccination to avoid injury from a possible fall.

The 585 serious adverse events included 20 deaths. There was no common pattern to these deaths that would suggest they were caused by the vaccine. Where autopsy results were available, the cause of death was unrelated to vaccine.

Other serious adverse event reports following receipt of Gardasil were attributable to Guillain-Barre Syndrome, a rare neurologic disorder for which the typical attack rate is highest during adolescence. Further investigation by FDA and CDC found no increase in GBS cases beyond the expected number among Gardasil recipients.

Thromboembolic disorders also were reported following vaccination with Gardasil, most of which occurred in individuals with risk factors for clotting, such as oral contraceptive use.

In addition to VAERS, there also is a safety monitoring system called the Vaccine Safety Datalink Project, a collaboration between CDC and eight managed care organizations that is set up to investigate any possible safety signals arising from VAERS. Gardasil and all other vaccines are monitored with these systems on an ongoing basis. In the meantime, the CDC has not made any changes to its recommendations for the use of Gardasil based on the available information, nor has the FDA revised its prescribing information.

Gardasil, the first HPV vaccine to be licensed, was approved for use in girls and women aged 9-26 years. It was recommended by the CDC's Advisory Committee on Immunization Practices (ACIP) as a three-dose series for routine vaccination of girls aged 11-12 years, and for catch-up in girls and women aged 13-26 years.

The vaccine is made from noninfectious particles, not live or attenuated virus. It contains no thimerosal. It protects against HPV strains 16 and 18, which cause 70% of all cervical cancers, and strains 6 and 11, responsible for 90% of all genital warts in the United States. Data show that the vaccine is most effective when given prior to onset of sexual activity.

When speaking with a worried parent, I think it's critical to explain that association does not imply causation. I also would review the rationale behind giving the HPV vaccine and reiterate that maximum benefit is achieved by immunization before sexual debut.

Every year, about 12,000 women in the United States are diagnosed with cervical cancer and almost 4,000 die from it. Worldwide, cervical cancer is the second most common cancer in women, causing an estimated 470,000 new cases and 233,000 deaths per year. I don't think you can put a price on the value of saving lives by administering a vaccine, although of course plenty of health economists have tried to do just that.

Going forward, I think it behooves physicians who administer vaccines to stay abreast of the news. When you see a headline about any vaccine, check out the Web sites of the CDC (www.cdc.govwww.aap.org

As we're seeing from the recent measles outbreaks across the country, the majority of cases are not the result of vaccine failure but of failure to vaccinate. Our role is to help parents make the right decision. We must be armed with data to prevent associations between daily events from being interpreted as causation.

I am a member of global advisory boards on vaccine for Novartis, Wyeth, and GlaxoSmithKline, for which I receive honoraria.