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Protecting the Young Against Pertussis
The current pertussis outbreak occurring in California clearly demonstrates that we need to make a greater effort to vaccinate adults in order to protect infants too young to be completely vaccinated.
To quote the 2010 editorial by Dr. Alfred DeMaria Jr. and Dr. Susan Lett (Clin. Infect. Dis. 2010;50:1346-8), “If it does take a village to raise a child, then that village should be fully immunized against pertussis.”
Between January and July of this year, the California Department of Public Health received reports of a total 1,337 confirmed or probable cases of pertussis, which represents a fourfold increase from the 258 cases reported during the first half of 2009. If these rates persist throughout 2010, California will have its highest annual rate of pertussis since 1963 and the most cases reported since 1958, according the Centers for Disease Control and Prevention (MMWR 2010; 59:817).
During this outbreak, the CDPH expanded recommendations to off-label situations, including vaccination of those who are pregnant, older than 65 years, and aged 7-10 years.
As we've seen in the past, infants younger than 6 months of age—too young to have received the recommended three protective diphtheria-tetanus-acellular pertussis (DTaP) doses yet—are bearing the brunt of the illness, accounting for 89% of all the California cases. Disease incidence in children younger than 1 year of age was 38.5 cases per 100,000 population vs. 3.4 per 100,000 for all ages.
Of 634 case reports with available data, 105 (17%) were hospitalized, with 63% being younger than 3 months old. And, sadly, all six of the pertussis deaths reported as of July 13, 2010, were in previously healthy infants aged younger than 2 months at disease onset.
These deaths could have been prevented. A 2006-2008 study in the Netherlands demonstrated why the so-called “cocooning” effect really works. Of 560 not recently immunized household contacts of 164 hospitalized infants who were tested for Bordetella pertussis infection, 53% were infected and 14% had no symptoms. Among 96 households for which the most likely source of infection was established, 41% were siblings, 38% were mothers, and 17% were fathers.
The authors concluded that maintaining or boosting immunity to pertussis in parents and relatives could prevent 35%-55% of infant cases (Clin. Infect. Dis. 2010;50:1339-45).
The adolescent/adult tetanus-diphtheria-acellular pertussis vaccine (Tdap) has now been recommended for all adults as a replacement for the old Td vaccine. In practice, however, beyond the adolescent years, most adults receive it only if both they require tetanus prevention and the provider is aware of recent changes in the immunization recommendations.
As clinicians caring for children, we routinely vaccinate children as old as 6 years of age with DTaP and 10- to 18-year-olds with Tdap. But I believe we also have a role in helping to ensure that our youngest patients are protected by encouraging their adult contacts to be immunized with Tdap.
Certainly, most family physicians and med-ped (combined internal medicine and pediatrics) physicians are already doing this. Pediatricians who feel comfortable vaccinating parents/adult caregivers in their offices have a great opportunity, but others could still recommend that parents get the booster from their personal physician or a local health department clinic. And don't forget to suggest pertussis immunization for other adults who come into regular contact with the young infant, including grandparents and babysitters. Some health departments offer a price reduction if they're told that the Tdap is to protect a new infant in your family.
Pregnant women are a special situation. The U.S. Advisory Committee on Immunization Practices (ACIP) recommends pertussis immunization for women prior to conception and after birth if they have not received it within the past 2 years. The ACIP did not recommend Tdap for routine use during pregnancy because there is too little safety and efficacy data (MMWR 2008; 57[RR-4]:1-51).
However, the American College of Obstetricians and Gynecologists suggests vaccinating pregnant women if the risk is felt to be higher than the undefined risks of vaccine (Obstet. Gynecol. 2009;114:398-400). The American Academy of Pediatrics, for its part, recommends Tdap for pregnant adolescents in the same way as for nonpregnant adolescents (Pediatrics 2006; 117:965-78).
Dr. DeMaria and Dr. Lett also went on to write in their editorial that—when Tdap is given to pregnant women in the second or third trimester—counseling and administration is recommended.
Pediatricians might consider suggesting pertussis immunization to pregnant women who come in to “pediatrician shop,” and to those who have their older children accompanying them.
By the time this column is published, I will have a new grandchild. During talks with my son, it became clear to me that the cocooning concept has not reached enough health care professionals. I advised him that he, my daughter-in-law, and other in-laws receive Tdap before the baby's birth to maximize the chance of protection. My wife made sure she got hers.
In my view, Tdap for adult contacts is just as important as making sure the crib and car seat you buy for your baby are safe. Here's a potentially lethal disease that's resurgent in parts of the country, and we have a tool to protect our newborns against it. Shouldn't we make every effort to do so?
The current pertussis outbreak occurring in California clearly demonstrates that we need to make a greater effort to vaccinate adults in order to protect infants too young to be completely vaccinated.
To quote the 2010 editorial by Dr. Alfred DeMaria Jr. and Dr. Susan Lett (Clin. Infect. Dis. 2010;50:1346-8), “If it does take a village to raise a child, then that village should be fully immunized against pertussis.”
Between January and July of this year, the California Department of Public Health received reports of a total 1,337 confirmed or probable cases of pertussis, which represents a fourfold increase from the 258 cases reported during the first half of 2009. If these rates persist throughout 2010, California will have its highest annual rate of pertussis since 1963 and the most cases reported since 1958, according the Centers for Disease Control and Prevention (MMWR 2010; 59:817).
During this outbreak, the CDPH expanded recommendations to off-label situations, including vaccination of those who are pregnant, older than 65 years, and aged 7-10 years.
As we've seen in the past, infants younger than 6 months of age—too young to have received the recommended three protective diphtheria-tetanus-acellular pertussis (DTaP) doses yet—are bearing the brunt of the illness, accounting for 89% of all the California cases. Disease incidence in children younger than 1 year of age was 38.5 cases per 100,000 population vs. 3.4 per 100,000 for all ages.
Of 634 case reports with available data, 105 (17%) were hospitalized, with 63% being younger than 3 months old. And, sadly, all six of the pertussis deaths reported as of July 13, 2010, were in previously healthy infants aged younger than 2 months at disease onset.
These deaths could have been prevented. A 2006-2008 study in the Netherlands demonstrated why the so-called “cocooning” effect really works. Of 560 not recently immunized household contacts of 164 hospitalized infants who were tested for Bordetella pertussis infection, 53% were infected and 14% had no symptoms. Among 96 households for which the most likely source of infection was established, 41% were siblings, 38% were mothers, and 17% were fathers.
The authors concluded that maintaining or boosting immunity to pertussis in parents and relatives could prevent 35%-55% of infant cases (Clin. Infect. Dis. 2010;50:1339-45).
The adolescent/adult tetanus-diphtheria-acellular pertussis vaccine (Tdap) has now been recommended for all adults as a replacement for the old Td vaccine. In practice, however, beyond the adolescent years, most adults receive it only if both they require tetanus prevention and the provider is aware of recent changes in the immunization recommendations.
As clinicians caring for children, we routinely vaccinate children as old as 6 years of age with DTaP and 10- to 18-year-olds with Tdap. But I believe we also have a role in helping to ensure that our youngest patients are protected by encouraging their adult contacts to be immunized with Tdap.
Certainly, most family physicians and med-ped (combined internal medicine and pediatrics) physicians are already doing this. Pediatricians who feel comfortable vaccinating parents/adult caregivers in their offices have a great opportunity, but others could still recommend that parents get the booster from their personal physician or a local health department clinic. And don't forget to suggest pertussis immunization for other adults who come into regular contact with the young infant, including grandparents and babysitters. Some health departments offer a price reduction if they're told that the Tdap is to protect a new infant in your family.
Pregnant women are a special situation. The U.S. Advisory Committee on Immunization Practices (ACIP) recommends pertussis immunization for women prior to conception and after birth if they have not received it within the past 2 years. The ACIP did not recommend Tdap for routine use during pregnancy because there is too little safety and efficacy data (MMWR 2008; 57[RR-4]:1-51).
However, the American College of Obstetricians and Gynecologists suggests vaccinating pregnant women if the risk is felt to be higher than the undefined risks of vaccine (Obstet. Gynecol. 2009;114:398-400). The American Academy of Pediatrics, for its part, recommends Tdap for pregnant adolescents in the same way as for nonpregnant adolescents (Pediatrics 2006; 117:965-78).
Dr. DeMaria and Dr. Lett also went on to write in their editorial that—when Tdap is given to pregnant women in the second or third trimester—counseling and administration is recommended.
Pediatricians might consider suggesting pertussis immunization to pregnant women who come in to “pediatrician shop,” and to those who have their older children accompanying them.
By the time this column is published, I will have a new grandchild. During talks with my son, it became clear to me that the cocooning concept has not reached enough health care professionals. I advised him that he, my daughter-in-law, and other in-laws receive Tdap before the baby's birth to maximize the chance of protection. My wife made sure she got hers.
In my view, Tdap for adult contacts is just as important as making sure the crib and car seat you buy for your baby are safe. Here's a potentially lethal disease that's resurgent in parts of the country, and we have a tool to protect our newborns against it. Shouldn't we make every effort to do so?
The current pertussis outbreak occurring in California clearly demonstrates that we need to make a greater effort to vaccinate adults in order to protect infants too young to be completely vaccinated.
To quote the 2010 editorial by Dr. Alfred DeMaria Jr. and Dr. Susan Lett (Clin. Infect. Dis. 2010;50:1346-8), “If it does take a village to raise a child, then that village should be fully immunized against pertussis.”
Between January and July of this year, the California Department of Public Health received reports of a total 1,337 confirmed or probable cases of pertussis, which represents a fourfold increase from the 258 cases reported during the first half of 2009. If these rates persist throughout 2010, California will have its highest annual rate of pertussis since 1963 and the most cases reported since 1958, according the Centers for Disease Control and Prevention (MMWR 2010; 59:817).
During this outbreak, the CDPH expanded recommendations to off-label situations, including vaccination of those who are pregnant, older than 65 years, and aged 7-10 years.
As we've seen in the past, infants younger than 6 months of age—too young to have received the recommended three protective diphtheria-tetanus-acellular pertussis (DTaP) doses yet—are bearing the brunt of the illness, accounting for 89% of all the California cases. Disease incidence in children younger than 1 year of age was 38.5 cases per 100,000 population vs. 3.4 per 100,000 for all ages.
Of 634 case reports with available data, 105 (17%) were hospitalized, with 63% being younger than 3 months old. And, sadly, all six of the pertussis deaths reported as of July 13, 2010, were in previously healthy infants aged younger than 2 months at disease onset.
These deaths could have been prevented. A 2006-2008 study in the Netherlands demonstrated why the so-called “cocooning” effect really works. Of 560 not recently immunized household contacts of 164 hospitalized infants who were tested for Bordetella pertussis infection, 53% were infected and 14% had no symptoms. Among 96 households for which the most likely source of infection was established, 41% were siblings, 38% were mothers, and 17% were fathers.
The authors concluded that maintaining or boosting immunity to pertussis in parents and relatives could prevent 35%-55% of infant cases (Clin. Infect. Dis. 2010;50:1339-45).
The adolescent/adult tetanus-diphtheria-acellular pertussis vaccine (Tdap) has now been recommended for all adults as a replacement for the old Td vaccine. In practice, however, beyond the adolescent years, most adults receive it only if both they require tetanus prevention and the provider is aware of recent changes in the immunization recommendations.
As clinicians caring for children, we routinely vaccinate children as old as 6 years of age with DTaP and 10- to 18-year-olds with Tdap. But I believe we also have a role in helping to ensure that our youngest patients are protected by encouraging their adult contacts to be immunized with Tdap.
Certainly, most family physicians and med-ped (combined internal medicine and pediatrics) physicians are already doing this. Pediatricians who feel comfortable vaccinating parents/adult caregivers in their offices have a great opportunity, but others could still recommend that parents get the booster from their personal physician or a local health department clinic. And don't forget to suggest pertussis immunization for other adults who come into regular contact with the young infant, including grandparents and babysitters. Some health departments offer a price reduction if they're told that the Tdap is to protect a new infant in your family.
Pregnant women are a special situation. The U.S. Advisory Committee on Immunization Practices (ACIP) recommends pertussis immunization for women prior to conception and after birth if they have not received it within the past 2 years. The ACIP did not recommend Tdap for routine use during pregnancy because there is too little safety and efficacy data (MMWR 2008; 57[RR-4]:1-51).
However, the American College of Obstetricians and Gynecologists suggests vaccinating pregnant women if the risk is felt to be higher than the undefined risks of vaccine (Obstet. Gynecol. 2009;114:398-400). The American Academy of Pediatrics, for its part, recommends Tdap for pregnant adolescents in the same way as for nonpregnant adolescents (Pediatrics 2006; 117:965-78).
Dr. DeMaria and Dr. Lett also went on to write in their editorial that—when Tdap is given to pregnant women in the second or third trimester—counseling and administration is recommended.
Pediatricians might consider suggesting pertussis immunization to pregnant women who come in to “pediatrician shop,” and to those who have their older children accompanying them.
By the time this column is published, I will have a new grandchild. During talks with my son, it became clear to me that the cocooning concept has not reached enough health care professionals. I advised him that he, my daughter-in-law, and other in-laws receive Tdap before the baby's birth to maximize the chance of protection. My wife made sure she got hers.
In my view, Tdap for adult contacts is just as important as making sure the crib and car seat you buy for your baby are safe. Here's a potentially lethal disease that's resurgent in parts of the country, and we have a tool to protect our newborns against it. Shouldn't we make every effort to do so?
Multidrug-Resistant Shigellosis Outbreaks
As my community battles another large Shigella outbreak, I wanted to point out a few aspects of the infection that are often overlooked.
An estimated 450,000 cases of shigellosis occur every year in the United States, the majority among children who are not yet toilet trained. Here in the Kansas City area, we've had an ongoing Shigella sonnei outbreak since November 2009, with more than 250 cases diagnosed to date.
While the diarrhea is usually mild and self-limited, it is highly contagious through the fecal-oral route. Treatment is recommended for confirmed cases, both to stem transmission and to shorten disease duration. Of concern, resistance to trimethoprim-sulfamethoxazole has risen dramatically, from 47% in 1999–2003 to 89% in 2006. Ampicillin resistance also jumped, from 80% to 86%, while strains resistant to both drugs rose from 38% to 89% (MMWR 2006;55:1068–71).
However, azithromycin remains a good choice for treatment and is recommended in the Red Book as a potential treatment option for shigellosis. Dosing is 10 mg/kg one time on day 1 and then 5 mg/kg once a day for 4 more days (maximum 500 mg on day 1 and 250 mg thereafter). Microbiology labs do not routinely report azithromycin-susceptibility data, but randomly selected isolates have been tested during our current outbreak and thus far all are susceptible.
Most isolates are also susceptible to both ceftriaxone and ciprofloxacin, but both of those drugs are approximately five times more expensive than azithromycin is, and fluoroquinolones aren't approved for treating shigellosis in children younger than 18 years of age unless there are no other choices.
Some data also support the use of oral cephalosporins, but eradication rates are lower than with other drugs, so they currently are not recommended.
The last Shigella outbreak in Kansas City, in 2005, involved more than 400 cases over a period of 6 months and also featured a multidrug-resistant strain. Most children had mild disease, but we encountered an obstacle in that Missouri state law requires two negative stool cultures after treatment before the child can return to school or day care, which typically took 2–3 weeks to achieve. Appropriate treatment was often delayed because of empiric therapy with drugs to which strains were resistant and/or preauthorization requirements for using alternative drugs. Getting the families to come back for the repeat culture also was often a challenge.
There are few data to support exclusion policies that mandate two negative cultures. In contrast, some data suggest that such policies prolong the outbreak, in part because some parents will simply move their child to another day care center without mentioning the infection or drop them off at the local water park.
In some states, children with a single negative stool culture may attend child care but are excluded from interacting with other children. Such “cohorting” of convalescing children is better than excluding them entirely. This makes sense because data suggest that if the first convalescent stool culture is negative, the second one almost always is as well (Pediatr. Infect. Dis. J. 2010 May [doi:10.1097/INF.0b013e3181e4ee6e]). I would like to see a change in the regulations that would allow children to re-enter day care sooner.
Of course, it isn't surprising that day care attendance could facilitate transmission of Shigella. Ingestion of as few as 10 organisms is sufficient to produce infection. In a study a few years back, Dr. Andi Shane, a pediatric infectious disease specialist at Emory University, Atlanta, identified several risk factors for prolonged transmission in such settings, many of which are modifiable: soiled diapers accessible to children, water activities involving kiddie pools, volunteers who diapered infants, employed staff who had not received formal hand-washing education, hand-washing supplies that were kept out of the reach of children (and presumably the adults too!), and no adult supervision provided for hand washing in young children (Arch. Pediatr. Adolesc. Med. 2003;157:601–3).
The key to minimizing the transmission of shigellosis in day care centers is clear. Appropriate hand washing and diapering practices must be adhered to. This should include scheduled hand washing for everyone on arrival at the day care center, before meals, or after playing outdoors, along with supervised hand washing for young children. Banning kiddie pools could go a long way too but may not be a good idea on these hot summer days
Just to note: Shigellosis isn't exclusive to children. After our last day care outbreak, I alerted our community to the history related to the Rainbow Family Gathering, a national event orchestrated by a group promoting world peace. Poor sanitation coupled with common sources for food and water facilitated person-to-person spread and one of the largest outbreaks ever reported (J. Infect. Dis. 1990;162:1324–8).
As my community battles another large Shigella outbreak, I wanted to point out a few aspects of the infection that are often overlooked.
An estimated 450,000 cases of shigellosis occur every year in the United States, the majority among children who are not yet toilet trained. Here in the Kansas City area, we've had an ongoing Shigella sonnei outbreak since November 2009, with more than 250 cases diagnosed to date.
While the diarrhea is usually mild and self-limited, it is highly contagious through the fecal-oral route. Treatment is recommended for confirmed cases, both to stem transmission and to shorten disease duration. Of concern, resistance to trimethoprim-sulfamethoxazole has risen dramatically, from 47% in 1999–2003 to 89% in 2006. Ampicillin resistance also jumped, from 80% to 86%, while strains resistant to both drugs rose from 38% to 89% (MMWR 2006;55:1068–71).
However, azithromycin remains a good choice for treatment and is recommended in the Red Book as a potential treatment option for shigellosis. Dosing is 10 mg/kg one time on day 1 and then 5 mg/kg once a day for 4 more days (maximum 500 mg on day 1 and 250 mg thereafter). Microbiology labs do not routinely report azithromycin-susceptibility data, but randomly selected isolates have been tested during our current outbreak and thus far all are susceptible.
Most isolates are also susceptible to both ceftriaxone and ciprofloxacin, but both of those drugs are approximately five times more expensive than azithromycin is, and fluoroquinolones aren't approved for treating shigellosis in children younger than 18 years of age unless there are no other choices.
Some data also support the use of oral cephalosporins, but eradication rates are lower than with other drugs, so they currently are not recommended.
The last Shigella outbreak in Kansas City, in 2005, involved more than 400 cases over a period of 6 months and also featured a multidrug-resistant strain. Most children had mild disease, but we encountered an obstacle in that Missouri state law requires two negative stool cultures after treatment before the child can return to school or day care, which typically took 2–3 weeks to achieve. Appropriate treatment was often delayed because of empiric therapy with drugs to which strains were resistant and/or preauthorization requirements for using alternative drugs. Getting the families to come back for the repeat culture also was often a challenge.
There are few data to support exclusion policies that mandate two negative cultures. In contrast, some data suggest that such policies prolong the outbreak, in part because some parents will simply move their child to another day care center without mentioning the infection or drop them off at the local water park.
In some states, children with a single negative stool culture may attend child care but are excluded from interacting with other children. Such “cohorting” of convalescing children is better than excluding them entirely. This makes sense because data suggest that if the first convalescent stool culture is negative, the second one almost always is as well (Pediatr. Infect. Dis. J. 2010 May [doi:10.1097/INF.0b013e3181e4ee6e]). I would like to see a change in the regulations that would allow children to re-enter day care sooner.
Of course, it isn't surprising that day care attendance could facilitate transmission of Shigella. Ingestion of as few as 10 organisms is sufficient to produce infection. In a study a few years back, Dr. Andi Shane, a pediatric infectious disease specialist at Emory University, Atlanta, identified several risk factors for prolonged transmission in such settings, many of which are modifiable: soiled diapers accessible to children, water activities involving kiddie pools, volunteers who diapered infants, employed staff who had not received formal hand-washing education, hand-washing supplies that were kept out of the reach of children (and presumably the adults too!), and no adult supervision provided for hand washing in young children (Arch. Pediatr. Adolesc. Med. 2003;157:601–3).
The key to minimizing the transmission of shigellosis in day care centers is clear. Appropriate hand washing and diapering practices must be adhered to. This should include scheduled hand washing for everyone on arrival at the day care center, before meals, or after playing outdoors, along with supervised hand washing for young children. Banning kiddie pools could go a long way too but may not be a good idea on these hot summer days
Just to note: Shigellosis isn't exclusive to children. After our last day care outbreak, I alerted our community to the history related to the Rainbow Family Gathering, a national event orchestrated by a group promoting world peace. Poor sanitation coupled with common sources for food and water facilitated person-to-person spread and one of the largest outbreaks ever reported (J. Infect. Dis. 1990;162:1324–8).
As my community battles another large Shigella outbreak, I wanted to point out a few aspects of the infection that are often overlooked.
An estimated 450,000 cases of shigellosis occur every year in the United States, the majority among children who are not yet toilet trained. Here in the Kansas City area, we've had an ongoing Shigella sonnei outbreak since November 2009, with more than 250 cases diagnosed to date.
While the diarrhea is usually mild and self-limited, it is highly contagious through the fecal-oral route. Treatment is recommended for confirmed cases, both to stem transmission and to shorten disease duration. Of concern, resistance to trimethoprim-sulfamethoxazole has risen dramatically, from 47% in 1999–2003 to 89% in 2006. Ampicillin resistance also jumped, from 80% to 86%, while strains resistant to both drugs rose from 38% to 89% (MMWR 2006;55:1068–71).
However, azithromycin remains a good choice for treatment and is recommended in the Red Book as a potential treatment option for shigellosis. Dosing is 10 mg/kg one time on day 1 and then 5 mg/kg once a day for 4 more days (maximum 500 mg on day 1 and 250 mg thereafter). Microbiology labs do not routinely report azithromycin-susceptibility data, but randomly selected isolates have been tested during our current outbreak and thus far all are susceptible.
Most isolates are also susceptible to both ceftriaxone and ciprofloxacin, but both of those drugs are approximately five times more expensive than azithromycin is, and fluoroquinolones aren't approved for treating shigellosis in children younger than 18 years of age unless there are no other choices.
Some data also support the use of oral cephalosporins, but eradication rates are lower than with other drugs, so they currently are not recommended.
The last Shigella outbreak in Kansas City, in 2005, involved more than 400 cases over a period of 6 months and also featured a multidrug-resistant strain. Most children had mild disease, but we encountered an obstacle in that Missouri state law requires two negative stool cultures after treatment before the child can return to school or day care, which typically took 2–3 weeks to achieve. Appropriate treatment was often delayed because of empiric therapy with drugs to which strains were resistant and/or preauthorization requirements for using alternative drugs. Getting the families to come back for the repeat culture also was often a challenge.
There are few data to support exclusion policies that mandate two negative cultures. In contrast, some data suggest that such policies prolong the outbreak, in part because some parents will simply move their child to another day care center without mentioning the infection or drop them off at the local water park.
In some states, children with a single negative stool culture may attend child care but are excluded from interacting with other children. Such “cohorting” of convalescing children is better than excluding them entirely. This makes sense because data suggest that if the first convalescent stool culture is negative, the second one almost always is as well (Pediatr. Infect. Dis. J. 2010 May [doi:10.1097/INF.0b013e3181e4ee6e]). I would like to see a change in the regulations that would allow children to re-enter day care sooner.
Of course, it isn't surprising that day care attendance could facilitate transmission of Shigella. Ingestion of as few as 10 organisms is sufficient to produce infection. In a study a few years back, Dr. Andi Shane, a pediatric infectious disease specialist at Emory University, Atlanta, identified several risk factors for prolonged transmission in such settings, many of which are modifiable: soiled diapers accessible to children, water activities involving kiddie pools, volunteers who diapered infants, employed staff who had not received formal hand-washing education, hand-washing supplies that were kept out of the reach of children (and presumably the adults too!), and no adult supervision provided for hand washing in young children (Arch. Pediatr. Adolesc. Med. 2003;157:601–3).
The key to minimizing the transmission of shigellosis in day care centers is clear. Appropriate hand washing and diapering practices must be adhered to. This should include scheduled hand washing for everyone on arrival at the day care center, before meals, or after playing outdoors, along with supervised hand washing for young children. Banning kiddie pools could go a long way too but may not be a good idea on these hot summer days
Just to note: Shigellosis isn't exclusive to children. After our last day care outbreak, I alerted our community to the history related to the Rainbow Family Gathering, a national event orchestrated by a group promoting world peace. Poor sanitation coupled with common sources for food and water facilitated person-to-person spread and one of the largest outbreaks ever reported (J. Infect. Dis. 1990;162:1324–8).
Should We Consider Giving MMR Earlier?
Parents' concern that children receive too many vaccines too soon can result in delay or avoidance of vaccination, with the measles-mumps-rubella vaccine often being delayed. However, a recent study showed no neurologic harm from on-time receipt of all the recommended vaccines—including MMR—from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, and children with on-time receipt of vaccines performed better on select neurologic testing than those delaying vaccine. Another study showed that children lose maternally derived measles antibody protection as early as 1 month of age.
The study by Dr. Michael J. Smith and Dr. Charles R. Woods of the University of Louisville (Ky.) addressed the “too many vaccines too close together” issue. Using publicly available Vaccine Safety Datalink data from a previous study on thimerosal exposure and neuropsychological outcomes, the authors found that getting all recommended vaccines per the ACIP recommended schedule was associated with better—not worse—performance on selected neurologic outcomes at age 7-10 years, even when such factors as socioeconomic status were controlled for (Pediatrics 2010;125:1134-41). Importantly, there were no statistically significant differences favoring the less-vaccinated children. The authors concluded—and, I agree—that these data add reassurance for parents who are concerned that children receive too many vaccines too soon.
In the other study, Belgian investigators measured measles antibodies in mothers and persistence of the maternal antibody transferred to infants (BMJ 2010;340:c1626[doi:10.1136/bmj.c1626]). They found that the 86 women with antibody from measles vaccine had significantly lower, yet still protective, measles IgG titers, being one-quarter as high as in 120 mothers with antibody from previous measles infection, and that cord blood and initial infant titers correlated with maternal titers.
Of concern is that maternally endowed measles antibody disappeared at a median of 3.8 months in infants of previously measles-infected mothers (only a few infants had antibody at 6 months of age), and at nearly 1 month of age in infants of vaccinated women (none had antibody at 6 months). Thus infants became vulnerable to measles even earlier than previously reported. If maternal antibody is from vaccine, their infants are susceptible for the 9-14 months just prior to the MMR if it is administered at 12-15 months of age.
While waning maternally endowed antibody by 6 months of age is expected for most infections, measles had seemed different. In the 1970s-1980s, MMR was given at 15 months of age. This was because maternal antibody reportedly persisted up to 12 months and prevented a vaccine “take” if the mothers' antibody came from measles infection (J. Pediatr 1977; 91:715-8).hA later report showed waning antibody sooner when mothers' immunity came from measles vaccine: no antibody in 71% of 9-month-olds and 95% of 12-month-olds Maediatrics 1995;96:447-50).httis set the stage for the earlier 12-month MMR option. Now we have increasing evidence of even younger age for disappearance of the vaccine-interfering yet protective antibody to measles.
These data also have implications for the infant traveler. Although MMR isn't currently licensed for infants less than 1 year of age, data like these are the rationale for the Redbook recommendation that MMR be given to infants at 6 months of age or older who will be traveling to measles-endemic countries or during measles outbreaks. Of note, this is considered an “invalid” dose and the 12- to 15-month dose is still needed to attend school.
It might surprise some that Switzerland is now a measles-endemic country apparently due to its low 71% measles immunization rate. In fact, the per capita Swiss measles attack rate is similar to Somalia's. This shows that developed countries will have reemergent measles if herd immunity is lost.
I think we can make a case for studying earlier MMR dosing, particularly with measles outbreaks occurring in the United States, and imported cases potentially now coming from developed countries. If herd immunity (greater than 90% immunized) is in place, the infants' gap in measles protection may not be so worrisome. But as MMR immunization rates decline and become particularly low in some pockets in our country, concern increases over potential larger outbreaks. Studies to evaluate MMR at age 9 months could be the first step. If the vaccine were effective, we could narrow the measles-vulnerable window and vaccinate at the 9-month wellness visit.
Parents' concern that children receive too many vaccines too soon can result in delay or avoidance of vaccination, with the measles-mumps-rubella vaccine often being delayed. However, a recent study showed no neurologic harm from on-time receipt of all the recommended vaccines—including MMR—from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, and children with on-time receipt of vaccines performed better on select neurologic testing than those delaying vaccine. Another study showed that children lose maternally derived measles antibody protection as early as 1 month of age.
The study by Dr. Michael J. Smith and Dr. Charles R. Woods of the University of Louisville (Ky.) addressed the “too many vaccines too close together” issue. Using publicly available Vaccine Safety Datalink data from a previous study on thimerosal exposure and neuropsychological outcomes, the authors found that getting all recommended vaccines per the ACIP recommended schedule was associated with better—not worse—performance on selected neurologic outcomes at age 7-10 years, even when such factors as socioeconomic status were controlled for (Pediatrics 2010;125:1134-41). Importantly, there were no statistically significant differences favoring the less-vaccinated children. The authors concluded—and, I agree—that these data add reassurance for parents who are concerned that children receive too many vaccines too soon.
In the other study, Belgian investigators measured measles antibodies in mothers and persistence of the maternal antibody transferred to infants (BMJ 2010;340:c1626[doi:10.1136/bmj.c1626]). They found that the 86 women with antibody from measles vaccine had significantly lower, yet still protective, measles IgG titers, being one-quarter as high as in 120 mothers with antibody from previous measles infection, and that cord blood and initial infant titers correlated with maternal titers.
Of concern is that maternally endowed measles antibody disappeared at a median of 3.8 months in infants of previously measles-infected mothers (only a few infants had antibody at 6 months of age), and at nearly 1 month of age in infants of vaccinated women (none had antibody at 6 months). Thus infants became vulnerable to measles even earlier than previously reported. If maternal antibody is from vaccine, their infants are susceptible for the 9-14 months just prior to the MMR if it is administered at 12-15 months of age.
While waning maternally endowed antibody by 6 months of age is expected for most infections, measles had seemed different. In the 1970s-1980s, MMR was given at 15 months of age. This was because maternal antibody reportedly persisted up to 12 months and prevented a vaccine “take” if the mothers' antibody came from measles infection (J. Pediatr 1977; 91:715-8).hA later report showed waning antibody sooner when mothers' immunity came from measles vaccine: no antibody in 71% of 9-month-olds and 95% of 12-month-olds Maediatrics 1995;96:447-50).httis set the stage for the earlier 12-month MMR option. Now we have increasing evidence of even younger age for disappearance of the vaccine-interfering yet protective antibody to measles.
These data also have implications for the infant traveler. Although MMR isn't currently licensed for infants less than 1 year of age, data like these are the rationale for the Redbook recommendation that MMR be given to infants at 6 months of age or older who will be traveling to measles-endemic countries or during measles outbreaks. Of note, this is considered an “invalid” dose and the 12- to 15-month dose is still needed to attend school.
It might surprise some that Switzerland is now a measles-endemic country apparently due to its low 71% measles immunization rate. In fact, the per capita Swiss measles attack rate is similar to Somalia's. This shows that developed countries will have reemergent measles if herd immunity is lost.
I think we can make a case for studying earlier MMR dosing, particularly with measles outbreaks occurring in the United States, and imported cases potentially now coming from developed countries. If herd immunity (greater than 90% immunized) is in place, the infants' gap in measles protection may not be so worrisome. But as MMR immunization rates decline and become particularly low in some pockets in our country, concern increases over potential larger outbreaks. Studies to evaluate MMR at age 9 months could be the first step. If the vaccine were effective, we could narrow the measles-vulnerable window and vaccinate at the 9-month wellness visit.
Parents' concern that children receive too many vaccines too soon can result in delay or avoidance of vaccination, with the measles-mumps-rubella vaccine often being delayed. However, a recent study showed no neurologic harm from on-time receipt of all the recommended vaccines—including MMR—from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, and children with on-time receipt of vaccines performed better on select neurologic testing than those delaying vaccine. Another study showed that children lose maternally derived measles antibody protection as early as 1 month of age.
The study by Dr. Michael J. Smith and Dr. Charles R. Woods of the University of Louisville (Ky.) addressed the “too many vaccines too close together” issue. Using publicly available Vaccine Safety Datalink data from a previous study on thimerosal exposure and neuropsychological outcomes, the authors found that getting all recommended vaccines per the ACIP recommended schedule was associated with better—not worse—performance on selected neurologic outcomes at age 7-10 years, even when such factors as socioeconomic status were controlled for (Pediatrics 2010;125:1134-41). Importantly, there were no statistically significant differences favoring the less-vaccinated children. The authors concluded—and, I agree—that these data add reassurance for parents who are concerned that children receive too many vaccines too soon.
In the other study, Belgian investigators measured measles antibodies in mothers and persistence of the maternal antibody transferred to infants (BMJ 2010;340:c1626[doi:10.1136/bmj.c1626]). They found that the 86 women with antibody from measles vaccine had significantly lower, yet still protective, measles IgG titers, being one-quarter as high as in 120 mothers with antibody from previous measles infection, and that cord blood and initial infant titers correlated with maternal titers.
Of concern is that maternally endowed measles antibody disappeared at a median of 3.8 months in infants of previously measles-infected mothers (only a few infants had antibody at 6 months of age), and at nearly 1 month of age in infants of vaccinated women (none had antibody at 6 months). Thus infants became vulnerable to measles even earlier than previously reported. If maternal antibody is from vaccine, their infants are susceptible for the 9-14 months just prior to the MMR if it is administered at 12-15 months of age.
While waning maternally endowed antibody by 6 months of age is expected for most infections, measles had seemed different. In the 1970s-1980s, MMR was given at 15 months of age. This was because maternal antibody reportedly persisted up to 12 months and prevented a vaccine “take” if the mothers' antibody came from measles infection (J. Pediatr 1977; 91:715-8).hA later report showed waning antibody sooner when mothers' immunity came from measles vaccine: no antibody in 71% of 9-month-olds and 95% of 12-month-olds Maediatrics 1995;96:447-50).httis set the stage for the earlier 12-month MMR option. Now we have increasing evidence of even younger age for disappearance of the vaccine-interfering yet protective antibody to measles.
These data also have implications for the infant traveler. Although MMR isn't currently licensed for infants less than 1 year of age, data like these are the rationale for the Redbook recommendation that MMR be given to infants at 6 months of age or older who will be traveling to measles-endemic countries or during measles outbreaks. Of note, this is considered an “invalid” dose and the 12- to 15-month dose is still needed to attend school.
It might surprise some that Switzerland is now a measles-endemic country apparently due to its low 71% measles immunization rate. In fact, the per capita Swiss measles attack rate is similar to Somalia's. This shows that developed countries will have reemergent measles if herd immunity is lost.
I think we can make a case for studying earlier MMR dosing, particularly with measles outbreaks occurring in the United States, and imported cases potentially now coming from developed countries. If herd immunity (greater than 90% immunized) is in place, the infants' gap in measles protection may not be so worrisome. But as MMR immunization rates decline and become particularly low in some pockets in our country, concern increases over potential larger outbreaks. Studies to evaluate MMR at age 9 months could be the first step. If the vaccine were effective, we could narrow the measles-vulnerable window and vaccinate at the 9-month wellness visit.
Bacterial Conjunctivitis and Resistance
The treatment of bacterial conjunctivitis has become more challenging in this era of increasing antimicrobial resistance.
Conjunctivitis in children is extremely common, accounting for an estimated 1%–4% of all pediatric office visits. Yet, with so much focus on otitis media, the impact of antimicrobial resistance on conjunctivitis treatment has been widely overlooked. This is despite that approximately one-third of children with bacterial conjunctivitis have concurrent otitis media, most commonly caused by Haemophilus influenzae. In fact, my interest in conjunctivitis stems from its connection with otitis media.
Many of the traditional topical ocular agents we've used in the past to treat bacterial conjunctivitis—including those of the aminoglycoside, polymixin B combination, and macrolide classes—are less effective than they once were, thanks to increasing resistance. At the same time, many of these agents have tolerability issues, which render them even less effective. After all, if a child won't allow the medicine to be placed in her eyes, it most certainly won't work.
Fluoroquinolones, while remaining highly effective with far less resistance, are about 10 times as expensive as older agents available generically. Is it worth the cost to speed up the cure and reduce the contagion of a self-limited disease by a day or two at the most? The answer to that depends on a variety of factors, including the degree of the child's discomfort, the potential burden to the parent of missing days from work, and whether the child attends day care. It's not a simple decision.
Of course, it's important to determine whether the conjunctivitis is bacterial. Acute bacterial conjunctivitis begins abruptly with early symptoms of irritation or foreign body sensation and tearing. Mucopurulent or purulent discharge, morning crusting, swelling, and comorbid otitis media are common indicators. In contrast, viral conjunctivitis is characterized by watery discharge and conjunctival injection, while allergic conjunctivitis is more likely to involve itching, stringy or ropy discharge, lid edema, red/hyperemic conjunctiva, and comorbid allergic rhinitis.
The age of the child is also predictive. Conjunctivitis in preschool children is most likely bacterial, usually either H. influenzae or Streptococcus pneumoniae. In a newborn, the cause is most likely chemical irritation (from silver nitrate), while in older children the conjunctivitis is usually viral or allergic.
Oral antibiotics are recommended for any child who has concurrent otitis media. But for uncomplicated bacterial conjunctivitis, topical ophthalmic agents are recommended over systemic agents because they achieve a greater concentration of antibiotic to the eye while avoiding systemic side effects. Most of the topicals discussed below are approved for children 1 year of age and older.
Aminoglycosides, including gentamicin, tobramycin, and neomycin, are most active against gram-negative bacteria such as Pseudomonas aeruginosa (except neomycin) and methicillin-sensitive Staphylococcus aureus (MSSA). However, they do not cover streptococci or methicillin-resistant Staph. aureus (MRSA), and studies have shown increasing resistance of Streptococcus pneumoniae to these agents, reaching 65% by 2006 in the Ocular TRUST (Tracking Resistance in U.S. Today) 1 survey (Am. J. Ophthalmol. 2008;145:951–8).
Polymixin B is active only against gram-negative bacteria and therefore is given in combination with other antibiotics, including trimethoprim, bacitracin, and neomycin/bacitracin, which broaden the coverage to include staphylococci, streptococci, and some gram-negative bacteria including H. influenzae. While most H. influenzae strains remain susceptible to polymixin B alone or in combination, there is high resistance among Strep. pneumoniae and MSSA isolates.
The macrolide erythromycin—used as a 0.5% ointment—is one of the oldest ocular antibiotics, but now is rarely effective in bacterial conjunctivitis because of the high resistance among Staphylococcus species and poor activity against H. influenzae. The newer topical macrolide azithromycin is also hampered by high levels of resistance. In the TRUST survey, resistance to azithromycin was 22% for Strep. pneumoniae isolates, 46% among MSSA bacteria, and 91% among MRSA isolates. Other studies have shown significant resistance among H. influenzae as well.
Fluoroquinolones offer broad-spectrum coverage against both gram-positive and gram-negative organisms. The older topical agents ofloxacin and ciprofloxacin have largely been replaced by the newer agents levofloxacin, moxifloxacin, gatifloxacin, and now besifloxacin, which was approved by the U.S. Food and Drug Administration in May 2009. Numerous randomized, double-masked, controlled clinical trials in children and adults with bacterial conjunctivitis have demonstrated clinical cure rates of approximately 66%–96% and microbial eradication rates ranging from 84% to 96% for the newer fluoroquinolones.
There has been almost no resistance to fluoroquinolones among Strep. pneumoniae or H. influenzae organisms, but there is some fluoroquinolone resistance among MSSA isolates and a high level for MRSA, reaching 85% in Ocular TRUST 1.
Although most topical ophthalmic antibiotics used for the treatment of bacterial conjunctivitis are generally safe and well tolerated, ocular adverse events can cause discomfort that leads to noncompliance. Topical aminoglycosides have been associated with corneal and conjunctival toxicity, especially when used frequently, as well as ocular allergic reactions. Bacitracin has been associated with cases of contact dermatitis in the conjunctival area, and the polymixin B combinations can also cause local irritation. Macrolides, too, can cause minor ocular irritation, redness, and hypersensitivity.
In contrast, the fluoroquinolones have been well tolerated and associated with less toxicity than the other ophthalmic antibacterial classes, although crystalline precipitates have been seen with ciprofloxacin when it is administered frequently.
The ideal treatment for acute bacterial conjunctivitis should be a well-tolerated, broad-spectrum, highly potent, and bactericidal agent with a high concentration on the ocular surface and a rapid kill time. Convenience in dosing is also an important consideration. The newer fluoroquinolones, with potent efficacy against H. influenzae and Strep. pneumoniae, may best fulfill those requirements. But of course, cost remains a problem for many.
The treatment of bacterial conjunctivitis has become more challenging in this era of increasing antimicrobial resistance.
Conjunctivitis in children is extremely common, accounting for an estimated 1%–4% of all pediatric office visits. Yet, with so much focus on otitis media, the impact of antimicrobial resistance on conjunctivitis treatment has been widely overlooked. This is despite that approximately one-third of children with bacterial conjunctivitis have concurrent otitis media, most commonly caused by Haemophilus influenzae. In fact, my interest in conjunctivitis stems from its connection with otitis media.
Many of the traditional topical ocular agents we've used in the past to treat bacterial conjunctivitis—including those of the aminoglycoside, polymixin B combination, and macrolide classes—are less effective than they once were, thanks to increasing resistance. At the same time, many of these agents have tolerability issues, which render them even less effective. After all, if a child won't allow the medicine to be placed in her eyes, it most certainly won't work.
Fluoroquinolones, while remaining highly effective with far less resistance, are about 10 times as expensive as older agents available generically. Is it worth the cost to speed up the cure and reduce the contagion of a self-limited disease by a day or two at the most? The answer to that depends on a variety of factors, including the degree of the child's discomfort, the potential burden to the parent of missing days from work, and whether the child attends day care. It's not a simple decision.
Of course, it's important to determine whether the conjunctivitis is bacterial. Acute bacterial conjunctivitis begins abruptly with early symptoms of irritation or foreign body sensation and tearing. Mucopurulent or purulent discharge, morning crusting, swelling, and comorbid otitis media are common indicators. In contrast, viral conjunctivitis is characterized by watery discharge and conjunctival injection, while allergic conjunctivitis is more likely to involve itching, stringy or ropy discharge, lid edema, red/hyperemic conjunctiva, and comorbid allergic rhinitis.
The age of the child is also predictive. Conjunctivitis in preschool children is most likely bacterial, usually either H. influenzae or Streptococcus pneumoniae. In a newborn, the cause is most likely chemical irritation (from silver nitrate), while in older children the conjunctivitis is usually viral or allergic.
Oral antibiotics are recommended for any child who has concurrent otitis media. But for uncomplicated bacterial conjunctivitis, topical ophthalmic agents are recommended over systemic agents because they achieve a greater concentration of antibiotic to the eye while avoiding systemic side effects. Most of the topicals discussed below are approved for children 1 year of age and older.
Aminoglycosides, including gentamicin, tobramycin, and neomycin, are most active against gram-negative bacteria such as Pseudomonas aeruginosa (except neomycin) and methicillin-sensitive Staphylococcus aureus (MSSA). However, they do not cover streptococci or methicillin-resistant Staph. aureus (MRSA), and studies have shown increasing resistance of Streptococcus pneumoniae to these agents, reaching 65% by 2006 in the Ocular TRUST (Tracking Resistance in U.S. Today) 1 survey (Am. J. Ophthalmol. 2008;145:951–8).
Polymixin B is active only against gram-negative bacteria and therefore is given in combination with other antibiotics, including trimethoprim, bacitracin, and neomycin/bacitracin, which broaden the coverage to include staphylococci, streptococci, and some gram-negative bacteria including H. influenzae. While most H. influenzae strains remain susceptible to polymixin B alone or in combination, there is high resistance among Strep. pneumoniae and MSSA isolates.
The macrolide erythromycin—used as a 0.5% ointment—is one of the oldest ocular antibiotics, but now is rarely effective in bacterial conjunctivitis because of the high resistance among Staphylococcus species and poor activity against H. influenzae. The newer topical macrolide azithromycin is also hampered by high levels of resistance. In the TRUST survey, resistance to azithromycin was 22% for Strep. pneumoniae isolates, 46% among MSSA bacteria, and 91% among MRSA isolates. Other studies have shown significant resistance among H. influenzae as well.
Fluoroquinolones offer broad-spectrum coverage against both gram-positive and gram-negative organisms. The older topical agents ofloxacin and ciprofloxacin have largely been replaced by the newer agents levofloxacin, moxifloxacin, gatifloxacin, and now besifloxacin, which was approved by the U.S. Food and Drug Administration in May 2009. Numerous randomized, double-masked, controlled clinical trials in children and adults with bacterial conjunctivitis have demonstrated clinical cure rates of approximately 66%–96% and microbial eradication rates ranging from 84% to 96% for the newer fluoroquinolones.
There has been almost no resistance to fluoroquinolones among Strep. pneumoniae or H. influenzae organisms, but there is some fluoroquinolone resistance among MSSA isolates and a high level for MRSA, reaching 85% in Ocular TRUST 1.
Although most topical ophthalmic antibiotics used for the treatment of bacterial conjunctivitis are generally safe and well tolerated, ocular adverse events can cause discomfort that leads to noncompliance. Topical aminoglycosides have been associated with corneal and conjunctival toxicity, especially when used frequently, as well as ocular allergic reactions. Bacitracin has been associated with cases of contact dermatitis in the conjunctival area, and the polymixin B combinations can also cause local irritation. Macrolides, too, can cause minor ocular irritation, redness, and hypersensitivity.
In contrast, the fluoroquinolones have been well tolerated and associated with less toxicity than the other ophthalmic antibacterial classes, although crystalline precipitates have been seen with ciprofloxacin when it is administered frequently.
The ideal treatment for acute bacterial conjunctivitis should be a well-tolerated, broad-spectrum, highly potent, and bactericidal agent with a high concentration on the ocular surface and a rapid kill time. Convenience in dosing is also an important consideration. The newer fluoroquinolones, with potent efficacy against H. influenzae and Strep. pneumoniae, may best fulfill those requirements. But of course, cost remains a problem for many.
The treatment of bacterial conjunctivitis has become more challenging in this era of increasing antimicrobial resistance.
Conjunctivitis in children is extremely common, accounting for an estimated 1%–4% of all pediatric office visits. Yet, with so much focus on otitis media, the impact of antimicrobial resistance on conjunctivitis treatment has been widely overlooked. This is despite that approximately one-third of children with bacterial conjunctivitis have concurrent otitis media, most commonly caused by Haemophilus influenzae. In fact, my interest in conjunctivitis stems from its connection with otitis media.
Many of the traditional topical ocular agents we've used in the past to treat bacterial conjunctivitis—including those of the aminoglycoside, polymixin B combination, and macrolide classes—are less effective than they once were, thanks to increasing resistance. At the same time, many of these agents have tolerability issues, which render them even less effective. After all, if a child won't allow the medicine to be placed in her eyes, it most certainly won't work.
Fluoroquinolones, while remaining highly effective with far less resistance, are about 10 times as expensive as older agents available generically. Is it worth the cost to speed up the cure and reduce the contagion of a self-limited disease by a day or two at the most? The answer to that depends on a variety of factors, including the degree of the child's discomfort, the potential burden to the parent of missing days from work, and whether the child attends day care. It's not a simple decision.
Of course, it's important to determine whether the conjunctivitis is bacterial. Acute bacterial conjunctivitis begins abruptly with early symptoms of irritation or foreign body sensation and tearing. Mucopurulent or purulent discharge, morning crusting, swelling, and comorbid otitis media are common indicators. In contrast, viral conjunctivitis is characterized by watery discharge and conjunctival injection, while allergic conjunctivitis is more likely to involve itching, stringy or ropy discharge, lid edema, red/hyperemic conjunctiva, and comorbid allergic rhinitis.
The age of the child is also predictive. Conjunctivitis in preschool children is most likely bacterial, usually either H. influenzae or Streptococcus pneumoniae. In a newborn, the cause is most likely chemical irritation (from silver nitrate), while in older children the conjunctivitis is usually viral or allergic.
Oral antibiotics are recommended for any child who has concurrent otitis media. But for uncomplicated bacterial conjunctivitis, topical ophthalmic agents are recommended over systemic agents because they achieve a greater concentration of antibiotic to the eye while avoiding systemic side effects. Most of the topicals discussed below are approved for children 1 year of age and older.
Aminoglycosides, including gentamicin, tobramycin, and neomycin, are most active against gram-negative bacteria such as Pseudomonas aeruginosa (except neomycin) and methicillin-sensitive Staphylococcus aureus (MSSA). However, they do not cover streptococci or methicillin-resistant Staph. aureus (MRSA), and studies have shown increasing resistance of Streptococcus pneumoniae to these agents, reaching 65% by 2006 in the Ocular TRUST (Tracking Resistance in U.S. Today) 1 survey (Am. J. Ophthalmol. 2008;145:951–8).
Polymixin B is active only against gram-negative bacteria and therefore is given in combination with other antibiotics, including trimethoprim, bacitracin, and neomycin/bacitracin, which broaden the coverage to include staphylococci, streptococci, and some gram-negative bacteria including H. influenzae. While most H. influenzae strains remain susceptible to polymixin B alone or in combination, there is high resistance among Strep. pneumoniae and MSSA isolates.
The macrolide erythromycin—used as a 0.5% ointment—is one of the oldest ocular antibiotics, but now is rarely effective in bacterial conjunctivitis because of the high resistance among Staphylococcus species and poor activity against H. influenzae. The newer topical macrolide azithromycin is also hampered by high levels of resistance. In the TRUST survey, resistance to azithromycin was 22% for Strep. pneumoniae isolates, 46% among MSSA bacteria, and 91% among MRSA isolates. Other studies have shown significant resistance among H. influenzae as well.
Fluoroquinolones offer broad-spectrum coverage against both gram-positive and gram-negative organisms. The older topical agents ofloxacin and ciprofloxacin have largely been replaced by the newer agents levofloxacin, moxifloxacin, gatifloxacin, and now besifloxacin, which was approved by the U.S. Food and Drug Administration in May 2009. Numerous randomized, double-masked, controlled clinical trials in children and adults with bacterial conjunctivitis have demonstrated clinical cure rates of approximately 66%–96% and microbial eradication rates ranging from 84% to 96% for the newer fluoroquinolones.
There has been almost no resistance to fluoroquinolones among Strep. pneumoniae or H. influenzae organisms, but there is some fluoroquinolone resistance among MSSA isolates and a high level for MRSA, reaching 85% in Ocular TRUST 1.
Although most topical ophthalmic antibiotics used for the treatment of bacterial conjunctivitis are generally safe and well tolerated, ocular adverse events can cause discomfort that leads to noncompliance. Topical aminoglycosides have been associated with corneal and conjunctival toxicity, especially when used frequently, as well as ocular allergic reactions. Bacitracin has been associated with cases of contact dermatitis in the conjunctival area, and the polymixin B combinations can also cause local irritation. Macrolides, too, can cause minor ocular irritation, redness, and hypersensitivity.
In contrast, the fluoroquinolones have been well tolerated and associated with less toxicity than the other ophthalmic antibacterial classes, although crystalline precipitates have been seen with ciprofloxacin when it is administered frequently.
The ideal treatment for acute bacterial conjunctivitis should be a well-tolerated, broad-spectrum, highly potent, and bactericidal agent with a high concentration on the ocular surface and a rapid kill time. Convenience in dosing is also an important consideration. The newer fluoroquinolones, with potent efficacy against H. influenzae and Strep. pneumoniae, may best fulfill those requirements. But of course, cost remains a problem for many.
Watch Out for Animal Bites
It's springtime, and that means you'll be seeing more children in your office with animal bites. Are you up to date on the latest treatment guidelines?
One of our community practitioners recently told me that he estimated that in the summer, at least once a week, they fielded a phone call or saw a child with an animal bite injury.
Most such injuries are minor, and usually inflicted by the family pet (dogs 80% of the time), but a recent review in our institution suggested that for children who come to the emergency department (ED) following an animal bite, nearly 7% have a serious injury resulting in hospitalization.
Nationally, it is estimated that millions of bites occur each year, and approximately 1% of all ED visits by children are related to animal bite injuries, so this is a substantial number of children. Practitioners should ensure that they have a standardized practice for caring for such children.
Ricky Ogden, a PharmD in our emergency department, presented a poster at the Infectious Diseases Society of America meeting in 2009 in Philadelphia detailing the epidemiology of animal bite injuries seen in our children's hospital ED from 2005 to 2008. He along with my ID colleagues reviewed a randomly selected subset of 400 patients; some of the interesting findings included that encounters occurred most often in April, May, and June, with Sunday being the most common day for an ED visit. Injuries to the face (50.7%) topped the list, and dogs (84%) were the most likely culprits.
In looking at animal bite prophylaxis, we were surprised to find that most prescriptions were given for an inappropriately long duration (7–10 days rather than the 2- to 3-day recommendation). If our experience is typical, this is a significant issue. Given that there are about 4.7 million bite wounds every year, that is a lot of unnecessary antibiotics..
Provision of care for the child with an animal bite is well outlined in the Red Book, but careful attention to all steps may be overlooked, particularly if the child is not cared for in his/her medical home or by a pediatric provider.
Documentation of the child's age, underlying diseases, and the bite encounter (animal, circumstances, and time of injury before health care provider visit) is key. In young infants or immunocompromised hosts, the risk of infection and serious outcome associated with animal bites increases. Wounds that are fresh (less than 12 hours old) and superficial require nothing more than cleansing and assessment of the need for a tetanus shot.
Assuming the child was previously healthy and is medically stable, your first order of business is to assess and characterize the wound and to provide cleansing, irrigation, and debridement. In the case of penetrating trauma, consider the possibility of occult fracture or damage to tendons or joints. For children with extensive wounds, surgical consultation may be necessary for certain types of hand injuries (potential compartment syndromes or artery, tendon, or ligament injuries) or in the case of cranial injuries.
The assessment of tetanus immunization status (and the need for rabies vaccine/immunoglobulin) is important; a notation that vaccines are “up to date” is not sufficient. We have noted that in children attending urgent care or walk-in retail clinics, the documentation of vaccine status is often overlooked or parents are simply asked if vaccines are “up to date.” This is an instance when it is particularly important to document the precise date when the last tetanus-containing vaccine was given in order to decide whether an additional dose of vaccine is necessary.
The decision to offer antibiotic prophylaxis in the child with an animal bite injury is guided by the assessment of several key pieces of information. You need to know when to initiate therapy, the correct drug to administer (amoxicillin-clavulanate), and the correct duration of therapy (2–3 days). For those with mild injuries and superficial abrasions, prophylaxis is not indicated. Wounds associated with devitalized tissue—especially crush injuries, puncture wounds, and bites to the face, hands or feet, or genitals—have a greater risk of complications, including infections.
For the child with an overtly infected wound, treatment is 10 days (and in those with wounds involving tendons, joints, or other deeper tissues, intravenous therapy should be utilized). The most common infecting organism with both dog and cat bites has always been Pasteurella multocida, but Staphylococcus aureus, Eikenella corrodens, Capnocytophaga species, some anaerobes, and some gram-negative organisms have been reported.
It is interesting to note that among infected wounds at our hospital, we found no methicillin-resistant Staphylococcus aureus despite that 70% of the children we see with skin abscesses (and we see a lot) are caused by this pathogen. For now, we are still recommending amoxicillin-clavulanate, but of course, culture the draining wound and carefully follow up. For those with true penicillin allergy, the combination of clindamycin plus trimethoprim-sulfamethoxazole can be used for nonreptile animal and human bites.
Stay tuned and enjoy the springtime weather and all of the fun it brings with it.
It's springtime, and that means you'll be seeing more children in your office with animal bites. Are you up to date on the latest treatment guidelines?
One of our community practitioners recently told me that he estimated that in the summer, at least once a week, they fielded a phone call or saw a child with an animal bite injury.
Most such injuries are minor, and usually inflicted by the family pet (dogs 80% of the time), but a recent review in our institution suggested that for children who come to the emergency department (ED) following an animal bite, nearly 7% have a serious injury resulting in hospitalization.
Nationally, it is estimated that millions of bites occur each year, and approximately 1% of all ED visits by children are related to animal bite injuries, so this is a substantial number of children. Practitioners should ensure that they have a standardized practice for caring for such children.
Ricky Ogden, a PharmD in our emergency department, presented a poster at the Infectious Diseases Society of America meeting in 2009 in Philadelphia detailing the epidemiology of animal bite injuries seen in our children's hospital ED from 2005 to 2008. He along with my ID colleagues reviewed a randomly selected subset of 400 patients; some of the interesting findings included that encounters occurred most often in April, May, and June, with Sunday being the most common day for an ED visit. Injuries to the face (50.7%) topped the list, and dogs (84%) were the most likely culprits.
In looking at animal bite prophylaxis, we were surprised to find that most prescriptions were given for an inappropriately long duration (7–10 days rather than the 2- to 3-day recommendation). If our experience is typical, this is a significant issue. Given that there are about 4.7 million bite wounds every year, that is a lot of unnecessary antibiotics..
Provision of care for the child with an animal bite is well outlined in the Red Book, but careful attention to all steps may be overlooked, particularly if the child is not cared for in his/her medical home or by a pediatric provider.
Documentation of the child's age, underlying diseases, and the bite encounter (animal, circumstances, and time of injury before health care provider visit) is key. In young infants or immunocompromised hosts, the risk of infection and serious outcome associated with animal bites increases. Wounds that are fresh (less than 12 hours old) and superficial require nothing more than cleansing and assessment of the need for a tetanus shot.
Assuming the child was previously healthy and is medically stable, your first order of business is to assess and characterize the wound and to provide cleansing, irrigation, and debridement. In the case of penetrating trauma, consider the possibility of occult fracture or damage to tendons or joints. For children with extensive wounds, surgical consultation may be necessary for certain types of hand injuries (potential compartment syndromes or artery, tendon, or ligament injuries) or in the case of cranial injuries.
The assessment of tetanus immunization status (and the need for rabies vaccine/immunoglobulin) is important; a notation that vaccines are “up to date” is not sufficient. We have noted that in children attending urgent care or walk-in retail clinics, the documentation of vaccine status is often overlooked or parents are simply asked if vaccines are “up to date.” This is an instance when it is particularly important to document the precise date when the last tetanus-containing vaccine was given in order to decide whether an additional dose of vaccine is necessary.
The decision to offer antibiotic prophylaxis in the child with an animal bite injury is guided by the assessment of several key pieces of information. You need to know when to initiate therapy, the correct drug to administer (amoxicillin-clavulanate), and the correct duration of therapy (2–3 days). For those with mild injuries and superficial abrasions, prophylaxis is not indicated. Wounds associated with devitalized tissue—especially crush injuries, puncture wounds, and bites to the face, hands or feet, or genitals—have a greater risk of complications, including infections.
For the child with an overtly infected wound, treatment is 10 days (and in those with wounds involving tendons, joints, or other deeper tissues, intravenous therapy should be utilized). The most common infecting organism with both dog and cat bites has always been Pasteurella multocida, but Staphylococcus aureus, Eikenella corrodens, Capnocytophaga species, some anaerobes, and some gram-negative organisms have been reported.
It is interesting to note that among infected wounds at our hospital, we found no methicillin-resistant Staphylococcus aureus despite that 70% of the children we see with skin abscesses (and we see a lot) are caused by this pathogen. For now, we are still recommending amoxicillin-clavulanate, but of course, culture the draining wound and carefully follow up. For those with true penicillin allergy, the combination of clindamycin plus trimethoprim-sulfamethoxazole can be used for nonreptile animal and human bites.
Stay tuned and enjoy the springtime weather and all of the fun it brings with it.
It's springtime, and that means you'll be seeing more children in your office with animal bites. Are you up to date on the latest treatment guidelines?
One of our community practitioners recently told me that he estimated that in the summer, at least once a week, they fielded a phone call or saw a child with an animal bite injury.
Most such injuries are minor, and usually inflicted by the family pet (dogs 80% of the time), but a recent review in our institution suggested that for children who come to the emergency department (ED) following an animal bite, nearly 7% have a serious injury resulting in hospitalization.
Nationally, it is estimated that millions of bites occur each year, and approximately 1% of all ED visits by children are related to animal bite injuries, so this is a substantial number of children. Practitioners should ensure that they have a standardized practice for caring for such children.
Ricky Ogden, a PharmD in our emergency department, presented a poster at the Infectious Diseases Society of America meeting in 2009 in Philadelphia detailing the epidemiology of animal bite injuries seen in our children's hospital ED from 2005 to 2008. He along with my ID colleagues reviewed a randomly selected subset of 400 patients; some of the interesting findings included that encounters occurred most often in April, May, and June, with Sunday being the most common day for an ED visit. Injuries to the face (50.7%) topped the list, and dogs (84%) were the most likely culprits.
In looking at animal bite prophylaxis, we were surprised to find that most prescriptions were given for an inappropriately long duration (7–10 days rather than the 2- to 3-day recommendation). If our experience is typical, this is a significant issue. Given that there are about 4.7 million bite wounds every year, that is a lot of unnecessary antibiotics..
Provision of care for the child with an animal bite is well outlined in the Red Book, but careful attention to all steps may be overlooked, particularly if the child is not cared for in his/her medical home or by a pediatric provider.
Documentation of the child's age, underlying diseases, and the bite encounter (animal, circumstances, and time of injury before health care provider visit) is key. In young infants or immunocompromised hosts, the risk of infection and serious outcome associated with animal bites increases. Wounds that are fresh (less than 12 hours old) and superficial require nothing more than cleansing and assessment of the need for a tetanus shot.
Assuming the child was previously healthy and is medically stable, your first order of business is to assess and characterize the wound and to provide cleansing, irrigation, and debridement. In the case of penetrating trauma, consider the possibility of occult fracture or damage to tendons or joints. For children with extensive wounds, surgical consultation may be necessary for certain types of hand injuries (potential compartment syndromes or artery, tendon, or ligament injuries) or in the case of cranial injuries.
The assessment of tetanus immunization status (and the need for rabies vaccine/immunoglobulin) is important; a notation that vaccines are “up to date” is not sufficient. We have noted that in children attending urgent care or walk-in retail clinics, the documentation of vaccine status is often overlooked or parents are simply asked if vaccines are “up to date.” This is an instance when it is particularly important to document the precise date when the last tetanus-containing vaccine was given in order to decide whether an additional dose of vaccine is necessary.
The decision to offer antibiotic prophylaxis in the child with an animal bite injury is guided by the assessment of several key pieces of information. You need to know when to initiate therapy, the correct drug to administer (amoxicillin-clavulanate), and the correct duration of therapy (2–3 days). For those with mild injuries and superficial abrasions, prophylaxis is not indicated. Wounds associated with devitalized tissue—especially crush injuries, puncture wounds, and bites to the face, hands or feet, or genitals—have a greater risk of complications, including infections.
For the child with an overtly infected wound, treatment is 10 days (and in those with wounds involving tendons, joints, or other deeper tissues, intravenous therapy should be utilized). The most common infecting organism with both dog and cat bites has always been Pasteurella multocida, but Staphylococcus aureus, Eikenella corrodens, Capnocytophaga species, some anaerobes, and some gram-negative organisms have been reported.
It is interesting to note that among infected wounds at our hospital, we found no methicillin-resistant Staphylococcus aureus despite that 70% of the children we see with skin abscesses (and we see a lot) are caused by this pathogen. For now, we are still recommending amoxicillin-clavulanate, but of course, culture the draining wound and carefully follow up. For those with true penicillin allergy, the combination of clindamycin plus trimethoprim-sulfamethoxazole can be used for nonreptile animal and human bites.
Stay tuned and enjoy the springtime weather and all of the fun it brings with it.
The Wakefield Paper
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.
Factors Affecting HPV Immunization
Could it be that our own cultural affiliations and beliefs might affect our patients' willingness to accept the human papillomavirus vaccine? A fascinating new study suggests just that.
To me, HPV vaccine should be a no-brainer. It protects against 60%-70% of cervical cancers, and is as safe as any other available vaccine. Yet, only about 40% of young females recommended to receive the vaccine have done so thus far. Why?
It may be in part because it is one of the most expensive vaccines in our repertoire, but it's covered by the Vaccines for Children program and now by most third-party payers. And it's not just a matter of 11- to 12-year-olds not getting vaccinated overall. In my area, only about two-thirds of adolescents who get the tetanus-diphtheria-acellular pertussis booster are concurrently receiving the HPV vaccine. It seems that they are refusing it specifically.
The HPV vaccine has been the object of misinformation and is controversial. Some people argue that it is unsafe or that it encourages young females to be more sexually active.
But a recent study actually suggests that girls getting HPV vaccine may be more cautious about sexual activity (Br. J. Cancer 2009;101:1502-4), yet the incorrect beliefs persist.
We hope that families will accept our advice on matters when they have concerns, but another new study sheds light on why families might not.
Yale University law professor Dan M. Kahan and his associates randomly surveyed 1,538 U.S. adults from a database of 40,000 scholarly public opinion poll respondents regarding their views on the HPV vaccine.
Individuals with cultural values favoring “authority” and/or “individualism” perceived the vaccine as risky, in part because they believed it would lead girls to engage in unsafe sex. But those favoring gender equality and/or community/government involvement in basic health care were more likely to see the vaccine as low risk and high benefit (Law Hum. Behav. 2010 Jan. 14 [doi:10.1007/s10979-009-9201-0
We all have suspected this to be the case, but now there are data to support that suspicion. Now here's the really interesting part: The researchers designed fictional “experts” who appeared to either share or oppose the respondents' cultural values. When views about HPV vaccines came from experts who respondents believed shared their values, they were more willing to accept the information. But when the views came from experts whom they perceived held values different from theirs, the subjects did not accept the experts' information.
So, when proauthority/individualism experts asserted the vaccine was risky, proauthority/individualism respondents agreed with them. When the egalitarian/procommunity experts argued that it was safe, egalitarian/procommunity respondents also agreed with them, solidifying overall disagreement about use of the vaccine.
However, when proauthority/individualism experts asserted that the vaccine was safe, proauthority/individualism respondents (who originally thought the vaccine was risky) moderated their original viewpoints, because the information came from experts who they perceived shared their values.
This held true for the opposite scenario, too: If egalitarian/procommunity experts argued the vaccine was risky, egalitarian/procommunity respondents shifted their belief toward its being risky.
As clinicians, we'd like to believe that our patients respect and trust us. But it's possible that when it comes to controversial recommendations, they may resist what we say if they don't identify enough with us based on our apparent values. If it is clear that our patient's family holds values widely disparate from ours, it might be helpful to utilize another more culturally congruent health professional in our practice to counsel about vaccination. This would vary by practice and from case to case, but could include people of similar race, religion, political viewpoint, or even regional accent.
Studies suggest that patients sometimes choose physicians to match their values. But with Medicaid and managed care, that may not always be possible. Using this type of approach may have more impact.
Surveys and discussion groups by the CDC suggest that scare tactics and scientific data may not successfully modify the opinion of parents who are disinclined toward vaccination (and I think most of us have the same experience). However, I did want to briefly mention recent data regarding HPV transmission in young adults that took me by surprise and may be persuasive for some patients.
Dr. Ann N. Burchell and her associates at McGill University, Montreal, evaluated female college/university students (aged 18-24 years) in self-described “stable” relationships exclusively with one male partner. The 263 couples had engaged in vaginal sex for a median of 3.9 months. HPV was detected in 64% of the couples. In 41% of the couples, both partners had the same HPV type. This risk of having the same strain was nearly four times more than what would be found by testing two random individuals. Also, oncogenic HPV-16 was the most common type, detected in 22% of couples (Epidemiology 2010;21:31-7).
In other words, one partner frequently came into the relationship with HPV and quickly transmitted it to the other. I was startled by the transmission frequency in these young adult females, who considered themselves in stable relationships. It suggests that acquisition is not just in early adolescence (although the risk of persistence is higher in that age group) and that catch-up immunization may be more important than some have thought. Perhaps these data won't convince all of your patients to get the HPV vaccine, but it may be helpful in some who are in their late teens or precollege age.
Could it be that our own cultural affiliations and beliefs might affect our patients' willingness to accept the human papillomavirus vaccine? A fascinating new study suggests just that.
To me, HPV vaccine should be a no-brainer. It protects against 60%-70% of cervical cancers, and is as safe as any other available vaccine. Yet, only about 40% of young females recommended to receive the vaccine have done so thus far. Why?
It may be in part because it is one of the most expensive vaccines in our repertoire, but it's covered by the Vaccines for Children program and now by most third-party payers. And it's not just a matter of 11- to 12-year-olds not getting vaccinated overall. In my area, only about two-thirds of adolescents who get the tetanus-diphtheria-acellular pertussis booster are concurrently receiving the HPV vaccine. It seems that they are refusing it specifically.
The HPV vaccine has been the object of misinformation and is controversial. Some people argue that it is unsafe or that it encourages young females to be more sexually active.
But a recent study actually suggests that girls getting HPV vaccine may be more cautious about sexual activity (Br. J. Cancer 2009;101:1502-4), yet the incorrect beliefs persist.
We hope that families will accept our advice on matters when they have concerns, but another new study sheds light on why families might not.
Yale University law professor Dan M. Kahan and his associates randomly surveyed 1,538 U.S. adults from a database of 40,000 scholarly public opinion poll respondents regarding their views on the HPV vaccine.
Individuals with cultural values favoring “authority” and/or “individualism” perceived the vaccine as risky, in part because they believed it would lead girls to engage in unsafe sex. But those favoring gender equality and/or community/government involvement in basic health care were more likely to see the vaccine as low risk and high benefit (Law Hum. Behav. 2010 Jan. 14 [doi:10.1007/s10979-009-9201-0
We all have suspected this to be the case, but now there are data to support that suspicion. Now here's the really interesting part: The researchers designed fictional “experts” who appeared to either share or oppose the respondents' cultural values. When views about HPV vaccines came from experts who respondents believed shared their values, they were more willing to accept the information. But when the views came from experts whom they perceived held values different from theirs, the subjects did not accept the experts' information.
So, when proauthority/individualism experts asserted the vaccine was risky, proauthority/individualism respondents agreed with them. When the egalitarian/procommunity experts argued that it was safe, egalitarian/procommunity respondents also agreed with them, solidifying overall disagreement about use of the vaccine.
However, when proauthority/individualism experts asserted that the vaccine was safe, proauthority/individualism respondents (who originally thought the vaccine was risky) moderated their original viewpoints, because the information came from experts who they perceived shared their values.
This held true for the opposite scenario, too: If egalitarian/procommunity experts argued the vaccine was risky, egalitarian/procommunity respondents shifted their belief toward its being risky.
As clinicians, we'd like to believe that our patients respect and trust us. But it's possible that when it comes to controversial recommendations, they may resist what we say if they don't identify enough with us based on our apparent values. If it is clear that our patient's family holds values widely disparate from ours, it might be helpful to utilize another more culturally congruent health professional in our practice to counsel about vaccination. This would vary by practice and from case to case, but could include people of similar race, religion, political viewpoint, or even regional accent.
Studies suggest that patients sometimes choose physicians to match their values. But with Medicaid and managed care, that may not always be possible. Using this type of approach may have more impact.
Surveys and discussion groups by the CDC suggest that scare tactics and scientific data may not successfully modify the opinion of parents who are disinclined toward vaccination (and I think most of us have the same experience). However, I did want to briefly mention recent data regarding HPV transmission in young adults that took me by surprise and may be persuasive for some patients.
Dr. Ann N. Burchell and her associates at McGill University, Montreal, evaluated female college/university students (aged 18-24 years) in self-described “stable” relationships exclusively with one male partner. The 263 couples had engaged in vaginal sex for a median of 3.9 months. HPV was detected in 64% of the couples. In 41% of the couples, both partners had the same HPV type. This risk of having the same strain was nearly four times more than what would be found by testing two random individuals. Also, oncogenic HPV-16 was the most common type, detected in 22% of couples (Epidemiology 2010;21:31-7).
In other words, one partner frequently came into the relationship with HPV and quickly transmitted it to the other. I was startled by the transmission frequency in these young adult females, who considered themselves in stable relationships. It suggests that acquisition is not just in early adolescence (although the risk of persistence is higher in that age group) and that catch-up immunization may be more important than some have thought. Perhaps these data won't convince all of your patients to get the HPV vaccine, but it may be helpful in some who are in their late teens or precollege age.
Could it be that our own cultural affiliations and beliefs might affect our patients' willingness to accept the human papillomavirus vaccine? A fascinating new study suggests just that.
To me, HPV vaccine should be a no-brainer. It protects against 60%-70% of cervical cancers, and is as safe as any other available vaccine. Yet, only about 40% of young females recommended to receive the vaccine have done so thus far. Why?
It may be in part because it is one of the most expensive vaccines in our repertoire, but it's covered by the Vaccines for Children program and now by most third-party payers. And it's not just a matter of 11- to 12-year-olds not getting vaccinated overall. In my area, only about two-thirds of adolescents who get the tetanus-diphtheria-acellular pertussis booster are concurrently receiving the HPV vaccine. It seems that they are refusing it specifically.
The HPV vaccine has been the object of misinformation and is controversial. Some people argue that it is unsafe or that it encourages young females to be more sexually active.
But a recent study actually suggests that girls getting HPV vaccine may be more cautious about sexual activity (Br. J. Cancer 2009;101:1502-4), yet the incorrect beliefs persist.
We hope that families will accept our advice on matters when they have concerns, but another new study sheds light on why families might not.
Yale University law professor Dan M. Kahan and his associates randomly surveyed 1,538 U.S. adults from a database of 40,000 scholarly public opinion poll respondents regarding their views on the HPV vaccine.
Individuals with cultural values favoring “authority” and/or “individualism” perceived the vaccine as risky, in part because they believed it would lead girls to engage in unsafe sex. But those favoring gender equality and/or community/government involvement in basic health care were more likely to see the vaccine as low risk and high benefit (Law Hum. Behav. 2010 Jan. 14 [doi:10.1007/s10979-009-9201-0
We all have suspected this to be the case, but now there are data to support that suspicion. Now here's the really interesting part: The researchers designed fictional “experts” who appeared to either share or oppose the respondents' cultural values. When views about HPV vaccines came from experts who respondents believed shared their values, they were more willing to accept the information. But when the views came from experts whom they perceived held values different from theirs, the subjects did not accept the experts' information.
So, when proauthority/individualism experts asserted the vaccine was risky, proauthority/individualism respondents agreed with them. When the egalitarian/procommunity experts argued that it was safe, egalitarian/procommunity respondents also agreed with them, solidifying overall disagreement about use of the vaccine.
However, when proauthority/individualism experts asserted that the vaccine was safe, proauthority/individualism respondents (who originally thought the vaccine was risky) moderated their original viewpoints, because the information came from experts who they perceived shared their values.
This held true for the opposite scenario, too: If egalitarian/procommunity experts argued the vaccine was risky, egalitarian/procommunity respondents shifted their belief toward its being risky.
As clinicians, we'd like to believe that our patients respect and trust us. But it's possible that when it comes to controversial recommendations, they may resist what we say if they don't identify enough with us based on our apparent values. If it is clear that our patient's family holds values widely disparate from ours, it might be helpful to utilize another more culturally congruent health professional in our practice to counsel about vaccination. This would vary by practice and from case to case, but could include people of similar race, religion, political viewpoint, or even regional accent.
Studies suggest that patients sometimes choose physicians to match their values. But with Medicaid and managed care, that may not always be possible. Using this type of approach may have more impact.
Surveys and discussion groups by the CDC suggest that scare tactics and scientific data may not successfully modify the opinion of parents who are disinclined toward vaccination (and I think most of us have the same experience). However, I did want to briefly mention recent data regarding HPV transmission in young adults that took me by surprise and may be persuasive for some patients.
Dr. Ann N. Burchell and her associates at McGill University, Montreal, evaluated female college/university students (aged 18-24 years) in self-described “stable” relationships exclusively with one male partner. The 263 couples had engaged in vaginal sex for a median of 3.9 months. HPV was detected in 64% of the couples. In 41% of the couples, both partners had the same HPV type. This risk of having the same strain was nearly four times more than what would be found by testing two random individuals. Also, oncogenic HPV-16 was the most common type, detected in 22% of couples (Epidemiology 2010;21:31-7).
In other words, one partner frequently came into the relationship with HPV and quickly transmitted it to the other. I was startled by the transmission frequency in these young adult females, who considered themselves in stable relationships. It suggests that acquisition is not just in early adolescence (although the risk of persistence is higher in that age group) and that catch-up immunization may be more important than some have thought. Perhaps these data won't convince all of your patients to get the HPV vaccine, but it may be helpful in some who are in their late teens or precollege age.
Predictions for 2010: Flu, Resistance, and More
It is time for the 2010 ID Consult predictions. Instead of starting with my usual Yogi Berra quote, this year I thought I'd tap “Dilbert” creator Scott Adams: “There are many methods for predicting the future. For example, you can read horoscopes, tea leaves, tarot cards, or crystal balls. Collectively, these methods are known as nutty methods. Or you can put well-researched facts into sophisticated computer 'models, more commonly referred to as a complete waste of time.'” Maybe this explains why pandemic influenza was not on my list last year!
Indeed, although I have almost always had something to say about influenza for the last several years in my January “predictions” column, I did not correctly predict the emergence of pandemic influenza, which came on like a sledge hammer in April 2009. One major lesson learned from this unprecedented experience was the importance of collaboration.
In our institution, our emergency department and urgent care volume peaked at levels never seen before. Finding additional space to see patients, scheduling additional providers, and streamlining documentation were major problems that required innovative solutions. The mix of the high volume of worried well with the occasional very sick patient required vigilance on everyone's part.
Subspecialty and community providers also rose to the challenge, and for now, everyone is relieved that disease rates have decreased steadily over the last 4 weeks. Still, we are seeing admissions that exceed what we would usually see for this time of year and expect this to continue through April.
Here are my predictions, with the first two based on our influenza experience:
1. All lessons learned will benefit us, if and when the next outbreak occurs (and it will not necessarily be influenza).
2. Influenza vaccine will be nationally mandated for all health care workers (HCWs). Our institution utilized a mandated policy that required that all HCWs had to have vaccine or a declination signed by Dec. 1. We were able to get 91% of our HCWs immunized, compared with 82% in the last couple years, which is great. Yet, there were still gaps in coverage in certain high-risk units and in individual physicians and nurses. Among those who declined vaccination, some said they would not get vaccine unless it was mandated. Protecting the vulnerable child within our hospitals while also keeping our colleagues well is a major motivation to utilize a mandated policy. I think next year will be the year.
3. More data will focus on the use of palivizumab. Major changes in the American Academy of Pediatrics' Red Book included standardization of a start date and maximum number of doses, as well as changes in eligibility criteria focusing on gestation and age at the start of the season. There is no question we will be revisiting some of these issues in the future.
4. Meningococcal disease will continue to decline in the United States. Meningococcal infections have steadily decreased in the United States over the last 12 years, although the reasons for this are not entirely clear. In 1997, the incidence was 1.1/100,000 population, decreasing to 0.8/100,000 in 2000 and down to 0.3/100,000 in 2008. The implementation of vaccine in and of itself does not explain this decline, because no vaccine is effective against serogroup B and its population-based rates also decreased.
5. Rotavirus cases will continue to decrease. Simpler guidelines for dosing the rotavirus vaccines will result in better coverage and a continued decrease in disease. It is still amazing to me that residents in this era may not care for a single hospitalized child with rotavirus gastroenteritis.
6. Practitioners will more proactively utilize hepatitis A vaccine for the close contacts of adopted infants arriving from high-risk countries. Several reported cases of adults who had not traveled internationally but became infected with hepatitis A within 60 days after the arrival of an international adoptee have prompted new recommendations. Practitioners should identify all who will provide care for the new arrival (including grandparents and babysitters) and ensure they receive hepatitis A immunization before the child arrives, preferably referring them as soon as the plan for adoption is made.
7. The 13-valent pneumococcal conjugate vaccine (PCV13/Prevnar 13) will be here by spring. The emergence of pneumococcus serotype 19A with its typical pattern of multidrug resistance fast-tracked this vaccine, and it looks like it will be ready for implementation soon. Straightforward recommendations from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices will be available, and we hope to see the impact of this strategy within the next couple of years. Will new serotypes emerge once again?
8. Clindamycin resistance rates for Staphylococcus aureus will continue to rise. In our institution, 25% of pneumococcal strains and 12% of S. aureus are resistant. My colleague Dr. Christopher Harrison believes that if pneumococcal serotype 19A decreases with PCV 13, clindamycin resistance rates for pneumococcus in general may decrease. The level of resistance at which recommendations for treatment of staphylococcal infection will need to be changed is not clear. Some think alternative treatment should be considered at above 10%.
9. Speaking of resistance, vancomycin may no longer be the cornerstone of therapy for methicillin-resistant S. aureus (MRSA) infection by year's end. In the past, a typical S. aureus minimum inhibitory concentration (MIC) for vancomycin was 0.25–0.5 μg/mL. More recently, MICs of 1 (now 60% or so of isolates) or higher (still just 1%) have been seen, a phenomenon that has been termed “MIC creep.” Data in the adult population suggest that even if dosing is pushed to 60 mg/kg per day—the dosing typically used for CNS infections—clinical failures may occur at higher MICs.
10. We will need better evidence to support the utility of newer antistaphylococcal drugs including linezolid, daptomycin, telavancin, and ceftobiprole. Linezolid remains a very expensive drug choice with predictable adverse reactions, particularly neutropenia. Dosing for daptomycin (a lipopeptide), telavancin (a lipoglycopeptide), and ceftobiprole (our first fifth generation cephalosporin) are still not set.
Lastly, I predict—or at least hope for—a happy, healthy, and productive 2010 for all
It is time for the 2010 ID Consult predictions. Instead of starting with my usual Yogi Berra quote, this year I thought I'd tap “Dilbert” creator Scott Adams: “There are many methods for predicting the future. For example, you can read horoscopes, tea leaves, tarot cards, or crystal balls. Collectively, these methods are known as nutty methods. Or you can put well-researched facts into sophisticated computer 'models, more commonly referred to as a complete waste of time.'” Maybe this explains why pandemic influenza was not on my list last year!
Indeed, although I have almost always had something to say about influenza for the last several years in my January “predictions” column, I did not correctly predict the emergence of pandemic influenza, which came on like a sledge hammer in April 2009. One major lesson learned from this unprecedented experience was the importance of collaboration.
In our institution, our emergency department and urgent care volume peaked at levels never seen before. Finding additional space to see patients, scheduling additional providers, and streamlining documentation were major problems that required innovative solutions. The mix of the high volume of worried well with the occasional very sick patient required vigilance on everyone's part.
Subspecialty and community providers also rose to the challenge, and for now, everyone is relieved that disease rates have decreased steadily over the last 4 weeks. Still, we are seeing admissions that exceed what we would usually see for this time of year and expect this to continue through April.
Here are my predictions, with the first two based on our influenza experience:
1. All lessons learned will benefit us, if and when the next outbreak occurs (and it will not necessarily be influenza).
2. Influenza vaccine will be nationally mandated for all health care workers (HCWs). Our institution utilized a mandated policy that required that all HCWs had to have vaccine or a declination signed by Dec. 1. We were able to get 91% of our HCWs immunized, compared with 82% in the last couple years, which is great. Yet, there were still gaps in coverage in certain high-risk units and in individual physicians and nurses. Among those who declined vaccination, some said they would not get vaccine unless it was mandated. Protecting the vulnerable child within our hospitals while also keeping our colleagues well is a major motivation to utilize a mandated policy. I think next year will be the year.
3. More data will focus on the use of palivizumab. Major changes in the American Academy of Pediatrics' Red Book included standardization of a start date and maximum number of doses, as well as changes in eligibility criteria focusing on gestation and age at the start of the season. There is no question we will be revisiting some of these issues in the future.
4. Meningococcal disease will continue to decline in the United States. Meningococcal infections have steadily decreased in the United States over the last 12 years, although the reasons for this are not entirely clear. In 1997, the incidence was 1.1/100,000 population, decreasing to 0.8/100,000 in 2000 and down to 0.3/100,000 in 2008. The implementation of vaccine in and of itself does not explain this decline, because no vaccine is effective against serogroup B and its population-based rates also decreased.
5. Rotavirus cases will continue to decrease. Simpler guidelines for dosing the rotavirus vaccines will result in better coverage and a continued decrease in disease. It is still amazing to me that residents in this era may not care for a single hospitalized child with rotavirus gastroenteritis.
6. Practitioners will more proactively utilize hepatitis A vaccine for the close contacts of adopted infants arriving from high-risk countries. Several reported cases of adults who had not traveled internationally but became infected with hepatitis A within 60 days after the arrival of an international adoptee have prompted new recommendations. Practitioners should identify all who will provide care for the new arrival (including grandparents and babysitters) and ensure they receive hepatitis A immunization before the child arrives, preferably referring them as soon as the plan for adoption is made.
7. The 13-valent pneumococcal conjugate vaccine (PCV13/Prevnar 13) will be here by spring. The emergence of pneumococcus serotype 19A with its typical pattern of multidrug resistance fast-tracked this vaccine, and it looks like it will be ready for implementation soon. Straightforward recommendations from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices will be available, and we hope to see the impact of this strategy within the next couple of years. Will new serotypes emerge once again?
8. Clindamycin resistance rates for Staphylococcus aureus will continue to rise. In our institution, 25% of pneumococcal strains and 12% of S. aureus are resistant. My colleague Dr. Christopher Harrison believes that if pneumococcal serotype 19A decreases with PCV 13, clindamycin resistance rates for pneumococcus in general may decrease. The level of resistance at which recommendations for treatment of staphylococcal infection will need to be changed is not clear. Some think alternative treatment should be considered at above 10%.
9. Speaking of resistance, vancomycin may no longer be the cornerstone of therapy for methicillin-resistant S. aureus (MRSA) infection by year's end. In the past, a typical S. aureus minimum inhibitory concentration (MIC) for vancomycin was 0.25–0.5 μg/mL. More recently, MICs of 1 (now 60% or so of isolates) or higher (still just 1%) have been seen, a phenomenon that has been termed “MIC creep.” Data in the adult population suggest that even if dosing is pushed to 60 mg/kg per day—the dosing typically used for CNS infections—clinical failures may occur at higher MICs.
10. We will need better evidence to support the utility of newer antistaphylococcal drugs including linezolid, daptomycin, telavancin, and ceftobiprole. Linezolid remains a very expensive drug choice with predictable adverse reactions, particularly neutropenia. Dosing for daptomycin (a lipopeptide), telavancin (a lipoglycopeptide), and ceftobiprole (our first fifth generation cephalosporin) are still not set.
Lastly, I predict—or at least hope for—a happy, healthy, and productive 2010 for all
It is time for the 2010 ID Consult predictions. Instead of starting with my usual Yogi Berra quote, this year I thought I'd tap “Dilbert” creator Scott Adams: “There are many methods for predicting the future. For example, you can read horoscopes, tea leaves, tarot cards, or crystal balls. Collectively, these methods are known as nutty methods. Or you can put well-researched facts into sophisticated computer 'models, more commonly referred to as a complete waste of time.'” Maybe this explains why pandemic influenza was not on my list last year!
Indeed, although I have almost always had something to say about influenza for the last several years in my January “predictions” column, I did not correctly predict the emergence of pandemic influenza, which came on like a sledge hammer in April 2009. One major lesson learned from this unprecedented experience was the importance of collaboration.
In our institution, our emergency department and urgent care volume peaked at levels never seen before. Finding additional space to see patients, scheduling additional providers, and streamlining documentation were major problems that required innovative solutions. The mix of the high volume of worried well with the occasional very sick patient required vigilance on everyone's part.
Subspecialty and community providers also rose to the challenge, and for now, everyone is relieved that disease rates have decreased steadily over the last 4 weeks. Still, we are seeing admissions that exceed what we would usually see for this time of year and expect this to continue through April.
Here are my predictions, with the first two based on our influenza experience:
1. All lessons learned will benefit us, if and when the next outbreak occurs (and it will not necessarily be influenza).
2. Influenza vaccine will be nationally mandated for all health care workers (HCWs). Our institution utilized a mandated policy that required that all HCWs had to have vaccine or a declination signed by Dec. 1. We were able to get 91% of our HCWs immunized, compared with 82% in the last couple years, which is great. Yet, there were still gaps in coverage in certain high-risk units and in individual physicians and nurses. Among those who declined vaccination, some said they would not get vaccine unless it was mandated. Protecting the vulnerable child within our hospitals while also keeping our colleagues well is a major motivation to utilize a mandated policy. I think next year will be the year.
3. More data will focus on the use of palivizumab. Major changes in the American Academy of Pediatrics' Red Book included standardization of a start date and maximum number of doses, as well as changes in eligibility criteria focusing on gestation and age at the start of the season. There is no question we will be revisiting some of these issues in the future.
4. Meningococcal disease will continue to decline in the United States. Meningococcal infections have steadily decreased in the United States over the last 12 years, although the reasons for this are not entirely clear. In 1997, the incidence was 1.1/100,000 population, decreasing to 0.8/100,000 in 2000 and down to 0.3/100,000 in 2008. The implementation of vaccine in and of itself does not explain this decline, because no vaccine is effective against serogroup B and its population-based rates also decreased.
5. Rotavirus cases will continue to decrease. Simpler guidelines for dosing the rotavirus vaccines will result in better coverage and a continued decrease in disease. It is still amazing to me that residents in this era may not care for a single hospitalized child with rotavirus gastroenteritis.
6. Practitioners will more proactively utilize hepatitis A vaccine for the close contacts of adopted infants arriving from high-risk countries. Several reported cases of adults who had not traveled internationally but became infected with hepatitis A within 60 days after the arrival of an international adoptee have prompted new recommendations. Practitioners should identify all who will provide care for the new arrival (including grandparents and babysitters) and ensure they receive hepatitis A immunization before the child arrives, preferably referring them as soon as the plan for adoption is made.
7. The 13-valent pneumococcal conjugate vaccine (PCV13/Prevnar 13) will be here by spring. The emergence of pneumococcus serotype 19A with its typical pattern of multidrug resistance fast-tracked this vaccine, and it looks like it will be ready for implementation soon. Straightforward recommendations from the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices will be available, and we hope to see the impact of this strategy within the next couple of years. Will new serotypes emerge once again?
8. Clindamycin resistance rates for Staphylococcus aureus will continue to rise. In our institution, 25% of pneumococcal strains and 12% of S. aureus are resistant. My colleague Dr. Christopher Harrison believes that if pneumococcal serotype 19A decreases with PCV 13, clindamycin resistance rates for pneumococcus in general may decrease. The level of resistance at which recommendations for treatment of staphylococcal infection will need to be changed is not clear. Some think alternative treatment should be considered at above 10%.
9. Speaking of resistance, vancomycin may no longer be the cornerstone of therapy for methicillin-resistant S. aureus (MRSA) infection by year's end. In the past, a typical S. aureus minimum inhibitory concentration (MIC) for vancomycin was 0.25–0.5 μg/mL. More recently, MICs of 1 (now 60% or so of isolates) or higher (still just 1%) have been seen, a phenomenon that has been termed “MIC creep.” Data in the adult population suggest that even if dosing is pushed to 60 mg/kg per day—the dosing typically used for CNS infections—clinical failures may occur at higher MICs.
10. We will need better evidence to support the utility of newer antistaphylococcal drugs including linezolid, daptomycin, telavancin, and ceftobiprole. Linezolid remains a very expensive drug choice with predictable adverse reactions, particularly neutropenia. Dosing for daptomycin (a lipopeptide), telavancin (a lipoglycopeptide), and ceftobiprole (our first fifth generation cephalosporin) are still not set.
Lastly, I predict—or at least hope for—a happy, healthy, and productive 2010 for all
Gardasil, Cervarix: Not Interchangeable
With the licensure of GlaxoSmithKline's human papillomavirus vaccine Cervarix in October, we will soon have two vaccines that prevent cervical cancer in women. But they're not interchangeable, and this could lead to problems.
Cervarix is expected to join Merck's Gardasil on the U.S. market in February 2010. For the first time ever in vaccine history, we will have a situation in which two competing vaccines have very different components and adjuvants that could complicate the decision for practicing physicians—as well as insurers and buying groups—regarding which one to use. I think we need to view human papillomavirus (HPV) vaccines as exceptions to the usual rules of “equivalent and interchangeable” and consider stocking both. Parents should be informed of the features of each vaccine, and the decision to use one or the other should be made with informed consent.
Most clinicians know that both vaccines protect against HPV serotypes 16 and 18, the dominant causes of cervical cancer. But Gardasil also protects against HPV-6 and −11, primarily associated with genital warts, and has recently received approval for use in males, which Cervarix has not. But other differences between the two vaccines are less well recognized, and I believe will turn out to be important.
Although both vaccines are manufactured with similar technology using viruslike particles, Cervarix contains a novel adjuvant, ASO4, that is believed to be responsible for its ability to generate a greater antibody response to HPV-16 and −18, compared with Gardasil. According to a head-to-head comparison conducted by GSK, geometric mean titers of serum neutralizing antibodies ranged from 2.3- to 4.8-fold higher for HPV-16 and 6.8- to 9.1-fold higher for HPV-18 after vaccination with Cervarix, compared with Gardasil, across all ages (Hum. Vaccin. 2009;5:705-19).
Although not proven, we might infer from those data that Cervarix might provide longer-lasting protection against HPV serotypes 16 and 18 and, therefore, a longer duration of time before a booster is needed. Both companies are studying duration of protection with their respective vaccines, and a just-published study showed sustained efficacy and immunogenicity of Cervarix up to 6.4 years (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61567-1]). For both vaccines, we should have answers before current vaccinees begin to lose protection.
Both vaccines are indicated for the prevention of cervical cancer and cervical intraepithelial neoplasia (CIN) grades 1–3 due to HPV-16 and −18, and cervical adenocarcinoma in situ. However, Gardasil also has indications for the prevention of vulvar and vaginal intraepithelial neoplasias, which Cervarix does not.
Although not specifically mentioned in Gardasil's label (www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf
Meanwhile, data included in the label for Cervarix (http://us.gsk.com/products/assets/us_cervarix.pdf
These differences may seem slight, but consider a case in which a young woman who received Gardasil later develops a case of cervical cancer due to HPV-31. Might she be quite upset that she wasn't informed that there was another vaccine that could have prevented it? Conversely, a male or female patient given Cervarix later develops genital warts, or a female develops cervical atypia associated with HPV-6 or −11. Might these patients similarly feel that they were denied the chance to have prevented those outcomes?
Who decides which vaccine is used? In managed care settings, the decision is often made based on cost when vaccines are equivalent, but what about the HPV vaccines where the products are not equivalent?
The same goes for the manufacturer-run vaccine buying groups that offer discounts to increasing numbers of participating physicians who sign contracts that impose strict limits on the amount of vaccine that can be purchased outside of the specified brands.
This has not happened before with vaccines: The two competing brands are not interchangeable. I believe that health plans and vaccine buying groups need to recognize these factors and grant an exception to HPV vaccines.
I think we all should stock both vaccines in our practices, and explain the differences to parents. I plan to distribute pamphlets to patients and families and let them choose, with signatures confirming informed consent. I serve as a consultant to both GSK and Merck & Co. and have shared this information with both companies.
This is going to be complicated.
With the licensure of GlaxoSmithKline's human papillomavirus vaccine Cervarix in October, we will soon have two vaccines that prevent cervical cancer in women. But they're not interchangeable, and this could lead to problems.
Cervarix is expected to join Merck's Gardasil on the U.S. market in February 2010. For the first time ever in vaccine history, we will have a situation in which two competing vaccines have very different components and adjuvants that could complicate the decision for practicing physicians—as well as insurers and buying groups—regarding which one to use. I think we need to view human papillomavirus (HPV) vaccines as exceptions to the usual rules of “equivalent and interchangeable” and consider stocking both. Parents should be informed of the features of each vaccine, and the decision to use one or the other should be made with informed consent.
Most clinicians know that both vaccines protect against HPV serotypes 16 and 18, the dominant causes of cervical cancer. But Gardasil also protects against HPV-6 and −11, primarily associated with genital warts, and has recently received approval for use in males, which Cervarix has not. But other differences between the two vaccines are less well recognized, and I believe will turn out to be important.
Although both vaccines are manufactured with similar technology using viruslike particles, Cervarix contains a novel adjuvant, ASO4, that is believed to be responsible for its ability to generate a greater antibody response to HPV-16 and −18, compared with Gardasil. According to a head-to-head comparison conducted by GSK, geometric mean titers of serum neutralizing antibodies ranged from 2.3- to 4.8-fold higher for HPV-16 and 6.8- to 9.1-fold higher for HPV-18 after vaccination with Cervarix, compared with Gardasil, across all ages (Hum. Vaccin. 2009;5:705-19).
Although not proven, we might infer from those data that Cervarix might provide longer-lasting protection against HPV serotypes 16 and 18 and, therefore, a longer duration of time before a booster is needed. Both companies are studying duration of protection with their respective vaccines, and a just-published study showed sustained efficacy and immunogenicity of Cervarix up to 6.4 years (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61567-1]). For both vaccines, we should have answers before current vaccinees begin to lose protection.
Both vaccines are indicated for the prevention of cervical cancer and cervical intraepithelial neoplasia (CIN) grades 1–3 due to HPV-16 and −18, and cervical adenocarcinoma in situ. However, Gardasil also has indications for the prevention of vulvar and vaginal intraepithelial neoplasias, which Cervarix does not.
Although not specifically mentioned in Gardasil's label (www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf
Meanwhile, data included in the label for Cervarix (http://us.gsk.com/products/assets/us_cervarix.pdf
These differences may seem slight, but consider a case in which a young woman who received Gardasil later develops a case of cervical cancer due to HPV-31. Might she be quite upset that she wasn't informed that there was another vaccine that could have prevented it? Conversely, a male or female patient given Cervarix later develops genital warts, or a female develops cervical atypia associated with HPV-6 or −11. Might these patients similarly feel that they were denied the chance to have prevented those outcomes?
Who decides which vaccine is used? In managed care settings, the decision is often made based on cost when vaccines are equivalent, but what about the HPV vaccines where the products are not equivalent?
The same goes for the manufacturer-run vaccine buying groups that offer discounts to increasing numbers of participating physicians who sign contracts that impose strict limits on the amount of vaccine that can be purchased outside of the specified brands.
This has not happened before with vaccines: The two competing brands are not interchangeable. I believe that health plans and vaccine buying groups need to recognize these factors and grant an exception to HPV vaccines.
I think we all should stock both vaccines in our practices, and explain the differences to parents. I plan to distribute pamphlets to patients and families and let them choose, with signatures confirming informed consent. I serve as a consultant to both GSK and Merck & Co. and have shared this information with both companies.
This is going to be complicated.
With the licensure of GlaxoSmithKline's human papillomavirus vaccine Cervarix in October, we will soon have two vaccines that prevent cervical cancer in women. But they're not interchangeable, and this could lead to problems.
Cervarix is expected to join Merck's Gardasil on the U.S. market in February 2010. For the first time ever in vaccine history, we will have a situation in which two competing vaccines have very different components and adjuvants that could complicate the decision for practicing physicians—as well as insurers and buying groups—regarding which one to use. I think we need to view human papillomavirus (HPV) vaccines as exceptions to the usual rules of “equivalent and interchangeable” and consider stocking both. Parents should be informed of the features of each vaccine, and the decision to use one or the other should be made with informed consent.
Most clinicians know that both vaccines protect against HPV serotypes 16 and 18, the dominant causes of cervical cancer. But Gardasil also protects against HPV-6 and −11, primarily associated with genital warts, and has recently received approval for use in males, which Cervarix has not. But other differences between the two vaccines are less well recognized, and I believe will turn out to be important.
Although both vaccines are manufactured with similar technology using viruslike particles, Cervarix contains a novel adjuvant, ASO4, that is believed to be responsible for its ability to generate a greater antibody response to HPV-16 and −18, compared with Gardasil. According to a head-to-head comparison conducted by GSK, geometric mean titers of serum neutralizing antibodies ranged from 2.3- to 4.8-fold higher for HPV-16 and 6.8- to 9.1-fold higher for HPV-18 after vaccination with Cervarix, compared with Gardasil, across all ages (Hum. Vaccin. 2009;5:705-19).
Although not proven, we might infer from those data that Cervarix might provide longer-lasting protection against HPV serotypes 16 and 18 and, therefore, a longer duration of time before a booster is needed. Both companies are studying duration of protection with their respective vaccines, and a just-published study showed sustained efficacy and immunogenicity of Cervarix up to 6.4 years (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61567-1]). For both vaccines, we should have answers before current vaccinees begin to lose protection.
Both vaccines are indicated for the prevention of cervical cancer and cervical intraepithelial neoplasia (CIN) grades 1–3 due to HPV-16 and −18, and cervical adenocarcinoma in situ. However, Gardasil also has indications for the prevention of vulvar and vaginal intraepithelial neoplasias, which Cervarix does not.
Although not specifically mentioned in Gardasil's label (www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf
Meanwhile, data included in the label for Cervarix (http://us.gsk.com/products/assets/us_cervarix.pdf
These differences may seem slight, but consider a case in which a young woman who received Gardasil later develops a case of cervical cancer due to HPV-31. Might she be quite upset that she wasn't informed that there was another vaccine that could have prevented it? Conversely, a male or female patient given Cervarix later develops genital warts, or a female develops cervical atypia associated with HPV-6 or −11. Might these patients similarly feel that they were denied the chance to have prevented those outcomes?
Who decides which vaccine is used? In managed care settings, the decision is often made based on cost when vaccines are equivalent, but what about the HPV vaccines where the products are not equivalent?
The same goes for the manufacturer-run vaccine buying groups that offer discounts to increasing numbers of participating physicians who sign contracts that impose strict limits on the amount of vaccine that can be purchased outside of the specified brands.
This has not happened before with vaccines: The two competing brands are not interchangeable. I believe that health plans and vaccine buying groups need to recognize these factors and grant an exception to HPV vaccines.
I think we all should stock both vaccines in our practices, and explain the differences to parents. I plan to distribute pamphlets to patients and families and let them choose, with signatures confirming informed consent. I serve as a consultant to both GSK and Merck & Co. and have shared this information with both companies.
This is going to be complicated.
Consider Vaccine Cost-Effectiveness
I believe the time has come to consider cost-effectiveness when deciding which vaccines the government—that's your tax dollars—will pay for.
At its October meeting, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention made a paradoxical decision: The committee gave a “permissive” recommendation for use of Merck's quadrivalent human papillomavirus (HPV) vaccine (Gardasil) in males aged 9–26 years, but then voted for coverage of the vaccine under the federal Vaccines for Children (VFC) program, which provides free vaccine to children up through 18 years of age who fall into certain need categories. The program covers approximately 48% of all U.S. children.
A permissive recommendation generally indicates that the vaccine is safe and effective but not cost effective. Permissive recommendations usually are not voted into the VFC program. Although the permissive recommendation still awaits approval by the CDC's director, ACIP's vote for VFC coverage is binding, so it is now official. We will have to wait and see what insurance companies do with the dichotomous signal.
A decade ago, ACIP rarely discussed cost when making its vaccine use recommendations. Now, cost-effectiveness analyses are routine. At the October ACIP meeting, Harrell Chesson, Ph.D., of the CDC, presented data from six studies—four published, two unpublished—demonstrating wide variation in cost per quality-adjusted life year (QALY) estimates for use of Gardasil in adolescent and young adult men, depending in large part on the vaccination status of the female population. In general, he showed that as coverage of Gardasil among females increases, the cost per QALY gained by male vaccination decreases.
Use of the vaccine in males is aimed primarily at preventing warts caused by HPV serotypes 6 and 11. The rates of penile and head/neck cancer caused by the cervical cancer HPV serotypes 16 and 18 are miniscule and do not even factor into the cost calculation. Prevention of transmission of HPV-16 and −18 to females through sexual contact is also a goal of the vaccine, but if it's already being routinely offered to females, the data suggest that there's very little additional gain costwise from giving it to males.
Indeed, Dr. Chesson concluded, “In most scenarios, adding male vaccination to female-only vaccination is not the most cost-effective use of public health resources. Improving vaccination coverage of females is likely to be a more effective—and cost-effective—strategy to reduce the overall burden of HPV-associated conditions.”
As readers who follow this column and my other writings know, I am a strong proponent of vaccines. In fact, I serve on the advisory boards for both Merck & Co. and GlaxoSmithKline, which manufactures the bivalent HPV vaccine Cervarix. But in an era where we're debating how to provide even basic health insurance for uninsured Americans, I am becoming concerned about whether our country can afford every vaccine for every person.
I'm looking ahead to other vaccines in the very near pipeline. In December we're likely to see approval of the 13-valent pneumococcal conjugate vaccine for the U.S. market. That vaccine is expected to cost more than the current PCV7 (Prevnar), thus raising the overall costs of routine immunization when the switch is made to the new vaccine. Beyond that we will need to provide catch-up vaccination as well for kids who already received PCV7 in order to provide protection against the newly emerging, virulent, and multidrug-resistant serotype 19A, which is included in PCV13 but not PCV7. This new “superbug” causes fatal sepsis, meningitis, and pneumonia. How can ACIP not vote that into VFC as well?
On the heels of PCV13, there are two new meningococcal conjugate vaccines awaiting licensure: GSK's Haemophilus influenzae type b (Hib)–Neisseria meningitidis serogroups C (MenC) and Y (MenY)–tetanus toxoid combination, and Novartis's MenACWY-CRM (Menveo). The Hib-MenCY-TT conjugate is likely to be licensed for infants at 2, 4, and 6 months of age, with a booster at 15–18 months. Menveo, which will compete with Menactra, is expected to first be licensed for use in adolescents, then toddlers, then infants. These vaccines also prevent a significant amount of serious and potentially fatal disease.
Although competition usually lowers cost in the marketplace, the same phenomenon generally isn't seen when new vaccine competitors enter the market. Rather, the major companies with competing vaccines make combination products with ingredients that differ from others so that staying within their family of products is more convenient than switching between companies.
Moreover, companies also provide price advantages to physicians through national buying groups that provide bigger discounts to those who purchase vaccines within their own family of products. This impacts any price reduction that might occur with brand competition.
So where should we draw the line? At one point or another, ACIP may have to say the government can't afford to pay for vaccines that do not have a strong cost-benefit argument behind them. Yes, the alternative is a two-tiered system where those who can afford the vaccine can get it, and those who can't, don't. ACIP has tried to avoid that scenario in the past, but I fear it won't be able to do so much longer.
I believe the time has come to consider cost-effectiveness when deciding which vaccines the government—that's your tax dollars—will pay for.
At its October meeting, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention made a paradoxical decision: The committee gave a “permissive” recommendation for use of Merck's quadrivalent human papillomavirus (HPV) vaccine (Gardasil) in males aged 9–26 years, but then voted for coverage of the vaccine under the federal Vaccines for Children (VFC) program, which provides free vaccine to children up through 18 years of age who fall into certain need categories. The program covers approximately 48% of all U.S. children.
A permissive recommendation generally indicates that the vaccine is safe and effective but not cost effective. Permissive recommendations usually are not voted into the VFC program. Although the permissive recommendation still awaits approval by the CDC's director, ACIP's vote for VFC coverage is binding, so it is now official. We will have to wait and see what insurance companies do with the dichotomous signal.
A decade ago, ACIP rarely discussed cost when making its vaccine use recommendations. Now, cost-effectiveness analyses are routine. At the October ACIP meeting, Harrell Chesson, Ph.D., of the CDC, presented data from six studies—four published, two unpublished—demonstrating wide variation in cost per quality-adjusted life year (QALY) estimates for use of Gardasil in adolescent and young adult men, depending in large part on the vaccination status of the female population. In general, he showed that as coverage of Gardasil among females increases, the cost per QALY gained by male vaccination decreases.
Use of the vaccine in males is aimed primarily at preventing warts caused by HPV serotypes 6 and 11. The rates of penile and head/neck cancer caused by the cervical cancer HPV serotypes 16 and 18 are miniscule and do not even factor into the cost calculation. Prevention of transmission of HPV-16 and −18 to females through sexual contact is also a goal of the vaccine, but if it's already being routinely offered to females, the data suggest that there's very little additional gain costwise from giving it to males.
Indeed, Dr. Chesson concluded, “In most scenarios, adding male vaccination to female-only vaccination is not the most cost-effective use of public health resources. Improving vaccination coverage of females is likely to be a more effective—and cost-effective—strategy to reduce the overall burden of HPV-associated conditions.”
As readers who follow this column and my other writings know, I am a strong proponent of vaccines. In fact, I serve on the advisory boards for both Merck & Co. and GlaxoSmithKline, which manufactures the bivalent HPV vaccine Cervarix. But in an era where we're debating how to provide even basic health insurance for uninsured Americans, I am becoming concerned about whether our country can afford every vaccine for every person.
I'm looking ahead to other vaccines in the very near pipeline. In December we're likely to see approval of the 13-valent pneumococcal conjugate vaccine for the U.S. market. That vaccine is expected to cost more than the current PCV7 (Prevnar), thus raising the overall costs of routine immunization when the switch is made to the new vaccine. Beyond that we will need to provide catch-up vaccination as well for kids who already received PCV7 in order to provide protection against the newly emerging, virulent, and multidrug-resistant serotype 19A, which is included in PCV13 but not PCV7. This new “superbug” causes fatal sepsis, meningitis, and pneumonia. How can ACIP not vote that into VFC as well?
On the heels of PCV13, there are two new meningococcal conjugate vaccines awaiting licensure: GSK's Haemophilus influenzae type b (Hib)–Neisseria meningitidis serogroups C (MenC) and Y (MenY)–tetanus toxoid combination, and Novartis's MenACWY-CRM (Menveo). The Hib-MenCY-TT conjugate is likely to be licensed for infants at 2, 4, and 6 months of age, with a booster at 15–18 months. Menveo, which will compete with Menactra, is expected to first be licensed for use in adolescents, then toddlers, then infants. These vaccines also prevent a significant amount of serious and potentially fatal disease.
Although competition usually lowers cost in the marketplace, the same phenomenon generally isn't seen when new vaccine competitors enter the market. Rather, the major companies with competing vaccines make combination products with ingredients that differ from others so that staying within their family of products is more convenient than switching between companies.
Moreover, companies also provide price advantages to physicians through national buying groups that provide bigger discounts to those who purchase vaccines within their own family of products. This impacts any price reduction that might occur with brand competition.
So where should we draw the line? At one point or another, ACIP may have to say the government can't afford to pay for vaccines that do not have a strong cost-benefit argument behind them. Yes, the alternative is a two-tiered system where those who can afford the vaccine can get it, and those who can't, don't. ACIP has tried to avoid that scenario in the past, but I fear it won't be able to do so much longer.
I believe the time has come to consider cost-effectiveness when deciding which vaccines the government—that's your tax dollars—will pay for.
At its October meeting, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention made a paradoxical decision: The committee gave a “permissive” recommendation for use of Merck's quadrivalent human papillomavirus (HPV) vaccine (Gardasil) in males aged 9–26 years, but then voted for coverage of the vaccine under the federal Vaccines for Children (VFC) program, which provides free vaccine to children up through 18 years of age who fall into certain need categories. The program covers approximately 48% of all U.S. children.
A permissive recommendation generally indicates that the vaccine is safe and effective but not cost effective. Permissive recommendations usually are not voted into the VFC program. Although the permissive recommendation still awaits approval by the CDC's director, ACIP's vote for VFC coverage is binding, so it is now official. We will have to wait and see what insurance companies do with the dichotomous signal.
A decade ago, ACIP rarely discussed cost when making its vaccine use recommendations. Now, cost-effectiveness analyses are routine. At the October ACIP meeting, Harrell Chesson, Ph.D., of the CDC, presented data from six studies—four published, two unpublished—demonstrating wide variation in cost per quality-adjusted life year (QALY) estimates for use of Gardasil in adolescent and young adult men, depending in large part on the vaccination status of the female population. In general, he showed that as coverage of Gardasil among females increases, the cost per QALY gained by male vaccination decreases.
Use of the vaccine in males is aimed primarily at preventing warts caused by HPV serotypes 6 and 11. The rates of penile and head/neck cancer caused by the cervical cancer HPV serotypes 16 and 18 are miniscule and do not even factor into the cost calculation. Prevention of transmission of HPV-16 and −18 to females through sexual contact is also a goal of the vaccine, but if it's already being routinely offered to females, the data suggest that there's very little additional gain costwise from giving it to males.
Indeed, Dr. Chesson concluded, “In most scenarios, adding male vaccination to female-only vaccination is not the most cost-effective use of public health resources. Improving vaccination coverage of females is likely to be a more effective—and cost-effective—strategy to reduce the overall burden of HPV-associated conditions.”
As readers who follow this column and my other writings know, I am a strong proponent of vaccines. In fact, I serve on the advisory boards for both Merck & Co. and GlaxoSmithKline, which manufactures the bivalent HPV vaccine Cervarix. But in an era where we're debating how to provide even basic health insurance for uninsured Americans, I am becoming concerned about whether our country can afford every vaccine for every person.
I'm looking ahead to other vaccines in the very near pipeline. In December we're likely to see approval of the 13-valent pneumococcal conjugate vaccine for the U.S. market. That vaccine is expected to cost more than the current PCV7 (Prevnar), thus raising the overall costs of routine immunization when the switch is made to the new vaccine. Beyond that we will need to provide catch-up vaccination as well for kids who already received PCV7 in order to provide protection against the newly emerging, virulent, and multidrug-resistant serotype 19A, which is included in PCV13 but not PCV7. This new “superbug” causes fatal sepsis, meningitis, and pneumonia. How can ACIP not vote that into VFC as well?
On the heels of PCV13, there are two new meningococcal conjugate vaccines awaiting licensure: GSK's Haemophilus influenzae type b (Hib)–Neisseria meningitidis serogroups C (MenC) and Y (MenY)–tetanus toxoid combination, and Novartis's MenACWY-CRM (Menveo). The Hib-MenCY-TT conjugate is likely to be licensed for infants at 2, 4, and 6 months of age, with a booster at 15–18 months. Menveo, which will compete with Menactra, is expected to first be licensed for use in adolescents, then toddlers, then infants. These vaccines also prevent a significant amount of serious and potentially fatal disease.
Although competition usually lowers cost in the marketplace, the same phenomenon generally isn't seen when new vaccine competitors enter the market. Rather, the major companies with competing vaccines make combination products with ingredients that differ from others so that staying within their family of products is more convenient than switching between companies.
Moreover, companies also provide price advantages to physicians through national buying groups that provide bigger discounts to those who purchase vaccines within their own family of products. This impacts any price reduction that might occur with brand competition.
So where should we draw the line? At one point or another, ACIP may have to say the government can't afford to pay for vaccines that do not have a strong cost-benefit argument behind them. Yes, the alternative is a two-tiered system where those who can afford the vaccine can get it, and those who can't, don't. ACIP has tried to avoid that scenario in the past, but I fear it won't be able to do so much longer.