Pediatric Infectious Disease Journal:
Vaccine Reports: PDF Only
Heterogeneity of Rotavirus Vaccine Efficacy among Infants in Developing Countries.
Gruber, Joann F. MSPH; Hille, Darcy A. MS, EMBA; Liu, G. Frank PhD; Kaplan, Susan S. MD; Nelson, Micki MS; Goveia, Michelle G. MD; Mast, T. Christopher PhD
Rotavirus is the leading cause of severe diarrhea worldwide in young children. Although rotavirus vaccine efficacy is high in developed countries, efficacy is lower in developing countries. Here, we investigated heterogeneity of rotavirus vaccine efficacy by infant characteristics in developing countries.
An exploratory, post-hoc analysis was conducted using randomized controlled trial data of the pentavalent rotavirus vaccine (RV5) conducted in Africa and Asia (NCT00362648). Infants received either three doses of vaccine/placebo and were followed for up to 2 years. Within subgroups, vaccine efficacy and 95% confidence intervals (CI) against rotavirus gastroenteritis were estimated using Poisson regression. We assessed heterogeneity of efficacy by age at first dose, gender, breastfeeding status, and nutrition status.
African children receiving the first dose at < 8 weeks had lower efficacy (23.7%; 95% CI: -8.2%, 46.3%) than those vaccinated at >= 8 weeks (59.1%; 95% CI: 34.0%, 74.6%). Marginally statistically significant differences were observed by age at first dose, gender, and underweight status in Ghana and gender in Asian countries.
Heterogeneity of efficacy was observed for age at first dose in African countries. This was an exploratory analysis; additional studies are needed to validate these results.
Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
Intussusception hospitalizations rise in some infants after initial RV vaccination
A spike in intussusception hospitalization rates occurred in children aged 8 to 11 weeks after children received initial doses of RotaTeq or Rotarix vaccine for rotavirus compared with prevaccine years, according to recent study results.
“A previous study of U.S. hospital discharge data found a small increased risk of intussusception hospitalizations among children 8 to 11 weeks of age in 2007 through 2009 compared with a prevaccine baseline from 2000 through 2005 but no sustained population level change intussusception hospitalization rates among all children less than 12 months of age,” Jacqueline E. Tate, PhD, from the division of viral diseases at the National Center for Immunization and Respiratory Diseases at the CDC, and colleagues wrote. “The objective of the current analysis is to update the previous analysis with 4 additional years of postvaccine introduction data from 2010 through 2013 to examine trends among all children less than 12 months of age as well as children in the age groups during which doses of (rotavirus vaccine [RotaTeq, Merck or Rotarix, GlaxoSmithKline; RV]) are recommended.”
Tate and colleagues pooled hospitalization rates of children from the State Inpatient Databases for 26 states that provided data annually from 2000 to 2013. The researchers analyzed trends for patients aged 6 to 14 weeks, 15 to 24 weeks and 25 to 34 weeks based on recommended ages to receive RV vaccinations. They also calculated rates with bridged-race postcensal population estimates, and they examined intussusception hospitalization rates in children 8 to 11 weeks specifically, when the majority of first dose administration occurred.
The researchers identified 15,231 intussusception hospitalizations in children aged younger than 12 months in the retrospective period. Among children aged 15 to 24 weeks and 25 to 34 weeks, analysis demonstrated no consistent or significant change in hospitalization rates before and after vaccinations. Infants aged 8 to 11 weeks, however, demonstrated a statistically significant increase in intussusception hospitalization from 46% to 101% (range: 16.7-22.9 per 100,000) in all postvaccine years vs. prevaccine baseline (11.4 per 100,000) except for 2011 (15,000 per 100,000) and 2013 (14.7 per 100,000).
“In our ecological evaluation, a small increased risk of intussusception was observed in children 8 to 11 weeks of age when the majority of rotavirus vaccine doses are given, and this increase is consistent with a small increased risk of intussusception observed in the first week after the first dose in postmarketing studies,” the researchers wrote. “However, given the magnitude of the declines in rotavirus disease compared with the small increased risk of intussusception, the public health benefits of rotavirus vaccination far exceed the increased risk of intussusception.” –by Kate Sherrer
Markers of Protection in Children & Adolescents 6 to 14 Years After Primary Hepatitis B Vaccination in Real Life
Not many data are available on long-term immunity against hepatitis B (HB) for children vaccinated under real-life conditions.
Two hundred and thirty-two children and adolescents vaccinated 6-14 years earlier in pediatric practices were examined for conditions of vaccination and markers of protection as anti-HBs, anamnestic response to a booster dose and cell-mediated immunity.
Fifty-six percent of the participants were vaccinated according to the German vaccination recommendations (group 1). In 44.0% (group 2), these recommendations were not followed. Anti-HBs concentrations of ≥10 IU/L were found in 53.1% of group 1 and 45.1% of group 2 participants. A booster dose resulted in 91 of 99 participants in having an anamnestic response, in 3 (5.9%) of group 1 and 5 (10.4%) of group 2 anti-HBs remained below 10 IU/L. In group 1, postbooster anti-HBs concentration was inversely correlated with time since the last vaccination. Cellular immune responses were seen in only 5% of revaccinated individuals before the booster, increasing to 30% thereafter.
Under real-life conditions about half of vaccinees have lost protecting antibodies 6-14 years after vaccination in infancy, but in approximately 90% of them, immune memory was demonstrated. However, as memory may wane, revaccination at a time when boostability is still present might be considered.
Source: Brunskole Hummel Iet al. Pediatr Infect Dis J. 2016 Mar;35(3):286-91.
Paul Offit Responds to News About HPV Vaccine 'Syndrome'
I am writing from the Vaccine Education Center at the Children's Hospital of Philadelphia, in response to a Medscape Medical News article published on August 11, 2016, titled "Chronic Symptoms After HPV Vaccine: Part of Wider Syndrome?" This news article covered a study by an Italian group that was recently published in Immunologic Research.This notion that the HPV vaccine can cause symptoms of chronic fatigue or fibromyalgia has been out there for years. And frankly, it's the reason that the Ministry of Health in Japan has decided not to recommend the HPV vaccine, which is sad because this issue has been looked at again and again.
First of all, the HPV vaccine was studied for safety in 30,000 people for 7 years before licensure. It has been formally studied both in phase 4 postlicensure studies and by the Vaccine Safety Datalink in more than a million people, and has been found not to cause chronic fatigue or fibromyalgia. When those symptoms do occur, they occur at the same rate in both vaccinated and unvaccinated groups.
We learned from these studies that the HPV vaccine doesn't prevent fibromyalgia or chronic fatigue in adolescents. That Medscape chose to highlight this article,as if it were in any way an advance, is disappointing. Frankly, this falls under the same category as the syndrome described by Andrew Wakefield—that the MMR vaccine caused intestinal symptoms and autism, which also was thoroughly debunked.
The problem is that this raises the same ill-founded belief that was raised by Katie Couric on her show that the HPV vaccine may cause chronic symptoms. As a consequence, at least a segment of society has become falsely concerned about the safety of this vaccine. We know that the HPV vaccine doesn't cause these problems, but people are making the choice not to have their children receive the vaccine; only 40% of girls and about 21% of boys are getting this vaccine.
Every year in this country, the HPV-9 [vaccine] would prevent about 29,000 cases of cancer—two thirds in girls, about one third in boys—and it would prevent about 4800 deaths. So when only 40% of girls and 21% of boys are getting this vaccine, we can assume that about 2000 children every year in this country are going to become adults who die, needlessly, from this infection.
I think we have scared people unnecessarily, in part because we have been a little concerned about bringing up the issue of sex in front of these children (and that can be uncomfortable), instead of just talking about what we should talk about: that this is a cancer-preventing vaccine that's being underutilized. So, I'm a little disappointed that Medscape chose, in any sense, to highlight an article claiming that the HPV vaccine caused chronic disease when such a claim is without basis. Thank you.
1. Palmieri B, Poddighe D, Vadala M, Laurino C, Carnovale C, Clementi E. Severe somatoform and dysautonomic syndromes after HPV vaccination: case series and review of literature. Immunol Res. 2016 Aug 9. [Epub ahead of print]
2. Centers for Disease Control and Prevention. Human Papillomavirus (HPV) Vaccine Safety.http://www.cdc.gov/vaccinesafety/vaccines/hpv-vaccine.html Accessed August 22, 2016.
3.Centers for Disease Control and Prevention. Frequently Asked Questions About HPV Vaccine Safety.http://www.cdc.gov/vaccinesafety/vaccines/hpv/hpv-safety-faqs.html#A5 Accessed August 22, 2016.
4.Godlee F, Smith J, Marcovitch H. Wakefield's article linking MMR vaccine and autism was fraudulent. BMJ. 2011;342:c7452.
5.Centers for Disease Control and Prevention. Teen Vaccination Coverage. http://www.cdc.gov/vaccines/parents/vacc-coverage-teens.html Accessed August 22, 2016.
6.Centers for Disease Control and Prevention, Communication and Education Branch, National Center for Immunization and Respiratory Diseases. Human Papillomavirus. The Pink Book. 2015.http://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html Accessed August 22, 2016.
Volume 34, Issue 48, 21 November 2016, Pages 5959–5967
Rabies pre-exposure prophylaxis elicits long-lasting immunity in humans
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Rabies pre-exposure prophylaxis schedule elicited a VNA response that was detectable over an extended period of time, up to 14 years in some subjects.
Females respond better than males to rabies vaccination.
One year or post-booster antibody may be utilised to predict longer term titres.
Despite the availability of safe and effective human vaccines, rabies remains a global threat, with an estimated 60,000 human deaths annually attributed to rabies. Pre-exposure prophylaxis against rabies infection is recommended for travelers to countries where rabies is endemic, and also for those with a higher risk of exposure. In this study, the rabies-specific neutralising antibody responses in a cohort of rabies-vaccinated recipients over a period of twenty years have been assessed. In particular, the antibody response to primary vaccinations and boosters, and the waning of antibody post primary vaccination and post booster were investigated. The significance of gender, age at vaccination, vaccine manufacturer and vaccination intervals were also evaluated. These data confirm that rabies vaccination can elicit a neutralising antibody response that can remain at detectable levels for a number of years, without additional booster vaccinations. The antibody response following both primary vaccination and booster was significantly influenced by the gender of the subject (p = 0.002 and 0.03 respectively), with supportive data that suggests an effect by the make of vaccine administered following primary vaccination, with significantly higher VNA titres observed for one vaccine manufactured prior to 2006 (p < 0.001) in a small subset of recipients (n = 5). Additionally, the decay rate was demonstrated through the overall decline in antibody titre for all individuals, which was a 37% and 27% reduction per 2-fold change in time following primary and booster vaccination respectively. Individuals within older age groups demonstrated a significantly faster decline in antibody titre following the primary vaccination course (p = 0.012). Rate of decline in antibody titre was also significantly influenced by the vaccine make following primary course (p < 0.001). The assessment of neutralising antibody titre decline has also provided an insight into the most appropriate timing for booster administration, and enabled the prediction of long term titres from post-vaccination antibody titres.
Volume 34, Issue 48, 21 November 2016, Pages 5912–5915
Rotavirus, vaccine failure or diagnostic error?
• Monica Lopez-Lacortb, •
• Ana Díez-Gandíaa,
• Javier Díez-Domingob,
Immunochromatography (ICG) is highly used in clinical settings for rotavirus (RV) diagnosis. The specificity of the tests differs by brand type and is not 100%, therefore its use when the prevalence of the disease is low (i.e. in vaccinated children) may result in a proportion of false positive diagnoses.
In some areas, vaccine effectiveness studies or surveillance is done using ICG. Our objective was to estimate the validity of ICG test in vaccinated children, and estimate the number of false positive results in the Valencian Region of Spain, where all RV infections are diagnosed using ICG and are not confirmed by PCR.
Population based registries were used to identify all results from the RV antigen tests performed between January 2008 and June 2012 in children under 37 months. Hospitalization and vaccination status of the patients were obtained by linking different databases through a unique identification number. The Positive Predictive Value of the ICG test depending on the vaccination status of the child, hospitalization and the rotavirus season was estimated by a Bayesian model of latent classes.
Of the 48,833 tests with valid results, 9429 were done in vaccinated children, and of those 3963 (42%) during the rotavirus season. The prevalence of positive results in vaccinated varied from 2.9 to 21.4% of the tests depending on the hospitalization and seasonality. The estimated PPV also varied from 27.1 to 84.6% when stratified by these two parameters. Globally it is calculated that approximately 267 out of the 520 (51.3%) positives in vaccinated children were false positive tests.
The large percentage of false positives, due to an excessive number of tests in vaccinated and out of the RV season, if interpreted as vaccine failures, can cause a loss of confidence in the vaccine and lower the estimates of vaccine effectiveness.
Single-dose Universal Hepatitis A Immunization in 1-year-old Children: High Prevalence of Protective Antibodies up to 9
Years After Vaccination
Pediatric Infectious Disease Journal: December 2016 - Volume 35 - Issue 12 - p 1339–1342
Single-dose hepatitis A virus (HAV) vaccination was implemented in all Argentinean children 12 months of age in 2005. Previous studies demonstrated high prevalence of protective antibody response 4 years after single-dose vaccination. This study assessed long-term seroprotection against HAV after vaccination.
Children who received 1 dose of HAV vaccine at 1 year of age at least 6 years before enrollment were included at 5 centers in Argentina between 2013 and 2014. Demographic and socioeconomic characteristics were collected through a questionnaire. Blood samples were tested for anti-HAV antibodies. Antibody values ≥10 mIU/mL were considered seroprotective. Logistic regression analysis was performed to evaluate the association between demographic and socioeconomic variables and seroprotection.
A total of 1088 children were included, with a median postvaccination interval of 7.7 years (range 6.3–9.2 years). Of these children, 97.4% (95% confidence interval: 96.3%–98.3%) had protective antibodies against HAV. No association between demographic or socioeconomic variables and seroprotection was found. Geometric mean concentration of antibody levels against HAV was 170.5 mUI/mL (95% confidence interval: 163.2–178.2 mUI/mL).
Single-dose universal hepatitis A immunization in 1-year-old children resulted in sustained immunologic protection for up to 9 years in Argentina. These findings, along with the low current disease burden, confirm the success of the intervention.
Available online 7 November 2016
Changes in empyema among U.S. children in the pneumococcal conjugate vaccine era
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Parapneumonic empyema started increasing among U.S. children before PCV7 introduction in 2000, and continued afterwards.
PCV13 introduction was associated with a reduction in parapneumonic empyema among U.S. children.
The empyema rate reached a historical low among children <2 years after PCV13 introduction.
Parapneumonic empyema, a serious complication of pneumonia, started increasing among U.S. children before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, and continued afterwards. This increase was due in part to pneumococcal serotypes not included in PCV7 that were included in the new 13-valent (PCV13) vaccine introduced in 2010. We assessed changes in the incidence of empyema hospitalizations among U.S. children after PCV13 introduction.
We calculated annualized empyema hospitalization rates among U.S. children <18 years using Nationwide Inpatient Sample and Census data (1997–2013) for four periods based on PCV7 and PCV13 introductions. Relative rates (RR) and 95% confidence intervals (CI) were calculated by age group and sex, comparing PCV7 [early-PCV7 (2001–2005) and late-PCV7 (2006–2009)] and PCV13 (2011–2013) periods with the pre-PCV7 period (1997–1999). Secondary analyses examined changes in pneumococcal, streptococcal, staphylococcal and unspecified empyema.
Among children <18 years of age, annualized empyema hospitalization rates peaked at 3.6 per 100,000 in the late-PCV7 period compared with 2.1 per 100,000 in the pre-PCV7 period [RR: 1.70 (95% CI: 1.11–2.60)]. However, annualized rates in the post-PCV13 period declined to 2.0 per 100,000, similar to rates in the pre-PCV7 period. Empyema rates among children <2 years were lower in the post-PCV13 period compared to the pre-PCV7 period [RR: 0.77 (95% CI: 0.61–0.96)], but rates in the two periods among children 2–4 and 5–17 years were similar. Most empyema were of unspecified etiology. Pneumococcal and unspecified empyema declined after PCV13 introduction.
Although empyema hospitalization rates among U.S. children peaked after PCV7 introduction, rates decreased substantially following the introduction of PCV13.
Intussusception Rates Before and After the Introduction of Rotavirus Vaccine
Recent US studies have identified a small increased risk of intussusception after rotavirus vaccination, mainly after the first dose. We examined trends in intussusception hospitalizations before (2000–2005) and after (2007–2013) rotavirus vaccine introduction to assess whether this observed temporal risk translates into more hospitalized cases at the population level.
Intussusception hospitalizations in children <12 months of age were abstracted from the State Inpatient Database maintained by the Healthcare Cost and Utilization Project for 26 states that provided data from 2000 to 2013. Rates were calculated using bridged-race postcensal population estimates. Trends were analyzed by age groups (6–14 weeks, 15–24 weeks, and 25–34 weeks) based on the recommended ages for vaccine administration as well as 8–11 weeks when the majority of first doses are given. Rate ratios were calculated by using Poisson regression.
No consistent change in intussusception hospitalization rates was observed among all children <12 months of age and among children 15 to 24 weeks and 25 to 34 weeks of age. The intussusception hospitalization rate for children aged 8 to 11 weeks was significantly elevated by 46% to 101% (range: 16.7–22.9 per 100 000) in all postvaccine years except 2011 and 2013 compared with the prevaccine baseline (11.7 per 100 000).
The increase in the intussusception hospitalization rate in children 8 to 11 weeks when the majority of first doses of vaccine are given is consistent with recent US postlicensure studies. Given the magnitude of declines in rotavirus disease compared with this small increase in intussusception, the benefits of rotavirus vaccination outweigh the increase risk of intussusception.
Available online 10 November 2016
Simultaneous vaccination with MMR and DTaP-IPV-Hib and rate of hospital admissions with any infections: A nationwide register based cohort study
• Nationwide retrospective cohort study of Danish children aged 15 months to 4 years.
•Comparison of the live MMR + the inactivated DTaP-IPV-Hib vaccine vs MMR alone.
•27% higher rate of admissions for lower respiratory infections for MMR + DTaP-IPV-Hib.
•No significant association with admissions for other types of infections.
•Adjustment for a long range of potential confounders including exact age.
In Denmark, live measles, mumps, and rubella vaccine (MMR) is associated with a reduced risk of infectious disease admissions, particularly for lower respiratory tract infections. In low-income countries, simultaneous vaccination (i.e. vaccination at the same visit) with live and inactivated vaccines may increase child mortality compared with the live vaccine alone. We examined the hypothesis that simultaneous administration of MMR and the inactivated DTaP-IPV-Hib vaccine compared with MMR alone is associated with higher incidence of infectious disease admissions
Nationwide, retrospective, register based cohort study of 520,859 children born in Denmark 1997–2006, who were followed from 15 months to 4 years of age. Incidence rate ratios (IRRs) of hospital admissions were estimated by Cox regression and adjusted for background factors including exact age.
By 2 years of age, 4965 children had simultaneous MMR and DTaP-IPV-Hib as their most recent vaccination. Compared with MMR alone, simultaneous administration was associated with a higher rate of lower respiratory tract infections (adjusted incidence rate ratio (IRR), 1.27; 95% confidence interval (CI), 1.13–1.42). There was no effect on other infections. Overall, simultaneous administration was associated with a 7% (95% CI, 0–15%) increase in infectious disease admissions.
Simultaneous administration of MMR and DTaP-IPV-Hib compared with MMR alone may increase the rate of hospital admissions related to lower respiratory tract infections. These findings require replication in other high-income settings.
(Jacqueline E. Tate, et al. Pediatrics. 2016
Pediatric Infectious Disease Journal:
Original Studies: PDF Only
Survey of Household Contacts of Infants with Laboratory Confirmed Pertussis Infection During a National Pertussis Outbreak In England and Wales.
Kara, Edna O. MD; Campbell, Helen MSc; Ribeiro, Sonia BA; Fry, Norman K. PhD; Litt, David PhD; Eletu, Seyi PhD; Amirthalingam, Gayatri MFPH
Background: Highest rates of pertussis occur in infants <3 months old, too young to be fully vaccinated. The 2012 national outbreak provided a valuable opportunity to study sources of infection for these infants at highest risk of severe complications and death.
Methods: Households of infants <3 months old with laboratory-confirmed pertussis between 08/2012 and 10/2013 were invited to complete a questionnaire with information on household members' demographics, relationship with the infant, chronology of cough onset where relevant, and vaccination history. Contacts were also invited to provide an oral fluid (OF) sample for anti-pertussis toxin IgG testing. Individuals with laboratory evidence of infection and cough onset up to 3 months prior to infant onset were considered probable sources of infection.
Results: In total 220 contacts from 63 families were included in the analysis. In 86% of households (54/63) at least one positive result was found with 44% (97/220) of all contacts testing positive. Around 29% (31/108) of non-coughers tested positive. A probable source of infection was found for 46% (29/63) of infant cases. Mothers were the probable source in 38% of cases, followed by siblings (31%) and fathers (10%).
Conclusion: Household contacts play an important role in the transmission of pertussis to infants and when identified, mothers were the main sources of infection. Immunization during pregnancy has a key role in preventing infant disease through passive protection from birth and reduced maternal exposure.
Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
Will Lack of Nasal Spray Flu Vaccine Cut Immunization Rate?
|September 29, 2016
Public health leaders worry that a government decision not to recommend a live attenuated influenza vaccine (LAIV; FluMist Quadrivalent, MedImmune) in the form of a nasal spray for the current flu season could cause more people, especially children, to go unimmunized.
Those worries emerged at a press conference today organized by the National Foundation for Infectious Diseases (NFID) to promote influenza vaccination. There, Tom Frieden, MD, MPH, director of the Centers for Disease Control and Prevention (CDC), noted that its Advisory Committee on Immunization Practices (ACIP) concluded that the nasal spray vaccine was ineffective in preventing flu illness in the prior 3 seasons and therefore should be removed from the vaccine supply for the 2016-2017 season. The American Academy of Pediatrics concurred.
FluMist was widely used in 2015-2016, accounting for roughly 14% of all flu vaccinations, and 33% of those in children. "For a lot of kids, it's certainly preferable to getting a shot," Dr Frieden said at the press conference.
Parents accustomed to having their children receive the nasal spray should not use that as a reason to skip immunization this fall, said NFID Vice President Patricia Whitley-Williams, MD, a professor of pediatrics at Rutgers Robert Wood Johnson Medical School. "Flu shots have proven to be effective, and parents need to make sure their children are protected."
"That's not an excuse," added NFID Medical Director William Schaffner, MD, about people forgoing a shot because they can't get the nasal spray. Dr Schaffner is a professor of preventive medicine at Vanderbilt University School of Medicine.
In an interview with the Washington Post, the CDC's Dr Frieden put these exhortations for people to get the jab in a clearer context. "We're concerned that vaccination rates could be lower this year because the mist isn't available," he said.
The overall flu vaccination rate in 2015-2016 was 45.6%, down from 47.1% the season before.
Hoping for a Nasal Spray Vaccine Comeback
At the press conference, Dr Frieden said the nation will have enough flu shots to make up for the loss of the nasal spray. "There are going to be between 157 million and 168 million doses," he said. "There's plenty for everyone."
The shots will come in the form of either inactivated or recombinant influenza vaccines.
However, Dr Frieden repeatedly said that he wants an effective LAIV nasal spray vaccine with ACIP approval back on the market. "We hope this option will be available as soon as possible," he said.
AstraZeneca, MedImmune's parent company, shares that goal. In a statement emailed to Medscape Medical News, AstraZeneca spokesperson Michele Meixell said the company is investigating why its LAIV nasal spray vaccine has performed poorly in recent seasons. The Food and Drug Administration and outside scientific experts are providing input.
"We have seen, through both our data and investigation in the labs, that the H1N1 strain [in the vaccine] is not replicating as well as it should," said Meixell. "Our goal is to select a better performing A/H1N1pdm09 LAIV strain for inclusion in future seasons, including the upcoming [2017-2018] season."
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