Post-vaccine Era Research Articles

Impact of HPV vaccination with Gardasil\xae in Switzerland

BackgroundGardasil®, a quadrivalent vaccine targeting low-risk (6, 11) and high-risk (16, 18) human papillomaviruses (HPV), has been offered to 11–14 year-old schoolgirls in Switzerland since 2008. To evaluate its success and its potential impact on cervical cancer screening, HPV genotypes were examined in 18-year-old girls five years later (sub-study 1) and in outpatients participating to cervical cancer screening before and after vaccine implementation (sub-study 2).MethodsFor sub-study 1, 3726 females aged 18 in 2013 were invited to fill a questionnaire on personal demographics and HPV risk factors and to provide a self-collected cervicovaginal sample for HPV genotyping and Chlamydia trachomatis PCR. Personal data were evaluated by univariable and multivariable statistics. In sub-study 2, the proportion of the vaccine-type HPV among anogenital HPV was examined with archived genotyping data of 8039 outpatients participating to cervical cancer screening from 1999 till 2015. The yearly evolution of this proportion was evaluated by segmented logistic regression.Results690 (18.5%) women participated to sub-study 1 and 327 (8.8%) provided a self-collected sample. Prevalence of Chlamydia trachomatis (4.6%) and demographics confirmed that the subjects were representative of sexually-active Swiss young women. Vaccine (five-year coverage: 77.5%) was preferentially accepted by contraceptive-pill users (P = 0.001) and samples were mainly provided by sexually-active subjects (P < 0.001). The proportion (4%) of the vaccine-type HPV in this population was lower than in sub-study 2 outpatients (n = 849, <26 years old) in the pre-vaccine era (25.7%). The proportion of the high-risk vaccine-type HPV decreased significantly (59%, P = 0.0048) in the outpatients during the post-vaccine era, yet this decrease was restricted to those aged less than 26 years (n = 673, P < 0.0001).ConclusionsThe low proportion of vaccine-type HPV in 18-year-old females and its rapid decrease in young women participating to cervical cancer screening extend the success of HPV vaccination to Switzerland. Our data suggest that cervical cancer screening is now entering a stage of reduced proportion of HPV16 and/or 18 in samples reported positive by cytology. In view of the high likelihood of reduced clinical specificity of cytology, primary screening modalities involving HPV testing and cytology should now be re-evaluated in Switzerland.

Role of rotavirus vaccination on an emerging G8P[8] rotavirus strain causing an outbreak in central Japan

BackgroundIn this study, we examined the effectiveness of RV1 and RV5 vaccines during an outbreak of G8P[8] rotavirus group A strain (G8P[8]-RVA). These vaccines were originally designed to provide protection against severe diseases caused by common circulating strains, whereas G8P[8]-RVA remains emerging strain and partially heterotypic to the vaccines. It is imperative to investigate vaccine effectiveness (VE) against G8P[8]-RVA because this strain appears to be predominant in recent years, particularly, in post-vaccine era. MethodsRVA infection and genotypes were confirmed by polymerase chain reaction (PCR) followed by sequence-based genotyping. VE was determined during an outbreak of G8P[8]-RVA in Shizuoka Prefecture, Japan, in February-July 2017, retrospectively, by comparing vaccination status of children suffering from acute gastroenteritis (AGE) between ‘PCR-positive’ and ‘PCR-negative’ cases using conditional logistic regression adjusted for age. ResultsAmong 80 AGE children, RVA was detected in 58 (73%), of which 53 (66%) was G8P[8]-RVA. The clinical characteristics of G8P[8]-RVA and other RVA strains were identically severe. Notably, the attack rates of G8P[8]-RVA in vaccinated (61.1%) and unvaccinated (65.5%) children were almost similar. Indeed, no substantial effectiveness were found against G8P[8]-RVA (VE, 14% [95% CI: −140% to 70%]) or other RVA strains (VE, 58% [95% CI: −20% to 90%]) for mild infections. However, these vaccines remained strongly effective against moderate (VE, 75% [95% CI: 1% to 40%]) and severe (VE, 92% [95% CI: 60% to 98%]) RVA infections. The disease severity including Vesikari score, duration and frequency of diarrhea, and body temperature were significantly lower in vaccinated children. ConclusionsThis study demonstrates the effectiveness of current RV vaccines against moderate and severe, but not against the mild infections during an outbreak caused by unusual G8P[8]-RVA, which was virtually not targeted in the vaccines.

Change in Human Papillomavirus Prevalence Among U.S. Women Aged 18-59 Years, 2009-2014.

To examine changes in prevalence of vaginal human papillomavirus (HPV) between 2009-2010 and 2013-2014 among both vaccinated and unvaccinated U.S. women. We evaluated HPV prevalence among women 18-59 years old using cross-sectional survey data from three different cycles of the National Health and Nutrition Examination Survey. Data were stratified into four age groups (18-26, 27-34, 35-44, and 45-49 years) to examine trends over time among women of different ages in the postvaccine era. Multivariable analyses, which controlled for descriptive variables, were used to examine the prevalence of quadrivalent vaccine-type HPV by vaccination status. We observed a significant decrease in the prevalence of vaccine-type HPV among women 18-59 years of age from 2009-2010 to 2013-2014. This decline was only significant in those 18-26 years old when the sample was stratified into the four age groups. Among vaccinated 18-26 year olds, HPV prevalence remained low from 2009-2010 (3.9%) to 2013-2014 (2.0%; prevalence ratio 0.51, 95% CI 0.18-1.46). Unvaccinated women 18-26 years old also demonstrated a significant decrease over time from 19.5% in 2009-2010 to 9.7% in 2013-2014 (prevalence ratio 0.44, 95% CI 0.22-0.91). Prevalence did not significantly change among unvaccinated women 26 years old or older. The decline in HPV infections among unvaccinated 18- to 26-year-old women suggests that young women in the United States are beginning to benefit from herd immunity resulting from the introduction of the HPV vaccine.

Seroepidemiology of varicella among elementary school children in northern Taiwan.

In Taiwan, varicella vaccine was included in the expanded program of immunization since 2004. A seroepidemiologic study in the postvaccine era is helpful to evaluate the efficiency of current varicella vaccination strategies. We used a multistage stratified systematic sampling design to classify 29 administrative districts of New Taipei City into five strata. In 2013, a total of 936 students from 14 primary schools were recruited and had blood drawn for serology tests for varicella-zoster virus-immunoglobulin-G via indirect chemiluminescence immunoassays. A history of clinical varicella and information on varicella vaccination status were obtained. Overall, the seroprevalence was 64.1%. For the five strata, the seropositive rate ranged from 54.2% (Stratum 5) to 71.7% (Stratum 2) with no significant difference. For each participating school, the seropositive rate ranged from 44.4% to 72.9% with a statistically significant difference (p<0.005). For school children in each grade, seropositive rate increased significantly from 53.2% for Grade 1 to 71.8% for Grade 3 (p=0.005) and increased steadily from 61.2% for Grade 4 to 71.2% for Grade 6 (p=0.17). A positive correlation was observed between the seropositive rate and geometric mean titers (p=0.035). Geometric mean titers and the rate of a history of clinical varicella were positively correlated with increasing class grades. Nine years after the introduction of the varicella vaccine into the expanded program of immunization in Taiwan, around two-thirds of elementary schoolchildren were seropositive for varicella-zoster virus. Further surveillance studies on clinical varicella cases are worthwhile to determine whether a second dose of varicella vaccine is needed in Taiwan.

Molecular analysis of group A rotaviruses detected in hospitalized children from Rawalpindi, Pakistan during 2014

As a part of strategy to control diarrheal diseases, World Health Organization (WHO) recommends to include rotavirus vaccines in national immunization programs. Sentinel surveillance networks have been established to monitor rotavirus disease burden and genotype distribution in both pre and post vaccine era in many countries. Unfortunately, due to lack of proper surveillance programs, data on rotavirus disease burden and genotype distribution from Pakistan is scarce. We investigated 502 stool samples from children (<5years) hospitalized due to gastroenteritis in Rawalpindi, Pakistan during 2014 for the presence of group A rotavirus (RVA) and its genotypic diversity. Among 147 ELISA positive samples, 131 were successfully genotyped for RVA. Common G types detected were G1 (23.6%), followed by G3 (22.9%), G12 (19.8%), G2 (19.08%) and G9 (9.9%). The most common P-type was P[8] (41.2%), followed by P[6] (29%) and P[4] (28.24%). G3P[8] (17.55%) was the most prevalent genotype combination followed by G12P[6] (16.7%), G2P[4] (15.2%) and G1P[8] (14.5%). Mixed infection of rotavirus G-P types was also observed in 6% of samples. Phylogenetic analysis of VP7 and VP4 genes of Pakistani strains showed that G1, G2, G9 and P[4], P[6], P[8] were closely related to strains circulating worldwide as well as previously reported strains from Pakistan. Pakistani G12P[8] strains NIH-BBH-3981 and NIH-BBH-4003 belonged to lineage 3 cluster 3a along with strains from USA and Italy whereas G12P[6] strains NIH-BBH-3978, NIH-BBH-4052 and NIH-BBH-4444 were closely related to strains from Italy, Thailand, United Kingdom and with previously reported G12 strains from Pakistan within lineage 3 cluster 3b. This pre-vaccination data supports the need for RVA vaccine inclusion at our national level and will be helpful in assessing the effect of vaccination on RVA genotype diversity due to vaccine selection pressure once post-vaccination data becomes available.

Whole-genome Sequencing for Surveillance of Invasive Pneumococcal Diseases in Ontario, Canada: Rapid Prediction of Genotype, Antibiotic Resistance and Characterization of Emerging Serotype 22F.

Background: Molecular typing is essential for inferring genetic relatedness between bacterial pathogens. In this study, we applied whole genome sequencing (WGS) for rapid prediction of sequence type and antibiotic resistance for invasive pneumococcal isolates.Methods: 240 isolates from adults (≥50 years old) in Ontario, Canada during 2009 to 2013 were subjected to WGS. Sequence type, antibiotic susceptibility and resistance were predicted directly from short reads. Emerging non-vaccine serotype 22F was further characterized by WGS.Results: Sequence type was successfully determined for 98.3% of isolates. The overall sensitivity and specificity for antibiotic resistance prediction were 95 and 100% respectively, compared to standard susceptibility testing methods. WGS-based phylogeny divided emerging 22F (ST433) strains into two distinct clades: clade A harboring a 23 kb-prophage and anti-phage PhD/Doc system and clade B with virulence-related proteases. Five isolates in clade A developed macrolide resistance via 5.1 kb mega element recombination (encoding mefE and msrD), while one isolate in clade B displayed quinolone resistance via a gyrA mutation.Conclusions: WGS is valuable for routine surveillance of pneumococcal clinical isolates and facilitates prediction of genotype and antibiotic resistance. The emergence of 22F in Ontario in the post-vaccine era and evidence of evolution and divergence of the 22F population warrants heightened pneumococcal molecular surveillance.

Prevalence of Human Papillomavirus in Self-Collected Cervicovaginal Swabs in Young Women in the United States Between 2003 and 2012.

To evaluate whether there was a change in prevalence of human papillomavirus (HPV) in the United States correlated with the introduction of HPV vaccines in both vaccinated and unvaccinated women. We performed a retrospective review of prevalence data for women aged 18-29 years living in the United States using the National Health and Nutrition Examination Surveys, which is an ongoing series of cross-sectional surveys. Participants provided responses to standardized questions and self-collected cervicovaginal swabs in which a Linear Array HPV Assay was used to determine HPV prevalence. A total of 783 women from the prevaccine era (2003-2004) and 1,526 from the postvaccine era (2007-2012) were analyzed. Among women aged 18-29 years, the prevalence of vaccine-type HPV declined among women receiving one or more doses of vaccine (P=.003): 10.1% (95% confidence interval [CI] 7.1-13.8%) in the prevaccine era to 4.2% (95% CI 3.3-10.9%) in the postvaccine era. There was no change in prevalence of nonvaccine-type HPV among women receiving one or more doses of vaccine (P>.05). There was also no change in prevalence of vaccine-type HPV among unvaccinated women from the prevaccine era 10.1% (95% CI 7.1-13.8%) to 8.8% (95% CI 5.6-12.9%) in the postvaccine era (P=.4). Vaccine coverage increased to 31.5% of eligible women aged 18-29 years as of 2011-2012. Six years after introduction of HPV vaccination in the United States, there has been a decrease in the prevalence of vaccine-type HPV among women correlated with receiving one or more vaccine doses with no change in nonvaccine-type HPV. Furthermore, there has been no change in prevalence of vaccine-type HPV among unvaccinated women.

Community-acquired pneumonia in the post 13-valent pneumococcal conjugate vaccine era.

This review covers the outpatient management of pediatric community-acquired pneumonia (CAP), discussing the changing microbiology of CAP since the introduction of the 13-valent pneumococcal conjugate vaccine in 2010, and providing an overview of national guideline recommendations for diagnostic evaluation and treatment. Rates of invasive pneumococcal disease and pneumococcal antibiotic resistance have plummeted since widespread 13-valent pneumococcal conjugate vaccine immunization. Viruses remain the most common cause of CAP in young children; children over age 5 years have increased rates of Mycoplasma pneumoniae. A recent national guideline offers recommendations for office-based diagnostic evaluation and treatment of pediatric CAP. This review offers a discussion of the above findings with practical recommendations for the office-based practitioner in the evaluation and treatment of an infant (>3 months) or child with suspected CAP.

Varicella in pediatric oncology patients in the post-vaccine era—Analysis of routine hospital data from Bavaria (Germany), 2005–2011

ABSTRACTVaricella in oncology patients can result in serious complications. We analyzed trends in hospitalization rates and characteristics of pediatric oncology and non-oncology patients hospitalized with varicella during the first 7 years after introduction of routine varicella vaccination. Our data included children <17 years of age with an International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) main or secondary discharge diagnosis of varicella identified by annual database queries in 22–29 pediatric hospitals in Bavaria (Germany) in 2005–2011. Of a total of 1,245 varicella-associated hospitalizations, 42 children (median age 4 years, interquartile range 3–5) had an underlying malignancy (67% with acute lymphoblastic leukemia). Overall, additional diagnoses potentially associated with varicella were reported less often in oncology than in non-oncology varicella patients (62% vs. 77%, p = 0.041), suggesting earlier hospitalization of high-risk patients. Acute hematological diagnoses (29% vs. 3%, p < 0.001) and coinfections (invasive 12% vs. 2%, p = 0.001; noninvasive 19% vs. 8%, p = 0.019) were more frequent, whereas neurological (5% vs. 19%, p = 0.023) and upper respiratory tract diagnoses (2% vs. 16%, p = 0.014) were less frequent in oncology compared to non-oncology varicella patients. Oncology varicella patients showed a longer hospital stay (median 5 vs. 3 days, p < 0.001). Hospitalization rates in non-oncology varicella patients declined constantly since 2006, from 114.8 (2006) to 30.5 (2011) per 1,000 pediatric beds. The rates of varicella-associated hospitalizations in oncology patients indicated an overall decreasing trend (3.8, 1.9, 4.6, 3.5, 0.4, 2.1 and 0.6 cases per 1,000 pediatric beds in 2005–2011). Thus, pediatric oncology patients potentially profit from herd protection effects, resulting from increasing vaccine coverage in the general population.

Emergence of human G2P[4] rotaviruses containing animal derived gene segments in the post-vaccine era.

The introduction of Rotarix into the Belgian immunization program in June 2006 coincided with an increase of the relative prevalence of G2P[4] strains. However, the genetic composition of these persistent G2P[4] strains has not been investigated. Therefore, we have investigated the NSP4 gene of 89 Belgian G2P[4] strains detected between 1999 and 2013, covering both pre- and post-vaccination periods. The NSP4 genes were divided over seven separate clusters of which six were more closely related to animal than to human strains. The NSP4 genes that clustered more closely to animal DS-1-like strains were isolated after 2004–2005 and were found throughout multiple seasons. Complete genome sequencing of 28 strains identified several other gene segments that clustered more closely to animal than to human DS-1-like strains. These findings suggest that frequent interspecies reassortments may have played a role in the spread of G2P[4] rotaviruses in the post-vaccination period in Belgium.

Detection of the first G6P[14] human rotavirus strain in an infant with diarrhoea in Ghana.

BackgroundRotaviruses with G6P[14] specificity are mostly isolated in cattle and have been established as a rare cause of gastroenteritis in humans. This study reports the first detection of G6P[14] rotavirus strain in Ghana from the stool of an infant during a hospital-based rotavirus surveillance study in 2010.MethodsViral RNA was extracted and rotavirus VP7 and VP4 genes amplified by one step RT-PCR using gene-specific primers. The DNA was purified, sequenced and genotypes determined using BLAST and RotaC v2.0. Phylogenetic tree was constructed using maximum likelihood method in MEGA v6.06 software and statistically supported by bootstrapping with 1000 replicates. Phylogenetic distances were calculated using the Kimura-2 parameter model.ResultsThe study strain, GHA-M0084/2010 was characterised as G6P[14]. The VP7 gene of the Ghanaian strain clustered in G6 lineage-III together with artiodactyl and human rotavirus (HRV) strains. It exhibited the highest nucleotide (88.1 %) and amino acid (86.9 %) sequence identity with Belgian HRV strain, B10925. The VP8* fragment of the VP4 gene was closely related to HRV strains detected in France, Italy, Spain and Belgium. It exhibited the strongest nucleotide sequence identity (87.9 %) with HRV strains, PA169 and PR/1300 (Italy) and the strongest amino acid sequence identity (89.3 %) with HRV strain R2775/FRA/07 (France).ConclusionThe study reports the first detection of G6P[14] HRV strain in an infant in Ghana. The detection of G6P[14], an unusual strain pre-vaccine introduction in Ghana, suggests a potential compromise of vaccine effectiveness and indicates the necessity for continuous surveillance in the post vaccine era.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0643-y) contains supplementary material, which is available to authorized users.

Update on Diarrhea.

1. Nicholas J. CaJacob, MD*,† 2. Mitchell B. Cohen, MD*,† 1. *Departments of Pediatric Gastroenterology, Hepatology, and Nutrition and 2. †Pediatrics, University of Alabama at Birmingham, Birmingham, AL. The mainstay of management of infectious diarrheal illness in children remains supportive care with oral or intravenous rehydration. In the postvaccine era, norovirus has supplanted rotavirus as the leading cause of gastroenteritis presenting to medical facilities in the United States. After reading this article, the reader should be able to: 1. Recognize the common pathogens associated with infectious diarrhea and develop a management plan. 2. Identify the key differences between infectious and noninfectious causes of diarrhea. 3. Effectively treat a child with cow milk protein intolerance. 4. Recognize that antidiarrheal and antimotility agents are not indicated or recommended in the treatment of infectious diarrhea. 5. Understand the changing epidemiology of infectious diarrhea in the postvaccine era. Diarrhea is a worldwide problem that is frequently encountered in the practice of pediatric medicine. According to the World Health Organization, diarrheal illness is the second leading cause of death in children younger than age 5 years, accounting for 760,000 deaths per year in this age group. (1) The overwhelming majority of diarrheal illnesses are due to acute infectious diarrhea, commonly referred to as acute gastroenteritis (AGE). The degree of dehydration, assessed by both history and physical examination, is the most important indicator of disease severity. However, most children who have infectious diarrhea are not dehydrated and can be successfully treated at home with replacement of ongoing fluid losses using oral rehydration solution (ORS). The routine use of antibiotics and antidiarrheal agents is not recommended for treatment of acute diarrhea and may cause harm. Restrictive diets are not necessary; the adverse effects on nutritional status during diarrheal illness can be lessened or prevented by rapid reinstitution of a regular …

Pleural effusion with negative culture: a challenge for pneumococcal diagnosis in children

BackgroundPneumococcal parapneumonic effusion seems to be increasing in children in the postvaccine era and is frequently associated with negative culture. Due to the low yield of culture, culture-independent tools are evaluated. MethodsCulture-negative pleural fluid specimens from 38 children with parapneumonic effusion were examined for pneumococcal lytA by quantitative polymerase chain reaction (qPCR) and soluble antigen (C-polysaccharide) using an immunochromatographic test (BinaxNow Streptococcus pneumoniae). ResultsIn 81% (30/37) and 63% (24/38) of the specimens, a positive result was obtained by qPCR and antigen detection, respectively. Most mismatches were observed in specimens with low quantities of pneumococcal DNA and a negative antigen test. ConclusionsOur results suggest an imperfect relationship between the 2 described methods. The immunochromatographic assay is a simple diagnostic tool, which can be used when resources are limited, and even after antibiotic use, but negative results may require confirmation through a more sensitive test, such as qPCR.

Complete genome analysis of contemporary G12P[8] rotaviruses reveals heterogeneity within Wa-like genomic constellation

G12 rotaviruses are globally emergent rotaviruses causing severe childhood gastroenteritis. Little is known about the evolution and diversity of G12P[8] rotaviruses and the possible role that widespread vaccine use, globally, has had on their emergence. In Sicily, Italy, surveillance activity for rotaviruses has been conducted uninterruptedly since 1985, thus representing a unique observatory for the study of human rotaviruses in the pre- and post-vaccine era. G12 rotaviruses were first detected only in 2012 and between 2012 and 2014 they accounted for 8.7% of all rotavirus-associated infections among children, with peaks of 27.8% in 2012/2013 and 21% in 2014. We determined and analyzed the full-genome of 22 G12P[8] rotaviruses collected during the 2012-2014. Although all G12P[8] rotaviruses exhibited a typical Wa-like genotype constellation (G12P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1), phylogenetic analysis allowed distinguishing either two or three (sub)lineages in each genome segment. On the basis of the segregation patterns into lineages/sublineages, 20 G12P[8] rotaviruses could be grouped into three stable major genomic sub-constellations, whilst two strains displayed unique genome architectures, likely due to ressortment with co-circulating strains. Altogether, these findings indicate that the onset and prolonged circulation of G12 rotaviruses was due to repeated introductions of different G12 rotaviruses circulating globally. Importantly, as regional rotavirus vaccination was initiated in 2012 reaching a 45% coverage in newborns in 2014, a correlation between the appearance and spread of G12 rotaviruses and the enacted vaccination program could not be drawn. Constant epidemiologic surveillance remains important to monitor the epidemiological dynamics of human rotaviruses.

Invasive Pneumococcal Disease in Canadian Children, 2000-2014: The Canadian Immunization Monitoring Program, Active

Abstract BACKGROUND: Before implementation of the first conjugate IPD vaccine program in 2002, invasive pneumococcal disease (IPD) accounted for most severe, invasive bacterial infections in Canadian children. Conjugate vaccine programs in children were implemented with the expectation that the burden of disease from IPD would improve. OBJECTIVES: To describe the changes in Canadian epidemiology of pediatric IPD before and after the implementation of conjugate pneumo-coccal vaccine programs. DESIGN/METHODS: The Canadian Immunization Monitoring Program, Active (IMPACT) captures all in- and out-patient lab-confirmed IPD cases presenting at its 12 tertiary care pediatric hospitals across Canada. Nurses abstract case details from the hospital chart onto a standardized report form. Case isolates are serotyped at a central reference laboratory. All participating centers have local ethics and/or administrative approvals. RESULTS: From 2000-2014 IMPACT centers identified 3,328 IPD cases. Annual case numbers decreased by 48% (323 to 168) over this time period. Annually, vaccine preventable serotypes accounted for on average 89% (n=288) of cases in the pre-conjugate vaccine era (2000-2003) and 34% (n=56) in the post-13-valent conjugate vaccine era (2011-2014), with 73% (n=41/56) due to serotypes 19A, 3 and 6a. The age distribution of cases shifted upward over the time period with 16% (n=204) of cases occurring in children 5 years of age and older in the pre-vaccine era compared to 32% (n=217) in the post 13-valent vaccine era. This shift was due to decreases in cases occurring in children 0-4 years of age, rather than a significant increase in the number of cases occurring in older children. The most frequent presentation of IPD was radiologic-confirmed pneumonia (n=1119), with complicated pneumonia (pneumonia with empyema or pleural effusion) accounting for 36% (405/1119) of cases, followed by bacteremia only (n=919) and meningitis (n=532). The proportion of cases presenting with complicated pneumonia increased significantly (from 6% -24%; p&amp;lt;0.0001) between the pre-conjugate and post 13-valent conjugate eras. The proportion of cases presenting with meningitis did not change over the time periods (15% pre-conjugate era vs. 16% post-13-valent conjugate era; p=0.46). However, the proportion of meningitis caused by vaccine preventable serotypes decreased significantly (from 85%-26%; p&amp;lt;0.0001). CONCLUSION: The epidemiology of pediatric IPD has changed with the introduction of conjugate vaccine programs. IPD has been reduced by almost 50% in the post-13-valent conjugate vaccine era and vaccine sero-types account for just one-third of cases. However, complicated pneumonia is seen more frequently in the post-13-valent conjugate vaccine era.

HPV Vaccination Does Not Provide Herd Immunity for Unvaccinated Women or Cross-Protection for Nonvaccine HPV Types [12

INTRODUCTION: To determine if the human papillomavirus (HPV) vaccination offers cross-protection against nonvaccine HPV types and whether introduction of the vaccination has offered herd immunity to unvaccinated women. METHODS: We collected and analyzed HPV prevalence data for females aged 18–29 from the prevaccine era (2007–2008) and postvaccine era (2009–2012) using the National Health and Nutrition Examination Surveys (NHANES); 1628 female respondents aged 18–29, representing 21,135,134 females in the United States non-institutionalized civilian population, provided vaginal swabs across three consecutive NHANES survey cycles. RESULTS: Among females aged 18–29, the prevalence of high risk HPV among women who received at least one dose of the HPV vaccine decreased from 67% (95% confidence interval [CI] 50.7–81.4) in 2007–2008 to 41.5% (95% CI, 30.5–53.1) in 2011–2012; among the women vaccinated for HPV in the postvaccine era, the prevalence of HPV-16 and -18 was 6.4% versus 93.6% for all other high risk HPV types. There was no difference in prevalence in high risk HPV for women who did not receive the vaccine; 49.5% (95% CI, 42.5–56.6) in 2007–2008 versus 50.8% (95% CI, 43.0–58.7) in 2011–2012. CONCLUSION/IMPLICATIONS: The prevalence of high risk HPV significantly decreased among females aged 18–29 years who received the HPV vaccine, but there appeared to be no cross-protection against nonvaccine HPV types. These findings may offer support for usage of the investigational 9-valent HPV vaccine. There also was no evidence to suggest protection against HPV infection for unvaccinated women.

Sustained Reduction of Childhood Diarrhea-Related Mortality and Hospitalizations in Mexico After Rotavirus Vaccine Universalization.

Mexico implemented routine childhood vaccination against rotavirus in 2007. We describe trends in hospitalization and deaths from diarrhea among children aged <5 years in Mexico before and 7 years after implementation of rotavirus vaccination. We obtained data on deaths and hospitalizations from diarrhea, from January 2003 through December 2014, in Mexican children <5 years of age. We compared diarrhea-related mortality and hospitalizations in the postvaccine era with the prevaccine baseline from 2003 to 2006. Compared with the prevaccine baseline, we observed a 53% reduction (95% confidence interval [CI], 47%-58%) in diarrhea-related mortality and a 47% reduction (95% CI, 45%-48%) in diarrhea-related hospitalizations in postvaccine years, translating to 959 deaths and 5831 hospitalizations averted every year in Mexican children aged <5 years. Prevaccine peaks in diarrhea-related mortality and hospitalizations during the rotavirus season months were considerably diminished in postvaccine years, with greater declines observed during the rotavirus season compared with non-rotavirus season months. We document a substantial and sustained decline in diarrhea-related hospitalizations and deaths in Mexican children associated with implementation of rotavirus vaccination. These results highlight the public health benefits that could result in countries that adopt rotavirus vaccination into their national immunization programs.

How to determine protective immunity in the post-vaccine era

abstractThe ability to determine an individual's susceptibility to infection relies heavily on the assay used, and the ability to correlate results of the assay to a clinical interpretation. Current rubella immunity screening methods identify total rubella IgG antibodies circulating in the serum, however both humoral and cell mediated immune responses have been shown to contribute to protection from infection. Therefore, antibody screening assays may under-estimate immunity in some populations. In fact, waning antibody titers over time in a large prenatal population were recently documented in North America, and the trend has been echoed in other countries that have achieved elimination through universal rubella vaccination. Despite decreasing antibody titers, the number of acute rubella cases has not increased in these populations, suggesting that the lower antibody levels may still be protective. Based on the changing epidemiology in universally vaccinated populations, it may be time to reassess the level of antibody that indicates immunity to rubella infection.

Factors associated with mumps meningitis and the possible impact of vaccination.

PurposeMumps meningitis is a common complication of mumps infection; however, information on mumps meningitis in the postvaccine era is limited. The purpose of the present study was to determine factors associated with mumps meningitis and to discuss the effect of vaccination on this disease.MethodsWe retrospectively reviewed patients younger than 19 years with mumps, diagnosed at a university hospital in Korea between 2003 and 2013. Patients were divided into groups with and without meningitis, and the clinical features of the 2 groups were compared.ResultsThe study enrolled 119 patients: 19 patients with meningitis and 100 patients without. Univariate analysis showed that older age (median: 15 years vs. 9.5 years, respectively), a longer interval from last vaccination (median: 10.2 years vs. 4.8 years, respectively), and febrile presentation (94.7% vs. 31.0%, respectively) were significantly associated with mumps meningitis. Sex, number of vaccination doses, bilateral parotitis, and the presence of complications other than meningitis did not differ between the 2 groups. In multivariate logistic regression analysis, age (odds ratio, 1.38; 95% confidence interval, 1.01–1.89; P=0.04) and fever (odds ratio, 30.46; 95% confidence interval, 3.27–283.61; P<0.01) remained independent factors for mumps meningitis.ConclusionClinicians in the postvaccine era should be aware of the possibility of mumps meningitis in febrile cases of mumps in adolescents, regardless of the number of vaccination doses. To establish the role of vaccination in mumps meningitis, further studies will be necessary.

Tdap in every pregnancy: circling the wagons around the newborn.

The resurgence of pertussis in the United States and many other countries in the world has become a major problem, with no immediate solution in sight. In 2014, the >10 000 reported cases of pertussis in California surpassed a recent previous record set in 2010 and all other records in the postvaccine era. The national experience mimics that of California, with rising numbers of cases widespread over the last 4 years. Sadly, the rising disease rate is accompanied by an increase in deaths from pertussis, almost exclusively in young infants. Why is this happening? We have learned that the immunity induced by acellular pertussis vaccines, the only type of vaccine used in the United States since the late 1990s, is not durable and wanes rapidly over just a few years. No sooner is 1 cohort of children protected from pertussis through immunization than another, older, cohort becomes susceptible again. We merely are treading water in our efforts to control pertussis with currently available vaccines. As well outlined in the Global Pertussis Initiative review and position statement by Forsyth et al1 in this issue of Pediatrics , we must circle the wagons around young infants. Very young infants suffer the greatest morbidity and almost exclusively the mortality related to pertussis, before they can be immunized. Couple this with an inability to … Address correspondence to Mark H. Sawyer, MD, 3020 Children’s Way, MC 5124, San Diego, CA 92123. E-mail: mhsawyer{at}ucsd.edu