Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants

BackgroundOral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated.MethodsIn urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea.ResultsCampylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (−0.08 change in log titer per tenfold increase in quantity; P = 0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64–0.96; P = 0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05–1.71; P = 0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity.ConclusionIn this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses.ClinicalTrials.gov Identifier: NCT01375647.     

Effectiveness of enterovirus A71 vaccine in severe hand,foot, and mouth disease cases in Guangxi,China

BackgroundHand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is a major public health issue in China that poses severe risks to children’s health, especially those under the age of 3. Since 2016, EV71 vaccines developed by three Chinese manufacturers have been approved for use, and clinical trials of these vaccines have demonstrated protection against EV-A71 infection. However, few studies have assessed the effectiveness of these vaccines in real-world settings.MethodsA test-negative design case-control study was used to estimate vaccine effectiveness (VE) in cases of severe HFMD. We obtained information including EV-A71 vaccination status from the Local Center for Disease Control and Prevention (CDC) on all severe HFMD cases under 12 years in age in Guangxi, China, from Jan. 1, 2017, to Dec. 31, 2018. Enterovirus infection was laboratory confirmed by local CDCs. Individuals with a positive EV-A71 nucleic acid test result were assigned to the case group, and those with negative EV-A71 nucleic acid test results were assigned to the control group. We estimated VE using logistic regression.ResultsA total of 2779 severe HFMD cases were enrolled in the study; 838 children were EV-A71 positive cases, and 1941 children were EV-A71 negative controls. The proportion of EV-A71 positive cases aged 6–36 months was lower than that for EV-A71 negative controls. EV-A71 infection was associated with an increased risk of mortality (aOR, 8.8; 95% CI, 1.3–61.6). The adjusted VE was 81.4% and 88.3% for one dose and two doses, respectively.ConclusionOur findings suggest that the rate of EV-A71 has fallen among severe HFMD cases in Guangxi and that the risk for EV-A71 infection in 6–36-month-old children has been reduced by use of the vaccine. Inactivated vaccines performed well in severe HFMD cases in a real-world setting.     

Country specific predictions of the cost-effectiveness of malaria vaccine RTS,S/AS01 in endemic Africa

BackgroundRTS,S/AS01 is a safe and moderately efficacious vaccine considered for implementation in endemic Africa. Model predictions of impact and cost-effectiveness of this new intervention could aid in country adoption decisions.MethodsThe impact of RTS,S was assessed in 43 countries using an ensemble of models of Plasmodium falciparum epidemiology. Informed by the 32 months follow-up data from the phase 3 trial, vaccine effectiveness was evaluated at country levels of malaria parasite prevalence, coverage of control interventions and immunization. Benefits and costs of the program incremental to routine malaria control were evaluated for a four dose schedule: first dose administered at six months, second and third - before 9 months, and fourth dose at 27 months of age. Sensitivity analyses around vaccine properties, transmission, and economic inputs were conducted.ResultsIf implemented in all 43 countries the vaccine has the potential to avert 123 (117; 129) million malaria episodes over the first 10 years. Burden averted averages 18,413 (range of country median estimates 156–40,054) DALYs per 100,000 fully vaccinated children with much variation across settings primarily driven by differences in transmission intensity. At a price of $5 per dose program costs average $39.8 per fully vaccinated child with a median cost-effectiveness ratio of $188 (range $78–$22,448) per DALY averted; the ratio is lower by one third - $136 (range $116–$220) - in settings where parasite prevalence in children aged 2–10 years is at or above 10%.ConclusionRTS,S/AS01 has the potential to substantially reduce malaria burden in children across Africa. Conditional on assumptions on price, coverage, and vaccine properties, adding RTS,S to routine malaria control interventions would be highly cost-effective. Implementation decisions will need to further consider feasibility of scaling up existing control programs, and operational constraints in reaching children at risk with the schedule.     

Cost-effectiveness analysis of catch-up hepatitis A vaccination among unvaccinated/partially-vaccinated children

BackgroundSince 2006, the US Centers for Disease Control and Prevention has recommended hepatitis A (HepA) vaccination routinely for children aged 12–23 months to prevent hepatitis A virus (HAV) infection. However, a substantial proportion of US children are unvaccinated and susceptible to infection. We present results of economic modeling to assess whether a one-time catch-up HepA vaccination recommendation would be cost-effective.MethodsWe developed a Markov model of HAV infection that followed a single cohort from birth through death (birth to age 95 years). The model compared the health and economic outcomes from catch-up vaccination interventions for children at target ages from two through 17 years vs. outcomes resulting from maintaining the current recommendation of routine vaccination at age one year with no catch-up intervention.ResultsOver the lifetime of the cohort, catch-up vaccination would reduce the total number of infections relative to the baseline by 741 while increasing doses of vaccine by 556,989. Catch-up vaccination would increase net costs by $10.2 million, or $2.38 per person. The incremental cost of HepA vaccine catch-up intervention at age 10 years, the midpoint of the ages modeled, was $452,239 per QALY gained. Across age-cohorts, the cost-effectiveness of catch-up vaccination is most favorable at age 12 years, resulting in an Incremental Cost-Effectiveness Ratio of $189,000 per QALY gained.ConclusionsGiven the low baseline of HAV disease incidence achieved by current vaccination recommendations, our economic model suggests that a catch-up vaccination recommendation would be less cost-effective than many other vaccine interventions, and that HepA catch-up vaccination would become cost effective at a threshold of $50,000 per QALY only when incidence of HAV rises about 5.0 cases per 100,000 population.     

Incidence,direct costs and duration of hospitalization of patients hospitalized with community acquired pneumonia: A nationwide retrospective claims database analysis

BackgroundCommunity-acquired pneumonia (CAP) is one of the most common acute infections associated with a substantial clinical and economic burden. There have been few studies assessing incidence rate, duration of hospitalization, and costs of hospitalized CAP by age and care-setting.MethodsA retrospective study was conducted using a nationwide Dutch database containing healthcare claims data of 16.7 million inhabitants. Patients with at least one claim with a discharge diagnosis of CAP between January 2008 and December 2011 were selected. The main outcome measures considered were the incidence rate, duration of hospitalization, and the direct costs of hospitalized CAP stratified by age and care-setting.ResultsIn total, 195,372 CAP cases were included in the analysis resulting in an average incidence of 295 per 100,000 population per year. Sixty-three percent (123,357) of the included patients were hospitalized for 1 or more nights, of which 5.9% (n = 7241) spent at least one night in the Intensive Care Unit (ICU). Overall, these 123,357 patients spent 824,985 days in the hospital of which 48,324 were spent on the ICU. The mean duration of hospitalization of ICU patients and general ward patients was 15.2 days and 6.2 days, respectively. The total costs related to all 195,372 CAP episodes during these 4 years were €711 million, with the majority (76%) occurring among those aged 50 years and older. Median (and mean) costs were dependent on age and type of care with costs ranging from €344 (€482) per episode for 0–9 year olds treated in the outpatient hospital setting up to €10,284 (€16,374) per episode for 50–64 year olds admitted to the ICU.ConclusionThere is a large variation in terms of incidence, disease burden and costs across different age groups and the treatment setting. Effective interventions, targeted at older adults, to prevent pneumonia could reduce the (financial) burden due to pneumonia.     

Cost–benefit comparison of two proposed overseas programs for reducing chronic Hepatitis B infection among refugees: Is screening essential?

BackgroundRefugees are at an increased risk of chronic Hepatitis B virus (HBV) infection because many of their countries of origin, as well as host countries, have intermediate-to-high prevalence rates. Refugees arriving to the US are also at risk of serious sequelae from chronic HBV infection because they are not routinely screened for the virus overseas or in domestic post-arrival exams, and may live in the US for years without awareness of their infection status.MethodsA cohort of 26,548 refugees who arrived in Minnesota and Georgia during 2005–2010 was evaluated to determine the prevalence of chronic HBV infection. This prevalence information was then used in a cost–benefit analysis comparing two variations of a proposed overseas program to prevent or ameliorate the effects of HBV infection, titled ‘Screen, then vaccinate or initiate management’ (SVIM) and ‘Vaccinate only’ (VO). The analyses were performed in 2013. All values were converted to US 2012 dollars.ResultsThe estimated six year period-prevalence of chronic HBV infection was 6.8% in the overall refugee population arriving to Minnesota and Georgia and 7.1% in those ≥6 years of age. The SVIM program variation was more cost beneficial than VO. While the up-front costs of SVIM were higher than VO ($154,084 vs. $73,758; n = 58,538 refugees), the SVIM proposal displayed a positive net benefit, ranging from $24 million to $130 million after only 5 years since program initiation, depending on domestic post-arrival screening rates in the VO proposal.ConclusionsChronic HBV infection remains an important health problem in refugees resettling to the United States. An overseas screening policy for chronic HBV infection is more cost–beneficial than a ‘Vaccination only’ policy. The major benefit drivers for the screening policy are earlier medical management of chronic HBV infection and averted lost societal contributions from premature death.     

Pre-vaccination evolution of antibodies among infants 0, 3 and 6 months of age: A longitudinal analysis of measles,enterovirus 71 and coxsackievirus 16

BackgroundDue to waning levels of maternal antibodies (measles; enterovirus 71, EV71; and coxsackievirus A16, CoxA16), some infants may lose protection against infection prior to vaccination. Using a longitudinal design, we examine how maternal antibody levels evolve over time in infants prior to vaccination.MethodsIn 2013–2014, we collected sera at ages 0, 3 and 6 months from infants. We assayed for levels of measles IgG antibody (717, 233 and 75 sample sera tested at months 0, 3 and 6, respectively), and neutralizing antibodies for EV71 and CoxA16 (225, 217, and 72). Demographic and health information were collected, and a linear mixed model (LMM) was used to describe antibody levels over time.ResultsPre-vaccination monotonic antibody decreases were observed for measles (1410, 195 and 22 mIU/ml, p < 0.001), EV71 (1:19.9, 6.3 and 4.5, p < 0.001) and CoxA16 (1:16.3, 5.9, and 4.5, p < 0.001). At 6 months of age, only 2.7% (95%CI, 0.6–8.3), 6.8% (95%CI, 2.7–14.4) and 5.6% (95%CI, 1.9–12.7) of infants were antibody positive for measles, EV71 and CoxA16, respectively. LMM findings indicated that infants with higher antibody titers at birth experienced a greater loss of antibody level. An infection rate of 1.3% (95%CI, 0.1–6.1) was reported for both EV71 and CoxA16.ConclusionsFurther modifications of vaccination strategies for measles, earlier vaccination for EV71 infection, and deployment of a CoxA16 vaccine need to be considered to limit infection among the very young.     

Cost effectiveness of a targeted age-based West Nile virus vaccination program

BackgroundWest Nile virus (WNV) is the leading cause of domestically-acquired arboviral disease in the United States. Several WNV vaccines are in various stages of development. We estimate the cost-effectiveness of WNV vaccination programs targeting groups at increased risk for severe WNV disease.MethodsWe used a mathematical model to estimate costs and health outcomes of vaccination with WNV vaccine compared to no vaccination among seven cohorts, spaced at 10 year intervals from ages 10 to 70 years, each followed until 90-years-old. U.S. surveillance data were used to estimate WNV neuroinvasive disease incidence. Data for WNV seroprevalence, acute and long-term care costs of WNV disease patients, quality-adjusted life-years (QALYs), and vaccine characteristics were obtained from published reports. We assumed vaccine efficacy to either last lifelong or for 10 years with booster doses given every 10 years.ResultsThere was a statistically significant difference in cost-effectiveness ratios across cohorts in both models and all outcomes assessed (Kruskal-Wallis test p < 0.0001). The 60-year-cohort had a mean cost per neuroinvasive disease case prevented of $664,000 and disability averted of $1,421,000 in lifelong model and $882,000 and $1,887,000, respectively in 10-year immunity model; these costs were statistically significantly lower than costs for other cohorts (p < 0.0001). Vaccinating 70-year-olds had the lowest cost per death averted in both models at around $4.7 million (95%CI $2–$8 million). Cost per disease case averted was lowest among 40- and 50-year-old cohorts and cost per QALY saved lowest among 60-year cohorts in lifelong immunity model. The models were most sensitive to disease incidence, vaccine cost, and proportion of persons developing disease among infected.ConclusionsAge-based WNV vaccination program targeting those at higher risk for severe disease is more cost-effective than universal vaccination. Annual variation in WNV disease incidence, QALY weights, and vaccine costs impact the cost effectiveness ratios.     

Impact of the national rotavirus vaccination programme on acute gastroenteritis in England and associated costs averted

BackgroundIntroduction of infant oral rotavirus vaccination in the UK in July 2013 has resulted in decreased hospitalisations and Emergency Department (ED) visits for acute gastroenteritis (AGE), for both adults and children. We investigated reductions in AGE incidence seen in primary care in the two years after vaccine introduction, and estimated the healthcare costs averted across healthcare settings in the first year of the vaccination programme.MethodsWe used primary care data from the Clinical Practice Research Datalink and age-stratified time-series analyses to derive adjusted incidence rate ratios (IRR_a) for AGE in the first two years of the post-vaccination era (July 2013-April 2015) compared to the pre-vaccination era (July 2008-June 2013). We estimated cases averted among children aged <5 years in the first year of the vaccination programme by comparing observed numbers of AGE cases in 2013–2014 to numbers predicted from the time-series models. We then estimated the healthcare costs averted for general practice consultations, ED visits and hospitalisations.ResultsIn general practice, AGE rates in infants (the target group for vaccination) decreased by 15% overall after vaccine introduction (IRR_a = 0.85; 95%CI = 0.76–0.95), and by 41% in the months of historically high rotavirus circulation (IRR_a = 0.59; 95%CI = 0.53–0.66). Rates also decreased in other young children and to a lesser degree in older individuals, indicating herd immunity. Across all three settings (general practice, EDs, and hospitalisations) an estimated 87,376 (95% prediction interval: 62,588–113,561) AGE visits by children aged <5 years were averted in 2013–14, associated with an estimated £12.5 million (9,209–16,198) reduction in healthcare costs.ConclusionsThe marked decreases in the general practice AGE burden after rotavirus vaccine introduction mirror decreases seen in other UK healthcare settings. Overall, these decreases are associated with substantial averted healthcare costs.     

肠道病毒71型疫苗上市后疫苗保护效果和免疫原性分析

目的 分析肠道病毒71型（EV-A71）疫苗上市接种后的疫苗保护效果和免疫原性。方法 采用队列研究于2017年10－12月在上海市静安区招募符合纳入标准的预防接种门诊受种者为研究对象,按0、30 d程序接种疫苗者纳入接种组,不接种疫苗者纳入对照组,随访观察1年,评估疫苗保护效果和接种2剂次疫苗后抗体水平及阳转率。结果 共纳入3 018名8~20月龄的儿童,接种组1 211人,对照组1 807人,经过1年随访,EV-A71疫苗对EV-A71感染引起的手足口病保护率为100.00%（95% CI：-66.99%~100.00%）。接种组中124人检测了中和抗体,接种首剂疫苗后60 d抗体几何平均滴度（GMT）为41.76（95% CI：35.60~49.34）,接种后365 d GMT为28.44（95% CI：23.59~34.54）。结论 EV-A71疫苗对于儿童有良好的免疫应答,EV-A71感染引起的手足口病病例较少,需进一步观察。     

Immunogenicity and performance of an enterovirus 71 virus-like-particle vaccine in nonhuman primates

A vaccine against human enterovirus 71 (EV-A71) is urgently needed to combat outbreaks of EV-A71 and in particular, the serious neurological complications that manifest during these outbreaks. In this study, an EV-A71 virus-like-particle (VLP) based on a B5 subgenogroup (EV-A71-B5 VLP) was generated using an insect cell/baculovirus platform. Biochemical analysis demonstrated that the purified VLP had a highly native procapsid structure and initial studies in vivo demonstrated that the VLPs were immunogenic in mice. The impact of VLP immunization on infection was examined in non-human primates using a VLP prime-boost strategy prior to EV-A71 challenge. Rhesus macaques were immunized on day 0 and day 21 with VLPs (100 μg/dose) containing adjuvant or with adjuvant alone (controls), and were challenged with EV-A71 on day 42. Complete blood counts, serum chemistry, magnetic resonance imaging (MRI) scans, and histopathology results were mostly normal in vaccinated and control animals after virus challenge demonstrating that the fatal EV-A71-B3 clinical isolate used in this study was not highly virulent in rhesus macaques. Viral genome and/or infectious virus were detected in blood, spleen or brain of two of three control animals, but not in any specimens from the vaccinated animals, indicating that VLP immunization prevented systemic spread of EV-A71 in rhesus macaques. High levels of IgM and IgG were detected in VLP-vaccinated animals and these responses were highly specific for EV-A71 particles and capsid proteins. Serum from vaccinated animals also exhibited similar neutralizing activity against different subgenogroups of EV-A71 demonstrating that the VLPs induced cross-neutralizing antibodies. In conclusion, our EV-A71-B5 VLP is safe, highly immunogenic, and prevents systemic EV-A71-B3 infection in nonhuman primates making it a viable attractive vaccine candidate for EV-A71.     

A safe and sensitive enterovirus A71 infection model based on human SCARB2 knock-in mice

Enterovirus A71 infection has become a severe threat for global public health. Vaccines for controlling and preventing Enterovirus A71 epidemics are highly demanded, however, vaccine evaluation has been hindered by the lack of suitable Enterovirus A71 infection animal models. Here we established an hSCARB2 knockin mouse model for real-time monitoring of enterovirus A71 infection in vivo. This model was sensitive to the infection of both replication-competent virus rEV71(FY)-EGFP and single round pseudotype virus pEV71(FY)-Luc. The intensity of bioluminescence correlated well with viral loads in infected tissues (R = 0.86, P < 0.01). Pathological changes recapitulated human infectious and clinical features of enterovirus A71, including both general characteristics of “hand foot and mouth” and the severe symptoms in the CNS. A formalin-inactivated enterovirus A71 vaccine can elicit antibodies in R26-hSCARB2 mice, which play effective roles in protecting knockin mice against enterovirus A71 infection as indicated by bioluminescence. Therefore, this work provides a safe, sensitive and visualizing model for exploring mechanisms of enterovirus A71 infection and examining human enterovirus A71 vaccines and antiviral therapies.     

2008-2018年中国5岁及以下儿童手足口病死亡病例流行病学特征

目的 分析2008-2018年我国≤5岁儿童手足口病死亡病例的特征,为制定针对性措施,减少死亡病例发生提供依据。方法 从全国疾病监测信息报告管理系统中收集2008-2018年手足口病监测数据,采用描述性分析方法分析手足口病死亡病例的人群特征、空间分布、诊断和报告情况及病原构成变化,采用logistic回归模型分析导致死亡的危险因素。结果 2008-2018年全国共报告手足口病≤5岁儿童死亡病例3 646例,男性多于女性（1.82：1）,以≤2岁儿童为主（87.71%）。2010年之后全国≤5岁儿童报告手足口病调整后的死亡率由0.87/10万下降至2018年的0.11/10万（APC=-23.20%）。2 523例实验室确诊的死亡病例中,2 323例（92.07%）为肠道病毒71型（EV-A71）感染,但柯萨奇病毒A组16型（CV-A16）和其他肠道病毒构成呈现增加趋势。死亡病例发病至诊断时间间隔M=2（P₂₅～P₇₅：2～4）d,发病至死亡时间间隔M=3（P₂₅～P₇₅：2～4）d。0～1岁、EV-A71感染、发病诊断时间间隔较长和居住地为农村是手足口病死亡的危险因素。结论 2010年后,我国手足口病死亡水平呈下降趋势;死亡病例中优势病原仍为EV-A71,应加强死亡病例中非EV-A71和非CV-A16肠道病毒基因分型;西部省份、农村地区和小年龄组病例应当加强EV 71灭活疫苗接种宣传,提高诊断、救治及时性,降低死亡风险。     

Public health impact of Rotarix vaccination among commercially insured children in the United States

BackgroundThis study (NCT01915888) assessed public health impact of Rotarix, GSK [RV1] vaccination.MethodsChildren born between 2007–2011 were identified from Truven Commercial Claims and Encounters Databases and observed until earlier of plan disenrollment or five years old. Children receiving one or two doses of RV1 during the vaccination window were assigned to incomplete and complete vaccination cohorts, respectively. Children without rotavirus (RV) vaccination (RV1 OR RotaTeq, Merck & Co., Inc. [RV5]) were assigned to the unvaccinated cohort. Claims with International Classification of Disease 9th edition (ICD-9) codes for diarrhea and RV infections were identified. First RV episode incidence, RV-related and diarrhea-related healthcare resource utilization were compared. Multivariate Poisson regression with generalized estimating equations was used to generate 95% confidence intervals (CIs) around incidence rate ratios (IRR) between cohorts while adjusting for gender, age and calendar year. Mean costs for first RV and diarrhea episodes were calculated with adjustment for gender and birth year; bootstrapping was used to determine statistically significant differences between cohorts.ResultsIncidence of first RV episodes was significantly reduced in complete and incomplete vaccination cohorts compared to the unvaccinated cohort (IRR = 0.17 [95%CI: 0.09–0.30] and IRR = 0.19 [95%CI: 0.06–0.58], respectively). RV-related inpatient, outpatient and emergency room (ER) visits were significantly lower for complete vaccination versus unvaccinated cohort. Diarrhea-related inpatient and ER visit rates were significantly lower for complete vaccination versus unvaccinated cohorts; outpatient rates were similar. RV-related and diarrhea-related resource utilization rates were significantly lower or no different for incomplete vaccination versus unvaccinated cohort. Compared with unvaccinated children, adjusted mean cost for first RV episode and first diarrhea episode per 1000 persons was $11,511 (95%CI: $9855-$12,024) and $46,772 (95%CI: $26,268-$66,604) lower, respectively, for completely vaccinated children.ConclusionsRV1 vaccination confers benefits in reduction of RV incidence, RV- and diarrhea-related healthcare resource utilization, and RV- and diarrhea-related healthcare costs.     

Estimated and reported incidence of pertussis in Estonian adults: A seroepidemiological study

ObjectivesRates of pertussis immunisation among children in Estonia are high (∼95%), but pertussis is still the most common vaccine preventable childhood disease. Adults are suspected to be sources of pertussis in children. We aimed to measure pertussis toxin (PT) IgG in adults to estimate pertussis infection activity and compare estimated and reported pertussis incidences.MethodsIn a cross-sectional serosurvey, consecutive leftover blood sera (n = 3327) from subjects aged 20–99 years old were collected at Quattromed HTI laboratories between the 7th January and 27th February 2013. Anti-PT IgG concentration was measured by ELISA (Euroimmun, Lübeck, Germany). Estimated annual pertussis incidence was calculated for 10-year age classes using de Melker et al. (2006. J Infect. 53(2):106–13) formula.ResultsThe mean number of samples in each 10-year age class was 466 (SD 20.5), except for 90–99 year olds which contained 65 samples.More than half of all subjects (58.1%) had anti-PT IgG <5.0 IU/mL, 2.7% had 62.5 to <125 IU/mL and 0.6% ≥125 IU/mL; no differences occurred between 10-year age classes.Estimated incidence of pertussis infection was 5.8% (95% CI 4.8–7.0) in 2012, with peaks observed in 20–29 year olds (11.0%; 95% CI 7.4–15.6) and 90–99 year olds (10.8%; 95% CI 3.0–26.2). Estimated pertussis incidence rate was 915 times higher than reported.Of 80 subjects with anti-PT IgG ≥62.5 IU/mL, 25 (31.3%) had complained of coughing to their GP during the previous six months.ConclusionThe frequency of pertussis infection was similar for all ages, suggesting similar Bordetella pertussis activity in adults and children. The wide gap between reported and estimated incidence indicates poor recognition of pertussis, likely owing to it being an asymptomatic or mild disease.     

Trends in compliance with two-dose influenza vaccine recommendations in children aged 6 months through 8 years, 2010–2015

BackgroundChildren aged 6 months through 8 years may require two doses of influenza vaccine for adequate immune response against the disease. However, poor two-dose compliance has been reported in the literature.MethodsWe analyzed data for >2.6 million children from six immunization information system (IIS) sentinel sites, and assessed full vaccination coverage and two-dose compliance in the 2010–2015 influenza vaccination seasons. Full vaccination was defined as having received at least the recommended number of influenza vaccine doses (one or two), based on recommendations from the Advisory Committee on Immunization Practices. Two-dose compliance was defined as the percentage of children during each season who received at least two doses of influenza vaccine among those who required two doses and initiated the series.ResultsAcross seasons, ⩾1-dose influenza vaccination coverage was mainly unchanged among 6–23 month olds (range: 60.9–66.6%), 2–4 year olds (range: 44.8–47.4%), and 5–8 year olds (range: 34.5–38.9%). However, full vaccination coverage showed increasing trends from 2010–11 season to 2014–15 season (6–23 months: 43.0–46.5%; 2–4 year olds: 26.3–39.7%; 5–8 year olds, 18.5–33.9%). Across seasons, two-dose compliance remained modest in children 6–23 months (range: 63.3–67.6%) and very low in older children (range: 11.6–18.7% in children 2–4 years and 6.8–13.3% in children 5–8 years). In the 2014–15 season, among children who required and received 2 doses, only half completed the two-dose series before influenza activity peaked.ConclusionsImproved messaging of the two-dose influenza vaccine recommendations is needed for providers and parents. Providers are encouraged to determine a child’s eligibility for two doses of influenza vaccine using the child’s vaccination history, and to vaccinate children early in the season so that two-dose series are completed before influenza peaks.     

Non-polio enteroviruses and their association with acute diarrhea in children in India

A causative agent in approximately 40% of diarrheal cases still remains unidentified. Though many enteroviruses (EVs) are transmitted through fecal-oral route and replicate in the intestinal cells, their association with acute diarrhea has not so far been recognized due to lack of detailed epidemiological investigations. This long-term, detailed molecular epidemiological study aims to conclusively determine the association of non-polio enteroviruses (NPEVs) with acute diarrhea in comaparison with rotavirus (RV) in children. Diarrheal stool specimens from 2161 children aged 0–2 years and 169 children between 2 and 9 years, and 1800 normal stool samples from age-matched healthy children between 0 and 9 years were examined during 2008–2012 for enterovirus (oral polio vaccine strains (OPVs) and NPEVs). Enterovirus serotypes were identified by complete VP1 gene sequence analysis. Enterovirus and rotavirus were detected in 19.01% (380/2330) and 13.82% (322/2330) diarrheal stools. During the study period, annual prevalence of EV- and RV-associated diarrhea ranged between 8% and 22%, but with contrasting seasonal prevalence with RV predominating during winter months and NPEV prevailing in other seasons. NPEVs are associated with epidemics-like outbreaks during which they are detected in up to 50% of diarrheic children, and in non-epidemic seasons in 0–10% of the patients. After subtraction of OPV-positive diarrheal cases (1.81%), while NPEVs are associated with about 17% of acute diarrhea, about 6% of healthy children showed asymptomatic NPEV excretion. Of 37 NPEV serotypes detected in diarrheal children, seven echovirus types 1, 7, 11, 13, 14, 30 and 33 are frequently observed, with E11 being more prevalent followed by E30. In conclusion, NPEVs are significantly associated with acute diarrhea, and NPEVs and rotavirus exhibit contrasting seasonal predominance. This study signifies the need for a new direction of research on enteroviruses involving systematic analysis of their contribution to diarrheal burden.     

Les dépenses de soins remboursés durant la dernière année de vie,en 2008, en France

BackgroundTo measure the reimbursed health expenditures in the last year of life and the proportion it represents in total reimbursement costs in 2008, to analyse the structure of such expenditures and to identify costs by cause of death.MethodsData were obtained from the French national insurance information system (SNIIRAM). Data from the national hospital discharge database were linked to the outpatient reimbursement database for patients covered by the general health insurance scheme (n = 49 million persons). The cost of the last year of life was calculated for the exhaustive population (361,328 deaths in 2008). The supposed cause of death was mainly derived from the primary diagnosis of the last hospital stay during which the patient died.ResultsThe average reimbursed expenses during the last year of life were estimated at 22,000 € per person in 2008, with 12,500 € accounting for public hospital costs. Reimbursed health expenditures varied according to different medical causes of death: 52,300 € for HIV disease and about 40,000 € for tumors. A negative effect of age on the expenditure during the last year of life was observed. Health care spending increased with shorter time before death, the last month of life corresponding to 28% of reimbursed expenditures during the last year of life. Health care use in the last year of life represented 10.5% of the total health expenditures in 2008.ConclusionThis study found results similar to those observed in the past or in other countries. Our results show in particular that the weight of health expenditures during the last year of life on total health expenditures remains stable over the years.     

Rapid impact of rotavirus vaccine introduction to the National Immunization Plan in Southern Israel: Comparison between 2 distinct populations

BackgroundRotavirus vaccines were licensed in Israel in 2007, and in 2011 the pentavalent-vaccine (RV5) was introduced into the Israeli National Immunization plan.AimTo determine the effect of rotavirus-vaccines on the incidence of hospital visits due to rotavirus gastroenteritis (RVGE) and all-cause diarrhea in Jewish and Bedouin children <5 year residing in southern Israel.MethodsWe conducted a population-based, prospective, observational study. Data from 2006 through 2013 were analyzed. Our hospital is the only medical center in the region, enabling age-specific incidences calculation.ResultsIn the pre-vaccine period, the overall RVGE hospital visits rates per 1000 in children <12, 12–23 and 24–59 m were 16.1, 18.6 and 1.4 in Jewish children, respectively. The respective rates in Bedouin children were 26.4, 12.5 and 0.7 (P < 0.001 for <12 m).Hospitalization rates were higher among Bedouin than among Jewish children (60.0% vs. 39.7%, P < 0.001). Vaccine uptake was faster in the Jewish vs. the Bedouin population.In the year following RV5 introduction, RVGE hospital visits rates declined by 82%, 70% (P < 0.001 both) and 36% (P = 0.092) in Jewish children <12, 12–23 and 24–59 m, respectively. In Bedouin children, the respective RVGE rates declined by 70% (P < 0.001), 21% (P = ns) and 14% (P = ns).Throughout the study, RVGE rates declined significantly in children <12, and 12–23 m by 80% and 88% in Jewish children, respectively, and by 62 and 75% in Bedouin children, respectively (P < 0.001 for all declines). In children 24–59 m, RVGE rates declined by 46% (P = 0.025) in Jewish children, but no reduction was observed in Bedouin children. The dynamics of all-cause diarrhea rates were similar to that of RVGE.ConclusionsSignificant reductions of RVGE rates were observed, following Rota-vaccine introduction in southern Israel in both Jewish and Bedouin children. However, the impact was faster and more profound in Jewish children, probably related to higher vaccine uptake and possibly to lifestyle differences.