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Latin American countries were among the first to adopt rotavirus vaccines into national immunization programs; we reviewed one decade of their experience with rotavirus vaccination.We systematically reviewed manuscripts published January 1990-January 2018 to assess rotavirus vaccine effectiveness (VE) via meta-analysis; describe trends in rotavirus and acute gastroenteritis (AGE)-associated hospitalizations and mortality before and after vaccine introduction; and estimate annual hospitalizations and deaths averted by rotavirus vaccination in Latin American and Caribbean children5 years. Rotavirus vaccines demonstrated VE against rotavirus hospitalization of 76% (95% CI: 58-87) in low-mortality countries and 67% (95% CI: 54-76) in high-mortality countries for children1 year of age. Reductions of 64.0% (interquartile range (IQR): 49.9-69.2) were observed in rotavirus hospitalizations, 32.8% (IQR 29.0-40.3) in AGE hospitalizations, and 53.5% (IQR: 40.4-57.1) in AGE-related mortalities in children5 years. In 2015, an estimated 125,000 rotavirus-associated hospitalizations and 800 rotavirus-related deaths were prevented in countries that implemented rotavirus vaccines.Rotavirus vaccines remain an effective tool against diarrheal disease. The continued success of rotavirus vaccines provides evidence for adoption in Latin American and Caribbean countries that have not yet introduced it, and improvement within those with low coverage.

Background Rotavirus vaccine was planned to be introduced in the National Immunization Program of Myanmar in 2020. Reported potential association of a small increased risk of intussusception after rotavirus vaccination in some countries is a major safety concern and it is mandatory to collect baseline information before vaccine introduction. Methods Retrospective study reviewed medical records of intussusception cases for past 3 years (2015–2018) and prospective, active study was conducted from August 2018 to January 2020 at three tertiary children hospitals where pediatric surgical facility is present. Brighton Level 1 Criteria was used for confirmation of intussusception among children 3days after onset) is significantly associated with requirement of surgery (61/85, 71.8%), which in turn is significantly associated with longer hospital stay (296/452, 65.5%) (p < 0.05). Conclusions Intussusception occurrence is most frequent between 5-7 months age group which is old enough to be vaccinated under the schedule that has now been introduced in Myanmar. More than half of the cases were treated by surgery and late arrival to hospital enhances requirement of surgery and poor outcome. Findings of this baseline surveillance provide important facts for public health officials in balancing risks and benefits of rotavirus vaccine introduction, defining targeted age and dosage scheduling and facilitate monitoring system in post-vaccination., Intussusception, baseline surveillance, rotavirus vaccination, Myanmar.

Using nationwide data from the Health Insurance Review and Assessment service, we assessed the impact of rotavirus vaccines, introduced in South Korea, in 2007, on changes in the prevalence of factors (age, sex, and geographic location) associated with rotavirus gastroenteritis (RVGE) and rotavirus-associated benign convulsions with mild gastroenteritis (RaCwG). We analyzed health records of children younger than 3 years who visited clinical facilities and were diagnosed with RVGE or RaCwG between 2007 and 2019. The annual mid-year population (MYP) was obtained from the Korean Statistical Information Service. The annual prevalence of RVGE, RaCwG and associated factors were statistically analyzed. Overall, 219,686, and 4032, children were confirmed to have RVGE and RaCwG, respectively. Although the annual prevalence of RVGE decreased significantly, that of RaCwG did not. The annual ratio of RaCwG to RVGE was significantly high. Compared to the prevalence of RVGE, the prevalence of RaCwG was significantly lower in rural areas. The age of RaCwG patients was significantly lower than that of the MYP and that of RVGE patients. The decrease in the number of RaCwG patients after rotavirus vaccination was not as pronounced as the decrease in the number of RVGE patients.

Background: Rotavirus is a leading cause of viral acute gastroenteritis (AGE) in infants. Neonates hospitalized in neonatal intensive care units (NICUs) are at risk of rotavirus infections with severe outcomes. The administration of rotavirus vaccines is only recommended, in the United States and Canada, upon discharge from the NICU despite rotavirus vaccine being proven safe and effective in these populations, due to risks of live-attenuated vaccine administration in immunocompromised patients and theoretical risks of rotavirus vaccines strains shedding and transmission. We summarized recent evidence regarding rotavirus vaccines administration in the NICU setting and safety of rotavirus vaccines in preterm infants. Methods: We conducted a rapid review of the literature from the past 10 years, searching Medline and Embase, including all study types except reviews, reporting on rotavirus vaccine 1 and rotavirus vaccine 5; NICU setting; shedding or transmission; and/or safety in preterm. One reviewer performed data extraction and quality assessment. Results: In total, 31 articles were analyzed. Vaccine-derived virus shedding following rotavirus vaccination existed for nearly all infants, mostly during the first week after dose 1, with rare transmission described only in the household setting. No case of transmission in the NICU was reported. Adverse events were mild to moderate, occurring in 10%–60% of vaccinated infants. Extreme premature infants or with underlying gastrointestinal failure requiring surgery presented more severe adverse events. Conclusions: Recommendations regarding rotavirus vaccine administration in the NICU should be reassessed in light of the relative safety and absence of transmission of rotavirus vaccine strains in the NICU.Funding: NoneDisclosures: Sicard Mélanie: I reference the use of rotavirus vaccines in the NICU setting, which is not recommended; I discuss possible reassessment of these recommendations.

Rotavirus is the leading cause of vaccine-preventable diarrhea among children under 5 globally. Rotavirus vaccination has been shown to prevent severe rotavirus infections with varying efficacy and effectiveness by region.We sought to generate updated region-specific estimates of rotavirus vaccine efficacy and effectiveness. We systematically reviewed published vaccine efficacy and effectiveness studies to assess the region-specific effect of rotavirus vaccination on select diarrheal morbidity and mortality outcomes in children under 5 years of age. We employed meta-analytic methods to generate pooled effect sizes by Millennium Development Goal region.Rotavirus vaccination was both efficacious and effective in preventing rotavirus diarrhea, severe rotavirus diarrhea and rotavirus hospitalizations among children under 5 across all regions represented by the 48 included studies. Efficacy against severe rotavirus diarrhea ranged from 90.6% [95% confidence interval (CI): 82.3-95.0] in the developed region to 88.4% (95% CI: 67.1-95.9) in Eastern/Southeastern Asia, 79.6% (95% CI: 71.3-85.5) in Latin America and the Caribbean, 50.0% (95% CI: 34.4-61.9) in Southern Asia and 46.1% (95% CI: 29.1-59.1) in sub-Saharan Africa. Region-specific effectiveness followed a similar pattern. There was also evidence of vaccine efficacy against severe diarrhea and diarrheal hospitalizations.Our findings confirm the protective efficacy and effectiveness of rotavirus vaccination against rotavirus diarrheal outcomes among children under 5 globally.

Background To minimise vaccine-associated risk of intussusception following rotavirus vaccination, Norway adopted very strict age limits for initiating and completing the vaccine series at the time rotavirus vaccination was included in the national immunisation programme, October 2014. Although Norway has a high coverage for routine childhood vaccines, these stringent age limits could negatively affect rotavirus coverage. We documented the status and impact of rotavirus vaccination on other infant vaccines during the first year after its introduction. Methods We used individual vaccination data from the national immunisation register to calculate coverage for rotavirus and other vaccines and examine adherence with the recommended schedules. We identified factors associated with completing the full rotavirus series by performing multiple logistic regression analyses. We also evaluated potential changes in uptake and timeliness of other routine vaccines after the introduction of rotavirus vaccine using the Kaplan-Meier method. Results The national coverage for rotavirus vaccine achieved a year after the introduction was 89% for one dose and 82% for two doses, respectively. Among fully rotavirus-vaccinated children, 98% received both doses within the upper age limit and 90% received both doses according to the recommended schedule. The child’s age at the initiation of rotavirus series and being vaccinated with diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b (DTaP/IPV/Hib) and pneumococcal vaccines were the strongest predictors of completing the full rotavirus series. No major changes in uptake and timeliness of other paediatric vaccines were observed after introduction of rotavirus vaccine. Conclusions Norway achieved a high national coverage and excellent adherence with the strict age limits for rotavirus vaccine administration during the first year of introduction, indicating robustness of the national immunisation programme. Rotavirus vaccination did not impact coverage or timeliness of other infant vaccines.

Background and objective: Rotavirus gastroenteritis is the most common cause of acute dehydrating diarrhoea among children younger than five years and globally the most important cause of severe diarrhea in this age group. Most children acquire rotavirus infection before they turn two years of age. Rotavirus vaccination can prevent rotavirus infection. This study aimed to assess healthcare providers' knowledge regarding rotavirus vaccine. Methods: A cross-sectional descriptive study was conducted on 100 healthcare providers at four healthcare centers (Azady, Tayrawa, Mala Fandi and Zhyian), during July to August 2014. Data were collected through the use self-reporting questionnaire format, which was developed for the purpose of the study. A socio-demographic sheet was also constructed to determine characteristics of the subjects. Results: Most of the healthcare providers were in the‎ age group 33-42 years old (31%), 51%, were male, 80% were married, 56% were graduated from the institute, half of them had work experience between 2-11 years and 29% were working in ‎vaccination room. Fifty-four (54%) of healthcare providers had average knowledge while 24 (24%) and 22 (22%) of them had a poor and good knowledge, respectively‎. Conclusion: More than half of healthcare providers had average knowledge regarding rotavirus vaccine

This study describes epidemiological trends for acute rotavirus gastroenteritis (RVGE) in Belgium in children aged

The epidemiology of naturally occurring intussusception is known to increase significantly between the ages of 3 and 8 months. Post-licensure studies have reported a fivefold and twofold increase in intussusception in the first week after the first dose and second dose, respectively, of current rotavirus vaccines (RVs).We carried out a public health risk analysis to model the impact of age at first vaccination in relation to rotavirus vaccination and risk of intussusception in infants.We created a static model for a birth cohort followed until 1 year old to estimate the number of excess intussusception hospitalizations which could be caused by three different infant rotavirus vaccination schedules. A relative risk of 5.45 in the first 7 days after the first dose and 1.75 in the first 7 days after the second dose was used in the model.We estimated that the risk of intussusception would be the lowest at about 1 in 49,000 if both first and second dose RVs were given at3 months of age followed by 1 in 41,000 if first dose RVs were given at3 months and second dose RVs were given at 3-5 months. It would be highest at about 1 in 11,000 if infants received both doses when3 months old.Our epidemiological example illustrates the importance of ensuring that the first two doses of RVs are administered in infants3 months old whenever possible to minimize the risk of intussusception as an adverse event following rotavirus vaccination.

Two rotavirus vaccines have been licensed in >100 countries worldwide since 2006. As of October 2105 these vaccines have been implemented in the national immunization programs of 79 countries including 36 low-income countries that are eligible for support for vaccine purchase from Gavi the Vaccine Alliance. Rotavirus vaccines were initially introduced in Australia and countries of the Americas and Europe after completion of successful clinical trials in these regions and the impact of routine vaccination in reducing the health burden of severe childhood gastroenteritis in these regions has been well documented. Because of concerns around the performance of orally administered rotavirus vaccines in developing countries vaccine implementation in these settings only began after additional clinical trials were completed and the World Health Organization issued a global recommendation for use of rotavirus vaccines in 2009. This supplementary issue of Clinical Infectious Diseases includes a collection of articles describing the impact and effectiveness of routine rotavirus vaccination in developing countries that were among the early adopters of rotavirus vaccine. The data highlight the benefits of vaccination and should provide valuable evidence to sustain vaccine use in these countries and encourage other countries to adopt routine rotavirus vaccination to reduce the health burden of severe childhood gastroenteritis. (c) The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions e-mail journals.permissions@oup.com.

Objetivos: Pretendemos conhecer os fatores associados à não realização e as recomendações do médico de medicina geral e familiar (MGF) e do pediatra acerca destas vacinas. Tipo de estudo: observacional, transversal, descritivo. Local: USF da zona norte do País (Braga - USF de Ruães). População: Crianças com idades compreendidas entre os 2 e os 4 anos de idade; pediatras e MGF de Braga. Métodos: Consulta do processo clínico eletrónico da criança juntamente com um questionário realizado por via telefónica, respondido pelos pais ou encarregados de educação, no período de agosto de 2014 a janeiro de 2015. Para avaliação das recomendações dos médicos MGF e pediatra foi aplicado um questionário eletrónico, de resposta online, a médicos de pediatria e MGF. Os dados foram analisados com recurso ao programa Statistical Package for the Social Sciences (SPSS®, Chicago, IL, USA), versão 17.0 para Microsoft Windows®. Resultados: Amostra de 180 crianças, dos 2-4 anos de idade. A taxa de cobertura vacinal contra Streptococcus pneumoniae 13-valente foi de 81,7%. Não se encontrou relação estatisticamente significativa entre o desemprego e a não realização das vacinas extra-PNV. Verificamos uma maior vacinação contra Neisseria meningitidis do serogrupo B e contra o vírus da hepatite A (VHA) na ausência de insuficiência económica (p value de Fisher=0,008 e p=0,046, respetivamente). Verificou-se uma associação entre a realização da vacina contra o rotavírus e frequência de infantário (p=0,029). Observou-se também uma associação estatisticamente significativa entre as crianças cuja escolaridade do pai ou da mãe era licenciatura/bacharelato e a realização das vacinas contra o rotavírus e anti-VHA. O elemento informador das vacinas extra-PNV foi o médico de família em 46%. A realização de todas as vacinas extra-PNV (exceto gripe sazonal) foi superior nas crianças que eram ou tinham sido seguidas por pediatra. Quanto ao questionário aplicado aos médicos obtivemos uma amostra total de 30 MGF e 30 pediatras. Revelou que a vacina mais aconselhada em ambos os grupos foi a contra Streptococcus pneumoniae. A ordem de importância atribuída às vacinas extra-PNV foi a mesma entre os dois grupos de profissionais. A principal razão para nem sempre aconselharem a vacina contra Streptococcus pneumoniae foi o preço. Conclusões: Para a maioria destas vacinas, desemprego e insuficiência económica não são fundamentais na decisão de não vacinar, o que salienta o esforço por parte dos pais em garantir a vacinação. É urgente a tomada de medidas que permitam um acesso mais justo às diferentes opções vacinais. Aims: We aim to know the factors associated with compliance with recommendations for vaccination of children outside the national vaccination plan among patients of general practitioners (GP) and pediatricians. Type of Study: Cross-sectional study. Local: Ruães Family Health Unit (Cávado I Group of Health Centres). Population: Children aged 2-4 years old and pediatricians and GP from Braga. Methods: Electronic health records of children were studied. A questionnaire was administered by telephone interview of parents or guardians from August 2014 to January 2015. We used an electronic questionnaire with online response by GP and pediatricians to evaluate GP and pediatricians' compliance with recommendations. Data were analyzed using the Statistical Package for Social Sciences (SPSS, Chicago, IL, USA), version 17.0 for Microsoft Windows®. Results: We selected a sample of 180 children, aged of 2-4 years old. Vaccination coverage against Streptococcus pneumoniae was 81.7%. There was no statistically significant association between unemployment of the parent or guardian and non-compliance vaccines outside the plan. We found higher rates of vaccination against Neisseria meningitidis serogroup B and against hepatitis A virus (HAV) in the absence of economic difficulties (p value of Fisher=0.008 and p=0.046, respectively). Association between rotavirus vaccination and kindergarten attendance was statistically significant (p=0.029). There was also a statistically significant association between university-level education of the father or mother and rotavirus and hepatitis A vaccination. Vaccines outside the national plan were recommended by the family doctor in 46% of cases. Vaccination with vaccines outside the national plan was higher in children who were or had been followed by pediatrician (except flu vaccine). The sample of 30 GP and 30 pediatricians revealed that the most commonly recommended vaccine was that against Streptococcus pneumoniae. The order of importance attributed to vaccines was the same in both groups of professionals. The main reason for not recommending the Streptococcus pneumoniae vaccine was its price. Discussion and conclusions: For most vaccines, unemployment and economic difficulties are not decisive factors in the decision not to vaccinate. This emphasizes the parents' role in vaccination. Measures are required to ensure a fair access to different vaccine options.

Producción Científica, Rotavirus vaccines (RV) have decreased the infant morbidity and mortality in countries that included RV in their national schedule. Rotavirus vaccination is recommended by the Spanish Society of Pediatrics; however, Spain, as most countries in Europe, has authorized commercialization but not included RV in its national vaccination program. We assessed the impact of RV on the rotavirus hospitalization rate through an interrupted time series analysis. There was a 46.8% (95% CI: 29.3–60.2) decrease on the rotavirus hospitalizations rate in the study region after RV commercialization in 2006. Currently there is limited evidence about the impact of RV in Europe, especially among countries not offering systematic vaccination in their national schedule. Documentation of RV coverage, effectiveness and impact is urgently needed in these countries.

In Canada, rotavirus vaccine is recommended for all infants, but not all provinces/territories have publicly funded programs. We compared public and healthcare provider (HCP) knowledge, attitudes, beliefs, and behaviors in a province with a public health nurse-delivered, publicly funded rotavirus vaccination program to a province with a publicly funded, physician-delivered program. A third province with no vaccination program acted as a control.Information about knowledge, attitudes, beliefs, and behaviors of parents whose children were eligible for the universal program and healthcare providers responsible for administering the vaccine were collected through the use of two validated surveys distributed in public health clinics, physicians' offices, and via e-mail. Early and postvaccine-program survey results were compared.A total of 722 early implementation and 709 postimplementation parent surveys and 180 early and 141 postimplementation HCP surveys were analyzed. HCP and public attitudes toward rotavirus vaccination were generally positive and didn't change over time. More parents postprogram were aware of the NACI recommendation and the vaccination program and reported that their healthcare provider discussed rotavirus infection and vaccine with them. Prior to the program across all sites, more physicians than nurses were aware of the national recommendation regarding rotavirus vaccine. In the postprogram survey, however, more nurses were aware of the national recommendation and their provincial universal rotavirus vaccination program. Nurses had higher knowledge scores than physicians in the postprogram survey (p0.001). Parents of young infants were also more knowledgeable about rotavirus and rotavirus vaccine in the two areas where universal programs were in place (p0.001).Implementation of a universal rotavirus vaccination program was associated with an increase in knowledge and more positive attitudes toward rotavirus vaccine amongst parents of eligible infants. Nurses involved in a public health-delivered vaccination program were more knowledgeable and had more positive attitudes toward the vaccine than physicians in a jurisdiction where vaccine was physician-delivered.

Introduction Rotavirus (RV) vaccination was introduced in Belgium in 2006. With the high uptake it had (>85%), a sharp decline in hospitalizations was observed during the first years after vaccine introduction. The objective of this study was to investigate whether this decline was maintained and to simulate projections. Methods The Rotavirus Belgium Impact Study allowed an analysis of the RV vaccine impact amongst children in 11 hospitals in Belgium over a 9-year period (2005–2013) with 2 years pre- and 7 years post-vaccine introduction. Results were compared by year and by subsequent birth cohort aging up to 5 years. The two different analysis methods helped dismantling the different (direct and indirect) effects of vaccine protection to simulate future hospitalization trends. Results During the whole observation period, 40,552 RV detection tests were performed of which 5832 were positive (14.4%). After RV vaccine introduction, a significant reduction in number of tests performed (−38%) was combined with a dramatic drop in numbers of positive tests (−76.6%). The decreases were spectacular during the first two years of vaccine introduction; after that period, the decrease flattened. Cross-sectional comparison with cohort data showed that the initial drop was heavily influenced by the herd effect of the vaccine. Cohort analysis demonstrated a low rate of residual disease over time, suggesting another infection source other than the child population. Conclusion The residual disease will be maintained in the community when a same vaccination strategy is continued over time, starting vaccination of children only at 6 weeks’ time. Funding GlaxoSmithKline Biologicals SA. Trial registration ClinicalTrials.gov identifier, NCT01563146. Electronic supplementary material The online version of this article (doi:10.1007/s40121-015-0099-1) contains supplementary material, which is available to authorized users.

Using real-time RT-PCR, we screened stool samples from children aged &lt, 5 years presenting with diarrhea and admitted to Kilifi County Hospital, coastal Kenya, pre- (2003 and 2013) and post-rotavirus vaccine introduction (2016 and 2019) for five viruses, namely rotavirus group A (RVA), norovirus GII, adenovirus, astrovirus and sapovirus. Of the 984 samples analyzed, at least one virus was detected in 401 (40.8%) patients. Post rotavirus vaccine introduction, the prevalence of RVA decreased (23.3% vs. 13.8%, p &lt, 0.001) while that of norovirus GII increased (6.6% vs. 10.9%, p = 0.023). The prevalence of adenovirus, astrovirus and sapovirus remained statistically unchanged between the two periods: 9.9% vs. 14.2%, 2.4% vs. 3.2 %, 4.6% vs. 2.6%, (p = 0.053, 0.585 and 0.133), respectively. The median age of diarrhea cases was higher post vaccine introduction (12.5 months, interquartile range (IQR): 7.9&ndash, 21 vs. 11.2 months pre-introduction, IQR: 6.8&ndash, 16.5, p &lt, 0.001). In this setting, RVA and adenovirus cases peaked in the dry months while norovirus GII and sapovirus peaked in the rainy season. Astrovirus did not display clear seasonality. In conclusion, following rotavirus vaccine introduction, we found a significant reduction in the prevalence of RVA in coastal Kenya but an increase in norovirus GII prevalence in hospitalized children.

Background and objective Since 2013, a biennial rotavirus pattern has emerged in the Netherlands with alternating high and low endemic years and a nearly 50% reduction in rotavirus hospitalization rates overall, while infant rotavirus vaccination has remained below 1% throughout. As the rotavirus vaccination cost-effectiveness and risk-benefit ratio in high-income settings is highly influenced by the total rotavirus disease burden, we re-evaluated two infant vaccination strategies, taking into account this recent change in rotavirus epidemiology. Methods We used updated rotavirus disease burden estimates derived from (active) surveillance to evaluate (1) a targeted strategy with selective vaccination of infants with medical risk conditions (prematurity, low birth weight, or congenital conditions) and (2) universal vaccination including all infants. In addition, we added herd protection as well as vaccine-induced intussusception risk to our previous cost-effectiveness model. An age- and risk-group structured, discrete-time event, stochastic multi-cohort model of the Dutch pediatric population was used to estimate the costs and effects of each vaccination strategy. Results The targeted vaccination was cost-saving under all scenarios tested from both the healthcare payer and societal perspective at rotavirus vaccine market prices (€135/child). The cost-effectiveness ratio for universal vaccination was €51,277 at the assumed vaccine price of €75/child, using a societal perspective and 3% discount rates. Universal vaccination became cost-neutral at €32/child. At an assumed vaccine-induced intussusception rate of 1/50,000, an estimated 1707 hospitalizations and 21 fatal rotavirus cases were averted by targeted vaccination per vaccine-induced intussusception case. Applying universal vaccination, an additional 571 hospitalizations and

BACKGROUND: Diarrheal diseases are the third leading cause of disease and death in children younger than 5 years of age in Africa and were responsible for an estimated 30 million cases of severe diarrhea (95% credible interval, 27 million to 33 million) and 330,000 deaths (95% credible interval, 270,000 to 380,000) in 2015. The development of targeted approaches to address this burden has been hampered by a paucity of comprehensive, fine-scale estimates of diarrhea-related disease and death among and within countries. METHODS: We produced annual estimates of the prevalence and incidence of diarrhea and diarrhea-related mortality with high geographic detail (5 km2) across Africa from 2000 through 2015. Estimates were created with the use of Bayesian geostatistical techniques and were calibrated to the results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016. RESULTS: The results revealed geographic inequality with regard to diarrhea risk in Africa. Of the estimated 330,000 childhood deaths that were attributable to diarrhea in 2015, more than 50% occurred in 55 of the 782 first-level administrative subdivisions (e.g., states). In 2015, mortality rates among first-level administrative subdivisions in Nigeria differed by up to a factor of 6. The case fatality rates were highly varied at the national level across Africa, with the highest values observed in Benin, Lesotho, Mali, Nigeria, and Sierra Leone. CONCLUSIONS: Our findings showed concentrated areas of diarrheal disease and diarrhea-related death in countries that had a consistently high burden as well as in countries that had considerable national-level reductions in diarrhea burden. (Funded by the Bill and Melinda Gates Foundation.).

We report the first case, to our knowledge, in Italy, of a severe combined immunodeficiency patient with a persistent rotavirus infection due to a vaccine derived strain. Rotavirus was detected by enzyme immunoassays and RT-PCR in stool specimens for five months. The persistent infection was resolved after complete immune reconstitution achieved by hematopoietic stem cell transplantation. This case underlines the importance of neonatal SCID_screening.

Oral rotavirus vaccines have consistently underperformed in low-income countries. In this issue of Cell Host & Microbe,Harris et al. (2018b) explore whether vaccine response can be enhanced via antibiotic-mediated modification of the bacterial microbiota.

[no abstract]

Background Before the introduction of rotavirus vaccine in the United States in 2006, rotavirus infection was the leading cause of severe gastroenteritis among US children. Methods To evaluate the long-term impact of rotavirus vaccination on disease burden in the United States, CDC analyzed national laboratory testing data for rotavirus from laboratories participating in CDC’s National Respiratory and Enteric Viruses Surveillance System (NREVSS) during the pre- (2000–2006) and post-vaccine (2007–2018) periods. Results Nationally, the median annual percentage of positive rotavirus tests declined from 25.6% (range: 25.2–29.4%) in the pre-vaccine era to 6.1% (range: 2.6–11.1%) in the post-vaccine period. When comparing the pre- and post-vaccine era, the annual peak in rotavirus positivity declined from a median of 43.1% (range: 43.8–56.3%) to a median 14.0% (range: 4.8–27.3%) while the season duration was reduced from a median of 26 weeks (range: 23–27 weeks) to 9 weeks (range: 0–18 weeks). In the post-vaccine period, a biennial pattern emerged with alternating years of low and high rotavirus activity. Conclusion The implementation of rotavirus vaccine has dramatically reduced the disease burden and altered seasonal patterns of rotavirus in the United States; these changes have been sustained over 11 post-vaccine introduction seasons. Disclosures All Authors: No reported Disclosures.

Giriş: Rotavirüs bütün dünyada yenidoğan bebek ve küçük çocuklarda görülen gastroenteritlerin en yaygın ve önemli sebeplerindendir. Rotavirüsinfeksiyonuna karşı başlıca korunma yöntemi aşılamadır. Bu çalışmanın amacı 0–2 yaş çocuğu olan ailelerin sosyodemografik özellikleri de göz önünde bulundurularak, Rotavirüs aşısı hakkındaki bilgi düzeylerini ve aşının uygulanmasına karşı tutumlarını saptamaktır. Yöntemler: Çalışma, Nisan 2011- Nisan 2012 tarihleri arasında Ankara Eğitim ve Araştırma Hastanesi Çocuk Hastalıkları Polikliniği ve Çocuk Acil Servisi’ne müracaat eden ailelere anket uygulanarak gerçekleştirildi. İstatistiksel analizler SPSS 19 programı ile yapıldı. Bulgular: Toplam 1005 ebeveyne anket uygulandı. 857 (%85,3) katılımcının Rotavirüs aşısını bilmediği, 873 (%86,9) kaılımcının da Rotavirüsten haberdar olmadığı saptandı. Rotavirüs aşısını bilen 148 katılımcının sadece 36’sı çocuğuna aşıyı yaptırdığını belirtti. Sonuç: Bu araştırmada, Rotavirüs aşısının bilinirliğinin ve uygulanma sıklığının beklenenden çok düşük olduğu saptandı. Aşılamada ailelerin sosyodemografik özelliklerinin ve hekimlerin tutumlarının etkili olduğu söylenebilir. Aşılama oranlarının artırılmasında başta hekimler olmak üzere sağlık personelinin rotavirus aşılaması konusunda ebeveynleri bilgilendirmesi önem taşımaktadır., Background: Rotavirus is the most common and important cause ofgastroenteritis in the newborn and young children worldwide. Vaccination is themain way to prevent Rotavirus infection. The aim of the present study is todetermine the level of knowledge about the Rotavirus vaccine and attitudestowards the vaccination in families having children between the ages of 0 and 2taking the socio-demographic characteristics into account. Methods: The study was carried out by applying a questionnaire tothe parents who admitted to the Pediatrics Outpatient Clinic and PediatricEmergency Department of Ankara Research and Training Hospital between April2011 and April 2012. Statistical analyses were performed by using the SPSS 19program. Results: A total of 1005parents were surveyed; 857 (85.3%) participants were not aware of Rotavirusvaccination and 873 (86.9%) were not aware of Rotavirus. Among 148 participantswho knew Rotavirus vaccination, only 36 had vaccination. Conclusion: Awareness of Rotavirus vaccine and its frequency ofapplication were found much lower than expected. Socio-demographiccharacteristics of the parents and the attitudes of the physicians may besuggested to affect the frequency of vaccination. In order to increasevaccination rates, it is important for health care professionals and especiallyfor physicians to inform the parents about Rotavirus vaccination.

Postlicensure evaluations have identified an association between rotavirus vaccination and intussusception in several high- and middle-income countries. We assessed the association between monovalent human rotavirus vaccine and intussusception in lower-income sub-Saharan African countries.Using active surveillance, we enrolled patients from seven countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) who had intussusception that met international (Brighton Collaboration level 1) criteria. Rotavirus vaccination status was confirmed by review of the vaccine card or clinic records. The risk of intussusception within 1 to 7 days and 8 to 21 days after vaccination among infants 28 to 245 days of age was assessed by means of the self-controlled case-series method.Data on 717 infants who had intussusception and confirmed vaccination status were analyzed. One case occurred in the 1 to 7 days after dose 1, and 6 cases occurred in the 8 to 21 days after dose 1. Five cases and 16 cases occurred in the 1 to 7 days and 8 to 21 days, respectively, after dose 2. The risk of intussusception in the 1 to 7 days after dose 1 was not higher than the background risk of intussusception (relative incidence [i.e., the incidence during the risk window vs. all other times], 0.25; 95% confidence interval [CI]

The Fifth European Expert Meeting on Rotavirus Vaccination was convened in Utrecht, The Netherlands, in March 2017. The 2-day meeting included invited lectures as well as original oral and poster presentations and brought together experts from 21 countries. Summary findings of the meeting include: Rotavirus vaccination programmes in Europe have resulted in reductions of 60-90% in rotavirus outpatient visits and hospitalizations. Long term trends indicate this impact is sustained over the years. Herd effects, protecting unvaccinated children and neonates too young to be vaccinated have been observed in many European countries. Early evidence now also suggests that rotavirus vaccination may be instrumental in the prevention of celiac disease. Special attention should be given to preterm infants, who may age out of the vaccination window before hospital discharge and to HIV infected children who are at increased risk of severe rotavirus AGE. There is a small but increased risk of IS following rotavirus vaccination and parents should therefore be informed about possible signs and symptoms of IS. New insights in rotavirus genetic susceptibility and interactions with microbiome may open opportunities for interventions to improve protection by vaccination, in particular in LMIC. The development of several novel rotavirus vaccines discussed at the meeting is also promising in this respect.

INTRODUCTION: Rotavirus vaccines protect against the leading cause of severe childhood diarrhoea, and have been introduced in many low-income African countries. The Gambia introduced Rotateq(®) (RV5) into their national immunization program in 2013. We revieweddata from an active rotavirus sentinel surveillancesite for early evidence of vaccine impact. METHODS: We compared rotavirus prevalence in diarrhoeal stool in children< 5 years of age admittedat the Edward Francis Small Teaching Hospital sentinel surveillance site before (2013) andafterRV5 introduction (2015–2016) in the Gambia. The rotavirus-percent positive was separately compared for all diarrhoealhospitalizations and for hospitalizations with severe symptoms. Rotavirus prevalence was compared annually for the pre-vaccine year of 2013 with post-vaccine years of 2015 and 2016 using chi-square or Fisher’s exact tests and the p-value to establish significant relationship was set at p < 0.05. All analyses were completed in SAS 9.3 (SAS Analytics, North Carolina). RESULTS: Rotavirus prevalence among all diarrhoeahospitalizations decreased from 22% in 2013 to 11% in 2015 (p = 0.04), while remaining unchanged in 2016 (18%, p = 0.56). For hospitalizations that were clinically severe and/or treated with intravenous fluids (mean of 46 per year), the rotavirus prevalence decreased from 33% in 2013 to 8% in 2015 (p = 0.04), and to 15% in 2016 (p = 0.08). The children with age

BackgroundRotavirus disease rates dramatically declined among children MethodsData from the Healthcare Cost and Utilization Project State Inpatient Databases were used to conduct a time-series analysis of monthly hospital discharges across age groups for acute gastroenteritis and rotavirus from 2000 to 2013. Rate ratios were calculated comparing prevaccine and postvaccine eras.ResultsFollowing vaccine introduction, a decrease in rotavirus hospitalizations occurred with a shift toward biennial patterns across all ages. The 0–4-year age group experienced the largest decrease in rotavirus hospitalizations (rate ratio, 0.14; 95% confidence interval, .09–.23). The 5–19-year and 20–59-year age groups experienced significant declines in rotavirus hospitalization rates overall; the even postvaccine calendar years were characterized by progressively lower rates, and the odd postvaccine years were associated with reductions in rates that diminished over time. Those aged ≥60 years experienced the smallest change in rotavirus hospitalization rates overall, with significant reductions in even postvaccine years compared with prevaccine years (rate ratio, 0.51; 95% confidence interval, .39–.66).ConclusionsIndirect impacts of infant rotavirus vaccination are apparent in the emergence of biennial patterns in rotavirus hospitalizations that extend to all age groups ineligible for vaccination. These observations are consistent with the notion that young children are of primary importance in disease transmission and that the initial postvaccine period of dramatic population-wide impacts will be followed by more complex incidence patterns across the age range in the long term.

OBJECTIVES A two-dose oral monovalent rotavirus vaccine (RV1) was introduced into the Kenyan National Immunization Program in July 2014. We assessed trends in hospitalisation for rotavirus-specific acute gastroenteritis (AGE) and strain distribution among children

BACKGROUND: The effectiveness of rotavirus vaccines in low and very low birth weight infants (LBW and VLBW) weighing

INTRODUCTION: In preparation for the introduction of a rotavirus vaccine into the routine immunization program of Bangladesh in 2018, we report data and highlight evolving genotypes from five years of active hospital-based rotavirus surveillance which began in July 2012. METHODS: We enrolled and collected fresh stool from every fourth child < 5 years admitted with acute gastroenteritis (AGE) at 8 participating surveillance hospitals. Rotavirus infections were detected by enzyme immune assay. Twenty-five percent of rotavirus isolates were genotyped using reverse transcription polymerase chain reaction. RESULTS: We found that 64% (4832/7562) of children < 5 years of age admitted with AGE had evidence of rotavirus infection. The majority (57%) of patients with rotavirus infection were

INTRODUCTION: Ghana introduced monovalent rotavirus vaccine in April 2012. We sought to determine the long-term impact of routine rotavirus vaccination on rotavirus gastroenteritis hospitalizations in Ghana during the first 4 years following rotavirus vaccine introduction. METHODS: Active sentinel surveillance for acute gastroenteritis hospitalizations among children

Introduction: Prior to 2006, nearly every U.S. child was infected with rotavirus by 5 years of age, and rotavirus was the leading cause of severe childhood gastroenteritis. In February 2006 and June 2008, the Advisory Committee on Immunization Practices recommended a live attenuated pentavalent rotavirus vaccine (RV5) and a monovalent rotavirus vaccine (RV1), respectively, for routine vaccination of infants in the United States. Areas covered: We reviewed U.S. data on coverage, vaccine effectiveness (VE), and vaccine impact from 2006 to 2017. National rotavirus vaccine coverage estimates increased since vaccine introduction but plateaued at 71–75% in 2013–2015, a level 15–20% lower than that of other routine childhood vaccines. Pooled VE of full series RV5 and RV1 against rotavirus-associated hospitalizations and emergency department visits were 84% (95% CI: 80–87%) and 83% (95% CI: 72–89%), respectively. Vaccine introduction resulted in a median decline in rotavirus-associated hospitalizations and emergency department visits of 80% and 57%, respectively, along with indirect protection of unvaccinated age groups and a decrease in health-care costs. A biennial pattern in rotavirus detection emerged post-vaccine implementation. Expert Commentary: The increasing use of rotavirus vaccines has substantially diminished the burden and changed the epidemiology of rotavirus disease in U.S. children; efforts to increase rotavirus vaccine coverage should continue.

Background and aim of the works:Rotavirus (RV) is considered the main cause of gastroenteritis in children from 0 to 59 months and vaccination represents the only strategy to prevent hospitalizations due to RV. In 2013 Sicilian Region introduced universal RV vaccination for all newborns. The present study aims to estimate the reduction rotavirus gastroenteritis (RVGE) hospitalization rates among Sicilian children and their relations with vaccination coverages of the nine Sicilian Local Health Units (LHUs). Methods: Were analyzed hospital discharge records including a diagnosis of RVGE occurred from January 2009 to December 2017 in hospitalized children aged 0 to 59 months, residents in Sicily. Were reported data on complete RV vaccination cycles among Sicilian children under 12 months of age (vaccination coverage). Results: A 49.2% overall reduction of RVGE hospitalization rates was reported after RV vaccination introduction. A more considerable reduction of hospitalization rates was observed among children aged 0 to 11 months (-61.4%), followed by children aged 12-23 months (-51.2%) and 24-35 months (-48.8%). In all the nine Sicilian Local Health Units (LHUs), a reduction of RVGE hospitalization rates was observed after RV vaccine implementation. Conclusions: This study demonstrated the significant impact of RV vaccination on RVGE hospitalization rates in Sicily, especially among children aged 0 to 23 months. The reduction in RVGE hospitalization rates observed in the Sicilian LHUs after universal vaccination program implementation, were generally higher or consistent with average vaccination coverage reported from 2013 to 2017. (www.actabiomedica.it)

International audience; With social policies increasingly directed toward enhancing equity through health programs, it is important that methods for estimating the health and economic benefits of these programs by subpopulation be developed, to assess both equity concerns and the programs’ total impact. We estimated the differential health impact (measured as the number of deaths averted) and household economic impact (measured as the number of cases of medical impoverishment averted) of ten antigens and their corresponding vaccines across income quintiles for forty-one low- and middle-income countries. Our analysis indicated that benefits across these vaccines would accrue predominantly in the lowest income quintiles. Policy makers should be informed about the large health and economic distributional impact that vaccines could have, and they should view vaccination policies as potentially important channels for improving health equity. Our results provide insight into the distribution of vaccine-preventable diseases and the health benefits associated with their prevention.

Diarrhoea is one of the world's leading killers of children, and globally, rotavirus is the most common cause of severe diarrhoea among under five children. In Bangladesh, rotavirus kills nearly 6,000 under five children in each year. To reduce the burden of childhood rotavirus diseases, universal rotavirus vaccination is recommended by World Health Organization. The objective of this study is to assess the cost-effectiveness of introducing universal childhood rotavirus vaccination with the newly developed ROTAVAC vaccine in national Expanded Programme of Immunization in Bangladesh. We developed a decision model to examine the potential impact of vaccination in Bangladesh and to examine the effect if the vaccination is applied in the nationwide immunization program schedule. Introduction of childhood universal rotavirus vaccination in Bangladesh scenario appears as highly cost-effective and would offer substantial future benefits for the young population if vaccinated today. The cost per DALY averted of introducing the rotavirus vaccine compared to status quo is approximately US$ 740.27 and US$ 728.67 per DALY averted from the health system and societal perspective respectively which is “very cost-effective” using GDP threshold level according to World Health Organization definition. The results of this analysis seek to contribute to an evidence-based recommendation about the introduction of universal rotavirus vaccination in national Expanded Programme of Immunization (EPI) in Bangladesh.

There are two internationally available WHO-prequalified oral rotavirus vaccines (Rotarix and RotaTeq), two rotavirus vaccines licensed in India (Rotavac and Rotasiil), one in China (Lanzhou lamb rotavirus vaccine) and one in Vietnam (Rotavin-M1), and several candidates in development. Rotavirus vaccination has been rolled out in Latin American countries and is beginning to be deployed in sub-Saharan African countries but middle- and low-income Asian countries have lagged behind in rotavirus vaccine introduction. We provide a mini-review of the leading newer-generation rotavirus vaccines and compare them with Rotarix and RotaTeq. We discuss how the development and future availability of newer-generation rotavirus vaccines that address the programmatic needs of poorer countries may help scale-up rotavirus vaccination where it is needed.

BACKGROUND: Rotavirus vaccination has reduced diarrhoeal morbidity and mortality globally. The monovalent rotavirus vaccine was introduced into the public immunization program in South Africa (SA) in 2009 and led to approximately 50% reduction in rotavirus hospitalization in young children. The aim of this study was to investigate the rotavirus genotype distribution in SA before and after vaccine introduction. MATERIALS AND METHODS: In addition to pre-vaccine era surveillance conducted from 2002 to 2008 at Dr George Mukhari Hospital (DGM), rotavirus surveillance among children

BACKGROUND Rwanda introduced pentavalent rotavirus vaccine into its national immunization program in 2012. To determine the long-term impact of rotavirus vaccine on disease burden in a high burden setting, we examined trends in rotavirus and all-cause diarrhea hospitalizations in the first four years following rotavirus vaccine introduction. METHODS We used data from an active surveillance system, from a review of pediatric ward registries, and from the Health Management Information System to describe trends in rotavirus and all-cause diarrhea hospitalizations from January 2009 through December 2016. Percent reductions were calculated to compare the number of all-cause and rotavirus diarrhea hospitalizations pre- and post-rotavirus vaccine introduction. RESULTS The proportion of diarrhea hospitalizations due to rotavirus declined by 25-44% among all children

Background In 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. Methods RVA 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. Results Among 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. Conclusions This 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.

Background Antibiotic exposure around the time of rotavirus (RV) immunization has been suggested to diminish immune responses, but data are sparse. Methods We retrospectively analyzed data from a randomized RV vaccine study (NCT01266850) outlined in the Table. Concomitant antibiotic use, defined as receipt of an antibiotic 14 days before or 7 days after RV immunization, was recorded. The primary outcome was RV-specific IgA seroresponse (IgA ≥20 U/mL) by ELISA obtained 1 month after the last dose of RV vaccine and geometric mean titer (GMT) to strain WC3 (RV5 backbone) or strain 89–12 (RV1 backbone). Only subjects who received all scheduled vaccine doses and phlebotomy were included. Data were assessed for homogeneity across vaccine schedule groups, stratified by antibiotic exposure. We examined differences in seroresponse adjusting for treatment group, gender, race, ethnicity, and study site using logistic regression models. Results Of the 1384 immunized children, 1174 (85%) met inclusion criteria. Table: Treatment Allocation and Effect of Antibiotic Exposure on Seroresponses Groups 1 2 3 4 5 Immunization Schedule Rotateq® (RV5) 3 doses N = 206 RV5, RV1, RV1 N = 207 RV5, RV5, RV1N = 194 Rotarix® (RV1) 2 dosesN = 287 RV1, RV5, RV5N = 280 Seroresponse: Antibiotic Exposed 21/25 (84%) 20/20 (100%) 18/22 (82%) 13/15 (87%) 32/32 (100%) Seroresponse: Antibiotic Not-Exposed 167/181 (92%) 168/187 (90%) 158/172 (92%) 209/272 (77%) 238/248 (96%) Nearly 10% (n = 114) of participants were antibiotic exposed; group 4 had the least antibiotic exposure (P = 0.05). No differences in GMT or seroresponses were observed to either WC3 or 89–12 (figure) by antibiotic exposure. In the multivariable logistic regression model, there were no significant differences for gender, race, ethnicity, site, or antibiotic exposure (P-value ≥0.5 for IgA seroresponse). The only observed difference in seroresponses was by RV vaccine group (P < 0.0001). Conclusion Antibiotic administration around the time of RV vaccine did not diminish RV-specific IgA seroresponses observed 1 month after the last RV vaccine dose. Figure: Proportion mounting IgA seroresponse to rotavirus immunization, stratified by antibiotic exposure status Disclosures E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support. C. B. Creech, Pfizer: Grant Investigator, Research grant. Novartis: Grant Investigator, Research grant. A. L. Shane, International Scientific Association of Probiotics and Prebiotics: Member, Reimbursement of travel and lodging for attendance and presentations at international scientific meetings 2016 and prior and support for attendance at meeting at FDA in 2017 to discuss probiotic and prebiotic research. K. Edwards, Novartis: Grant Investigator, Research grant. Novartis: Scientific Advisor, Consulting fee.

ResumenLos diseños de investigación clínica, cuyo propósito es responder preguntas sobre causalidad, se pueden clasificar en relación con cuatro ejes: el número de grupos de estudio, la aplicación de una maniobra experimental, la direccionalidad causa-efecto y la fuente de la que se recaban los datos. Los diseños básicos más utilizados en epidemiología son el ensayo clínico, el estudio de cohortes, el estudio de casos y controles y la encuesta transversal. Este texto pretende facilitar la identificación y comprensión de cada uno de estos diseños mediante ejemplos relacionados con la asociación entre la vacunación con rotavirus y la invaginación intestinal.AbstractDesign of clinical research whose purpose is to answer questions about causality can be classified in relation to four axes: the number of study groups, the implementation of an experimental maneuver, cause-effect directionality and source from which the data are collected. The basic designs used in epidemiology are the clinical trial, the cohort study, the case-control study and the cross-sectional survey. This text aims to facilitate the identification and understanding of each of these designs through examples related to the association between rotavirus vaccination and intussusception.

Background & objectives Preterm infants are at highest risk for severe rotavirus gastroenteritis. While rotavirus vaccination is recommended for age-eligible, clinically stable preterm infants, controversy exists regarding vaccination of these infants during hospitalization. The objectives of this study were to examine tolerance of pentavalent rotavirus vaccination (RV5) among hospitalized infants and nosocomial rotavirus transmission in the neonatal intensive care units (NICU) at two urban hospitals. Methods A retrospective, medical chart review of patients receiving RV5 vaccine was conducted to examine clinical histories of vaccine recipients. Average risk differences of gastrointestinal complications were estimated between the three days prior and up to four weeks following RV5 vaccination. A generalized linear regression model was used to examine the association between days since RV5 administration and daily feeding totals, using fixed effects to account for individual-level clustering. Rates of nosocomial rotavirus from active surveillance were compared between pre- and post-NICU-based vaccination periods. Results From July 1, 2011 to March 30, 2013, RV5 vaccination was initiated for 102 NICU patients. No changes in the average risk of gastrointestinal complications or daily feeding among participants overall were detected following RV5 administration. Rates of nosocomial rotavirus were similar during the periods before and after NICU-based vaccination. Conclusions On average, RV5 appeared to be well tolerated among vaccine recipients, with no increase in nosocomial rotavirus transmission observed following NICU-based rotavirus vaccination. While the benefits of a RV5 NICU-based vaccination program for otherwise eligible preterm infants seem to outweigh the possible risk of vaccine virus transmission, further studies are needed.