BACKGROUND:Rotavirus results in more diarrhoea-related deaths in children under five years than any other single agent in countries with high childhood mortality. It is also a common cause of diarrhoea-related hospital admissions in countries with low childhood mortality. Rotavirus vaccines that have been prequalified by the World Health Organization (WHO) include a monovalent vaccine (RV1; Rotarix, GlaxoSmithKline), a pentavalent vaccine (RV5; RotaTeq, Merck), and, more recently, another monovalent vaccine (Rotavac, Bharat Biotech). OBJECTIVES:To evaluate rotavirus vaccines prequalified by the WHO (RV1, RV5, and Rotavac) for their efficacy and safety in children. SEARCH METHODS:On 4 April 2018 we searched MEDLINE (via PubMed), the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, and BIOSIS. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies and relevant systematic reviews. SELECTION CRITERIA:We selected randomized controlled trials (RCTs) in children comparing rotavirus vaccines prequalified for use by the WHO versus placebo or no intervention. DATA COLLECTION AND ANALYSIS:Two review authors independently assessed trial eligibility and assessed risks of bias. One review author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analysis by country mortality rate and used GRADE to evaluate evidence certainty. MAIN RESULTS:Fifty-five trials met the inclusion criteria and enrolled a total of 216,480 participants. Thirty-six trials (119,114 participants) assessed RV1, 15 trials (88,934 participants) RV5, and four trials (8432 participants) Rotavac. RV1 Children vaccinated and followed up the first year of life In low-mortality countries, RV1 prevents 84% of severe rotavirus diarrhoea cases (RR 0.16, 95% CI 0.09 to 0.26; 43,779 participants, 7 trials; high-certainty evidence), and probably prevents 41% of cases of severe all-cause diarrhoea (RR 0.59, 95% CI 0.47 to 0.74; 28,051 participants, 3 trials; moderate-certainty evidence). In high-mortality countries, RV1 prevents 63% of severe rotavirus diarrhoea cases (RR 0.37, 95% CI 0.23 to 0.60; 6114 participants, 3 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (RR 0.73, 95% CI 0.56 to 0.95; 5639 participants, 2 trials; high-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, RV1 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.14 to 0.23; 36,002 participants, 9 trials; high-certainty evidence), and probably prevents 37% of severe all-cause diarrhoea episodes (rate ratio 0.63, 95% CI 0.56 to 0.71; 39,091 participants, 2 trials; moderate-certainty evidence). In high-mortality countries RV1 probably prevents 35% of severe rotavirus diarrhoea cases (RR 0.65, 95% CI 0.51 to 0.83; 13,768 participants, 2 trials; high-certainty evidence), and 17% of severe all-cause diarrhoea cases (RR 0.83, 95% CI 0.72 to 0.96; 2764 participants, 1 trial; moderate-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.88 95% CI 0.83 to 0.93; high-certainty evidence). There were 30 cases of intussusception reported in 53,032 children after RV1 vaccination and 28 cases in 44,214 children after placebo or no intervention (RR 0.70, 95% CI 0.46 to 1.05; low-certainty evidence). RV5 Children vaccinated and followed up the first year of life In low-mortality countries, RV5 probably prevents 92% of severe rotavirus diarrhoea cases (RR 0.08, 95% CI 0.03 to 0.22; 4132 participants, 5 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 57% of severe rotavirus diarrhoea (RR 0.43, 95% CI 0.29 to 0.62; 5916 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (RR 0.80, 95% CI 0.58 to 1.11; 1 trial, 4085 participants; moderate-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, RV5 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.08 to 0.39; 7318 participants, 4 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 41% of severe rotavirus diarrhoea cases (RR 0.59, 95% CI 0.43 to 0.82; 5885 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (RR 0.85, 95% CI 0.75 to 0.98; 5977 participants, 2 trials; high-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.86 to 1.01; moderate to high-certainty evidence). There were 16 cases of intussusception in 43,629 children after RV5 vaccination and 20 cases in 41,866 children after placebo (RR 0.77, 95% CI 0.41 to 1.45; low-certainty evidence). Rotavac Children vaccinated and followed up the first year of life Rotavac has not been assessed in any RCT in countries with low child mortality. In India, a high-mortality country, Rotavac probably prevents 57% of severe rotavirus diarrhoea cases (RR 0.43, 95% CI 0.30 to 0.60; 6799 participants, moderate-certainty evidence); the trial did not report on severe all-cause diarrhoea at one-year follow-up. Children vaccinated and followed up for two years Rotavac probably prevents 54% of severe rotavirus diarrhoea cases in India (RR 0.46, 95% CI 0.35 to 0.60; 6541 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (RR 0.84, 95% CI 0.71 to 0.98; 6799 participants, 1 trial; moderate-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.85 to 1.02; moderate-certainty evidence). There were eight cases of intussusception in 5764 children after Rotavac vaccination and three cases in 2818 children after placebo (RR 1.33, 95% CI 0.35 to 5.02; very low-certainty evidence). There was insufficient evidence of an effect on mortality from any rotavirus vaccine (198,381 participants, 44 trials; low- to very low-certainty evidence), as the trials were not powered to detect an effect at this endpoint. AUTHORS' CONCLUSIONS:RV1, RV5, and Rotavac prevent episodes of rotavirus diarrhoea. Whilst the relative effect estimate is smaller in high-mortality than in low-mortality countries, there is a greater number of episodes prevented in these settings as the baseline risk is much higher. We found no increased risk of serious adverse events.

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Vaccines for preventing rotavirus diarrhoea: vaccines in use

Purpose of reviewAs of 2019, four rotavirus vaccines have been prequalified by the WHO for use worldwide. This review highlights current knowledge regarding rotavirus vaccines available, and provides a brief summary of the rotavirus vaccine pipeline.Recent findingsData generated from use of currentl

Current and new rotavirus vaccines

Subnational mapping of under-5 and neonatal mortality trends in India: the Global Burden of Disease Study 2000–17

Summary Background The duration of protection offered by rotavirus vaccines varies across the world, and this variation is important to understanding and predicting the effects of the vaccines. There is now a large body of evidence on the efficacy of live oral rotavirus vaccines in different settings, but these data have never been synthesised to obtain robust estimates of efficacy by duration of follow-up. Our aim is to estimate the efficacy of live oral rotavirus vaccines at each point during follow-up and by mortality stratum. Methods In our meta-regression study, we identified all randomised controlled trials of rotavirus vaccines published until April 4, 2018, using the results of a Cochrane systematic review, and cross checked these studies against those identified by another systematic review. We excluded trials that were based on special populations, trials without an infant schedule, and trials without clear reporting of numbers of enrolled infants and events in different periods of follow-up. For all reported periods of follow-up, we extracted the mean duration of follow-up (time since administration of the final dose of rotavirus vaccination), the number of enrolled infants, and case counts for rotavirus-positive severe gastroenteritis in both non-vaccinated and vaccinated groups. We used a Bayesian hierarchical Poisson meta-regression model to estimate the pooled cumulative vaccine efficacy (VE) and its waning with time for three mortality strata. We then converted these VE estimates into instantaneous VE (iVE). Findings In settings with low mortality (15 observations), iVE pooled for infant schedules of Rotarix and RotaTeq was 98% (95% credibility interval 93–100) 2 weeks following the final dose of vaccination and 94% (87–98) after 12 months. In medium-mortality settings (11 observations), equivalent estimates were 82% (74–92) after 2 weeks and 77% (67–84) after 12 months. In settings with high mortality (24 observations), there were five different vaccines with observation points for infant schedules. The pooled iVE was 66% (48–81) after 2 weeks of follow-up and 44% (27–59) after 12 months. Interpretation Rotavirus vaccine efficacy is lower and wanes more rapidly in high-mortality settings than in low-mortality settings, but the earlier peak age of disease in high-mortality settings means that live oral rotavirus vaccines are still likely to provide substantial benefit. Funding Bill & Melinda Gates Foundation.

Efficacy of live oral rotavirus vaccines by duration of follow-up: a meta-regression of randomised controlled trials.

Rotavirus is the leading cause of diarrheal death among children   65% of children had at least one rotavirus diarrhea illness by 5 years of age and rotavirus accounted for > 40% of all-cause diarrhea hospitalizations globally. Two live, oral rotavirus vaccines have been implemented nationally in > 100 countries since 2006 and their use has substantially reduced the burden of severe diarrheal illness in all settings. Vaccine efficacy and effectiveness estimates suggest there is a gradient in vaccine performance between low child-mortality countries (> 90%) and medium and high child-mortality countries (57–75%). Additionally, an increased risk of intussusception (~ 1–6 per 100,000 vaccinated infants) following vaccination has been documented in some countries, but this is outweighed by the large benefits of vaccination. Two additional live, oral rotavirus vaccines were recently licensed and these have improved on some programmatic limitations of earlier vaccines, such as heat stability, cost, and cold-chain footprint. Non-replicating rotavirus vaccines that are parenterally administered are in clinical testing, and these have the potential to reduce the performance differential and safety concerns associated with live oral rotavirus vaccines.

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Rotavirus Vaccines: Effectiveness, Safety, and Future Directions.

Background: India with 2.2 million incident cases annually contributed to around 25% of global incidence. Along with conventional indicators, magnitude of treatment delay would prove as a performance indicator for tuberculosis (TB) control in high TB burden countries like India. Objectives: The objectives of the study were to find out the magnitude of treatment delay among the TB patients, to describe the factors responsible for delay in treatment, if any, and to assess the knowledge of patients in a rural area about TB and directly observed treatment short course (DOTS). Study Design: Descriptive cross-sectional study was conducted among patients registered in the DOTS center at Mahatma Gandhi Institute of Medical Sciences Sewagram. Materials and Methods: Information of all 40 new sputum smear-positive TB patients registered at DOTS center between February and April 2015 was collected. Of these, thirty patients could be contacted successfully and were included in the study after obtaining consent. Data were entered in Microsoft Excel and analyzed using Epi Info software. Mean and median delay in terms of days were estimated. Mann–Whitney U-test was used to determine factors associated with treatment delay. Descriptive analysis using frequency and percentage was carried out to assess the knowledge regarding TB and DOTS. Results: Median delay was 35.5 days with diagnostic delay comprising 84% of it. Male patients and patients belonging to Below Poverty Line (BPL) families had significantly (P

Delay in initiation of treatment of tuberculosis: A cross-sectional study from rural Wardha

Japanese encephalitis (JE) disease among children continues in central India despite vaccination implemented in the routine immunization program. Therefore, we planned to estimate the JE vaccination effectiveness among children by undertaking a 1:2 individually‐matched population‐based case‐control study from August 2018 to October 2020. The laboratory‐confirmed JE cases aged 1–15 years were enrolled along with neighborhood controls without fever and encephalitis matched on the residence area, age and sex. The JE vaccination history was enquired from parents and verified independently from the vaccination cards available at home and records at health facilities. We enrolled 35 JE cases and 70 matched controls. The vaccination effectiveness of 86.7% (95% confidence interval [CI]: 30.8–94.7) was estimated on the per‐protocol analysis of 31 case‐control sets. The screening method provided an effectiveness of 89.5% (CI: 78.9–94.7) on using the population vaccination coverage of 90% reported earlier in the same area. In conclusion, JE vaccination offered a moderate level of protection among children in JE medium‐endemic central India, similar to reports from high‐endemic areas in India. The operational aspects of vaccination program implementation need to be evaluated to assess the impact of vaccination on the disease burden of JE in medium‐endemic regions of India.

Effectiveness of Japanese encephalitis vaccination among children in central India

Introduction: Prevalence of noncommunicable diseases (NCDs) is increasing rapidly in developing countries like India. The commonly attributable modifiable risk factors of NCDs include raised blood pressure (13%), tobacco use (9%), physical inactivity (6%), and obesity (5%). This quasi-experimental study with a pre-post design was conducted with an objective to assess the effect of Participatory Health Promotion initiative (PHPI) on tobacco use among adolescents. PHPI included distribution of personalized health card, tobacco-tar experiment demonstration, use of body mapping technique to emphasize hazards of tobacco on different body organs, and sensitization in small groups. Methods: Baseline tobacco use and health risk assessment were conducted by adapting WHO ASSIST tool among 200 students who were randomly selected from a secondary high school. All students in the school were then exposed to the PHPI. The postmeasurement was done among another 200 randomly selected students after 3 months. Results: The number of current tobacco users reduced from 29 (14.5%) in the baseline to 9 (4.5%) in the postmeasurement with a P

Effect of Participatory Health Promotion Initiative on Tobacco Use among Adolescents: A School-Based Quasi-Experimental Pilot Study from Central India

Background: Dengue is a common vector-borne disease in countries like India, where it occurs in specific pockets including many in Maharashtra. During July–August 2018, an outbreak of dengue was suspected in a village of Wardha district, following an increase in the number of fever cases from the village, which demanded an urgent outbreak investigation to be carried out before it progressed into an epidemic/larger outbreak. Objectives: The aim of this study was to find out more cases, source of infection and to recommend necessary actions to control the dengue outbreak. Materials and Methods: This was a cross-sectional epidemiological study, where we used pre-tested, pre-designed epidemiological case sheets obtained from Integrated Disease Surveillance Program (IDSP). A case definition was proposed before beginning the investigation. Line listing, collection of blood samples, distribution of paracetamol tablets to fever cases, and making a spot map were some of the important steps carried out during the investigation. Results: Out of a total of 64 suspected fever cases, 36 cases fulfilled the case definition of dengue, set for the purpose of outbreak investigation. Twenty-three of them got admitted in different hospitals among whom two of them died. Apart from that, four of them were found to be positive for both dengue IgM and NS1 antigen in their blood samples. It was age group of 21–30 years which was mostly affected. Compared to males, the female population suffered more from the illness. House, container, and Breteau index were found to be 0.26, 0.09, and 0.32, respectively. Conclusion: Following the investigation, a detailed report was made, which was shared with the district health authority. The report also contained recommendations for necessary actions to be taken to control this outbreak and to further prevent such outbreaks in future.

Outbreak investigation and containment measures of dengue fever in rural Wardha: A field epidemiological study

Background: The objective of the study was to study the association between exposure to early childhood development (ECD) interventions and responsive feeding and nutritional status among 6-35 months’ children.Methods: The present analytical cross-sectional study was conducted with 360 children from a primary health centre (PHC) area under the ECD project and 360 children from comparison PHC area. The anthropometric measurement and responsive feeding was assessed and compared among 6-35 months’ children.Results: There was significant difference in mean scores of ECD activity (p=0.001) and responsive feeding (p<0.001) in ECD area as to comparison area. In the ECD program area, the proportion of children who were malnourished (33.3%) were less as compared to control area (53.9%).Conclusions: The present study shows ECD interventions at community level delivered through frontline workers resulted in improved responsive feeding practices better nutritional outcomes for children.

Exposure to early childhood development interventions and its association with responsive feeding and nutritional status of 6 to 35 months old children

Abhishek V Raut

Papers

Delay in initiation of treatment of tuberculosis: A cross-sectional study from rural Wardha

Effectiveness of Japanese encephalitis vaccination among children in central India

Effect of Participatory Health Promotion Initiative on Tobacco Use among Adolescents: A School-Based Quasi-Experimental Pilot Study from Central India

Outbreak investigation and containment measures of dengue fever in rural Wardha: A field epidemiological study

Exposure to early childhood development interventions and its association with responsive feeding and nutritional status of 6 to 35 months old children