Introduction Of Rotavirus Vaccine Research Articles

Major Changes in Spatiotemporal Trends of US Rotavirus Laboratory Detections After Rotavirus Vaccine Introduction-2009-2021.

For the 15 years before rotavirus vaccine introduction in 2006, annual rotavirus activity in the United States showed a distinct spatiotemporal pattern, peaking first in the Southwest and last in the Northeast. We modeled spatiotemporal trends in rotavirus laboratory detections from 2009 to 2021. Laboratories reporting to the National Respiratory and Enteric Virus Surveillance System were eligible for inclusion in a given surveillance year (July to June) if ≥1 polymerase chain reaction or enzyme immunoassay rotavirus test per week was reported during ≥26 weeks and totaling ≥100 annual tests. For each laboratory, the season peak was the week with the highest 7-week moving average of the number of rotavirus positive tests during the national season, defined as the period with a 3-week moving average of >10% rotavirus positivity lasting ≥2 consecutive weeks. We input peak week as a continuous variable and the geospatial coordinates of each laboratory into a spherical variogram model for Kriging spatial interpolation. We also created a state-level bivariate choropleth map using tertiles of the 2010-2019 average birth rates and rotavirus vaccine coverage. Following the established biennial trend, the 2010-2011, 2012-2013, 2014-2015, 2016-2017, and 2018-2019 surveillance years had >10% rotavirus positivity for ≥2 weeks and were included in the geospatial analysis. During all 5 seasons included in the geospatial analysis, the earliest peak week occurred in Oklahoma, Arkansas, and the western Gulf coast, a pattern markedly different from prevaccine seasons. These states also had the average lowest rotavirus vaccine coverage and highest birth rate, suggesting that more rapid accumulation of susceptible children drives annual rotavirus season activity. Increasing vaccine coverage remains a key tool in reducing rotavirus burden.

Case fatality risk of diarrhoeal pathogens: a systematic review and meta-analysis.

BackgroundEstimates of the relative contribution of different pathogens to all-cause diarrhoea mortality are needed to inform global diarrhoea burden models and prioritize interventions. We aimed to investigate and estimate heterogeneity in the case fatality risk (CFR) of different diarrhoeal pathogens.MethodsWe conducted a systematic review and meta-analysis of studies that reported cases and deaths for 15 enteric pathogens published between 1990 and 2019. The primary outcome was the pathogen-specific CFR stratified by age group, country-specific under-5 mortality rate, setting, study year and rotavirus vaccine introduction status. We developed fixed-effects and multilevel mixed-effects logistic regression models to estimate the pooled CFR overall and for each pathogen, controlling for potential predictors of heterogeneity.ResultsA total of 416 studies met review criteria and were included in the analysis. The overall crude CFR for all pathogens was 0.65%, but there was considerable heterogeneity between and within studies. The overall CFR estimated from a random-effects model was 0.04% (95% CI: 0.026%–0.062%), whereas the pathogen-specific CFR estimates ranged from 0% to 2.7%. When pathogens were included as predictors of the CFR in the overall model, the highest and lowest odds ratios were found for enteropathogenic Escherichia coli (EPEC) [odds ratio (OR) = 3.0, 95% CI: 1.28–7.07] and rotavirus (OR = 0.23, 95% CI: 0.13–0.39), respectively.ConclusionWe provide comprehensive estimates of the CFR across different diarrhoeal pathogens and highlight pathogens for which more studies are needed. The results motivate the need for diarrhoeal interventions and could help prioritize pathogens for vaccine development.

Impact and effectiveness of monovalent rotavirus vaccine in Tajik children

BackgroundIn 2015, Tajikistan became the second country in Central Asia to introduce rotavirus vaccine into its national immunization program. Before vaccine introduction, rotavirus was estimated to cause > 40% of pediatric diarrhea hospitalizations in Tajikistan. We aimed to assess the impact of rotavirus vaccine introduction on rotavirus disease burden and estimate rotavirus vaccine effectiveness (VE). MethodsUsing surveillance data from 2013 through 2019, we examined trends in monthly hospital admissions among children < 5 years old, before and after rotavirus vaccine introduction. Poisson regression was used to quantify decreases. VE was estimated using a test-negative case control design, with data from admissions during 2017 – 2019. Immunization records were obtained from clinics. ResultsAmong enrolled children, rotavirus positivity declined from 42% to 25% in the post-vaccine introduction period, a decrease of 41% (95% Confidence Interval [CI]: 36 – 45%). Declines were greatest in children < 12 months of age. Estimated VE of a complete course of rotavirus vaccine was 55% (95% CI: 21 – 73%) among children 5 – 59 months of age and 64% (95% CI: 36 – 80%) among children 5 – 23 months of age. VE point estimates were higher among children receiving both doses of rotavirus vaccine non-concurrently with OPV and among children receiving their first dose of rotavirus vaccine at 4 – 11 months of age, but CIs were wide and overlapping. ConclusionsOur data demonstrate that rotavirus vaccine introduction was associated with a substantial reduction in pediatric rotavirus hospitalization burden in Tajikistan, and that rotavirus vaccination is effective in Tajik children.

Impact of polio vaccines (oral polio vaccine - OPV or inactivated polio vaccine - IPV) on rotavirus vaccine-associated intussusception

ABSTRACT Although safe, rotavirus vaccines have been associated with increased intussusception risk. In Brazil, after the oral human rotavirus vaccine (OHRV) introduction in the childhood immunization, in 2006, increased intussusception risk was identified after the second OHRV dose, whereas in other countries, higher risk was associated to the first vaccine dose. It was hypothesized that the concomitant use of oral poliovirus vaccine (OPV) in Brazil might explain this difference. In 2012, the inactivated polio vaccine (IPV) was adopted in the first two doses of Brazilian childhood immunization schedule, creating an opportunity to study the subject. Our objective was analyzing the impact of polio vaccines on rotavirus-associated intussusception. We used surveillance data on intussusception in infants living in São Paulo State. Two periods were considered: an OPV-period (March 2006 to June 2012) and an IPV-period (October 2012 to December 2017). The period from June to September 2012 were considered as transition. Self-controlled case series analysis with event-dependent exposure was performed, considering two risk periods (7 and 21 days post-vaccination). We identified 325 intussusception cases in infants reported to the surveillance systems during the study period. The statistical analysis included 221 cases that occurred within 60 days after vaccination. Overall, a higher intussusception risk was observed in the first week after vaccination for both the first (Relative Incidence [RI] = 4.3, 95%CI 2.8–6.5, p < .001) and second vaccine doses (RI = 4.2, 95%CI 2.7–6.4; p < .001). There were no statistically significant differences in intussusception risk according to the rotavirus vaccine dose and the polio vaccine (OPV or IPV) administered concomitantly.

Impact of Vaccination on Rotavirus Genotype Diversity: A Nearly Two-Decade-Long Epidemiological Study before and after Rotavirus Vaccine Introduction in Sicily, Italy.

Sicily was the first Italian region to introduce rotavirus (RV) vaccination with the monovalent G1P[8] vaccine Rotarix® in May 2012. In this study, the seasonal distribution and molecular characterization of RV strains detected over 19 years were compared to understand the effect of Rotarix® on the evolutionary dynamics of human RVs. A total of 7846 stool samples collected from children < 5 years of age, hospitalized with acute gastroenteritis, were tested for RV detection and genotyping. Since 2013, vaccine coverage has progressively increased, while the RV prevalence decreased from 36.1% to 13.3% with a loss of seasonality. The local distribution of RV genotypes changed over the time possibly due to vaccine introduction, with a drastic reduction in G1P[8] strains replaced by common and novel emerging RV strains, such as equine-like G3P[8] in the 2018–2019 season. Comparison of VP7 and VP4 amino acid (aa) sequences with the cognate genes of Rotarix® and RotaTeq® vaccine strains showed specific aa changes in the antigenic epitopes of VP7 and of the VP8* portion of VP4 of the Italian RV strains. Molecular epidemiological surveillance data are required to monitor the emergence of novel RV strains and ascertain if these strains may affect the efficacy of RV vaccines.

Antiviral Activity of Olanexidine-Containing Hand Rub against Human Noroviruses.

ABSTRACTHuman norovirus (HuNoV) is the leading cause of epidemic and sporadic acute gastroenteritis worldwide. HuNoV transmission occurs predominantly by direct person-to-person contact, and its health burden is associated with poor hand hygiene and a lack of effective antiseptics and disinfectants. Specific therapies and methods to prevent and control HuNoV spread previously were difficult to evaluate because of the lack of a cell culture system to propagate infectious virus. This barrier has been overcome with the successful cultivation of HuNoV in nontransformed human intestinal enteroids (HIEs). Here, we report using the HIE cultivation system to evaluate the virucidal efficacy of an olanexidine gluconate-based hand rub (OLG-HR) and 70% ethanol (EtOH70%) against HuNoVs. OLG-HR exhibited fast-acting virucidal activity against a spectrum of HuNoVs including GII.4 Sydney[P31], GII.4 Den Haag[P4], GII.4 New Orleans[P4], GII.3[P21], GII.17[P13], and GI.1[P1] strains. Exposure of HuNoV to OLG-HR for 30 to 60 s resulted in complete loss of the ability of virus to bind to the cells and reduced in vitro binding to glycans in porcine gastric mucin. By contrast, the virucidal efficiency of EtOH70% on virus infectivity was strain specific. Dynamic light scattering (DLS) and electron microscopy of virus-like particles (VLPs) show that OLG-HR treatment causes partial disassembly and possibly conformational changes in VP1, interfering with histo-blood group antigen (HBGA) binding and infectivity, whereas EtOH70% treatment causes particle disassembly and clumping of the disassembled products, leading to loss of infectivity while retaining HBGA binding. The highly effective inactivation of HuNoV infectivity by OLG-HR suggests that this compound could reduce HuNoV transmission.

Effectiveness of Monovalent Rotavirus Vaccine in Mozambique, a Country with a High Burden of Chronic Malnutrition.

Mozambique introduced monovalent rotavirus vaccine (Rotarix®) in September 2015. We evaluated the effectiveness of Rotarix® under conditions of routine use in Mozambican children hospitalized with acute gastroenteritis (AGE). A test negative case-control analysis was performed on data collected during 2017–2019 from children <5 years old, admitted with AGE in seven sentinel hospital sites in Mozambique. Adjusted VE was calculated for ≥1 dose of vaccine vs. zero doses using unconditional logistic regression, where VE = (1 − aOR) × 100%. VE estimates were stratified by age group, AGE severity, malnutrition, and genotype. Among 689 children eligible for analysis, 23.7% were rotavirus positive (cases) and 76.3% were negative (controls). The adjusted VE of ≥1 dose in children aged 6–11 months was 52.0% (95% CI, −11, 79), and −24.0% (95% CI, −459, 62) among children aged 12–23 months. Estimated VE was lower in stunted than non-stunted children (14% (95% CI, −138, 66) vs. 59% (95% CI, −125, 91)). Rotavirus vaccination appeared moderately effective against rotavirus gastroenteritis hospitalization in young Mozambican children. VE point estimates were lower in older and stunted children, although confidence intervals were wide and overlapped across strata. These findings provide additional evidence for other high-mortality countries considering rotavirus vaccine introduction.

Leveraging Beneficial Off-Target Effects of Live-Attenuated Rotavirus Vaccines.

Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalisations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Guérin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity. Indeed, rotavirus vaccines have been reported to provide greater than expected reductions in acute gastroenteritis caused by other enteropathogens, that have mostly been attributed to herd protection and prior underestimation of rotavirus disease. Whether rotavirus vaccines also alter the immune system to reduce non targeted gastrointestinal infections has not been studied directly. Here we review the current understanding of the mechanisms underlying off-target effects of vaccines and propose a mechanism by which the live-attenuated neonatal rotavirus vaccine, RV3-BB, could promote protection beyond the targeted pathogen. Finally, we consider how vaccine developers may leverage these properties to improve health outcomes in children, particularly those in low-income countries where disease burden and mortality is disproportionately high relative to developed countries.

Safety and reactogenicity of a liquid formulation of human rotavirus vaccine (porcine circovirus-free): A phase III, observer-blind, randomized, multi-country study

BackgroundThe introduction of rotavirus vaccines in national immunization programs has decreased mortality and hospitalizations due to diarrhea. GSK’s live-attenuated, human rotavirus vaccine (HRV) is a 2-dose vaccine for oral administration. Following the detection of porcine circovirus type 1 (PCV-1) in HRV, a PCV-free (no detection of PCV-1 and PCV-2 according to the detection limits of tests used) HRV was developed. The immunogenicity, reactogenicity and safety of a liquid (liq) PCV-free HRV were assessed in two prior studies. The present study aimed to generate additional reactogenicity and safety data. MethodsThis phase III, observer-blind, randomized, controlled multi-country study enrolled healthy 6–12-week-old infants. Infants were randomized to receive 2 doses of either the liq PCV-free HRV (N = 677) or the lyophilized (lyo) HRV (N = 674) 1–2 months apart. Solicited adverse events (AEs) were recorded for 8 days after each dose, unsolicited AEs for 31 days and serious AEs (SAEs) from dose 1 until the end of the 6-month safety follow-up. ResultsThe occurrence of solicited general AEs was comparable between the liq PCV-free HRV and the lyo HRV groups, with irritability/fussiness being the most frequently reported (74.9% [95% confidence interval: 71.4–78.1] and 72.1% [68.6–75.5]). Unsolicited AEs were reported for 29.7% (26.3–33.3) and 30.6% (27.1–34.2) of infants in the liq PCV-free HRV and the lyo HRV group. A total of 39 and 38 infants reported at least one SAE, respectively. The most common SAEs were upper respiratory tract (0.7% and 0.9%) and urinary tract infections (0.9% and 0.6%). One SAE (constipation) in the liq PCV-free HRV group was considered as potentially causally related to vaccination by the investigator. No deaths were reported. ConclusionsThe study showed that the reactogenicity and safety profiles of the liq PCV-free HRV and the lyo HRV are similar.ClinicalTrials.gov identifier: NCT03954743.

The Current Epidemiology of Rotavirus Infection in Children Less than 5 Years of Age after Introduction of RV Vaccine in India

Rotavirus is a major cause of severe acute gastroenteritis in infants and young children worldwide. It is responsible for 40% of childhood hospitalization. It has been estimated that about 23% of diarrhoeal death occurs due to the rotavirus infection in India. To study the epidemiology of rotavirus infection in children less than 5 years of age at a tertiary care teaching hospital. A total of 240 stool samples were collected from children &lt;5 years of age suffering from acute diarrhea at a tertiary health care referral hospital in Western Uttar Pradesh, India. Rotavirus antigen was detected in stool by Enzyme immunoassay (EIA) which utilizes monoclonal antibodies directed against VP6 antigen. Molecular genotyping was done by nested multiplex PCR. The rotavirus antigen positivity rate was found to be 14.58% in this study. There was male preponderance and the male: female ratio was 1.5:1. Rotavirus diarrhoea was reported predominantly (42.85 %) in the age group of 13 to 24 months. The most common circulating G/P genotype strain was G9P[4] accounting for 36% of cases. Rotavirus remains a major cause of diarrhoea in children &lt;5 years of age in Uttar Pradesh. However, the positivity rate has decreased after introduction of rotavirus vaccine into the Universal immunization program (UIP) in UP.

Trends in Rotavirus Laboratory Detections and Internet Search Volume Before and After Rotavirus Vaccine Introduction and in the Context of the Coronavirus Disease 2019 Pandemic-United States, 2000-2021.

BackgroundSince rotavirus vaccines became available in the United States in 2006, there have been reductions in rotavirus hospitalizations, changes in seasonality, and the emergence of a biennial trend of rotavirus activity. Reductions in other pathogens have been associated with coronavirus disease 2019 (COVID-19) mitigation measures. We assessed ongoing rotavirus disease trends during the COVID-19 pandemic.MethodsWe report a 3-week moving average of the number of rotavirus tests, positive tests, and the percent positivity from laboratories reporting to the National Respiratory and Enteric Virus Surveillance System (NREVSS) from July 2000 through June 2021. To complement NREVSS data, we analyzed Google internet search interest in “rotavirus” from July 2004 to June 2021.ResultsDeclines in rotavirus activity following vaccine introduction and the biennial trend are evident through the 2018–2019 surveillance year. In 2019–2021, rotavirus test positivity was below the historic ranges during the months of typically high rotavirus activity, and precipitous declines were noted in March 2020.ConclusionsIn the 15 years since rotavirus vaccine was introduced, the number of laboratory-detected rotavirus infections has been consistently lower than during the prevaccine era. During the COVID-19 pandemic, rotavirus activity was suppressed. There may be many rotavirus-susceptible children during the 2021–2022 rotavirus season.

Defining the Recipe for an Optimal Rotavirus Vaccine Introduction in a High-Income Country in Europe.

Observational data over 15 years of rotavirus vaccine introduction in Belgium have indicated that rotavirus hospitalisations in children aged <5 years plateaued at a higher level than expected, and was followed by biennial disease peaks. The research objective was to identify factors influencing these real-world vaccine impact data. We constructed mathematical models simulating rotavirus-related hospitalisations by age group and year for those children. Two periods were defined using different model constructs. First, the vaccine uptake period encompassed the years required to cover the whole at-risk population. Second, the post-uptake period covered the years in which a new infection/disease equilibrium was reached. The models were fitted to the observational data using optimisation programmes with regression and differential equations. Modifying parameter values identified factors affecting the pattern of hospitalisations. Results indicated that starting vaccination well before the peak disease season in the first year and rapidly achieving high coverage was critical in maximising early herd effect and minimising secondary sources of infection. This, in turn, would maximise the reduction in hospitalisations and minimise the size and frequency of subsequent disease peaks. The analysis and results identified key elements to consider for countries initiating an optimal rotavirus vaccine launch programme.

Explaining the formation of a plateau in rotavirus vaccine impact on rotavirus hospitalisations in Belgium

BackgroundObservational data on the reduction in hospitalisations after rotavirus vaccine introduction in Belgium suggest that vaccine impact plateaued at an unexpectedly high residual hospitalisation rate. The objective of this analysis was to identify factors that influence real-world vaccine impact. MethodsData were collected on hospitalisations in children aged ≤ 5 years with rotavirus disease from 11 hospitals since 2005 (the RotaBIS study). The universal rotavirus vaccination campaign started late in 2006. A mathematical model simulated rotavirus hospitalisations in different age groups using vaccine efficacy and herd effect, influenced by vaccine coverage, vaccine waning, and secondary infection sources. The model used optimisation analysis to fit the simulated curve to the observed data, applying Solver add-in software. It also simulated an ‘ideal’ vaccine introduction maximising hospitalisation reduction (maximum coverage, maximum herd effect, no waning), and compared this with the best-fit simulated curve. Modifying model input values identified factors with the largest impact on hospitalisations. ResultsCompared with the ‘ideal’ simulation, observed data showed a slower decline in hospitalisations and levelled off after three years at a higher residual hospitalisation rate. The slower initial decline was explained by the herd effect in unvaccinated children. The higher residual hospitalisation rate was explained by starting the vaccine programme in November, near the rotavirus seasonal peak. This resulted in low accumulated vaccine coverage during the first rotavirus disease peak season, with the consequential appearance of secondary infection sources. This in turn reduced the herd effect, resulting in a diminished net impact. ConclusionsOur results indicate that countries wishing to maximise the impact of rotavirus vaccination should start vaccinating well ahead of the rotavirus seasonal disease peak. This maximises herd effect during the first year leading to rapid and high reduction in hospitalisations. Secondary infection sources explain the observed data in Belgium better than vaccine waning.

Incidence, Clinical Characteristics, and Genotype Distribution of Rotavirus in a Neonatal Intensive Care Unit 5 Years After Introducing Rotavirus Vaccine.

BackgroundRotavirus (RV) is a common cause of viral gastroenteritis in children worldwide. We aimed to investigate the incidence, symptoms, and genotype of RV infection in a neonatal intensive care unit (NICU) in South Korea 5 years after the introduction of RV vaccination to evaluate its effect on newborn infants.MethodsA total of 431 fecal specimens were collected from patients admitted to NICU between April 20, 2012 and September 10, 2013. Enzyme-linked immunoassays were used to detect RV antigen. Nested multiplex polymerase chain reaction was used for genotyping.ResultsThe overall incidence of RV infection was 43.9% and was significantly higher in preterm infants, infants born in the study hospital, low birth weight infants, and cesarean births (P < 0.05). Symptoms of diarrhea, poor feeding, abdominal distension, and apnea were significantly higher in infants with RV infection than those without infection. RV infection gradually increased depending on infant care at home, postpartum clinic, or hospital (26.0, 45.1, and 60.2%, respectively; P = 0.000). The dominant RV genotype in the NICU was G4P[6] at 95.4%.ConclusionCurrent RV vaccines did not affect the incidence of RV infection in newborn and preterm infants in the NICU. Most RV-positive patients in the NICU had symptoms, and the incidence of RV infection was relatively higher in hospitals and postpartum clinics with group life than home. The dominant RV genotype was G4P[6] across study groups.

Bacterial diarrhoea.

This review describes recent findings about the burden of bacterial diarrhoea and its potential complications, newer diagnostics, the emerging threat of multidrug resistance, and the promise of vaccines in development. Introduction of rotavirus vaccines in over 110 countries has changed the landscape of diarrheal pathogens. In upper middle and high-income countries, the incidence of rotavirus-specific and all-cause gastroenteritis has declined substantially, and norovirus has become the major pathogen in many settings. Bacterial pathogens cause approximately 10-15% of episodes, most often Shigella, nontyphoidal Salmonella (NTS) Campylobacter and Shiga toxin-producing Escherichia coli (STEC). In lower income countries, bacterial pathogens remain a major cause of medically attended diarrhoea with Shigella, Campylobacter and enterotoxigenic Escherichia coli (ETEC) predominating. Multidrug-resistant strains of Shigella, NTS and, Campylobacter have emerged globally requiring judicious use of antibiotics according to current guidance. Management of bacterial diarrhoea includes standard fluid and electrolyte therapy, vigilance for potential complications, and use of antibiotics for children who have moderate-severe illness due to pathogens for which efficacy has been demonstrated, or for those at high risk for severe disease. The threat of multiply resistant strains provides impetus for preventive strategies such as development of vaccines.

An increasing trend of human sapovirus infection in Japan, 2009 to 2019: An emerging public health concern

BackgroundHuman sapovirus (SaV) is an important etiologic agent of childhood diarrhea. This study aims to investigate the burden of SaV infection in childhood diarrhea in Japan from 2009–2019, to understand the changes in SaV infection after the introduction of rotavirus (RV) vaccination in Japan in 2011. MethodsStool samples were collected from children aged ≤ 12 years old with acute gastroenteritis (AGE) who visited outpatient clinics of six prefectures in Japan. The viral RNA was detected by RT-PCR and genogroups and genotypes were determined through sequence-based analysis. ResultsAmong 5697 stool samples, 318 (5.6%) samples remained SaV-positives showing the highest prevalence in June and 12–24 month aged children. The most predominant genotype was GI.1 (56.8%), followed by GI.2 (19.2%), GII.1 (10.8%), GIV.1 (9.4%), GI.3 (1.7%), GII.2 (1.4%), GII.3 and GII.5 (0.3%). Importantly, an increasing trend (P = 0.016) of SaV infection was observed during this period. In particular, SaV-detection rate was increased significantly (P = 0.033) from 4.3% in pre-rotavirus (RV)-vaccination era to 6.1% in post-RV-vaccination era. We provided evidence that this increase in SaV infection was mainly attributed by coinfections. ConclusionsThe upward trend of SaV infection, particularly after the introduction of RV-vaccination, is an emerging concern. Attention should be paid to control this upward trend of SaV infection to ensure maximum benefits of implementation of RV vaccines towards reducing overall childhood diarrhea worldwide.

Does Anybody Want an Injectable Rotavirus Vaccine, and Why? Understanding the Public Health Value Proposition of Next-Generation Rotavirus Vaccines.

Routine infant immunization with live, oral rotavirus vaccines (LORVs) has had a major impact on severe gastroenteritis disease. Nevertheless, in high morbidity and mortality settings rotavirus remains an important cause of disease, partly attributable to the sub-optimal clinical efficacy of LORVs in those settings. Regardless of the precise immunological mechanism(s) underlying the diminished efficacy, the introduction of injectable next-generation rotavirus vaccines (iNGRV), currently in clinical development, could offer a potent remedy. In addition to the potential for greater clinical efficacy, precisely how iNGRVs are delivered (multiple doses to young infants; alongside LORVs or as a booster; co-formulated with Diphtheria-Tetanus-Pertussis (DTP)-containing vaccines), their pricing, and their storage and cold chain characteristics could each have major implications on the resultant health outcomes, on cost-effectiveness as well as on product preferences by national stakeholders and healthcare providers. To better understand these implications, we critically assessed whether there is a compelling public health value proposition for iNGRVs based on potential (but still hypothetical) vaccine profiles. Our results suggest that the answer is highly dependent on the specific use cases and potential attributes of such novel vaccines. Notably, co-formulation of iNGRVs with similar or greater efficacy than LORVs with a DTP-containing vaccine, such as DTP-Hib-HepB, scored especially high on potential impact, cost-effectiveness, and strength of preference by national stakeholders and health care providers in lower and middle income countries.

Molecular Epidemiology of Rotavirus Strains in Symptomatic and Asymptomatic Children in Manhiça District, Southern Mozambique 2008-2019.

Group A rotaviruses remain the leading cause of diarrhoea in children aged <5 years. Mozambique introduced rotavirus vaccine (Rotarix®) in September 2015. We report rotavirus genotypes circulating among symptomatic and asymptomatic children in Manhiça District, Mozambique, pre- and post-vaccine introduction. Stool was collected from enrolled children and screened for rotavirus by enzyme-immuno-sorbent assay. Positive specimens were genotyped for VP7 (G genotypes) and VP4 (P genotypes) by the conventional reverse transcriptase polymerase chain reaction. The combination G12P[8] was more frequently observed in pre-vaccine than in post-vaccine introduction, in moderate to severe diarrhoea (34%, 61/177 vs. 0, p < 0.0001) and controls (23%, 26/113 vs. 0, p = 0.0013) and mixed genotypes (36%, 24/67 vs. 7% 4/58, p = 0.0003) in less severe diarrhoea. We observed changes in post-vaccine compared to pre-vaccine introduction, where G3P[4] and G3P[8] were prevalent in moderate to severe diarrhoea (10%, 5/49 vs. 0, p = 0.0002; and 14%, 7/49 vs. 1%, 1/177, p < 0.0001; respectively), and in less severe diarrhoea (21%, 12/58 vs. 0, p = 0.003; and 24%, 14/58 vs. 0, p < 0.0001; respectively). Our surveillance demonstrated the circulation of similar genotypes contemporaneously among cases and controls, as well as switching from pre- to post-vaccine introduction. Continuous surveillance is needed to evaluate the dynamics of the changes in genotypes following vaccine introduction.

The effect of introduction of routine immunization for rotavirus vaccine on paediatric admissions with diarrhoea and dehydration to Kenyan Hospitals: an interrupted time series study

Background: Dehydration secondary to diarrhoea is a major cause of hospitalization and mortality in children aged less than five years. Most diarrhoea cases in childhood are caused by rotavirus, and routine introduction of rotavirus vaccine is expected to reduce the incidence and severity of dehydration secondary to diarrhoea in vaccinated infants. Previously, studies have examined changes in admissions with stools positive for rotavirus but this study reports on all admissions with dehydration secondary to diarrhoea regardless of stool rotavirus results. We aimed to assess the changes in all-cause severe diarrhoea and dehydration (DAD) admissions following the vaccine’s introduction. Methods: We examined changes in admissions of all clinical cases of DAD before and after introduction of routine vaccination with rotavirus vaccine in July 2014 in Kenya. We use data from 13 public hospitals currently involved in a clinical network, the Clinical Information Network (CIN). Routinely collected data for children aged 2-36 months were examined. We used a segmented mixed effects model to assess changes in the burden of diarrhoea and dehydration after introduction of rotavirus vaccine. For sensitivity analysis, we examined trends for non-febrile admissions (surgical or burns). Results: There were 17,708 patients classified as having both diarrhoea and dehydration. Average monthly admissions due to DAD for each hospital before vaccine introduction (July 2014) was 35 (standard deviation: ±22) and 17 (standard deviation: ±12) after vaccine introduction. Segmented mixed effects regression model showed there was a 33% (95% CI, 30% to 38%) decrease in DAD admissions immediately after the vaccine was introduced to the Kenya immunization program in July 2014. There was no change in admissions due to non-febrile admissions pre-and post-vaccine introduction. Conclusion: The rotavirus vaccine, after introduction into the Kenya routine immunization program resulted in reduction of all-cause admissions of diarrhoea and dehydration in children to public hospitals.

Adoption of BOT Model to Introduce Vaccines: Tablet Approach

Objective: The introduction of the rotavirus vaccine (RVV) in India is one of the major achievements of the immunization program of India. Faced with various challenges, including different product specifications and competing for other program priorities, the introduction of the rotavirus vaccine in the universal immunization program was a monumental task. Considering the successful introduction of RVV, there is a need for a knowledge transfer tool that can enable policymakers and other countries to adopt it to formulate informed strategies and introduce new vaccines. Methods: The review was conducted in two phases. In the first stage, a literature review was conducted to identify and analyze all the published literature on Build-Operate-Transfer (BOT) model and RVV introduction in India. In the second phase, an analysis of the shortlisted literature was conducted utilizing the framework method. Results: Following the analysis, several similarities were observed between the approach to rotavirus vaccine introduction, and BOT model. Hence, based on the above analogy new public health project implementation framework, TaBLET (Technical Advice, Build capacity, Leverage partnerships, Engineer innovations, Transfer assets) approach, was proposed. Conclusion: This article has proposed a new TaBLET approach adapted from the BOT model. The RVV introduction has shown that a project implementation framework like TaBLET can be successfully employed for efficiently utilizing existing resources, increased outreach with existing human resources, and complete transfer of tangible and intangible assets, which can be imbibed in the existing health system. This article highlights the genesis and the multifactorial benefits of the TaBLET approach in introducing new vaccines as well as in other allied health care programs.