Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi.

High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine.

Impact of rotavirus vaccination in Malawi from 2012 to 2022 compared to model predictions before, during, and after the COVID-19 pandemic.

Background: Rotarix rotavirus vaccine was introduced into the Malawi national immunization program in October 2012. We used a previously developed mathematical models to estimate overall vaccine effectiveness over a 10-year period following rotavirus vaccine introduction.

Methods: We analyzed data on children <5 years old hospitalized with acute gastroenteritis in Blantyre, Malawi from January 2012 to June 2022, compared to pre-vaccination data.

Diarrhea Case Surveillance in the Enterics for Global Health Surveillance Study: Epidemiologic Methods.

Background: is a leading cause of acute watery diarrhea, dysentery, and diarrhea-attributed linear growth faltering, a precursor to stunting and lifelong morbidity. Several promising vaccines are in development and field efficacy trials will require a consortium of potential vaccine trial sites with up-to-date diarrhea incidence data.

Methods: The Enterics for Global Health (EFGH) surveillance study will employ facility-based enrollment of diarrhea cases aged 6-35 months with 3 months of follow-up to establish incidence rates and document clinical, anthropometric, and financial consequences of diarrhea at 7 country sites (Mali, Kenya, The Gambia, Malawi, Bangladesh, Pakistan, and Peru).

Quantifying the Cost of Diarrhea in the Enterics for Global Health (EFGH) Surveillance Study.

Background: Comparative costs of public health interventions provide valuable data for decision making. However, the availability of comprehensive and context-specific costs is often limited. The Enterics for Global Health (EFGH) surveillance study-a facility-based diarrhea surveillance study across 7 countries-aims to generate evidence on health system and household costs associated with medically attended diarrhea in children.

The Enterics for Global Health (EFGH) Surveillance Study in Malawi.

Background: Malawi is among 7 countries participating in the Enterics for Global Health (EFGH) surveillance study, which aims to determine the incidence of medically attended diarrhea attributed to , a leading bacterial cause of diarrhea in children in low-resource settings.

Methods: We describe the EFGH study site in the densely populated informal settlement of Ndirande Township, Blantyre, Malawi. We explore the site's geographical location, demographic characteristics, and the healthcare-seeking behavior of its population, particularly for childhood diarrhea.

Microbiological Methods Used in the Enterics for Global Health Surveillance Study.

Background: is a major cause of diarrhea in young children worldwide. Multiple vaccines targeting are in development, and phase 3 clinical trials are imminent to determine efficacy against shigellosis.

Methods: The Enterics for Global Health (EFGH) surveillance study is designed to determine the incidence of medically attended shigellosis in 6- to 35-month-old children in 7 resource-limited settings.

Draft genomes of from patients with cholera-like illness during the 2022-2023 cholera outbreak in Malawi.

is an increasingly recognized etiological agent of acute gastroenteritis. Here, we report five draft genomes of isolated from suspected cholera cases during the 2022-2023 cholera outbreak in Malawi.

Association Between Maternal Breastmilk Microbiota Composition and Rotavirus Vaccine Response in African, Asian, and European Infants: A Prospective Cohort Study.

Background: Maternal breastmilk is a source of pre- and pro-biotics that impact neonatal gut microbiota colonization. Because oral rotavirus vaccines (ORVs) are administered at a time when infants are often breastfed, breastmilk microbiota composition may have a direct or indirect influence on vaccine take and immunogenicity.

Methods: Using standardized methods across sites, we compared breastmilk microbiota composition in relation to geographic location and ORV response in cohorts prospectively followed from birth to 18 weeks of age in India (n = 307), Malawi (n = 119), and the United Kingdom ([UK] n = 60).

Comparative whole genome analysis reveals re-emergence of human Wa-like and DS-1-like G3 rotaviruses after Rotarix vaccine introduction in Malawi.

G3 rotaviruses rank among the most common rotavirus strains worldwide in humans and animals. However, despite a robust long-term rotavirus surveillance system from 1997 at Queen Elizabeth Central Hospital in Blantyre, Malawi, these strains were only detected from 1997 to 1999 and then disappeared and re-emerged in 2017, 5 years after the introduction of the Rotarix rotavirus vaccine. Here, we analysed representative twenty-seven whole genome sequences (G3P[4], = 20; G3P[6], = 1; and G3P[8], = 6) randomly selected each month between November 2017 and August 2019 to understand how G3 strains re-emerged in Malawi.

Histo-blood group antigen profile of Australian Aboriginal children and seropositivity following oral rotavirus vaccination.

Background: Histo-blood group antigens (HBGAs) may influence immune responses to rotavirus vaccination.

Methods: HBGA phenotyping was determined by detection of antigens A, B, H and Lewis a and b in saliva using enzyme-linked immunosorbent assay. Secretor status was confirmed by lectin antigen assay if A, B and H antigens were negative or borderline (OD ± 0.

Predicting Norovirus in England Using Existing and Emerging Syndromic Data: Infodemiology Study.

Background: Norovirus is associated with approximately 18% of the global burden of gastroenteritis and affects all age groups. There is currently no licensed vaccine or available antiviral treatment. However, well-designed early warning systems and forecasting can guide nonpharmaceutical approaches to norovirus infection prevention and control.

Public acceptability of a technology-mediated stool sample collection platform to inform community-based surveillance of infectious intestinal disease: a pilot study.

Background: In the UK approximately a quarter of the population experience infectious intestinal disease (IID) each year. However, only 2% present to primary care, preventing a true determination of community burden and pathogen aetiology. The aim of this pilot study was to gauge public acceptability of a technology-mediated platform for reporting episodes of IID and for providing stool samples.

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.

Neonatal rotavirus vaccine (RV3-BB) immunogenicity and safety in a neonatal and infant administration schedule in Malawi: a randomised, double-blind, four-arm parallel group dose-ranging study.

Background: Rotavirus vaccines reduce rotavirus-related deaths and hospitalisations but are less effective in high child mortality countries. The human RV3-BB neonatal G3P[6] rotavirus vaccine administered in a neonatal schedule was efficacious in reducing severe rotavirus gastroenteritis in Indonesia but had not yet been evaluated in African infants.

Methods: We did a phase 2, randomised, double-blind, parallel group dose-ranging study of three doses of oral RV3-BB rotavirus vaccine in infants in three primary health centres in Blantyre, Malawi.

Reduction in Severity of All-Cause Gastroenteritis Requiring Hospitalisation in Children Vaccinated against Rotavirus in Malawi.

Rotavirus is the major cause of severe gastroenteritis in children aged <5 years. Introduction of the G1P[8] Rotarix rotavirus vaccine in Malawi in 2012 has reduced rotavirus-associated hospitalisations and diarrhoeal mortality. However, the impact of rotavirus vaccine on the severity of gastroenteritis presented in children requiring hospitalisation remains unknown.

Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants.

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK.

Plasma Rotavirus-specific IgA and Risk of Rotavirus Vaccine Failure in Infants in Malawi.

Background: Rotavirus vaccine efficacy is reduced in low-income populations, but efforts to improve vaccine performance are limited by lack of clear correlates of protection. Although plasma rotavirus (RV)-specific immunoglobulin A (IgA) appears strongly associated with protection against rotavirus gastroenteritis in high-income countries, weaker association has been observed in low-income countries. We tested the hypothesis that lower RV-specific IgA is associated with rotavirus vaccine failure in Malawian infants.