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. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.

Introduction Rotavirus vaccine (Rotarix®, RV1) has reduced diarrhea-associated hospitalizations and deaths in Malawi. We examined the trends in circulating rotavirus genotypes in Malawi over a 22-year period to assess the impact of RV1 introduction on strain distribution. Methods Data on rotavirus-positive stool specimens among children age <5 years hospitalized with diarrhea in Blantyre, Malawi before (July 1997 – October 2012, n=1765) and after (November 2012 – October 2019, n=934) RV1 introduction were analyzed. Rotavirus G and P genotypes were assigned using reverse transcription polymerase chain reaction. Results A rich rotavirus strain diversity circulated throughout the 22-year period; Shannon (H) and Simpson diversity (D) indices did not differ between the pre- and post-vaccine periods (H’ p < 0.149: D’ p < 0.287). Overall, G1 (n=268/924; 28.7%), G2 (n=308/924; 33.0%), G3 (n=72/924; 7.7%) and G12 (n=109/924; 11.8%) were the most prevalent genotypes identified following RV1 introduction. The prevalence of G1P[8] and G2P[4] genotypes declined each successive year following RV1 introduction, and were not detected after 2018. Genotype G3 re-emerged and became the predominant genotype from 2017. No evidence of genotype selection was observed seven years post-RV1 introduction. Conclusion Rotavirus strain diversity and genotype variation in Malawi is likely driven by natural mechanisms rather than vaccine pressure.

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies.