Desiree Witte

Diarrhea due to Shigella causes 60,000 deaths annually among children under five in low- and middle-income countries. This Enterics for Global Health sub-study examined host, clinical, and environmental factors linked to Shigella -attributable diarrhea in Malawian children and assessed seasonal variations. Data from 1,399 children aged 6–35 months presenting with diarrhea at a health centre in Blantyre, Southern Malawi from August 3, 2022, through August 2, 2024, were analyzed. Prevalence ratios of risk factors for Shigella -attributable diarrhea were estimated using modified Poisson regression. A Shigella case was defined by culture positivity or infection attributable to Shigella via quantitative polymerase chain reaction (qPCR). Multivariate analyses adjusted for age, wealth index quintile, and vaccination status. Effect modification by season (rainy vs. dry) was assessed for each predictor. Sensitivity analyses compared cases identified by culture or qPCR. Shigella -attributable diarrhea was found in 12.4% of children. Older age (12–35 months), dysentery, and diarrhea severity were positively associated with Shigella -attributed diarrhea in unadjusted and adjusted models; stunting and age-appropriate vaccination were significant only in unadjusted models. Seasonal effect modification occurred for wasting and Shigella infection in the dry season but not rainy season. Longer diarrhea duration was marginally linked to increased Shigella risk in the dry season only. Conversely, open defaecation/unimproved sanitation increased Shigella risk during the rainy season but not the dry season. Sensitivity analyses showed consistent risk patterns for culture- and qPCR-diagnosed cases. This study identified age, dysentery, and diarrhea severity as key factors for Shigella-attributed diarrhea. Seasonal effects influenced the relationships between Shigella infection and wasting, diarrhea duration, and sanitation. Policies prioritizing vulnerable populations and accounting for seasonal variations can help reduce the Shigella burden in children.

Introduction: Confidence in caregivers’ assessment of fever in their children, compared to thermometer readings, could help guide prompt care seeking and appropriate treatment in settings where access to reliable diagnostic tools is limited. Here, we evaluated the accuracy and drivers of caregiver-reported ‘hot-to-touch’ fever compared to digital thermometry among children in the Enterics for Global Health (EFGH) Shigella surveillance study. Methods: Children aged 6–35 months with medically attended diarrhea (MAD) enrolled in Kenya, Malawi, Bangladesh, and Peru between August 2022 and August 2024 were included. We trained caregivers to assess and record daily ‘hot-to-touch’ (subjective fever measurement) and digital (thermometer) axillary temperature (fever defined as ≥37.5°C) readings over for 14 days post-enrolment. We calculated site specific and overall accuracy of ‘hot-to-touch’ compared to thermometer-measured fever and used multivariable Poisson regression to identify factors associated with accurate detection. Results: The accuracy of caregiver-reported ‘hot-to-touch’ assessment ranged from 62.1% to72.0% overall and was highest in Bangladesh (83.2%–96.1%) and lowest in Malawi (47.4%–53.4%) over the 14 day assessment period. Accuracy was higher in children with chest indrawing (aPR=1.29, 95% CI: 1.04–1.60) and low respiratory rate (aPR=1.20, 95% CI: 1.11–1.29) and in children from wealthier households (Quintile 5: aPR=1.21, 95% CI: 1.01-1.44). Accuracy was lower among caregivers from households with ≥3 children (aPR=0.88, 95% CI: 0.79–0.99) and for children with low heart rate (aPR=0.76, 95% CI: 0.61–0.94). Conclusion: Suboptimal accuracy of hot-to-touch compared to digital thermometers in detecting fever in this study supports the need for digital thermometer use and context-specific strategies to enhance early detection of fever, particularly in communities living in resource-poor settings.

Diarrhea due to Shigella causes 60,000 deaths annually among children under five in low- and middle-income countries. This Enterics for Global Health sub-study examined host, clinical, and environmental factors linked to Shigella-attributable diarrhea in Malawian children and assessed seasonal variations. Data from 1,399 children aged 6 to 35 months presenting with diarrhea at a health centre in Blantyre, Southern Malawi, were analyzed. Prevalence ratios of risk factors for Shigella -attributable diarrhea were estimated using modified Poisson regression. A S higella case was defined by culture positivity or infection attributable to Shigella via quantitative polymerase chain reaction (qPCR). Multivariate analyses adjusted for age, wealth index quintile, and vaccination status. Effect modification by season (rainy vs. dry) was assessed for each predictor. Sensitivity analyses compared cases identified by culture or qPCR. Shigella -attributable diarrhea was found in 12.4% of children. Older age (12–35 months), dysentery, and diarrhea severity were positively associated with Shigella -attributed diarrhea in unadjusted and adjusted models; stunting and age-appropriate vaccination were significant only in unadjusted models. Seasonal effect modification occurred for wasting and Shigella infection in the dry season but not rainy season. Longer diarrhea duration was marginally linked to increased Shigella risk in the dry season only. Conversely, open defaecation/unimproved sanitation increased Shigella risk during the rainy season but not the dry season. Sensitivity analyses showed consistent risk patterns for culture- and qPCR-diagnosed cases. This study identified age, dysentery, and diarrhea severity as key factors for Shigella-attributed diarrhea. Seasonal effects influenced the relationships between Shigella infection and wasting, diarrhea duration, and sanitation. Policies prioritizing vulnerable populations and accounting for seasonal variations can help reduce the Shigella burden in children.

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. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (p < 0.005) and 3 (p < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease.

The SARS-CoV-2 Omicron variant has resulted in a high number of cases, but a relatively low incidence of severe disease and deaths, compared to the pre-Omicron variants. Therefore, we assessed the differences in symptom prevalence between Omicron and pre-Omicron infections in a sub-Saharan African population. We collected data from outpatients presenting at two primary healthcare facilities in Blantyre, Malawi, from November 2020 to March 2022. Eligible participants were aged >1month old, with signs suggestive of COVID-19, and those not suspected of COVID-19, from whom we collected nasopharyngeal swabs for SARS-CoV-2 PCR testing, and sequenced positive samples to identify infecting-variants. In addition, we calculated the risk of presenting with a given symptom in individuals testing SARS-CoV-2 PCR positive before and during the Omicron variant-dominated period. Among 5176 participants, 6.4% were under 5, and 77% were aged 18 to 50 years. SARS-CoV-2 infection prevalence peaked in January 2021 (Beta), July 2021 (Delta), and December 2021 (Omicron). We found that cough (risk ratio (RR), 1.50; 95% confidence interval (CI), 1.00 to 2.30), fatigue (RR 2.27; 95% CI, 1.29 to 3.86) and headache (RR 1.64; 95% CI, 1.15 to 2.34) were associated with a high risk of SARS-CoV-2 infection during the pre-Omicron period. In comparison, only headache (RR 1.41; 95% CI, 1.07 to 1.86) did associate with a high risk of SARS-CoV-2 infection during the Omicron-dominated period. In conclusion, clinical symptoms associated with Omicron infection differed from prior variants and were harder to identify clinically with current symptom guidelines. Our findings encourage regular review of case definitions and testing policies to ensure case ascertainment.