Olivia Lang Schultes

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.

Background: Shigella vaccine development is a critical priority due to high burden and long-term outcomes among children. Choosing a clinical efficacy endpoint for Shigella vaccine trials requires comparing existing diarrhea severity definitions among children with Shigella. Methods: Six- to 35-month-old children presenting with diarrhea were enrolled at 7 EFGH study sites. Among children with Shigella, 6 diarrhea severity definitions (Global Enteric Multicenter Study [GEMS] moderate-to-severe diarrhea [MSD], modified Vesikari score [MVS], MVS +/− dysentery, Clark score, MAL-ED score, and Shigella mortality score) were examined against 2 outcomes: change in length/height-for-age z-score (ΔLAZ/HAZ) over 3 months and death or hospitalization within 14 days. We compared the performance of each severity score to predict outcomes using linear regression and measures of diagnostic accuracy. Results: Moderate or severe diarrhea was negatively associated with ΔLAZ/HAZ by MVS (−0.07 z-score, 95% CI −0.10 to −0.03), MVS +/− dysentery (−0.05, 95% CI −0.09 to −0.02), and MAL-ED score (−0.04, 95% CI −0.07 to 0.00). GEMS MSD (93.6%), MAL-ED (87.2%), MVS +/− dysentery (85.1%), and MVS (80.9%) had high sensitivity in predicting death or hospitalization. Conclusions: MVS, MVS +/− dysentery, and MAL-ED score identified adverse outcomes following Shigella diarrhea and are viable options for a vaccine trial case definition.

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.

Despite a global reduction in neonatal deaths in the last few decades, high neonatal mortality rates persist in low- to middle-income countries. Mobile health interventions offer a promising solution to promote early newborn care (ENC) practices and improve neonatal health. The Mobile WACh NEO randomized controlled trial evaluated the effect of a text messaging communication intervention on neonatal health outcomes in Kenya from 2020 to 2023. Perinatal participants received automated messages from enrollment at 28–36 weeks gestation until six weeks postpartum and could message with a study nurse. This secondary analysis aimed to characterize participant text engagement and examine associations between engagement and maternal-neonatal health outcomes. Among 2,470 intervention participants retained through follow-up, median time in the intervention was 14 weeks. Participants received a median of 58 automated messages (average 0.58 per day), sent a median of 24 messages (average 0.25 per day), and received a median of 14 nurse responses (average 0.14 per day). Younger, more educated, unmarried, unemployed, and first-time mothers sent more messages, while those who had a lower social support score at baseline messaged less. Increased participant messaging was associated with greater increase in neonatal danger sign knowledge from baseline to six-week follow-up (Adj Est: 0.39; 95% CI: 0.09-0.68) and lower odds of early initiation of breastfeeding (aOR: 0.62; 95% CI: 0.45-0.86). Our findings contribute to the understanding of who can benefit from mobile health programs and how these interventions might impact behaviors and outcomes.

Background: Shigella is a major contributor to the global diarrhoeal burden in children under five. This analysis calculates the costs of Shigella-attributable medically-attended diarrhoea (MAD) in seven country sites. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study enrolled 9,476 children aged 6 to 35 months over 24 months. Unit costs per Shigella-attributable MAD visit were estimated from household, health system, and societal perspectives. We used multivariate models to determine the influence of patient- and facility-level characteristics on unit costs. We calculated the population-level economic burden of Shigella MAD within each site and conducted scenario analyses to understand the potential impact of four hypothetical vaccines on population-level costs. Findings: The mean societal cost per visit for 1944 children with Shigella MAD was US $9་63, (95% CI $9་05–$10་22), ranging from $4་40 (Pakistan) to $16་61 (Peru). Costs of all-cause diarrhoea were similar at $10·22 (95% CI $9·95–$10·50). Households bore the majority of costs. Across sites, costs increased significantly with diarrhoea severity. Dehydration had the greatest impact on costs, with cases of severe dehydration costing 2.72-times higher than cases without dehydration. Population-level societal costs (defined as total costs per site over a one-year period per 100 000 persons) ranged from $2163 in Pakistan to $17 363 in Mali. In Shigella vaccine scenario analyses, population costs averted ranged from 15% to 34%. Interpretation: Costs of Shigella-associated MAD are high and similar to costs of all-cause diarrhoea. A Shigellavaccine may avert over one-third of Shigella-associated healthcare seeking costs.

Background: Shigella has high global burden and serious long-term outcomes among young children. Increasing antibiotic resistance makes Shigella vaccine development a critical priority. Choosing the optimal clinical efficacy endpoint for Shigella vaccine trials requires comparing existing diarrhea severity definitions among children with Shigella . Methods: Six-to 35-month-old children presenting to a clinic with diarrhea were enrolled in Bangladesh, Kenya, Malawi, Mali, Pakistan, Peru, and The Gambia. Among children with Shigella , six dichotomized diarrhea severity definitions (GEMS moderate-to-severe diarrhea (MSD), Modified Vesikari Score (MVS), MVS +/− dysentery, Clark score, MAL-ED score, and Shigella mortality score) were examined against two outcomes: change in length/height-for-age z-score (ΔLAZ/HAZ) from enrollment to three-month follow-up and death or hospitalization within fourteen days of enrollment. We compared the performance of each severity score to predict outcomes using linear regression, measures of diagnostic accuracy, and Receiver Operating Characteristic (ROC) curves. Results: Among 1,968 children with Shigella , moderate or severe diarrhea was negatively associated with ΔLAZ/HAZ by three definitions: MVS (−0.07 z-score, 95% CI −0.10 to −0.03), MVS +/− dysentery (−0.05, 95% CI −0.09 to −0.02), and MAL-ED score (−0.04, 95% CI −0.07 to 0.00). GEMS MSD (93.6%), MAL-ED (87.2%), MVS +/− dysentery (85.1%), and MVS (80.9%) had high sensitivity in predicting death or hospitalization, while Shigella mortality had the largest area under the curve (91.0). Conclusions: MVS, MVS +/− dysentery, and the MAL-ED score identified adverse outcomes following Shigella diarrhea, indicating that they are viable options for a Shigella vaccine trial case definition. 40-word summary: We compared six diarrhea severity definitions among children 6-35 months with Shigella . Moderate-to-severe diarrhea as measured by Modified Vesikari Score (MVS), MVS +/− dysentery, and MAL-ED score was associated with reduced length/height-for-age z-score and hospitalization or mortality.

This ecological study analyzed the temporal pattern of clinically diagnosed and laboratory confirmed dengue cases in Belo Horizonte, Minas Gerais, Brazil from 1996 to 2017. The study was divided into two analytical parts, the first of which evaluated the association between dengue incidence and host and climatic factors. The second part encompassed data from 2002 to 2017 and examined dengue incidence in relation to virus serotype and an intra-urban socioeconomic index. Over 22 years there were 469,171 cases and four epidemic peaks. There was an increase in the number, severity, and lethality of cases over the last 10 years of the study period. Biological and environmental factors appear to modulate the behavior of dengue in a large urban center.