Maternal preconceptional and prenatal exposure to El Niño Southern Oscillation levels and child mortality: a multi-country study.

El Niño Southern Oscillation (ENSO) has been shown to relate to the epidemiology of childhood infectious diseases, but evidence for whether they increase child deaths is limited. Here, we investigate the impact of mothers' ENSO exposure during and prior to delivery on child mortality by constructing a retrospective cohort study in 38 low- and middle-income countries. We find that high levels of ENSO indices cumulated over 0-12 lagged months before delivery are associated with significant increases in risks of under-five mortality; with the hazard ratio ranging from 1.33 (95% confidence interval [CI], 1.26, 1.40) to 1.89 (95% CI, 1.78, 2.00). Child mortality risks are particularly related to maternal exposure to El Niño-like conditions in the 0th-1st and 6th-12th lagged months. The El Niño effects are larger in rural populations and those with unsafe sources of drinking water and less education. Thus, preventive interventions are particularly warranted for the socio-economically disadvantaged.

Exploring different health care providers´ perceptions on the management of diarrhoea in cholera hotspots in the Democratic Republic of Congo: A qualitative content analysis.

Global cholera guidelines support wider healthcare system strengthening interventions, alongside vertical outbreak responses, to end cholera. Well-trained healthcare providers are essential for a resilient health system and can create synergies with childhood diarrhoea, which has higher mortality. We explored how the main provider groups for diarrhoea in cholera hotspots interact, decide on treatment, and reflect on possible limiting factors and opportunities to improve prevention and treatment. We conducted focus group discussions in September 2022 with different healthcare provider types in two urban and two rural cholera hotspots in the North Kivu and Tanganyika provinces in the Eastern Democratic Republic of Congo. Content analysis was used with the same coding applied to all providers. In total 15 focus group discussions with medical doctors (n = 3), nurses (n = 4), drug shop vendors (n = 4), and traditional health practitioners (n = 4) were performed. Four categories were derived from the analysis. (i) Provider dynamics: scepticism between all cadres was prominent, whilst also acknowledging the important role all provider groups have in current case management. (ii) Choice of treatment: affordability and strong caregiver demands shaped by cultural beliefs strongly affected choice. (iii) Financial consideration on access: empathy was strong, with providers finding innovative ways to create access to treatment. Concurrently, financial incentives were important, and providers asked for this to be considered when subsiding treatment. (iv) How to improve: the current cholera outbreak response approach was appreciated however there was a strong wish for broader long-term interventions targeting root causes, particularly community access to potable water. Drug shops and traditional health practitioners should be considered for inclusion in health policies for cholera and other diarrhoeal diseases. Financial incentives for the provider to improve access to low-cost treatment and investment in access to potable water should furthermore be considered.

Improved water supply infrastructure to reduce acute diarrhoeal diseases and cholera in Uvira, Democratic Republic of the Congo: Results and lessons learned from a pragmatic trial.

BACKGROUND: Safely managed drinking water is critical to prevent diarrhoeal diseases, including cholera, but evidence on the effectiveness of piped water supply in reducing these diseases in low-income and complex emergency settings remains scarce. METHODS: We conducted a trial of water supply infrastructure improvements in Uvira (DRC). Our primary objective was to estimate the relationship between a composite index of water service quality and the monthly number of suspected cholera cases admitted to treatment facilities and, as a secondary analysis, the number of cases confirmed by rapid diagnostic tests. Other exposures included the quantity of supplied water and service continuity. We used Poisson generalised linear models with generalised estimating equations to estimate incidence rate ratios. FINDINGS: Associations between suspected cholera incidence and water service quality (RR 0·86, 95% CI 0·73-1·01), quantity (RR 0·80, 95% CI 0·62-1·02) and continuity (RR 0·81, 95% CI 0·77-0·86) were estimated. The magnitudes of the associations were similar between confirmed cholera incidence and water service quality (RR 0·84, 95% CI 0·73-0·97), quantity (RR 0·76, 95% CI 0·61-0·94) and continuity (RR 0·75, 95% CI 0·69-0·81). These results suggest that an additional 5 L/user/day or 1.2 hour per day of water production could reduce confirmed cholera by 24% (95% CI 6-39%) and 25% (95% CI 19-31%), respectively. INTERPRETATION: Ensuring a sufficient and continuous piped water supply may substantially reduce the burden of endemic cholera and diarrhoeal diseases but evaluating this rigorously is challenging. Pragmatic strategies are needed for public health research on complex interventions in protracted emergency settings. TRIAL REGISTRATION: The trial is registered in ClinicalTrials.gov ID NCT02928341. https://classic.clinicaltrials.gov/ct2/show/NCT02928341.

Enhanced cholera surveillance to improve vaccination campaign efficiency.

Systematic testing for Vibrio cholerae O1 is rare, which means that the world's limited supply of oral cholera vaccines (OCVs) may not be delivered to areas with the highest true cholera burden. Here we used a phenomenological model with subnational geographic targeting and fine-scale vaccine effects to model how expanding V. cholerae testing affected impact and cost-effectiveness for preventive vaccination campaigns across different bacteriological confirmation and vaccine targeting assumptions in 35 African countries. Systematic testing followed by OCV targeting based on confirmed cholera yielded higher efficiency and cost-effectiveness and slightly fewer averted cases than status quo scenarios targeting suspected cholera. Targeting vaccine to populations with an annual incidence rate greater than 10 per 10,000, the testing scenario averted 10.8 (95% prediction interval (PI) 9.4-12.6) cases per 1,000 fully vaccinated persons while the status quo scenario averted 6.9 (95% PI 6.0-7.8) cases per 1,000 fully vaccinated persons. In the testing scenario, testing costs increased by US$31 (95% PI 25-39) while vaccination costs reduced by US$248 (95% PI 176-326) per averted case compared to the status quo. Introduction of systematic testing into cholera surveillance could improve efficiency and reach of global OCV supply for preventive vaccination.

Facility capacity and provider knowledge for cholera surveillance and diarrhoea case management in cholera hotspots in the Democratic Republic of Congo - a mixed-methods study.

BACKGROUND: Wider healthcare-strengthening interventions are recommended in cholera hotspots and could benefit other types of diarrhoeal diseases which contribute to greater mortality than cholera. OBJECTIVE: Describe facility capacity and provider knowledge for case management of diarrhoea and cholera surveillance in cholera hotspots in the Democratic Republic of Congo (DRC) among health facilities, drug shops, and traditional health practitioners. METHODS: We conducted a sequential exploratory mixed-method study, using focus group discussions, facility audits, and provider knowledge questionnaires during September and October 2022 in North Kivu and Tanganyika provinces, Eastern DRC. Content analysis was used for qualitative data. Quantitative data were summarised by facility level and healthcare provider type. Audit and knowledge scores (range 0-100) were generated. Multivariable linear regression estimated association between scores and explanatory factors. Qualitative and quantitative data were triangulated during interpretation. RESULTS: Overall, 244 facilities and 308 providers were included. The mean audit score for health facilities was 51/100 (SD: 17). Private facilities had an -11.6 (95% CI, -16.7 to -6.6) lower adjusted mean score compared to public. Mean knowledge score was 59/100 (95% CI, 57 to 60) for health facility personnel, 46/100 (95% CI, 43 to 48) for drug shop vendors and 37/100 (95% CI, 34 to 39) for traditional health practitioners. Providers had particularly low knowledge concerning when to check for low blood sugar, use of nasogastric tubes, and dosing schedules. Knowledge about case definitions for cholera was similar between groups (range 41-58%) except for traditional health practitioners for the definition during an outbreak 15/73 (21%). CONCLUSIONS: Increasing awareness of cholera case definitions in this context could help improve cholera surveillance and control. Increased support and supervision, especially for private providers, could help ensure facilities are equipped to provide safe care. More nuanced aspects of case management should be emphasised in provider training.

Cholera Deaths During Outbreaks in Uvira, Eastern Democratic Republic of the Congo, 10-35 Months After Mass Vaccination.

Our understanding of the burden and drivers of cholera mortality is hampered by limited surveillance and confirmation capacity. Leveraging enhanced clinical and laboratory surveillance in the cholera-endemic community of Uvira, eastern Democratic Republic of Congo, we describe cholera deaths across 3 epidemics between September 2021 and September 2023 following mass vaccination.

Effectiveness of one dose of killed oral cholera vaccine in an endemic community in the Democratic Republic of the Congo: a matched case-control study.

BACKGROUND: A global shortage of cholera vaccines has increased the use of single-dose regimens, rather than the standard two-dose regimen. There is sparse evidence on single-dose protection, particularly in children. In 2020, a mass vaccination campaign was conducted in Uvira, an endemic urban setting in eastern Democratic Republic of the Congo, resulting in largely single-dose coverage. We examined the effectiveness of a single-dose of the oral cholera vaccine Euvichol-Plus in this high-burden setting. METHODS: In this matched case-control study, we recruited individuals with medically attended confirmed cholera in the two cholera treatment facilities in the city of Uvira. The control group consisted of age-matched, sex-matched, and neighbourhood-matched community individuals. We recruited across two distinct periods: Oct 14, 2021, to March 10, 2022 (12-17 months after vaccination), and Nov 21, 2022, to Oct 18, 2023 (24-36 months after vaccination). Study staff administered structured questionnaires to all participants to capture demographics, household conditions, potential confounding variables, and vaccination status. The odds of vaccination for the case and control groups were contrasted in conditional logistic regression models to estimate unadjusted and adjusted vaccine effectiveness. FINDINGS: We enrolled 658 individuals with confirmed cholera and 2274 matched individuals for the control group. 99 (15·1%) individuals in the case group were younger than 5 years at the time of vaccination. The adjusted single-dose vaccine effectiveness was 52·7% (95% CI 31·4 to 67·4) 12-17 months after vaccination and 44·7% (24·8 to 59·4) 24-36 months after vaccination. Although protection in the first 12-17 months after vaccination was similar for children aged 1-4 years and older individuals, the estimate of protection in children aged 1-4 years appeared to wane during the third year after vaccination (adjusted vaccine effectiveness 32·9%, 95% CI -30·7 to 65·5), with CIs spanning the null. INTERPRETATION: A single dose of Euvichol-Plus provided substantial protection against medically attended cholera for at least 36 months after vaccination in this cholera-endemic setting. Although the evidence provides support for similar levels of protection in young children and others in the short term, protection among children younger than 5 years might wane significantly during the third year after vaccination. FUNDING: Wellcome Trust and Gavi, the Vaccine Alliance.