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.

Genomic Microevolution of Vibrio cholerae O1, Lake Tanganyika Basin, Africa.

Africa's Lake Tanganyika basin is a cholera hotspot. During 2001-2020, Vibrio cholerae O1 isolates obtained from the Democratic Republic of the Congo side of the lake belonged to 2 of the 5 clades of the AFR10 sublineage. One clade became predominant after acquiring a parC mutation that decreased susceptibility to ciprofloxacin.

Prevalence and diversity of enteric pathogens among cholera treatment centre patients with acute diarrhea in Uvira, Democratic Republic of Congo.

BACKGROUND: Cholera remains a major global health challenge. Uvira, in the Democratic Republic of the Congo (DRC), has had endemic cholera since the 1970's and has been implicated as a possible point of origin for national outbreaks. A previous study among this population, reported a case confirmation rate of 40% by rapid diagnostic test (RDT) among patients at the Uvira Cholera Treatment Centre (CTC). This study considers the prevalence and diversity of 15 enteric pathogens in suspected cholera cases seeking treatment at the Uvira CTC. METHODS: We used the Luminex xTAG® multiplex PCR to test for 15 enteric pathogens, including toxigenic strains of V. cholerae in rectal swabs preserved on Whatman FTA Elute cards. Results were interpreted on MAGPIX® and analyzed on the xTAG® Data Analysis Software. Prevalence of enteric pathogens were calculated and pathogen diversity was modelled with a Poisson regression. RESULTS: Among 269 enrolled CTC patients, PCR detected the presence of toxigenic Vibrio cholerae in 38% (103/269) of the patients, which were considered to be cholera cases. These strains were detected as the sole pathogen in 36% (37/103) of these cases. Almost half (45%) of all study participants carried multiple enteric pathogens (two or more). Enterotoxigenic Escherichia coli (36%) and Cryptosporidium (28%) were the other most common pathogens identified amongst all participants. No pathogen was detected in 16.4% of study participants. Mean number of pathogens was highest amongst boys and girls aged 1-15 years and lowest in women aged 16-81 years. Ninety-three percent of toxigenic V. cholerae strains detected by PCR were found in patients having tested positive for V. cholerae O1 by RDT. CONCLUSIONS: Our study supports previous results from DRC and other cholera endemic areas in sub-Sahara Africa with less than half of CTC admissions positive for cholera by PCR. More research is required to determine the causes of severe acute diarrhea in these low-resource, endemic areas to optimize treatment measures. TRIAL REGISTRATION: This study is part of the impact evaluation study entitled: "Impact Evaluation of Urban Water Supply Improvements on Cholera and Other Diarrheal Diseases in Uvira, Democratic Republic of Congo" registered on 10 October 2016 at clinicaltrials.gov Identification number: NCT02928341 .

Confirmation of cholera by rapid diagnostic test amongst patients admitted to the cholera treatment centre in Uvira, Democratic Republic of the Congo.

INTRODUCTION: Cholera is endemic in the Eastern provinces of the Democratic Republic of the Congo since 1978, and Uvira in South-Kivu has been reporting suspected cholera cases nearly every week for over a decade. The clinical case definition for suspected cholera is relatively non-specific, and cases are rarely confirmed by laboratory methods, especially in endemic settings. This may lead to over-estimation of cholera cases and limit effective public health responses. METHODS AND RESULTS: Between April 2016 and November 2017, 69% of the 2,059 patients admitted to the Uvira Cholera Treatment Centre (CTC) were tested for cholera with rapid diagnostic tests (RDTs). Of those admitted as suspected cholera cases, only 40% tested positive for cholera, equivalent to an estimated annual incidence of suspected/confirmed cholera in Uvira of 43.8 and 16.3 cases per 10,000 inhabitants respectively. A multivariable logistic regression indicates that boys aged 2 to 4 years, girls aged 5 to 15 years and adult men are respectively 1.9, 2.1 and 1.8 times more likely to test positive than adult women. On the contrary, boys under 2 are 10 times less likely to test positive. The odds of testing positive also increase as weekly admissions to the CTC rise, with up to a 5-fold increase observed during the weeks with the highest numbers of admissions compared to the lowest ones. Other predictors of cholera confirmation include duration of stay at the CTC, clinical outcome of admission, lower weekly rainfall and area of residence in Uvira, with the northern part of town having the highest confirmation rate. CONCLUSION: Cholera is an on-going public health problem in Uvira but the majority of suspected cases admitted to the CTC were found to be negative for cholera after RDT testing. These findings may have important implications for cholera control strategies in favour of interventions that address cholera and other diarrhoeal diseases alike.