Browsing by Author "Debes, Amanda K."

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Contrasting Epidemiology of Cholera in Bangladesh and Africa.
(2021-Dec-20) Sack, David A.; Debes, Amanda K.; Ateudjieu, Jerome; Bwire, Godfrey; Ali, Mohammad; Ngwa, Moise C.; Mwaba, John; Chilengi, Roma; Orach, Christopher C.; Boru, Waqo; Mohamed, Ahmed A.; Ram, Malathi; George, Christine M.; Stine, Colin O.
In Bangladesh and West Bengal cholera is seasonal, transmission occurs consistently annually. By contrast, in most African countries, cholera has inconsistent seasonal patterns and long periods without obvious transmission. Transmission patterns in Africa occur during intermittent outbreaks followed by elimination of that genetic lineage. Later another outbreak may occur because of reintroduction of new or evolved lineages from adjacent areas, often by human travelers. These then subsequently undergo subsequent elimination. The frequent elimination and reintroduction has several implications when planning for cholera's elimination including: a) reconsidering concepts of definition of elimination, b) stress on rapid detection and response to outbreaks, c) more effective use of oral cholera vaccine and WASH, d) need to readjust estimates of disease burden for Africa, e) re-examination of water as a reservoir for maintaining endemicity in Africa. This paper reviews major features of cholera's epidemiology in African countries which appear different from the Ganges Delta.
Identification of cholera hotspots in Zambia: A spatiotemporal analysis of cholera data from 2008 to 2017.
(2020-Apr) Mwaba, John; Debes, Amanda K.; Shea, Patrick; Mukonka, Victor; Chewe, Orbrie; Chisenga, Caroline C.; Simuyandi, Michelo; Kwenda, Geoffrey; Sack, David; Chilengi, Roma; Ali, Mohammad
The global burden of cholera is increasing, with the majority (60%) of the cases occurring in sub-Saharan Africa. In Zambia, widespread cholera outbreaks have occurred since 1977, predominantly in the capital city of Lusaka. During both the 2016 and 2018 outbreaks, the Ministry of Health implemented cholera vaccination in addition to other preventative and control measures, to stop the spread and control the outbreak. Given the limitations in vaccine availability and the logistical support required for vaccination, oral cholera vaccine (OCV) is now recommended for use in the high risk areas ("hotspots") for cholera. Hence, the aim of this study was to identify areas with an increased risk of cholera in Zambia. Retrospective cholera case data from 2008 to 2017 was obtained from the Ministry of Health, Department of Public Health and Disease Surveillance. The Zambian Central Statistical Office provided district-level population data, socioeconomic and water, sanitation and hygiene (WaSH) indicators. To identify districts at high risk, we performed a discrete Poisson-based space-time scan statistic to account for variations in cholera risk across both space and time over a 10-year study period. A zero-inflated negative binomial regression model was employed to identify the district level risk factors for cholera. The risk map was generated by classifying the relative risk of cholera in each district, as obtained from the space-scan test statistic. In total, 34,950 cases of cholera were reported in Zambia between 2008 and 2017. Cholera cases varied spatially by year. During the study period, Lusaka District had the highest burden of cholera, with 29,080 reported cases. The space-time scan statistic identified 16 districts to be at a significantly higher risk of having cholera. The relative risk of having cholera in these districts was significantly higher and ranged from 1.25 to 78.87 times higher when compared to elsewhere in the country. Proximity to waterbodies was the only factor associated with the increased risk for cholera (P<0.05). This study provides a basis for the cholera elimination program in Zambia. Outside Lusaka, the majority of high risk districts identified were near the border with the DRC, Tanzania, Mozambique, and Zimbabwe. This suggests that cholera in Zambia may be linked to movement of people from neighboring areas of cholera endemicity. A collaborative intervention program implemented in concert with neighboring countries could be an effective strategy for elimination of cholera in Zambia, while also reducing rates at a regional level.
Prevalence and Patterns of Enteric Co-Infections Among Individuals Presenting with Cholera-like Diarrheal Disease During Seasonal Cholera Outbreaks
(Pathogens, 2025-11-30) Kuntawala, Dhvani H.; Bosomprah, Samuel; Phiri, Bernard; Ng’ombe, Harriet; Liswaniso, Fraser; Muchimba, Mutinta; Silwamba, Suwilanji; Chibesa, Kennedy; Nzangwa, Bertha T.; Luchen, Charlie C.; Mwape, Innocent; Tigere, Sekayi F.; Simuyandi, Michelo; Mbewe, Nyuma; Chilengi, Roma; Debes, Amanda K.; Thomson, Nicholas R.; Sack, David A.; Chisenga, Caroline C.
Abstract Cholera remains a major public health challenge, and co-infections can complicate clinical outcomes. In a cross-sectional study, we investigated the prevalence and patterns of enteric co-infections during Zambia’s 2023–2024 cholera outbreak and evaluated their implications for disease severity. 240 suspected cholera patients were enrolled from five healthcare facilities in Lusaka. Stools were tested for 11 enteric pathogens using the Bosphore® Gastroenteritis Panel Kit v2 on the QuantStudio 5 qPCR, with Vibrio cholerae confirmed by real-time PCR (quantitative PCR). Co-infections were highly prevalent, affecting 79.2% of participants. Campylobacter was the most frequently detected pathogen (70.0%), followed by Norovirus GI/GII (20.0%). Persons living with HIV were significantly more likely to present with co-infections than their counterparts (adjusted PR 1.27, 95% CI: 1.07–1.51; p = 0.008). Participants with confirmed V. cholerae + coinfections (N = 62) were less likely to developed moderate to severe disease compared to those with mono-infections (adjusted PR 0.59, 95% CI: 0.38–0.90; p = 0.014). These findings highlight the high prevalence and complexity of co-infections during cholera outbreaks, potentially contributing to antimicrobial resistance. They also highlight the need for targeted clinical management, particularly among persons living with HIV.
Serum vibriocidal responses when second doses of oral cholera vaccine are delayed 6 months in Zambia.
(2021-Jul-22) Mwaba, John; Chisenga, Caroline C.; Xiao, Shaoming; Ng'ombe, Harriet; Banda, Elena; Shea, Patrick; Mabula-Bwalya, Chileshe; Mwila-Kazimbaya, Katayi; Laban, Natasha M.; Alabi, Peter; Chirwa-Chobe, Masuzyo; Simuyandi, Michelo; Harris, Jason; Iyer, Anita S.; Bosomprah, Samuel; Scalzo, Paul; Murt, Kelsey N.; Ram, Malathi ; Kwenda, Geoffrey; Ali, Mohammad; Sack, David A.; Chilengi, Roma; Debes, Amanda K.
Two-dose killed oral cholera vaccines (OCV) are currently being used widely to control cholera. The standard dose-interval for OCV is 2 weeks; however, during emergency use of the vaccine, it may be more appropriate to use the available doses to quickly give a single dose to more people and give a delayed second dose when more vaccine becomes available. This study is an open label, randomized, phase 2 clinical trial of the vibriocidal response induced by OCV, comparing the responses when the second dose was given either 2 weeks (standard dose interval) or 6 months (extended dose interval) after the first dose. Vaccine was administered to healthy participants > 1 year of age living in the Lukanga Swamps area of Zambia. Three age cohorts (<5 years, 5-14 years, and ≥ 15 years) were randomized to the either dose-interval. The primary outcome was the vibriocidal GMT 14 days after the second dose. 156 of 172 subjects enrolled in the study were included in this analysis. The Inaba vibriocidal titers were not significantly different 14 days post dose two for a standard dose-interval GMT: 45.6 (32-64.9), as compared to the GMT 47.6 (32.6-69.3), for the extended dose-interval, (p = 0.87). However, the Ogawa vibriocidal GMTs were significantly higher 14 days post dose two for the extended-dose interval at 87.6 (58.9-130.4) compared to the standard dose-interval group at 49.7 (34.1-72.3), p = 0.04. Vibriocidal seroconversion rates (a > 4-fold rise in vibriocidal titer) were not significantly different between dose-interval groups. This study demonstrated that vibriocidal titers 14 days after a second dose when given at an extended\ dose interval were similar to the standard dose-interval. The findings suggest that a flexible dosing schedule may be considered when epidemiologically appropriate. The trial was registered at Clinical Trials.gov (NCT03373669).
Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data.
(2023-Mar) Badr, Hamada S.; Colston, Josh M.; Nguyen, Nhat-Lan H.; Chen, Yen T.; Burnett, Eleanor; Ali, Syed A.; Rayamajhi, Ajit; Satter, Syed M.; Van Trang, Nguyen; Eibach, Daniel; Krumkamp, Ralf; May, Jürgen; Adegnika, Ayola A.; Manouana, Gédéon P.; Kremsner, Peter G.; Chilengi, Roma; Hatyoka, Luiza ; Debes, Amanda K.; Ateudjieu, Jerome ; Faruque, Abu S. G.; Hossain, Mahangir J.; Kanungo, Suman; Kotloff, Karen L.; Mandomando, Inácio; Nisar, Imran M.; Omore, Richard; Sow, Samba O.; Zaidi, Anita K. M.; Lambrecht, Nathalie; Adu, Bright; Page, Nicola; Platts-Mills, James A.; Freitas, Cesar F.; Pelkonen, Tuula; Ashorn, Per; Maleta, Kenneth; Ahmed, Tahmeed; Bessong, Pascal; Bhutta, Zulfiqar A.; Mason, Carl; Mduma, Estomih; Olortegui, Maribel P.; Peñataro, Pablo Y.; Lima, Aldo A. M.; Kang, Gagandeep; Humphrey, Jean; Ntozini, Robert ; Prendergast, Andrew J.; Okada, Kazuhisa; Wongboot, Warawan; Langeland, Nina; Moyo, Sabrina J.; Gaensbauer, James; Melgar, Mario; Freeman, Matthew; Chard, Anna N.; Thongpaseuth, Vonethalom; Houpt, Eric; Zaitchik, Benjamin F.; Kosek, Margaret N.
BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation.
Statistical Modelling of Waning Immunity After Shanchol Vaccination: A Prospective Cohort Study
(Vaccines, 2026-01-30) Bosomprah, Samuel; Liswaniso, Fraser; Phiri, Bernard; Chibuye, Mwelwa; Luchen, Charlie C.; Ng’ombe, Harriet; Chibesa, Kennedy; Ngosa, Dennis; Muchimba, Mutinta; Debes, Amanda K.; Chilengi, Roma; Sack, David A.; Chisenga, Caroline C.
Abstract Introduction: Cholera remains a major public health threat in endemic settings, and oral cholera vaccine (Shanchol™) campaigns are increasingly used amid constrained global supply. However, practical decisions on revaccination require clearer, setting-specific estimates of how rapidly vaccine-induced vibriocidal antibodies peak and wane. Methods: We conducted a prospective cohort kinetics analysis in Lukanga Swamps (Central Province, Zambia), enrolling adults (18–65 years) stratified by prior Shanchol™ exposure (0, 1, or 2 previous doses). All participants received two Shanchol™ doses 14 days apart, with serum collected at baseline and days 14, 28, 60, and 90 (end of follow-up). Ogawa and Inaba vibriocidal titres were measured using a complement-based assay and analysed on the log10 scale. Serotype-specific mixed-effects models with natural cubic splines for time (knots: 14, 28, 60 days) assessed trajectories by prior-dose strata, adjusting for age, sex, and HIV status. Peak timing and post-peak half-life were derived from model-based predictions with participant-level bootstrap CIs (1000 replications). Results: The analysis included 225 participants: 68 (30.2%) with zero prior doses, 89 (39.6%) with one, and 68 (30.2%) with two; median age was 33 years (IQR 25–49), 56.4% were female, and 19.2% were HIV-positive. Modelled titres for both serotypes rose steeply after vaccination, peaking around day 36–37 across prior-dose strata. Ogawa titres reached half of peak by about day 73–78, corresponding to post-peak half-lives of 37–41 days; Inaba declined more slowly with half-lives of 42–46 days. Confidence intervals overlapped across prior-dose strata, indicating minimal differences by vaccination history. Conclusions: In this cholera-endemic adult population, Shanchol™ induced vibriocidal responses that peaked at ~5 weeks and waned over the following 5–7 weeks, with broadly similar kinetics regardless of prior vaccination and slightly slower decay for Inaba than Ogawa. These parameters can inform booster timing in hotspot settings.
Three transmission events of Vibrio cholerae O1 into Lusaka, Zambia.
(2021-Jun-14) Mwaba, John; Debes, Amanda K.; Murt, Kelsey N.; Shea, Patrick; Simuyandi, Michelo; Laban, Natasha; Kazimbaya, Katayi; Chisenga, Caroline C.; Li, Shan; Almeida, Mathieu; Meisel, Jacquelyn S.; Shibemba, Aaron; Kantenga, Timothy; Mukonka, Victor; Kwenda, Geoffrey; Sack, David A.; Chilengi, Roma; Stine, Colin O.
BACKGROUND: Cholera has been present and recurring in Zambia since 1977. However, there is a paucity of data on genetic relatedness and diversity of the Vibrio cholerae isolates responsible for these outbreaks. Understanding whether the outbreaks are seeded from existing local isolates or if the outbreaks represent separate transmission events can inform public health decisions. RESULTS: Seventy-two V. cholerae isolates from outbreaks in 2009/2010, 2016, and 2017/2018 in Zambia were characterized using multilocus variable number tandem repeat analysis (MLVA) and whole genome sequencing (WGS). The isolates had eight distinct MLVA genotypes that clustered into three MLVA clonal complexes (CCs). Each CC contained isolates from only one outbreak. The results from WGS revealed both clustered and dispersed single nucleotide variants. The genetic relatedness of isolates based on WGS was consistent with the MLVA, each CC was a distinct genetic lineage and had nearest neighbors from other East African countries. In Lusaka, isolates from the same outbreak were more closely related to themselves and isolates from other countries than to isolates from other outbreaks in other years. CONCLUSIONS: Our observations are consistent with i) the presence of random mutation and alternative mechanisms of nucleotide variation, and ii) three separate transmission events of V. cholerae into Lusaka, Zambia. We suggest that locally, case-area targeted invention strategies and regionally, well-coordinated plans be in place to effectively control future cholera outbreaks.