Browsing by Author "Sack D"

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Comparative analysis of cholera serum vibriocidal antibodies from Convalescent and vaccinated adults in Zambia.
(2024-Aug-13) Ng'ombe H; Bosomprah S; Phiri B; Muchimba M; Liswaniso F; Chibuye M; Luchen CC; Chibesa K; Musukuma-Chifulo K; Mwape K; Tigere S; Silwamba S; Sinkala A; Simuyandi M; Mbewe N; Kapaya F; Cunningham AF; Chilengi R; Sack D; Chisenga CC; Centre for Infectious Disease Research in Zambia, Corner of Lukasu and Danny Pule Roads, Mass Media, Lusaka, Zambia; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana. Electronic address: Samuel.Bosomprah@cidrz.org.; Zambia National Public Health Institute, Stand 1186, Corner of Chaholi & Addis Ababa Roads Rhodes Park, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Corner of Lukasu and Danny Pule Roads, Mass Media, Lusaka, Zambia.; Ministry of Health, Levy Mwanawasa University Teaching Hospital, Chainama, Off Great East, P.0 Box 310084, Lusaka, Zambia.; Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.; John Hopkins University, 615 N Wolfe St, Baltimore, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Cholera is responsible for 1.3 to 4.0 million cholera cases globally and poses a significant threat, with Zambia reporting 17,169 cases as of 4th February 2024. Recognizing the crucial link between natural cholera infections and vaccine protection, this study aimed to assess immune responses post cholera infection and vaccination. This was a comparative study consisting of 50 participants enrolled during a cholera outbreak in Zambia's Eastern Province and an additional 56 participants who received oral cholera vaccinations in Zambia's Central Province. Vibriocidal antibodies were plotted as geometric mean titres in the naturally infected and vaccinated individuals. A significant difference (p < 0.047) emerged when comparing naturally infected to fully vaccinated individuals (2 doses) on day 28 against V. cholerae Ogawa. Those who received two doses of the oral cholera vaccine had higher antibody titres than those who were naturally infected. Notably, the lowest titres occurred between 0-9 days post onset, contrasting with peak responses at 10-19 days. This study addresses a critical knowledge gap in understanding cholera immunity dynamics, emphasizing the potential superiority of vaccination-induced immune responses. We recommend post infection vaccination after 40 days for sustained immunity and prolonged protection, especially in cholera hotspots.
Diagnostic accuracy of saliva-based testing as a Vibrio cholerae surveillance tool among naturally infected patients.
(2025-Jan-21) Chisenga CC; Phiri B; Ng'ombe H; Muchimba M; Liswaniso F; Bernshtein B; Cunningham AF; Sack D; Bosomprah S; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham, UK.; Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Alter Lab, Ragon Institute of MGH, MIT and Harvard, Boston, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Saliva, as a diagnostic medium, offers a promising alternative to blood by virtue of its non-invasive collection, which enhances patient compliance, especially in paediatric and geriatric populations. In this study, we assessed the utility of saliva as a non-invasive medium for measuring Vibrio cholerae-specific serum antibodies in naturally infected individuals. We tested paired serum and saliva samples obtained from a total of 63 patients with cholera enrolled in a cohort study. Vibriocidal antibodies assay (IgM/IgG) as markers for accurate determination was used to determine cholera-specific antibody levels. Using receiver operating characteristics (ROC) curve, we found that the best cut-off that maximizes (sensitivity + specificity) is 10 titres. At this saliva titre, the sensitivity is 76.9% (95%CI: 60.9%, 87.7%) and specificity is 80.0% (95%CI: 56.6%, 92.5%). Using Spearman's correlation coefficient, we also found evidence of a positive correlation between V. cholerae saliva and serum antibodies (rho = 0.66, P < 0.001). In conclusion, saliva-based diagnostic cholera tests have high diagnostic accuracy and would be advantageous, cheaper, and quicker for early diagnosis of severe cholera outcomes.
Identification of cholera hotspots in Zambia: A spatiotemporal analysis of cholera data from 2008 to 2017.
(2020-Apr) Mwaba J; Debes AK; Shea P; Mukonka V; Chewe O; Chisenga C; Simuyandi M; Kwenda G; Sack D; Chilengi R; Ali M; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Zambia National Public Health Institute, Lusaka, Zambia.; University of Zambia, School of Health Sciences, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Seroconversion and Kinetics of Vibriocidal Antibodies during the First 90 Days of Re-Vaccination with Oral Cholera Vaccine in an Endemic Population.
(2024-Apr-08) Chisenga CC; Phiri B; Ng'ombe H; Muchimba M; Musukuma-Chifulo K; Silwamba S; Laban NM; Luchen C; Liswaniso F; Chibesa K; Mubanga C; Mwape K; Simuyandi M; Cunningham AF; Sack D; Bosomprah S; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.; Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individuals resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled and re-vaccinated with two doses of Shanchol™, regardless of previous vaccination, and followed-up for 90 days. Bloods were collected at baseline before re-vaccination, at day 14 prior to second dosing, and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60, and 90 days across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly, irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.