Browsing by Author "Shea P"

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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.
Serum vibriocidal responses when second doses of oral cholera vaccine are delayed 6 months in Zambia.
(2021-Jul-22) Mwaba J; Chisenga CC; Xiao S; Ng'ombe H; Banda E; Shea P; Mabula-Bwalya C; Mwila-Kazimbaya K; Laban NM; Alabi P; Chirwa-Chobe M; Simuyandi M; Harris J; Iyer AS; Bosomprah S; Scalzo P; Murt KN; Ram M; Kwenda G; Ali M; Sack DA; Chilengi R; Debes AK; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: adebes1@jhu.edu.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.; Research Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Research Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.; Research Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; London School of Hygiene and Tropical Medicine, United Kingdom.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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).
Three transmission events of Vibrio cholerae O1 into Lusaka, Zambia.
(2021-Jun-14) Mwaba J; Debes AK; Murt KN; Shea P; Simuyandi M; Laban N; Kazimbaya K; Chisenga C; Li S; Almeida M; Meisel JS; Shibemba A; Kantenga T; Mukonka V; Kwenda G; Sack DA; Chilengi R; Stine OC; Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, USA.; Zambia National Public Health Institute, Lusaka, Zambia.; Department of Biomedical Sciences, University of Zambia School of Health Sciences, Lusaka, Zambia.; Department of Pathology and Microbiology, University Teaching Hospitals, Lusaka, Zambia.; University of Maryland School of Medicine, Baltimore, MD, USA.; University of Maryland, College Park, College Park, MD, USA.; University of Maryland School of Medicine, Baltimore, MD, USA. cstine@som.umaryland.edu.; Université Paris-Saclay, INRAE, MGP, 78350, Jouy-en-Josas, France.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.