Journal Article > ResearchFull Text
Lancet Planet Health. 2020 December 1; Volume 4; DOI:10.1016/S2542-5196(20)30255-2
Jones FK, Wamala JF, Rumunu J, Mawien PN, Kol MT, et al.
Lancet Planet Health. 2020 December 1; Volume 4; DOI:10.1016/S2542-5196(20)30255-2
Background
Between 2014 and 2017, successive cholera epidemics occurred in South Sudan within the context of civil war, population displacement, flooding, and drought. We aim to describe the spatiotemporal and molecular features of the three distinct epidemic waves and explore the role of vaccination campaigns, precipitation, and population movement in shaping cholera spread in this complex setting.
Methods
In this descriptive epidemiological study, we analysed cholera linelist data to describe the spatiotemporal progression of the epidemics. We placed whole-genome sequence data from pandemic Vibrio cholerae collected throughout these epidemics into the global phylogenetic context. Using whole-genome sequence data in combination with other molecular attributes, we characterise the relatedness of strains circulating in each wave and the region. We investigated the association of rainfall and the instantaneous basic reproduction number using distributed lag non-linear models, compared county-level attack rates between those with early and late reactive vaccination campaigns, and explored the consistency of the spatial patterns of displacement and suspected cholera case reports.
Findings
The 2014 (6389 cases) and 2015 (1818 cases) cholera epidemics in South Sudan remained spatially limited whereas the 2016–17 epidemic (20 438 cases) spread among settlements along the Nile river. Initial cases of each epidemic were reported in or around Juba soon after the start of the rainy season, but we found no evidence that rainfall modulated transmission during each epidemic. All isolates analysed had similar genotypic and phenotypic characteristics, closely related to sequences from Uganda and Democratic Republic of the Congo. Large-scale population movements between counties of South Sudan with cholera outbreaks were consistent with the spatial distribution of cases. 21 of 26 vaccination campaigns occurred during or after the county-level epidemic peak. Counties vaccinated on or after the peak incidence week had 2·2 times (95% CI 2·1–2·3) higher attack rates than those where vaccination occurred before the peak.
Interpretation
Pandemic V cholerae of the same clonal origin was isolated throughout the study period despite interepidemic periods of no reported cases. Although the complex emergency in South Sudan probably shaped some of the observed spatial and temporal patterns of cases, the full scope of transmission determinants remains unclear. Timely and well targeted use of vaccines can reduce the burden of cholera; however, rapid vaccine deployment in complex emergencies remains challenging.
Between 2014 and 2017, successive cholera epidemics occurred in South Sudan within the context of civil war, population displacement, flooding, and drought. We aim to describe the spatiotemporal and molecular features of the three distinct epidemic waves and explore the role of vaccination campaigns, precipitation, and population movement in shaping cholera spread in this complex setting.
Methods
In this descriptive epidemiological study, we analysed cholera linelist data to describe the spatiotemporal progression of the epidemics. We placed whole-genome sequence data from pandemic Vibrio cholerae collected throughout these epidemics into the global phylogenetic context. Using whole-genome sequence data in combination with other molecular attributes, we characterise the relatedness of strains circulating in each wave and the region. We investigated the association of rainfall and the instantaneous basic reproduction number using distributed lag non-linear models, compared county-level attack rates between those with early and late reactive vaccination campaigns, and explored the consistency of the spatial patterns of displacement and suspected cholera case reports.
Findings
The 2014 (6389 cases) and 2015 (1818 cases) cholera epidemics in South Sudan remained spatially limited whereas the 2016–17 epidemic (20 438 cases) spread among settlements along the Nile river. Initial cases of each epidemic were reported in or around Juba soon after the start of the rainy season, but we found no evidence that rainfall modulated transmission during each epidemic. All isolates analysed had similar genotypic and phenotypic characteristics, closely related to sequences from Uganda and Democratic Republic of the Congo. Large-scale population movements between counties of South Sudan with cholera outbreaks were consistent with the spatial distribution of cases. 21 of 26 vaccination campaigns occurred during or after the county-level epidemic peak. Counties vaccinated on or after the peak incidence week had 2·2 times (95% CI 2·1–2·3) higher attack rates than those where vaccination occurred before the peak.
Interpretation
Pandemic V cholerae of the same clonal origin was isolated throughout the study period despite interepidemic periods of no reported cases. Although the complex emergency in South Sudan probably shaped some of the observed spatial and temporal patterns of cases, the full scope of transmission determinants remains unclear. Timely and well targeted use of vaccines can reduce the burden of cholera; however, rapid vaccine deployment in complex emergencies remains challenging.
Journal Article > LetterFull Text
Emerg Infect Dis. 2023 February 1; Volume 29 (Issue 2); DOI:10.3201/eid2902.221495
Azman AS, Gignoux E, Nesbitt R, Rumunu J, Aggarwal R, et al.
Emerg Infect Dis. 2023 February 1; Volume 29 (Issue 2); DOI:10.3201/eid2902.221495
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 2017 December 4; Volume 98 (Issue 2); DOI:10.4269/ajtmh.17-0339
Bliss JR, Bouhenia M, Hale P, Couturier BA, Iyer AS, et al.
Am J Trop Med Hyg. 2017 December 4; Volume 98 (Issue 2); DOI:10.4269/ajtmh.17-0339
Displaced persons living in camps are at an increased risk of diarrheal diseases. Subclinical carriage of pathogens may contribute to the spread of disease, especially for microbes that require a low infectious dose. Multiplex real-time polymerase chain reaction was performed to detect a panel of 20 bacterial, viral, and protozoal targets, and we report a high prevalence of enteropathogen carriage, including Shigella spp. or enteroinvasive Escherichia coli in 14%, among a sample of 88 asymptomatic individuals in an internally displaced persons camp in South Sudan. Further studies are needed to determine the contribution of such carriage to the spread of disease.
Journal Article > ResearchFull Text
Lancet Global Health. 2016 November 1; Volume 4 (Issue 11); e856-e863.; DOI:10.1016/S2214-109X(16)30211-X
Azman AS, Parker LA, Rumunu J, Tadesse F, Grandesso F, et al.
Lancet Global Health. 2016 November 1; Volume 4 (Issue 11); e856-e863.; DOI:10.1016/S2214-109X(16)30211-X
BACKGROUND
Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention.
METHODS
We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India).
FINDINGS
Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0).
INTERPRETATION
One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings.
Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention.
METHODS
We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India).
FINDINGS
Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0).
INTERPRETATION
One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2024 January 22; Volume 18 (Issue 1); e0011661.; DOI:10.1371/journal.pntd.0011661
Nesbitt RC, Asilaza VK, Gignoux EM, Koyuncu A, Gitahi P, et al.
PLoS Negl Trop Dis. 2024 January 22; Volume 18 (Issue 1); e0011661.; DOI:10.1371/journal.pntd.0011661
INTRODUCTION
Hepatitis E (HEV) genotypes 1 and 2 are the common cause of jaundice and acute viral hepatitis that can cause large-scale outbreaks. HEV infection is associated with adverse fetal outcomes and case fatality risks up to 31% among pregnant women. An efficacious three-dose recombinant vaccine (Hecolin) has been licensed in China since 2011 but until 2022, had not been used for outbreak response despite a 2015 WHO recommendation. The first ever mass vaccination campaign against hepatitis E in response to an outbreak was implemented in 2022 in Bentiu internally displaced persons camp in South Sudan targeting 27,000 residents 16–40 years old, including pregnant women.
METHODS
We conducted a vaccination coverage survey using simple random sampling from a sampling frame of all camp shelters following the third round of vaccination. For survey participants vaccinated in the third round in October, we asked about the onset of symptoms experienced within 72 hours of vaccination. During each of the three vaccination rounds, passive surveillance of adverse events following immunisation (AEFI) was put in place at vaccination sites and health facilities in Bentiu IDP camp.
RESULTS
We surveyed 1,599 individuals and found that self-reported coverage with one or more dose was 86% (95% CI 84–88%), 73% (95% CI 70–75%) with two or more doses and 58% (95% CI 55–61%) with three doses. Vaccination coverage did not differ significantly by sex or age group. We found no significant difference in coverage of at least one dose between pregnant and non-pregnant women, although coverage of at least two and three doses was 8 and 14 percentage points lower in pregnant women. The most common reasons for non-vaccination were temporary absence or unavailability, reported by 60% of unvaccinated people. Passive AEFI surveillance captured few mild AEFI, and through the survey we found that 91 (7.6%) of the 1,195 individuals reporting to have been vaccinated in October 2022 reported new symptoms starting within 72 hours after vaccination, most commonly fever, headache or fatigue.
CONCLUSIONS
We found a high coverage of at least one dose of the Hecolin vaccine following three rounds of vaccination, and no severe AEFI. The vaccine was well accepted and well tolerated in the Bentiu IDP camp community and should be considered for use in future outbreak response.
Hepatitis E (HEV) genotypes 1 and 2 are the common cause of jaundice and acute viral hepatitis that can cause large-scale outbreaks. HEV infection is associated with adverse fetal outcomes and case fatality risks up to 31% among pregnant women. An efficacious three-dose recombinant vaccine (Hecolin) has been licensed in China since 2011 but until 2022, had not been used for outbreak response despite a 2015 WHO recommendation. The first ever mass vaccination campaign against hepatitis E in response to an outbreak was implemented in 2022 in Bentiu internally displaced persons camp in South Sudan targeting 27,000 residents 16–40 years old, including pregnant women.
METHODS
We conducted a vaccination coverage survey using simple random sampling from a sampling frame of all camp shelters following the third round of vaccination. For survey participants vaccinated in the third round in October, we asked about the onset of symptoms experienced within 72 hours of vaccination. During each of the three vaccination rounds, passive surveillance of adverse events following immunisation (AEFI) was put in place at vaccination sites and health facilities in Bentiu IDP camp.
RESULTS
We surveyed 1,599 individuals and found that self-reported coverage with one or more dose was 86% (95% CI 84–88%), 73% (95% CI 70–75%) with two or more doses and 58% (95% CI 55–61%) with three doses. Vaccination coverage did not differ significantly by sex or age group. We found no significant difference in coverage of at least one dose between pregnant and non-pregnant women, although coverage of at least two and three doses was 8 and 14 percentage points lower in pregnant women. The most common reasons for non-vaccination were temporary absence or unavailability, reported by 60% of unvaccinated people. Passive AEFI surveillance captured few mild AEFI, and through the survey we found that 91 (7.6%) of the 1,195 individuals reporting to have been vaccinated in October 2022 reported new symptoms starting within 72 hours after vaccination, most commonly fever, headache or fatigue.
CONCLUSIONS
We found a high coverage of at least one dose of the Hecolin vaccine following three rounds of vaccination, and no severe AEFI. The vaccine was well accepted and well tolerated in the Bentiu IDP camp community and should be considered for use in future outbreak response.
Journal Article > ResearchFull Text
Lancet Global Health. 2024 November 1; Volume 12 (Issue 11); e1881-e1890.; DOI:10.1016/S2214-109X(24)00321-8
Nesbitt RC, Azman AS, Asilaza VK, Edwards JK, Gitahi P, et al.
Lancet Global Health. 2024 November 1; Volume 12 (Issue 11); e1881-e1890.; DOI:10.1016/S2214-109X(24)00321-8
Conference Material > Abstract
Nesbitt RC, Rumunu J, Asilaza VK, Gitahi P, Nkemenang P, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/qdmj-8n51
INTRODUCTION
A three-dose recombinant vaccine against hepatitis E, Hecolin, has been licensed for use in China since 2011. While not recommended for routine use due to lack of evidence on burden in the general population, in 2015 WHO recommended the vaccine be considered in outbreaks. As of early 2022 however, the vaccine had not been used in outbreak settings. A reduced-dose vaccination schedule, if effective, could make the vaccine an important outbreak response tool. In response to an increase in hepatitis E cases in a camp for internally displaced people in Bentiu, South Sudan in late 2021, MSF and South Sudan’s MoH implemented the first ever mass reactive vaccination campaign against hepatitis E virus (HEV). Three vaccination rounds took place in March, April, and October 2022, targeting 26,848 individuals aged 16-40 years, including pregnant women. We set up enhanced surveillance and conducted a case-control study to estimate two-dose vaccine effectiveness (VE).
METHODS
All suspected cases presenting to the MSF hospital who were eligible for vaccination and provided consent were enrolled in the study, comprising a questionnaire, laboratory examinations and a follow-up visit after 2-4 weeks. Vaccine-eligible suspect cases were matched to community controls. We estimated twodose VE against probable (anti-HEV IgM positive with elevated alanine transaminase, or a four-fold rise in IgG in paired samples) and confirmed (HEV RNA positive) hepatitis E using conditional logistic regression models.
ETHICS
This study was approved by the MSF and South Sudan Ethics Review Boards.
RESULTS
Considering the period two weeks after the second vaccination round between 11 May and 30 December 2022, 287 vaccine-eligible suspect hepatitis E cases were enrolled, including one probable and 16 confirmed cases. Among probable and confirmed cases, two (11.8%) were vaccinated with two or more doses compared to 40 (40%) of their 100 matched controls. We estimated a VE of 86.5% (95% confidence interval, CI, 36.3–97.1) for one/two doses and 83.9% (95% CI, -33.1–98.1%) for two doses. In addition to this direct protection, we observed a 5.5-fold decrease in the incidence rate of probable/confirmed cases hepatitis E cases before and after the second dose campaign (including those not eligible for vaccination). Laboratory confirmation of hepatitis E infection is ongoing, and we expect to revise VE estimates and incidence based on these results.
CONCLUSION
Following the first mass reactive vaccination campaign against hepatitis E, incidence has declined. Preliminary VE estimates suggest that the short-term protection provided by this reduced dose regimen may be high and potentially sufficient for outbreak response.
CONFLICTS OF INTEREST
None declared
A three-dose recombinant vaccine against hepatitis E, Hecolin, has been licensed for use in China since 2011. While not recommended for routine use due to lack of evidence on burden in the general population, in 2015 WHO recommended the vaccine be considered in outbreaks. As of early 2022 however, the vaccine had not been used in outbreak settings. A reduced-dose vaccination schedule, if effective, could make the vaccine an important outbreak response tool. In response to an increase in hepatitis E cases in a camp for internally displaced people in Bentiu, South Sudan in late 2021, MSF and South Sudan’s MoH implemented the first ever mass reactive vaccination campaign against hepatitis E virus (HEV). Three vaccination rounds took place in March, April, and October 2022, targeting 26,848 individuals aged 16-40 years, including pregnant women. We set up enhanced surveillance and conducted a case-control study to estimate two-dose vaccine effectiveness (VE).
METHODS
All suspected cases presenting to the MSF hospital who were eligible for vaccination and provided consent were enrolled in the study, comprising a questionnaire, laboratory examinations and a follow-up visit after 2-4 weeks. Vaccine-eligible suspect cases were matched to community controls. We estimated twodose VE against probable (anti-HEV IgM positive with elevated alanine transaminase, or a four-fold rise in IgG in paired samples) and confirmed (HEV RNA positive) hepatitis E using conditional logistic regression models.
ETHICS
This study was approved by the MSF and South Sudan Ethics Review Boards.
RESULTS
Considering the period two weeks after the second vaccination round between 11 May and 30 December 2022, 287 vaccine-eligible suspect hepatitis E cases were enrolled, including one probable and 16 confirmed cases. Among probable and confirmed cases, two (11.8%) were vaccinated with two or more doses compared to 40 (40%) of their 100 matched controls. We estimated a VE of 86.5% (95% confidence interval, CI, 36.3–97.1) for one/two doses and 83.9% (95% CI, -33.1–98.1%) for two doses. In addition to this direct protection, we observed a 5.5-fold decrease in the incidence rate of probable/confirmed cases hepatitis E cases before and after the second dose campaign (including those not eligible for vaccination). Laboratory confirmation of hepatitis E infection is ongoing, and we expect to revise VE estimates and incidence based on these results.
CONCLUSION
Following the first mass reactive vaccination campaign against hepatitis E, incidence has declined. Preliminary VE estimates suggest that the short-term protection provided by this reduced dose regimen may be high and potentially sufficient for outbreak response.
CONFLICTS OF INTEREST
None declared
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2017 June 8; Volume 11 (Issue 6); e0005652.; DOI:10.1371/journal.pntd.0005652
Parker LA, Rumunu J, Jamet C, Kenyi Y, Lino RL, et al.
PLoS Negl Trop Dis. 2017 June 8; Volume 11 (Issue 6); e0005652.; DOI:10.1371/journal.pntd.0005652
INTRODUCTION
In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area.
METHODOLOGY/PRINCIPAL FINDINGS
Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign (‘case-triggered’ interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0–73.7) and was highest among children ages 5–14 years (90.0%, 95% CI 85.7–94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68–0.96). In the case-triggered interventions, each lasting 1–2 days, coverage varied (range: 30–87%) with an average of 51.0% (95% CI 41.7–60.3).
CONCLUSIONS/SIGNIFICANCE
Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.
In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area.
METHODOLOGY/PRINCIPAL FINDINGS
Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign (‘case-triggered’ interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0–73.7) and was highest among children ages 5–14 years (90.0%, 95% CI 85.7–94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68–0.96). In the case-triggered interventions, each lasting 1–2 days, coverage varied (range: 30–87%) with an average of 51.0% (95% CI 41.7–60.3).
CONCLUSIONS/SIGNIFICANCE
Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.
Conference Material > Poster
Nesbitt RC, Rumunu J, Asilaza VK, Gitahi P, Nkemenang P, et al.
MSF Scientific Day International 2023. 2023 June 7
Journal Article > LetterFull Text
Lancet Infect Dis. 2022 August 1; Volume 22 (Issue 8); 1110-1111.; DOI:10.1016/S1473-3099(22)00421-2
Ciglenecki I, Rumunu J, Wamala JF, Nkemenang P, Duncker J, et al.
Lancet Infect Dis. 2022 August 1; Volume 22 (Issue 8); 1110-1111.; DOI:10.1016/S1473-3099(22)00421-2