Journal Article > ResearchFull Text
Sci Rep. 2016 October 24; Volume 6; 35742.; DOI:10.1038/srep35742
Iyer AS, Ryan ET, Martin S, Legros D, Lessler J, et al.
Sci Rep. 2016 October 24; Volume 6; 35742.; DOI:10.1038/srep35742
Despite recent large-scale cholera outbreaks, little is known about the immunogenicity of oral cholera vaccines (OCV) in African populations, particularly among those at highest cholera risk. During a 2015 preemptive OCV campaign among internally displaced persons in South Sudan, a year after a large cholera outbreak, we enrolled 37 young children (1-5 years old), 67 older children (6-17 years old) and 101 adults (≥18 years old), who received two doses of OCV (Shanchol) spaced approximately 3 weeks apart. Cholera-specific antibody responses were determined at days 0, 21 and 35 post-immunization. High baseline vibriocidal titers (>80) were observed in 21% of the participants, suggesting recent cholera exposure or vaccination. Among those with titers ≤80, 90% young children, 73% older children and 72% adults seroconverted (≥4 fold titer rise) after the 1(st) OCV dose; with no additional seroconversion after the 2(nd) dose. Post-vaccination immunological endpoints did not differ across age groups. Our results indicate Shanchol was immunogenic in this vulnerable population and that a single dose alone may be sufficient to achieve similar short-term immunological responses to the currently licensed two-dose regimen. While we found no evidence of differential response by age, further immunologic and epidemiologic studies are needed.
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
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 > ReviewFull Text
Bull World Health Organ. 2014 September 29; Volume 92 (Issue 12); 881-893.; DOI:10.2471/BLT.14.139949
Martin S, Lopez AMZ, Bellos A, Deen JL, Ali MI, et al.
Bull World Health Organ. 2014 September 29; Volume 92 (Issue 12); 881-893.; DOI:10.2471/BLT.14.139949
OBJECTIVE
To describe and analyse the characteristics of oral cholera vaccination campaigns; including location, target population, logistics, vaccine coverage and delivery costs.
METHODS
We searched PubMed, the World Health Organization (WHO) website and the Cochrane database with no date or language restrictions. We contacted public health personnel, experts in the field and in ministries of health and did targeted web searches.
FINDINGS
A total of 33 documents were included in the analysis. One country, Viet Nam, incorporates oral cholera vaccination into its public health programme and has administered approximately 10.9 million vaccine doses between 1997 and 2012. In addition, over 3 million doses of the two WHO pre-qualified oral cholera vaccines have been administered in more than 16 campaigns around the world between 1997 and 2014. These campaigns have either been pre-emptive or reactive and have taken place under diverse conditions, such as in refugee camps or natural disasters. Estimated two-dose coverage ranged from 46 to 88% of the target population. Approximate delivery cost per fully immunized person ranged from 0.11-3.99 United States dollars.
CONCLUSIONS
Experience with oral cholera vaccination campaigns continues to increase. Public health officials may draw on this experience and conduct oral cholera vaccination campaigns more frequently.
To describe and analyse the characteristics of oral cholera vaccination campaigns; including location, target population, logistics, vaccine coverage and delivery costs.
METHODS
We searched PubMed, the World Health Organization (WHO) website and the Cochrane database with no date or language restrictions. We contacted public health personnel, experts in the field and in ministries of health and did targeted web searches.
FINDINGS
A total of 33 documents were included in the analysis. One country, Viet Nam, incorporates oral cholera vaccination into its public health programme and has administered approximately 10.9 million vaccine doses between 1997 and 2012. In addition, over 3 million doses of the two WHO pre-qualified oral cholera vaccines have been administered in more than 16 campaigns around the world between 1997 and 2014. These campaigns have either been pre-emptive or reactive and have taken place under diverse conditions, such as in refugee camps or natural disasters. Estimated two-dose coverage ranged from 46 to 88% of the target population. Approximate delivery cost per fully immunized person ranged from 0.11-3.99 United States dollars.
CONCLUSIONS
Experience with oral cholera vaccination campaigns continues to increase. Public health officials may draw on this experience and conduct oral cholera vaccination campaigns more frequently.
Journal Article > ResearchFull Text
Vaccine. 2019 September 10; Volume 38 Suppl 1; A132-A140.; DOI:10.1016/j.vaccine.2019.08.086
Pezzoli L, Cavailler P, Mengel M, Matzger H, Lorenson T, et al.
Vaccine. 2019 September 10; Volume 38 Suppl 1; A132-A140.; DOI:10.1016/j.vaccine.2019.08.086
Vaccination is a key intervention to prevent and control cholera in conjunction with water, sanitation and hygiene activities. An oral cholera vaccine (OCV) stockpile was established by the World Health Organization (WHO) in 2013. We reviewed its use from July 2013 to all of 2018 in order to assess its role in cholera control. We computed information related to OCV deployments and campaigns conducted including setting, target population, timelines, delivery strategy, reported adverse events, coverage achieved, and costs. In 2013–2018, a total of 83,509,941 OCV doses have been requested by 24 countries, of which 55,409,160 were approved and 36,066,010 eventually shipped in 83 deployments, resulting in 104 vaccination campaigns in 22 countries. OCVs had in general high uptake (mean administrative coverage 1st dose campaign at 90.3%; 2nd dose campaign at 88.2%; mean survey-estimated two-dose coverage at 69.9%, at least one dose at 84.6%) No serious adverse events were reported. Campaigns were organized quickly (five days median duration). In emergency settings, the longest delay was from the occurrence of the emergency to requesting OCV (median: 26 days). The mean cost of administering one dose of vaccine was 2.98 USD. The OCV stockpile is an important public health resource. OCVs were generally well accepted by the population and their use demonstrated to be safe and feasible in all settings. OCV was an inexpensive intervention, although timing was a limiting factor for emergency use. The dynamic created by the establishment of the OCV stockpile has played a role in the increased use of the vaccine by setting in motion a virtuous cycle by which better monitoring and evaluation leads to better campaign organization, better cholera control, and more requests being generated. Further work is needed to improve timeliness of response and contextualize strategies for OCV delivery in the various settings.
Journal Article > CommentaryFull Text
PLOS Med. 2015 November 17; Volume 12 (Issue 11); e1001901.; DOI:10.1371/journal.pmed.1001901
Abubakar A, Azman AS, Rumunu J, Ciglenecki I, Helderman T, et al.
PLOS Med. 2015 November 17; Volume 12 (Issue 11); e1001901.; DOI:10.1371/journal.pmed.1001901
SUMMARY POINTS
• A global oral cholera vaccine (OCV) stockpile was established in 2013 to improve rapid access to the vaccine in outbreaks and emergencies in which cholera risk is high. The first deployment from the global OCV stockpile was to South Sudan in 2014 because of high cholera risk from massive population displacements within the civil war.
•. 256,700 doses of OCV were delivered, with high coverage, throughout the country as part of a comprehensive cholera prevention strategy by multiple agencies, some of which had little to no previous experience with this vaccine.
• A cholera epidemic began during vaccination, and a basic comparison of epidemic curves in vaccinated and unvaccinated areas suggests little to no transmission occurred in vaccinated areas, though more in depth analysis is needed.
• This deployment highlights the feasibility of effective deployments from the OCV stockpile and the importance of strong coordination between governmental and nongovernmental agencies in cholera prevention and control planning from the assessment of cholera risk to the deployment of the vaccines.
•. A larger global supply of OCV is urgently needed to cover those most in need. With limited vaccine availability now and likely in the upcoming years, more work is needed on deciding how to most efficiently use the vaccine, which may include alternative dosing regimens and targeting specific subpopulation
• A global oral cholera vaccine (OCV) stockpile was established in 2013 to improve rapid access to the vaccine in outbreaks and emergencies in which cholera risk is high. The first deployment from the global OCV stockpile was to South Sudan in 2014 because of high cholera risk from massive population displacements within the civil war.
•. 256,700 doses of OCV were delivered, with high coverage, throughout the country as part of a comprehensive cholera prevention strategy by multiple agencies, some of which had little to no previous experience with this vaccine.
• A cholera epidemic began during vaccination, and a basic comparison of epidemic curves in vaccinated and unvaccinated areas suggests little to no transmission occurred in vaccinated areas, though more in depth analysis is needed.
• This deployment highlights the feasibility of effective deployments from the OCV stockpile and the importance of strong coordination between governmental and nongovernmental agencies in cholera prevention and control planning from the assessment of cholera risk to the deployment of the vaccines.
•. A larger global supply of OCV is urgently needed to cover those most in need. With limited vaccine availability now and likely in the upcoming years, more work is needed on deciding how to most efficiently use the vaccine, which may include alternative dosing regimens and targeting specific subpopulation
Journal Article > Meta-AnalysisFull Text
Clin Infect Dis. 2017 November 21; Volume 66 (Issue 12); 1960-1971.; DOI:10.1093/cid/cix1039
Lopez AMZ, Deen JL, Azman AS, Luguero FJ, Kanungo S, et al.
Clin Infect Dis. 2017 November 21; Volume 66 (Issue 12); 1960-1971.; DOI:10.1093/cid/cix1039
In addition to improved water supply and sanitation, the two-dose killed oral cholera vaccine (OCV) is an important tool for the prevention and control of cholera. We aimed to document the immunogenicity and protection (efficacy and effectiveness) conferred by a single OCV dose against cholera. The meta-analysis showed an estimated 73% and 77% of individuals seroconverted to the Ogawa and Inaba serotypes, respectively, after an OCV first dose. The estimates of single-dose vaccine protection from available studies are 87% at 2 months decreasing to 33% at 2 years. Current immunologic and clinical data suggest that protection conferred by a single dose of killed OCV may be sufficient to reduce short-term risk in outbreaks or other high-risk settings, which may be especially useful when vaccine supply is limited. However, until more data suggests otherwise, a second dose should be given as soon as circumstances allow to ensure robust protection.
Journal Article > ResearchFull Text
PLOS One. 2016 December 19; Volume 11 (Issue 12); DOI:10.1371/journal.pone.0168257
Ontweka L, Deng LO, Rauzier J, Debes AK, Tadesse F, et al.
PLOS One. 2016 December 19; Volume 11 (Issue 12); DOI:10.1371/journal.pone.0168257
Cholera rapid diagnostic tests (RDT) could play a central role in outbreak detection and surveillance in low-resource settings, but their modest performance has hindered their broad adoption. The addition of an enrichment step may improve test specificity. We describe the results of a prospective diagnostic evaluation of the Crystal VC RDT (Span Diagnostics, India) with enrichment step and of culture, each compared to polymerase chain reaction (PCR), during a cholera outbreak in South Sudan. RDTs were performed on alkaline peptone water inoculated with stool and incubated for 4-6 hours at ambient temperature. Cholera culture was performed from wet filter paper inoculated with stool. Molecular detection of Vibrio cholerae O1 by PCR was done from dry Whatman 903 filter papers inoculated with stool, and from wet filter paper supernatant. In August and September 2015, 101 consecutive suspected cholera cases were enrolled, of which 36 were confirmed by PCR. The enriched RDT had 86.1% (95% CI: 70.5-95.3) sensitivity and 100% (95% CI: 94.4-100) specificity compared to PCR as the reference standard. The sensitivity of culture versus PCR was 83.3% (95% CI: 67.2-93.6) for culture performed on site and 72.2% (95% CI: 54.8-85.8) at the international reference laboratory, where samples were tested after an average delay of two months after sample collection, and specificity was 98.5% (95% CI: 91.7-100) and 100% (95% CI: 94.5-100), respectively. The RDT with enrichment showed performance comparable to that of culture and could be a sustainable alternative to culture confirmation where laboratory capacity is limited.
Journal Article > ReviewFull Text
Lancet Infect Dis. 2017 July 17; Volume 17 (Issue 10); DOI:10.1016/S1473-3099(17)30359-6
Bi Q, Ferreras E, Pezzoli L, Legros D, Ivers LI, et al.
Lancet Infect Dis. 2017 July 17; Volume 17 (Issue 10); DOI:10.1016/S1473-3099(17)30359-6
Journal Article > ResearchFull Text
Vaccine. 2019 June 19; Volume 37 (Issue 28); DOI:10.1016/j.vaccine.2019.05.044
Grandesso F, Kasambara W, Page AL, Debes AK, Mbangome M, et al.
Vaccine. 2019 June 19; Volume 37 (Issue 28); DOI:10.1016/j.vaccine.2019.05.044
Background: In response to a cholera outbreak among mobile, difficult-to-reach fishermen on Lake Chilwa, Malawi in 2016, a novel vaccine distribution strategy exploited the proven vaccine thermostability. Fishermen, while taking the first vaccine dose under supervision, received the second dose in a sealed bag, and were told to drink it two weeks later. This study assessed short-term vaccine protection of this strategy.
Methods: Patients with diarrhoea admitted to health facilities around lake were interviewed and a stool sample collected for PCR testing. Vaccine effectiveness was assessed in a case-control test-negative design by comparing cases (PCR-positive for V. cholerae O1) and controls (patients with diarrhoea but PCR-negative) and with the screening method that compared the proportions of vaccinated among cholera cases versus the general fishermen population.
Results: Of 145 study participants, 120 were fishermen living on the lake. Vaccine effectiveness at three-months was 90.0% [95%CI:38.8;98.4] among fishermen and 83.3% [95%CI: 20.8; 96.5] among all participants in the case-control test-negative design, and 97.5% [95%CI: 90.9;99.3] with the screening method.
Conclusion: This strategy was effective in providing short-term protection in fishermen against cholera. Further research is needed to determine the adding value of the second dose and to identify the optimal vaccination strategies for different contexts.
Methods: Patients with diarrhoea admitted to health facilities around lake were interviewed and a stool sample collected for PCR testing. Vaccine effectiveness was assessed in a case-control test-negative design by comparing cases (PCR-positive for V. cholerae O1) and controls (patients with diarrhoea but PCR-negative) and with the screening method that compared the proportions of vaccinated among cholera cases versus the general fishermen population.
Results: Of 145 study participants, 120 were fishermen living on the lake. Vaccine effectiveness at three-months was 90.0% [95%CI:38.8;98.4] among fishermen and 83.3% [95%CI: 20.8; 96.5] among all participants in the case-control test-negative design, and 97.5% [95%CI: 90.9;99.3] with the screening method.
Conclusion: This strategy was effective in providing short-term protection in fishermen against cholera. Further research is needed to determine the adding value of the second dose and to identify the optimal vaccination strategies for different contexts.