• Cholera Rapid Test with Enrichment Step Has Diagnostic Performance Equivalent to Culture

      Ontweka, LN; Deng, LO; Rauzier, J; Debes, AK; Tadesse, F; Parker, LA; Wamala, JF; Bior, BK; Lasuba, M; But, AB; et al. (Public Library of Science, 2016-12-19)
      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.
    • Effectiveness of One Dose of Oral Cholera Vaccine in Response to an Outbreak: A Case-Cohort Study

      Azman, AS; Parker, LA; Rumunu, J; Tadesse, F; Grandesso, F; Deng, LL; Lino, RL; Bior, BK; Lasuba, M; Page, AL; et al. (Elsevier, 2016-11-01)
      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.
    • High Prevalence of Shigella or Enteroinvasive Escherichia coli Carriage among Residents of an Internally Displaced Persons Camp in South Sudan

      Bliss, J; Bouhenia, M; Hale, P; Couturier, BA; Iyer, AS; Rumunu, J; Martin, S; Wamala, JF; Abubakar, A; Sack, DA; et al. (American Society of Tropical Medicine and Hygiene, 2017-12-04)
      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.
    • Immune Responses to an Oral Cholera Vaccine in Internally Displaced Persons in South Sudan

      Iyer, AS; Bouhenia, M; Rumunu, J; Abubakar, A; Gruninger, RJ; Pita, J; Lino, RL; Deng, LL; Wamala, JF; Ryan, ET; et al. (Nature Publishing Group, 2016-10-24)
      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.
    • Immunogenicity and Protection from a Single Dose of Internationally available killed oral Cholera Vaccine: a systematic review and meta-analysis

      Lopez, AL; Deen, J; Azman, AS; Luquero, FJ; Kanungo, S; Dutta, S; von Seidlein, L; Sack, DA (Oxford University Press, 2017-11-21)
      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.
    • Population-Level Effect of Cholera Vaccine on Displaced Populations, South Sudan, 2014

      Azman, AS; Rumunu, J; Abubakar, A; West, H; Ciglenecki, I; Helderman, T; Wamala, JF; Vázquez, OR; Perea, W; Sack, DA; et al. (Center for Disease Control, 2016-06-01)
      Following mass population displacements in South Sudan, preventive cholera vaccination campaigns were conducted in displaced persons camps before a 2014 cholera outbreak. We compare cholera transmission in vaccinated and unvaccinated areas and show vaccination likely halted transmission within vaccinated areas, illustrating the potential for oral cholera vaccine to stop cholera transmission in vulnerable populations.
    • The Scenario Approach for Countries Considering the Addition of Oral Cholera Vaccination in Cholera Preparedness and Control Plans

      Deen, J; von Seidlein, L; Luquero, FJ; Troeger, C; Reyburn, R; Lopez, AL; Debes, A; Sack, DA (Elsevier, 2016-01-01)
      Oral cholera vaccination could be deployed in a diverse range of situations from cholera-endemic areas and locations of humanitarian crises, but no clear consensus exists. The supply of licensed, WHO-prequalified cholera vaccines is not sufficient to meet endemic and epidemic needs worldwide and so prioritisation is needed. We have developed a scenario approach to systematically classify situations in which oral cholera vaccination might be useful. Our scenario approach distinguishes between five types of cholera epidemiology based on experiences from around the world and provides evidence that we hope will spur the development of detailed guidelines on how and where oral cholera vaccines could, and should, be most rationally deployed.