Cholera Control by Case-area Targeted Interventions (CATIs)

Official title

Case-area Targeted Interventions (CATIs) Among Household Contacts and Neighbouring Households After Defining Cholera Hotspot Areas in Bangladesh: The Effectiveness of OCV and Potential Impact on Cholera Control

Overview

To evaluate the effectiveness of the CATI approach among household contacts in the reduction of cumulative incidence of cholera and explore the genome analysis and immune response of V. cholerae antigen from different hotspots in Dhaka city, cholera cases will be enrolled by rapid diagnostic test (RDT) from the diarrhoeal patients coming to icddr,b Dhaka hospital. Hotspots will be defined as the households (HHs) surrounding the RDT-positive cholera case (around 20-40m radius). The 'Case area targeted interventions' (CATI) will be given by administrating Oral Cholera Vaccine (OCV) with either one dose or two doses of OCV 1 month apart among household contacts (≥1-year age and non-pregnant women) and contacts of the contacts residing in the adjacent HHs. The passive surveillance for cholera will be followed using the icddr,b hospital, and other health facilities. Data on each individual's states of the clusters (e.g., susceptible, exposed, infectious, or recovered) will be tracked throughout the 3 years study follow-up.

Detailed description

Background (brief):

1. Burden: Annually, 2.8 million cases and 95,000 deaths due to cholera are estimated to occur in cholera-endemic countries of Asia, Latin and Central America, and sub-Saharan Africa. The risk of cholera infection within the household and also around the households of cholera cases is higher than in the overall population. Outbreaks of cholera are unpredictable and can occur both in endemic settings and nonendemic areas depending on environmental conditions, climate change, or any humanitarian crisis where sanitary infrastructure is being disrupted. New phenotypes and genotypes of V. cholerae strains are constantly evolving with outbreaks, resulting in an increased risk of antimicrobial resistance (AMR). 2. Knowledge gap: Standard cholera outbreak response and traditional vaccination campaign is time consuming, costly and usually delayed. A rapid response comprising an early detection of cholera case, hotspot identification and delivery of a rapid response to households around the case could reduce the transmission of disease. But it is not established that whether this early detection of cases and rapid intervention will reduce cholera transmission, also what number of oral cholera vaccine (OCV) will effectively reduce the transmission. 3. Relevance: Availability of OCV is scarce but necessary for rapid response as it an effective short-term single intervention to shortened the epidemic period and cholera cases. This study aims to evaluate the effectiveness of the CATI approach (single/two doses at 1-month intervals) among household contacts and their neighbours in the reduction of the incidence of cholera

Hypothesis: Case area targeted intervention with OCV reduce the incidence of cholera after defining cholera hotspot.

Objectives: This study aims to evaluate the effectiveness of the CATI approach (OCV- one dose, two doses at one-month interval) among household contacts in the reduction of cumulative incidence of cholera and explore the genome analysis and immune response of V. cholerae antigen from different hotspots in Dhaka city.

Methods: The investigators will enroll cholera cases (index) by rapid diagnostic test (RDT) from the diarrhoeal patients coming to icddr,b Dhaka Hospital in and around Dhaka city based on our inclusion and exclusion criteria. Hotspots will be defined as the households (HHs) surrounding the RDT-positive cholera case (around 20-40m radius). The CATIs will be given by administrating OCV with either one dose or two doses of OCV 1 month apart among household contacts (≥1-year age and non-pregnant women) and contacts of the contacts residing in the adjacent HHs. The investigators will enrol on average 150 participants in each cluster of the index cases on the same day of the enrolment within the nearest geographic boundary (around 20-40m radius). Passive surveillance for cholera will be followed using the icddr,b hospital, and other selected health facilities. Data on each individual's states of the clusters (e.g., susceptible, exposed, infectious, or recovered) will be tracked throughout the 3 years study follow-up.

Interventions

• Biological Cholvax
  Produced in Bangladesh and Licenced by the Directorate of Drug Administration (DGDA) for use in Bangladesh

Primary outcome measures

• Number of culture-confirmed V. cholerae [Time frame: From enrollment to 3 years follow-up period.]

Eligibility criteria

Index case eligibility

Inclusion criteria

• Some to severe dehydrated diarrheal patient
• Provide signed informed consent form

Exclusion criteria

1\. Resident in a ward already covered by OCV since 2015

Vaccination Eligibility

Inclusion criteria

• Aged ≥1 year and non-pregnant
• Meeting the definition of IHC and NHC
• Provide signed informed consent form

Exclusion criteria

• History of taking OCV
• Currently suffering from diarrhea
• < 1 year of age
• Pregnant women (verbally confirmed)
• Index case

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Bangladesh · 1 center

• International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b) — Dhaka

Publications

• Ratnayake R, Peyraud N, Ciglenecki I, Gignoux E, Lightowler M, Azman AS, Gakima P, Ouamba JP, Sagara JA, Ndombe R, Mimbu N, Ascorra A; Epicentre and MSF CATI Working Group; Welo PO, Mukamba Musenga E, Miwanda B, Boum Y 2nd, Checchi F, Edmunds WJ, Luquero F, Porten K, Finger F. Effectiveness of case-area targeted interventions including vaccination on the control of epidemic cholera: protocol for a PMID 35793924
• Kanungo S, Desai SN, Nandy RK, Bhattacharya MK, Kim DR, Sinha A, Mahapatra T, Yang JS, Lopez AL, Manna B, Bannerjee B, Ali M, Dhingra MS, Chandra AM, Clemens JD, Sur D, Wierzba TF. Flexibility of oral cholera vaccine dosing-a randomized controlled trial measuring immune responses following alternative vaccination schedules in a cholera hyper-endemic zone. PLoS Negl Trop Dis. 2015 Mar 12;9(3):e0003 PMID 25764513
• Ateudjieu J, Yakum MN, Goura AP, Tembei Ayok M, Guenou E, Kangmo Sielinou CB, Kiadjieu FF, Tsafack M, Douanla Koutio IM, Tchio-Nighie KH, Tchokomeni H, Ntsekendio PN, Sack DA. An innovative approach in monitoring oral cholera vaccination campaign: integration of a between-round survey. BMC Public Health. 2022 Feb 5;22(1):238. doi: 10.1186/s12889-022-12610-5. PMID 35123444
• Qadri F, Wierzba TF, Ali M, Chowdhury F, Khan AI, Saha A, Khan IA, Asaduzzaman M, Akter A, Khan A, Begum YA, Bhuiyan TR, Khanam F, Chowdhury MI, Islam T, Chowdhury AI, Rahman A, Siddique SA, You YA, Kim DR, Siddik AU, Saha NC, Kabir A, Cravioto A, Desai SN, Singh AP, Clemens JD. Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh. N Engl J Med. 2016 May 5;374(18):1723-32. doi PMID 27144848
• Azman AS, Luquero FJ, Ciglenecki I, Grais RF, Sack DA, Lessler J. Correction: The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study. PLoS Med. 2016 Mar 11;13(3):e1001989. doi: 10.1371/journal.pmed.1001989. eCollection 2016 Mar. No abstract available. PMID 26966905
• Sarker MHR, Das SK, Sujon H, Moriyama M, Rahman MM, Uzzaman MN, Banu S, Shahid AS, Das J, Khan SH, Chisti MJ, Faruque A, Ahmed T. Changing Water-Sanitation Determinants of Cholera over Two Decades in Bangladesh. Am J Trop Med Hyg. 2023 Jun 5;109(2):368-375. doi: 10.4269/ajtmh.22-0575. Print 2023 Aug 2. PMID 37277103
• Jones FK, Bhuiyan TR, Muise RE, Khan AI, Slater DM, Hutt Vater KR, Chowdhury F, Kelly M, Xu P, Kovac P, Biswas R, Kamruzzaman M, Ryan ET, Calderwood SB, LaRocque RC, Lessler J, Charles RC, Leung DT, Qadri F, Harris JB, Azman AS. Identifying Recent Cholera Infections Using a Multiplex Bead Serological Assay. mBio. 2022 Dec 20;13(6):e0190022. doi: 10.1128/mbio.01900-22. Epub 2022 Oct 26. PMID 36286520
• Rahman M, Sack DA, Mahmood S, Hossain A. Rapid diagnosis of cholera by coagglutination test using 4-h fecal enrichment cultures. J Clin Microbiol. 1987 Nov;25(11):2204-6. doi: 10.1128/jcm.25.11.2204-2206.1987. PMID 3693549

Identifiers

NCT: NCT07685574 · PR-24004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗