A Baseline Study in Support of Clinical Evaluation of an Oral Shigella Vaccine Development in Africa

NCT04312906 | Completed

• 1 other identifier: ShigOraVax Epi
• Study Type: observational
• Target: 1,334
• Locations: 2 countries
• Sites: 3

Brief Summary

This study aims to address the paucity of accurate incidence data of diarrheal diseases associated with Shigella in Zambia and Burkina Faso. Given the limited feasibility of the current complex diagnostic methods used to detect Shigella in endemic and developing countries due to the costs, the none availability of reagents and a requirement of expensive and complex machinery, we suggest to use a rapide, easy-to-use, cost-effective, and robust Polymerase Chain Reaction (PCR) based rapid tool, the Loop-mediated isothermal amplification (LAMP) based diagnostic assay (ES-RLDT). This baseline study will enable us to generate an accurate estimate of Shigella incidence so as to inform future trials' designs of an oral vaccine development (ShigOraVax) in Burkina Faso and Zambia. This project is part of the EDCTP2 programme supported by the European Union under grant agreement "No RIA2018V-2308

Conditions

Diarrhea; Diarrhea Infectious

Keywords

diarrhea; Shigella; Vaccine

Outcome Measures

Primary Outcomes (1)

• Incidence of Shigella diarrheal disease in children under fives in Zambia and Burkina Faso

  number of children testing Shigella positive during course of study

  1 year

Secondary Outcomes (4)

• Attributable fraction for Shigella among all-cause MSD in children under 5 years

  1 year

• Incidence of ETEC diarrheal disease in children under fives in Zambia and Burkina Faso

  1 year

• Antimicrobial susceptibility/resistance of isolates to common antibiotics

  1 year

• Predictive accuracy of the modified diarrhoea severity scoring tool among children presenting with MSD

  1 year

Interventions

no intervention OTHER

No intervention

Eligibility Criteria

• Age: Up to 5 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Children under 5 years of age living in the study catchment areas

You may qualify if:

• Children who are under five years, are resident in the catchment areas of participating health facilities and whose parents or guardians have no anticipated plan to leave the area for the next 12 months;
• Willing to submit child biological samples for testing and/or storage;
• Parent or guardian providing written informed consenting to the study.

You may not qualify if:

• Any child born after the Census has taken place(Zambia) or whose household was not randomly selected from the database (Burkina Faso)
• Current participation in a research with the use of any drug or vaccine.
• Parent or guardian unwilling to provide consent
• Any confirmed or suspected immunosuppressive or immuniodeficiency condition based on medical history and physical examination (No testing will be done for HIV)
• A family history of congenital or hereditary immunodeficiency
• Major congenital defects
• Immunosuppresive therapy within 3 months prior to recruitment

Sponsors & Collaborators

• Centre for Infectious Disease Research in Zambia: lead
• European Vaccine Initiative: collaborator
• Groupe de Recherche Action en Sante: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (3)

Schiphra Hospital

Ouagadougou, Burkina Faso

Location

Arthur Davidson Childrens Hospital

Ndola, Copperbelt, 10101, Zambia

Location

Chainda South Health Facility

Lusaka, 10101, Zambia

Location

Related Publications (4)

• Kotloff KL, Winickoff JP, Ivanoff B, Clemens JD, Swerdlow DL, Sansonetti PJ, Adak GK, Levine MM. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull World Health Organ. 1999;77(8):651-66.

  PMID: 10516787 BACKGROUND

• Platts-Mills JA, Liu J, Rogawski ET, Kabir F, Lertsethtakarn P, Siguas M, Khan SS, Praharaj I, Murei A, Nshama R, Mujaga B, Havt A, Maciel IA, McMurry TL, Operario DJ, Taniuchi M, Gratz J, Stroup SE, Roberts JH, Kalam A, Aziz F, Qureshi S, Islam MO, Sakpaisal P, Silapong S, Yori PP, Rajendiran R, Benny B, McGrath M, McCormick BJJ, Seidman JC, Lang D, Gottlieb M, Guerrant RL, Lima AAM, Leite JP, Samie A, Bessong PO, Page N, Bodhidatta L, Mason C, Shrestha S, Kiwelu I, Mduma ER, Iqbal NT, Bhutta ZA, Ahmed T, Haque R, Kang G, Kosek MN, Houpt ER; MAL-ED Network Investigators. Use of quantitative molecular diagnostic methods to assess the aetiology, burden, and clinical characteristics of diarrhoea in children in low-resource settings: a reanalysis of the MAL-ED cohort study. Lancet Glob Health. 2018 Dec;6(12):e1309-e1318. doi: 10.1016/S2214-109X(18)30349-8. Epub 2018 Oct 1.

  PMID: 30287127 BACKGROUND

• GBD Diarrhoeal Diseases Collaborators. Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect Dis. 2017 Sep;17(9):909-948. doi: 10.1016/S1473-3099(17)30276-1. Epub 2017 Jun 1.

  PMID: 28579426 BACKGROUND

• Song T, Toma C, Nakasone N, Iwanaga M. Sensitive and rapid detection of Shigella and enteroinvasive Escherichia coli by a loop-mediated isothermal amplification method. FEMS Microbiol Lett. 2005 Feb 1;243(1):259-63. doi: 10.1016/j.femsle.2004.12.014.

  PMID: 15668027 BACKGROUND

Related Links

• Information about the project
• Information about the call

Biospecimen

Retention: SAMPLES WITH DNA

Stool- Isolates will be grown on horse blood agar and Shigella Salmonella agar plates overnight at 37°C to detect potential contamination. Only pure ETEC and Shigella cultures will be used for DNA extraction. For Illumina whole genome sequencing, we will use the Genomic DNA kit (Promega) for DNA extraction according to the manufacturer's instructions. For Single-Molecule Real Time (SMRT) sequencing (Pacific Bioscience) which requires long intact strands of DNA, we will use the phenol-chloroform extraction method described by Mentzer and others (2014). The DNA will be stored in E buffer and sequenced at the Wellcome Trust Sanger Institute.

MeSH Terms

Conditions

Diarrhea; Dysentery; Dysentery, Bacillary

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Sophie Hourard

  European Vaccine Initiative

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2020
• First Posted: March 18, 2020
• Study Start: September 14, 2020
• Primary Completion: November 30, 2021
• Study Completion: November 30, 2021
• Last Updated: July 20, 2022

Record last verified: 2022-07

Locations

ZA (2); BU (1)