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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04312906
Recruitment Status : Completed
First Posted : March 18, 2020
Last Update Posted : July 20, 2022
Sponsor:
Collaborators:
European Vaccine Initiative
Groupe de Recherche Action en Sante
European and Developing Countries Clinical Trials Partnership (EDCTP)
Information provided by (Responsible Party):
Centre for Infectious Disease Research in Zambia

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


Condition or disease Intervention/treatment
Diarrhea Diarrhea Infectious Other: no intervention

Detailed Description:

This is an observational, cohort study to determine the incidence of Shigella in children under 5 years in Zambia and Burkina Faso.

We will first identify the population at risk i.e children that will form the cohort of children to be followed up in the study. In Zambia, this will be done through a household census that will be conducted to identify children under 5 years in the catchment areas served by the selected health facility. In Burkina Faso, the study will be conducted in the Ouagadougou Health and Demographic Surveillance System (OHDSS) catchment area. Children under five years old will be randomly selected from the OHDSS database. The heads of households or guardians of the randomly selected children will be approached for the informed consenting process to enrol into the cohort study.

We will then follow up these children using active and passive surveillance systems follow for the duration of the study. During passive follow-up, a surveillance system will be set up at the selected health facilities serving the catchment populations. Parents/guardians of enrolled children will be asked to take their child to designated health facilities once they develop an episode of diarrhoea. At presentation, a clinical evaluation will be performed on the child and the data recorded. A stool sample/rectal swab will then be collected. Once a stool sample is tested positive for Shigella, the participant will be actively followed up and monitored on days 3, 5, 7 and 9 to inquire about the disease outcome and to collect blood and stool samples.

Active follow-ups will include a combined home and clinic visits. The parents or guardians of participants enrolled in the study will be contacted through phone calls and/or home visits by trained study staff every month to collect information on the child health status. They will enquire on whether the child had an episode of diarrhoea and fever in the preceding four weeks, the use of healthcare services for the diarrhoea episode and any treatment received for the diarrhoea and fever. If an episode of diarrhoea is detected during any of the active visits, the parents/guardians will be encouraged to take the child to the clinic for appropriate management. The child will then go through the passive surveillance procedures.

MSD cases will be defined as a three or more loose stools or at least one bloody/mucoid stool within a 24 hour period (WHO, 2005). A diarrhoea episode will be defined as new if the diarrhea definition is met after seven days free of diarrhoea or dysentery. A Shigella case will be defined as any loose stool with LAMP confirmed Shigella.

In Ndola, the burden of shigella disease will be determined in under five children presenting with moderate to severe diarrhea and admitted to Arthur Davison children's hospital in Ndola.

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Study Type : Observational
Actual Enrollment : 1334 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Baseline Study in Support of Clinical Evaluation of an Oral Shigella Vaccine Development in Africa
Actual Study Start Date : September 14, 2020
Actual Primary Completion Date : November 30, 2021
Actual Study Completion Date : November 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diarrhea Vaccines


Intervention Details:
  • Other: no intervention
    No intervention


Primary Outcome Measures :
  1. Incidence of Shigella diarrheal disease in children under fives in Zambia and Burkina Faso [ Time Frame: 1 year ]
    number of children testing Shigella positive during course of study


Secondary Outcome Measures :
  1. Attributable fraction for Shigella among all-cause MSD in children under 5 years [ Time Frame: 1 year ]
    the number of children presenting with MSD with confirmed Shigella

  2. Incidence of ETEC diarrheal disease in children under fives in Zambia and Burkina Faso [ Time Frame: 1 year ]
    the number of children presenting with MSD with confirmed ETEC

  3. Antimicrobial susceptibility/resistance of isolates to common antibiotics [ Time Frame: 1 year ]
    Proportion of shigella isolates resistant to common antibiotics

  4. Predictive accuracy of the modified diarrhoea severity scoring tool among children presenting with MSD [ Time Frame: 1 year ]
    Proportion of MSD cases confirmed by the modified severity score


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.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Children under 5 years of age living in the study catchment areas
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04312906


Locations
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Burkina Faso
Schiphra Hospital
Ouagadougou, Burkina Faso
Zambia
Arthur Davidson Childrens Hospital
Ndola, Copperbelt, Zambia, 10101
Chainda South Health Facility
Lusaka, Zambia, 10101
Sponsors and Collaborators
Centre for Infectious Disease Research in Zambia
European Vaccine Initiative
Groupe de Recherche Action en Sante
European and Developing Countries Clinical Trials Partnership (EDCTP)
Investigators
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Study Director: Sophie Hourard European Vaccine Initiative
Additional Information:
Publications:
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.

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Responsible Party: Centre for Infectious Disease Research in Zambia
ClinicalTrials.gov Identifier: NCT04312906    
Other Study ID Numbers: ShigOraVax Epi
First Posted: March 18, 2020    Key Record Dates
Last Update Posted: July 20, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre for Infectious Disease Research in Zambia:
diarrhea
Shigella
Vaccine
Additional relevant MeSH terms:
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Dysentery, Bacillary
Dysentery
Diarrhea
Signs and Symptoms, Digestive
Infections
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases