Clinical trial NCT04312906: A Baseline Study in Support of Clinical Evaluation of an Oral Shigella Vaccine Development in Africa
Official title: A Baseline Study in Support of Clinical Evaluation of an Oral Shigella Vaccine Development in Africa
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diarrhea
Diarrhea Infectious
Keywords: diarrhea
Shigella
Vaccine
Lead sponsor: Centre for Infectious Disease Research in Zambia
Sponsor class: OTHER
Collaborators: name: European Vaccine Initiative
name: Groupe de Recherche Action en Sante
name: European and Developing Countries Clinical Trials Partnership (EDCTP)
First posted: 2020-03-18
Enrollment: 1334
Sex: ALL
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children under 5 years of age living in the study catchment areas

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

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.

Eligibility 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

Primary outcomes:
measure: Incidence of Shigella diarrheal disease in children under fives in Zambia and Burkina Faso
timeFrame: 1 year
Secondary outcomes:
measure: Attributable fraction for Shigella among all-cause MSD in children under 5 years
timeFrame: 1 year
measure: Incidence of ETEC diarrheal disease in children under fives in Zambia and Burkina Faso
timeFrame: 1 year
measure: Antimicrobial susceptibility/resistance of isolates to common antibiotics
timeFrame: 1 year
measure: Predictive accuracy of the modified diarrhoea severity scoring tool among children presenting with MSD
timeFrame: 1 year
Other outcomes:
Locations:
city: Ouagadougou
country: Burkina Faso
facility: Schiphra Hospital
city: Ndola
country: Zambia
facility: Arthur Davidson Childrens Hospital
state: Copperbelt
city: Lusaka
country: Zambia
facility: Chainda South Health Facility
Study officials:
affiliation: European Vaccine Initiative
name: Sophie Hourard
role: STUDY_DIRECTOR
References:
citation: 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.
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citation: 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.
citation: 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.