Clinical trial NCT02744469: Benin Population Diversity of Tuberculosis and Implications
Official title: Implications of the Population Structure of the Mycobacterium Tuberculosis Complex in Benin for Tuberculosis Presentation, Diagnosis and Outcome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tuberculosis
Keywords: Tuberculosis
population structure
implications
lineages
spoligotyping
sputum
resistance
culture
diagnostics
outcome
new/retreatment patient
Lead sponsor: Laboratoire de Référence des Mycobactéries
Sponsor class: OTHER_GOV
Collaborators: name: Direction Générale de la Coopération au Développement, Belgique
name: Institute of Tropical Medicine, Belgium
name: Universiteit Antwerpen
name: Laboratoire de Référence des Mycobactéries, Benin republic
name: Centre National Hospitalier Universitaire de Pneumo-Phtisiologie de Cotonou, Benin
name: Centres de Diagnostic et de Traitement de la tuberculose, National Tuberculosis Programme, Benin
First posted: 2016-04-20
Enrollment: 1490
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: There is a National Tuberculosis Program in Benin with a network of 57 TB (tuberculosis) 'diagnosis and treatment centers' (TB clinics). In order to be able to ensure a realistic (cost, time, personnel) strong quality control of data to record on fields in TB clinics, a smaller number of TB clinics where most of Benin TB patients are diagnosed is selected instead of including all the 57 TB clinics. Participants will be recruited from the 4 largest TB clinics of each of Benin's 6 (former) departments (Atlantique/Littoral, Oueme/Plateau, Mono/Couffo, Zou/Collines, Borgou/Alibori, Atacora/Donga), amounting to 24 TB clinics.

Brief summary: Tuberculosis is a public health problem caused by a microbe. This microbe may differ from one patient to another. The purpose of this study is to know to which extent, each of these various microbes is involved in tuberculosis disease in Benin. This study will also find out whether the type that affects a patient, depends on patient characteristics and whether the difference affects the outcome of the treatment. Finally the study will also help to find out whether diagnostic tests are reliable for all types of the microbe. This information will be used after the study to inform decision making in order to improve tuberculosis control.

Detailed description: The overall aim of this study is to determine the population structure of Mycobacterium tuberculosis complex in Benin, and implications for tuberculosis presentation, diagnosis and outcome The primary objective is to compare the characteristics of ancestral lineages of Mycobacterium tuberculosis complex, such as M. africanum West African 1 (Lineage 5), with modern M. tuberculosis in Benin.

This study will build on the system of nationwide surveillance already implemented for retreatment patients and recruit in addition a representative random sample of new patients. So for this study sputa from retreatment patients and from a sample of new patients, from the 24 tuberculosis (TB) clinics (Centres de Diagnostic et de Traitement de la Tuberculose) selected all over the country (Benin), will be shipped from TB clinics to the ''Laboratoire de Référence des Mycobactéries'' (LRM), Cotonou (National Reference Laboratory for Mycobacteria, Cotonou) if they consent. All retreatment patients will be recruited into the study and each 4 new patients detected after detection of a retreatment patient will also be recruited into the study.

At enrolment, a questionnaire will be used to collect from consenting participants information such as: Participant place of residence (rural or urban as determined by population density); ethnic group; age; sex; Human Immuno-deficiency Virus (HIV) status; Bacillus Calmette Guerin (BCG) vaccine scar...

Spoligotype analysis will be used to determine the population structure, as it allows the classification of most Mycobacterium tuberculosis complex isolates in lineages, including strains with single or few copies of IS6110.

The external quality evaluation (assurance quality) of the laboratory analyses to be performed at the LRM (National Reference Laboratory for Mycobacteria) in Cotonou, Benin during the study, will be performed by the Institute of Tropical Medicine of Antwerp in Belgium.

Eligibility criteria: Inclusion Criteria:

* New or retreatment tuberculosis patients with Acid Fast Bacilli-positive microscopy,
* Diagnosed in a participating TB clinic of Benin,
* Aged ≥15 years (Patients aged less than 15 years old will not be included in this study as acid-fast-bacilli microscopy is rarely positive in children)
* Who has given his/her informed consent (if adult potential participant:≥18 years old) OR who has given his/her assent in addition to the informed consent of his/her legal representative (if potential participant aged 15-\<18 years)

Exclusion Criteria:

* Extra-pulmonary TB only,
* New patient who has started taking the TB treatment drugs.
* Retreatment patient who has started taking the TB retreatment drugs.
* Very low sputum quantity (at least 5 milliliters total sputum is acceptable) and potential participant refusing to give more sputum

Primary outcomes:
measure: Lineage
timeFrame: At enrollment
Secondary outcomes:
measure: Spoligotype (family)
timeFrame: At enrollment
measure: Treatment failure or success as evidenced by microscopy result (for new and retreatment patients)
timeFrame: At Month 6 for new patient; at Month 8 for retreatment patients
measure: Treatment failure or success as evidenced by culture result (for rifampicin resistant patients)
timeFrame: At Month 20 for rifampicin resistant patients
measure: Relapse ascertainment (by questioning and retrospective check of microscopy evidence in TB clinics)
timeFrame: At Month 18 for new patients; at Month 20 for retreatment patients; at Month 32 for rifampicin resistant patients
measure: Chest X-ray findings
timeFrame: At enrollment
measure: Culture positivity
timeFrame: At enrollment
measure: Phenotypic Drug-resistance or susceptibility
timeFrame: At enrollment (if positive culture)
measure: Genotypic resistance to rifampin (GeneXpert)
timeFrame: At enrollment
measure: (Phenotypic)Type of Mycobacteria (tuberculous or non-tuberculous)
timeFrame: At enrollment (if positive culture)
measure: (Mpt64's)Type of Mycobacteria (tuberculous or non-tuberculous)
timeFrame: At enrollment (if positive culture)
Other outcomes:
measure: Acid-Fast Bacilli microcopy result
timeFrame: 1 Day
measure: Acid-Fast Bacilli microcopy on pooled sputum
timeFrame: At enrollment
measure: Drug resistance or susceptibility (Novel diagnostic tests)
timeFrame: At enrollment
Locations:
city: Antwerp
country: Belgium
facility: Institute of Tropical Medicine
city: Djougou
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Djougou
state: Atacora/Donga
city: Matéri
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Matéri
state: Atacora/Donga
city: Natitingou
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Natitingou
state: Atacora/Donga
city: Tanguiéta
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Tanguiéta
state: Atacora/Donga
city: Abomey-Calavi
country: Benin
facility: Centre de Diagnostic et de Traitement de la tuberculose d'Abomey-Calavi
state: Atlantique/Littoral
city: Allada
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose d'Allada
state: Atlantique/Littoral
city: Cotonou
country: Benin
facility: Centre National Hospitalier Universitaire de Pneumo-Phtisiologie de Cotonou
state: Atlantique/Littoral
city: Ouidah
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Ouidah
state: Atlantique/Littoral
city: Bembèrèkè
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Bembèrèkè HE
state: Borgou/Alibori
city: Kandi
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Kandi
state: Borgou/Alibori
city: Nikki
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Nikki Hopital Sounou-Séro
state: Borgou/Alibori
city: Parakou
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Parakou CSCom
state: Borgou/Alibori
city: Cotonou
country: Benin
facility: Laboratoire de Référence des Mycobactéries
state: Littoral
city: Aplahoué
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose d'Aplahoué
state: Mono/Couffo
city: Bopa
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Bopa
state: Mono/Couffo
city: Comè
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Comè
state: Mono/Couffo
city: Houéyogbé
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Houéyogbé
state: Mono/Couffo
city: Avrankou
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Avrankou
state: Oueme/Plateau
city: Pobe
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Pobè
state: Oueme/Plateau
city: Porto-Novo
country: Benin
facility: Centre de Pneumo-Phtisiologie d'Akron
state: Oueme/Plateau
city: Sakété
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Sakété
state: Oueme/Plateau
city: Abomey
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose d'Abomey
state: Zou/Collines
city: Bohicon
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Bohicon
state: Zou/Collines
city: Dassa-Zoumè
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Dassa-Zoumè
state: Zou/Collines
city: Zagnanado
country: Benin
facility: Centre de Diagnostic et de Traitement de la Tuberculose de Zagnanado
state: Zou/Collines
Study officials:
affiliation: Laboratoire de Référence des Mycobactéries, Benin
name: Dissou Affolabi, MD PhD Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Tropical Medicine, Belgium
name: Bouke de Jong, MD PhD Prof
role: PRINCIPAL_INVESTIGATOR
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