Benin Population Diversity of Tuberculosis and Implications

Tuberculosis Clinical Trial

— BeniDiT  

Official title:

Implications of the Population Structure of the Mycobacterium Tuberculosis Complex in Benin for Tuberculosis Presentation, Diagnosis and Outcome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02744469
• Other study ID #: LRM-N°030-15/12/2015
• Secondary ID: CNERS N°030 of 1
• Status: Completed
• Start date: April 12, 2016
• Est. completion date: December 12, 2019

Study information

• Verified date: February 2021
• Source: Laboratoire de Référence des Mycobactéries
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1490
• Est. completion date: December 12, 2019
• Est. primary completion date: January 8, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Other:
• No intervention (observational study)

Locations

Country	Name	City	State
Belgium	Institute of Tropical Medicine	Antwerp
Benin	Centre de Diagnostic et de Traitement de la Tuberculose d'Abomey	Abomey	Zou/Collines
Benin	Centre de Diagnostic et de Traitement de la tuberculose d'Abomey-Calavi	Abomey-Calavi	Atlantique/Littoral
Benin	Centre de Diagnostic et de Traitement de la Tuberculose d'Allada	Allada	Atlantique/Littoral
Benin	Centre de Diagnostic et de Traitement de la Tuberculose d'Aplahoué	Aplahoué	Mono/Couffo
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Avrankou	Avrankou	Oueme/Plateau
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Bembèrèkè HE	Bembèrèkè	Borgou/Alibori
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Bohicon	Bohicon	Zou/Collines
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Bopa	Bopa	Mono/Couffo
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Comè	Comè	Mono/Couffo
Benin	Centre National Hospitalier Universitaire de Pneumo-Phtisiologie de Cotonou	Cotonou	Atlantique/Littoral
Benin	Laboratoire de Référence des Mycobactéries	Cotonou	Littoral
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Dassa-Zoumè	Dassa-Zoumè	Zou/Collines
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Djougou	Djougou	Atacora/Donga
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Houéyogbé	Houéyogbé	Mono/Couffo
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Kandi	Kandi	Borgou/Alibori
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Matéri	Matéri	Atacora/Donga
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Natitingou	Natitingou	Atacora/Donga
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Nikki Hopital Sounou-Séro	Nikki	Borgou/Alibori
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Ouidah	Ouidah	Atlantique/Littoral
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Parakou CSCom	Parakou	Borgou/Alibori
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Pobè	Pobe	Oueme/Plateau
Benin	Centre de Pneumo-Phtisiologie d'Akron	Porto-Novo	Oueme/Plateau
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Sakété	Sakété	Oueme/Plateau
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Tanguiéta	Tanguiéta	Atacora/Donga
Benin	Centre de Diagnostic et de Traitement de la Tuberculose de Zagnanado	Zagnanado	Zou/Collines

Sponsors (7)

Lead Sponsor	Collaborator
Laboratoire de Référence des Mycobactéries	Centre National Hospitalier Universitaire de Pneumo-Phtisiologie de Cotonou, Benin, Centres de Diagnostic et de Traitement de la tuberculose, National Tuberculosis Programme, Benin, Direction Générale de la Coopération au Développement, Belgique, Institute of Tropical Medicine, Belgium, Laboratoire de Référence des Mycobactéries, Benin republic, Universiteit Antwerpen

Countries where clinical trial is conducted

Belgium,  Benin, 

References & Publications (13)

Affolabi D, Anyo G, Faïhun F, Sanoussi N, Shamputa IC, Rigouts L, Kestens L, Anagonou S, Portaels F. First molecular epidemiological study of tuberculosis in Benin. Int J Tuberc Lung Dis. 2009 Mar;13(3):317-22. — View Citation

Affolabi D, Faïhun F, Sanoussi N, Anyo G, Shamputa IC, Rigouts L, Kestens L, Anagonou S, Portaels F. Possible outbreak of streptomycin-resistant Mycobacterium tuberculosis Beijing in Benin. Emerg Infect Dis. 2009 Jul;15(7):1123-5. doi: 10.3201/eid1507.080697. — View Citation

Asante-Poku A, Yeboah-Manu D, Otchere ID, Aboagye SY, Stucki D, Hattendorf J, Borrell S, Feldmann J, Danso E, Gagneux S. Mycobacterium africanum is associated with patient ethnicity in Ghana. PLoS Negl Trop Dis. 2015 Jan 8;9(1):e3370. doi: 10.1371/journal.pntd.0003370. eCollection 2015 Jan. — View Citation

Brudey K, Driscoll JR, Rigouts L, Prodinger WM, Gori A, Al-Hajoj SA, Allix C, Aristimuño L, Arora J, Baumanis V, Binder L, Cafrune P, Cataldi A, Cheong S, Diel R, Ellermeier C, Evans JT, Fauville-Dufaux M, Ferdinand S, Garcia de Viedma D, Garzelli C, Gazzola L, Gomes HM, Guttierez MC, Hawkey PM, van Helden PD, Kadival GV, Kreiswirth BN, Kremer K, Kubin M, Kulkarni SP, Liens B, Lillebaek T, Ho ML, Martin C, Martin C, Mokrousov I, Narvskaïa O, Ngeow YF, Naumann L, Niemann S, Parwati I, Rahim Z, Rasolofo-Razanamparany V, Rasolonavalona T, Rossetti ML, Rüsch-Gerdes S, Sajduda A, Samper S, Shemyakin IG, Singh UB, Somoskovi A, Skuce RA, van Soolingen D, Streicher EM, Suffys PN, Tortoli E, Tracevska T, Vincent V, Victor TC, Warren RM, Yap SF, Zaman K, Portaels F, Rastogi N, Sola C. Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology. BMC Microbiol. 2006 Mar 6;6:23. — View Citation

Castets M. [Mycobacterium africanum (author's transl)]. Med Trop (Mars). 1979 Mar-Apr;39(2):145-8. French. — View Citation

de Jong BC, Antonio M, Gagneux S. Mycobacterium africanum--review of an important cause of human tuberculosis in West Africa. PLoS Negl Trop Dis. 2010 Sep 28;4(9):e744. doi: 10.1371/journal.pntd.0000744. Review. — View Citation

de Jong BC, Hill PC, Aiken A, Awine T, Antonio M, Adetifa IM, Jackson-Sillah DJ, Fox A, Deriemer K, Gagneux S, Borgdorff MW, McAdam KP, Corrah T, Small PM, Adegbola RA. Progression to active tuberculosis, but not transmission, varies by Mycobacterium tuberculosis lineage in The Gambia. J Infect Dis. 2008 Oct 1;198(7):1037-43. doi: 10.1086/591504. — View Citation

de Jong BC, Hill PC, Brookes RH, Otu JK, Peterson KL, Small PM, Adegbola RA. Mycobacterium africanum: a new opportunistic pathogen in HIV infection? AIDS. 2005 Oct 14;19(15):1714-5. — View Citation

Gagneux S, Small PM. Global phylogeography of Mycobacterium tuberculosis and implications for tuberculosis product development. Lancet Infect Dis. 2007 May;7(5):328-37. Review. — View Citation

Gehre F, Antonio M, Faïhun F, Odoun M, Uwizeye C, de Rijk P, de Jong BC, Affolabi D. The first phylogeographic population structure and analysis of transmission dynamics of M. africanum West African 1--combining molecular data from Benin, Nigeria and Sierra Leone. PLoS One. 2013 Oct 15;8(10):e77000. doi: 10.1371/journal.pone.0077000. eCollection 2013. — View Citation

Kamerbeek J, Schouls L, Kolk A, van Agterveld M, van Soolingen D, Kuijper S, Bunschoten A, Molhuizen H, Shaw R, Goyal M, van Embden J. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J Clin Microbiol. 1997 Apr;35(4):907-14. — View Citation

Parwati I, van Crevel R, van Soolingen D, van der Zanden A. Application of spoligotyping to noncultured Mycobacterium tuberculosis bacteria requires an optimized approach. J Clin Microbiol. 2003 Nov;41(11):5350-1. — View Citation

Yin X, Zheng L, Lin L, Hu Y, Zheng F, Hu Y, Wang Q. Commercial MPT64-based tests for rapid identification of Mycobacterium tuberculosis complex: a meta-analysis. J Infect. 2013 Nov;67(5):369-77. doi: 10.1016/j.jinf.2013.06.009. Epub 2013 Jun 22. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Acid-Fast Bacilli microcopy result	Acid-Fast Bacilli microcopy result on patients' sputa determined using the Ziehl-Neelsen method or the auramine method depending on which of these methods is used at the various tuberculosis clinics where participants will be enrolled.	1 Day
Other	Acid-Fast Bacilli microcopy on pooled sputum	Acid-Fast Bacilli microcopy result on the pooled sputum of each participant. The pooled sputum results from the addition of the 2 leftover routine sputa of a participant to the third sputum given after informed consent. This Acid-Fast Bacilli microcopy on pooled sputum will be done after shipment of the pooled sputum to the Reference Laboratory (LRM), using auramine method.	At enrollment
Other	Drug resistance or susceptibility (Novel diagnostic tests)	Drug resistance pattern for 1st and 2nd lines drugs using novel diagnostic tests.	At enrollment
Primary	Lineage	Mycobacterium tuberculosis lineage as determined by the spoligotyping pattern. The lineage will be determined using the specimen collected at participant enrolment. Spoligotyping will be done on sputum, or on culture isolate if failed on sputum and culture is positive.	At enrollment
Secondary	Spoligotype (family)	Mycobacterium tuberculosis spoligotype (family) as determined by the spoligotyping pattern. The lineage will be determined using the specimen collected at participant enrolment.	At enrollment
Secondary	Treatment failure or success as evidenced by microscopy result (for new and retreatment patients)	Treatment failure will be ascertained at the end of the treatment period using microscopy for detection of acid-fast bacilli in participant' sputa. Treatment failure or success will be measured using microscopy, only for new and retreatment patients.	At Month 6 for new patient; at Month 8 for retreatment patients
Secondary	Treatment failure or success as evidenced by culture result (for rifampicin resistant patients)	Treatment failure will be ascertained at the end of the 20 months treatment period by culturing sputa from rifampicin resistant participants.	At Month 20 for rifampicin resistant patients
Secondary	Relapse ascertainment (by questioning and retrospective check of microscopy evidence in TB clinics)	Participants will be called and will be asked whether they have experienced another episode of tuberculosis. This will be retrospectively confirmed in the TB clinic by checking microscopy results for the new episode of tuberculosis.	At Month 18 for new patients; at Month 20 for retreatment patients; at Month 32 for rifampicin resistant patients
Secondary	Chest X-ray findings	Chest X-ray will be performed in participants to be enrolled in Cotonou and Porto-Novo, the 2 biggest TB clinics and where X-ray is available.	At enrollment
Secondary	Culture positivity	Isolation of mycobacteria (in vitro mycobacterial growth) in culture	At enrollment
Secondary	Phenotypic Drug-resistance or susceptibility	Drug resistance as determined using phenotypic drug susceptibility testing on 1st and 2nd line anti-tuberculous drugs	At enrollment (if positive culture)
Secondary	Genotypic resistance to rifampin (GeneXpert)	Resistance of Mycobacterium tuberculosis to rifampin as determined using the GeneXpert Mtb/Rif test.	At enrollment
Secondary	(Phenotypic)Type of Mycobacteria (tuberculous or non-tuberculous)	Group of Mycobacteria (tuberculous or non-tuberculous) as determined by the result of phenotypic drug sensitivity testing on para-nitro-benzoic acid	At enrollment (if positive culture)
Secondary	(Mpt64's)Type of Mycobacteria (tuberculous or non-tuberculous)	Group of Mycobacteria (tuberculous or non-tuberculous) as determined using the Mpt64 antigen test	At enrollment (if positive culture)