BeniDiT: Benin Population Diversity of Tuberculosis and Implications
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| New patients ''New tuberculosis patients'' are patients just diagnosed for tuberculosis, and who were never treated for tuberculosis or who are treated for less than 1 month. In total, 1192 new patients will be recruited. |
Other: No intervention (observational study)
|
| Retreatment patients ''Retreatment tuberculosis patients'' are patients just diagnosed for tuberculosis and who were previously treated for tuberculosis (for a duration of 1 month at least). This group includes: patients with treatment relapse, failure and patients who return after default. In total, 298 retreatment patients will be recruited. |
Other: No intervention (observational study)
|
Outcome Measures
Primary Outcome Measures
- Lineage [At enrollment]
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.
Secondary Outcome Measures
- Spoligotype (family) [At enrollment]
Mycobacterium tuberculosis spoligotype (family) as determined by the spoligotyping pattern. The lineage will be determined using the specimen collected at participant enrolment.
- Treatment failure or success as evidenced by microscopy result (for new and retreatment patients) [At Month 6 for new patient; at Month 8 for 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.
- Treatment failure or success as evidenced by culture result (for rifampicin resistant patients) [At Month 20 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.
- Relapse ascertainment (by questioning and retrospective check of microscopy evidence in TB clinics) [At Month 18 for new patients; at Month 20 for retreatment patients; at Month 32 for rifampicin resistant patients]
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.
- Chest X-ray findings [At enrollment]
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.
- Culture positivity [At enrollment]
Isolation of mycobacteria (in vitro mycobacterial growth) in culture
- Phenotypic Drug-resistance or susceptibility [At enrollment (if positive culture)]
Drug resistance as determined using phenotypic drug susceptibility testing on 1st and 2nd line anti-tuberculous drugs
- Genotypic resistance to rifampin (GeneXpert) [At enrollment]
Resistance of Mycobacterium tuberculosis to rifampin as determined using the GeneXpert Mtb/Rif test.
- (Phenotypic)Type of Mycobacteria (tuberculous or non-tuberculous) [At enrollment (if positive culture)]
Group of Mycobacteria (tuberculous or non-tuberculous) as determined by the result of phenotypic drug sensitivity testing on para-nitro-benzoic acid
- (Mpt64's)Type of Mycobacteria (tuberculous or non-tuberculous) [At enrollment (if positive culture)]
Group of Mycobacteria (tuberculous or non-tuberculous) as determined using the Mpt64 antigen test
Other Outcome Measures
- Acid-Fast Bacilli microcopy result [1 Day]
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.
- Acid-Fast Bacilli microcopy on pooled sputum [At enrollment]
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.
- Drug resistance or susceptibility (Novel diagnostic tests) [At enrollment]
Drug resistance pattern for 1st and 2nd lines drugs using novel diagnostic tests.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
New or retreatment tuberculosis patients with Acid Fast Bacilli-positive microscopy,
-
Diagnosed in a participating TB clinic of Benin,
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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)
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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:
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Extra-pulmonary TB only,
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New patient who has started taking the TB treatment drugs.
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Retreatment patient who has started taking the TB retreatment drugs.
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Very low sputum quantity (at least 5 milliliters total sputum is acceptable) and potential participant refusing to give more sputum
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institute of Tropical Medicine | Antwerp | Belgium | ||
| 2 | Centre de Diagnostic et de Traitement de la Tuberculose de Djougou | Djougou | Atacora/Donga | Benin | |
| 3 | Centre de Diagnostic et de Traitement de la Tuberculose de Matéri | Matéri | Atacora/Donga | Benin | |
| 4 | Centre de Diagnostic et de Traitement de la Tuberculose de Natitingou | Natitingou | Atacora/Donga | Benin | |
| 5 | Centre de Diagnostic et de Traitement de la Tuberculose de Tanguiéta | Tanguiéta | Atacora/Donga | Benin | |
| 6 | Centre de Diagnostic et de Traitement de la tuberculose d'Abomey-Calavi | Abomey-Calavi | Atlantique/Littoral | Benin | |
| 7 | Centre de Diagnostic et de Traitement de la Tuberculose d'Allada | Allada | Atlantique/Littoral | Benin | |
| 8 | Centre National Hospitalier Universitaire de Pneumo-Phtisiologie de Cotonou | Cotonou | Atlantique/Littoral | Benin | 01BP321 |
| 9 | Centre de Diagnostic et de Traitement de la Tuberculose de Ouidah | Ouidah | Atlantique/Littoral | Benin | |
| 10 | Centre de Diagnostic et de Traitement de la Tuberculose de Bembèrèkè HE | Bembèrèkè | Borgou/Alibori | Benin | |
| 11 | Centre de Diagnostic et de Traitement de la Tuberculose de Kandi | Kandi | Borgou/Alibori | Benin | |
| 12 | Centre de Diagnostic et de Traitement de la Tuberculose de Nikki Hopital Sounou-Séro | Nikki | Borgou/Alibori | Benin | |
| 13 | Centre de Diagnostic et de Traitement de la Tuberculose de Parakou CSCom | Parakou | Borgou/Alibori | Benin | |
| 14 | Laboratoire de Référence des Mycobactéries | Cotonou | Littoral | Benin | 01BP321 |
| 15 | Centre de Diagnostic et de Traitement de la Tuberculose d'Aplahoué | Aplahoué | Mono/Couffo | Benin | |
| 16 | Centre de Diagnostic et de Traitement de la Tuberculose de Bopa | Bopa | Mono/Couffo | Benin | |
| 17 | Centre de Diagnostic et de Traitement de la Tuberculose de Comè | Comè | Mono/Couffo | Benin | |
| 18 | Centre de Diagnostic et de Traitement de la Tuberculose de Houéyogbé | Houéyogbé | Mono/Couffo | Benin | |
| 19 | Centre de Diagnostic et de Traitement de la Tuberculose de Avrankou | Avrankou | Oueme/Plateau | Benin | |
| 20 | Centre de Diagnostic et de Traitement de la Tuberculose de Pobè | Pobe | Oueme/Plateau | Benin | |
| 21 | Centre de Pneumo-Phtisiologie d'Akron | Porto-Novo | Oueme/Plateau | Benin | |
| 22 | Centre de Diagnostic et de Traitement de la Tuberculose de Sakété | Sakété | Oueme/Plateau | Benin | |
| 23 | Centre de Diagnostic et de Traitement de la Tuberculose d'Abomey | Abomey | Zou/Collines | Benin | |
| 24 | Centre de Diagnostic et de Traitement de la Tuberculose de Bohicon | Bohicon | Zou/Collines | Benin | |
| 25 | Centre de Diagnostic et de Traitement de la Tuberculose de Dassa-Zoumè | Dassa-Zoumè | Zou/Collines | Benin | |
| 26 | Centre de Diagnostic et de Traitement de la Tuberculose de Zagnanado | Zagnanado | Zou/Collines | Benin |
Sponsors and Collaborators
- Laboratoire de Référence des Mycobactéries
- Direction Générale de la Coopération au Développement, Belgique
- Institute of Tropical Medicine, Belgium
- Universiteit Antwerpen
- Laboratoire de Référence des Mycobactéries, Benin republic
- Centre National Hospitalier Universitaire de Pneumo-Phtisiologie de Cotonou, Benin
- Centres de Diagnostic et de Traitement de la tuberculose, National Tuberculosis Programme, Benin
Investigators
- Principal Investigator: Dissou Affolabi, MD PhD Prof, Laboratoire de Référence des Mycobactéries, Benin
- Principal Investigator: Bouke de Jong, MD PhD Prof, Institute of Tropical Medicine, Belgium
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- Castets M. [Mycobacterium africanum (author's transl)]. Med Trop (Mars). 1979 Mar-Apr;39(2):145-8. French.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- LRM-N°030-15/12/2015
- CNERS N°030 of 15th/12/2015
- ITM- N°1040/15
- EC UZA 15/49/532
- Belg registN°:B300201526865