Keywords
adverse effects
short-course treatment
oral route
Niger
How to Cite
Abstract
Introduction :
Drug-resistant tuberculosis is a major public health problem. Its treatment is constantly evolving. The aim of this study was to determine the frequency and nature of adverse effects associated with short-course oral treatment of drug-resistant tuberculosis. Patients and Method : This is a two-year prospective, descriptive study running from 1 April 2021 to 31 March 2023, including patients diagnosed with drug-resistant tuberculosis and placed on a short oral regimen (4-6 months of Linezolid LZD, Isoniazid HH, prothionamide Pto, levofloxacin Lfx, bedaquiline Bdq, clofazimine Cfz, pyrazinamide Z for the intensive phase/5 months LfxBdqCfzZ for the continuation phase) followed in treatment units in Niamey, Tahoua, Maradi and Zinder.
Results :
We included 114 patients, 80.71% of whom were male, with a sex ratio of 4.22. These patients had a mean age of 37.83 ± 16.30 years and a mean body mass index (BMI) of 17.61 kg/m² ± 3.47. The first treatment failure was the cause of resistance in 31.30%. Lung lesions were bilateral in 78.26%. The median time to treatment initiation was 10 days. The main adverse effects observed were vomiting (48.24%), anaemia (35.08%), peripheral neuropathies (27.19%) and hepatotoxicity (23.68%). Adverse effects occurred in 96.49% of patients, mainly during the first month of treatment. The therapeutic success rate was 73.68%, and the mortality rate was 15.33%.
Conclusion :
Adverse effects (AEs) are common and have been managed with a therapeutic success rate of 74.14%. Their systematic management and directly observed treatment (DOT) are an important part of the management of multidrug-resistant tuberculosis.
References
1. Organisation mondiale de la Santé. Rapport mondial sur la tuberculose 2024. Genève: Organisation mondiale de la Santé; 2024. Disponible sur: https://www.who.int/teams/global-programmeon-tuberculosis-and-lung-health/tbreports/global-tuberculosis-report-2024
2. Organisation mondiale de la Santé. Lignes directrices unifiées de l’OMS sur la tuberculose : traitement. Module 4 : traitement de la tuberculose pharmacorésistante. Genève: Organisation mondiale de la Santé; 2020.
3. Organisation mondiale de la Santé. Lignes directrices unifiées de l’OMS sur la tuberculose : traitement. Module 4 : traitement de la tuberculose pharmacorésistante. Mise à jour 2022. Genève: Organisation mondiale de la Santé; 2022.
4. Piubello A, Souleymane MB, Hassane S, Yakoubou A, Lempens P, Mahamadou S, et al. Management of multidrug-resistant tuberculosis with shorter treatment regimen in Niger: Nationwide programmatic achievements. Respir Med. 2020;161:105844.
5. Chariag M, Been S, Khalfallah N, Ben Mansour A, Daghfous H, Tritar F, et al. Facteurs prédictifs des effets indésirables liés au traitement antituberculeux de 2e ligne. Rev Mal Respir. 2025;17(7):134.
6. Ghadage DP, Kamat SJ, Kakodkar UC. Study of adverse drug reactions during drug resistant tuberculosis treatment. Indian J Tuberc. 2024;71(1):136-40.
7. Hadjer N, Haddad L, Nacef L, Aberrahim S, Azouz Y, Ouladkuoider M, et al. États des lieux de la tuberculose multi- ou pré-ultrarésistante dans une région de l’Ouest de l’Algérie de 2004 à 2024. Rev Mal Respir. 2025;17(1):197.
8. Chérif T, Ben S, Ben AM, Mince A, Daghfous H, Tritar F, et al. Tolérance aux médicaments antituberculeux de deuxième ligne. Rev Mal Respir. 2024;16(1):73-4.
9. Matambo R, Chimukangara B, Thebe P, Sandy C, Mandozana S, Makamure T, et al. Adverse events in patients on treatment for multidrugresistant tuberculosis in a programmatic setting in Zimbabwe. PLoS One. 2020;15(4):e0230848.
10. Wang S, Feng L, Xu C, Zhu L, Alffenaar JW. Second-line antituberculosis drug exposure thresholds predictive of adverse events in multidrug-resistant tuberculosis treatment. Int J Infect Dis. 2024;140:62-9.
11. Korotych O, Gurbanova E, Hovhannesyan A, Lomtadze N, Ciobanu A. Effectiveness and safety of modified fully oral 9-month treatment regimens for rifampicin-resistant tuberculosis: a prospective cohort study. BMC Infect Dis. 2024;24(10):4.
12. Boncoungou K, Halidou MS, Maiga S. Devenir des patients atteints de la tuberculose pulmonaire à bacilles pré-ultrarésistants au Burkina Faso. J Funct Vent Pulm. 2023;14(44):15.
13. Kombila UD, Manomba BC, Ibinga LD, Mounguengui D, N’gomanda F, Massolou R, et al. Difficultés et Obstacles dans la Prise en Charge de la Tuberculose Multirésistante au Centre Hospitalier et Universitaire de Libreville : Étude Rétrospective de 2017 à 2020. Health Sci Dis. 2021;22(11):53-8.
14. Poka-Mayap V, Balkissou A, Pefura-Yone EW, Kuaban C. Ototoxicité liée à la kanamycine au cours du traitement de la tuberculose multirésistante. Rev Mal Respir. 2020;37(5):377-84.
15. Laouali H, Ibrahim L. Tuberculose pulmonaire résistante à la rifampicine au centre hospitalier régional de Maradi, Niger (2014-2018). Bull Soc Pathol Exot. 2023;3:4.
16. Santé Tropicale. Journée internationale de la lutte contre le VIH-SIDA [En ligne]. 2024 [cité le 9 avr 2025]. Disponible sur: https://www.santetropicale.com/actus.asp?id=3 4318&action=lire
17. Viluma A, Skrastina D, Bicans I, Busa I, Vangravs A, Freimane L, et al. Genotypic and phenotypic comparison of drug resistance profiles of clinical multidrug-resistant Mycobacterium tuberculosis isolates using whole genome sequencing in Latvia. BMC Infect Dis. 2023;23(1):632.
18. Yehouenou CL. Analyse des résistances phénotypiques et génotypiques des souches du complexe Mycobacterium tuberculosis isolées à l’hôpital Aristide Le Dantec en 2012 [Mémoire]. Dakar: Université Cheikh Anta Diop; 2012. Disponible sur: https://www.microcsb.sn/wpcontent/uploads/2024/12/Memoire-Dr-CarineLaurence-YEHOUENOU.pdf
19. Al-Mutairi N, Ahmad S, Mokaddas E. Discordance in Phenotypic and Genotypic Susceptibility Testing for Streptomycin Due to Nonsynonymous/Nonsense Mutations/Deletions in gidB Reading Frame among Clinical Isolates of Mycobacterium tuberculosis in Kuwait. Med Princ Pract. 2024;33(4):321-9.
20. Rodriguez M, Celis Y, Evans M, Marcelino E, De Los Santos S. Evaluation of a modified short, fully oral regimen for rifampicin-resistant tuberculosis in the Dominican Republic. BMC Infect Dis. 2025;25(1):196.
21. Nguyen B, Vu H, Nguyen T, Duong V, Cao T, Nguyen H, et al. Active surveillance for adverse events in patients on longer treatment regimens for multidrug-resistant tuberculosis in Vietnam. PLoS One. 2021;16(9):e0256637.
22. Huerga H, Khan U, Bastard M, Duffau C, Lachenal N, Yaftali P, et al. Safety outcome of a cohort of patients with multidrug-resistant tuberculosis in 14 countries treated with bedaquiline and delamanid and other secondline drugs. Clin Infect Dis. 2022;75(8):1307-14.
23. Sun T, Park H, Hahn J, Hong S, Lee YS, Choi JC, et al. A prospective patient registry to monitor the safety and effectiveness of bedaquiline in patients with multidrug-resistant tuberculosis in South Korea. BMC Infect Dis. 2023;23(1):15.
24. Tonéatti C, Bouxin-Metro A, Dormont J. Echelle ANRS de cotation de la gravité des événements indésirables graves chez l'adulte. Paris: ANRS; 2003.
25. Akubardia T, Saghinadze Y, Davtyan H, Tukvadze N, Tsereteli T, Kiria N, et al. Effectiveness and safety of a modified shorter, fully oral regimen for multidrug-resistant tuberculosis in Georgia, 2019-20. Int J Tuberc Lung Dis. 2021;25(10):816-23.
26. Borisov S, Danila E, Maryandyshev A, Dalcolmo M, Miliauskas S, Kuksa L, et al. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report. Eur Respir J. 2019;54(6):1901522.
27. Park HO, Kim SH, Moon SH, Byun JH, Kim JW, Lee CE, et al. Association between Body Mass Index and Sputum Culture Conversion among South Korean Patients with Multidrug-Resistant Tuberculosis in a Tuberculosis Referral Hospital. Infect Chemother. 2016;48(4):317–23.
28. Cutfield T, Morpeth L, Pietersen J, Noël T, Hjelmström A, Lewis C, et al. Treatment and outcomes of multidrug-resistant tuberculosis in Auckland, 1995-2018. Intern Med J. 2022;52(8):1352-60.
29. Taal I, Alemu D, Okeyo L, Sagymbekova A, Bekele A, Wasi K, et al. Safety and Effectiveness of Bedaquiline-Containing Shorter Treatment Regimens for Rifampicin-Resistant Tuberculosis in High Human Immunodeficiency Virus Burden Rural South Africa: A Retrospective Cohort Analysis. Clin Infect Dis. 2021;73(9):e3563-71.
30. Jafari M, Zarei M, Arab E, Zumla A. Delamanidcontaining regimens and multidrug-resistant tuberculosis: A systematic review and metaanalysis. J Glob Antimicrob Resist. 2022;29:90-103.
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Copyright (c) 2026 A Gagara Issoufou Madougou, B Souleymane Mahamadou, I Hamidou, M Souley Mamane, M Moussa, S Halidou Moussa, A Cheik Aboubacar, A Ahoussou Kabirou, I Lawan, A Soumana, M Bako, A Piubello