Targeted Nanopore Sequencing for Molecular Characterization of First-Line Drug Resistance and Treatment Outcomes Among Patients in the Republic of Congo
11 affiliations
- 1Fondation Congolaise pour la Recherche Médicale, Brazzaville P.O. Box 2672, Congo
- 2Faculté des Sciences et Techniques, Université Marien Ngouabi, Brazzaville P.O. Box 69, Congo
- 3Programme National de Lutte Contre la Tuberculose, Brazzaville P.O. Box 1066, Congo
- 4Laboratoire National de Référence des Mycobactéries, Brazzaville P.O. Box 1066, Congo
- 5Faculté des Sciences de la Santé, Université Marien Ngouabi, Brazzaville P.O. Box 2672, Congo
- 6Centre de Recherches Médicales de Lambaréné, Lambaréné P.O. Box 1437, Gabon
- 7Service de Pneumologie, Centre Hospitalier Universitaire, Brazzaville P.O. Box 32, Congo
- 8Centre Antituberculeux de Brazzaville, Brazzaville P.O. Box 1066, Congo
- 9Société Congolaise de Santé Mentale (SOCOSAM), Brazzaville P.O. Box 2672, Congo
- 10Institute of Tropical Medicine, University of Tübingen, Wilhelmstraße 27, 72074 Tübingen, Germany
- 11German Center for Infection Research, Tübingen Site, University of Tübingen, Wilhelmstraße 27, 72074 Tübingen, Germany
Abstract
Tuberculosis (TB) remains a major global public health concern, further complicated by the emergence and transmission of drug-resistant strains. Diversity within the Mycobacterium tuberculosis complex (MTBC) may also influence disease progression and treatment response. We conducted a longitudinal study among 126 Xpert MTB/RIF Ultra-confirmed TB patients enrolled and followed at the Antituberculosis Center of Brazzaville between July 2023 and November 2024. MTBC species were identified using the Genotype MTBC assay, and resistance-associated mutations in rpoB, katG, and embB were characterized by targeted Oxford Nanopore sequencing and interpreted using the WHO mutation catalogue and TB-Profiler. The overall treatment success rate was 81.7% (103/126). Among 109/126 samples successfully typed, M. tuberculosis accounted for 92.7% (101/109), Mycobacterium africanum for 3.7% (4/109), while mixed infection accounted for 0.9% (1/109) and inconclusive profiles for 2.8% (3/109). Resistance-associated mutations were assessed in 65 of the 126 enrolled patients with high-quality sequencing data. Among these 65 isolates, 32.3% (21/65) harbored resistance to at least one of the targeted first-line drugs, including isoniazid (23.1%; 15/65), rifampicin (15.4%; 10/65), and ethambutol (9.2%; 6/65). Multidrug-resistant TB was identified in 12.3% (8/65). The predominant mutations occurred at rpoB codon 435, katG codon 315, and embB codon 306. Treatment success was lower among patients infected with strains carrying a resistance-associated mutation (71.4%). Isoniazid resistance was associated with reduced odds of treatment success in unadjusted analysis (OR = 0.22, 95% CI: 0.05–0.93; p = 0.04). These findings suggest a considerable burden of genotypically predicted first-line drug resistance and support expanding molecular drug-susceptibility testing beyond rifampicin in TB surveillance and patient management in the Republic of Congo.
Related
- A New Era of Treatment Sequencing in Platinum-Resistant Ovarian Cancer: Integrating Immunotherapy, Antibody-Drug Conjugates, and Targeted Therapies.
- Targeted therapy in atopic dermatitis: Endotype heterogeneity, treatment sequencing, and lessons from a contracting pipeline: A narrative review
- Personalized Therapeutic Strategies in Glioblastoma: Bridging Molecular Markers and In Vivo Observations for Targeted Treatment
- Targeted Sequencing-Based Re-Evaluation of Candidate Immunogenetic Variants for Biologic Treatment Response and Difficult-to-Treat Rheumatoid Arthritis
- EGFR-mutant lung adenocarcinoma with leptomeningeal metastasis after osimertinib treatment: intrathecal chemotherapy combined with targeted therapy supported by cerebrospinal fluid next generation sequencing — a case report
BibTeX
@article{dello2026targeted,
title = {{Targeted Nanopore Sequencing for Molecular Characterization of First-Line Drug Resistance and Treatment Outcomes Among Patients in the Republic of Congo}},
author = {Mita Naomie Merveille Dello and Freisnel Hermeland Mouzinga and Breli Bonheur Ngouama and Darrel Ornelle Elion Assiana and Dechvie Jeannis Melissa Boumpouthoud and Jean Claude Djontu and Claujens Chastel Mfoutou Mapanguy and Emmanuel Fonfon Ebata-Mboussa and Beny Erudit Elenga and Jabar Babatunde Pacôme Achimi Abdul and Salomon Bonsi Tchuandom and Franck Hardain Okemba-Okombi and Michel Illoye Ayet and Etienne Nguimbi and Alain Maxime Mouanga and Ayola Akim Adegnika and Francine Ntoumi},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27208999},
url = {https://www.mdpi.com/1422-0067/27/20/8999},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Targeted Nanopore Sequencing for Molecular Characterization of First-Line Drug Resistance and Treatment Outcomes Among Patients in the Republic of Congo
AU - Mita Naomie Merveille Dello
AU - Freisnel Hermeland Mouzinga
AU - Breli Bonheur Ngouama
AU - Darrel Ornelle Elion Assiana
AU - Dechvie Jeannis Melissa Boumpouthoud
AU - Jean Claude Djontu
AU - Claujens Chastel Mfoutou Mapanguy
AU - Emmanuel Fonfon Ebata-Mboussa
AU - Beny Erudit Elenga
AU - Jabar Babatunde Pacôme Achimi Abdul
AU - Salomon Bonsi Tchuandom
AU - Franck Hardain Okemba-Okombi
AU - Michel Illoye Ayet
AU - Etienne Nguimbi
AU - Alain Maxime Mouanga
AU - Ayola Akim Adegnika
AU - Francine Ntoumi
PY - 2026
DA - 2026/10/11
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27208999
UR - https://www.mdpi.com/1422-0067/27/20/8999
AB - Tuberculosis (TB) remains a major global public health concern, further complicated by the emergence and transmission of drug-resistant strains. Diversity within the Mycobacterium tuberculosis complex (MTBC) may also influence disease progression and treatment response. We conducted a longitudinal study among 126 Xpert MTB/RIF Ultra-confirmed TB patients enrolled and followed at the Antituberculosis Center of Brazzaville between July 2023 and November 2024. MTBC species were identified using the Genotype MTBC assay, and resistance-associated mutations in rpoB, katG, and embB were characterized by targeted Oxford Nanopore sequencing and interpreted using the WHO mutation catalogue and TB-Profiler. The overall treatment success rate was 81.7% (103/126). Among 109/126 samples successfully typed, M. tuberculosis accounted for 92.7% (101/109), Mycobacterium africanum for 3.7% (4/109), while mixed infection accounted for 0.9% (1/109) and inconclusive profiles for 2.8% (3/109). Resistance-associated mutations were assessed in 65 of the 126 enrolled patients with high-quality sequencing data. Among these 65 isolates, 32.3% (21/65) harbored resistance to at least one of the targeted first-line drugs, including isoniazid (23.1%; 15/65), rifampicin (15.4%; 10/65), and ethambutol (9.2%; 6/65). Multidrug-resistant TB was identified in 12.3% (8/65). The predominant mutations occurred at rpoB codon 435, katG codon 315, and embB codon 306. Treatment success was lower among patients infected with strains carrying a resistance-associated mutation (71.4%). Isoniazid resistance was associated with reduced odds of treatment success in unadjusted analysis (OR = 0.22, 95% CI: 0.05–0.93; p = 0.04). These findings suggest a considerable burden of genotypically predicted first-line drug resistance and support expanding molecular drug-susceptibility testing beyond rifampicin in TB surveillance and patient management in the Republic of Congo.
SN - 1422-0067
ER -