Experiences in the introduction of bedaquiline pretomanid linezolid for drug-resistant tuberculosis in Kyrgyzstan.

Settings: In Kyrgyzstan, drug-resistant tuberculosis poses a significant challenge. Recognizing the potential of the BPaL regimen, the World Health Organization recommended its use for selected drug-resistant TB cases under operational research conditions in 2020. Objective: This report presents experiences and results from the BPaL operational research under the LIFT-TB project in Kyrgyzstan. Design: Prospective cohort study. Results: From August 2021 to June 2022, 50 patients were enrolled, achieving an 84 % treatment success rate. Although adverse events affected 11 patients (34.3 %), primarily linked to linezolid use (39 [78 %] patients started on 1200 mg linezolid daily), no unexpected adverse events occurred, and management was appropriate. The operational research emphasized proper patient inclusion, highlighting the crucial roles of psychological counselling support and active drug safety monitoring. Conclusion: With insights gained, Kyrgyzstan is now nationwide implementing the BPaLM/BPaL regimens for a broader drug-resistant TB patient group. The experiences, successes, and lessons from the BPaL operational research, along with the programmatic introduction, offer valuable guidance for global drug-resistant TB control strategies. This initiative becomes a resource for countries with similar drug-resistant TB burdens, promoting a collaborative global approach to address drug-resistant TB challenges.

Hearing aid support for patients with DR-TB in Ethiopia.

SETTING: Previous and current patients with drug-resistant TB (DR-TB) who had documented treatment-related hearing impairment due to second-line injectable (SLI) use were identified from different DR-TB treatment initiation centres in Ethiopia. OBJECTIVE: To assess selected patients with DR-TB for eligibility for hearing aids and provide hearing aids to 10 eligible patients. DESIGN: This was an observational cohort study. Patients were followed up for 8 months, with hearing assessments conducted at 1, 3 and 8 months to objectively assess hearing capacity. RESULTS: Of 12 patients assessed for hearing aids eligibility, 10 were fitted with hearing aids (type XTM XP P4) and followed up for 8 months. "Formal" improvement was observed only in one patient. However, "general quality of life" appeared to be improved in nine patients. CONCLUSION: Minimal "formal" improvement was observed. However, the study was too small to say whether hearing aids should, or should not, be recommended as a public health measure. This needs a larger better controlled follow-up study. The all-oral DR-TB treatment regimens should be used for all patients with DR-TB in Ethiopia. However, as a proportion of patients with DR-TB are likely to continue receiving SLIs in the foreseeable future, they will require close audiometry assessment and appropriate care.

CONTEXTE: Les patients, anciens et actuels, atteints de TB pharmacorésistante (DR-TB) ayant une déficience auditive documentée due à l'utilisation d'agents injectables de seconde ligne (SLI), ont été identifiés dans différents centres de traitement de la DR-TB en Éthiopie. OBJECTIF: Évaluer l'éligibilité des patients atteints de DR-TB sélectionnés à une aide auditive et fournir cette dernière à 10 patients éligibles. MÉTHODE: Il s'agissait d'une étude de cohorte observationnelle. Les patients ont été suivis pendant 8 mois, avec examens auditifs à 1, 3 et 8 mois pour évaluer de manière objective leur capacité auditive. RÉSULTATS: Sur 12 patients évalués pour éligibilité à une aide auditive, 10 ont été équipés (type XTM XP P4) et suivis pendant 8 mois. Une amélioration « formelle ¼ a été observée chez seulement un patient, mais la « qualité de vie globale ¼ de neuf patients semble s'être améliorée. CONCLUSION: Une amélioration « formelle ¼ minime a été observée. L'étude était cependant trop petite pour pouvoir recommander ou non les aides auditives en tant que mesure de santé publique. Une étude de suivi mieux contrôlée et plus vaste est nécessaire. Les schémas thérapeutiques entièrement par voie orale de la DR-TB doivent être utilisés chez tous les patients atteints de la maladie en Éthiopie. Cependant, puisque certains patients atteints de DR-TB sont susceptibles de continuer à recevoir des SLI dans un futur proche, un contrôle étroit par audiométrie et des soins appropriés seront nécessaires.

Introducing bedaquiline: experiences from the Challenge TB Project.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) remains a global public health crisis. In 2013, the World Health Organization recommended the introduction of bedaquiline (BDQ) for eligible DR-TB patients.METHODS: We conducted a retrospective review and analyses of project reports from 2016 to mid-2019 on the processes, activities implemented, available results on enrolment and interim treatment outcomes, across the 23 Challenge TB (CTB) supported countries.RESULTS: Initial introduction of BDQ-containing regimens in the 23 CTB-supported countries took on average 2 years, with subsequent nation-wide scale-up achieved in Ethiopia and Kyrgyzstan within a short time period. Successful implementation required critical interventions including advocacy, revision of policies and guidelines, capacity building of health care workers, and strengthening of laboratory networks. The number of countries providing BDQ increased from 9 to 23; 9398 patients were enrolled on bedaquiline containing regimens; 71% were culture-negative after 6 months of treatment; and the number of countries reporting serious adverse events increased (from 5 to 18). Major challenges included limited in-country coordination with drug regulatory agencies, unrealistic quantification and drug ordering, weak laboratory networks and reporting systems for drug safety.CONCLUSION: BDQ introduction required a systematic and programmatic approach. The initial time investment helped achieve initial introduction and scale-up of coverage, ownership and sustainability by National TB Programmes.

Smoking and alcohol consumption: Risk factors for pulmonary tuberculosis among the tribal community in central India.

Smoking and alcohol consumption are important risk factors for pulmonary tuberculosis (PTB). A cross-sectional survey was undertaken among the Gond tribe in Jabalpur district of Madhya Pradesh, and information on smoking and alcohol consumption was collected. As compared to females, males had an increased odds for PTB prevalence (odds ratio (OR) 3.2; 95% CI 486.4-1358.4; p=0.01). Similarly smokers and alcohol consumers had an increased odds for PTB compared to non-smokers and non-alcohol consumers, respectively [(OR 3.2; 95% CI 516.4-1986.4; p=0.003); (OR 3.2; 95% CI 480.8-2254.8; p=0.009)]. Persons who were both smokers and alcohol consumers had an equally increased odds of PTB than those who did not smoke and consumed alcohol (OR 4.1; 95% CI 477.6-2581.6; p=0.001). The study findings highlight the need to develop and implement culturally appropriate awareness raising activities among the tribal community to support TB control efforts.

Yield of pulmonary tuberculosis cases by symptoms: Findings from a community survey in Madhya Pradesh, central India.

A cross-sectional tuberculosis prevalence survey was undertaken in Jabalpur district, Madhya Pradesh, central India. All individuals were questioned for chest symptoms. Sputum samples were collected and examined for microscopy and culture. Overall prevalence of sputum positive pulmonary tuberculosis was found to be 255.3 per 100,000 population. Cough, with or without other symptoms, was present in 75.5% individuals and yielded 88.2% of the detected pulmonary tuberculosis cases. Elicitation of a previous history of treatment yielded 5.9%, and chest pain 4.5% cases. History of fever alone yielded no cases. The findings suggest that a history of fever alone may be safely excluded from the list of symptoms to be elicited in future TB prevalence surveys in India.

Tobacco smoking: a major risk factor for pulmonary tuberculosis--evidence from a cross-sectional study in central India.

BACKGROUND: This paper provides information on the association of tobacco smoking and alcohol consumption with pulmonary TB (PTB) in central India. METHODS: A community based cross-sectional TB prevalence survey was conducted in Jabalpur district of the central Indian state of Madhya Pradesh. The information on tobacco smoking and alcohol consumption was collected from individuals aged ≥15 years. Using logistic regression analysis, the risk factors for PTB were identified. RESULTS: A total of 94 559 individuals provided information on tobacco smoking and alcohol consumption. Persons aged 35-54 years and 55 years and above had, respectively, a 2.19 (95% CI 1.57-3.07) and a 3.26 (95% CI 2.23-4.77) times higher risk of developing PTB compared to persons aged below 35 years. Males had a 2.35 (95% CI 1.66-3.32) times higher risk than females. Tribals (indigenous population) had a 2.32 (95% CI 1.68-3.21) times higher risk than non-tribal population. The adjusted prevalence odds ratio for mild, moderate and heavy tobacco smokers were 2.28, 2.51 and 2.74 respectively as compared to non-smokers. Alcohol consumption was not found to be a risk factor on multivariate analysis. CONCLUSION: Tobacco smoking is significantly associated with PTB in this central Indian district. Smoking cessation services need to be integrated into the activities of the TB control programme.

Safety of cycloserine and terizidone for the treatment of drug-resistant tuberculosis: a meta-analysis.

Although cycloserine (CS) is recommended by the World Health Organization as a second-line agent for the treatment of multidrug-resistant tuberculosis (MDR-TB), safety concerns have impeded its uptake by several national TB programmes. Terizidone (TRD), a structural analogue of cycloserine, may be better tolerated. To assess the safety of CS and TRD for TB treatment, a systematic review and meta-analysis were conducted. From articles published up to December 2011, 27 studies with 2164 patients were included in our review of CS use. The pooled estimate for the frequencies of any adverse drug reaction (ADR) from CS was 9.1% (95%CI 6.4-11.7); it was 5.7% (95%CI 3.7-7.6) for psychiatric ADRs, and 1.1% (95%CI 0.2-2.1) for central nervous system (CNS) related ADRs. TRD showed no better to moderately better safety than CS in a systematic review of the available literature. The published evidence suggests that CS is associated with a higher frequency of psychiatric and CNS-related ADRs than other second-line drugs. While data were limited, treatment discontinuation rates appeared to be manageable. There were no significant differences in tolerability by region, study period or combination. As countries review and revise their treatment programmes, CS, and potentially TRD, should be included in MDR-TB treatment regimens. Adequate information on possible ADRs should be provided to patients, their families and attending health care workers. Greater attention to MDR-TB patients' mental health and a significant increase in resources devoted to pharmacovigilance and treatment of MDR-TB are essential.

Capilia test for identification of Mycobacterium tuberculosis in MGIT™-positive cultures.

BACKGROUND: The performance of the Capilia test for rapid identification of Mycobacterium tuberculosis complex (MTC) in Mycobacterium Growth Indicator Tube (MGIT) positive samples with contaminating organisms is not well documented. OBJECTIVE: To assess the diagnostic yield of the Capilia test in the rapid identification of MTC in MGIT-positive cultures. DESIGN: A total of 459 selected sputum samples were cultured using BACTEC™ MGIT™ 960. Tubes flagged positive by the MGIT instrument (MGIT-positive) were examined for acid-fast bacilli and cording in smears, spotted on blood agar (BA), subcultured for biochemical tests and tested using the Capilia test. Based on smear and growth on BA, MGIT-positive tubes were grouped into MGIT true-positive, MGIT-positive with contamination and MGIT contamination. Performance parameters of Capilia test such as sensitivity, specificity, efficiency, and positive and negative predictive values (PPV, NPV) for each of these groups were determined against biochemical tests as gold standard. RESULTS: Of the 346 MGIT-positives, respectively 233, 73 and 40 were MGIT true-positive, MGIT-positive with contamination and MGIT contamination. For the three groups, the PPV and NPV of the Capilia test were respectively 97%, 96% and 100%, and 32%, 27% and 60%. CONCLUSION: In settings with high contamination of MGIT cultures, the performance of the Capilia test is diminished.

Yield of culture of Mycobacterium tuberculosis complex in sputum samples transported from tribal areas.

BACKGROUND: There is little information on the recovery of Mycobacterium tuberculosis complex from sputum samples collected in the field for bacteriological examination. SETTING: Tribal areas in the State of Madhya Pradesh, in central India. METHODS: Sputum specimens collected from subjects with chest symptoms in a disease prevalence survey were refrigerated until transportation to the laboratory. The specimens were processed for microscopy and culture. The samples were grouped based on the delay in processing for culture from the day of collection into three groups: 0-3, 4-7 and ≥8 days, and the recovery of M. tuberculosis complex in these groups was analysed. The statistical analysis was performed using χ(2) test. RESULTS: Of the 3651 processed specimens, 114 were positive for M. tuberculosis complex by culture and 96 by smear microscopy. The differences in the proportion of 'smear-positive, culture-positive', 'smear-positive, culture-negative' and 'smear-negative, culture-positive' samples between the three groups were not significant. CONCLUSION: In difficult-to-reach areas with limited resources, refrigeration of sputum specimens until they are transported for processing at a reference laboratory for culture seems not to significantly affect the recovery of M. tuberculosis complex isolates.