Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications.

BACKGROUND: Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). METHODS: We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. RESULTS: Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. CONCLUSIONS: In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF-identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012-2017: A Retrospective Province-Wide Cohort Study.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. METHODS: of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan-Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. RESULTS: Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63-3.59), retreatment of TB (aOR 4.92, 95% CI 2.31-10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01-3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3-60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2-6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88-9.71). CONCLUSIONS: Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes.

Household Air Pollution Is Associated with Chronic Cough but Not Hemoptysis after Completion of Pulmonary Tuberculosis Treatment in Adults, Rural Eastern Democratic Republic of Congo.

Little is known about the respiratory health damage related to household air pollution (HAP) in survivors of pulmonary tuberculosis (PTB). In a population-based cross-sectional study, we determined the prevalence and associated predictors of chronic cough and hemoptysis in 441 randomly selected PTB survivors living in 13 remote health zones with high TB burden in the South Kivu province of the Democratic Republic of Congo (DRC). Trained community and health-care workers administered a validated questionnaire. In a multivariate logistic regression, chronic cough was independently associated with HAP (adjusted odds ratios (aOR) 2.10, 95% CI: 1.10⁻4.00) and PTB treatment >6 months (aOR 3.80, 95% CI: 1.62⁻8.96). Among women, chronic cough was associated with cooking ≥3 h daily (aOR 2.74, 95% CI: 1.25⁻6.07) and with HAP (aOR 3.93, 95% CI: 1.15⁻13.43). Independent predictors of hemoptysis were PTB retreatment (aOR 3.04, 95% CI: 1.04⁻5.09) and ignorance of treatment outcome (aOR 2.24, 95% CI: 1.09⁻4.58) but not HAP (aOR 1.86, 95% CI: 0.61⁻5.62). Exposure to HAP proved a major risk factor for chronic cough in PTB survivors, especially in women. This factor is amenable to intervention.

Patient-led active tuberculosis case-finding in the Democratic Republic of the Congo.

OBJECTIVE: To investigate the effect of using volunteer screeners in active tuberculosis case-finding in South Kivu, the Democratic Republic of the Congo, especially among groups at high risk of tuberculosis infection. METHODS: To identify and screen high-risk groups in remote communities, we trained volunteer screeners, mainly those who had themselves received treatment for tuberculosis or had a family history of the disease. A non-profit organization was created and screeners received training on the disease and its transmission at 3-day workshops. Screeners recorded the number of people screened, reporting a prolonged cough and who attended a clinic for testing, as well as test results. Data were evaluated every quarter during the 3-year period of the intervention (2014-2016). FINDINGS: Acceptability of the intervention was high. Volunteers screened 650 434 individuals in their communities, 73 418 of whom reported a prolonged cough; 50 368 subsequently attended a clinic for tuberculosis testing. Tuberculosis was diagnosed in 1 in 151 people screened, costing 0.29 United States dollars (US$) per person screened and US$ 44 per person diagnosed. Although members of high-risk groups with poorer access to health care represented only 5.1% (33 002/650 434) of those screened, they contributed 19.7% (845/4300) of tuberculosis diagnoses (1 diagnosis per 39 screened). The intervention resulted in an additional 4300 sputum-smear-positive pulmonary tuberculosis diagnoses, 42% (4 300/10 247) of the provincial total for that period. CONCLUSION: Patient-led active tuberculosis case-finding represents a valuable complement to traditional case-finding, and should be used to assist health systems in the elimination of tuberculosis.

Patient-led active tuberculosis case-finding in the Democratic Republic of the Congo

Objective To investigate the effect of using volunteer screeners in active tuberculosis case-finding in South Kivu, the Democratic Republic of the Congo, especially among groups at high risk of tuberculosis infection. Methods:To identify and screen high-risk groups in remote communities, we trained volunteer screeners, mainly those who had themselves received treatment for tuberculosis or had a family history of the disease. A non-profit organization was created and screeners received training on the disease and its transmission at 3-day workshops. Screeners recorded the number of people screened, reporting a prolonged cough and who attended a clinic for testing, as well as test results. Data were evaluated every quarter during the 3-year period of the intervention (2014­2016). Findings : Acceptability of the intervention was high. Volunteers screened 650 434 individuals in their communities, 73 418 of whom reported a prolonged cough; 50 368 subsequently attended a clinic for tuberculosis testing. Tuberculosis was diagnosed in 1 in 151 people screened, costing 0.29 United States dollars (US$) per person screened and US$ 44 per person diagnosed. Although members of high-risk groups with poorer access to health care represented only 5.1% (33 002/650 434) of those screened, they contributed 19.7% (845/4300) of tuberculosis diagnoses (1 diagnosis per 39 screened). The intervention resulted in an additional 4300 sputum-smear-positive pulmonary tuberculosis diagnoses, 42% (4 300/10 247) of the provincial total for that period. Conclusion:Patient-led active tuberculosis case-finding represents a valuable complement to traditional case-finding, and should be used to assist health systems in the elimination of tuberculosis

Prediction of Under-Detection of Paediatric Tuberculosis in the Democratic Republic of Congo: Experience of Six Years in the South-Kivu Province.

INTRODUCTION: In the field of tuberculosis (TB), and particularly in regard to paediatric TB (PedTB), clinical skills of health professionals play an important role in determining quality of care. In an era where novel diagnostic technologies and efficient treatment regimens are being made available for the poorest, we must not divert our attention from the importance of clinical skills, as this deliverable remains the cornerstone of individualized patient care and ultimately the best assurance for optimal use of resources. The aim of our work was to study the epidemiology of PedTB and the determinants of PedTB under-detection in the South-Kivu Province of the Democratic Republic of Congo (DRC), a setting with nearly no technical resources allowing to support the clinical diagnosis of PedTB, i.e. chest X-rays, rapid molecular tests or culture laboratories. METHODS: We collected TB notification data from 2010 to 2015 and analysed the space-time variations in notification for the different forms of TB among the 113 health facilities (HF) the South-Kivu Province, a region with a low HIV incidence. The different forms of TB notified were: smear positive pulmonary TB (SS+PTB), smear negative pulmonary TB (SS-PTB) and extra-pulmonary TB (EPTB). We further analysed the distribution of these different forms of the disease per age group and explored the possibility to predict the detection of PedTB. RESULTS: Significant differences were observed between HF in regard to the proportion of paediatric TB and the proportion of SS-TB among adults. We found a strong correlation between the proportion of PedTB and three major factors: the proportion of TB cases with no bacteriological confirmation (SS-TB) among adults, the number of TB cases notified by the HF and the fact that the HF was supported or not by Médecins Sans Frontières (MSF). The proportion of SS-TB among adults was found to be a valid indicator for predicting the level of detection of PedTB at the same HF. CONCLUSION: Our observations strongly suggest that under-detection of PedTB is associated with insufficient clinical skills and technical resources at the HF level which similarly affects other forms of the disease, in particular SS-TB. We demonstrated that, in the specific context of South-Kivu, under-detection of PedTB can be predicted by a low SS-TB/SS+PTB ratio in the adult population. In the context of severely under-resourced settings, this ratio could be used to rapidly identify HF that should benefit in priority from deeper evaluation, and eventually targeted interventions.