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.

Water supply interruptions and suspected cholera incidence: a time-series regression in the Democratic Republic of the Congo.

BACKGROUND: The eastern provinces of the Democratic Republic of the Congo have been identified as endemic areas for cholera transmission, and despite continuous control efforts, they continue to experience regular cholera outbreaks that occasionally spread to the rest of the country. In a region where access to improved water sources is particularly poor, the question of which improvements in water access should be prioritized to address cholera transmission remains unresolved. This study aimed at investigating the temporal association between water supply interruptions and Cholera Treatment Centre (CTC) admissions in a medium-sized town. METHODS AND FINDINGS: Time-series patterns of daily incidence of suspected cholera cases admitted to the Cholera Treatment Centre in Uvira in South Kivu Province between 2009 and 2014 were examined in relation to the daily variations in volume of water supplied by the town water treatment plant. Quasi-poisson regression and distributed lag nonlinear models up to 12 d were used, adjusting for daily precipitation rates, day of the week, and seasonal variations. A total of 5,745 patients over 5 y of age with acute watery diarrhoea symptoms were admitted to the CTC over the study period of 1,946 d. Following a day without tap water supply, the suspected cholera incidence rate increased on average by 155% over the next 12 d, corresponding to a rate ratio of 2.55 (95% CI: 1.54-4.24), compared to the incidence experienced after a day with optimal production (defined as the 95th percentile-4,794 m3). Suspected cholera cases attributable to a suboptimal tap water supply reached 23.2% of total admissions (95% CI 11.4%-33.2%). Although generally reporting less admissions to the CTC, neighbourhoods with a higher consumption of tap water were more affected by water supply interruptions, with a rate ratio of 3.71 (95% CI: 1.91-7.20) and an attributable fraction of cases of 31.4% (95% CI: 17.3%-42.5%). The analysis did not suggest any association between levels of residual chlorine in the water fed to the distribution network and suspected cholera incidence. Laboratory confirmation of cholera was not available for this analysis. CONCLUSIONS: A clear association is observed between reduced availability of tap water and increased incidence of suspected cholera in the entire town of Uvira in Eastern Democratic Republic of the Congo. Even though access to piped water supplies is low in Uvira, improving the reliability of tap water supply may substantially reduce the incidence of suspected cholera, in particular in neighbourhoods having a higher access to tap water. These results argue in favour of water supply investments that focus on the delivery of a reliable and sustainable water supply, and not only on point-of-use water quality improvements, as is often seen during cholera outbreaks.

Elimination of cholera in the democratic Republic of the Congo: the new national policy.

We evaluated published and unpublished data on cholera cases and deaths reported from clinical care facilities in the 56 health districts of the Democratic Republic of Congo to the National Ministry of Health during 2000-2011. Cholera incidence was highest in the eastern provinces bordering lakes and epidemics primarily originated in this region. Along with a strong seasonal component, our data suggest a potential Vibrio cholerae reservoir in the Rift Valley lakes and the possible contribution of the lakes' fishing industry to the spread of cholera. The National Ministry of Health has committed to the elimination-rather than control-of cholera in DRC and has adopted a new national policy built on improved alert, response, case management, and prevention. To achieve this goal and implement all these measures it will require strong partners in the international community with a similar vision.