Detection of Artemisinin Resistance Marker Kelch-13 469Y in Plasmodium falciparum, South Kivu, Democratic Republic of the Congo, 2022.

Partial artemisinin resistance has emerged in East Africa, posing a threat to malaria control across the continent. The Democratic Republic of the Congo carries one of the heaviest malaria burdens globally, and the South Kivu province directly borders current artemisinin resistance hot spots, but indications of such resistance have not been observed so far. We assessed molecular markers of antimalarial drug resistance in 256 Plasmodium falciparum isolates collected in 2022 in South Kivu, Democratic Republic of the Congo. One isolate carried the P. falciparum Kelch-13 469Y variant, a marker associated with partial artemisinin resistance and decreased lumefantrine susceptibility in Uganda. In addition, the multidrug resistance-1 mutation pattern suggested increased lumefantrine tolerance.

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.