Programmatic challenges in managing multidrug-resistant tuberculosis in Malawi.

Background: Multidrug-resistant tuberculosis (MDR-TB) is one of the most urgent challenges that Malawi tends to take a firm public health action. A recent increase in multidrug MDR-TB cases, a decrease in treatment success rate, and a double increase of lost-to-follow-up call into question the country's programmatic management of MDR-TB (PMDT). As such, the study aimed at exploring programmatic challenges in managing MDR-TB in Malawi. Methods: A comprehensive and nonsystematic search was made in PubMed and Google Scholar using mainly the keywords "MDR-TB" "extensively drug-resistant TB," Malawi. The study reviewed existing guidelines and gray literature and reviewed data obtained from the national TB program (NTP) as well. Results: The study found the following challenges affecting PMDT: decrease in funding, partial access to GeneXpert, delay in diagnosis, long treatment duration, lack of adequate personal protective equipment, the long turnaround time of culture results, failure to initiate all diagnosed patients on treatment, absence of alternative second-line medicines, and lack of transport from health facilities to patient homes. Conclusion: If the Malawi NTP is to achieve a vision of a "TB-free Malawi," rigorous efforts at all levels must be made, including mobilizing domestic resources for improved MDR-TB program performance. Developing partners should continue providing the much-needed funding to the Malawi government to stand in the wake of the MDR-TB crisis.

Molecular bacterial load assay versus culture for monitoring treatment response in adults with tuberculosis.

The lack of rapid, sensitive, and deployable tuberculosis diagnostic tools is hampering the early diagnosis of tuberculosis and early detection of treatment failures. The conventional sputum smear microscopy or Xpert MTB/RIF assay cannot distinguish between alive and dead bacilli and the culture method delays providing results. Tuberculosis molecular bacterial load assay is a reverse transcriptase real-time quantitative polymerase chain reaction that quantifies viable tuberculosis bacillary load as a marker of treatment response for patients on anti-tuberculosis therapy. However, results are not synthesized enough to inform its comparative advantage to tuberculosis culture technique which is yet the gold standard of care. With this review, we searched electronic databases, including PubMed, Embase, and Web of Science, from March 2011 up to February 2021 for clinical trials or prospective cohort studies that compared tuberculosis molecular bacterial load assay with tuberculosis culture in adults. We included eight studies that meet the inclusion criteria. Tuberculosis molecular bacterial load assay surpasses culture in monitoring patients with tuberculosis during the first few weeks of anti-tuberculosis treatment. It is more desirable over culture for its shorter time to results, almost zero rates of contamination, need for less expertise on the method, early rate of decline, lower running cost, and reproducibility. Its rapid and specific tuberculosis treatment monitoring competency benefits patients and healthcare providers to monitor changes of bacillary load among isolates with drug-susceptible or resistance to anti-tuberculosis regimens. Despite of the high installing cost of the tuberculosis molecular bacterial load assay method, molecular expertise, and a well-equipped laboratory, tuberculosis molecular bacterial load assay is a cost-effective method with comparison to culture in operational running. To achieve maximum utility in high tuberculosis burden settings, an intensive initial investment in nucleic acid extraction and polymerase chain reaction equipment, training in procedures, and streamlining laboratory supply procurement systems are crucial. More evidence is needed to demonstrate the potential large-scale and sustainable use of tuberculosis molecular bacterial load assay over culture in resource-constrained settings.

Pyrosequencing for diagnosis of multidrug and extensively drug-resistant tuberculosis: A systemic review and meta-analysis.

BACKGROUND: Multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) pose major threats to global health. Diagnosis accuracy and delay have been the major drivers for the upsurge of M/XDR-TB. Pyrosequencing (PSQ) is a novel, real-time DNA sequencing for rapid detection of mutations associated with M/XDR-TB. We aimed to systematically synthesize the evidence on the diagnostic accuracy of PSQ for M/XDR-TB. METHODS: We conducted an electronic search of PubMed, Embase, Biosis, Web of Science, and Google Scholar up to March 2020. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool to assess the quality of studies, the BRMA (bivariate random-effects meta-analysis) model to synthesize diagnostic accuracies, and the Rev-Man 5.4 software to perform the meta-analyses. We analyzed dichotomous data using the risk ratio (RR) with a 95% confidence interval. PROSPERO Registration ID: CRD42020200817. RESULTS: The analysis included seven studies, with a total sample of 3,165. At 95% confidence interval, the pooled sensitivity and specificity of PSQ were 89.7 (CI: 83.5-93.8) and 97.8 (CI: 94.9-99.1) for Isoniazid, 94.6 (CI: 90.9-96.8) and 98.5 (CI: 96.5-99.3) for Rifampicin, 87.9 (CI: 81.2-92.4) and 98.8 (CI: 97.2-99.5) for Fluoroquinolone, 83.5 (CI: 72.8-90.5) and 99.4 (CI: 98.3-99.8) for Amikacin, 79 (CI: 67-8-87) and 97.9 (CI: 95.5-99) for Capreomycin, and 69.6 (CI: 57-79.8) and 98.2 (CI: 95.9-99.2) for Kanamycin. The overall pooled sensitivity and specificity were 85.8 (CI: 76.7-91.7) and 98.5 (CI: 96.5-99.3), respectively. CONCLUSION: According to the pooled data, PSQ is highly sensitive and specific for detecting M/XDR-TB, both from clinical specimens and culture isolates, and within a shorter turnaround time. We suggest a continued synthesis of the evidence on the cost-effectiveness and technical feasibilities of PSQ in low-income countries context, including sub-Saharan Africa.