Drug-resistant tuberculosis in high-risk groups, Zimbabwe.

To estimate prevalence of multidrug-resistant tuberculosis (MDR TB) in Harare, Zimbabwe, in 2012, we performed microbiologic testing on acid-fast bacilli smear-positive sputum samples from patients previously treated for TB. Twenty (24%) of 84 specimens were consistent with MDR TB. A national drug-resistance survey is needed to determine MDR TB prevalence in Zimbabwe.

Health care seeking patterns of rifampicin-resistant tuberculosis patients in Harare, Zimbabwe: A prospective cohort study.

BACKGROUND: Delays in seeking and accessing treatment for rifampicin-resistant tuberculosis (RR-TB) and multi-drug resistant (MDR-TB) are major impediments to TB control in high-burden, resource-limited settings. METHOD: We prospectively determined health-seeking behavioural patterns and associations with treatment outcomes and costs among 68 RR-TB patients attending conveniently selected facilities in a decentralised system in Harare, Zimbabwe. RESULTS: From initial symptoms to initiation of effective treatment, patients made a median number of three health care visits (IQR 2-4 visits) at a median cost of 13% (IQR 6-31%) of their total annual household income (mean cost, US$410). Cumulatively, RR-TB patients most frequently first visited private facilities, i.e., private pharmacies (30%) and other private health care providers (24%) combined. Median patient delay was 26 days (IQR 14-42 days); median health system delay was 97 days (IQR 30-215 days) and median total delay from symptom onset to initiation of effective treatment was 132 days (IQR 51-287 days). The majority of patients (88%) attributed initial delay in seeking care to "not feeling sick enough." Total delay, total cost and number of health care visits were not associated with treatment or clinical outcomes, though our study was not adequately powered for these determinations. CONCLUSIONS: Despite the public availability of rapid molecular TB tests, patients experienced significant delays and high costs in accessing RR-TB treatment. Active case finding, integration of private health care providers and enhanced service delivery may reduce treatment delay and TB associated costs.

A suggested algorithm for detection of multi drug-resistant tuberculosis in Zimbabwe.

INTRODUCTION: Rapid genotypic and phenotypic methods for multi-drug-resistant-tuberculosis (MDR-TB) detection are now widely available. Zimbabwe adopted the use of GeneXpert-MTB/RIF, microscopic-observation-drug-susceptibility-assay (MODS) and Mycobacteria-Growth-Indicator-Tube (MGIT) drug-susceptibility-testing (DST). Data is limited on the ideal combination of use of these methods in resource limited settings. METHODOLOGY: Between August 2014 to July 2015, 211 sputa from MDR-TB suspects were tested with GeneXpert-MTB/RIF, MODS, manual-MGIT and Lowenstein-Jensen (LJ)-DST to determine diagnostic accuracy and turnaround-time (TAT), with LJ-DST as the gold standard. A performance score ranking table for diagnostic accuracy, TAT, costs, facilities and expertise requirements, was used to determine the most favourable tool. RESULTS: GeneXpert-MTB/RIF sensitivity was 96% (95%CI:80-100) and specificity was 95% (95%CI:90-97). MODS sensitivity was 88% (95%CI:68-97) and specificity was 97% (95%CI:87-100). Manual MGIT-DST had slightly lower sensitivity of 80% (95%CI:59-93). Median time to detection of MDR-TB was <1 day (IQR:0-0) for Xpert, 14 days (IQR:11-31) for MODS, 21 days (IQR:7-22) for MGIT-DST and 28 days (IQR:25-28) for LJ-DST. Operational costs for MODS, MGIT-DST, and GeneXpert-MTB/RIF were $21.20, $27.52 and $39.76 respectively. From a summation of scores including facility and expertise requirements per diagnostic technique, GeneXpert-MTB/RIF was the most favourable tool, followed by MODS and MGIT-DST. CONCLUSIONS: For best scale-up of MDR-TB diagnosis in Zimbabwe, GeneXpert-MTB/RIF can be used for rapid detection of TB in smear negative cases, RIF-susceptibility for early treatment initiation and probable MDR-TB. MODS can rapidly confirm probable MDR-TB detected by GeneXpert-MTB/RIF, manual-MGIT can provide early results for susceptibility to other antibiotics, with affordable costs, with LJ-DST confirming discordant DSTs.

Microscopic-observation drug-susceptibility assay for the diagnosis of drug-resistant tuberculosis in Harare, Zimbabwe.

INTRODUCTION: Limited data exist on use of the microscopic-observation drug-susceptibility (MODS) assay among persons suspected of MDR-TB living in high HIV-prevalence settings. METHODS: We retrospectively reviewed available clinical and drug susceptibility data for drug-resistant TB suspects referred for culture and drug-susceptibility testing between April 1, 2011 and March 1, 2012. The diagnostic accuracy of MODS was estimated against a reference standard including Löwenstein-Jensen (LJ) media and manual liquid (BACTEC MGIT) culture. The accuracy of MODS drug-susceptibility testing (DST) was assessed against a reference standard absolute concentration method. RESULTS: One hundred thirty-eight sputum samples were collected from 99 drug-resistant TB suspects; in addition, six previously cultured MDR isolates were included for assessment of DST accuracy. Among persons with known HIV infection status, 39/59 (66%) were HIV-infected. Eighty-six percent of patients had a history of prior TB treatment, and 80% of individuals were on antituberculous treatment at the time of sample collection. M. tuberculosis was identified by reference standard culture among 34/98 (35%) MDR-TB suspects. Overall MODS sensitivity for M. tuberculosis detection was 85% (95% CI, 69-95%) and specificity was 93% (95% CI, 84-98%); diagnostic accuracy did not significantly differ by HIV infection status. Median time to positivity was significantly shorter for MODS (7 days; IQR 7-15 days) than MGIT (12 days; IQR 6-16 days) or LJ (28 days; IQR 21-35 days; p<0.001). Of 33 specimens with concurrent DST results, sensitivity of the MODS assay for detection of resistance to isoniazid, rifampin, and MDR-TB was 88% (95% CI, 68-97%), 96% (95% CI, 79-100%), and 91% (95% CI, 72-99%), respectively; specificity was 89% (95% CI, 52-100%), 89% (95% CI, 52-100%), and 90% (95% CI, 56-100%), respectively. CONCLUSION: In a high HIV-prevalence setting, MODS diagnosed TB and drug-resistant TB with high sensitivity and shorter turnaround time compared with standard culture and DST methods.