Gridlock from diagnosis to treatment of multidrug-resistant tuberculosis in Tanzania: low accessibility of molecular diagnostic services and lack of healthcare worker empowerment in 28 districts of 5 high burden TB regions with mixed methods evaluation.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) outcomes are adversely impacted by delay in diagnosis and treatment. METHODS: Mixed qualitative and quantitative approaches were utilized to identify healthcare system related barriers to implementation of molecular diagnostics for MDR-TB. Randomly sampled districts from the 5 highest TB burden regions were enrolled during the 4th quarter of 2016. District TB & Leprosy Coordinators (DTLCs), and District AIDS Coordinators (DACs) were interviewed, along with staff from all laboratories within the selected districts where molecular diagnostics tests for MDR-TB were performed. Furthermore, the 2015 registers were audited for all drug-susceptible but retreatment TB cases and TB collaborative practices in HIV clinics, as these patients were in principal targeted for drug susceptibility testing by rapid molecular diagnostics. RESULTS: Twenty-eight TB districts from the 5 regions had 399 patients reviewed for retreatment with a drug-susceptible regimen. Only 160 (40%) had specimens collected for drug-susceptibility testing, and of those specimens only 120 (75%) had results communicated back to the clinic. MDR-TB was diagnosed in 16 (13.3%) of the 120 specimens but only 12 total patients were ultimately referred for treatment. Furthermore, among the HIV/AIDS clinics served in 2015, the median number of clients with TB diagnosis was 92 cases [IQR 32-157] yet only 2 people living with HIV were diagnosed with MDR-TB throughout the surveyed districts. Furthermore, the districts generated 53 front-line healthcare workers for interviews. DTLCs with intermediate or no knowledge on the clinical application of XpertMTB/RIF were 3 (11%), and 10 (39%), and DACs with intermediate or no knowledge were 0 (0%) and 2 (8%) respectively (p = 0.02). Additionally, 11 (100%) of the laboratories surveyed had only the 4-module XpertMTB/RIF equipment. The median time that XpertMTB/RIF was not functional in the 12 months prior to the investigation was 2 months (IQR 1-4). CONCLUSIONS: Underutilization of molecular diagnostics in high-risk groups was a function of a lack of front-line healthcare workforce empowerment and training, and a lack of equipment access, which likely contributed to the observed delay in MDR-TB diagnosis in Tanzania.

Gridlock from Diagnosis to Treatment of Multidrug-Resistant Tuberculosis (MDR-TB) in Tanzania: Illuminating Potential Factors for Possible Intervention.

SETTINGS: Kibong'oto Infectious Diseases Hospital, Kilimanjaro, Tanzania. OBJECTIVE: Characterise multidrug-resistant tuberculosis (MDR-TB)-treated cases during the scaling up of molecular diagnostics using Xpert MTB/RIF and GenoType MTBDRplus. DESIGN: Retrospective cohort study. RESULTS: A total of 223 MDR-TB patients were referred to the Kibong'oto Infectious Disease Hospital from January 2013 through December 2014. Four cities-Dar es Salaam, Mbeya, Mwanza, and Tanga-contributed 144 (65%) of referrals. Of the total referred patients, HIV coinfection was found in 92 (41%) and 180 (81%) had history of previous TB treatment. Molecular drug susceptibility testing (DST) contributed 201 (91%) of referrals and resulted in a shorter time from diagnosis to start of treatment, 30 days (95% confidence interval [CI], 26-37), compared to conventional phenotypic DST, 212 days (95% CI, 151-272; P<.001). Molecular DST found higher proportions of MDR-TB children and people living with HIV without prior treatment, 5 (12%) and 24 (56%), respectively, compared to those with previous treatment for TB, 4 (2%) and 68 (38%), respectively. The median CD4 count correspondingly was 131 cells/µl (IQR, 109-131) and 200 cells/µl (IQR, 94-337) for MDR-TB diagnosed by phenotypic and molecular diagnostics (P=.70). Despite the more rapid time to treatment initiation among patients diagnosed by molecular DST, treatment outcomes, including time to sputum culture conversion, did not differ compared to those diagnosed with conventional phenotypic DST. Regardless of the method of diagnosis, MDR-TB/HIV coinfected patients who died had lower CD4 counts (mean 86 ± 87 cells/µl) than survivors (mean 274 ± 224 cells/µl; P=.02). CONCLUSION: Molecular diagnostics appear to speedup the time to treatment initiation, but may not improve other treatment outcomes.

The Influence of Mining and Human Immunodeficiency Virus Infection Among Patients Admitted for Retreatment of Tuberculosis in Northern Tanzania.

In tuberculosis (TB)-prevalent settings, patients admitted for retreatment of TB may account for a high burden of poor treatment outcome. We performed a retrospective cohort study to characterize retreatment patients and outcomes at a TB referral hospital in northern Tanzania. From 2009 to 2013, 185 patients began a retreatment regimen, the majority for relapse after prior treatment completion. Men accounted for an unexpected majority (88%), 36 (20%) were human immunodeficiency virus (HIV) infected and for 45 (24%) mining was their primary occupation. A poor outcome (death, default, or persistent smear positivity after 7 months of treatment) was found in 37 (23%). HIV infection was the only significant predictor of poor outcome (adjusted odds ratio [aOR] = 2.50, 95% confidence interval [CI] = 1.07-5.83, P = 0.034). Interventions to minimize need for retreatment or improve retreatment success may be regionally specific. In our setting, community-based diagnosis and management among at-risk subpopulations such as miners and those HIV infected appear of highest yield.