Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.
IntroductionSuccessful treatment of tuberculosis depends to a large extent on good adherence to treatment regimens, which relies on directly observed treatment (DOT). This in turn requires frequent visits to health facilities. High costs to patients, stigma and burden to the health system challenged the DOT approach. Digital adherence technologies (DATs) have emerged as possibly more feasible alternatives to DOT but there is conflicting evidence on their effectiveness and feasibility. Our primary objective is to evaluate whether the implementation of DATs with daily monitoring and a differentiated response to patient adherence would reduce poor treatment outcomes compared with the standard of care (SOC). Our secondary objectives include: to evaluate the proportion of patients lost to follow-up; to compare effectiveness by DAT type; to evaluate the feasibility and acceptability of DATs; to describe factors affecting the longitudinal engagement of patients with the intervention and to use a simple model to estimate the epidemiological impact and cost-effectiveness of the intervention from a health system perspective.Methods and analysisThis is a pragmatic two-arm cluster-randomised trial in the Philippines, South Africa, Tanzania and Ukraine, with health facilities as the unit of randomisation. Facilities will first be randomised to either the DAT or SOC arm, and then the DAT arm will be further randomised into medication sleeve/labels or smart pill box in a 1:1:2 ratio for the smart pill box, medication sleeve/label or the SOC respectively. We will use data from the digital adherence platform and routine health facility records for analysis. In the main analysis, we will employ an intention-to-treat approach to evaluate treatment outcomes.Ethics and disseminationThe study has been approved by the WHO Research Ethics Review Committee (0003296), and by country-specific committees. The results will be shared at national and international meetings and will be published in peer-reviewed journals.Trial registration numberISRCTN17706019.
In Tanzania sputum culture for tuberculosis (TB) is resource intensive and available only at zonal facilities. In this study overnight pooled sputum collection technique was compared with standard spot morning collection among pulmonary TB suspects at Kibong'oto National TB Hospital in Tanzania. A spot sputum specimen performed at enrollment, an overnight pooled sputum, and single morning specimen were collected from 50 subjects and analyzed for quality, quantity, and time to detection in Bactec MGIT system. Forty-six (92%) subjects' overnight pooled specimens had a volume ≥5 mls compared to 37 (37%) for the combination of spot and single morning specimens (P < 0.001). Median time to detection was 96 hours (IQR 87–131) for the overnight pooled specimens compared to 110.5 hours (IQR is 137 right 137–180) for the combination of both spot and single morning specimens (P = 0.001). In our setting of limited TB culture capacity, we recommend a single pooled sputum to maximize yield and speed time to diagnosis.
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.
Drug-resistant tuberculosis (TB) is emerging as a new and serious public health challenge. We present the first case with confirmed extensive drug-resistant TB in Tanzania in a patient who had prior exposure to anti-TB drugs and a history of imprisonment in South Africa. The addition of bedaquiline to the treatment regime resulted in positive to negative sputum conversion. After a total of 30 months on treatment he was declared cured, remaining clinically stable and culture-negative throughout the follow-up. Close monitoring is important in managing drug-resistant TB cases, and good surveillance is required to detect drug-resistant TB to prevent further transmission.
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