Diagnosis and Interim Treatment Outcomes from the First Cohort of Multidrug-Resistant Tuberculosis Patients in Tanzania.

Kibong'oto National Tuberculosis Hospital (KNTH), Kilimanjaro, Tanzania. Characterize the diagnostic process and interim treatment outcomes from patients treated for multidrug-resistant tuberculosis (MDR-TB) in Tanzania. A retrospective cohort study was performed among all patients treated at KNTH for pulmonary MDR-TB between November 2009 and September 2011. Sixty-one culture-positive MDR-TB patients initiated therapy, 60 (98%) with a prior history of TB treatment. Forty-one (67%) were male and 9 (14%) were HIV infected with a mean CD4 count of 424 (±106) cells/µl. The median time from specimen collection to MDR-TB diagnosis and from diagnosis to initiation of MDR-TB treatment was 138 days (IQR 101-159) and 131 days (IQR 32-233), respectively. Following treatment initiation four (7%) patients died (all HIV negative), 3 (5%) defaulted, and the remaining 54 (89%) completed the intensive phase. Most adverse drug reactions were mild to moderate and did not require discontinuation of treatment. Median time to culture conversion was 2 months (IQR 1-3) and did not vary by HIV status. In 28 isolates available for additional second-line drug susceptibility testing, fluoroquinolone, aminoglycoside and para-aminosalicylic acid resistance was rare yet ethionamide resistance was present in 9 (32%). The majority of MDR-TB patients from this cohort had survived a prolonged referral process, had multiple episodes of prior TB treatment, but did not have advanced AIDS and converted to culture negative early while completing an intensive inpatient regimen without serious adverse event. Further study is required to determine the clinical impact of second-line drug susceptibility testing and the feasibility of alternatives to prolonged hospitalization

Comparison of Overnight Pooled and Standard Sputum Collection Method for Patients with Suspected Pulmonary Tuberculosis in Northern Tanzania.

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

Use of a molecular bacterial load assay to distinguish between active TB and post-TB lung disease

Authors acknowledge financial support from the EDCTP2 programme supported by the European Union project (grant #: TMA2016SF-1463-REMODELTZ) and DELTAS Africa Initiative (Afrique One-ASPIRE /DEL-15-008). The Afrique One-ASPIRE is funded by a consortium of donors including the African Academy of Sciences, Alliance for Accelerating Excellence in Science in Africa, the New Partnership for Africa's Development Planning and Coordinating Agency, the Wellcome Trust (107753/A/15/Z), and the UK Government. PMM, SKH and SGM were also supported by NIH U01AI115594.Publisher PDFPeer reviewe

What are the barriers to the diagnosis and management of chronic respiratory disease in sub-Saharan Africa? A qualitative study with healthcare workers, national and regional policy stakeholders in five countries

Objectives Chronic respiratory diseases (CRD) are among the top four non-communicable diseases globally. They are associated with poor health and approximately 4 million deaths every year. The rising burden of CRD in low/middle-income countries will strain already weak health systems. This study aimed to explore the perspectives of healthcare workers and other health policy stakeholders on the barriers to effective diagnosis and management of CRD in Kenya, Malawi, Sudan, Tanzania and Uganda. Study design Qualitative descriptive study. Settings Primary, secondary and tertiary health facilities, government agencies and civil society organisations in five sub-Saharan African countries. Participants We purposively selected 60 national and district-level policy stakeholders, and 49 healthcare workers, based on their roles in policy decision-making or health provision, and conducted key informant interviews and in-depth interviews, respectively, between 2018 and 2019. Data were analysed through framework approach. Results We identified intersecting vicious cycles of neglect of CRD at strategic policy and healthcare facility levels. Lack of reliable data on burden of disease, due to weak information systems and diagnostic capacity, negatively affected inclusion in policy; this, in turn, was reflected by low budgetary allocations for diagnostic equipment, training and medicines. At the healthcare facility level, inadequate budgetary allocations constrained diagnostic capacity, quality of service delivery and collection of appropriate data, compounding the lack of routine data on burden of disease. Conclusion Health systems in the five countries are ill-equipped to respond to CRD, an issue that has been brought into sharp focus as countries plan for post-COVID-19 lung diseases. CRD are underdiagnosed, under-reported and underfunded, leading to a vicious cycle of invisibility and neglect. Appropriate diagnosis and management require health systems strengthening, particularly at the primary healthcare level

Balkan: od geografije do fantazije, Katarina Luketić

BACKGROUND: Tuberculosis is the world's leading infectious disease killer. We aimed to identify shorter, safer drug regimens for the treatment of tuberculosis. METHODS: We did a randomised controlled, open-label trial with a multi-arm, multi-stage design. The trial was done in seven sites in South Africa and Tanzania, including hospitals, health centres, and clinical trial centres. Patients with newly diagnosed, rifampicin-sensitive, previously untreated pulmonary tuberculosis were randomly assigned in a 1:1:1:1:2 ratio to receive (all orally) either 35 mg/kg rifampicin per day with 15-20 mg/kg ethambutol, 20 mg/kg rifampicin per day with 400 mg moxifloxacin, 20 mg/kg rifampicin per day with 300 mg SQ109, 10 mg/kg rifampicin per day with 300 mg SQ109, or a daily standard control regimen (10 mg/kg rifampicin, 5 mg/kg isoniazid, 25 mg/kg pyrazinamide, and 15-20 mg/kg ethambutol). Experimental treatments were given with oral 5 mg/kg isoniazid and 25 mg/kg pyrazinamide per day for 12 weeks, followed by 14 weeks of 5 mg/kg isoniazid and 10 mg/kg rifampicin per day. Because of the orange discoloration of body fluids with higher doses of rifampicin it was not possible to mask patients and clinicians to treatment allocation. The primary endpoint was time to culture conversion in liquid media within 12 weeks. Patients without evidence of rifampicin resistance on phenotypic test who took at least one dose of study treatment and had one positive culture on liquid or solid media before or within the first 2 weeks of treatment were included in the primary analysis (modified intention to treat). Time-to-event data were analysed using a Cox proportional-hazards regression model and adjusted for minimisation variables. The proportional hazard assumption was tested using Schoelfeld residuals, with threshold p<0.05 for non-proportionality. The trial is registered with ClinicalTrials.gov (NCT01785186). FINDINGS: Between May 7, 2013, and March 25, 2014, we enrolled and randomly assigned 365 patients to different treatment arms (63 to rifampicin 35 mg/kg, isoniazid, pyrazinamide, and ethambutol; 59 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, SQ109; 57 to rifampicin 20 mg/kg, isoniazid, pyrazinamide, and SQ109; 63 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, and moxifloxacin; and 123 to the control arm). Recruitment was stopped early in the arms containing SQ109 since prespecified efficacy thresholds were not met at the planned interim analysis. Time to stable culture conversion in liquid media was faster in the 35 mg/kg rifampicin group than in the control group (median 48 days vs 62 days, adjusted hazard ratio 1.78; 95% CI 1.22-2.58, p=0.003), but not in other experimental arms. There was no difference in any of the groups in time to culture conversion on solid media. 11 patients had treatment failure or recurrent disease during post-treatment follow-up: one in the 35 mg/kg rifampicin arm and none in the moxifloxacin arm. 45 (12%) of 365 patients reported grade 3-5 adverse events, with similar proportions in each arm. INTERPRETATION: A dose of 35 mg/kg rifampicin was safe, reduced the time to culture conversion in liquid media, and could be a promising component of future, shorter regimens. Our adaptive trial design was successfully implemented in a multi-centre, high tuberculosis burden setting, and could speed regimen development at reduced cost. FUNDING: The study was funded by the European and Developing Countries Clinical Trials partnership (EDCTP), the German Ministry for Education and Research (BmBF), and the Medical Research Council UK (MRC)