Objectives: Early diagnosis and timely treatment are key elements of a successful healthcare system. We assessed the role of socioeconomic and cultural norms in accelerating or decelerating uptake and utilisation of health technologies into policy and practice.

Setting: Secondary and tertiary level healthcare facilities (HCFs) in three East African countries. Level of HCF was selected based on the WHO recommendation for implantation of tuberculosis (TB) molecular diagnostics.

Participants: Using implementation of TB diagnostics as a model, we purposively selected participants (TB patients, carers, survivors, healthcare practitioners, community members, opinion leaders and policy-makers) based on their role as stakeholders. In-depth interviews, key informant interviews and focus group discussions were held to collect the data between 2016 and 2018. The data were transcribed, translated, coded and analysed by thematic-content analysis.

Results: A total of 712 individuals participated in the study. Socioeconomic and cultural factors such as poverty, stigma and inadequate knowledge about causes of disease and available remedies, cultural beliefs were associated with low access and utilisation of diagnostic and treatment tools for TB. Poverty made people hesitate to seek formal healthcare resulting in delayed diagnosis and resorting to self-medication and cheap herbal alternatives. Fear of stigma made people hide their sickness and avoid reporting for follow-up treatment visits. Inadequate knowledge and beliefs were fertile ground for aggravated stigma and believing that diseases like TB are caused by spirits and thus cured by spiritual rituals or religious prayers. Cultural norms were also the basis of gender-based imbalance in accessing care, 'I could not go to hospital without my husband's permission', TB survivor.

Conclusion: Our findings show that socioeconomic and cultural factors are substantial 'roadblocks' to accelerating the uptake and utilisation of diagnostic and treatment tools. Resolving these barriers should be given equal attention as is to health system barriers.

Tuberculosis (TB) is the leading cause of death from an infectious disease and the roll-out of rapid molecular diagnostics for rifampin resistance has resulted in a steady rise in the number of patients with multidrug-resistant (MDR)-TB referred for treatment. Pyrazinamide is used in susceptible TB treatment for 6 months when used in combination with rifampin, isoniazid and ethambutol and is an important companion drug in novel MDR-TB trials. This study was undertaken to determine the prevalence of pyrazinamide resistance by either phenotypic or pncA testing among patients admitted to a referral hospital in Tanzania for drug-susceptible and MDR-TB treatment.

Due to poor quality of research and research output, most African research scientist face, EDCTP designed for scientists from developing countries to work with pharmaceutical and research institute partners to learn how to lead clinical drug and vaccine trials. The ultimate goal is to reduce research bottlenecks as more new products enter the development pipeline, and develop strong research capability in low- and-middle income countries with infectious diseases.I receive 12 months of on-the-job training in R&D project management, Good Clinical Practice and regulatory requirements

Background: Early access to diagnosis is crucial for effective management of any disease including tuberculosis (TB). We investigated the barriers and opportunities to maximise uptake and utilisation of molecular diagnostics in routine healthcare settings.

Methods: Using the implementation of WHO approved TB diagnostics, Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) and Line Probe Assay (LPA) as a benchmark, we evaluated the barriers and how they could be unlocked to maximise uptake and utilisation of molecular diagnostics.

Results: Health officers representing 190 districts/counties participated in the survey across Kenya, Tanzania and Uganda. The survey findings were corroborated by 145 healthcare facility (HCF) audits and 11 policy-maker engagement workshops. Xpert MTB/RIF coverage was 66%, falling behind microscopy and clinical diagnosis by 33% and 1%, respectively. Stratified by HCF type, Xpert MTB/RIF implementation was 56%, 96% and 95% at district, regional and national referral hospital levels. LPA coverage was 4%, 3% below culture across the three countries. Out of 111 HCFs with Xpert MTB/RIF, 37 (33%) used it to full capacity, performing ≥8 tests per day of which 51% of these were level five (zonal consultant and national referral) HCFs. Likewise, 75% of LPA was available at level five HCFs. Underutilisation of Xpert MTB/RIF and LPA was mainly attributed to inadequate-utilities, 26% and human resource, 22%. Underfinancing was the main reason underlying failure to acquire molecular diagnostics. Second to underfinancing was lack of awareness with 33% healthcare administrators and 49% practitioners were unaware of LPA as TB diagnostic. Creation of a national health tax and decentralising its management was proposed by policy-makers as a booster of domestic financing needed to increase access to diagnostics.

Conclusion: Our findings suggest higher uptake and utilisation of molecular diagnostics at tertiary level HCFs contrary to the WHO recommendation. Country-led solutions are crucial for unlocking barriers to increase access to diagnostics.

Background: Despite effort to diagnose tuberculosis (TB) in the Human Immunodeficiency Virus (HIV) infected population, 45% of adults with HIV that had a previously unknown reason for death, demonstrated TB was the cause by autopsy examination. We aimed to assess the clinical outcomes of implementation a new algorithm for diagnosis and treatment of tuberculosis (TB) related sepsis among PLHIV presenting with life-threatening illness.

Methods: This study is a prospective cohort conducted in three-referral hospitals in Kilimanjaro, recruited 97 PLHIV from February through June 2018. Patients provided urine and sputum samples for testing lateral flow - lipoarabinomannan (LF-LAM) and Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) assays, respectively. Anti-TB was prescribed to patients with positive LF-LAM or Xpert MTB/RIF or received broad-spectrum antibiotics but deteriorated.

Results: Of 97 patients, 84 (87%) provided urine and sputa, and 13 (13%) provided only urine. The mean age (95% confidence interval) was 40 (38-43) years and 52 (54%) were female. In 84 patients, LF-LAM increased TB detection from 26 (31%) by Xpert MTB/RIF to 41 (55%) by both tests. Of 97 patients, 69 (71%) prescribed anti-TB, 67% (46/69) and 33% (23/69) had definitive and probable TB respectively. Sixteen (16.5%) patients died, of which one died before treatment, 73% (11/15) died within 7 days of admission. The 30-day survival was similar in both treatment groups (log rank = 0.1574). Mortality was significantly higher among hospitalized patients compared to outpatients (P ≤ 0.027).

Conclusion: Implementation of new algorithm increased TB case detection in patients that could have been missed by Xpert MTB/RIF assay. Survival of PLHIV with confirmed or probable TB was comparable to those of PLHIV that were treated with broad-spectrum antibiotics alone. Further work should focus on the optimal timing and content of the immediate antimicrobial regimen for sepsis among PLHIV in TB-endemic settings.

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.