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Background: Adolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations., Methods: Adolescents aged 12-18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 h for reading. A TST of ≥10 mm if HIV negative or ≥ 5 mm if HIV positive, was considered positive., Results: Of 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1, 95% CI 29.2-35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2-3.1). Risk factors for a positive TST included being male (OR 1.3, 95% CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95% CI 1.2,1.8), having a BCG scar (OR 1.5,95% CI 1.2,1.8), living in a rural area (OR 1.4, 95% CI 1.1,1.9), and being out of school (OR 1.8, 95% CI 1.4,2.3)., Conclusion: We conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.

Background: Access to quality hypertension care is often poor in sub-Saharan Africa. Some community pharmacies offer hypertension monitoring services, with and without involvement of medical doctors. To directly connect pharmacy staff and cardiologists a care model including a mobile application (mHealth) for remote patient monitoring was implemented and pilot tested in Lagos, Nigeria. Pharmacists provided blood pressure measurements and counselling. Cardiologists enrolled patients in the pilot program and remotely monitored them, for which patients paid a monthly fee. We evaluated the feasibility of this care model at five private community pharmacies. Outcome measures were retention in care, blood pressure change, quality of care, and patients' and healthcare providers' satisfaction with the care model., Methods: Patients participated in the care model's pilot at one of the five pharmacies for approximately 6-8 months from February 2016. We conducted structured patient interviews and blood pressure measurements at pilot entry and exit, and used exports of the mHealth-application, in-depth interviews and focus group discussions with patients, pharmacists and cardiologists., Results: Of 336 enrolled patients, 236 (72%) were interviewed at pilot entry and exit. According to the mHealth data 71% returned to the pharmacy after enrollment, with 3.3 months (IQR: 2.2-5.4) median duration of activity in the mHealth-application. Patients self-reported more visits than recorded in the mHealth data. Pharmacists mentioned use of paper records, understaffing, the application not being user-friendly, and patients' unwillingness to pay as reasons for underreporting. Mean systolic blood pressure decreased 9.9 mmHg (SD: 18). Blood pressure on target increased from 24 to 56% and an additional 10% had an improved blood pressure at endline, however this was not associated with duration of mHealth activity. Patients were satisfied because of accessibility, attention, adherence and information provision., Conclusion: Patients, pharmacists and cardiologists adopted the care model, albeit with gaps in mHealth data. Most patients were satisfied, and their mean blood pressure significantly reduced. Usage of the mHealth application, pharmacy incentives, and a modified financing model are opportunities for improvement. In addition, costs of implementation and availability of involved healthcare providers need to be investigated before such a care model can be further implemented.

Background: Globally, 40% of all tuberculosis (TB) cases, 65% paediatric cases and 75% multi-drug resistant TB (MDR-TB) cases are missed due to underreporting and/or under diagnosis. A recent Kenyan TB prevalence survey found that a significant number of TB cases are being missed here. Understanding spatial distribution and patterns of use of TB diagnostic tests as per the guidelines could potentially help improve TB case detection by identifying diagnostic gaps., Methods: We used 2015 Kenya National TB programme data to map TB case notification rates (CNR) in different counties, linked with their capacity to perform diagnostic tests (chest x-rays, smear microscopy, Xpert MTB/RIF®, culture and line probe assay). We then ran hierarchical regression models for adults and children to specifically establish determinants of use of Xpert® (as per Kenyan guidelines) with county and facility as random effects., Results: In 2015, 82,313 TB cases were notified and 7.8% were children. The median CNR/100,000 amongst 0-14yr olds was 37.2 (IQR 20.6, 41.0) and 267.4 (IQR 202.6, 338.1) for ≥15yr olds respectively. 4.8% of child TB cases and 12.2% of adult TB cases had an Xpert® test done, with gaps in guideline adherence. There were 2,072 microscopy sites (mean microscopy density 4.46/100,000); 129 Xpert® sites (mean 0.31/100,000); two TB culture laboratories and 304 chest X-ray facilities (mean 0.74/100,000) with variability in spatial distribution across the 47 counties. Retreatment cases (i.e. failures, relapses/recurrences, defaulters) had the highest odds of getting an Xpert® test compared to new/transfer-in patients (AOR 7.81, 95% CI 7.33-8.33). Children had reduced odds of getting an Xpert® (AOR 0.41, CI 0.36-0.47). HIV-positive individuals had nearly twice the odds of getting an Xpert® test (AOR 1.82, CI 1.73-1.92). Private sector and higher-level hospitals had a tendency towards lower odds of use of Xpert®., Conclusions: We noted under-use and gaps in guideline adherence for Xpert® especially in children. The under-use despite considerable investment undermines cost-effectiveness of Xpert®. Further research is needed to develop strategies enhancing use of diagnostics, including innovations to improve access (e.g. specimen referral) and overcoming local barriers to adoption of guidelines and technologies.

Background: Molecular resistance detection (MRD) of resistance to second-line anti-tuberculous drugs provides faster results than phenotypic tests, may shorten treatment and allow earlier separation among patients with and without second-line drug resistance., Methods: In a decision-analytical model we simulated a cohort of patients diagnosed with TB in a setting where drug resistant TB is highly prevalent and requires initial hospitalization, to explore the potential benefits of a high-throughput MRD-assay for reducing potential nosocomial transmission of highly resistant strains, and total costs for diagnosis of drug resistance, treatment and hospitalization. In the base case scenario first-line drug resistance was diagnosed with WHO-endorsed molecular tests, and second-line drug resistance with culture and phenotypic methods. Three alternative scenarios were explored, each deploying high-throughput MRD allowing either detection of second-line mutations in cultured isolates, directly on sputum, or MRD with optimized markers., Results: Compared to a base case scenario, deployment of high-throughput MRD reduced total costs by 17-21 %. The period during which nosocomial transmission may take place increased by 15 % compared to the base case if MRD had currently reported suboptimal sensitivity and required cultured isolates; increased by 7 % if direct sputum analysis were possible including in patients with smear-negative TB, and reduced by 24 % if the assay had improved markers, but was still performed on cultured isolates. Improved clinical sensitivity of the assay (additional markers) by more than 35 % would be needed to avoid compromising infection control., Conclusions: Further development of rapid second-line resistance testing should prioritize investment in optimizing markers above investments in a platform for direct analysis of sputum.

Background: To inform the choice of an appropriate screening and diagnostic algorithm for tuberculosis (TB) screening initiatives in different epidemiological settings, we compare algorithms composed of currently available methods., Methods: Of twelve algorithms composed of screening for symptoms (prolonged cough or any TB symptom) and/or chest radiography abnormalities, and either sputum-smear microscopy (SSM) or Xpert MTB/RIF (XP) as confirmatory test we model algorithm outcomes and summarize the yield, number needed to screen (NNS) and positive predictive value (PPV) for different levels of TB prevalence., Results: Screening for prolonged cough has low yield, 22% if confirmatory testing is by SSM and 32% if XP, and a high NNS, exceeding 1000 if TB prevalence is ≤0.5%. Due to low specificity the PPV of screening for any TB symptom followed by SSM is less than 50%, even if TB prevalence is 2%. CXR screening for TB abnormalities followed by XP has the highest case detection (87%) and lowest NNS, but is resource intensive. CXR as a second screen for symptom screen positives improves efficiency., Conclusions: The ideal algorithm does not exist. The choice will be setting specific, for which this study provides guidance. Generally an algorithm composed of CXR screening followed by confirmatory testing with XP can achieve the lowest NNS and highest PPV, and is the least amenable to setting-specific variation. However resource requirements for tests and equipment may be prohibitive in some settings and a reason to opt for symptom screening and SSM. To better inform disease control programs we need empirical data to confirm the modeled yield, cost-effectiveness studies, transmission models and a better screening test.

Background: The two issues mostly affecting the success of tuberculosis (TB) control programmes are delay in presentation and non-adherence to treatment. It is important to understand the factors that contribute to these issues, particularly in resource limited settings, where rates of tuberculosis are high. The objective of this study is to assess health-seeking behaviour and health care experiences among persons with pulmonary tuberculosis, and identify the reasons patients might not complete their treatment., Methods: We performed qualitative one-on-one in-depth interviews with pulmonary tuberculosis patients in nine health facilities in rural western Kenya. Thirty-one patients, 18 women and 13 men, participated in the study. All reside in an area of western Kenya with a Health and Demographic Surveillance System (HDSS). They had attended treatment for up to 4 weeks on scheduled TB clinic days in September and October 2005.The nine sites all provide diagnostic and treatment services. Eight of the facilities were public (3 hospitals and 5 health centres) and one was a mission health centre., Results: Most patients initially self-treated with herbal remedies or drugs purchased from kiosks or pharmacies before seeking professional care. The reported time from initial symptoms to TB diagnosis ranged from 3 weeks to 9 years. Misinterpretation of early symptoms and financial constraints were the most common reasons reported for the delay.We also explored potential reasons that patients might discontinue their treatment before completing it. Reasons included being unaware of the duration of TB treatment, stopping treatment once symptoms subsided, and lack of family support., Conclusions: This qualitative study highlighted important challenges to TB control in rural western Kenya, and provided useful information that was further validated in a quantitative study in the same area.