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Background Household contact tracing provides TB screening and TB preventive therapy (TPT) to contacts at high risk of TB disease. However, it is resource intensive, inconvenient, and often poorly implemented. We investigated a novel model aiming to improve uptake. Methods Between May and December 2014, we randomised patient with TB who consented to participate in the trial to either standard of care (SOC) or intervention (PACTS) arms. Participants randomised to PACTS received one screening/triage tool (adapted from WHO integrated management of adolescent and adult illnesses [IMAI] guidelines) and sputum pots for each reported household contact. The tool guided participants through symptom screening; TPT (6-months of isoniazid) eligibility; and sputum collection for contacts. Patients randomised to SOC were managed in accordance with national guidelines, that is, they received verbal instruction on who to bring to clinics for investigation using national guidelines. Main outcome and measures The primary outcome was the proportion of adult contacts receiving treatment for TB within 3 months of randomisation. Secondary outcomes were the proportions of child contacts under age 5 years (U5Y) who were commenced on, and completed, TPT. Data were analyzed by logistic regression with random effects to adjust for household clustering. Results Two hundred and fourteen index TB participants were block-randomized from two sites (107 PACTS, reporting 418 contacts; and 107 SOC, reporting 420 contacts). Overall, 62.8% of index TB participants were HIV-positive and 52.1% were TB culture-positive. 250 otherwise eligible TB patients declined participation and 6 households (10 PACTS, 6 SOC) were lost to follow-up and were not included in the analysis. By three months, nine contacts (PACTS: 6, [1.4%]; SOC: 3, [0.7%]) had TB diagnosed, with no difference between groups (adjusted odds ratio [aOR]: 2.18, 95% CI: 0.60–7.95). Eligible PACTS contacts (37/96, 38.5%) were more likely to initiate TPT by 3-months compared to SOC contacts (27/101, 26.7%; aOR 2.27, 95% CI: 1.04–4.98). U5Y children in the PACTS arm (47/81 58.0%) were more likely to have initiated TPT before the 3-month visit compared to SOC children (36/89, 41.4%; aOR: 2.31, 95% CI: 1.05–5.06). Conclusions and relevance A household-centred patient-delivered symptom screen and IPT eligibility assessment significantly increased timely TPT uptake among U5Y children, but did not significantly increase TB diagnosis. This model needs to be optimized for acceptability, given low participation, and investigated in other low resource settings. Clinical trial registration TRIAL REGISTRATION NUMBER: ISRCTN81659509 https://www.isrctn.com/ISRCTN81659509?q=&filters=conditionCategory:Respiratory,recruitmentCountry:Malawi,ageRange:Mixed&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search. 19 July 2012.

Introduction Invasive infections caused by Salmonella enterica serovar Typhi and Paratyphi A are estimated to account for 12–27 million febrile illness episodes worldwide annually. Determining the true burden of typhoidal Salmonellae infections is hindered by lack of population-based studies and adequate laboratory diagnostics.\ud \ud The Strategic Typhoid alliance across Africa and Asia study takes a systematic approach to measuring the age-stratified burden of clinical and subclinical disease caused by typhoidal Salmonellae infections at three high-incidence urban sites in Africa and Asia. We aim to explore the natural history of Salmonella transmission in endemic settings, addressing key uncertainties relating to the epidemiology of enteric fever identified through mathematical models, and enabling optimisation of vaccine strategies.\ud \ud Methods/design Using census-defined denominator populations of ≥100 000 individuals at sites in Malawi, Bangladesh and Nepal, the primary outcome is to characterise the burden of enteric fever in these populations over a 24-month period. During passive surveillance, clinical and household data, and laboratory samples will be collected from febrile individuals. In parallel, healthcare utilisation and water, sanitation and hygiene surveys will be performed to characterise healthcare-seeking behaviour and assess potential routes of transmission. The rates of both undiagnosed and subclinical exposure to typhoidal Salmonellae (seroincidence), identification of chronic carriage and population seroprevalence of typhoid infection will be assessed through age-stratified serosurveys performed at each site. Secondary attack rates will be estimated among household contacts of acute enteric fever cases and possible chronic carriers.\ud \ud Ethics and dissemination This protocol has been ethically approved by the Oxford Tropical Research Ethics Committee, the icddr,b Institutional Review Board, the Malawian National Health Sciences Research Committee and College of Medicine Research Ethics Committee and Nepal Health Research Council. The study is being conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained before study enrolment. Results will be submitted to international peer-reviewed journals and presented at international conferences.\ud \ud Trial registration number ISRCTN 12131979.\ud \ud Ethics references Oxford (Oxford Tropical Research Ethics Committee 39-15).\ud \ud Bangladesh (icddr,b Institutional Review Board PR-15119).\ud \ud Malawi (National Health Sciences Research Committee 15/5/1599).\ud \ud Nepal (Nepal Health Research Council 306/2015).

OBJECTIVES\ud To evaluate the effect of storing commonly used rapid diagnostic tests above manufacturer-recommended temperature (at 37°C), and the accuracy of delayed reading of oral fluid kits with relevance to HIV self-testing programmes.\ud \ud DESIGN\ud A quality assurance study of OraQuick (OraSure), Determine HIV 1/2™ (Alere) and Uni-Gold™ (Recombigen®).\ud \ud METHODS\ud Consecutive adults (≥18y) attending Ndirande Health Centre in urban Blantyre, Malawi in January to April 2012 underwent HIV testing with two of each of the three rapid diagnostic test kits stored for 28 days at either 18°C (optimally-stored) or at 37°C (pre-incubated). Used OraQuick test kits were stored in a laboratory for delayed day 1 and subsequent monthly re-reading was undertaken for one year.\ud \ud RESULTS\ud Of 378 individuals who underwent parallel testing, 5 (1.3%) were dropped from the final analysis due to discordant or missing reference standard results (optimally-stored Determine and Uni-Gold). Compared to the diagnostic reference standard, OraQuick had a sensitivity of 97.2% (95% CI: 93.6-99.6). There were 7 false negative results among all test kits stored at 37°C and three false negatives among optimally stored kits. Excellent agreement between pre-incubated tests and optimally-stored tests with Kappa values of 1.00 for Determine and Uni-Gold; and 0.97 (95% CI: 0.95; 1.00) for OraQuick were observed. There was high visual stability on re-reading of OraQuick, with only 1/375 pre-incubated and 1/371 optimally-stored OraQuick kits changing from the initial result over 12 months.\ud \ud CONCLUSION\ud Erroneous results observed during HIV testing in low income settings are likely to be due to factors other than suboptimal storage conditions. Re-reading returned OraQuick kits may offer a convenient and accurate quality assurance approach, including in HIV self-testing programmes.