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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. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) infected adults are at a higher risk of pneumococcal colonisation and disease, even while receiving antiretroviral therapy (ART). To help evaluate potential indirect effects of vaccination of HIV-infected adults, we assessed whether HIV-infected adults disproportionately contribute to household transmission of pneumococci. We constructed a hidden Markov model to capture the dynamics of pneumococcal carriage acquisition and clearance observed during a longitudinal household-based nasopharyngeal swabbing study, while accounting for sample misclassifications. Households were followed-up twice weekly for approximately 10 months each year during a three-year study period for nasopharyngeal carriage detection via real-time PCR. We estimated the effect of participant's age, HIV status, presence of a HIV-infected adult within the household and other covariates on pneumococcal acquisition and clearance probabilities. Of 1,684 individuals enrolled, 279 (16.6%) were younger children (<5 years-old) of whom 4 (1.5%) were HIV-infected and 726 (43.1%) were adults (≥18 years-old) of whom 214 (30.4%) were HIV-infected, most (173, 81.2%) with high CD4+ count. The observed range of pneumococcal carriage prevalence across visits was substantially higher in younger children (56.9–80.5%) than older children (5–17 years-old) (31.7–50.0%) or adults (11.5–23.5%). We estimate that 14.4% (95% Confidence Interval [CI]: 13.7–15.0) of pneumococcal-negative swabs were false negatives. Daily carriage acquisition probabilities among HIV-uninfected younger children were similar in households with and without HIV-infected adults (hazard ratio: 0.95, 95%CI: 0.91–1.01). Longer average carriage duration (11.4 days, 95%CI: 10.2–12.8 vs 6.0 days, 95%CI: 5.6–6.3) and higher median carriage density (622 genome equivalents per millilitre, 95%CI: 507–714 vs 389, 95%CI: 311.1–435.5) were estimated in HIV-infected vs HIV-uninfected adults. The use of ART and antibiotics substantially reduced carriage duration in all age groups, and acquisition rates increased with household size. Although South African HIV-infected adults on ART have longer carriage duration and density than their HIV-uninfected counterparts, they show similar patterns of pneumococcal acquisition and onward transmission. Author summary: We assessed the contribution of HIV-infected adults to household pneumococcal transmission by applying a hidden Markov model to pneumococcal cohort data comprising 115,595 nasopharyngeal samples from 1,684 individuals in rural and urban settings in South Africa. We estimated 14.4% of sample misclassifications (false negatives), representing 85.6% sensitivity of a test that was used to detect pneumococcus. Pneumococcal carriage prevalence and acquisition rates, and average duration were usually higher in younger or older children than adults. The use of ART and antibiotics reduced the average carriage duration across all age and HIV groups, and carriage acquisition risks increased in larger household sizes. Despite the longer average carriage duration and higher median carriage density in HIV-infected than HIV-uninfected adults, we found similar carriage acquisition and onward transmission risks in the dual groups. These findings suggest that vaccinating HIV-infected adults on ART with PCV would reduce their risk for pneumococcal disease but may add little to the indirect protection against carriage of the rest of the population. [ABSTRACT FROM AUTHOR]

Background: Avoiding unintended pregnancies through family planning is a WHO strategy for preventing mother to child transmission of HIV (PMTCT) and maternal morbidity/mortality. We investigated factors associated with unintended index pregnancy, unmet contraceptive need, future pregnancy intention and current contraceptive use among Malawian women living with HIV in the Option B+ era. Methods: Women who tested HIV positive at 4–26 weeks postpartum were enrolled into a cross-sectional study at high-volume Under-5 clinics. Structured baseline interviews included questions on socio-demographics, HIV knowledge, partner's HIV status/disclosure, ART use, pregnancy intention and contraceptive use. Logistic regression was used to determine factors associated with outcomes. Results: We enrolled 578 HIV-positive women between May 2015-May 2016; median maternal age was 28 years (y) (interquartile-range [IQR]: 23–32), median parity was 3 deliveries (IQR: 2–4) and median infant age was 7 weeks (IQR: 6–12). Overall, 41.8% women reported unintended index pregnancy, of whom 35.0% reported unmet contraceptive need and 65.0% contraceptive failure. In multivariable analysis, unintended index pregnancy was higher in ≥35y vs. 14-24y (adjusted Odds Ratio [aOR]: 2.1, 95% Confidence Interval [95%CI]: 1.0–4.2) and in women with parity ≥3 vs. primiparous (aOR: 2.9, 95%CI: 1.5–5.6). Unmet contraceptive need at conception was higher in 14-24y vs. ≥35y (aOR: 4.2, 95%CI: 1.8–9.9), primiparous vs. ≥3 (aOR: 8.3, 95%CI: 1.8–39.5), and women with a partner of unknown HIV-status (aOR: 2.2, 95%CI: 1.2–4.0). Current contraceptive use was associated with being on ART in previous pregnancy (aOR: 2.5, 95%CI: 1.5–3.9). Conclusions: High prevalence of unintended index pregnancy and unmet contraceptive need among HIV-positive women highlight the need for improved access to contraceptives. To help achieve reproductive goals and elimination of MTCT of HIV, integration of family planning into HIV care should be strengthened to ensure women have timely access to a wide range of family planning methods with low failure risk. [ABSTRACT FROM AUTHOR]

Background: Poor rates of linkage from HIV diagnosis to ART initiation are a major barrier to universal coverage of ART in sub-Saharan Africa, with reasons for failure poorly understood. In the first study of this kind at primary care level, we investigated the pathway to care in the Malawian National Programme, one of the strongest in Africa. Methods and Findings: A prospective cohort study was undertaken at two primary care clinics in Blantyre, Malawi. Newly diagnosed HIV-positive adults (>15 years) were followed for 6-months to assess completion of eligibility assessments, initiation of ART and death. Two hundred and eighty participants were followed for 82.6 patient-years. ART eligibility assessments were problematic: only 134 (47.9%) received same day WHO staging and 121 (53.2%) completed assessments by 6-months. Completion of CD4 measurement (stage 1/2 only) was 81/153 (52.9%). By 6-months, 87/280 (31.1%) had initiated ART with higher uptake in participants who were ART eligible (68/91, 74.7%), and among participants who received same-day staging (52/134 [38.8%] vs. 35/146 [24.0%] p = 0.007). Non-completion of ART eligibility assessments (adjusted hazard ratio: 0.11, 95% CI: 0.06-0.21) was associated with failure to initiate ART. Retention in pre-ART care for non-ART initiators was low (55/193 [28.5%]). Of the 15 (5.4%) deaths, 11 (73.3%) occurred after ART initiation. Conclusions: Although uptake of ART was high and prompt for patients with known eligibility, there was frequent failure to complete eligibility assessment and poor retention in pre-ART care. HIV care programmes should urgently evaluate the way patients are linked to ART. In particular, there is a critical need for simplified, same-day ART eligibility assessments, reduced requirements for hospital visits, and active defaulter follow-up. [ABSTRACT FROM AUTHOR]