Impact of Community-Wide Tuberculosis Active Case Finding and Human Immunodeficiency Virus Testing on Tuberculosis Trends in Malawi.

BACKGROUND: Tuberculosis case-finding interventions are critical to meeting World Health Organization End TB strategy goals. We investigated the impact of community-wide tuberculosis active case finding (ACF) alongside scale-up of human immunodeficiency virus (HIV) testing and care on trends in adult tuberculosis case notification rates (CNRs) in Blantyre, Malawi. METHODS: Five rounds of ACF for tuberculosis (1-2 weeks of leafleting, door-to-door enquiry for cough and sputum microscopy) were delivered to neighborhoods ("ACF areas") in North-West Blantyre between April 2011 and August 2014. Many of these neighborhoods also had concurrent HIV testing interventions. The remaining neighborhoods in Blantyre City ("non-ACF areas") provided a non-randomized comparator. We analyzed TB CNRs from January 2009 until December 2018. We used interrupted time series analysis to compare tuberculosis CNRs before ACF and after ACF, and between ACF and non-ACF areas. RESULTS: Tuberculosis CNRs increased in Blantyre concurrently with start of ACF for tuberculosis in both ACF and non-ACF areas, with a larger magnitude in ACF areas. Compared to a counterfactual where pre-ACF CNR trends continued during ACF period, we estimated there were an additional 101 (95% confidence interval [CI] 42 to 160) microbiologically confirmed (Bac+) tuberculosis diagnoses per 100 000 person-years in the ACF areas in 3 and a half years of ACF. Compared to a counterfactual where trends in ACF area were the same as trends in non-ACF areas, we estimated an additional 63 (95% CI 38 to 90) Bac + diagnoses per 100 000 person-years in the same period. CONCLUSIONS: Tuberculosis ACF was associated with a rapid increase in people diagnosed with tuberculosis in Blantyre.

Strategies to improve antiretroviral therapy (ART) initiation and early engagement among men in sub-Saharan Africa: A scoping review of interventions in the era of universal treatment.

OBJECTIVES: Men in sub-Saharan Africa (SSA) have lower rates of antiretroviral therapy (ART) initiation and higher rates of early default than women. Little is known about effective interventions to improve men's outcomes. We conducted a scoping review of interventions aimed to increase ART initiation and/or early retention among men in SSA since universal treatment policies were implemented. METHODS: Three databases, HIV conference databases and grey literature were searched for studies published between January 2016 to May 2021 that reported on initiation and/or early retention among men. Eligibility criteria included: participants in SSA, data collected after universal treatment policies were implemented (2016-2021), quantitative data on ART initiation and/or early retention for males, general male population (not exclusively focused on key populations), intervention study (report outcomes for at least one non-standard service delivery strategy), and written in English. RESULTS: Of the 4351 sources retrieved, 15 (reporting on 16 interventions) met inclusion criteria. Of the 16 interventions, only two (2/16, 13%) exclusively focused on men. Five (5/16, 31%) were randomised control trials (RCT), one (1/16, 6%) was a retrospective cohort study, and 10 (10/16, 63%) did not have comparison groups. Thirteen (13/16, 81%) interventions measured ART initiation and six (6/16, 37%) measured early retention. Outcome definitions and time frames varied greatly, with seven (7/16, 44%) not specifying time frames at all. Five types of interventions were represented: optimising ART services at health facilities, community-based ART services, outreach support (such as reminders and facility escort), counselling and/or peer support, and conditional incentives. Across all intervention types, ART initiation rates ranged from 27% to 97% and early retention from 47% to 95%. CONCLUSIONS: Despite years of data of men's suboptimal ART outcomes, there is little high-quality evidence on interventions to increase men's ART initiation or early retention in SSA. Additional randomised or quasi-experimental studies are urgently needed.

Linkage to HIV Care Following HIV Self-testing Among Men: Systematic Review of Quantitative and Qualitative Studies from Six Countries in Sub-Saharan Africa.

Gender disparities are pervasive throughout the HIV care continuum in sub-Saharan Africa, with men testing, receiving treatment, and achieving viral suppression at lower rates, and experiencing mortality at higher rates, compared with women. HIV self-testing (HIVST) has been shown to be highly acceptable among men in sub-Saharan Africa. However, evidence on linkage to HIV care following a reactive HIVST result is limited. In this systematic review, we aimed to synthesize the quantitative and qualitative literature from sub-Saharan Africa on men's rates of linkage to HIV care after receiving a reactive HIVST result. We systematically searched 14 bibliometric databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram was used to document the screening results. The Mixed Methods Appraisal Tool (MMAT) was used to assess the methodological quality of the included studies. Of 22,446 references screened, 15 articles were eligible for inclusion in this review. Linkage to HIV care following a reactive HIVST result was subject to several barriers: financial constraints due to travelling costs, potential long waiting hours at the clinics, stigma, discrimination, and privacy concerns. Men's rates of seeking confirmatory testing and linking to HIV care following a reactive HIVST result were inconsistent across studies. Combining financial incentives with HIVST was found to increase the likelihood of linking to HIV care following a reactive HIVST result. The variable rates of linkage to HIV care following a reactive HIVST result suggest a need for further research and development into strategies to increase linkage to HIV care.

Understanding the Unique Barriers and Facilitators that Affect Men's Initiation and Retention in HIV Care: A Qualitative Study to Inform Interventions for Men Across the Treatment Cascade in Malawi.

Men in sub-Saharan Africa are underrepresented in antiretroviral therapy (ART) programs. Our secondary analysis of 40 in-depth interviews with Malawian men living with HIV examined barriers and facilitators for ART initiation versus retention. Interviewees included men who never initiated or initiated ART late (initiation respondents, n = 19); and men who initiated ART but were late for an appointment (retention respondents, n = 21). Transcribed interviews were coded using deductive and inductive coding techniques and analyzed using constant comparison methods. Long wait times, frequent facility visits, and insufficient in-clinic privacy were barriers for initiation and retention. Poor knowledge of ART was primarily a barrier for initiation; unexpected travel was a barrier for retention. Key facilitators for initiation and retention included previous positive experiences with health facilities. Having examples of successful men using ART primarily facilitated initiation; support from spouses and male peers facilitated retention. Results may inform interventions to increase men's engagement in ART services.

Effect of postpartum anaemia on maternal health-related quality of life: a systematic review and meta-analysis.

BACKGROUND: Postpartum anaemia remains a persistent and severe public health issue in many parts of the world. Studies have reported mixed findings on the effects of anaemia during the postpartum period on maternal health-related quality of life (HRQoL). We conducted this systematic review to summarise available evidence to inform public health practitioners on whether 1) anaemia negatively impact maternal health-related quality of life and 2) whether iron supplementation in anaemic women can improve maternal HRQoL during the postpartum period. METHODS: This review's protocol was registered online with PROSPERO (CRD42020206618). We extensively searched Embase, PubMed, Cochrane and Scopus through the HINARI website to identify studies that reported either association or effect of postpartum anaemia on fatigue, depression and mother-child interaction. We restricted our search to studies of human females published in English language from databases inception until August 2020. We followed a Cochrane guideline for reporting systematic reviews and meta-analysis to synthesise data. RESULTS: Twenty-seven studies were included in this systematic review, with some reporting all three domains (fatigue, depression and mother-child interaction) of HRQoL. Seven observational studies with pooled dichotomous outcomes showed that iron deficient or anaemic women were 1.66 times more likely to experience symptoms of depression than non-anaemic or iron-replete women [RR = 1.66 (95% CI: 1.28; 2.16), I2 = 67.0%, P < 0.01]. In three randomized controlled trials (RCTs), pooled continuous data showed statistically significant reduction in fatigue scores in women who received iron supplementation than the control group [MD: -1.85 (95% CI: -3.04; -0.67), I2 = 65.0%, p < 0.06]. Two of the four included studies showed that anaemic mothers were less responsive and had negative feelings towards their children than non-anaemic mothers. CONCLUSION: Evidence from this review suggests that postpartum anaemia negatively affects health-related quality of life and that iron replenishment improves both symptoms of fatigue and depression. Nevertheless, it remains unclear whether postpartum anaemia affects mother-child interaction.

Effects of Coronavirus Disease Pandemic on Tuberculosis Notifications, Malawi.

The coronavirus disease (COVID-19) pandemic might affect tuberculosis (TB) diagnosis and patient care. We analyzed a citywide electronic TB register in Blantyre, Malawi and interviewed TB officers. Malawi did not have an official COVID-19 lockdown but closed schools and borders on March 23, 2020. In an interrupted time series analysis, we noted an immediate 35.9% reduction in TB notifications in April 2020; notifications recovered to near prepandemic numbers by December 2020. However, 333 fewer cumulative TB notifications were received than anticipated. Women and girls were affected more (30.7% fewer cases) than men and boys (20.9% fewer cases). Fear of COVID-19 infection, temporary facility closures, inadequate personal protective equipment, and COVID-19 stigma because of similar symptoms to TB were mentioned as reasons for fewer people being diagnosed with TB. Public health measures could benefit control of both TB and COVID-19, but only if TB diagnostic services remain accessible and are considered safe to attend.

Computer-aided X-ray screening for tuberculosis and HIV testing among adults with cough in Malawi (the PROSPECT study): A randomised trial and cost-effectiveness analysis.

BACKGROUND: Suboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD). METHODS AND FINDINGS: In this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening). Participants and study staff were not blinded to intervention allocation, but investigator blinding was maintained until final analysis. The primary outcome was time to TB treatment. Secondary outcomes included proportion with same-day TB treatment; prevalence of undiagnosed/untreated bacteriologically confirmed TB on day 56; and undiagnosed/untreated HIV. Analysis was done on an intention-to-treat basis. Cost-effectiveness analysis used a health-provider perspective. Between 15 November 2018 and 27 November 2019, 8,236 were screened for eligibility, with 473, 492, and 497 randomly allocated to SOC, HIV, and HIV-TB screening arms; 53 (11%), 52 (9%), and 47 (9%) were lost to follow-up, respectively. At 56 days, TB treatment had been started in 5 (1.1%) SOC, 8 (1.6%) HIV screening, and 15 (3.0%) HIV-TB screening participants. Median (IQR) time to TB treatment was 11 (6.5 to 38), 6 (1 to 22), and 1 (0 to 3) days (hazard ratio for HIV-TB versus SOC: 2.86, 1.04 to 7.87), with same-day treatment of 0/5 (0%) SOC, 1/8 (12.5%) HIV, and 6/15 (40.0%) HIV-TB screening arm TB patients (p = 0.03). At day 56, 2 SOC (0.5%), 4 HIV (1.0%), and 2 HIV-TB (0.5%) participants had undiagnosed microbiologically confirmed TB. HIV screening reduced the proportion with undiagnosed or untreated HIV from 10 (2.7%) in the SOC arm to 2 (0.5%) in the HIV screening arm (risk ratio [RR]: 0.18, 0.04 to 0.83), and 1 (0.2%) in the HIV-TB screening arm (RR: 0.09, 0.01 to 0.71). Incremental costs were US$3.58 and US$19.92 per participant screened for HIV and HIV-TB; the probability of cost-effectiveness at a US$1,200/quality-adjusted life year (QALY) threshold was 83.9% and 0%. Main limitations were the lower than anticipated prevalence of TB and short participant follow-up period; cost and quality of life benefits of this screening approach may accrue over a longer time horizon. CONCLUSIONS: DCXR-CAD with universal HIV screening significantly increased the timeliness and completeness of HIV and TB diagnosis. If implemented at scale, this has potential to rapidly and efficiently improve TB and HIV diagnosis and treatment. TRIAL REGISTRATION: clinicaltrials.gov NCT03519425.

Socio-cultural and economic barriers, and facilitators influencing men's involvement in antenatal care including HIV testing: a qualitative study from urban Blantyre, Malawi.

BACKGROUND: Male partner involvement in antenatal care (ANC) is associated with positive maternal and neonatal outcomes. However, only a handful of men attend ANC with their partners. This study aimed to understand the underlying barriers and facilitators influencing men's ANC attendance including HIV testing in Blantyre, Malawi. METHODS: Data were collected during a formative qualitative study of a cluster-randomised trial. Six focus group discussions (FGDs) with 42 men and women and 20 in-depth interviews (IDIs) were conducted at three primary health centres in urban Blantyre, Malawi. FGD participants were purposively sampled with IDI participants subsequently sampled after FGD participation. Thematic analysis was used to analyse the data. RESULTS: The economic requirement to provide for their families exerted pressure on men and often negatively affected their decision to attend ANC together with their pregnant partners despite obvious benefits. Peer pressure and the fear to be seen by peers queueing for services at ANC, an environment traditionally viewed as a space for women and children made men feel treated as trespassers and with some level of hostility rendering them feeling emasculated when they attend ANC. Health system problems associated with overall organization of the ANC services, which favours women created resistance among men to be involved. An association between ANC and HIV testing services discouraged men from attending ANC because of their fear of testing HIV-positive in the presence of their partners. The availability of a male friendly clinic offering a private, quick, supportive/sensitive and flexible service was considered to be an important incentive that would facilitate men's ANC attendance. Men described compensation to cover transport and opportunity cost for attending the clinic as a motivator to attending ANC services and accepting an HIV test. CONCLUSION: Peer and economic influences were the most influential barriers of men attending ANC and testing for HIV with their pregnant partners. Addressing these socio-economic barriers and having a male friendly clinic are promising interventions to promote male ANC attendance in this setting.

'Too old to test?': A life course approach to HIV-related risk and self-testing among midlife-older adults in Malawi.

BACKGROUND: Despite the aging HIV epidemic, increasing age can be associated with hesitancy to test. Addressing this gap is a critical policy concern and highlights the urgent need to identify the underlying factors, to improve knowledge of HIV-related risks as well as uptake of HIV testing and prevention services, in midlife-older adults. METHODS: We conducted five focus group discussions and 12 in-depth interviews between April 2013 and November 2016 among rural and urban Malawian midlife-older (≥30 years) men and women. Using a life-course theoretical framework we explored how age is enacted socially and its implications on HIV testing and sexual risk behaviours. We also explore the potential for HIV self-testing (HIVST) to be part of a broader strategy for engaging midlife-older adults in HIV testing, prevention and care. Thematic analysis was used to identify recurrent themes and variations. RESULTS: Midlife-older adults (30-74 years of age) associated their age with respectability and identified HIV as "a disease of youth" that would not affect them, with age protecting them against infidelity and sexual risk-taking. HIV testing was felt to be stigmatizing, challenging age norms, threatening social status, and implying "lack of wisdom". These norms drove self-testing preferences at home or other locations deemed age and gender appropriate. Awareness of the potential for long-standing undiagnosed HIV to be carried forward from past relationships was minimal, as was understanding of treatment-as-prevention. These norms led to HIV testing being perceived as a threat to status by older adults, contributing to low levels of recent HIV testing compared to younger adults. CONCLUSIONS: Characteristics associated with age-gender norms and social position encourage self-testing but drive poor HIV-risk perception and unacceptability of conventional HIV testing in midlife-older adults. There is an urgent need to provide targeted messages and services more appropriate to midlife-older adults in sub-Saharan Africa. HIVST which has often been highlighted as a tool for reaching young people, may be a valuable tool for engaging midlife-older age groups who may not otherwise test.

Men's comfort in distributing or receiving HIV self-test kits from close male social network members in Dar Es Salaam, Tanzania: baseline results from the STEP project.

BACKGROUND: A variety of strategies have been used to reach men with HIV self-testing services, including social network-based HIV self-test kits distribution. However, few studies have assessed men's comfort to distribute to or receive HIV self-test kits from close male friends within the same social network. In this study, we assessed men's comfort to distribute to and/or receive HIV self-test kits from close male friends and associated factors among men who socialize in networks locally referred to as "camps" in Tanzania. METHODS: Data are from the baseline survey of a cluster-randomized controlled trial conducted in June 2019 with 18 social networks or "camps" in Dar es Salaam, Tanzania. Participants were 18-year-old or older male camp members who were HIV-negative at the time of enrolment. We used the Generalized Estimating Equations (GEE) to assess factors associated with being comfortable to distribute to and/or receive HIV self-test kits from close male members within one's social network. RESULTS: Of 505 participants, 67.9% (n = 342) reported being comfortable to distribute to while 68.2% (n = 344) were comfortable to receive HIV self-test kits from their close male friends. Ever having heard about HIV self-testing (Adjusted Prevalence Ratio (Adj. PR): 1.6; 95% Confidence Interval [CI]: 1.3, 1.9), willingness to self-test for HIV in front of a sexual partner (Adj. PR: 3.0; 95%CI: 1.5, 6.1) and exposure to peer-led HIV self-testing education and promotion (Adj. PR: 1.4; 95%CI: 1.2, 1.7) were significantly associated with being comfortable to distribute HIV self-test kits to close male members within one's social network. Similar results were observed for being comfortable to receive HIV self-test kits from a close male friend within one's social network. CONCLUSIONS: Overall, these findings suggest that distribution of HIV self-test kits through close male friends could improve the proportion of men reached with HIV self-testing services and improve HIV testing rates in this population where uptake remains low. However, additional promotional strategies such as peer-led HIV self-testing education are needed to raise awareness and increase the proportion of men who are comfortable to receive and/or distribute HIV self-testing kits.

Analysis of maternal serum vitamin D concentrations at birth in women presenting with spontaneous preterm birth: A case-control study.

Vitamin D is a potent immune system modulator; its deficiency correlates with increased susceptibility to infections. We evaluated the status of maternal serum vitamin D in women with spontaneous preterm birth. In this case-control study, the maternal serum concentration of vitamin D (25OH D) was measured in 95 women delivering preterm and 92 women having a term birth. Vitamin D sufficiency was found in 79% of the mothers who delivered preterm and 80.4% of the mothers who had term birth (p=0.822). There was a negative correlation between maternal serum concentration of 25 Hydroxyvitamin D and maternal age in the preterm birth group (p=0.043). In conclusion, there was no difference in maternal serum concentrations of 25 Hydroxyvitamin D between women delivering preterm compared to those having term birth. Maternal serum concentration of 25 Hydroxyvitamin D is not associated with occurrence of preterm birth.

Use and awareness of and willingness to self-test for HIV: an analysis of cross-sectional population-based surveys in Malawi and Zimbabwe.

BACKGROUND: Many southern African countries are nearing the global goal of diagnosing 90% of people with HIV by 2020. In 2016, 84 and 86% of people with HIV knew their status in Malawi and Zimbabwe, respectively. However, gaps remain, particularly among men. We investigated awareness and use of, and willingness to self-test for HIV and explored sociodemographic associations before large-scale implementation. METHODS: We pooled responses from two of the first cross-sectional Demographic and Health Surveys to include HIV self-testing (HIVST) questions in Malawi and Zimbabwe in 2015-16. We investigated sociodemographic factors and sexual risk behaviours associated with previously testing for HIV, and past use, awareness of, and future willingness to self-test using univariable and multivariable logistic regression, adjusting for the sample design and limiting analysis to participants with a completed questionnaire and valid HIV test result. We restricted analysis of willingness to self-test to Zimbabwean men, as women and Malawians were not systematically asked this question. RESULTS: Of 31,385 individuals, 31.2% of men had never tested compared with 16.5% of women (p < 0.001). For men, the likelihood of having ever tested increased with age. Past use and awareness of HIVST was very low, 1.2 and 12.6%, respectively. Awareness was lower among women than men (9.1% vs 15.3%, adjusted odds ratio [aOR] = 1.55; 95% confidence interval [CI]: 1.37-1.75), and at younger ages, and lower education and literacy levels. Willingness to self-test among Zimbabwean men was high (84.5%), with greater willingness associated with having previously tested for HIV, being at high sexual risk (highest willingness [aOR = 3.74; 95%CI: 1.39-10.03, p < 0.009]), and being ≥25 years old. Wealthier men had greater awareness of HIVST than poorer men (p < 0.001). The highest willingness to self-test (aOR = 3.74; 95%CI: 1.39-10.03, p < 0.009) was among men at high HIV-related sexual risk. CONCLUSIONS: In 2015-16, many Malawian and Zimbabwean men had never tested for HIV. Despite low awareness and minimal HIVST experience, willingness to self-test was high among Zimbabwean men, especially older men with moderate-to-high HIV-related sexual risk. These data provide a valuable baseline against which to investigate population-level uptake of HIVST as programmes scale up. Programmes introducing, or planning to introduce, HIVST should consider including relevant questions in population-based surveys.

HIV self-testing alone or with additional interventions, including financial incentives, and linkage to care or prevention among male partners of antenatal care clinic attendees in Malawi: An adaptive multi-arm, multi-stage cluster randomised trial.

BACKGROUND: Conventional HIV testing services have been less comprehensive in reaching men than in reaching women globally, but HIV self-testing (HIVST) appears to be an acceptable alternative. Measurement of linkage to post-test services following HIVST remains the biggest challenge, yet is the biggest driver of cost-effectiveness. We investigated the impact of HIVST alone or with additional interventions on the uptake of testing and linkage to care or prevention among male partners of antenatal care clinic attendees in a novel adaptive trial. METHODS AND FINDINGS: An adaptive multi-arm, 2-stage cluster randomised trial was conducted between 8 August 2016 and 30 June 2017, with antenatal care clinic (ANC) days (i.e., clusters of women attending on a single day) as the unit of randomisation. Recruitment was from Ndirande, Bangwe, and Zingwangwa primary health clinics in urban Blantyre, Malawi. Women attending an ANC for the first time for their current pregnancy (regardless of trimester), 18 years and older, with a primary male partner not known to be on ART were enrolled in the trial after giving consent. Randomisation was to either the standard of care (SOC; with a clinic invitation letter to the male partner) or 1 of 5 intervention arms: the first arm provided women with 2 HIVST kits for their partners; the second and third arms provided 2 HIVST kits along with a conditional fixed financial incentive of $3 or $10; the fourth arm provided 2 HIVST kits and a 10% chance of receiving $30 in a lottery; and the fifth arm provided 2 HIVST kits and a phone call reminder for the women's partners. The primary outcome was the proportion of male partners who were reported to have tested for HIV and linked into care or prevention within 28 days, with referral for antiretroviral therapy (ART) or circumcision accordingly. Women were interviewed at 28 days about partner testing and adverse events. Cluster-level summaries compared each intervention versus SOC using eligible women as the denominator (intention-to-treat). Risk ratios were adjusted for male partner testing history and recruitment clinic. A total of 2,349/3,137 (74.9%) women participated (71 ANC days), with a mean age of 24.8 years (SD: 5.4). The majority (2,201/2,233; 98.6%) of women were married, 254/2,107 (12.3%) were unable to read and write, and 1,505/2,247 (67.0%) were not employed. The mean age for male partners was 29.6 years (SD: 7.5), only 88/2,200 (4.0%) were unemployed, and 966/2,210 (43.7%) had never tested for HIV before. Women in the SOC arm reported that 17.4% (71/408) of their partners tested for HIV, whereas a much higher proportion of partners were reported to have tested for HIV in all intervention arms (87.0%-95.4%, p < 0.001 in all 5 intervention arms). As compared with those who tested in the SOC arm (geometric mean 13.0%), higher proportions of partners met the primary endpoint in the HIVST + $3 (geometric mean 40.9%, adjusted risk ratio [aRR] 3.01 [95% CI 1.63-5.57], p < 0.001), HIVST + $10 (51.7%, aRR 3.72 [95% CI 1.85-7.48], p < 0.001), and phone reminder (22.3%, aRR 1.58 [95% CI 1.07-2.33], p = 0.021) arms. In contrast, there was no significant increase in partners meeting the primary endpoint in the HIVST alone (geometric mean 17.5%, aRR 1.45 [95% CI 0.99-2.13], p = 0.130) or lottery (18.6%, aRR 1.43 [95% CI 0.96-2.13], p = 0.211) arms. The lottery arm was dropped at interim analysis. Overall, 46 male partners were confirmed to be HIV positive, 42 (91.3%) of whom initiated ART within 28 days; 222 tested HIV negative and were not already circumcised, of whom 135 (60.8%) were circumcised as part of the trial. No serious adverse events were reported. Costs per male partner who attended the clinic with a confirmed HIV test result were $23.73 and $28.08 for the HIVST + $3 and HIVST + $10 arms, respectively. Notable limitations of the trial included the relatively small number of clusters randomised to each arm, proxy reporting of the male partner testing outcome, and being unable to evaluate retention in care. CONCLUSIONS: In this study, the odds of men's linkage to care or prevention increased substantially using conditional fixed financial incentives plus partner-delivered HIVST; combinations were potentially affordable. TRIAL REGISTRATION: ISRCTN 18421340.

Disparities in access to diagnosis and care in Blantyre, Malawi, identified through enhanced tuberculosis surveillance and spatial analysis.

BACKGROUND: A sizeable fraction of tuberculosis (TB) cases go undiagnosed. By analysing data from enhanced demographic, microbiological and geospatial surveillance of TB registrations, we aimed to identify modifiable predictors of inequitable access to diagnosis and care. METHODS: Governmental community health workers (CHW) enumerated all households in 315 catchment areas during October-December 2015. From January 2015, government TB Officers routinely implemented enhanced TB surveillance at all public and private TB treatment registration centres within Blantyre (18 clinics in total). This included collection from registering TB patients of demographic and clinical characteristics, a single sputum sample for TB microscopy and culture, and geolocation of place of residence using an electronic satellite map application. We estimated catchment area annual TB case notification rates (CNRs), stratified by microbiological status. To identify population and area-level factors predictive of CHW catchment area TB case notification rates, we constructed Bayesian spatially autocorrelated regression models with Poisson response distributions. Worldpop data were used to estimate poverty. RESULTS: In total, the 315 CHW catchment areas comprised 753,489 people (range 162 to 13,066 people/catchment area). Between 2015 and 2017, 6077 TB cases (61% male; 99% HIV tested; 67% HIV positive; 55% culture confirmed) were geolocated, with 3723 (61%) resident within a CHW catchment area. In adjusted models, greater distance to the nearest TB registration clinic was negatively correlated with TB CNRs, which halved for every 3.2-fold (95% CI 2.24-5.21) increase in distance. Poverty, which increased with distance from clinics, was negatively correlated with TB CNRs; a 23% increase (95% CI 17-34%) in the mean percentage of the population living on less than US$2 per day corresponded to a halving of the TB case notification rates. CONCLUSIONS: Using enhanced surveillance of TB cases in Blantyre, we show an ecological relationship consistent with an 'inverse care law' whereby poorer neighbourhoods and those furthest from TB clinics have lower relative CNRs. If confirmed as low case detection, then pro-poor strategies to facilitate equitable access to TB diagnosis and treatment are required.

Developing national strategies for reaching men with HIV testing services in Tanzania: results from the male catch-up plan.

BACKGROUND: According to the 2016-2017 Tanzania HIV Impact Survey, 55% of men diagnosed with HIV during the survey self-reported that they were unaware of their HIV status. As a response, the Government of Tanzania launched a Test and Treat campaign in June 2018 with a focus on reaching men and developed the 2018-2020 Male Catch-Up plan. This article reports (1) the enablers and barriers of HIV testing services (HTS) uptake among men (2) and describes the strategies that were proposed as part of the Male Catch-Up Plan to address some of these barriers. METHOD: Qualitative in-depth interviews were conducted with 23 men in Dar es Salaam to explore HTS enablers and barriers. To develop the Male Catch-Up Plan strategies, a desk review of published studies, and analyses of national implementers of HIV/AIDS interventions were conducted. An additional 123 interviews were also carried out with key implementers of HIV/AIDS interventions, healthcare workers, secondary school boys and members of the community in Iringa and Tanga. RESULTS: Enablers of HTS included the desire to check one's health, high HIV risk perception, wanting to protect oneself if tested negative, and being encouraged by their sexual partners. Barriers of HTS were fear of a positive test result, and low HIV risk perception. Proposed strategies from the Male Catch-Up Plan to address these barriers included non-biomedical and biomedical approaches. Non-biomedical strategies are social and cultural approaches to promote an enabling environment to encourage health seeking behavior, safe behavior, and providing peer education programs and social marketing to promote condoms. Biomedical approaches consisted of expanding targeted HIV testing, HIV self-testing, and integrating HIV services with other health services. CONCLUSION: A number of barriers contribute to the low uptake of HTS among men in Tanzania. National strategies have been developed to address these HTS barriers and guide the national Test and Treat campaign focusing on increasing HTS uptake among men.

Scaling up HIV self-testing in sub-Saharan Africa: a review of technology, policy and evidence.

PURPOSE OF REVIEW: HIV self-testing (HIVST) can provide complementary coverage to existing HIV testing services and improve knowledge of status among HIV-infected individuals. This review summarizes the current technology, policy and evidence landscape in sub-Saharan Africa and priorities within a rapidly evolving field. RECENT FINDINGS: HIVST is moving towards scaled implementation, with the release of WHO guidelines, WHO prequalification of the first HIVST product, price reductions of HIVST products and a growing product pipeline. Multicountry evidence from southern and eastern Africa confirms high feasibility, acceptability and accuracy across many delivery models and populations, with minimal harms. Evidence on the effectiveness of HIVST on increased testing coverage is strong, while evidence on demand generation for follow-on HIV prevention and treatment services and cost-effective delivery is emerging. Despite these developments, HIVST delivery remains limited outside of pilot implementation. SUMMARY: Important technology gaps include increasing availability of more sensitive HIVST products in low and middle-income countries. Regulatory and postmarket surveillance systems for HIVST also require further development. Randomized trials evaluating the effectiveness and cost-effectiveness under multiple distribution models, including unrestricted delivery and with a focus on linkage to HIV prevention and treatment, remain priorities. Diversification of studies from west and central Africa and around blood-based products should be addressed.

A targeted approach for routine viral load monitoring in Malawian adults on antiretroviral therapy.

OBJECTIVES: WHO recommends HIV viral load (VL) testing 6 months after antiretroviral therapy (ART) initiation and every 12 months thereafter, but cost prohibits routine, universal VL testing in many developing countries. We sought to devise a targeted approach to routine VL monitoring that could reduce cost and identify those at low risk for virologic failure (VF). METHODS: We analysed screening data from a clinical trial enrolling adults on ART in Malawi. We identified risk factors associated with VF and employed the Knill-Jones method to assign summary score identifying persons at lower risk for VF. RESULTS: Among 957 adults, prevalence of VF was 9.4%. Factors independently associated with VF included age <38 years (OR 3.44, 95% CI 2.01-5.89), ART duration >2.5 years (OR 2.98, 95% CI 1.79-4.96), ART adherence <95% (OR 1.76, 95% CI 1.06-2.94), CD4 count <200 cells/µl (OR 5.94, 95% CI 3.27-10.78), haemoglobin <13 g/dl (OR 2.76, 95% CI 1.70-4.50) and CD8 count >885 cells/µl (OR 2.10, 95% CI 1.28-3.44). Our VF prediction summary score included all factors above except CD8 count and was fairly accurate with validated area under receiver operating characteristic curve of 0.76. Implementation could reduce VL testing by 65%. CONCLUSION: A simple score incorporating age, ART duration and adherence, and CD4 count can accurately identify adults at low risk for VF in a sub-Saharan African setting. In areas with high ART utilisation and limited VL testing capacity, a targeted approach could optimise routine VL monitoring while identifying adults in need of alternate ART regimens.

Brain swelling is independent of peripheral plasma cytokine levels in Malawian children with cerebral malaria.

BACKGROUND: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-related mortality. CM is characterized by elevated circulating pro-inflammatory cytokines TNF and IFN-γ and anti-inflammatory cytokine IL-10, however whether cytokine levels correlate with brain swelling severity is unknown. This study therefore was conducted to investigate the relationship between cytokine levels and brain swelling severity in children presenting with CM. METHODS: A total of 195 Malawian children presenting with CM were recruited and had the concentrations of plasma cytokines determined and compared to brain swelling severity, determined by MRI examination, and graded as severe, moderate, mild or none. RESULTS: Levels of IL-1ß, IL-6, IL-8 and IL-10 did not differ between CM patients with and without severe brain swelling. Compared to children without brain swelling, IL-12 levels were higher in children with severe swelling (p < 0.01, no swelling 1 pg/mL, IQR [1] vs. severe swelling 18.7 pg/mL, IQR [1-27]), whereas TNF concentrations were higher in children with moderate brain swelling compared to children with no swelling (p < 0.01, no swelling 3 pg/mL, IQR [1-20] vs. moderate swelling 24 pg/mL, IQR [8-58]. Multivariate analysis showed that no single cytokine independently predicted brain swelling. CONCLUSION: Severe brain swelling in paediatric CM was independent of tested blood pro-inflammatory and anti-inflammatory cytokines which are markers of systemic inflammation.

Discordance, Disclosure and Normative Gender Roles: Barriers to Couple Testing Within a Community-Level HIV Self-Testing Intervention in Urban Blantyre, Malawi.

A community-based HIV self-testing study in Blantyre, Malawi demonstrated that not all individuals living in couples tested with their partner. We describe factors dissuading individuals in couples from self-testing with their partner. Data were drawn from qualitative study exploring consequences of HIV self-testing within couples. In-depth interviews were conducted with 33 individuals living in couples who tested alone. Participants expressed fear of dealing with HIV-discordant relationships. Failure to self-test with a partner was correlated with gender, with more men than women overtly declining or unconsciously unable to have joint HIV self-test. Men feared exposure of infidelity and were often not available at home for economic reasons. Barriers to uptake of couple HIV self-testing seemed to be shaped by gendered dichotomies of social-relationships. To help achieve the first 90% of the UNAIDS 90:90:90 goals, it is important to overcome structural barriers to realise the full potential of HIV self-testing.

Cost and quality of life analysis of HIV self-testing and facility-based HIV testing and counselling in Blantyre, Malawi.

BACKGROUND: HIV self-testing (HIVST) has been found to be highly effective, but no cost analysis has been undertaken to guide the design of affordable and scalable implementation strategies. METHODS: Consecutive HIV self-testers and facility-based testers were recruited from participants in a community cluster-randomised trial ( ISRCTN02004005 ) investigating the impact of offering HIVST in addition to facility-based HIV testing and counselling (HTC). Primary costing studies were undertaken of the HIVST service and of health facilities providing HTC to the trial population. Costs were adjusted to 2014 US$ and INT$. Recruited participants were asked about direct non-medical and indirect costs associated with accessing either modality of HIV testing, and additionally their health-related quality of life was measured using the EuroQol EQ-5D. RESULTS: A total of 1,241 participants underwent either HIVST (n = 775) or facility-based HTC (n = 446). The mean societal cost per participant tested through HIVST (US$9.23; 95 % CI: US$9.14-US$9.32) was lower than through facility-based HTC (US$11.84; 95 % CI: US$10.81-12.86). Although the mean health provider cost per participant tested through HIVST (US$8.78) was comparable to facility-based HTC (range: US$7.53-US$10.57), the associated mean direct non-medical and indirect cost was lower (US$2.93; 95 % CI: US$1.90-US$3.96). The mean health provider cost per HIV positive participant identified through HIVST was higher (US$97.50) than for health facilities (range: US$25.18-US$76.14), as was the mean cost per HIV positive individual assessed for anti-retroviral treatment (ART) eligibility and the mean cost per HIV positive individual initiated onto ART. In comparison to the facility-testing group, the adjusted mean EQ-5D utility score was 0.046 (95 % CI: 0.022-0.070) higher in the HIVST group. CONCLUSIONS: HIVST reduces the economic burden on clients, but is a costlier strategy for the health provider aiming to identify HIV positive individuals for treatment. The provider cost of HIVST could be substantially lower under less restrictive distribution models, or if costs of oral fluid HIV test kits become comparable to finger-prick kits used in health facilities.