Missing men with tuberculosis: the need to address structural influences and implement targeted and multidimensional interventions.

Tuberculosis (TB) is treatable but is the leading infectious cause of death worldwide, with men over-represented in some key aspects of the disease burden. Men's TB epidemiological scenario occurs within a wider public health and historical context, including their prior sidelining in health discussions. Differences are however noticeable in how some Western countries and high TB and HIV burden low and middle-income countries (LMIC) including in Africa have approached the subject(s) of men and health. The former have a comparatively long history of scholarship, and lately are implementing actions targeting men's health and wellness, both increasingly addressing multilevel social and structural determinants. In contrast, in the latter men have received attention primarily for their sexual practices and role in HIV and AIDS and gender-based violence; moreover, interventions, guided by the public health approach, have stressed short-term, measurable and medical goals. Debates and the limited available empirical literature on men's engagement with TB-related healthcare are nevertheless indicating need for a shift, within TB work with men in high burden LMICs towards, structural and multicomponent interventions

The effect of demand-side financial incentives for increasing linkage into HIV treatment and voluntary medical male circumcision: A systematic review and meta-analysis of randomised controlled trials in low- and middle-income countries

INTRODUCTION: Linkage to HIV treatment is a vital step in the cascade of HIV services and is critical to slowing down HIV transmission in countries with high HIV prevalence. Equally, linkage to voluntary medical male circumcision (VMMC) has been shown to decrease HIV transmission by 60% and increasing numbers of men receiving VMMC has a substantial impact on HIV incidence. However, only 48% of newly diagnosed HIV positive people link to HIV treatment let alone access HIV prevention methods such as VMMC globally. METHODS: A systematic review investigating the effect of demand-side financial incentives (DSFIs) on linkage into HIV treatment or VMMC for studies conducted in low- and middle-income countries. We searched the title, abstract and keywords in eight bibliographic databases: MEDLINE, EMBASE, Web of Science, Econlit, Cochrane, SCOPUS, IAS Conference database of abstracts, and CROI Conference database of abstracts. Searches were done in December 2016 with no time restriction. We fitted random effects (RE) models and used forest plots to display risk ratios (RR) and 95% CIs separately for the linkage to VMMC outcome. The RE model was also used to assess heterogeneity for the linkage to HIV treatment outcome. RESULTS: Of the 1205 citations identified from searches, 48 full text articles were reviewed culminating in nine articles in the final analysis. Five trials investigated the effect of DSFIs on linkage to HIV treatment while four trials investigated linkage to VMMC. Financial incentives improved linkage to HIV treatment in three of the five trials that investigated this outcome. Significant improvements were observed among postpartum women RR 1.26 (95% CI: 1.08; 1.48), among people who inject drugs RR 1.42 (95% CI: 1.09; 1.96), and among people testing at the clinic RR 1.10 (95% CI: 1.07; 1.14). One of the two trials that did not find significant improvement in linkage to ART was among people testing HIV positive in clinics RR 0.96 (95% CI: 0.81; 1.16) while the other was among new HIV positive individuals identified through a community testing study RR 0.82 (95% CI: 0.56; 1.22). We estimate an average 4-fold increase in the uptake of circumcision among HIV negative uncircumcised men from our fitted RE model with overall RR 4.00 (95% CI: 2.17; 7.37). There was negligible heterogeneity in the estimates from the different studies with I-squared = 0.0%; p = 0.923. CONCLUSIONS: Overall, DSFIs appeared to improve linkage for both HIV treatment and VMMC with greater effect for VMMC. Demand-side financial incentives could improve linkage to HIV treatment or VMMC in low- and middle-income countries although uptake by policy makers remains a challenge

Acceptability of woman-delivered HIV self-testing to the male partner, and additional interventions: a qualitative study of antenatal care participants in Malawi

In the era of ambitious HIV targets, novel HIV testing models are required for hard-to-reach groups such as men, who remain underserved by existing services. Pregnancy presents a unique opportunity for partners to test for HIV, as many pregnant women will attend antenatal care (ANC). We describe the views of pregnant women and their male partners on HIV self-test kits that are woman-delivered, alone or with an additional intervention. A formative qualitative study to inform the design of a multi-arm multi-stage cluster-randomized trial, comprised of six focus group discussions and 20 in-depth interviews, was conducted. ANC attendees were purposively sampled on the day of initial clinic visit, while men were recruited after obtaining their contact information from their female partners. Data were analysed using content analysis, and our interpretation is hypothetical as participants were not offered self-test kits. Providing HIV self-test kits to pregnant women to deliver to their male partners was highly acceptable to both women and men. Men preferred this approach compared with standard facility-based testing, as self-testing fits into their lifestyles which were characterized by extreme day-to-day economic pressures, including the need to raise money for food for their household daily. Men and women emphasized the need for careful communication before and after collection of the self-test kits in order to minimize the potential for intimate partner violence although physical violence was perceived as less likely to occur. Most men stated a preference to first self-test alone, followed by testing as a couple. Regarding interventions for optimizing linkage following self-testing, both men and women felt that a fixed financial incentive of approximately USD$2 would increase linkage. However, there were concerns that financial incentives of greater value may lead to multiple pregnancies and lack of child spacing. In this low-income setting, a lottery incentive was considered overly disappointing for those who receive nothing. Phone call reminders were preferred to short messaging service. Woman-delivered HIV self-testing through ANC was acceptable to pregnant women and their male partners. Feedback on additional linkage enablers will be used to alter pre-planned trial arms

CONservative TReatment of Appendicitis in Children – a randomised controlled feasibility Trial (CONTRACT)

Objective To establish the feasibility of a multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy in children with uncomplicated acute appendicitis.Design Feasibility randomised controlled trial with embedded qualitative study to inform recruiter training to optimise recruitment and the design of a future definitive trial.Setting Three specialist paediatric surgery centres in the UK.Patients Children (aged 4–15 years) with a clinical diagnosis of uncomplicated acute appendicitis.Interventions Appendicectomy or a non-operative treatment pathway (comprising broad-spectrum antibiotics and active observation).Main outcome measures Primary outcome measure was the proportion of eligible patients recruited. Secondary outcomes evaluated adherence to interventions, data collection during follow-up, safety of treatment pathways and clinical course.Results Fifty per cent of eligible participants (95% CI 40 to 59) approached about the trial agreed to participate and were randomised. Repeated bespoke recruiter training was associated with an increase in recruitment rate over the course of the trial from 38% to 72%. There was high acceptance of randomisation, good patient and surgeon adherence to trial procedures and satisfactory completion of follow-up. Although more participants had perforated appendicitis than had been anticipated, treatment pathways were found to be safe and adverse event profiles acceptable.Conclusion Recruitment to a randomised controlled trial examining the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy for the treatment of uncomplicated acute appendicitis in children is feasible.Trial registration number ISRCTN15830435

ART initiations following community-based distribution of HIV self-tests: meta-analysis and meta-regression of STAR Initiative data.

INTRODUCTION: Measuring linkage after community-based testing, particularly HIV self-testing (HIVST), is challenging. Here, we use data from studies of community-based HIVST distribution, conducted within the STAR Initiative, to assess initiation of antiretroviral therapy (ART) and factors driving differences in linkage rates. METHODS: Five STAR studies evaluated HIVST implementation in Malawi, Zambia and Zimbabwe. New ART initiations during the months of intervention at clinics in HIVST and comparison areas were presented graphically, and study effects combined using meta-analysis. Meta-regression was used to estimate associations between the impact of community-based HIVST distribution and indicators of implementation context, intensity and reach. Effect size estimates used (1) prespecified trial definitions of ART timing and comparator facilities and (2) exploratory definitions accounting for unexpected diffusion of HIVST into comparison areas and periods with less distribution of HIVST than was expected. RESULTS: Compared with arms with standard testing only, ART initiations were higher in clinics in HIVST distribution areas in 4/5 studies. The prespecified meta-analysis found positive but variable effects of HIVST on facility ART initiations (RR: 1.14, 95% CI 0.93 to 1.40; p=0.21). The exploratory meta-analysis found a stronger impact of HIVST distribution on ART initiations (RR: 1.29, 95% CI 1.08 to 1.55, p=0.02).ART initiations were higher in studies with greater self-reported population-level intensity of HIVST use (RR: 1.12; 95% CI 1.04 to 1.21; p=0.02.), but did not differ by national-level indicators of ART use among people living with HIV, number of HIVST kits distributed per 1000 population, or self-reported knowledge of how to link to care after a reactive HIVST. CONCLUSION: Community-based HIVST distribution has variable effect on ART initiations compared with standard testing service alone. Optimising both support for and approach to measurement of effective and timely linkage or relinkage to HIV care and prevention following HIVST is needed to maximise impact and guide implementation strategies

Conservative treatment for uncomplicated appendicitis in children:the CONTRACT feasibility study, including feasibility RCT

Background Whilst non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, comparative randomised trial data reporting important outcomes compared to appendicectomy are lacking.ObjectivesTo ascertain the feasibility of conducting a multi-centre randomised controlled trial (RCT) testing the effectiveness and cost-effectiveness of a non-operative treatment pathway compared to appendicectomy for the treatment of uncomplicated acute appendicitis in children.•DesignMixed methods study including: a feasibility RCT; embedded and parallel qualitative and survey studies; parallel health economic feasibility study; development of a core outcome set.Setting Three specialist NHS Paediatric Surgical Units in EnglandParticipants Children (aged 4-15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility RCT. Children, their families, recruiting clinicians and other healthcare professionals involved in caring for children with appendicitis took part in the qualitative study. UK Specialist Paediatric Surgeons took part in the survey. Specialist Paediatric Surgeons, Adult General Surgeons who treat children, and children and young people who previously had appendicitis along with their families took part in the core outcomes set development.Interventions Participants in the feasibility RCT were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy.Main outcome measures Primary outcome measure was the proportion of eligible patients recruited to the feasibility trial.Data sourcesNHS casenotes, questionnaire responses, transcribed audio recordings of recruitment discussions and qualitative interviewsResults Overall, 50% (95%CI 40-59) of 115 eligible participants approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow rates of 89%, 85% and 85% at six weeks, three months and six months respectively). More participants had perforated appendicitis than had been anticipated.Qualitative work enabled us to: communicate about the trial effectively with patients and families; design and deliver bespoke training to optimise recruitment; and understand how to optimise design and delivery of a future trial.The health economic study, indicated that the main cost drivers are the ward stay cost and the cost of the operation, and has informed quality of life assessment methods for future work.A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes.There is adequate surgeon interest to justify proceeding to an effectiveness trial with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol.LimitationsSince the feasibility RCT was only performed in three centres we cannot guarantee successful recruitment across a larger number of sites. However, our qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have moved over time.Conclusions A future effectiveness trial is feasible following limited additional preparation to establish appropriate outcome measures and case identification. We recommend a limited package of qualitative work be included to optimise recruitment at new centres in particular.Future work Prior to proceeding to an effectiveness trial we need to: develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis; reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved.Study registration ISRCTN15830435.Funding detailsNIHR HTA programm

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

Modelling costs of community-based HIV self-testing programmes in Southern Africa at scale: an econometric cost function analysis across five countries.

BACKGROUND: Following success demonstrated with the HIV Self-Testing AfRica Initiative, HIV self-testing (HIVST) is being added to national HIV testing strategies in Southern Africa. An analysis of the costs of scaling up HIVST is needed to inform national plans, but there is a dearth of evidence on methods for forecasting costs at scale from pilot projects. Econometric cost functions (ECFs) apply statistical inference to predict costs; however, we often do not have the luxury of collecting large amounts of location-specific data. We fit an ECF to identify key drivers of costs, then use a simpler model to guide cost projections at scale. METHODS: We estimated the full economic costs of community-based HIVST distribution in 92 locales across Malawi, Zambia, Zimbabwe, South Africa and Lesotho between June 2016 and June 2019. We fitted a cost function with determinants related to scale, locales organisational and environmental characteristics, target populations, and per capita Growth Domestic Product (GDP). We used models differing in data intensity to predict costs at scale. We compared predicted estimates with scale-up costs in Lesotho observed over a 2-year period. RESULTS: The scale of distribution, type of community-based intervention, percentage of kits distributed to men, distance from implementer's warehouse and per capita GDP predicted average costs per HIVST kit distributed. Our model simplification approach showed that a parsimonious model could predict costs without losing accuracy. Overall, ECF showed a good predictive capacity, that is, forecast costs were close to observed costs. However, at larger scale, variations of programme efficiency over time (number of kits distributed per agent monthly) could potentially influence cost predictions. DISCUSSION: Our empirical cost function can inform community-based HIVST scale-up in Southern African countries. Our findings suggest that a parsimonious ECF can be used to forecast costs at scale in the context of financial planning and budgeting

Does community-based distribution of HIV self-tests increase uptake of HIV testing? Results of pair-matched cluster randomised trial in Zambia.

OBJECTIVES: Ending HIV by 2030 is a global priority. Achieving this requires alternative HIV testing strategies, such as HIV self-testing (HIVST) to reach all individuals with HIV testing services (HTS). We present the results of a trial evaluating the impact of community-based distribution of HIVST in community and facility settings on the uptake of HTS in rural and urban Zambia. DESIGN: Pair-matched cluster randomised trial. METHODS: In catchment areas of government health facilities, OraQuick HIVST kits were distributed by community-based distributors (CBDs) over 12 months in 2016-2017. Within matched pairs, clusters were randomised to receive the HIVST intervention or standard of care (SOC). Individuals aged ≥16 years were eligible for HIVST. Within communities, CBDs offered HIVST in high traffic areas, door to door and at healthcare facilities. The primary outcome was self-reported recent testing within the previous 12 months measured using a population-based survey. RESULTS: In six intervention clusters (population 148 541), 60 CBDs distributed 65 585 HIVST kits. A recent test was reported by 66% (1622/2465) in the intervention arm compared with 60% (1456/2429) in SOC arm (adjusted risk ratio 1.08, 95% CI 0.94 to 1.24; p=0.15). Uptake of the HIVST intervention was low: 24% of respondents in the intervention arm (585/2493) used an HIVST kit in the previous 12 months. No social harms were identified during implementation. CONCLUSION: Despite distributing a large number of HIVST kits, we found no evidence that this community-based HIVST distribution intervention increased HTS uptake. Other models of HIVST distribution, including secondary distribution and community-designed distribution models, provide alternative strategies to reach target populations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02793804)

Comparison of community-led distribution of HIV self-tests kits with distribution by paid distributors: a cluster randomised trial in rural Zimbabwean communities.

BACKGROUND: We compared community-led versus an established community-based HIV self-testing (HIVST) model in rural Zimbabwe using a cluster-randomised trial. METHODS: Forty village groups were randomised 1:1 using restricted randomisation to community-led HIVST, where communities planned and implemented HIVST distribution for 4 weeks, or paid distribution (PD), where distributors were paid US$50 to distribute kits door-to-door over 4 weeks. Individual level primary outcomes compared household survey responses by arm 4 months post-intervention for: (1) newly diagnosed HIV during/within 4 months following HIVST distribution, (2) linkage to confirmatory testing, pre-exposure prophylaxis or voluntary medical male circumcision during/within 4 months following HIVST distribution. Participants were not masked to allocation; analysis used masked data. Trial analysis used random-effects logistic regression.Distribution costs compared: (1) community-led HIVST, (2) PD HIVST and (3) PD costs when first implemented in 2016/2017. RESULTS: From October 2018 to August 2019, 27 812 and 36 699 HIVST kits were distributed in community-led and PD communities, respectively. We surveyed 11 150 participants and 5683 were in community-led arm. New HIV diagnosis was reported by 211 (3.7$6.29 and US$10.25 for PD and community-led HIVST, both lower than 2016/2017 costs for newly implemented PD (US$14.52). No social harms were reported. CONCLUSIONS: Community-led HIVST can perform as well as paid distribution, with lower costs in the first year. These costs may reduce with programme maturity/learning. TRIAL REGISTRATION NUMBER: PACTR201811849455568