A chronological discourse analysis of ancillary care provision in guidance documents for research conduct in the global south.

INTRODUCTION: Numerous guidelines and policies for ethical research practice have evolved over time, how this translates to global health practice in resource-constrained settings is unclear. The purpose of this paper is to describe how the concept of ancillary care has evolved over time and how it is included in the ethics guidelines and policy documents that guide the conduct of research in the global south with both an international focus and providing a specific example of Malawi, where the first author lives and works, as a case study. METHODS: Discourse analysis was conducted on 34 international ethics guidelines and policy documents. Documents were purposively selected if they contained a set of key terms that reflect the concept of ancillary care. Following a process of inductive discourse analysis, five key interrelated text phrases relating to ancillary care were extracted from the documents. The evolution of these phrases over time was explored as they represented the development of the concept of ancillary care as a component of ethical health research guidance and practice. RESULTS: We found key interrelated phrases that represent discourses regarding the evolution of ancillary care including participant protection; provide care as appropriate; supererogation; patient needs prevail over science; and ancillary care as an obligation. Arguments for the provision of ancillary care were characterised by safeguarding the safety, health rights and well-being of study participants. However, despite the evolution of discourse around ethical obligations to provide ancillary care, this is rarely made explicit within guidance documents, leaving interpretive space for differential application in practice. CONCLUSION: While there have been major changes to the ethics guidance that reflect significant evolution in the ethical conduct of research, the specific vocabulary or language used to explain the ethics of researchers' ancillary care obligations to the health needs of their research participants, lacks clarity and consistency. As a result, the concept of ancillary care continues to be under-represented in local ethical guidelines and regulations, with no clear directives for country-level research ethics committees to apply in regulating ancillary care responsibilities.

Power and Powerlessness in a Group Based Digital Story Telling Project-An Exploration of Community Perceptions of Health Concerns in Urban Malawi.

Digital Story Telling (DST) is an art-based research method used to explore embodied experience of health and initiate dialogue with under-represented groups on issues affecting them. It involves engaging participants to create and share their stories using photos, drawings, and audio recordings in short videos. Benefits of DST include enhancing co-creation of knowledge, empowering participants to confront dominant narratives and revise inaccurate representations. We report our experiences and reflections of using DST to explore community perceptions of health concerns in urban Malawi. Community leaders were briefed about the project before and after study related activities. Three participatory workshops were organized to train community members in DST, support them to develop videos and discuss their experiences of DST. Twenty-six participants from two high density urban communities consented to be part of the workshops. They were all new to DST. All the 26 participants were invited together to the three workshops and their DSTs were developed in smaller groups (n = 7), based on their geographical location. Although we engaged residents from selected communities to share priority health concerns, all the seven groups presented challenges pertaining to Water, Sanitation and Hygiene (WASH), and their powerlessness to address the complex challenges. The collective focus on WASH showed that DST effectively empowered communities to present priority health concerns. The inability of community members to address the challenges without external assistance or failure to use findings from DST to generate social change however raise questions on the ideals of empowerment and social justice. In addition, lack of financial resources or technical know-how to produce digital stories and unequal power relationships between service providers and community, may affect the use of DST for community activism among socio-economically disadvantaged groups. We conclude that DST empowered participants to articulate genuine health challenges that they felt powerless to address. We question the realization of "empowerment" and social justice of vulnerable participants in cases where structural challenges present obstacles to effectively address social inequalities.

Paediatric Emergency Triage, Assessment and Treatment (ETAT) - preparedness for implementation at primary care facilities in Malawi.

BACKGROUND: The majority of deaths amongst children under 5 years are still due to preventable infectious causes. Emergency care has been identified as a key health system weakness, and referrals are often challenging. OBJECTIVE: We aimed to establish how prepared frontline facilities in Malawi are to implement WHO Emergency Triage Assessment and Treatment (ETAT) guidelines, to support policy and planning decisions. METHODS: We conducted a concurrent mixed-methods study, including facility audit; healthcare provider survey; focus group discussions (FGD) and semi-structured interviews with facility staff. The study was conducted in two districts in Malawi, Zomba and Mchinji, between January and May 2019. We included all frontline facilities, including dispensaries, primary health centres, rural and community hospitals. Quantitative data were described using proportions, means and linear regression. Qualitative data was analysed using a framework approach. Data were analysed separately and then triangulated into common themes. RESULTS: Forty-seven facilities and 531 healthcare providers were included in the audit and survey; 6 FGDs and 5 interviews were completed. Four common themes emerged: (1) current emergency case management; (2) referral practices; (3) trained staff capacity; (4) opportunities and barriers for ETAT. Triage was conducted in most facilities with various methods described, and 53% reporting all staff are responsible. Referrals were common, but challenging due to issues in transportation. Twelve percent of survey respondents had ETAT training, with clinical officers (41%) reporting this more frequently than other cadres. Training was associated with increased knowledge, independent of cadre. The main barriers to ETAT implementation were the lack of resources, but opportunities to improve quality of care were reported. CONCLUSIONS: Malawian frontline facilities are already providing a level of emergency paediatric care, but issues in training, drug supplies and equipment were present. To effectively scale-up ETAT, policies need to include supply chain management, maintenance and strengthening referral communication.

Partner-delivered HIV self-test kits with and without financial incentives in antenatal care and index patients with HIV in Malawi: a three-arm, cluster-randomised controlled trial.

BACKGROUND: Secondary distribution of HIV self-testing (HIVST) kits by patients attending clinic services to their partners could improve the rate of HIV diagnosis. We aimed to investigate whether secondary administration of HIVST kits, with or without an additional financial incentive, via women receiving antenatal care (ANC) or via people newly diagnosed with HIV (ie, index patients) could improve the proportion of male partners tested or the number of people newly diagnosed with HIV. METHODS: We did a three-arm, open-label, pragmatic, cluster-randomised trial of 27 health centres (clusters), eligible if they were a government primary health centre providing ANC, HIV testing, and ART services, across four districts of Malawi. We recruited women (aged ≥18 years) attending their first ANC visit and whose male partner was available, not already taking ART, and not already tested for HIV during this pregnancy (ANC cohort), and people (aged ≥18 years) with newly diagnosed HIV during routine clinic HIV testing who had at least one sexual contact not already known to be HIV-positive (index cohort). Centres were randomly assigned (1:1:1), using a public selection of computer-generated random allocations, to enhanced standard of care (including an invitation for partners to attend HIV testing services), HIVST only, or HIVST plus a US$10 financial incentive for retesting. The primary outcome for the ANC cohort was the proportion of male partners reportedly tested, as ascertained by interview with women in this cohort at day 28. The primary outcome for the index cohort was the geometric mean number of new HIV-positive people identified per facility within 28 days of enrolment, as measured by observed HIV test results. Cluster-level summaries compared intervention with standard of care by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03705611. FINDINGS: Between Sept 8, 2018, and May 2, 2019, nine clusters were assigned to each trial arm, resulting in 4544 eligible women in the ANC cohort (1447 [31·8%] in the standard care group, 1465 [32·2%] in the HIVST only group, and 1632 [35·9%] in HIVST plus financial incentive group) and 708 eligible patients in the index cohort (234 [33·1%] in the standard care group, 169 [23·9%] in the HIVST only group, and 305 [42·9%] in the HIVST plus financial incentive group). 4461 (98·2%) of 4544 eligible women in the ANC cohort and 645 (91·1%) of 708 eligible patients in the index cohort were recruited, of whom 3378 (75·7%) in the ANC cohort and 439 (68·1%) in the index cohort were interviewed after 28 days. In the ANC cohort, the mean proportion of reported partner testing per cluster was 35·0% (SD 10·0) in the standard care group, 73·0% in HIVST only group (13·1, adjusted risk ratio [RR] 1·71, 95% CI 1·48-1·98; p<0·0001), and 65·2% in the HIVST plus financial incentive group (11·6, adjusted RR 1·62, 1·45-1·81; p<0·0001). In the index cohort, the geometric mean number of new HIV-positive sexual partners per cluster was 1·35 (SD 1·62) for the standard care group, 1·91 (1·78) for the HIVST only group (incidence rate ratio adjusted for number eligible as an offset in the negative binomial model 1·65, 95% CI 0·49-5·55; p=0·3370), and 3·20 (3·81) for the HIVST plus financial incentive group (3·11, 0·99-9·77; p=0·0440). Four self-resolving, temporary marital separations occurred due to disagreement in couples regarding HIV self-test kits. INTERPRETATION: Although administration of HIVST kits in the ANC cohort, even when offered alongside a financial incentive, did not identify significantly more male patients with HIV than did standard care, out-of-clinic options for HIV testing appear more acceptable to many male partners of women with HIV, increasing test uptake. Viewed in the current context, this approach might allow continuation of services despite COVID-19-related lockdowns. FUNDING: Unitaid, through the Self-Testing Africa Initiative.

Effect of community-led delivery of HIV self-testing on HIV testing and antiretroviral therapy initiation in Malawi: A cluster-randomised trial.

BACKGROUND: Undiagnosed HIV infection remains substantial in key population subgroups including adolescents, older adults, and men, driving ongoing transmission in sub-Saharan Africa. We evaluated the impact, safety, and costs of community-led delivery of HIV self-testing (HIVST), aiming to increase HIV testing in underserved subgroups and stimulate demand for antiretroviral therapy (ART). METHODS AND FINDINGS: This cluster-randomised trial, conducted between October 2018 and July 2019, used restricted randomisation (1:1) to allocate 30 group village head clusters in Mangochi district, Malawi to the community-led HIVST intervention in addition to the standard of care (SOC) or the SOC alone. The intervention involved mobilising community health groups to lead the design and implementation of 7-day HIVST campaigns, with cluster residents (≥15 years) eligible for HIVST. The primary outcome compared lifetime HIV testing among adolescents (15 to 19 years) between arms. Secondary outcomes compared: recent HIV testing (in the last 3 months) among older adults (≥40 years) and men; cumulative 6-month incidence of ART initiation per 100,000 population; knowledge of the preventive benefits of HIV treatment; and HIV testing stigma. Outcomes were measured through a post-intervention survey and at neighboring health facilities. Analysis used intention-to-treat for cluster-level outcomes. Community health groups delivered 24,316 oral fluid-based HIVST kits. The survey included 90.2% (3,960/4,388) of listed participants in the 15 community-led HIVST clusters and 89.2% (3,920/4,394) of listed participants in the 15 SOC clusters. Overall, the proportion of men was 39.0% (3,072/7,880). Most participants obtained primary-level education or below, were married, and reported a sexual partner. Lifetime HIV testing among adolescents was higher in the community-led HIVST arm (84.6%, 770/910) than the SOC arm (67.1%, 582/867; adjusted risk difference [RD] 15.2%, 95% CI 7.5% to 22.9%; p < 0.001), especially among 15 to 17 year olds and boys. Recent testing among older adults was also higher in the community-led HIVST arm (74.5%, 869/1,166) than the SOC arm (31.5%, 350/1,111; adjusted RD 42.1%, 95% CI 34.9% to 49.4%; p < 0.001). Similarly, the proportions of recently tested men were 74.6% (1,177/1,577) and 33.9% (507/1,495) in the community-led HIVST and SOC arms, respectively (adjusted RD 40.2%, 95% CI 32.9% to 47.4%; p < 0.001). Knowledge of HIV treatment benefits and HIV testing stigma showed no differences between arms. Cumulative incidence of ART initiation was respectively 305.3 and 226.1 per 100,000 population in the community-led HIVST and SOC arms (RD 72.3, 95% CI -36.2 to 180.8; p = 0.18). In post hoc analysis, ART initiations in the 3-month post-intervention period were higher in the community-led HIVST arm than the SOC arm (RD 97.7, 95% CI 33.4 to 162.1; p = 0.004). HIVST uptake was 74.7% (2,956/3,960), with few adverse events (0.6%, 18/2,955) and at US$5.70 per HIVST kit distributed. The main limitations include the use of self-reported HIV testing outcomes and lack of baseline measurement for the primary outcome. CONCLUSIONS: In this study, we found that community-led HIVST was effective, safe, and affordable, with population impact and coverage rapidly realised at low cost. This approach could enable community HIV testing in high HIV prevalence settings and demonstrates potential for economies of scale and scope. TRIAL REGISTRATION: Clinicaltrials.gov NCT03541382.

Capacity Building for Health Care Workers and Support Staff in Pediatric Emergency Triage Assessment and Treatment (ETAT) at Primary Health Care Level in Resource Limited Settings: Experiences from Malawi.

Primary health care facilities offer an entry point to the health care system in Malawi. Challenges experienced by these facilities include limited resources (both material and human), poor or inadequate knowledge, skills and attitudes of health care workers in emergency management, and delay in referral from primary care level to other levels of care. These contribute to poor outcomes including children dying within the first 24 hours of hospital admission. Training of health care workers and support staff in Emergency Triage Assessment and Treatment (ETAT) at primary care levels can help improve care of children with acute and severe illnesses. Health care workers and support staff in the primary care settings were trained in pediatric ETAT. The training package for health care workers was adapted from the Ministry of Health ETAT training for district and tertiary health care. Content for support staff focused on non-technical responsibility for lifesaving in emergency situations. The primary health care facilities were provided with a minimum treatment package comprising emergency equipment, supplies and drugs. Supportive supervisory visits were conducted quarterly. The training manual for health care workers was adapted from the Ministry of Health package and the support staff training manual was developed from the adapted package. Eight hundred and seventy-seven participants were trained (336 health care workers and 541 support staff). Following the training, triaging of patients improved and patients were managed as emergency, priority or non-urgent. This reduced the number of referral cases and children were stabilized before referral. Capacity building of health care workers and support staff in pediatric ETAT and the provision of a basic health center package improved practice at the primary care level. The practice was sustained through institutional mentorship and pre-service and in-service training. The practice of triage and treatment including stabilization of children with dangerous signs at the primary health care facility improves emergency care of patients, reduces the burden of patients on referral hospitals and increases the number of successful referrals.

Hypothetical acceptability of hospital-based post-mortem pediatric minimally invasive tissue sampling in Malawi: The role of complex social relationships.

BACKGROUND: Child mortality rates remain unacceptably high in low-resource settings. Cause of death (CoD) is often unknown. Minimally invasive tissue sampling (MITS)-using biopsy needles to obtain post-mortem samples-for histopathological and microbiologic investigation is increasingly being promoted to improve child and adult CoD attribution. "MITS in Malawi" is a sub-study of the Childhood Acute Illness & Nutrition (CHAIN) Network, which aims to identify biological and socioeconomic mortality risk factors among young children hospitalized for acute illness or undernutrition. MITS in Malawi employs standard MITS and a novel post-mortem endoscopic intestinal sampling approach to better understand CoD among children with acute illness and/or malnutrition who die during hospitalization. AIM: To understand factors that may impact MITS acceptability and inform introduction of the procedure to ascertain CoD among children with acute illness or malnutrition who die during hospitalization in Malawi. METHODS: We conducted eight focus group discussions with key hospital staff and community members (religious leaders and parents of children under 5) to explore attitudes towards MITS and inform consent processes prior to commencing the MITS in Malawi study. We used thematic content analysis drawing on a conceptual framework developed from emergent themes and MITS acceptability literature. RESULTS: Feelings of power over decision-making within the hospital and household, trust in health systems, and open and respectful health worker communication with parents were important dimensions of MITS acceptability. Other facilitating factors included the potential for MITS to add CoD information to aid sense-making of death and contribute to medical knowledge and new interventions. Potential barriers to acceptability included fears of organ and blood harvesting, disfigurement to the body, and disruption to transportation and burial plans. CONCLUSION: Social relationships and power dynamics within healthcare systems and households are a critical component of MITS acceptability, especially given the sensitivity of death and autopsy.

Sex, power, marginalisation and HIV amongst young fishermen in Malawi: Exploring intersecting inequalities.

Through scale-up of effective treatment and prevention, HIV incidence rates are falling across Southern and Eastern Africa. However, key population groups, including people living in fishing communities, continue to face an elevated risk of infection and have high rates of undiagnosed disease. We set out to investigate how intersecting inequalities make young fishermen working on the southern shores of Lake Malawi particularly vulnerable to HIV-infection. We used qualitative research methods including observations (over a 15-month period), in-depth interviews (59) and focus group discussions (16) with a range of male and female participants living and working in two fishing villages. We found that the roles that men occupied in the fishing industry depended on several factors, including their age, socio-economic position and the amount of experience they had in the industry. In turn these roles shaped their lives, including exposure to occupational risks, mobility, living conditions, economic remuneration and social standing within the community. In this context, younger and poorer men occupied roles with the lowest social standing in the industry. Nevertheless, in these communities where poverty was pervasive, young fishermen were able to exert the power they gained through access to money and fish over poorer younger women - pressuring them into sex and increasing the risk of HIV for both men and women. Drawing on an intersectionality framework, we contextualised these findings to consider how young men's social location, relationships and experiences of both privilege and marginalisation were shaped by broader economic and political processes. We conclude that interventions to prevent HIV in fishing communities need to address how power plays out in the broader social and economic environment.

Structural coercion in the context of community engagement in global health research conducted in a low resource setting in Africa.

BACKGROUND: While community engagement is increasingly promoted in global health research to improve ethical research practice, it can sometimes coerce participation and thereby compromise ethical research. This paper seeks to discuss some of the ethical issues arising from community engagement in a low resource setting. METHODS: A qualitative study design focusing on the engagement activities of three biomedical research projects as ethnographic case studies was used to gain in-depth understanding of community engagement as experienced by multiple stakeholders in Malawi. Data was collected through participant observation, 43 In-depth interviews and 17 focus group discussions with community leaders, research staff, community members and research participants. Thematic analysis was used to analyse and interpret the findings. RESULTS: The results showed that structural coercion arose due to an interplay of factors pertaining to social-economic context, study design and power relations among research stakeholders. The involvement of community leaders, government stakeholders, and power inequalities among research stakeholders affected some participants' ability to make autonomous decisions about research participation. These results have been presented under the themes of perception of research as development, research participants' motivation to access individual benefits, the power of vernacular translations to influence research participation, and coercive power of leaders. CONCLUSION: The study identified ethical issues in community engagement practices pertaining to structural coercion. We conclude that community engagement alone did not address underlying structural inequalities to ensure adequate protection of communities. These results raise important questions on how to balance between engaging communities to improve research participation and ensure that informed consent is voluntarily given.

Community-led delivery of HIV self-testing to improve HIV testing, ART initiation and broader social outcomes in rural Malawi: study protocol for a cluster-randomised trial.

BACKGROUND: Prevention of new HIV infections is a critical public health issue. The highest HIV testing gaps are in men, adolescents 15-19 years old, and adults 40 years and older. Community-based HIV testing services (HTS) can contribute to increased testing coverage and early HIV diagnosis, with HIV self-testing (HIVST) strategies showing promise. Community-based strategies, however, are resource intensive, costly and not widely implemented. A community-led approach to health interventions involves supporting communities to plan and implement solutions to improve their health. This trial aims to determine if community-led delivery of HIVST can improve HIV testing uptake, ART initiation, and broader social outcomes in rural Malawi. METHODS: The trial uses a parallel arm, cluster-randomised design with group village heads (GVH) and their defined catchment areas randomised (1:1) to community-led HIVST or continue with the standard of the care (SOC). As part of the intervention, informal community health cadres are supported to plan and implement a seven-day HIVST campaign linked to HIV treatment and prevention. Approximately 12 months after the initial campaign, intervention GVHs are randomised to lead a repeat HIVST campaign. The primary outcome includes the proportion of adolescents 15-19 years old who have tested for HIV in their lifetime. Secondary outcomes include recent testing in adults 40 years and older and men; ART initiation; knowledge of HIV prevention; and HIV testing stigma. Outcomes will be measured through cross-sectional surveys and clinic registers. Economic evaluation will determine the cost per person tested, cost per person diagnosed, and incremental cost effectiveness ratio. DISCUSSION: To the best of our knowledge, this is the first trial to assess the effectiveness of community-led HTS, which has only recently been enabled by the introduction of HIVST. Community-led delivery of HIVST is a promising new strategy for providing periodic HIV testing to support HIV prevention in rural communities. Further, introduction of HIVST through a community-led framework seems particularly apt, with control over healthcare concurrently devolved to individuals and communities. TRIAL REGISTRATION: Clinicaltrials.gov registry ( NCT03541382 ) registered 30 May 2018.

Exploring social harms during distribution of HIV self-testing kits using mixed-methods approaches in Malawi.

INTRODUCTION: HIV self-testing (HIVST) provides couples and individuals with a discreet, convenient and empowering testing option. As with all HIV testing, potential harms must be anticipated and mitigated to optimize individual and public health benefits. Here, we describe social harms (SHs) reported during HIVST implementation in Malawi, and propose a framework for grading and responding to harms, according to their severity. METHODS: We report findings from six HIVST implementation studies in Malawi (2011 to 2017) that included substudies investigating SH reports. Qualitative methods included focus group discussions, in-depth interviews and critical incident interviews. Earlier studies used intensive quantitative methods (post-test questionnaires for intimate partner violence, household surveys, investigation of all deaths in HIVST communities). Later studies used post-marketing reporting with/without community engagement. Pharmacovigilance methodology (whereby potentially life-threatening/changing events are defined as "serious") was used to grade SH severity, assuming more complete passive reporting for serious events. RESULTS: During distribution of 175,683 HIVST kits, predominantly under passive SH reporting, 25 serious SHs were reported from 19 (0.011%) self-testers, including 15 partners in eight couples with newly identified HIV discordancy, and one perinatally infected adolescent. There were no deaths or suicides. Marriage break-up was the most commonly reported serious SH (sixteen individuals; eight couples), particularly among serodiscordant couples. Among new concordant HIV-positive couples, blame and frustration was common but rarely (one episode) led to serious SHs. Among concordant HIV-negative couples, increased trust and stronger relationships were reported. Coercion to test or disclose was generally considered "well-intentioned" within established couples. Women felt empowered and were assertive when offering HIVST test kits to their partners. Some women who persuaded their partner to test, however, did report SHs, including verbal or physical abuse and economic hardship. CONCLUSIONS: After more than six years of large-scale HIVST implementation and in-depth investigation of SHs in Malawi, we identified approximately one serious reported SH per 10,000 HIVST kits distributed, predominantly break-up of married serodiscordant couples. Both "active" and "passive" reporting systems identified serious SH events, although with more complete capture by "active" systems. As HIVST is scaled-up, efforts to support and further optimize community-led SH monitoring should be prioritized alongside HIVST distribution.

The effectiveness and cost-effectiveness of community-based lay distribution of HIV self-tests in increasing uptake of HIV testing among adults in rural Malawi and rural and peri-urban Zambia: protocol for STAR (self-testing for Africa) cluster randomized evaluations.

BACKGROUND: Knowledge of HIV status remains below target in sub-Saharan Africa, especially among men and adolescents. HIV self-testing (HIVST) is a novel approach that enables unique distribution strategies, with potential to be highly decentralised and to provide complementary coverage to facility-based testing approaches. However, substantial gaps in evidence remain on the effectiveness and cost-effectiveness of HIVST, particularly in rural settings, and on approaches to facilitate linkage to confirmatory HIV testing, prevention, and treatment services. This protocol describes two cluster-randomized trials (CRT) included within the UNITAID/PSI HIV Self-Testing Africa (STAR) project. METHODS: Two independent CRTs were designed around existing reproductive health programmes in rural Malawi and rural/peri-urban Zambia. Common features include use of constrained randomisation to allocate health clinic catchment areas to either standard HIV testing (SOC) or SOC plus community-based distribution of OraQuick HIV Self Tests (Bethlehem, PA USA, assembled in Thailand) by trained lay distributors selected by the community. Community-based distribution agents will be trained (3-day curriculum) to provide brief demonstration of kit use and interpretation, information and encouragement to access follow up services, and management of social harm. The primary outcome of both CRTs is the proportion of the population aged 16 years and older who tested for HIV within the 12-month intervention period. Secondary outcomes in both trials include lifetime HIV testing, antiretroviral therapy (ART) initiation and ART use. Circumcision status among males will be a secondary outcome in Zambia and clinic-level demand for ART will be a secondary outcome in Malawi. Outcomes will be measured using cross-sectional household surveys, and routine data extraction from participating clinics. Costing studies will be used to evaluate the cost-effectiveness of the intervention arm. Qualitative research will be used to guide distribution and explore reasons for testing and linkage to onward care. DISCUSSION: The STAR-Malawi and STAR-Zambia trials will provide rigorous evidence of whether community-based lay HIVST distribution is an effective and cost-effective approach to increasing coverage of HIV testing and demand for follow-on HIV services in rural and peri-urban communities in sub-Saharan Africa. TRIAL REGISTRATION: Clinicaltrials.gov, Malawi: NCT02718274 , 18 March 2016; Zambia: NCT02793804 , 3 June 2016. Protocol date: 21 February 2018.

Prophylactic antibiotics to reduce pelvic infection in women having miscarriage surgery - The AIMS (Antibiotics in Miscarriage Surgery) trial: study protocol for a randomized controlled trial.

BACKGROUND: The estimated annual global burden of miscarriage is 33 million out of 210 million pregnancies. Many women undergoing miscarriage have surgery to remove pregnancy tissues, resulting in miscarriage surgery being one of the most common operations performed in hospitals in low-income countries. Infection is a serious consequence and can result in serious illness and death. In low-income settings, the infection rate following miscarriage surgery has been reported to be high. Good quality evidence on the use of prophylactic antibiotics for surgical miscarriage management is not available. Given that miscarriage surgery is common, and infective complications are frequent and serious, prophylactic antibiotics may offer a simple and affordable intervention to improve outcomes. METHODS: Eligible patients will be approached once the diagnosis of miscarriage has been made according to local practice. Once informed consent has been given, participants will be randomly allocated using a secure internet facility (1:1 ratio) to a single dose of oral doxycycline (400 mg) and metronidazole (400 mg) or placebo. Allocation will be concealed to both the patient and the healthcare providers. A total of 3400 women will be randomised, 1700 in each arm. The medication will be given approximately 2 hours before surgery, which will be provided according to local practice. The primary outcome is pelvic infection 2 weeks after surgery. Women will be invited to the hospital for a clinical assessment at 2 weeks. Secondary outcomes include overall antibiotic use, individual components of the primary outcome, death, hospital admission, unplanned consultations, blood transfusion, vomiting, diarrhoea, adverse events, anaphylaxis and allergy, duration of clinical symptoms, and days before return to usual activities. An economic evaluation will be performed to determine if prophylactic antibiotics are cost-effective. DISCUSSION: This trial will assess whether a single dose of doxycycline (400 mg) and metronidazole (400 mg) taken orally 2 hours before miscarriage surgery can reduce the incidence of pelvic infection in women up to 2 weeks after miscarriage surgery. TRIAL REGISTRATION: Registered with the ISRCTN (international standard randomised controlled trial number) registry: ISRCTN 97143849 . (Registered on April 17, 2013).

'We are the eyes and ears of researchers and community': Understanding the role of community advisory groups in representing researchers and communities in Malawi.

Community engagement to protect and empower participating individuals and communities is an ethical requirement in research. There is however limited evidence on effectiveness or relevance of some of the approaches used to improve ethical practice. We conducted a study to understand the rationale, relevance and benefits of community engagement in health research. This paper draws from this wider study and focuses on factors that shaped Community Advisory Group (CAG) members' selection processes and functions in Malawi. A qualitative research design was used; two participatory workshops were conducted with CAG members to understand their roles in research. Workshop findings were triangulated with insights from ethnographic field notes, key informant interviews with stakeholders, focus group discussions with community members and document reviews. Data were coded manually and thematic content analysis was used to identify main issues. Results have shown that democratic selection of CAG members presented challenges in both urban and rural settings. We also noted that CAG members perceived their role as a form of employment which potentially led to ineffective representation of community interests. We conclude that democratic voting is not enough to ensure effective representation of community's interests of ethical relevance. CAG members' abilities to understand research ethics, identify potential harms to community and communicate feedback to researchers is critical to optimise engagement of lay community and avoid tokenistic engagement.

Investigating interventions to increase uptake of HIV testing and linkage into care or prevention for male partners of pregnant women in antenatal clinics in Blantyre, Malawi: study protocol for a cluster randomised trial.

BACKGROUND: Despite large-scale efforts to diagnose people living with HIV, 54% remain undiagnosed in sub-Saharan Africa. The gap in knowledge of HIV status and uptake of follow-on services remains wide with much lower rates of HIV testing among men compared to women. Here, we design a study to investigate the effect on uptake of HIV testing and linkage into care or prevention of partner-delivered HIV self-testing alone or with an additional intervention among male partners of pregnant women. METHODS: A phase II, adaptive, multi-arm, multi-stage cluster randomised trial, randomising antenatal clinic (ANC) days to six different trial arms. Pregnant women accessing ANC in urban Malawi for the first time will be recruited into either the standard of care (SOC) arm (invitation letter to the male partner offering HIV testing) or one of five intervention arms offering oral HIV self-test kits. Three of the five intervention arms will additionally offer the male partner a financial incentive (fixed or lottery amount) conditional on linkage after self-testing with one arm testing phone call reminders. Assuming that 25% of male partners link to care or prevention in the SOC arm, six clinic days, with a harmonic mean of 21 eligible participants, per arm will provide 80% power to detect a 0.15 absolute difference in the primary outcome. Cluster proportions will be analysed by a cluster summaries approach with adjustment for clustering and multiplicity. DISCUSSION: This trial applies adaptive methods which are novel and efficient designs. The methodology and lessons learned here will be important as proof of concept of how to design and conduct similar studies in the future. Although small, this trial will potentially present good evidence on the type of effective interventions for improving linkage into ART or prevention. The trial results will also have important policy implications on how to implement HIVST targeting male partners of pregnant women who are accessing ANC for the first time while paying particular attention to safety concerns. Contamination may occur if women in the intervention arms share their self-test kits with women in the SOC arm. TRIAL REGISTRATION: ISRCTN, ID: 18421340 . Registered on 31 March 2016.

Considerations for a Human Rights Impact Assessment of a Population Wide Treatment for HIV Prevention Intervention.

Increasing attention is being paid to the potential of anti-retroviral treatment (ART) for HIV prevention. The possibility of eliminating HIV from a population through a universal test and treat intervention, where all people within a population are tested for HIV and all positive people immediately initiated on ART, as part of a wider prevention intervention, was first proposed in 2009. Several clinical trials testing this idea are now in inception phase. An intervention which relies on universally testing the entire population for HIV will pose challenges to human rights, including obtaining genuine consent to testing and treatment. It also requires a context in which people can live free from fear of stigma, discrimination and violence, and can access services they require. These challenges are distinct from the field of medical ethics which has traditionally governed clinical trials and focuses primarily on patient researcher relationship. This paper sets out the potential impact of a population wide treatment as prevention intervention on human rights. It identifies five human right principles of particular relevance: participation, accountability, the right to health, non-discrimination and equality, and consent and confidentiality. The paper proposes that explicit attention to human rights can strengthen a treatment as prevention intervention, contribute to mediating likely health systems challenges and offer insights on how to reach all sections of the population.

Uptake, Accuracy, Safety, and Linkage into Care over Two Years of Promoting Annual Self-Testing for HIV in Blantyre, Malawi: A Community-Based Prospective Study.

BACKGROUND: Home-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population. METHODS AND FINDINGS: Following enumeration of 14 neighbourhoods in urban Blantyre, Malawi, trained resident volunteer-counsellors offered oral HIVST kits (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test) to adult (≥16 y old) residents (n = 16,660) and reported community events, with all deaths investigated by verbal autopsy. Written and demonstrated instructions, pre- and post-test counselling, and facilitated HIV care assessment were provided, with a request to return kits and a self-completed questionnaire. Accuracy, residency, and a study-imposed requirement to limit HIVST to one test per year were monitored by home visits in a systematic quality assurance (QA) sample. Overall, 14,004 (crude uptake 83.8%, revised to 76.5% to account for population turnover) residents self-tested during months 1-12, with adolescents (16-19 y) most likely to test. 10,614/14,004 (75.8%) participants shared results with volunteer-counsellors. Of 1,257 (11.8%) HIV-positive participants, 26.0% were already on antiretroviral therapy, and 524 (linkage 56.3%) newly accessed care with a median CD4 count of 250 cells/µl (interquartile range 159-426). HIVST uptake in months 13-24 was more rapid (70.9% uptake by 6 mo), with fewer (7.3%, 95% CI 6.8%-7.8%) positive participants. Being "forced to test", usually by a main partner, was reported by 2.9% (95% CI 2.6%-3.2%) of 10,017 questionnaire respondents in months 1-12, but satisfaction with HIVST (94.4%) remained high. No HIVST-related partner violence or suicides were reported. HIVST and repeat HTC results agreed in 1,639/1,649 systematically selected (1 in 20) QA participants (99.4%), giving a sensitivity of 93.6% (95% CI 88.2%-97.0%) and a specificity of 99.9% (95% CI 99.6%-100%). Key limitations included use of aggregate data to report uptake of HIVST and being unable to adjust for population turnover. CONCLUSIONS: Community-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings.

A novel community health worker tool outperforms WHO clinical staging for assessment of antiretroviral therapy eligibility in a resource-limited setting.

The accuracy of a novel community health worker antiretroviral therapy eligibility assessment tool was examined in community members in Blantyre, Malawi. Nurses independently performed World Health Organization (WHO) staging and CD4 counts. One hundred ten (55.6%) of 198 HIV-positive participants had a CD4 count of <350 cells per cubic millimeter. The community health worker tool significantly outperformed WHO clinical staging in identifying CD4 count of <350 cells per cubic millimeter in terms of sensitivity (41% vs. 19%), positive predictive value (75% vs. 68%), negative predictive values (53% vs. 47%), and area under the receiver-operator curve (0.62 vs. 0.54; P = 0.017). Reliance on WHO staging is likely to result in missed and delayed antiretroviral therapy initiation.

Recognising and treatment seeking for acute bacterial meningitis in adults and children in resource-poor settings: a qualitative study.

OBJECTIVE: High mortality burden from Acute Bacterial Meningitis (ABM) in resource-poor settings has been frequently blamed on delays in treatment seeking. We explored treatment-seeking pathways from household to primary health care and referral for ABM in Malawi. DESIGN: A cross-sectional qualitative study using narrative in-depth interviews, semi-structured interviews and focus group discussions. PARTICIPANTS: Adults and children with proven and probable acute bacterial meningitis and/or their carers; adults from urban and peri-urban communities; and primary health care workers (HCW). SETTING: Queen Elizabeth Central Hospital (QECH), urban and peri-urban private and government primary health centres and communities in Blantyre District, Malawi. RESULTS: Whilst communities associated meningitis with a stiff neck, in practice responses focused on ability to recognise severe illness. Misdiagnosis of meningitis as malaria was common. Subsequent action by families depended on the extent to which normal social life was disrupted by the illness and depended on the age and social position of the sufferer. Seizures and convulsions were considered severe symptoms but were often thought to be malaria. Presumptive malaria treatment at home often delayed formal treatment seeking. Further delays in treatment seeking were caused by economic barriers and perceptions of inefficient or inadequate primary health services. CONCLUSIONS: Given the difficulties in diagnosis of meningitis where malaria is common, any intervention for ABM at primary level must focus on recognising severe illness, and encouraging action at the household, community and primary health levels. Overcoming barriers to recognition and social constraints at community level require broad community-based strategies and may provide a route to addressing poor clinical outcomes.

Suboptimal patterns of provider initiated HIV testing and counselling, antiretroviral therapy eligibility assessment and referral in primary health clinic attendees in Blantyre, Malawi.

OBJECTIVE: To understand reasons for suboptimal and delayed uptake of antiretroviral therapy (ART) by describing the patterns of HIV testing and counselling (HTC) and outcomes of ART eligibility assessments in primary clinic attendees. METHODS: All clinic attendances and episodes of HTC were recorded at two clinics in Blantyre. A cohort of newly diagnosed HIV-positive adults (>15 years) was recruited and exit interviews undertaken. Logistic regression models were constructed to investigate factors associated with referral to start ART. Qualitative interviews were conducted with providers and patients. RESULTS: There were 2398 episodes of HTC during 18,021 clinic attendances (13.3%) between January and April 2011. The proportion of clinic attendees undergoing HTC was lowest in non-pregnant women (6.3%) and men (8.5%), compared with pregnant women (47.2%). Men had more advanced HIV infection than women (79.7% WHO stage 3 or 4 vs. 56.4%). Problems with WHO staging and access to CD4 counts affected ART eligibility assessments; only 48% completed ART eligibility assessment, and 54% of those reporting WHO stage 3/4 illnesses were not referred to start ART promptly. On multivariate analysis, HIV-positive pregnant women were significantly less likely to be referred directly for ART initiation (adjusted OR: 0.29, 95% CI: 0.13-0.63). CONCLUSIONS: These data show that provider-initiated testing and counselling (PITC) has not yet been fully implemented at primary care clinics. Suboptimal ART eligibility assessments and referral (reflecting the difficulties of WHO staging in primary care) mean that simplified eligibility assessment tools are required to reduce unnecessary delay and attrition in the pre-ART period. Simplified initiation criteria for pregnant women, as being introduced in Malawi, should improve linkage to ART.