Fourth Controlled Human Infection Model (CHIM) meeting - CHIMs in endemic countries, May 22-23, 2023.

Earlier meetings laid the foundations for Controlled Human Infection Models (CHIMs), also known as human challenge studies and human infection studies, including Good Manufacturing Practice (GMP) production of the challenge agent, CHIM ethics, environmental safety in CHIM, recruitment, community engagement, advertising and incentives, pre-existing immunity, and clinical, immunological, and microbiological endpoints. The fourth CHIM meeting focused on CHIM studies being conducted in endemic countries. Over the last ten years we have seen a vast expansion of the number of countries in Africa performing CHIM studies, as well as a growing number of different challenge organisms being used. Community and public engagement with assiduous ethical and regulatory oversight has been central to successful introductions and should be continued, in more community-led or community-driven models. Valuable initiatives for regulation of CHIMs have been undertaken but further capacity building remains essential.

Ethical considerations around volunteer payments in a malaria human infection study in Kenya: an embedded empirical ethics study.

Human Infection Studies (HIS) have emerged as an important research approach with the potential to fast track the global development of vaccines and treatments for infectious diseases, including in low resource settings. Given the high level of burdens involved in many HIS, particularly prolonged residency and biological sampling requirements, it can be challenging to identify levels of study payments that provide adequate compensation but avoid 'undue' levels of inducement to participate. Through this embedded ethics study, involving 97 healthy volunteers and other research stakeholders in a malaria HIS programme in Kenya, and using in-depth interviews, focus group discussions and observations during and after a malaria HIS, we give a grounded account of ethical issues emerging in relation to study payments in this setting. While careful community, national, international scientific and ethics review processes meant that risks of serious harm were highly unlikely, the levels of motivation to join HIS seen could raise concerns about study payments being too high. Particular value was placed on the reliability, rather than level, of study payment in this setting, where subsistence livelihoods are common. Study volunteers were generally clear about the study aims at the point of recruitment, and this knowledge was retained over a year later, although most reported experiencing more burdens than anticipated at enrolment. Strict study screening procedures, regular clinical and laboratory monitoring of volunteers, with prompt treatment with antimalarial at predetermined endpoints suggested that the risks of serious harm were highly unlikely. Ethical concerns emerged in relation to volunteers' attempts to conceal symptoms, hoping to prolong residency periods and increase study payments; and volunteers making decisions that compromised important family relationships and personal values. Our findings support an interpretation that, although study volunteers were keen to join the study to access cash payments, they also paid attention to other features of the study and the general clinical research landscape, including levels of risk associated with study participation. Overall, our analysis shows that the ethical concerns emerging from the study payments can be addressed through practical measures, hinged on reducing burdens and strengthening communication, raising important issues for research policy and planning.

Government regulation of private health insurance.

BACKGROUND: The strain on public resources to meet the healthcare needs of populations through publicly-provided health insurance programmes is increasing and many governments turn to private health insurance (PHI) to ease the pressure on government budgets. With the goal of improving access to basic health care for citizens through PHI programmes, several high-income countries have developed strong regulations for PHI schemes. Low- and middle-income countries have the opportunity to learn from this experience to optimise PHI. If poorly regulated, PHI can hardly achieve an adequate quantity or quality of population coverage, as can be seen in the USA where a third of adults younger than 65 years of age have no insurance, sporadic coverage or coverage that exposes them to high out-of-pocket healthcare costs. OBJECTIVES: To assess the effects of policies that regulate private health insurance on utilisation, quality, and cost of health care provided. SEARCH METHODS: In November 2019 we searched CENTRAL; MEDLINE; Embase; Sociological Abstracts and Social Services Abstracts; ICTRP; ClinicalTrials.gov; and Web of Science Core Collection for papers that have cited the included studies. This complemented the search conducted in February 2017 in IBSS; EconLit; and Global Health. We also searched selected grey literature databases and web-sites.  SELECTION CRITERIA: Randomised trials, non-randomised trials, interrupted time series (ITS) studies, and controlled before-after (CBA) studies conducted in any population or setting that assessed one or more of the following interventions that governments use to regulate private health insurance: legislation and licensing, monitoring, auditing, and intelligence. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, and assessed risk of bias and certainty of the evidence resolving discrepancies by consensus. We planned to summarise the results (using random-effects or fixed-effect meta-analysis) to produce an overall summary if an average intervention effect across studies was considered meaningful, and we would have discussed the implications of any differences in intervention effects across studies. However, due to the nature of the data obtained, we have provided a narrative synthesis of the findings. MAIN RESULTS: We included seven CBA studies, conducted in the USA, and that directly assessed state laws on cancer screening. Only for-profit PHI schemes were addressed in the included studies and no study addressed other types of PHI (community and not for-profit). The seven studies were assessed as having 'unclear risk' of bias. All seven studies reported on utilisation of healthcare services, and one study reported on costs. None of the included studies reported on quality of health care and patient health outcomes. We assessed the certainty of evidence for patient health outcomes, and utilisation and costs of healthcare services as very low. Therefore, we are uncertain of the effects of government mandates on for-profit PHI schemes. AUTHORS' CONCLUSIONS: Our review suggests that, from currently available evidence, it is uncertain whether policies that regulate private health insurance have an effect on utilisation of healthcare services, costs, quality of care, or patient health outcomes. The findings come from studies conducted in the USA and might therefore not be applicable to other countries; since the regulatory environment could be different. Studies are required in countries at different income levels because the effects of government regulation of PHI are likely to differ across these income and health system settings. Further studies should assess the different types of regulation (including regulation and licensing, monitoring, auditing, and intelligence). While regulatory research on PHI remains relatively scanty, future research can draw on the rich body of research on the regulation of other health financing interventions such as user fees and results-based provider payments.

Predictors of teenage pregnancy among girls aged 13-19 years in Uganda: a community based case-control study.

BACKGROUND: Teenage pregnancy is a serious public health and social problem, with 95% occurring in developing countries. The aim of the study was to investigate the behavioural, familial and social factors associated with teenage pregnancy among girls aged 13-19 years in Lira District, Uganda. METHODS: Primary data from a case-control study of teenage girls (aged 13-19 years) in Lira District, Uganda was analysed. A Structured questionnaire was administered using face-to-face interviews to collect data on 495 participants, identified through simple random sampling from 32 villages in two counties in Lira District. Data analyses were done using SPSS Statistics 23 for descriptive, bivariate (i.e. Chi-square tests) and multivariable analyses (i.e. logistics regression) used for determining independent associations. RESULTS: A total of 495 teenage girls participated in the study, however, final analyses were undertaken for 480 respondents. At bivariable analysis, all variables except alcohol consumption were significantly associated with teenage pregnancy. Among the behavioural factors assessed, multivariable analyses showed that having multiple sexual partners, frequent sex and irregular contraceptive use increased the likelihood of teenage pregnancy. Among familial factors, being married was found to increase the likelihood of teenage pregnancy. Peer pressure, sexual abuse and lack of control over sex was observed to increase the likelihood of teenage pregnancy. CONCLUSIONS: Demographic, behavioural, familial and social factors are important predictors of teenage pregnancy in Lira District. Interventions focussing on: retaining pregnant and married girls at school, information on sexual and reproductive health of teenage girls, improving access to and information about contraceptive use among teenage girls, improving socio-economic status of households, and law enforcement on sexual abuse among girls may come a long way to improving adolescent sexual and health services in the low-income settings.

Global health inequalities and the need for solidarity: a view from the Global South.

Although the world has experienced remarkable progress in health care since the last half of the 20th century, global health inequalities still persist. In some poor countries life expectancy is between 37-40 years lower than in rich countries; furthermore, maternal and infant mortality is high and there is lack of access to basic preventive and life-saving medicines, as well a high prevalence of neglected diseases, HIV/AIDS, tuberculosis, and malaria. Moreover, globalization has made the world more connected than before such that health challenges today are no longer limited within national or regional boundaries, making all persons equally vulnerable. Because of this, diseases in the most affluent countries are closely connected with diseases in the poorest countries. In this paper, we argue that, because of global health inequalities, in a situation of equal vulnerability, there is need for global solidarity not only as a means of reducing health inequalities, but also as a way of putting up a united force against global health challenges. We argue for an African approach to solidarity in which the humanity of a person is not determined by his/her being human or rational capacity, but by his/her capacity to live a virtuous life. According to this view of solidarity, because no one is self-sufficient, no individual can survive alone. If we are to collectively flourish in a world where no individual, nation or region has all the health resources or protection needed for survival, we must engage in solidarity where we remain compassionate and available to one another at all times.

A qualitative study exploring the determinants of maternal health service uptake in post-conflict Burundi and Northern Uganda.

BACKGROUND: Armed conflict has been described as an important contributor to the social determinants of health and a driver of health inequity, including maternal health. These conflicts may severely reduce access to maternal health services and, as a consequence, lead to poor maternal health outcomes for a period extending beyond the conflict itself. As such, understanding how maternal health-seeking behaviour and utilisation of maternal health services can be improved in post-conflict societies is of crucial importance. This study aims to explore the determinants (barriers and facilitators) of women's uptake of maternal, sexual and reproductive health services (MSRHS) in two post-conflict settings in sub-Saharan Africa; Burundi and Northern Uganda, and how uptake is affected by exposure to armed conflict. METHODS: This is a qualitative study that utilised in-depth interviews and focus group discussions (FGDs) for data collection. One hundred and fifteen participants took part in the interviews and FGDs across the two study settings. Participants were women of reproductive age, local health providers and staff of non-governmental organizations. Issues explored included the factors affecting women's utilisation of a range of MSRHS vis-à-vis conflict exposure. The framework method, making use of both inductive and deductive approaches, was used for analyzing the data. RESULTS: A complex and inter-related set of factors affect women's utilisation of MSRHS in post-conflict settings. Exposure to armed conflict affects women's utilisation of these services mainly through impeding women's health seeking behaviour and community perception of health services. The factors identified cut across the individual, socio-cultural, and political and health system spheres, and the main determinants include women's fear of developing pregnancy-related complications, status of women empowerment and support at the household and community levels, removal of user-fees, proximity to the health facility, and attitude of health providers. CONCLUSIONS: Improving women's uptake of MSRHS in post-conflict settings requires health system strengthening initiatives that address the barriers across the individual, socio-cultural, and political and health system spheres. While addressing financial barriers to access is crucial, attention should be paid to non-financial barriers as well. The goal should be to develop an equitable and sustainable health system.

Perceptions of the effects of armed conflict on maternal and reproductive health services and outcomes in Burundi and Northern Uganda: a qualitative study.

BACKGROUND: Armed conflict potentially poses serious challenges to access and quality of maternal and reproductive health (MRH) services, resulting in increased maternal morbidity and mortality. The effects of armed conflict may vary from one setting to another, including the mechanisms/channels through which the conflict may lead to poor access to and quality of health services. This study aims to explore the effects of armed conflict on MRH in Burundi and Northern Uganda. METHODS: This is a descriptive qualitative study that used in-depth interviews (IDIs) and focus group discussions (FGDs) with women, health providers and staff of NGOs for data collection. Issues discussed include the effects of armed conflict on access and quality of MRH services and outcomes, and the mechanisms through which armed conflict leads to poor access and quality of MRH services. A total of 63 IDIs and 8 FGDs were conducted involving 115 participants. RESULTS: The main themes that emerged from the study were: armed conflict as a cause of limited access to and poor quality of MRH services; armed conflict as a cause of poor MRH outcomes; and armed conflict as a route to improved access to health care. The main mechanisms through which the conflict led to poor access and quality of MRH services varied across the sites: attacks on health facilities and looting of medical supplies in both sites; targeted killing of health personnel and favouritism in the provision of healthcare in Burundi; and abduction of health providers in Northern Uganda. The perceived effects of the conflict on MRH outcomes included: increased maternal and newborn morbidity and mortality; high prevalence of HIV/AIDS and SGBV; increased levels of prostitution, teenage pregnancy and clandestine abortion; and high fertility levels. Relocation to government recognised IDP camps was perceived to improve access to health services. CONCLUSIONS: The effects of armed conflict on MRH services and outcomes are substantial. The mechanisms through which armed conflict leads to poor access and quality of MRH services vary from one setting to another. All these issues need to be considered in the design and implementation of interventions to improve MRH in these settings.

Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.

Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent P. falciparum infections, and was associated with a lower risk of clinical episodes of malaria. Nine of the 14 vaccine candidates tested induced Ab-NK, including some less well-characterized antigens: P41, P113, MSP11, RHOPH3, and Pf_11363200. These data highlight an important role of Ab-NK activity in immunity against malaria and provide a potential mechanism for evaluating vaccine candidates.

'Labouring' on the frontlines of global health research: mapping challenges experienced by frontline workers in Africa and Asia.

Drawing on the reflections and discussions from a special session at the 2021 Global Health Bioethics Network summer school, this paper has summarised the key challenges faced by Frontline Workers (FWs) across research sites in Africa and Asia in performing the everyday 'body work' entailed in operationalising global health research. Using a 'body work' lens, we specifically explore and map key challenges that FWs face in Africa and Asia and the physical, social, ethical, emotional, and political labour involved in operationalising global health in these settings. The research encounter links with wider social and economic structures, and spatial dimensions and impacts on the FWs' performance and well-being. Yet, FWs' 'body-work' and the embedded emotions during the research encounter remain hidden and undervalued.

Understanding the benefits and burdens associated with a malaria human infection study in Kenya: experiences of study volunteers and other stakeholders.

BACKGROUND: Human infection studies (HIS) that involve deliberately infecting healthy volunteers with a pathogen raise important ethical issues, including the need to ensure that benefits and burdens are understood and appropriately accounted for. Building on earlier work, we embedded social science research within an ongoing malaria human infection study in coastal Kenya to understand the study benefits and burdens experienced by study stakeholders in this low-resource setting and assess the wider implications for future research planning and policy. METHODS: Data were collected using qualitative research methods, including in-depth interviews (44), focus group discussions (10) and non-participation observation. Study participants were purposively selected (key informant or maximal diversity sampling), including volunteers in the human infection study, study staff, community representatives and local administrative authorities. Data were collected during and up to 18 months following study residency, from sites in Coastal and Western Kenya. Voice recordings of interviews and discussions were transcribed, translated, and analysed using framework analysis, combining data- and theory-driven perspectives. FINDINGS: Physical, psychological, economic and social forms of benefits and burdens were experienced across study stages. Important benefits for volunteers included the study compensation, access to health checks, good residential living conditions, new learning opportunities, developing friendships and satisfaction at contributing towards a new malaria vaccine. Burdens primarily affected study volunteers, including experiences of discomfort and ill health; fear and anxiety around aspects of the trial process, particularly deliberate infection and the implications of prolonged residency; anxieties about early residency exit; and interpersonal conflict. These issues had important implications for volunteers' families, study staff and the research institution's reputation more widely. CONCLUSION: Developing ethically and scientifically strong HIS relies on grounded accounts of volunteers, study staff and the wider community, understood in the socioeconomic, political and cultural context where studies are implemented. Recognition of the diverse, and sometimes perverse, nature of potential benefits and burdens in a given context, and who this might implicate, is critical to this process. Prior and ongoing stakeholder engagement is core to developing these insights.

Equity in aid allocation and distribution: A qualitative study of key stakeholders in Northern Uganda.

The Sustainable Development Goals have spurred a growing interest in and focus on equitable development. In theory, donors can play an important role in promoting equity within a country by providing services, influencing government policies and incorporating equity into decision-making. However, we know little about whether this actually happens on the ground. We conduct what we believe is the first study to explore the extent to which equity is prioritised in the allocation and distribution of aid, based on in-depth interviews with government officials, bilateral and international donors, and implementing partners operating in Northern Uganda. We find that a broad category of people are perceived to be marginalised/vulnerable, with a substantial segment largely untargeted by major donor programmes. Various stakeholders employ a wide range of strategies to identify the most vulnerable individuals and groups, including the use of available data and statistics, consultation and engagement with relevant stakeholders, and undertaking primary data collection. The strategies used to incorporate equity in aid allocation and distribution include: targeting the regions of Northern Uganda and Karamoja in particular, targeting both refugees and host populations in refugee-hosting districts, prioritising the critically vulnerable in any aid distribution process, and using specific tools and consultants to ensure that major equity issues are addressed in proposals. Challenges undermining the process include poor understanding of the concept of equity among some implementing partners, lack of comprehensively disaggregated data, corruption, and political interference in choice of aid location from government officials and donors.

The evolving role of traditional birth attendants in maternal health in post-conflict Africa: A qualitative study of Burundi and northern Uganda.

OBJECTIVES: Many conflict-affected countries are faced with an acute shortage of health care providers, including skilled birth attendants. As such, during conflicts traditional birth attendants have become the first point of call for many pregnant women, assisting them during pregnancy, labour and birth, and in the postpartum period. This study seeks to explore how the role of traditional birth attendants in maternal health, especially childbirth, has evolved in two post-conflict settings in sub-Saharan Africa (Burundi and northern Uganda) spanning the period of active warfare to the post-conflict era. METHODS: A total of 63 individual semi-structured in-depth interviews and 8 focus group discussions were held with women of reproductive age, local health care providers and staff of non-governmental organisations working in the domain of maternal health who experienced the conflict, across urban, semi-urban and rural settings in Burundi and northern Uganda. Discussions focused on the role played by traditional birth attendants in maternal health, especially childbirth during the conflict and how the role has evolved in the post-conflict era. Transcripts from the interviews and focus group discussions were analysed by thematic analysis (framework approach). RESULTS: Traditional birth attendants played a major role in childbirth-related activities in both Burundi and northern Uganda during the conflict, with some receiving training and delivery kits from the local health systems and non-governmental organisations to undertake deliveries. Following the end of the conflict, traditional birth attendants have been prohibited by the government from undertaking deliveries in both Burundi and northern Uganda. In Burundi, the traditional birth attendants have been integrated within the primary health care system, especially in rural areas, and re-assigned the role of 'birth companions'. In this capacity they undertake maternal health promotion activities within their communities. In northern Uganda, on the other hand, traditional birth attendants have not been integrated within the local health system and still appear to undertake clandestine deliveries in some rural areas. CONCLUSION: The prominent role of traditional birth attendants in childbirth during the conflicts in Burundi and northern Uganda has been dwindling in the post-conflict era. Traditional birth attendants can still play an important role in facilitating facility and skilled attended births if appropriately integrated with the local health system.

The Effect of Armed Conflict on the Utilization of Maternal Health Services in Uganda: A Population-based Study.

INTRODUCTION: Maternal mortality rates can be adversely affected by armed conflict, implying a greater level of vulnerability among women, and is often linked to the lack of or limited access to maternal healthcare during conflict. Previous research in Uganda has shown that armed conflict negatively impacts women's utilization of maternal healthcare services for a multitude of reasons at the individual, health-system and political levels. METHODS: This study compared aggregated Demographic and Health Surveys data from 13 districts in Northern Uganda, a conflict-affected region, with data from the rest of the country, for the use of maternal healthcare services for the years 1988, 1995, 2000, 2006 and 2011, using statistical analyses and logistic regression. Specific indicators for maternal healthcare utilization included contraceptive use, antenatal care, skilled assistance at birth and institutional delivery. RESULTS: Use of contraception and institutional deliveries among women in Northern Uganda was significantly lower compared to the rest of the country. However, skilled assistance at birth among women in Northern Uganda was significantly higher. CONCLUSIONS: The findings in this study show that armed conflict can have a negative impact on aspects of maternal healthcare such as contraceptive use and institutional deliveries; however, other indicators such as skilled assistance at birth were seen to be better among conflict-affected populations. This reiterates the complex nature of armed conflict and the interplay of different factors such as conflict intensity, existing health systems and services, and humanitarian interventions that could influence maternal healthcare utilization. KEY WORDS: Armed conflict, maternal health utilization, Northern Uganda, contraception, skilled assistance at birth, antenatal care, institutional delivery.

Barriers in the Delivery of Emergency Obstetric and Neonatal Care in Post-Conflict Africa: Qualitative Case Studies of Burundi and Northern Uganda.

OBJECTIVES: Maternal and neonatal mortality and morbidity rates are particularly grim in conflict, post-conflict and other crisis settings, a situation partly blamed on non-availability and/or poor quality of emergency obstetric and neonatal care (EmONC) services. The aim of this study was to explore the barriers to effective delivery of EmONC services in post-conflict Burundi and Northern Uganda, in order to provide policy makers and other relevant stakeholders context-relevant data on improving the delivery of these lifesaving services. METHODS: This was a qualitative comparative case study that used 42 face-to-face semi-structured in-depth interviews and 4 focus group discussions for data collection. Participants were 32 local health providers and 37 staff of NGOs working in the area of maternal health. Data was analysed using the framework approach. RESULTS: The availability, quality and distribution of EmONC services were major challenges across the sites. The barriers in the delivery of quality EmONC services were categorised into two major themes; human resources-related challenges, and systemic and institutional failures. While some of the barriers were similar, others were unique to specific sites. The common barriers included shortage of qualified staff; lack of essential installations, supplies and medications; increasing workload, burn-out and turnover; and poor data collection and monitoring systems. Barriers unique to Northern Uganda were demoralised personnel and lack of recognition; poor referral system; inefficient drug supply system; staff absenteeism in rural areas; and poor coordination among key personnel. In Burundi, weak curriculum; poor harmonisation and coordination of training; and inefficient allocation of resources were the unique challenges. To improve the situation across the sites, efforts are ongoing to improve the training and recruitment of more staff; harmonise and strengthen the curriculum and training; increase the number of EmONC facilities; and improve staff supervision, monitoring and support. CONCLUSIONS: Post-conflict health systems face different challenges in the delivery of EmONC services and as such require context-specific interventions to improve the delivery of these services.