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.

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.

Always leave the audience wanting more: An entertaining approach to stimulate engagement with health research among publics in coastal Kenya through 'Magnet Theatre'.

Background: Magnet Theatre (MT), a form of participatory community theatre, is one of several public engagement approaches used to facilitate engagement between KEMRI-Wellcome Trust Research Programme (KWTRP) researchers and public audiences in Coastal Kenya. We describe how we used MT as an entertaining forum where audiences learn about research, and where researchers learn about how the public views research. Methods: Drama scripts depicting community interaction with different aspects of research were developed iteratively with research staff, a theatre company and community members. Six fortnightly theatre outreaches per site over two months, attracting a total of 1454 audience members were held in Mida, a rural village 30 km north of Kilifi; and in Mtwapa, a peri-urban town 45 km to the south. Audiences were presented with dramatized health research-related dilemmas and subsequently invited to enact their responses. Evaluation comprised, notes and observations from meetings, rehearsals and outreaches, transcripts from a review workshop with repeat audience members (n=21), a reflection meeting with KWTRP engagement staff (n=12), and a group discussion with the theatre company (n=9). Discussions were recorded, transcribed, translated to English and analysed using thematic approach. Results: Despite being costly in terms of time and expense, we argue that MT in public spaces can assist audience members to navigate 'border-crossings' between everyday contexts and scientific/research concepts. This can enable audiences to share their views and concerns and enact their responses to research-related dilemmas. Conclusions: While reporting on MT's successes, drawing from literature on rumours, we acknowledge the limitations of individual engagement activities in providing long-term solutions to address alternative interpretations and rumours about research, in the context of local and global inequities. MT, however, presents an opportunity for researchers to express respect to public audiences through making research more accessible and providing opportunities to listen to public views and concerns.

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.

Deliberately infecting healthy volunteers with malaria parasites: Perceptions and experiences of participants and other stakeholders in a Kenyan-based malaria infection study.

Controlled human malaria infection (CHMI) studies involve the deliberate infection of healthy volunteers with malaria parasites under controlled conditions to study immune responses and/or test drug or vaccine efficacy. An empirical ethics study was embedded in a CHMI study at a Kenyan research programme to explore stakeholders' perceptions and experiences of deliberate infection and moral implications of these. Data for this qualitative study were collected through focus group discussions, in-depth interviews and non-participant observation. Sixty-nine participants were involved, including CHMI study volunteers, community representatives and research staff. Data were managed using QSR Nvivo 10 and analysed using an inductive-deductive approach, guided by ethics literature. CHMI volunteers had reasonable understanding of the study procedures. Decisions to join were influenced by study incentives, trust in the research institution, their assessment of associated burdens and motivation to support malaria vaccine development. However, deliberate malaria infection was a highly unusual research strategy for volunteers, community representatives and some study staff. Volunteers' experiences of physical, emotional and social burdens or harms were often greater than anticipated initially, and fluctuated over time, related to specific procedures and events. Although unlikely to deter volunteers' participation in similar studies in furture, we argue that the dissonance between level of understanding of the burdens involved and actual experiences are morally relevant in relation to community engagement, informed consent processes, and ongoing support for volunteers and research staff. We further argue that ethics oversight of CHMI studies should take account of these issues in deciding whether consent, engagement and the balance of benefits and harms are reasonable in a given context.

Socio-ecological determinants of alcohol, tobacco, and drug use behavior of adolescents in Kilifi County at the Kenyan coast.

Alcohol, tobacco, and other drug use form a risk factor for health and social problems during adolescence. From a socio-ecological model, perceptions of 85 young people and 10 stakeholders on the types of alcohol, tobacco, and other drugs used and the predisposing and protective factors were explored; among adolescents at the Kenyan Coast in the Kilifi County. We found that the consumption of home-brewed alcohol, tobacco and marijuana smoking, and khat chewing was common and requires multi-component and community-centered intervention. Countering alcohol, tobacco, and other drug use needs enforcement of strong measures to regulate access to alcohol, tobacco, and other drugs for minors; addressing social and cultural norms; strategies for poverty alleviation; and community empowerment.

Who should decide about children's and adolescents' participation in health research? The views of children and adults in rural Kenya.

BACKGROUND: International research guidance has shifted towards an increasingly proactive inclusion of children and adolescents in health research in recognition of the need for more evidence-based treatment. Strong calls have been made for the active involvement of children and adolescents in developing research proposals and policies, including in decision-making about research participation. Much evidence and debate on this topic has focused on high-income settings, while the greatest health burdens and research gaps occur in low-middle income countries, highlighting the need to take account of voices from more diverse contexts. METHODS: Between January and March 2014, 56 community representatives and secondary school students were involved in eight group discussions to explore views on the acceptability of involving children and adolescents in research, and how these groups should be involved in decision-making about their own participation. Discussions were voice-recorded and transcriptions analyzed using Framework Analysis, combining deductive and inductive approaches. RESULTS: Across these discussions, the idea of involving children and adolescents in decision-making about research participation was strongly supported given similar levels of responsibility carried in everyday life; existing capacity that should be recognized; the opportunity for learning involved; varying levels of parental control; and generational shifts towards greater understanding of science for adolescents than their parents. Joint decision-making processes were supported for older children and adolescents, with parental control influenced by perceptions of the risks involved in participation. CONCLUSIONS: Moves towards more active involvement of children and adolescents in planning studies and in making decisions about their participation are supported by these findings from Kenya. Important emerging considerations include the need to take account of the nature of proposed studies and prevailing attitudes and understanding of research in identifying children's and adolescents' roles. More research is needed to expand diversity and develop approaches to joint assent and consent processes that would fairly represent children's and adolescents' wishes and interests, towards their long term benefit.

Young people's and stakeholders' perspectives of adolescent sexual risk behavior in Kilifi County, Kenya: A qualitative study.

A lack of research exists around the most common forms of sexual risk behaviors among adolescents, including their underlying factors, in Sub-Saharan Africa. Using an Ecological Model of Adolescent Behavior, we explore the perceptions of 85 young people and 10 stakeholders on sexual risk behavior of adolescents in Kilifi County on the coast of Kenya. Our findings show that transactional sex, early sexual debut, coerced sex, and multiple sexual partnerships are prevalent. An urgent need exists to develop measures to counter sexual risk behaviors. The results contribute to understanding the range of risks and protective factors in differing contexts, tackling underlying issues at individual, family, local institutional, wider socio-economic, and political levels.

Research Stakeholders' Views on Benefits and Challenges for Public Health Research Data Sharing in Kenya: The Importance of Trust and Social Relations.

BACKGROUND: There is increasing recognition of the importance of sharing research data within the international scientific community, but also of the ethical and social challenges this presents, particularly in the context of structural inequities and varied capacity in international research. Public involvement is essential to building locally responsive research policies, including on data sharing, but little research has involved stakeholders from low-to-middle income countries. METHODS: Between January and June 2014, a qualitative study was conducted in Kenya involving sixty stakeholders with varying experiences of research in a deliberative process to explore views on benefits and challenges in research data sharing. In-depth interviews and extended small group discussions based on information sharing and facilitated debate were used to collect data. Data were analysed using Framework Analysis, and charting flow and dynamics in debates. FINDINGS: The findings highlight both the opportunities and challenges of communicating about this complex and relatively novel topic for many stakeholders. For more and less research-experienced stakeholders, ethical research data sharing is likely to rest on the development and implementation of appropriate trust-building processes, linked to local perceptions of benefits and challenges. The central nature of trust is underpinned by uncertainties around who might request what data, for what purpose and when. Key benefits perceived in this consultation were concerned with the promotion of public health through science, with legitimate beneficiaries defined differently by different groups. Important challenges were risks to the interests of study participants, communities and originating researchers through stigmatisation, loss of privacy, impacting autonomy and unfair competition, including through forms of intentional and unintentional 'misuse' of data. Risks were also seen for science. DISCUSSION: Given background structural inequities in much international research, building trust in this low-to-middle income setting includes ensuring that the interests of study participants, primary communities and originating researchers will be promoted as far as possible, as well as protected. Important ways of building trust in data sharing include involving the public in policy development and implementation, promoting scientific collaborations around data sharing and building close partnerships between researchers and government health authorities to provide checks and balances on data sharing, and promote near and long-term translational benefits.

Involving Research Stakeholders in Developing Policy on Sharing Public Health Research Data in Kenya: Views on Fair Process for Informed Consent, Access Oversight, and Community Engagement.

Increased global sharing of public health research data has potential to advance scientific progress but may present challenges to the interests of research stakeholders, particularly in low-to-middle income countries. Policies for data sharing should be responsive to public views, but there is little evidence of the systematic study of these from low-income countries. This qualitative study explored views on fair data-sharing processes among 60 stakeholders in Kenya with varying research experience, using a deliberative approach. Stakeholders' attitudes were informed by perceptions of benefit and concerns for research data sharing, including risks of stigmatization, loss of privacy, and undermining scientific careers and validity, reported in detail elsewhere. In this article, we discuss institutional trust-building processes seen as central to perceptions of fairness in sharing research data in this setting, including forms of community involvement, individual prior awareness and agreement to data sharing, independence and accountability of governance mechanisms, and operating under a national framework.

Best Practices for Ethical Sharing of Individual-Level Health Research Data From Low- and Middle-Income Settings.

Sharing individual-level data from clinical and public health research is increasingly being seen as a core requirement for effective and efficient biomedical research. This article discusses the results of a systematic review and multisite qualitative study of key stakeholders' perspectives on best practices in ethical data sharing in low- and middle-income settings. Our research suggests that for data sharing to be effective and sustainable, multiple social and ethical requirements need to be met. An effective model of data sharing will be one in which considered judgments will need to be made about how best to achieve scientific progress, minimize risks of harm, promote fairness and reciprocity, and build and sustain trust.

Short communication: High prevalence of transmitted antiretroviral drug resistance among newly HIV type 1 diagnosed adults in Mombasa, Kenya.

Abstract In view of the recent antiretroviral therapy (ART) scale-up in Kenya, surveillance of transmitted HIV drug resistance (TDR) is important. A cross-sectional survey was conducted among newly HIV-1 diagnosed, antiretroviral-naive adults in Mombasa, Kenya. Surveillance drug resistance mutations (SDRMs) were identified according to the 2009 WHO list. HIV-1 subtypes were determined using REGA and SCUEAL subtyping tools. Genotypic test results were obtained for 68 of 81 participants, and SDRMs were identified in 9 samples. Resistance to nonnucleoside reverse transcriptase inhibitors (K103N) occurred in five participants, yielding a TDR prevalence of 7.4% (95% confidence interval 2.4-16.3%). Frequencies of HIV-1 subtypes were A (70.6%), C (5.9%), D (2.9%), and unique recombinant forms (20.6%). The TDR prevalence found in this survey is higher than previously reported in different regions in Kenya. These findings justify increased vigilance with respect to TDR surveillance in African regions where ART programs are scaled-up in order to inform treatment guidelines.

Secrecy, disclosure and accidental discovery: perspectives of diaphragm users in Mombasa, Kenya.

The diaphragm is receiving renewed attention as a promising female-controlled method of preventing HIV and other sexually-transmitted infections. It is anticipated that female-controlled technologies will reduce women's biological susceptibility and assist in counteracting their sociocultural vulnerability to HIV. Understanding the subjective experiences of diaphragm users in different settings has the potential to inform the development and promotion of such methods. This paper explores the perspectives of female sex workers and women attending sexual and reproductive health services in Mombasa, Kenya. Data are reported from focus group discussions and in-depth interviews with women and men, following a prospective study investigating diaphragm continuation rates over six months. Discussions highlighted covert use of the diaphragm, during sex work or with casual partners, and coital independence as favourable attributes. These features were especially pronounced compared with male condoms. Few difficulties with diaphragm use were reported, although its insertion and removal occasionally presented problems. Many women--especially those in long term partnerships--wished to disclose its use but found the disclosure process highly problematic. Accidental discovery often resulted in partner conflict. Although future uptake of the diaphragm may be high in this setting, its use may be limited to certain types of relationships and relationship context.

Acceptability of the diaphragm in Mombasa Kenya: a 6-month prospective study.

OBJECTIVES: If proven acceptable, safe and effective, the diaphragm could be used as a female-controlled method of preventing both sexually-transmitted infections (STIs) and pregnancy. This study's aim was to assess the acceptability and safety of the diaphragm among sexually-active women in Mombasa, Kenya. METHODS: We conducted a 6-month prospective study among female sex workers (FSWs), and women attending sexual and reproductive health services. Diaphragm acceptability was assessed using continuation rates and factors associated with acceptability. Safety evaluations included colposcopy findings and incidence of urinary tract infections (UTIs) and STIs. RESULTS: Half the 185 participants were FSWs who had less schooling and were less likely to be married than other women. After 6 months, 55% (56/102) of sexually-active women reported having used the diaphragm each sex act during the preceding month. Women liked using the diaphragm (95%, 104/109), and 96% (125/130) reported willingness to continue using it. Colposcopy did not reveal significantly more vaginal or cervical lesions. Use of the diaphragm was not associated with an increase in bacterial vaginosis or UTIs. A pregnancy rate of 12 per 100 women/years was observed. CONCLUSION: After 6 months of diaphragm use in this setting, continuation rates were sustained, user satisfaction was high and adverse effects were few.