Ethical considerations in Controlled Human Malaria Infection studies in low resource settings: Experiences and perceptions of study participants in a malaria Challenge study in Kenya [version 2; referees: 2 approved]

Background: The range and amount of volunteer infection studies, known as Controlled Human Infection Model (CHMI) studies, in Low-Middle Income Countries (LMICs) is increasing with rapid technological advancement, world-class laboratory facilities and increasing capacity development initiatives. However, the ethical issues these studies present in LMICs have not been empirically studied. We present findings of a descriptive social science study nested within a malaria volunteer infection study, on-going at the time of writing, at the KEMRI-Wellcome Trust Research Programme (KWTRP) on the Kenyan Coast. Methods: The study included non-participant observations, five group discussions with more than half of the CHMI study participants, two in-depth interviews with study team members, and an exit questionnaire administered to the participants. Results: Participants understood the key elements of the study, including that they would be deliberately infected with malaria parasites and may get malaria as a result, there would be regular blood draws, and they would spend up to 24 days in a residence facility away from their homes. The greatest motivation for participation was the monetary compensation of 20 USD per overnight stay given as a lump-sum at the end of their residency stay. Also appreciated were the health screening tests prior to enrolment and the positive relations with the study team. Concerns raised included the amount and regularity of blood draws experienced, and concerns that this type of research may feed into on-going rumours about research generally. Conclusion: With the increasing range and number of CHMI studies being conducted in LMICs, current ethical guidance are inadequate. This study highlights some of the ethical issues that could emerge in these settings, emphasizing the heavy responsibility placed on research review and regulatory systems, researchers and funders, as well as the importance of carefully tailored community engagement and consent processes

Human Challenge Studies in Endemic Settings

This open access book provides an extensive review of ethical and regulatory issues related to human infection challenge studies, with a particular focus on the expansion of this type of research into endemic settings and/or low- and middle-income countries (LMICs). Human challenge studies (HCS) involve the intentional infection of research participants, and this type of research is rapidly increasing in frequency worldwide. HCS are widely considered to be an especially promising approach to vaccine development, including for pathogens endemic to LMICs. However, challenge studies are sometimes controversial and raise complex ethical issues, some of which are especially salient in endemic and/or LMIC settings. Informed by qualitative interviews with experts in infectious diseases and bioethics, this book highlights areas of ethical consensus and controversy concerning this kind of research. As the first volume to focus on ethical issues associated with human challenge studies, it sets the agenda for further work in this important area of global health research; contributes to current debates in research ethics; and aims to inform regulatory policy and research practice. Insofar as it focuses on HCS in (endemic) settings where diseases are present and/or widespread, much of the analysis provided here is directly relevant to HCS involving pandemic diseases including COVID19

Characterizing altruistic motivation in potential volunteers for SARS-CoV-2 challenge trials

In human challenge trials, volunteers are deliberately infected with a pathogen to accelerate vaccine development and answer key scientific questions. In the U.S., preparations for challenge trials with the novel coronavirus are complete, and in the U.K., challenge trials have recently begun. However, ethical concerns have been raised about the potential for invalid consent or exploitation. These concerns largely reflect worries that challenge trial volunteers may be unusually risk-seeking or too economically vulnerable to refuse the payments these trials provide, rather than being motivated primarily by altruistic goals. We conducted the first large-scale survey of intended human challenge trial volunteers and found that SARS-CoV-2 challenge trial volunteers exhibit high levels of altruistic motivations without any special indication of poor risk perception or economic vulnerability. Findings indicate that challenge trials with the novel coronavirus can attract volunteers with background conditions, attitudes, and motivations that should allay key ethical concerns

Controlled human infection models as a tool for malaria and schistosomiasis vaccine research

Controlled human infection (CHI) models are an important research tool. Healthy volunteers are experimentally infected with a pathogen. In malaria research the model has been used for decades. Here, the model was used to test new Plasmodium falciparum strains, NF135.C10 an NF166.C8, and compare these with the commonly used strain NF54. In addition, a genetically modified malaria vaccine, PfSPZ-GA1, was tested. Unfortunately only few volunteers were protected against malaria.For schistosomiasis, a controlled human schistosomiasis infection (CoHSI) model was developed and hereafter a dose finding study with single-sex male only cercariae was performed. This study showed that in 80% of volunteers 20 cercariae were effective to induce an infection. Although the use of 30 cercariae resulted in 100% infection rate two out of three volunteers developed Katayama syndrome. These side effects were less after infection with 20 cercariae.At last suggestions were made to further improve the CHI model by the use of historical controls. Although this study design can only be used in CHI’s with well-know outcomes these study will be safer by reducing the cumulative risks as less volunteers can be used for these trials. LUMC / Geneeskund