Ethical challenges posed by human infection challenge studies in endemic settings

Abstract

Human infection challenge studies (HCS) involve intentionally infecting research participants with pathogens, often with the ultimate aim of developing new interventions against infectious diseases. Despite ethical concerns about research involving vulnerable populations, there are both scientific and ethical reasons to consider conducting more HCS in low- and middle-income countries where neglected diseases are often endemic. HCS researchers can reduce the risks to participants (and the risks of transmission from participants to others) by controlling multiple factors (e.g. related to the laboratory environment, participant selection, the pathogen, and the timing of treatment); but HCS nonetheless raise important ethical issues, some of which may be particularly pertinent to HCS in endemic settings. This article provides background on HCS in general, as well as recent HCS in low- and middle-income countries, and an overview of the ethical issues associated with HCS in endemic settings.

Human infection challenge studies in endemic settings and/or low-income and middle-income countries: key points of ethical consensus and controversy

“…For example, LMIC HCS would arguably be more generalisable and thus have a stronger scientific and ethical rationale in cases where there are (more) relevant features (eg, in terms of naturally acquired immunity, co-infections, genetics, microbiome, nutrition, etc) shared by potential (LMIC) study participants and the (LMIC) population(s) most at risk of the (locally endemic) infection in question. 15 There will sometimes be difficult ethical trade-offs between the scientific aim to produce generalisable results and the protection of participants. For example, the use of wild-type strains in HCS may increase risks to participants (compared with the use of attenuated strains); but, assuming risks to participants can be adequately controlled, it may sometimes be more ethically justifiable to use wild-type strains where the use of other strains would provide less informative results (eg, regarding vaccine effectiveness).…”

Exploring willingness to participate in future Human Infection Studies in Lusaka, Zambia: A nested qualitative exploratory study

“…Information requirements for HIS are complex and long and thus most researchers target educated participants [7] bringing its own ethical issue of representation and unjust exclusion of those not educated [6]. Researchers must therefore devise ways in which participants from all walks of life, regardless of education, can access HIS information in a simple and precise way and can ask questions in myriad ways to enhance retention of information and comprehension [7,13,15].…”

“…Similar to requirements reported from Kenya [18], facilities need to cater to more than medical concerns to include comfort, entertainment, family visitations (if possible), and provision to meet pressing worldly obligations such as examinations and funerals. These provisions bring with them considerations of measures that protect participants from infections carried by visitors and the visitors, infection from the facility [6]. Additionally, women may have other requirements such as for menstrual hygiene management, contraception, and a room-mate to feel safe.…”

“…Thus, vaccines remain the most viable short to medium term option for diarrhoeal disease control. However, vaccines developed in non-endemic countries have proven to be less effective in LMIC settings [6] highlighting the urgent need to develop new effective vaccines and improve already existing ones among disease-endemic populations.…”

“…HIS can accelerate vaccine development by facilitating an understanding of pathophysiology and mechanics of immune response under highly controlled conditions and to efficiently test vaccine or drug efficacy. The intentional infection of healthy study participants with a viable challenge agent or pathogen under highly controlled conditions [6], could potentially raise public concerns, queries, and ethical complexities particular to LMIC settings; including concerns around communal pressure to participate, local language wording in information sheets, beliefs on blood collection, adequacy of infection control measures in the community, and appropriateness of compensation given levels of poverty [7]. Additionally, the daily risk posed in some LMIC environments makes it difficult to control HIS participants' exposure to additional diseases or the spread of infection into the larger community without residency requirements [7].…”