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Human infection studies (HIS) have generally been used as a tool in the pathway for vaccine development in high income settings. Over the last decade, this model has been implemented in LMICs with the aim of accelerating development of next generation vaccines that would perform better in these settings. However, in most LMICs, the ethics and regulatory framework for the conduct of these studies are not in place. In Zambia, these studies are yet to be conducted and thus we conducted a stakeholder engagement workshop in October 2019. We engaged with bioethicists, regulatory authority, and scientists from within Zambia and other African countries to anticipate and address foreseeable ethical and regulatory issues when conducting HIS in Zambia for the first time. The workshop largely focused on sensitizing the stakeholders on the benefits of these studies with the following main points for consideration on the implementation of these studies in Zambia: need for in-country legal framework and guidelines; need for adequate informed consent based on comprehensive understanding of the concept of HIS and study requirements; and requirements for heightened vigilance to assure participant safety including good ethical and clinical practice with regulatory, ethical, data safety, and community oversight. Additionally, the workshop emphasized the need for rigorous health screening prior to enrolment; suitable infrastructure for containment; and personnel to provide appropriate treatment including emergency resuscitation and evacuation if indicated. Specific recommendations included compensation for burden of participation; access to care and provision for study related injury (e.g. no-fault insurance); and withdrawal and exit procedures to preserve individual and community safety. Finally, the meeting concluded that researchers should actively engage key gate keepers including civic leaders such as parliamentarians, universities, researchers, potential participants and laypersons to avoid circulation of misinformation.

Controlled human infection (CHI) models are gaining recognition as an approach to accelerating vaccine development, for use in both non-endemic and endemic populations: they can facilitate identification of the most promising candidate vaccines for further trials and advance understanding of protective immunity. Helminths present a continuing health burden in sub-Saharan Africa. Vaccine development for these complex organisms is particularly challenging, partly because protective responses are akin to mechanisms of allergy. A CHI model for Schistosoma mansoni (CHI-S) has been developed at Leiden University Medical Centre, the Netherlands. However, responses to schistosome infections, and candidate vaccines, are likely to be different among people from endemic settings compared to schistosome-naïve Dutch volunteers. Furthermore, among volunteers from endemic regions who have acquired immune responses through prior exposure, schistosome challenge can be used to define responses associated with clinical protection, and thus to guide vaccine development. To explore the possibility of establishing the CHI-S in Uganda, a Stakeholders’ Meeting was held in Entebbe in 2017. Regulators, community members, researchers and policy-makers discussed implementation challenges and recommended preparatory steps: risk assessment; development of infrastructure and technical capacity to produce the infectious challenge material in Uganda; community engagement from Parliamentary to grass-roots level; pilot studies to establish approaches to assuring fully informed consent and true voluntariness, and strategies for selection of volunteers who can avoid natural infection during the 12-week CHI-S; the building of regulatory capacity; and the development of study protocols and a product dossier in close consultation with ethical and regulatory partners. It was recommended that, on completion, the protocol and product dossier be reviewed for approval in a joint meeting combining ethical, regulatory and environment management authorities. Most importantly, representatives of schistosomiasis-affected communities emphasised the urgent need for an effective vaccine and urged the research community not to delay in the development process.

Controlled human infection (CHI) models are gaining recognition as an approach to accelerating vaccine development, for use in both non-endemic and endemic populations: they can facilitate identification of the most promising candidate vaccines for further trials and advance understanding of protective immunity. Helminths present a continuing health burden in sub-Saharan Africa. Vaccine development for these complex organisms is particularly challenging, partly because protective responses are akin to mechanisms of allergy. A CHI model for Schistosoma mansoni (CHI-S) has been developed at Leiden University Medical Centre, the Netherlands. However, responses to schistosome infections, and candidate vaccines, are likely to be different among people from endemic settings compared to schistosome-naïve Dutch volunteers. Furthermore, among volunteers from endemic regions who have acquired immune responses through prior exposure, schistosome challenge can be used to define responses associated with clinical protection, and thus to guide vaccine development. To explore the possibility of establishing the CHI-S in Uganda, a Stakeholders’ Meeting was held in Entebbe in 2017. Regulators, community members, researchers and policy-makers discussed implementation challenges and recommended preparatory steps: risk assessment; development of infrastructure and technical capacity to produce the infectious challenge material in Uganda; community engagement from Parliamentary to grass-roots level; pilot studies to establish approaches to assuring fully informed consent and true voluntariness, and strategies for selection of volunteers who can avoid natural infection during the 12-week CHI-S; the building of regulatory capacity; and the development of study protocols and a product dossier in close consultation with ethical and regulatory partners. It was recommended that, on completion, the protocol and product dossier be reviewed for approval in a joint meeting combining ethical, regulatory and environment management authorities. Most importantly, representatives of schistosomiasis-affected communities emphasised the urgent need for an effective vaccine and urged the research community not to delay in the development process.