Establishing a controlled hookworm human infection (CHHI) model for Africa: A report from the stakeholders meeting held in Lambaréné, Gabon, November 10–11, 2019

Abstract

Background Hookworm is a major contributor to worldwide disease burden with over 230 million people infected. It has been identified as one of the Neglected Tropical Diseases that can be controlled and even eliminated through mass drug administration and other effective interventions. Mathematical models have shown that hookworm can only be eliminated via a vaccine. Controlled Hookworm Human Infection (CHHI) models can facilitate rapid development of vaccines and drugs. Methods As a first step towards the establishment of CHHI in Africa, we held a stakeholders meeting in Lamberene, Gabon from 10 to 11 November 2019. Results Discussions revolved around the roles of the different regulatory institutions concerned; the need to strengthen existing regulatory capacity and the role of legislation; creating Gabon-specific ethical guidelines to govern Controlled Human Infection (CHI) studies; development of a study protocol; consideration of cultural and social peculiarities; the need for regular joint review meetings between interested parties throughout the process of protocol implementation; and participant compensation. Moreover, operational considerations concerning the introduction of CHHI in Gabon include the use of the local strain of hookworm for the challenge infections, capacity building for the local production of challenge material, and the establishment of adequate quality assurance procedures. Conclusion The workshop addressed several of the anticipated hurdles to the successful implementation of CHHI in Gabon. It is our aim that this report will stimulate interest in the implementation of this model in the sub-Saharan African setting.

Ethical and practical considerations arising from community consultation on implementing controlled human infection studies using Schistosoma mansoni in Uganda

“…This process of engagement was recommended by Ugandan stakeholders in preparation for CHI-S (Elliott et al, 2018 ). Similarly, other CHI studies have also recommended and conducted community engagements with the target communities in disease-endemic countries such as Zambia (Kunda-Ng’andu et al, 2021 ), Vietnam (Kestelyn et al, 2019 ), India (Vaz et al, 2019 , 2020 ), Malawi (Kapumba et al, 2020 ), Kenya (Njue et al, 2018 ), and Gabon (Alabi et al, 2021 ). The studies showed that participants are able to understand the processes involved during a CHI.…”

Organoids as tools to investigate gastrointestinal nematode development and host interactions

“…Thus, organoids could overcome barriers in research focused on aspects of the infection that are host-restricted and cannot be replicated using an animal model due to significant interspecies differences (Duque-Correa et al, 2020a). This is particularly relevant for human GI nematodes that do not have any system for investigation besides controlled infections that have limited experimental read outs (Diemert et al, 2018;Alabi et al, 2021;Pritchard et al, 2021). The lack of models for human infective nematodes has driven the use of nematode parasites of rodents or other mammals, which have similar life cycles or induce comparable pathogenesis as human infective species.…”

“…The recreation of the life cycle of human and livestock GI nematodes in vitro using organoids could revolutionise the helminthology field by allowing not only a better understanding of their pathogenesis but also of their "beneficial" effects on the control of inflammation. Organoids could become a key tool to interpret the results of controlled hookworm and whipworm human infections (Diemert et al, 2018;Alabi et al, 2021;Chapman et al, 2021) and on the identification of parasite ES molecules produced by specific larval/adult stages that mediate anti-inflammatory actions of GI nematodes (Maizels et al, 2018). Moreover, organoids could also have a great impact on the development of new anthelmintics and on studies of anthelmintic resistance by allowing investigations on the effects of drugs on the different life cycle stages.…”