Lessons learnt from the first controlled human malaria infection study conducted in Nairobi, Kenya.

Susanne H Hodgson,Charles Magiri,Daniel Njenga,Caroline Ogwang,Bernhards Ogutu,Simon J Draper,Peter F Billingsley,Patricia Njuguna,Andrew O Cole,Elizabeth Juma,Ken Awuondo,Roma Chilengi,Stephen L Hoffman,Faith Osier,Kevin Marsh,Amina Salim,Brett Lowe,Sassy Molyneux

doi:10.1186/s12936-015-0671-x

Abstract

BackgroundControlled human malaria infection (CHMI) studies, in which healthy volunteers are infected with Plasmodium falciparum to assess the efficacy of novel malaria vaccines and drugs, have become a vital tool to accelerate vaccine and drug development. CHMI studies provide a cost-effective and expeditious way to circumvent the use of large-scale field efficacy studies to deselect intervention candidates. However, to date few modern CHMI studies have been performed in malaria-endemic countries.MethodsAn open-label, randomized pilot CHMI study was conducted using aseptic, purified, cryopreserved, infectious P. falciparum sporozoites (SPZ) (Sanaria® PfSPZ Challenge) administered intramuscularly (IM) to healthy Kenyan adults (n = 28) with varying degrees of prior exposure to P. falciparum. The purpose of the study was to establish the PfSPZ Challenge CHMI model in a Kenyan setting with the aim of increasing the international capacity for efficacy testing of malaria vaccines and drugs, and allowing earlier assessment of efficacy in a population for which interventions are being developed. This was part of the EDCTP-funded capacity development of the CHMI platform in Africa.DiscussionThis paper discusses in detail lessons learnt from conducting the first CHMI study in Kenya. Issues pertinent to the African setting, including community sensitization, consent and recruitment are considered. Detailed reasoning regarding the study design (for example, dose and route of administration of PfSPZ Challenge, criteria for grouping volunteers according to prior exposure to malaria and duration of follow-up post CHMI) are given and changes other centres may want to consider for future studies are suggested.ConclusionsPerforming CHMI studies in an African setting presents unique but surmountable challenges and offers great opportunity for acceleration of malaria vaccine and drug development. The reflections in this paper aim to aid other centres and partners intending to use the CHMI model in Africa.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0671-x) contains supplementary material, which is available to authorized users.

Highlights

Controlled human malaria infection (CHMI) studies, in which healthy volunteers are infected with Plasmodium falciparum to assess the efficacy of novel malaria vaccines and drugs, have become a vital tool to accelerate vaccine and drug development [1,2,3,4,5]
Three CHMI trials using Plasmodium falciparum sporozoites product (PfSPZ) Challenge have been conducted in malaria-endemic regions: the first in Tanzania [12], the second in Kenya [13] and the third in Gabon (Lell et al, unpublished)., This paper provides a discussion of the experiences and lessons learnt conducting the first CHMI study in Kenya which should be useful given the potential future importance of the African CHMI platform, planned African CHMI studies at new sites (SLH, pers comm) and the unique challenges faced when performing CHMI studies in the developing world
The study was conducted at the Kenya Medical Research Institute (KEMRI) Centre for Clinical Research, Nairobi, Kenya according to the principles of the Declaration of Helsinki, in accordance with Good Clinical Practice and in line with World Health Organization (WHO) guidelines on the conduct of sporozoite CHMI studies [14]

Summary

Introduction

Controlled human malaria infection (CHMI) studies, in which healthy volunteers are infected with Plasmodium falciparum to assess the efficacy of novel malaria vaccines and drugs, have become a vital tool to accelerate vaccine and drug development. CHMI studies provide a cost-effective and expeditious way to circumvent the use of large-scale field efficacy studies to deselect intervention candidates. To date few modern CHMI studies have been performed in malaria-endemic countries. CHMI studies in malarianaïve volunteers have been shown to accurately predict vaccine efficacy in the target African paediatric population [6] and provide a cost-effective and expeditious way to circumvent the use of large-scale field efficacy studies to deselect intervention candidates [7,8]. Conducting CHMI trials in malaria-endemic rather than ‘northern’ malaria-naïve countries has a number of key advantages. To date, CHMI trials have rarely been conducted in malaria-endemic regions, primarily because of the lack of access to the appropriate parasite culture and insectary facilities necessary for mosquito-bite CHMI studies [1,6,8]

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