Controlled Human Malaria Infection Studies in Africa—Past, Present, and Future

Abstract

Controlled human infection studies have contributed significantly to the understanding of pathogeneses and treatment of infectious diseases. In malaria, deliberately infecting humans with malaria parasites was used as a treatment for neurosyphilis in the early 1920s. More recently, controlled human malaria infection (CHMI) has become a valuable, cost-effective tool to fast-track the development and evaluation of new anti-malarial drugs and/or vaccines. CHMI studies have also been used to define host/parasite interactions and immunological correlates of protection. CHMI involves infecting a small number of healthy volunteers with malaria parasites, monitoring their parasitemia and providing anti-malarial treatment when a set threshold is reached. In this review we discuss the introduction, development, and challenges of modern-day Plasmodium falciparum CHMI studies conducted in Africa, and the impact of naturally acquired immunity on infectivity and vaccine efficacy. CHMIs have shown to be an invaluable tool particularly in accelerating malaria vaccine research. Although there are limitations of CHMI studies for estimating public health impacts and for regulatory purposes, their strength lies in proof-of-concept efficacy data at an early stage of development, providing a faster way to select vaccines for further development and providing valuable insights in understanding the mechanisms of immunity to malarial infection.

Advancements and Challenges in Developing Malaria Vaccines: Targeting Multiple Stages of the Parasite Life Cycle

“…194 It also plays a crucial role in identifying immune correlates of protection against malaria 195 as well as assessing the efficacy of malaria vaccine candidates. 196 In CHMI studies, some individuals may develop protective immune responses that effectively control infection, while others may not. By comparing the immune responses between protected and nonprotected individuals, one can identify differences in immune factors that are associated with protection.…”

“…CHMI trials have become increasingly important for studying vaccines and developing effective treatment strategies . It also plays a crucial role in identifying immune correlates of protection against malaria as well as assessing the efficacy of malaria vaccine candidates . In CHMI studies, some individuals may develop protective immune responses that effectively control infection, while others may not.…”

Five decades of clinical assessment of whole-sporozoite malaria vaccines

“…Nevertheless, efforts have been made to standardize mosquito-administered CHMI ( 27 ), reducing the impact of this biological variability. On the other hand, PfSPZ Challenge enhances access to CHMI, including in malaria-endemic regions [( 28 , 29 ) and recently reviewed in ( 30 )], which otherwise would be limited to the few research facilities with the capability to carry out Pf infections of mosquitoes for experimental purposes ( 25 ).…”