Controlled Human Malaria Infection Models

Controlled Human Malaria Infection (CHMI) models provide a powerful platform for investigating malaria pathogenesis, immune responses and the efficacy of vaccines and therapeutics under tightly regulated conditions. Traditionally reliant on exposure to infected mosquitoes, the field has evolved to embrace intramuscular and direct venous inoculation of aseptic, cryopreserved Plasmodium sporozoites, enabling precise dosing and broader geographical implementation. CHMI protocols encompass both liver-stage (pre-erythrocytic) and blood-stage challenges, allowing detailed measurement of the pre-patent period, parasite multiplication rates and host inflammatory signatures. Blood-stage models using purified merozoites support assessment of late-stage vaccine candidates and genetic resistance factors in volunteers. The expansion of CHMI into endemic regions has facilitated studies of naturally acquired immunity, while standardisation of quantitative PCR methods has improved sensitivity in detecting low-density parasitaemia. By accelerating proof-of-concept trials and refining correlates of protection, CHMI models remain central to the global effort to develop effective malaria interventions and transmission-blocking strategies.

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Controlled Human Malaria Infection Models publication trend

The graph below shows the total number of articles in controlled human malaria infection models across all publications each year (not limited to Nature Index journals).

Technical terms

Controlled Human Malaria Infection (CHMI): A research method in which healthy volunteers are deliberately infected with malaria parasites under strict clinical conditions to study disease progression and evaluate interventions.

Sporozoite: The infectious form of the malaria parasite transmitted from mosquitoes or by injection, which migrates to the liver to begin the infection cycle.

Merozoite: The blood-stage form of the parasite released from the liver that invades red blood cells and multiplies asexually.

Parasitaemia: The density of malaria parasites in a person’s bloodstream, measured by quantitative PCR or microscopy.

Pre-patent period: The time interval between parasite inoculation and the first detectable appearance of parasites in the peripheral blood.

References

1. Plasmodium vivax Controlled Human Malaria Infection – Progress and Prospects. Trends in Parasitology (2016).
2. Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naïve volunteers: effect of injection volume and dose on infectivity rates. Malaria Journal (2015).
3. Comparison of Clinical and Parasitological Data from Controlled Human Malaria Infection Trials. PLOS ONE (2012).
4. Evaluating controlled human malaria infection in Kenyan adults with varying degrees of prior exposure to Plasmodium falciparum using sporozoites administered by intramuscular injection. Frontiers in Microbiology (2014).
5. Increased sample volume and use of quantitative reverse-transcription PCR can improve prediction of liver-to-blood inoculum size in controlled human malaria infection studies. Malaria Journal (2015).
6. The Dantu blood group prevents parasite growth in vivo: Evidence from a controlled human malaria infection study. eLife (2023).
7. The challenges of Plasmodium vivax human malaria infection models for vaccine development. Frontiers in Immunology (2023).