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Chemoprophylaxis Vaccination: Phase I Study to Explore Stage-specific Immunity to Plasmodium falciparum in US Adults
- Source :
- Clin Infect Dis
- Publication Year :
- 2019
-
Abstract
- Background Chemoprophylaxis vaccination with sporozoites (CVac) with chloroquine induces protection against a homologous Plasmodium falciparum sporozoite (PfSPZ) challenge, but whether blood-stage parasite exposure is required for protection remains unclear. Chloroquine suppresses and clears blood-stage parasitemia, while other antimalarial drugs, such as primaquine, act against liver-stage parasites. Here, we evaluated CVac regimens using primaquine and/or chloroquine as the partner drug to discern whether blood-stage parasite exposure impacts protection against homologous controlled human malaria infection. Methods In a Phase I, randomized, partial double-blind, placebo-controlled study of 36 malaria-naive adults, all CVac subjects received chloroquine prophylaxis and bites from 12–15 P. falciparum–infected mosquitoes (CVac-chloroquine arm) at 3 monthly iterations, and some received postexposure primaquine (CVac-primaquine/chloroquine arm). Drug control subjects received primaquine, chloroquine, and uninfected mosquito bites. After a chloroquine washout, subjects, including treatment-naive infectivity controls, underwent homologous, PfSPZ controlled human malaria infection and were monitored for parasitemia for 21 days. Results No serious adverse events occurred. During CVac, all but 1 subject in the study remained blood-smear negative, while only 1 subject (primaquine/chloroquine arm) remained polymerase chain reaction–negative. Upon challenge, compared to infectivity controls, 3/3 chloroquine arm subjects displayed delayed patent parasitemia (P = .01) but not sterile protection, while 3/11 primaquine/chloroquine subjects remained blood-smear negative. Conclusions CVac-primaquine/chloroquine is safe and induces sterile immunity to P. falciparum in some recipients, but a single 45 mg dose of primaquine postexposure does not completely prevent blood-stage parasitemia. Unlike previous studies, CVac-chloroquine did not produce sterile immunity. Clinical Trials Registration NCT01500980.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
Adult
Primaquine
030231 tropical medicine
Plasmodium falciparum
Parasitemia
Chemoprevention
03 medical and health sciences
Antimalarials
0302 clinical medicine
Drug control
Chloroquine
parasitic diseases
medicine
Animals
Humans
Malaria, Falciparum
Articles and Commentaries
biology
business.industry
Vaccination
medicine.disease
biology.organism_classification
030104 developmental biology
Infectious Diseases
Sporozoites
Chemoprophylaxis
Immunology
business
Malaria
medicine.drug
Subjects
Details
- ISSN :
- 15376591
- Volume :
- 71
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
- Accession number :
- edsair.doi.dedup.....0a0b777700a95bcc18d065e597166460