We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Chemoprophylaxis Vaccination: Phase I Study to Explore Stage-specific Immunity to Plasmodium falciparum in US Adults.
- Authors
Healy, Sara A; Murphy, Sean C; Hume, Jen C C; Shelton, Lisa; Kuntz, Steve; Voorhis, Wesley C Van; Moodie, Zoe; Metch, Barbara; Wang, Ruobing; Silver-Brace, Tiffany; Fishbaugher, Matthew; Kennedy, Mark; Finney, Olivia C; Chaturvedi, Richa; Marcsisin, Sean R; Hobbs, Charlotte V; Warner-Lubin, Margaret; Talley, Angela K; Wong-Madden, Sharon; Stuart, Ken
- Abstract
Background Chemoprophylaxis vaccination with sporozoites (CVac) with chloroquine induces protection against a homologous Plasmodium falciparum sporozoite (Pf SPZ) 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, Pf SPZ 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
DRUG therapy for malaria; CHEMOPREVENTION; CHLOROQUINE; PLACEBOS; POLYMERASE chain reaction; PRIMAQUINE; PROTOZOA; RANDOMIZED controlled trials; BLIND experiment; PARASITEMIA
- Publication
Clinical Infectious Diseases, 2020, Vol 71, Issue 6, p1481
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/ciz1010