Chemoprophylaxis Vaccination: Phase I Study to Explore Stage-specific Immunity to Plasmodium falciparum in US Adults.
Clin Infect Dis
; 71(6): 1481-1490, 2020 09 12.
Article
en En
| MEDLINE
| ID: mdl-31621832
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Malaria Falciparum
/
Antimaláricos
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Animals
/
Humans
Idioma:
En
Revista:
Clin Infect Dis
Asunto de la revista:
DOENCAS TRANSMISSIVEIS
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos