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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/69243
Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naive volunteers: effect of injection volume and dose on infectivity rates
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BACKGROUND: Controlled human malaria infection (CHMI) by
mosquito bite is a powerful tool for evaluation of vaccines and
drugs against Plasmodium falciparum malaria. However, only a
small number of research centres have the facilities required to
perform such studies. CHMI by needle and syringe could help to
accelerate the development of anti-malaria interventions by
enabling centres worldwide to employ CHMI. METHODS: An
open-label CHMI study was performed with aseptic, purified,
cryopreserved P. falciparum sporozoites (PfSPZ Challenge) in 36
malaria naive volunteers. In part A, the effect of the
inoculation volume was assessed: 18 participants were injected
intramuscularly (IM) with a dose of 2,500 PfSPZ divided into two
injections of 10 microL (n = 6), 50 microL (n = 6) or 250 microL
(n = 6), respectively. In part B, the injection volume that
resulted in highest infectivity rates in part A (10 microL) was
used to formulate IM doses of 25,000 PfSPZ (n = 6) and 75,000
PfSPZ (n = 6) divided into two 10-microL injections. Results
from a parallel trial led to the decision to add a positive
control group (n = 6), each volunteer receiving 3,200 PfSPZ in a
single 500-microL injection by direct venous inoculation (DVI).
RESULTS: Four/six participants in the 10-microL group, 1/6 in
the 50-microL group and 2/6 in the 250-microL group developed
parasitaemia. Geometric mean (GM) pre-patent periods were 13.9,
14.0 and 15.0 days, respectively. Six/six (100%) participants
developed parasitaemia in the 25,000 and 75,000 PfSPZ IM and
3,200 PfSPZ DVI groups. GM pre-patent periods were 12.2, 11.4
and 11.4 days, respectively. Injection of PfSPZ Challenge was
well tolerated and safe in all groups. CONCLUSIONS: IM injection
of 75,000 PfSPZ and DVI injection of 3,200 PfSPZ resulted in
infection rates and pre-patent periods comparable to the bite of
five PfSPZ-infected mosquitoes. Remarkably, it required
23.4-fold more PfSPZ administered IM than DVI to achieve the
same parasite kinetics. These results allow for translation of
CHMI from research to routine use, and inoculation of PfSPZ by
IM and DVI regimens. TRIAL REGISTRATION: ClinicalTrials.gov
NCT01771848.
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GÓMEZ PÉREZ, Gloria p., LEGARDA, Almudena, MUÑOZ, José, SIM, B. kim lee, BALLESTER, Maria rosa, DOBAÑO, Carlota, MONCUNILL PIÑAS, Gemma, CAMPO, Joseph j., CISTERÓ, Pau, JIMÉNEZ, Alfons, BARRIOS, Diana, MORDMÜLLER, Benjamin, PARDOS, Josefina, NAVARRO, Mireia, ZITA, Cecilia justino, NHAMUAVE, Carlos arlindo, GARCÍA-BASTEIRO, Alberto l., SANZ, Ariadna, ALDEA, Marta, MANOJ, Anita, GUNASEKERA, Anusha, BILLINGSLEY, Peter f., APONTE, John j., JAMES, Eric r., GUINOVART, Caterina, ANTONIJOAN ARBÓS, Rosa ma. (rosa maría), KREMSNER, Peter g., HOFFMAN, Stephen l., ALONSO, Pedro. Controlled human malaria infection by intramuscular and direct
venous inoculation of cryopreserved Plasmodium falciparum
sporozoites in malaria-naive volunteers: effect of injection
volume and dose on infectivity rates. _Malaria Journal_. 2015. Vol. 14, núm. 306, pàgs. 1-13. [consulta: 8 de febrer de 2026]. ISSN: 1475-2875. [Disponible a: https://hdl.handle.net/2445/69243]