# name
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

# metadata.dc.description.abstract[].value
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.

# metadata.dc.relation.isformatof[].value
Reproducció del document publicat a:
                http://dx.doi.org/10.1186/s12936-015-0817-x

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
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