# name
Direct venous inoculation of Plasmodium falciparum sporozoites
                for controlled human malaria infection: a dose-finding trial in
                two centres

# metadata.dc.description.abstract[].value
BACKGROUND: Controlled human malaria infection (CHMI)
                accelerates development of anti-malarial interventions. So far,
                CHMI is done by exposure of volunteers to bites of five
                mosquitoes carrying Plasmodium falciparum sporozoites (PfSPZ), a
                technique available in only a few centres worldwide.
                Mosquito-mediated CHMI is logistically complex, exact PfSPZ
                dosage is impossible and live mosquito-based interventions are
                not suitable for further clinical development. METHODS: An
                open-labelled, randomized, dose-finding study in 18-45 year old,
                healthy, malaria-naive volunteers was performed to assess if
                intravenous (IV) injection of 50 to 3,200 aseptic, purified,
                cryopreserved PfSPZ is safe and achieves infection kinetics
                comparable to published data of mosquito-mediated CHMI. An
                independent study site verified the fully infectious dose using
                direct venous inoculation of PfSPZ. Parasite kinetics were
                assessed by thick blood smear microscopy and quantitative real
                time PCR. RESULTS: IV inoculation with 50, 200, 800, or 3,200
                PfSPZ led to parasitaemia in 1/3, 1/3, 7/9, and 9/9 volunteers,
                respectively. The geometric mean pre-patent period (GMPPP) was
                11.2 days (range 10.5-12.5) in the 3,200 PfSPZ IV group.
                Subsequently, six volunteers received 3,200 PfSPZ by direct
                venous inoculation at an independent investigational site. All
                six developed parasitaemia (GMPPP: 11.4 days, range: 10.4-12.3).
                Inoculation of PfSPZ was safe. Infection rate and pre-patent
                period depended on dose, and injection of 3,200 PfSPZ led to a
                GMPPP similar to CHMI with five PfSPZ-infected mosquitoes. The
                infectious dose of PfSPZ predicted dosage of
                radiation-attenuated PfSPZ required for successful vaccination.
                CONCLUSIONS: IV inoculation of PfSPZ is safe, well tolerated and
                highly reproducible. It shall further accelerate development of
                anti-malarial interventions through standardization and
                facilitation of CHMI. Beyond this, rational dose selection for
                whole PfSPZ-based immunization and complex study designs are now
                possible. TRIAL REGISTRATION: ClinicalTrials.gov NCT01624961 and
                NCT01771848 .

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

# metadata.dc.title[].value
Direct venous inoculation of Plasmodium falciparum sporozoites
                for controlled human malaria infection: a dose-finding trial in
                two centres