Miniatura

Fitxers

mordmuller2015_1858.pdf (1.21 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2015-03-18

Llicència de publicació

cc by (c) Mordmüller et al., 2015
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/68720

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

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

http://dx.doi.org/10.1186/s12936-015-0628-0

Resum

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 .

Matèries

Malària, Plasmodium falciparum, Vacunació, Assaigs clínics

Matèries (anglès)

Malaria, Plasmodium falciparum, Vaccination, Clinical trials

Citació

Col·leccions

Articles publicats en revistes (ISGlobal)

Citació

MORDMÜLLER, Benjamin, SUPAN, Christian, SIM, B. kim lee, GÓMEZ PÉREZ, Gloria p., OSPINA SALAZAR, Carmen lucelly, HELD, Jana, BOLTE, Stefanie, ESEN, Meral, TSCHAN, Serena, JOANNY, Fanny, LAMSFUS CALLE, Carlos, LOHR, Sascha jz., LALREMRUATA, Albert, GUNASEKERA, Anusha, JAMES, Eric r., BILLINGSLEY, Peter f., RICHMAN, Adam, CHAKRAVARTY, Sumana, LEGARDA, Almudena, MUÑOZ, José, ANTONIJOAN ARBÓS, Rosa ma. (rosa maría), BALLESTER, Maria rosa, HOFFMAN, Stephen l., ALONSO, Pedro, KREMSNER, Peter g.. Direct venous inoculation of Plasmodium falciparum sporozoites
                for controlled human malaria infection: a dose-finding trial in
                two centres. _Malaria Journal_. 2015. Vol. 14, núm. 117. [consulta: 20 de gener de 2026]. ISSN: 1475-2875. [Disponible a: https://hdl.handle.net/2445/68720]

Exportar metadades

JSON - METS

Compartir registre