Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naïve volunteers : effect of injection volume and dose on infectivity rates
Gómez-Pérez, Gloria P. (University of Amsterdam)
Legarda, Almudena (Institut de Salut Global de Barcelona)
Muñoz Gutiérrez, José (Institut de Salut Global de Barcelona)
Sim, B. Kim Lee (Sanaria Inc, Rockville, MD USA)
Ballester, Maria Rosa (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Dobaño, Carlota (Institut de Salut Global de Barcelona)
Moncunill, Gemma (Institut de Salut Global de Barcelona)
Campo, Joseph J. (Antigen Discovery, Inc, Irvine, USA)
Cisteró, Pau (Institut de Salut Global de Barcelona)
Jimenez, Alfons (Institut de Salut Global de Barcelona)
Barrios, Diana (Institut de Salut Global de Barcelona)
Mordmüller, Benjamin (Institut für Tropenmedizin, Tübingen, Germany)
Pardos, Josefina (Institut de Salut Global de Barcelona)
Navarro, Mireia (Institut de Salut Global de Barcelona)
Zita, Cecilia Justino (Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique)
Nhamuave, Carlos Arlindo (Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique)
García-Basteiro, Alberto L.. (Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique)
Sanz, Ariadna (Institut de Salut Global de Barcelona)
Aldea, Marta (Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique)
Manoj, Anita (Sanaria Inc, Rockville, USA)
Gunasekera, Anusha (Sanaria Inc, Rockville, USA)
Billingsley, Peter F. (Sanaria Inc, Rockville, USA)
Aponte, John J. (Institut de Salut Global de Barcelona)
James, Eric R. (Sanaria Inc, Rockville, MD USA)
Guinovart, Caterina (Institut de Salut Global de Barcelona)
Antonijoan Arbós, Rosa Ma. (Institut d'Investigació Biomèdica Sant Pau)
Kremsner, Peter G. (Institut für Tropenmedizin, Eberhard Karls Universität Tübingen and German Centre for Infection Research, 72074 Tübingen, Germany)
Hoffman, Stephen L. (Sanaria Inc, Rockville, USA)
Alonso, Pedro L. (Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique)

Fecha:	2015
Resumen:	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. An open-label CHMI study was performed with aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) in 36 malaria naïve 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 µL (n = 6), 50 µL (n = 6) or 250 µL (n = 6), respectively. In part B, the injection volume that resulted in highest infectivity rates in part A (10 µL) was used to formulate IM doses of 25,000 PfSPZ (n = 6) and 75,000 PfSPZ (n = 6) divided into two 10-µL 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-µL injection by direct venous inoculation (DVI). Four/six participants in the 10-µL group, 1/6 in the 50-µL group and 2/6 in the 250-µL 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. 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. The online version of this article (doi:10. 1186/s12936-015-0817-x) contains supplementary material, which is available to authorized users.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Controlled human malaria infection ; Malaria ; Plasmodium falciparum ; Cryopreserved sporozoites ; Human challenge infection
Publicado en:	Malaria journal, Vol. 14 (august 2015) , ISSN 1475-2875

DOI: 10.1186/s12936-015-0817-x
PMID: 26245196

13 p, 1.2 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
Artículos > Artículos de investigación
Artículos > Artículos publicados