Controlled Human Malaria Infection of Tanzanians by Intradermal Injection of Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites

• DOI: 10.4269/ajtmh.14-0119
• Publication Date: 2014-07-29T03:10:40Z
• Authors: Seif Shekalaghe; Mastidia Rutaihwa; Peter F. Billingsley; Mwajuma Chemba; Claudia A. Dauben...; Eric R. James; Maximillian Mpina; Omar Ali Juma; Tobias Schindler; Eric Huber; Anusha Gunasekera; Anita Manoj; Beatus Simon; Elizabeth Saverino; L. W. Preston Church; Cornelus C. Hermsen; Robert W. Sauerwein; Christopher Plowe; Meera Venkatesan; Philip Sasi; Omar Lweno; Paul Mutani; Ali Hamad; Ali Mohammed; Alwisa Urassa; Tutu Mzee; Debbie Padilla; Adam Ruben; B. Kim Lee Sim; Marcel Tanner; Salim Abdulla; Stephen L. Hoffman
• Keywords: Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Adult; Cryopreservation; Male; Genotype; Injections, Intradermal; Plasmodium falciparum; Articles; Parasitemia; Tanzania; 3. Good health; Young Adult; Double-Blind Method; alpha-Thalassemia; Sporozoites; Malaria Vaccines; Animals; Humans; Malaria, Falciparum

Controlled human malaria infection (CHMI) by mosquito bite has been used to assess anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic, purified, cryopreserved Pf sporozoites, PfSPZ Challenge, were used to infect Dutch volunteers by intradermal injection. We conducted a double-blind, placebo-controlled trial to assess safety and infectivity of PfSPZ Challenge in adult male Tanzanians. Volunteers were injected intradermally with 10,000 (N = 12) or 25,000 (N = 12) PfSPZ or normal saline (N = 6). PfSPZ Challenge was well tolerated and safe. Eleven of 12 and 10 of 11 subjects, who received 10,000 and 25,000 PfSPZ respectively, developed parasitemia. In 10,000 versus 25,000 PfSPZ groups geometric mean days from injection to Pf positivity by thick blood film was 15.4 versus 13.5 (P = 0.023). Alpha-thalassemia heterozygosity had no apparent effect on infectivity. PfSPZ Challenge was safe, well tolerated, and infectious.