Controlled human malaria infection of Tanzanians by intradermal injection of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites.

Seif Shekalaghe,Stephen L Hoffman,Ali Hamad,Anita Manoj,Beatus Simon,Eric Huber,L W Preston Church,Mastidia Rutaihwa,Tobias Schindler,Debbie Padilla,Salim Abdulla,Mwajuma Chemba,Marcel Tanner,Alwisa Urassa,Ali Mohammed,Elizabeth Saverino,B Kim Lee Sim,Paul Mutani,Eric R James,Philip Sasi,Peter F Billingsley,Maximillian Mpina,Cornelus C Hermsen,Meera Venkatesan,Robert W Sauerwein,Tutu Mzee,Anusha Gunasekera,Omar Lweno,Christopher V Plowe ,Omar Juma ,Adam J Ruben ,Claudia Daubenberger

doi:10.4269/ajtmh.14-0119

Seif Shekalaghe, Stephen L Hoffman + Show 30 more

Open Access

https://doi.org/10.4269/ajtmh.14-0119

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Abstract

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.

Highlights

Controlled human malaria infection (CHMI), intentional infection of subjects with malaria parasites, has been used for treating patients with syphilis[1,2] and in research for nearly a century.[3]
In the bridging group the infection rate, but not the pre-patent period, was comparable to that observed for the same dose in young adult Dutch subjects. These findings provide the foundation for using CHMI with Pf sporozoites (PfSPZ) Challenge to assess the protective efficacy of antimalarial vaccines and drugs in Africa
Eleven volunteers who received 10,000 PfSPZ (Table 2A) and 10 volunteers who received 25,000 PfSPZ (Table 2B) developed parasitemia detected by thick blood smear and confirmed by quantitative polymerase chain reaction (qPCR)

Summary

Introduction

Controlled human malaria infection (CHMI), intentional infection of subjects with malaria parasites, has been used for treating patients with syphilis[1,2] and in research for nearly a century.[3] Since the development in the 1980s of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures,[4,5,6] CHMI has been used repeatedly and successfully in more than 1,500 volunteers in the United States and Europe.[6,7,8,9,10] Africa suffers the most morbidity and mortality from malaria, and could benefit significantly by using CHMI to facilitate development of new vaccines, drugs, and diagnostics for malaria, and for understanding innate and acquired resistance to the parasites that cause malaria. There was infection, but no dose response, presumably because increasing the dose did not increase the numbers of sporozoites that exited the skin, entered the circulation, and invaded hepatocytes.[12]

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