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

Seif Shekalaghe, Mastidia Rutaihwa, Peter F Billingsley, Mwajuma Chemba, Claudia A Daubenberger, 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, Seif Shekalaghe, Mastidia Rutaihwa, Peter F Billingsley, Mwajuma Chemba, Claudia A Daubenberger, 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

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.

Conflict of interest statement

Disclosure: Sanaria Inc. manufactured PfSPZ Challenge, and Protein Potential LLC is affiliated with Sanaria. Thus, all authors associated with Sanaria or Protein Potential have potential conflicts of interest. There are no other conflicts of interest.

© The American Society of Tropical Medicine and Hygiene.

Figures

Figure 1.
Figure 1.
Flow chart of recruitment and study design.
Figure 2.
Figure 2.
Parasite density as measured by qPCR in the 10,000 (A) and 25,000 (B) PfSPZ dose groups. Panels A (N = 11) and B (N = 10) show individual and geometric mean parasite density (parasites/mL) of positive volunteers from day of inoculation through last day of positivity after initiation of treatment. Panel C shows an overlay of geometric mean parasite densities with confidence intervals (95%) of positive volunteers in each group (Black line = Group 1, 10,000 PfSPZ; Grey line = Group 2, 25,000 PfSPZ).* *For Panel B, the geometric mean was calculated excluding the single volunteer who first became positive on Day 16.

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