Use of prophylactic NSAIDs to improve tolerability of malaria-associated symptoms at high doses of Sanaria® PfSPZ-CVac (PfSPZ Challenge under chloroquine prophylaxis)

Authors

• DM Cook
• A Mwakingwe-Omari
• SA Healy
• J Lane
• S Pfeiffer
• S Kalhori
• C Wyatt
• I Zaidi
• T Murshedkar
• A Ruben
• S Chakravarty
• A Manoj
• A Gunasekera
• B Kim Lee Sim
• PF Billingsley
• ER James
• TL Richie
• SL Hoffman
• PE Duffy

Abstract

Introduction: Symptoms associated with malaria infection are common in malaria vaccine trials that administer live malaria sporozoites given under antimalarial chemoprophylaxis, a vaccine strategy termed CVac. This approach has achieved high-level (>90%) protection in malaria-naïve volunteers in recent clinical trials. Reducing the severity of malaria-associated symptoms (MAS) would significantly improve the tolerability and viability of this promising vaccine strategy. Background: An ongoing clinical trial (NCT03083847) at the NIH Clinical Center is evaluating healthy malaria-naïve adult volunteers immunized by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated Plasmodium falciparum sporozoites (PfSPZ Challenge) while taking antimalarial chemoprophylaxis (PfSPZ-CVac) using either chloroquine (CQ) or pyrimethamine as the antimalarial chemoprophylaxis agent. A pilot arm received a high dose (200K) of sporozoites of PfSPZ Challenge in August and September of 2017. This group experienced several severe symptoms including fever, chills, and myalgia. In an effort to improve tolerability in the future it was decided to administer prophylactic non-steroidal anti-inflammatory drugs (NSAIDs) during the main phase of the study in January 2018 in a comparable arm. Methods: Participants in the CQ arm (n=5) of the main study of NCT03083847 were asked to take their choice of NSAID (either ibuprofen or naproxen) whether or not they felt any malaria-associated symptoms. Participants were seen twice daily for clinic visits during this time period. Their symptoms were graded by severity according to the FDA’s Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Results: Participants in the pilot group (n=4, no prophylactic NSAIDs) experienced 19 mild symptoms, 5 moderate symptoms, and 3 severe symptoms. For the main study group (n=5, prophylactic NSAIDs) there were 23 mild symptoms and no moderate or severe symptoms. Conclusions: There was a small (3.1%) per-person reduction in mild malaria-associated symptoms in the group using prophylactic NSAIDs. More impressively, there were no moderate or severe symptoms reported at all in the prophylactic NSAIDs group. This indicates that the use of prophylactic NSAIDs may reduce or eliminate severe malaria-associated symptoms if used during future PfSPZ-CVac trials, furthering the effort to develop an effective malaria vaccine.

Scientific Focus Area: Microbiology and Infectious Diseases

This page was last updated on Friday, March 26, 2021