Malaria Challenge With NF54 Strain
Condition: Plasmodium Falciparum Infection
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine how many infected mosquito bites are required to
      reliably give volunteers a case of malaria. It is expected that volunteers will develop
      malaria and may have symptoms. Safety is the main concern. A malaria challenge is given by
      allowing a volunteer to receive 1, 3, or 5 mosquito's bites. Then participants are carefully
      followed and blood is tested. The study will also look at how immune systems (the cells and
      substances that protect the body from infection and foreign matter) respond after mosquito
      bite challenges. About 38 subjects (aged 18-40 years) from the greater Baltimore, Maryland
      (United States) community will participate and may stay overnight for 10 days at a local
      medical center. Procedures include medical screening, assignment to a dose group, a mosquito
      bite challenge, and 56 day follow-up. Volunteers will be contacted by telephone at 6 and 12
      months after the malaria challenge.
    

Detailed description: 
      This is a randomized trial of the aseptically raised anopheles mosquito malaria challenge.
      Adults aged 18-40 years will be randomized to one group of 18 subjects (Part A) or a second
      group of 20 subjects (Part B). Adults will be randomized to receive 1, 3 or 5 bites of
      Anopheles (A.) stephensi mosquitoes infected with the NF54 strain of chloroquine-sensitive
      Plasmodium (P.) falciparum. Part B will be informed by the results of Part A. Thus, a total
      of approximately 38 adults will receive a malaria challenge. The challenge for Part A will be
      given on day 0 with the subsequent group (Part B) commencing after a 56 day safety review.
      Solicited adverse events will be recorded on the days of malaria challenge, outpatient days
      5-7, 19-28, 35, 42, 49, and 56 post-challenge event. Inpatient analysis will occur from Days
      8-18 or until three-day directly observed therapy for P. falciparum infection is complete.
      Additional outpatient, post-malaria infection follow-up will occur weekly for 4 weeks.
      Unsolicited adverse events will be recorded for 56 days after each malaria challenge event.
      Participants will receive a telephone follow-up six and twelve months after enrollment. The
      primary objective is to develop and evaluate the safety and tolerability of a new human
      malaria challenge model using aseptically-raised anopheles mosquitoes infected with the NF54
      isolate of P. falciparum and reared under current Good Manufacturing Practices (cGMPs)
      conditions. Secondary objectives are to obtain information on the minimum number of A.
      stephensi bites required to safely achieve 100 percent adult human volunteer infectivity
      (Malaria challenge, Part A); obtain information on the minimum quantity of A. stephensi bites
      in a second challenge study to achieve 100 percent adult human volunteer infectivity (Malaria
      challenge, Part B); develop molecular diagnostic techniques for rapid and accurate real-time
      diagnosis of P. falciparum infection to assess the role as a new diagnostic standard for P.
      falciparum challenge studies.
    

Intervention name(s): NF54 P. falciparum isolate
Intervention type(s): Biological
Intervention description(s): 1, 3, 5 or N bites from aseptically-raised Anopheles stephensi female mosquitoes infected with Plasmodium falciparum parasites of the NF54 strain.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: Plasmodium falciparum, NF54, Anopheles stephensi, mosquito, malaria