A Systems Biology Approach to Malaria Immunity
Condition: Plasmodium Falciparum Infection
MeSH terms: Infections; Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase I study that will assess the acquisition of immunity to Pf malaria over the
      course of 5 sequential Controlled Human Malaria Infections (CHMI) over 2-4 years, in 10
      healthy adult participants. 10 subjects will initially be challenged with 5 uninfected
      mosquitoes (mock), followed by 5 challenges with 5 mosquitoes infected with drug sensitive,
      P. falciparum parasites (strain NF54) 2, 8, 14-20, 20-32, and 32-36 months later. For the
      final four infective CMHIs six additional immunologic malaria-naïve subjects will be enrolled
      and challenged as infectivity controls. If dropouts occur within the original 10 person
      cohort, and two or more CHMI remain, back-up replacement volunteers will be recruited to
      undergo successive CHMI with the core group. All volunteers (repeat CHMI subjects and
      infectivity controls) will be evaluated as part of an inpatient stay (or outpatient daily
      follow-up) to diagnose Pf malaria infection and treat with Coartem(R)
      (artemether/lumefantrine) or Malarone(R) (Atovaquone/proguanil). Daily observation will occur
      from Study Days 9-19 or until three-day directly observed therapy for P. falciparum infection
      is complete and two negative smears separated by a time interval >12 hours have been
      documented. A third negative smear >12 hours after the previous two daily smears will be
      documented to affirm malaria cure. Infectivity Controls enrolled as part of CHMI #5 will be
      treated based on concomitant us qPCR results. The repeat CHMI subjects will have additional
      outpatient visits days 1, 3, 5, and 7 after the challenge to obtain blood samples to monitor
      the development of immunity. The study is expected to last for 48 months and will include
      approximately 34 healthy male and female volunteers (10 active study volunteers and 18 naïve
      controls to confirm Pf infectivity during the 2nd -5th CHMI challenges) ages 18 to 50 years,
      inclusive, from the greater Baltimore community. The primary objective of this study is to
      determine whether protective immunity against parasite infection develops following repeat
      CHMI.
    

Detailed description: 
      This is a phase I study that will assess the acquisition of immunity to Pf malaria over the
      course of 5 sequential Controlled Human Malaria Infections (CHMI) over 2-4 years, in 10
      healthy adult participants. 10 subjects will initially be challenged with 5 uninfected
      mosquitoes (mock), followed by 5 challenges with 5 mosquitoes infected with drug sensitive,
      P. falciparum parasites (strain NF54) 2, 8, 14-20, 20-32, and 32-36 months later. For the
      final four infective CMHIs six additional immunologic malaria-naïve subjects will be enrolled
      and challenged as infectivity controls. If dropouts occur within the original 10 person
      cohort, and two or more CHMI remain, back-up replacement volunteers will be recruited to
      undergo successive CHMI with the core group. All volunteers (repeat CHMI subjects and
      infectivity controls) will be evaluated as part of an inpatient stay (or outpatient daily
      follow-up) to diagnose Pf malaria infection and treat with Coartem(R)
      (artemether/lumefantrine) or Malarone(R) (Atovaquone/proguanil). Daily observation will occur
      from Study Days 9-19 or until three-day directly observed therapy for P. falciparum infection
      is complete and two negative smears separated by a time interval >12 hours have been
      documented. A third negative smear >12 hours after the previous two daily smears will be
      documented to affirm malaria cure. Infectivity Controls enrolled as part of CHMI #5 will be
      treated based on concomitant us qPCR results. The repeat CHMI subjects will have additional
      outpatient visits days 1, 3, 5, and 7 after the challenge to obtain blood samples to monitor
      the development of immunity. The study is expected to last for 48 months and will include
      approximately 34 healthy male and female volunteers (10 active study volunteers and 18 naïve
      controls to confirm Pf infectivity during the 2nd -5th CHMI challenges) ages 18 to 50 years,
      inclusive, from the greater Baltimore community. The primary objective of this study is to
      determine whether protective immunity against parasite infection develops following repeat
      CHMI. The secondary objectives are to: 1) determine whether clinical signs and symptoms of
      malaria decrease in intensity and duration following repeat CHMI, 2) track the production of
      antibodies that react with P. falciparum sporozoites and blood stage parasites.
    

Intervention name(s): NF54 P. falciparum malaria challenge
Intervention type(s): Biological
Intervention description(s): Aseptically-raised A. stephensi female mosquitoes infected with aseptically-raised P. falciparum parasites of the NF54 strain.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Biology; falciparum; Immunity; Infections; Malaria; Pf; Plasmodium; Systems