Malaria infection Infections and Infestations Plasmodium falciparum malaria
Conditions
Interventions
Bites of irradiated Plasmodium falciparum-infected Anopheles stephensi mosquitoes delivered at different time intervals for a total of at least 1000 bites. Controls were mock-infected irradiated An. s
six subjects who completed six immunizations and one subject who completed five immunizations (total seven subjects) received CHMI in the second cohort in 2002.
2. Mock-immunized group: In parallel
Sponsors
US Army Medical Research and Materiel Command
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy adults (male or non-pregnant female) 18-50 years of age or re-enrollees up to age 55 years 2. Available to participate for expected duration of an initial immunization series and challenge, for immunization and mock- immunization groups
Exclusion criteria
Exclusion criteria: 1. Age 50 (>60 for re-enrollees). Reason for exclusion of children: increased risks associated with the blood volumes needed for this study in individuals undergoing growth or of small body size ( 110 lbs. in order to be apheresed at the NIH facility 4. Known immunodeficiency (e.g. HIV positive), history of autoimmune or connective tissue disease, splenectomy, use of steroids or non-steroidal anti-inflammatory drugs, or any immunosuppressive therapy. Reason for exclusion: immune deficiency or immunosuppressive therapy could affect the immunological responses of volunteers and thus the results of the outcome measurements performed in this study 5. Evidence of active (acute or chronic) hepatitis B or C infection. Reason for exclusion: a serious, underlying medical condition could affect the immunological responses of volunteers (as above) or could increase the risk or severity of adverse events associated with participation in this study. 6. Clinical or laboratory evidence of significant hepatic, renal, cardiac, immunologic or hematologic disease. Reason for exclusion: same as for 5. 7. History of malaria infection, exposure to malaria infection, or receipt of a malaria vaccine. Reason for exclusion: New group 1 volunteers: a principal objective of Stage A is to study the transition from non-immune to immune status, and this will not be possible if volunteers are partially immune prior to immunization; Group 2 volunteers (infectivity controls): any pre-existing immunity could prevent these volunteers from acquiring malaria following challenge, falsely indicating that the challenge sporozoites were not viable; Group 3 volunteers (immunology controls): these are the malaria-negative controls for our laboratory assays, and thus cannot have a history of malaria or exposure to malaria. NB1: This criterion does not apply to the six volunteers from the previous irradiated sporozoite protocol who may elect to enroll in this protocol. NB2: If it is impossible to find enough volunteers meeting this criterion, it may be relaxed for Groups 1 and 3 (e.g., volunteers will not be excluded because of history of exposure to malaria) 8. History of anaphylactic reaction to mosquito bites for Groups 1 and 2 volunteers, or Group 3 volunteers if they are to undergo mock-immunization. Reason for exclusion: to avoid increased risk of anaphylaxis 9. Any other significant finding which in the opinion of the investigator would increase the risk of an adverse outcome for volunteers in this protocol, or to compromise the scientific objectives of this protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to parasitemia: starting seven days after CHMI daily Giemsa-stained thick blood films from each subject, examined by microscopy for the presence of P. falciparum blood stage parasites. Symptomatic, undiagnosed subjects will have additional smears performed at the discretion of the study doctor, not to exceed one smear every 8-12 hours. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety and tolerability of immunization by 1,000 bites of irradiated Pf-infected mosquitoes after examination and verbal questioning of subjects for local adverse events on day of immunization and at 24, 48 and 72 hours and one and two weeks after each immunization 2. Correlates of protection by providing immune samples to measure immunological responses and the targeted Pf antigens two weeks after each immunization and prior to CHMI administered by bites of P. falciparum-infected mosquitoes | — |
Countries
United States of America
Outcome results
None listed