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Entomologist s’ Role in the Clinical Trials of Investigational Malaria Vaccines and Drugs

Entomologist s’ Role in the Clinical Trials of Investigational Malaria Vaccines and Drugs. MAJ Jittawadee R. Murphy, PhD Department of Mosquito Biology Division of Entomology Walter Reed Army Institute of Research Silver Spring, MD. DoD Pest Management Workshop, 9 FEB 10. Outline.

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Entomologist s’ Role in the Clinical Trials of Investigational Malaria Vaccines and Drugs

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  1. Entomologists’ Role in the Clinical Trials of Investigational Malaria Vaccines and Drugs MAJ Jittawadee R. Murphy, PhD Department of Mosquito Biology Division of Entomology Walter Reed Army Institute of Research Silver Spring, MD DoD Pest Management Workshop, 9 FEB 10

  2. Outline • Human malaria challenge • Production of malaria infected mosquitoes • Preparation for the challenge • Challenge day • Challenge using imported infected mosquitoes • Summary DoD Pest Management Workshop, 9 FEB 10

  3. Human malaria challenge Malaria Life Cycle Background • R&D of anti-malarial vaccines and drugs • Evaluation of effectiveness mouse, non-human primate model  human challenge • Clinical Trial Center (CTC) and Entomology • Scheduling is critical • CTC- recruit volunteers, Human Use Protocol, administer vaccine or drug, close contact with Ento for challenge DoD Pest Management Workshop, 9 FEB 10

  4. Production of malaria infected mosquitoes • Axenic cultures of malaria parasites from asexual to sexual stages i. e. rings to gametocytes to infect mosq. • 2. Mosquito colonization- Anopheles stephensi Plasmodium falciparumWT NF54 - 8 weeks 3D7 - 6 wks DoD Pest Management Workshop, 9 FEB 10

  5. Prod. of mal. infected mosquitoes (2 of 3) • 3. Membrane feeding of mosquitoes with human blood/serum mixed with gametocyte cultures • 4. Incubating infected mosquitoes (26°C, 80%RH) DoD Pest Management Workshop, 9 FEB 10

  6. Prod. of mal. infected mosquitoes (3 of 3) • Dissection of mosquitoes: • midguts for oocysts at 7 days post-feed • salivary glands for sporozoites at 14 days post-feed • Gold Standard sporozoite ratings: 0 -4 DoD Pest Management Workshop, 9 FEB 10

  7. Preparation for the challenge • Select the highest infectious batches of mosquitoes- starve overnight • Preparation of challenge room • Volunteers’ seats • Timers, surgical towels • Volunteers’ sign-in sheets • Physician and crash cart space • Preparation of dissection room • Dissection scopes and tools • Dissection result forms DoD Pest Management Workshop, 9 FEB 10

  8. Challenge Day • Objective– 5 infective bites/volunteer • Aspirate 5 mosquitoes / carton (pint-size) • Volunteers arrive, sign-in • Moderator, physician, dissectors DoD Pest Management Workshop, 9 FEB 10

  9. Challenge Day (2 of 2) • Expose volunteer’s arm to bites for 5 minutes • Dissect for sporozoite ratings • Ratings 2-4 (11- >1,000 spz.) = infective bites DoD Pest Management Workshop, 9 FEB 10

  10. Challenge using imported infected mosquitoes Plasmodium vivax– infected mosquitoes imported from Thailand • AFRIMS (Armed Forces Research Institute of Med.Sciences) • Hand carry infected mosquitoes • Permits: CDC, USDA APHIS, DOT • Airport & Airlines notified/approved in advance: X-ray exemption at check-in, lay over 2. Courier arrival DoD Pest Management Workshop, 9 FEB 10

  11. Challenge using imported infected mosquitoes(2 of 2) 3. Mosquitoes: ideally at oocyst stage • Unpack- cartons in IATA-approved EXAKT packs, in pelican case • Dissect, rate sporozoite infection • Select the highest infectious mosquitoes for challenge • Perform malaria human challenge

  12. Performing Challenges Off Site Challenges at: Oxford Univ., England, U. of MD, Baltimore, Kenya? • Produce malaria-infected mosquitoes • Pack in 4-layered IATA-approved containers • Hand carry at sporozoite stage in pelican case • Permits- DOT, TSA, Airlines, X-ray exemption DoD Pest Management Workshop, 9 FEB 10

  13. Summary • Entomologists play an important role from beginning to end • Challenging job for entomologists • Pressure for successful challenges The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. DoD Pest Management Workshop, 9 FEB 10

  14. Acknowledgements • WRAIR Mosquito Biology Dept. • Megan Dowler, Tatyana Savranskaya, Brooke Bozick, Michael Porter, Kyle Loughlin, Dr. Jackie Williams, and LTC Michael O’Neil • WRAIR Clinical Trial Center • USMMVP (US Military Malaria Vaccine Program) • AFRIMS Entomology Dept. • NMRC: CDR David Fryauff DoD Pest Management Workshop, 9 FEB 10

  15. Questions? DoD Pest Management Workshop, 9 FEB 10

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