Presentation is loading. Please wait.

Presentation is loading. Please wait.

Entomologists’ Role in the Clinical Trials of Investigational Malaria Vaccines and Drugs MAJ Jittawadee R. Murphy, PhD Department of Mosquito Biology Division.

Similar presentations


Presentation on theme: "Entomologists’ Role in the Clinical Trials of Investigational Malaria Vaccines and Drugs MAJ Jittawadee R. Murphy, PhD Department of Mosquito Biology Division."— Presentation transcript:

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 DoD Pest Management Workshop, 9 FEB 10 1.Human malaria challenge 2.Production of malaria infected mosquitoes 3.Preparation for the challenge 4.Challenge day 5.Challenge using imported infected mosquitoes 6.Summary

3 Human malaria challenge DoD Pest Management Workshop, 9 FEB 10 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 Malaria Life CycleBackground

4 Production of malaria infected mosquitoes DoD Pest Management Workshop, 9 FEB 10 1.Axenic cultures of malaria parasites from asexual to sexual stages i. e. rings to gametocytes to infect mosq. 2. Mosquito colonization- Anopheles stephensi Plasmodium falciparum WT NF weeks 3D7 - 6 wks

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

6 Prod. of mal. infected mosquitoes (3 of 3) DoD Pest Management Workshop, 9 FEB 10 5.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

7 Preparation for the challenge DoD Pest Management Workshop, 9 FEB 10 1.Select the highest infectious batches of mosquitoes- starve overnight 2.Preparation of challenge room  Volunteers’ seats  Timers, surgical towels  Volunteers’ sign-in sheets  Physician and crash cart space 3.Preparation of dissection room  Dissection scopes and tools  Dissection result forms

8 Challenge Day DoD Pest Management Workshop, 9 FEB 10 1.Objective – 5 infective bites/volunteer  Aspirate 5 mosquitoes / carton (pint-size) 2.Volunteers arrive, sign-in  Moderator, physician, dissectors

9 Challenge Day (2 of 2) DoD Pest Management Workshop, 9 FEB 10 3.Expose volunteer’s arm to bites for 5 minutes 4.Dissect for sporozoite ratings  Ratings 2-4 (11- >1,000 spz.) = infective bites

10 Challenge using imported infected mosquitoes Plasmodium vivax – infected mosquitoes imported from Thailand  AFRIMS (Armed Forces Research Institute of Med.Sciences) 1.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 4.Dissect, rate sporozoite infection 5.Select the highest infectious mosquitoes for challenge 6.Perform malaria human challenge

12 Performing Challenges Off Site Challenges at: Oxford Univ., England, U. of MD, Baltimore, Kenya? 1.Produce malaria-infected mosquitoes 2.Pack in 4-layered IATA-approved containers 3.Hand carry at sporozoite stage in pelican case 4.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


Download ppt "Entomologists’ Role in the Clinical Trials of Investigational Malaria Vaccines and Drugs MAJ Jittawadee R. Murphy, PhD Department of Mosquito Biology Division."

Similar presentations


Ads by Google