BACKGROUND: Since 1986, investigators at Walter Reed Army Institute of Research (WRAIR) have been using controlled human malaria challenge (CHMI) in malaria-naive adults in order to define the protective efficacy of a malaria vaccine and thus guide programmatic decisions on vaccine candidates. Adapting this model to the dengue field could provide similar evidential support for a vaccine or therapeutic product. METHODS: After completing a vaccine regimen, volunteers are bitten by 5 malaria-infected female Anopheles mosquitoes in a controlled environment. Volunteers are then monitored daily for peripheral parasitemia in a hotel setting with 24-hour access to a nurse and physician. If a single verified parasite is detected, effective antimalarials are promptly administered. RESULTS: The vast majority of the over 1000 volunteers having participated in CHMI clinical studies have done so at US military research centers. Numerous pre-erythrocytic and erythrocytic vaccine candidates have been evaluated safely and without any related serious adverse events using this model, including the soon-to-be licensed RTS,S malaria vaccine. CONCLUSION: The lessons learned from over 25 years of experience in consistent, careful preparation and execution of the CHMI model at WRAIR can provide a foundation from which the dengue field can begin to develop a rigorous and safe "CHDI" model.
BACKGROUND: Since 1986, investigators at Walter Reed Army Institute of Research (WRAIR) have been using controlled humanmalaria challenge (CHMI) in malaria-naive adults in order to define the protective efficacy of a malaria vaccine and thus guide programmatic decisions on vaccine candidates. Adapting this model to the dengue field could provide similar evidential support for a vaccine or therapeutic product. METHODS: After completing a vaccine regimen, volunteers are bitten by 5 malaria-infected female Anopheles mosquitoes in a controlled environment. Volunteers are then monitored daily for peripheral parasitemia in a hotel setting with 24-hour access to a nurse and physician. If a single verified parasite is detected, effective antimalarials are promptly administered. RESULTS: The vast majority of the over 1000 volunteers having participated in CHMI clinical studies have done so at US military research centers. Numerous pre-erythrocytic and erythrocytic vaccine candidates have been evaluated safely and without any related serious adverse events using this model, including the soon-to-be licensed RTS,S malaria vaccine. CONCLUSION: The lessons learned from over 25 years of experience in consistent, careful preparation and execution of the CHMI model at WRAIR can provide a foundation from which the dengue field can begin to develop a rigorous and safe "CHDI" model.
Authors: DeAnna J Friedman-Klabanoff; Matthew B Laurens; Andrea A Berry; Mark A Travassos; Matthew Adams; Kathy A Strauss; Biraj Shrestha; Myron M Levine; Robert Edelman; Kirsten E Lyke Journal: Am J Trop Med Hyg Date: 2019-03 Impact factor: 2.345
Authors: Cysha E Hall; Lisa M Hagan; Elke Bergmann-Leitner; Donna M Tosh; Jason W Bennett; Jason A Regules; Ilin Chuang; Evelina Angov; Sheetij Dutta; Debasish Chattopadhyay; Anjali Yadava Journal: Infect Immun Date: 2019-02-21 Impact factor: 3.441
Authors: Martin R Gaudinski; Nina M Berkowitz; Azza H Idris; Emily E Coates; LaSonji A Holman; Floreliz Mendoza; Ingelise J Gordon; Sarah H Plummer; Olga Trofymenko; Zonghui Hu; Andrezza Campos Chagas; Sarah O'Connell; Manjula Basappa; Naomi Douek; Sandeep R Narpala; Christopher R Barry; Alicia T Widge; Renunda Hicks; Seemal F Awan; Richard L Wu; Somia Hickman; Diane Wycuff; Judy A Stein; Christopher Case; Brian P Evans; Kevin Carlton; Jason G Gall; Sandra Vazquez; Britta Flach; Grace L Chen; Joseph R Francica; Barbara J Flynn; Neville K Kisalu; Edmund V Capparelli; Adrian McDermott; John R Mascola; Julie E Ledgerwood; Robert A Seder Journal: N Engl J Med Date: 2021-08-11 Impact factor: 91.245
Authors: Jessica E Manning; David M Morens; Shaden Kamhawi; Jesus G Valenzuela; Matthew Memoli Journal: J Infect Dis Date: 2018-06-05 Impact factor: 5.226
Authors: Dorothy E Loy; Meagan A Rubel; Alexa N Avitto; Weimin Liu; Yingying Li; Gerald H Learn; Alessia Ranciaro; Eric Mbunwe; Charles Fokunang; Alfred K Njamnshi; Paul M Sharp; Sarah A Tishkoff; Beatrice H Hahn Journal: Int J Parasitol Date: 2018-02-21 Impact factor: 3.981