Scott Halstead

Scott Halstead is an American physician-scientist, virologist and epidemiologist known for his work in the fields of tropical medicine and vaccine development. He is considered one of the world's foremost authorities on viruses transmitted by mosquitoes, including Dengue, Japanese encephalitis, chikungunya and Zika.[1] He was one of the first researchers to identify the phenomenon known as antibody-dependent enhancement (ADE), where the antibodies generated from a first dengue infection can sometimes worsen the symptoms from a second infection.[2]

Scott Halstead
Born1930[1]
NationalityUnited States
OccupationPhysician-scientist, virologist and epidemiologist
Known forResearch with mosquito-borne illnesses

A former president of the global health organization American Society of Tropical Medicine and Hygiene (ASTMH), he also co-founded the Children's Vaccine Initiative, and founded the Pediatric Dengue Vaccine Initiative. He has published hundreds of papers and book chapters about viruses and diseases.

Early life and education

Scott Halstead was born in 1930 in Lucknow, India to Gordon P. and Helen Halstead, Methodist missionaries based in Lucknow.[3][4] In 1936, they moved to White Plains, NY, where he attended White Plains High School.[5]

He graduated from Yale University with a BA in sociology in 1951 and from Columbia University with a MD in 1955.[6][7]

Career

Early research

In 1957, Halstead was drafted by the U.S. Army Medical Corps.[1] He was assigned to the Department of Virus and Rickettsial Diseases (DVRD) in Sagamihara, Japan, and began studying mosquito-borne viruses.[7] He was then transferred to work as a virologist at the Department of Virus Diseases at the Walter Reed Army Institute of Research (WRAIR), in Washington, D.C.[7]

Dengue research

From 1961 to 1965, Halstead served as the director of the United States Army's SEATO infectious disease laboratory in Bangkok, Thailand.[1] During this time, he studied the dengue virus, and published research on the isolation and propagation of dengue virus in tissue culture; secondary infections in children; and dengue infection of infants born to dengue immune mothers.[8][9][10]

In 1965 Halstead left Bangkok to join the Yale Arbovirus Research Unit, part of the Yale School of Public Health. In a memoir published in 2002, he wrote that he worked at the newly opened Department of Epidemiology and Public Health, where he also worked on his dengue data set at Yale and published white papers that consolidated his research.[11]

In 1967 he presented the first paper describing severe dengue hemorrhagic fever as the result of a second infection by one of the other four types of dengue, a phenomenon now known as antibody-dependent enhancement (ADE).[9] This discovery influenced the future development of the dengue vaccine candidates.[9]

In 1968, Halstead retired from the Army. From 1968 to 1983, he served as the first chair of the Department of Tropical Medicine and Microbiology at the University of Hawaii School of Medicine, in Honolulu Hawaii.[3][5]

Public health and vaccine development

In 1983, Halstead joined the Health Sciences Division of the Rockefeller Foundation in New York as associate director, eventually becoming the group's director.[12][13]

During this period he helped found International Clinical Epidemiology Network (INCLEN), a global research and medical-education network designed to strengthen the research capacity of medical schools in the developing world.[14][15]

In 1990, while with the Rockefeller Foundation, Halstead co-founded the Children's Vaccine Initiative, now the Global Alliance for Vaccines and Immunization (GAVI).[16][14]

In 1991, Halstead was president of global health organization American Society of Tropical Medicine and Hygiene (ASTMH).[16]

From 1995 to 1997, he was director of infectious disease research for the U.S. Navy, becoming chief scientist in 1997.[17]

In 1999, he began working at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and remained a consultant with the U.S. Navy.[1][17]

In 2003, he founded the Pediatric Dengue Vaccine Initiative (PDVI) at the International Vaccine Institute, with $55M from the Gates Foundation. PDVI was founded to promote and fund basic science and applied clinical research to accelerate the development of dengue vaccines.[18] He served as director of research and development from 2003 to 2010.[17]

Dengvaxia controversy

Halstead played an important role during 2015–19 as a consultant and later as a scientific critic of Sanofi Pasteur’s Dengvaxia, the first dengue vaccine to be licensed for widespread use in countries where dengue is prevalent.[9] Based on his review and analysis of Sanofi's Phase 3 clinical trial data in 2016, he determined that the vaccine posed a substantial danger of contracting severe dengue to individuals who had no prior history of dengue infection.[9] Dr. Halstead and colleague Dr. Phillip Russell then proposed that the vaccine only be used after antibody testing, to rule out prior dengue exposure and avoid vaccination of sero-negative individuals.[19] Sanofi rebutted their analysis and sold Dengvaxia to the Philippines, where 700,000 school age children were vaccinated. An alarming rate of hospitalizations were found in vaccinated children following a dengue exposure.

After an analysis of Phase 3 clinical trial data, Sanofi scientists concluded that Halstead and Russell were correct and that Dengvaxia posed a significant risk for previously uninfected people. More cases were likely after vaccination due to a subsequent dengue infection.[20]

The led to the vaccine being banned in the Philippines, and Sanofi and Filipino public health officials were accused of malfeasance in proceeding with an unproven vaccination program. In 2018, Halstead served as an expert witness, testifying in person at Philippines Senate hearings on what became known as the Dengvaxia controversy.[21]

COVID-19

During the global COVID-19 pandemic that started in 2019, Halstead began researching protecting at-risk groups via antibody-based strategies including convalescent plasma and monoclonal antibodies.[22] He published papers about vaccine development and potential risks associated with ADE including vaccine hypersensitivity reactions, to assist with ongoing COVID-19 prevention.[23][24]

Awards and recognition

In 2017, Halstead received the Walter Reed Medal from ASTMH.[16]

See also

References

  1. Cohen, Jon (7 March 2016). "Q&A with Scott Halstead: Zika will subside in '5 years, max'". Science. doi:10.1126/science.aaf4154.
  2. Branswell, Helen (17 June 2018). "Dengue Vaccine Maker Struggles to Find a Diagnostic That Will Make Its Product Safe to Use". Scientific American.
  3. "Tropical Medicine celebrates a long record of faculty achievements and an upcoming birthday". University of Hawaii at Manoa. 2020-01-23. Retrieved 2020-09-20.
  4. Burke, Donald S. (1 March 1992). "Introduction to the 1991 Astmh Presidential Address". The American Journal of Tropical Medicine and Hygiene. 46 (3): 239–240. doi:10.4269/ajtmh.1992.46.239. PMID 1558262.
  5. "Dr. Scott B. Halstead" (PDF). White Plains Public Schools. 2016-03-07. Retrieved 2020-09-20.
  6. Whitehorn, James; Farrar, Jeremy (February 2014). Clinical Insights: Dengue: Transmission, Diagnosis & Surveillance. doi:10.2217/ebo.13.741. ISBN 978-1-78084-384-1.
  7. Glaser, Vicki (March 2007). "Interview with Scott B. Halstead, M.D.". Vector-Borne and Zoonotic Diseases. 7 (1): 99–105. doi:10.1089/vbz.2007.9998. PMID 17417962.
  8. Halstead, Scott B.; Sukhavachana, Pairatana; Nisalak, Ananda (May 1964). "In vitro Recovery of Dengue Viruses from Naturally Infected Human Beings and Arthropods". Nature. 202 (4935): 931–932. Bibcode:1964Natur.202..931H. doi:10.1038/202931a0. PMID 14190111. S2CID 4190929.
  9. Yasmin, Seema; Mukerjee, Madhusree (April 2019). "How the World's First Dengue Vaccination Drive Ended in Disaster". Scientific American.
  10. Halstead, S. B. (April 1970). "Observations related to pathogensis of dengue hemorrhagic fever. VI. Hypotheses and discussion". The Yale Journal of Biology and Medicine. 42 (5): 350–362. PMC 2591710. PMID 5419208.
  11. Halstead, Scott B. (December 2002). "Dengue hemorrhagic fever: two infections and antibody dependent enhancement, a brief history and personal memoir". Revista Cubana de Medicina Tropical. 54 (3): 171–179. PMID 15846943.
  12. "Layne Halstead, Dietitian, Weds". NY Times. 1988-06-26. Retrieved 2020-09-20.
  13. "HEALTH & WELL-BEING" (PDF). Rockefeller Foundation. 2014-01-01. Retrieved 2020-09-20.
  14. Muraskin, William (2014-01-01). The Politics of International Health: The Children's Vaccine Initiative and the Struggle to Develop Vaccines for the Third World. SUNY Press. ISBN 9780791439999. Retrieved 2020-09-20.
  15. Halstead, Scott B.; Tugwell, Peter; Bennett, Kathryn (January 1991). "The international clinical epidemiology network (inclen): A progress report". Journal of Clinical Epidemiology. 44 (6): 579–589. doi:10.1016/0895-4356(91)90222-u. PMID 2037863. S2CID 25472544.
  16. "Q&A with Dengue Expert Scott B. Halstead". American Society of Tropical Medicine and Hygiene. 2019-04-11. Retrieved 2020-09-20.
  17. "Scott B. Halstead". Marquis Top Health Care Providers. 2020-01-29. Retrieved 2020-09-20.
  18. "Research on Dengue Vaccine Gets A $55 Million Foundation Grant". Wall Street Journal. 2003-09-10. Retrieved 2020-09-20.
  19. "Sanofi restricts dengue vaccine but downplays antibody enhancement". CIDRAP. 2017-12-01. Retrieved 2020-09-20.
  20. Villamor, Felipe (1 December 2017). "Philippines Suspends Dengue Shots After Drug Firm's Warning". The New York Times.
  21. Fry, Erika (26 November 2019). "Epidemic of fear: How the trouble-ridden debut of a breakthrough vaccine sparked a panic". Fortune.
  22. Halstead, Scott B.; Akkina, Ramesh (29 May 2020). "COVID-19 and SARS Coronavirus 2: Antibodies for the Immediate Rescue and Recovery Phase". Frontiers in Immunology. 11: 1196. doi:10.3389/fimmu.2020.01196. PMC 7272599. PMID 32574267.
  23. Halstead, Scott B; Katzelnick, Leah (13 November 2020). "COVID-19 Vaccines: Should We Fear ADE?". The Journal of Infectious Diseases. 222 (12): 1946–1950. doi:10.1093/infdis/jiaa518. PMC 7454712. PMID 32785649.
  24. Garber, Ken (5 June 2020). "Coronavirus vaccine developers wary of errant antibodies". Nature Biotechnology. doi:10.1038/d41587-020-00016-w. PMID 32641838. S2CID 219908416.
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