Scott Halstead

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Scott Halstead
Scott Halstead fphoto.png
Born1930 [1]
NationalityAmerican
Occupation(s)Physician-scientist, virologist and epidemiologist
Known forResearch with mosquito-borne illnesses

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]

Contents

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 an 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]

That 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

Related Research Articles

<span class="mw-page-title-main">Vaccine</span> Pathogen-derived preparation that provides acquired immunity to an infectious disease

A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future.

<span class="mw-page-title-main">Dengue fever</span> Tropical disease caused by the dengue virus, transmitted by mosquito

Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin itching and skin rash. Recovery generally takes two to seven days. In a small proportion of cases, the disease develops into a more severe dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs.

<span class="mw-page-title-main">Herd immunity</span> Concept in epidemiology

Herd immunity is a form of indirect protection that applies only to contagious diseases. It occurs when a sufficient percentage of a population has become immune to an infection, whether through previous infections or vaccination, thereby reducing the likelihood of infection for individuals who lack immunity.

<span class="mw-page-title-main">Arbovirus</span> Common name for several species of virus

Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term arbovirus is a portmanteau word. Tibovirus is sometimes used to more specifically describe viruses transmitted by ticks, a superorder within the arthropods. Arboviruses can affect both animals and plants. In humans, symptoms of arbovirus infection generally occur 3–15 days after exposure to the virus and last three or four days. The most common clinical features of infection are fever, headache, and malaise, but encephalitis and viral hemorrhagic fever may also occur.

<i>Dengue virus</i> Species of virus

Dengue virus (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus. Four serotypes of the virus have been found, and a reported fifth has yet to be confirmed, all of which can cause the full spectrum of disease. Nevertheless, scientists' understanding of dengue virus may be simplistic as, rather than distinct antigenic groups, a continuum appears to exist. This same study identified 47 strains of dengue virus. Additionally, coinfection with and lack of rapid tests for Zika virus and chikungunya complicate matters in real-world infections.

A breakthrough infection is a case of illness in which a vaccinated individual becomes infected with the illness, because the vaccine has failed to provide complete immunity against the pathogen. Breakthrough infections have been identified in individuals immunized against a variety of diseases including mumps, varicella (Chickenpox), influenza, and COVID-19. The characteristics of the breakthrough infection are dependent on the virus itself. Often, infection of the vaccinated individual results in milder symptoms and shorter duration than if the infection were contracted naturally.

<span class="mw-page-title-main">Antibody-dependent enhancement</span> Antibodies rarely making an infection worse instead of better

Antibody-dependent enhancement (ADE), sometimes less precisely called immune enhancement or disease enhancement, is a phenomenon in which binding of a virus to suboptimal antibodies enhances its entry into host cells, followed by its replication. The suboptimal antibodies can result from natural infection or from vaccination. ADE may cause enhanced respiratory disease, but is not limited to respiratory disease. It has been observed in HIV, RSV virus and Dengue virus and is monitored for in vaccine development.

Immunization during pregnancy is the administration of a vaccine to a pregnant individual. This may be done either to protect the individual from disease or to induce an antibody response, such that the antibodies cross the placenta and provide passive immunity to the infant after birth. In many countries, including the US, Canada, UK, Australia and New Zealand, vaccination against influenza, COVID-19 and whooping cough is routinely offered during pregnancy.

<span class="mw-page-title-main">Rabies vaccine</span> Vaccines to prevent rabies in humans and animals

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<span class="mw-page-title-main">Mosquito-borne disease</span> Diseases caused by bacteria, viruses or parasites transmitted by mosquitoes

Mosquito-borne diseases or mosquito-borne illnesses are diseases caused by bacteria, viruses or parasites transmitted by mosquitoes. Nearly 700 million people get a mosquito-borne illness each year resulting in over 725,000 deaths.

A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses, intracellular bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.

The American Society of Tropical Medicine and Hygiene (ASTMH) is an Arlington, Virginia-based non-profit organization of scientists, clinicians, students and program professionals whose longstanding mission is to promote global health through the prevention and control of infectious and other diseases that disproportionately afflict the global poor. ASTMH members work in areas of research, health care and education that encompass laboratory science, international field studies, clinical care and country-wide programs of disease control. The current organization was formed in 1951 with the amalgamation of the American Society of Tropical Medicine, founded in 1903, and the National Malaria Society, founded in 1941.

<i>Zika virus</i> Species of flavivirus

Zika virus is a member of the virus family Flaviviridae. It is spread by daytime-active Aedes mosquitoes, such as A. aegypti and A. albopictus. Its name comes from the Ziika Forest of Uganda, where the virus was first isolated in 1947. Zika virus shares a genus with the dengue, yellow fever, Japanese encephalitis, and West Nile viruses. Since the 1950s, it has been known to occur within a narrow equatorial belt from Africa to Asia. From 2007 to 2016, the virus spread eastward, across the Pacific Ocean to the Americas, leading to the 2015–2016 Zika virus epidemic.

<span class="mw-page-title-main">Ira Longini</span> American biostatistician

Ira M. Longini is an American biostatistician and infectious disease epidemiologist.

Dengue vaccine is a vaccine used to prevent dengue fever in humans. Development of dengue vaccines began in the 1920s, but was hindered by the need to create immunity against all four dengue serotypes. As of 2023, there are two commercially available vaccines, sold under the brand names Dengvaxia and Qdenga.

<span class="mw-page-title-main">Edward Thomas Ryan</span>

Edward Thomas Ryan is an American microbiologist, immunologist, and physician at Harvard University and Massachusetts General Hospital. Ryan served as president of the American Society of Tropical Medicine and Hygiene from 2009 to 2010. Ryan is Professor of Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health, Professor of Medicine at Harvard Medical School, and Director of Global Infectious Diseases at the Massachusetts General Hospital. Ryan's research and clinical focus has been on infectious diseases associated with residing in, immigrating from, or traveling through resource-limited areas. Ryan is a Fellow of the American Society of Microbiology, the American Society of Tropical Medicine and Hygiene, the American College of Physicians, and the Infectious Diseases Society of America.

A Zika virus vaccine is designed to prevent the symptoms and complications of Zika virus infection in humans. As Zika virus infection of pregnant women may result in congenital defects in the newborn, the vaccine will attempt to protect against congenital Zika syndrome during the current or any future outbreak. As of April 2019, no vaccines have been approved for clinical use, however a number of vaccines are currently in clinical trials. The goal of a Zika virus vaccine is to produce specific antibodies against the Zika virus to prevent infection and severe disease. The challenges in developing a safe and effective vaccine include limiting side effects such as Guillain-Barré syndrome, a potential consequence of Zika virus infection. Additionally, as dengue virus is closely related to Zika virus, the vaccine needs to minimize the possibility of antibody-dependent enhancement of dengue virus infection.

The Dengvaxia controversy occurred in the Philippines when the dengue vaccine Dengvaxia was found to increase the risk of disease severity for some people who had received it.

Marylyn Martina Addo is a German infectiologist who is a Professor and the German Center for Infection Research (DZIF) Head of Infectious Disease at the University Medical Center Hamburg-Eppendorf. Addo has developed and tested vaccinations that protect people from Ebola virus disease and the MERS coronavirus EMC/2012. She is currently developing a viral vector based COVID-19 vaccine.

References

  1. 1 2 3 4 5 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. 1 2 "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. 1 2 "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. 1 2 3 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. 1 2 3 4 5 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. 1 2 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. 1 2 3 "Q&A with Dengue Expert Scott B. Halstead". American Society of Tropical Medicine and Hygiene. 2019-04-11. Retrieved 2020-09-20.
  17. 1 2 3 "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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