Scott B. Halstead's research while affiliated with Uniformed Services University of the Health Sciences and other places
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Publications (269)
My arbovirus career occurred in four stages, roughly 15 years each: US Army Medical Corps, University of Hawaii School of Medicine, Rockefeller Foundation and Pediatric Dengue Vaccine Initiative. I entered the Army through the Physicians Draft and was assigned to the Department of Viral and Rickettsial Diseases, 406th Medical General Laboratory, in...
Vaccine-associated enhanced disease (VAED) is a serious barrier to attaining successful virus vaccines in human and veterinary medicine. VAED occurs as two different immunopathologies, antibody-dependent enhancement (ADE) and vaccine-associated hypersensitivity (VAH). ADE contributes to the pathology of disease caused by four dengue viruses (DENV)...
The only licensed dengue vaccine, Dengvaxia ® , increases risk of severe dengue when given to individuals without prior dengue virus (DENV) infection but is protective against future disease in those with prior DENV immunity. The World Health Organization has recommended using rapid diagnostic tests (RDT) to determine history of prior DENV infectio...
In tropical and subtropical countries four dengue viruses (DENV) produce mild disease and a potentially fatal vascular permeability syndrome. Unique antigenic and biological properties of DENVs contribute to vaccine development delays. Three tissue culture-based tetravalent candidate dengue vaccines have advanced to phase 3 clinical testing. Sanofi...
Might COVID 19 vaccines sensitize humans to antibody dependent enhanced (ADE) breakthrough infections? This outcome is unlikely because coronavirus diseases in humans lack the clinical, epidemiological, biological or pathological attributes of ADE disease exemplified by the dengue viruses (DENV). In contrast to DENV, SARS and MERS CoVs predominantl...
Dengvaxia, a chimeric yellow fever tetravalent dengue vaccine developed by SanofiPasteur is widely licensed in dengue-endemic countries. In a large cohort study Dengvaxia was found to partially protect children who had prior dengue virus (DENV) infections but sensitized seronegative children to breakthrough DENV disease of enhanced severity. In 201...
Novel Coronavirus Disease (COVID-19): The Need for Immunoprevention at Industrial Scale.
Background:
Genetic risk factors for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and dengue fever (DF) are limited, in particular there are sparse data on genetic risk across diverse populations.
Methods:
We conducted a genome-wide association study (GWAS) in a derivation and validation sample of 7, 460 participants of Latin America...
Rationale for review
Dengue is a frequent cause of febrile illness among travellers and has overtaken malaria as the leading cause of febrile illness for those traveling to Southeast Asia. The purpose is to review the risk of dengue and severe dengue in travellers with a particular focus on the pathogenesis and clinical management of severe dengue....
Dengue viruses are endemic in most tropical and subtropical countries where they produce disease ranging from a mild fever to a severe, potentially fatal vascular permeability syndrome. We reviewed the status of development and testing in children of three vaccines designed to protect against the four dengue viruses. The first dengue virus vaccine,...
Chikungunya, dengue, yellow fever and Zika viruses share many attributes. All are complex and widespread zoonoses of subhuman primates that have made successful transitions to the urban Aedes aegypti transmission cycle. More important, they have an established record of travelling, having moved from their place of origin hundreds of years ago, some...
This is a selective review of recent publications on dengue clinical features, epidemiology, pathogenesis, and vaccine development placed in a context of observations made over the past half century. Four dengue viruses (DENVs) are transmitted by urban cycle mosquitoes causing diseases whose nature and severity are influenced by interacting factors...
Dengue viruses cause severe and sudden human epidemics worldwide. The secreted form of the nonstructural protein 1 (sNS1) of dengue virus causes vascular leakage, a hallmark of severe dengue disease. Here, we reverse engineered the T164S mutation of NS1, associated with the severity of dengue epidemics in the Americas, into a dengue virus serotype...
A tetravalent live-attenuated 3-dose vaccine composed of chimeras of yellow fever 17D and the four dengue viruses (CYD, also called Dengvaxia) completed phase 3 clinical testing in over 35,000 children leading to a recommendation that vaccine be administered to >/ = 9 year-olds residing in highly dengue- endemic countries. When clinical trial resul...
During a large scale clinical efficacy trial of the Sanofipasteur live-attenuated tetravalent dengue vaccine (Dengvaxia), features of hospitalized disease accompanying dengue infections in placebo recipients were closely similar to those in vaccinated children. However, the age specific hospitalization curves for these two populations differed. The...
Japanese encephalitis (JE) is the leading cause of viral neurological disease and disability in Asia. Some 50-80% of children with clinical JE die or have long-term neurologic sequelae. Since there is no cure, human vaccination is the only effective long-term control measure, and the World Health Organization recommends that at-risk populations rec...
The scientific community now possesses information obtained directly from human beings that makes it possible to understand why breakthrough-enhanced dengue virus (DENV) infections occurred in children receiving Sanofi Pasteur's Dengvaxia tetravalent live attenuated vaccine and to predict the possibility of breakthrough-enhanced DENV infections fol...
Zika virus (ZIKV) is a mosquito-borne flavivirus that has recently been responsible for a serious outbreak of disease in South and Central America. Infection with ZIKV has been associated with severe neurological symptoms and the development of microcephaly in unborn fetuses. Many of the regions involved in the current outbreak are known to be ende...
Newly proposed candidate Zika virus vaccines might or might not succeed in raising safe, effective, and durable protection against human Zika virus infections or syndromes. Analyses of a clinically tested and licensed dengue vaccine that failed to protect seronegative individuals from breakthrough or enhanced dengue infections suggest that poor T-c...
The sudden appearance of overt human Zika virus infections that cross the placenta to damage fetal tissues, target sexual organs, and are followed in some instances by Guillain-Barré syndrome raises questions regarding whether these outcomes are caused by genetic mutations or if prior infection by other flaviviruses affects disease outcome. Because...
Background
With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is...
Background
With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is...
Dengue is widespread throughout the tropics and local spatial variation in dengue virus transmission is strongly influenced by rainfall, temperature, urbanization and distribution of the principal mosquito vector Aedes aegypti. Currently, endemic dengue virus transmission is reported in the Eastern Mediterranean, American, South-East Asian, Western...
A tetravalent live attenuated vaccine composed of chimeras of yellow fever 17D and the four dengue viruses (chimeric yellow fever dengue [CYD]) manufactured by Sanofi Pasteur has completed phase III clinical testing in over 35,000 children 2-16 years of age. The vaccine was recently licensed in four countries. During the first 2 years of observatio...
The four dengue viruses (DENV) circulate among nearly one-half of the world's population in tropical and semitropical countries imposing a huge morbidity burden on travelers. Sanofipasteur has developed a tetravalent live-attenuated vaccine, Dengvaxia, recently approved by the World Health Organization and licensed in four dengue-endemic countries....
When studying some simple epidemiological models, such as the SIR model, for
which we consider three types of individuals: susceptible, infected or recovered. But
what if one is infected and eventually infective but does not have any symptoms? How
should such a dynamics be modeled in which we can have this kind of infected individuals?
To do this w...
Urological surgery evolved from the ancient practice of removing primary bladder stones from young boys. Bladder stones, once ubiquitous, long ago disappeared from the developed world while pockets of disease still exist in developing countries. Two epidemiological studies identified as precipitating events of bladder stone formation the practice o...
Clinical observations from the third year of the Sanofi Pasteur chimeric yellow fever dengue tetravalent vaccine (CYD) trials document both protection and vaccination-enhanced dengue disease among vaccine recipients. Children who were 5 years-old or younger when vaccinated experienced a DENV disease resulting in hospitalization at 5 times the rate...
New insights into toxicity of dengue virus protein NS1 provide context to previous work and prompt further questions.
Dengue virus (DENV) infections of humans were long thought to be self-limited and of low mortality. Beginning in the 1950s, at the time when four different DENVs were discovered, a lethal variant of dengue emerged. Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) initially observed in Southeast Asia now has spread throughout the world. Two...
During the decade of the 1960s, the epidemiology of a new dengue disease, dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), was described by collaborative research performed by Thai scientists from many institutions and by workers at the U.S. Army's SEATO Medical Research Laboratory in Bangkok, Thailand. Careful clinical and physiologic...
After an absence of ≈200 years, chikungunya returned to the American tropics in 2013. The virus is maintained in a complex African zoonotic cycle but escapes into an urban cycle at 40- to 50-year intervals, causing global pandemics. In 1823, classical chikungunya, a viral exanthem in humans, occurred on Zanzibar, and in 1827, it arrived in the Cari...
Dengue imposes a substantial economic and disease burden in most tropical and subtropical countries. Dengue incidence and severity have dramatically increased in Mexico during the past decades. Having objective and comparable estimates of the economic burden of dengue is essential to inform health policy, increase disease awareness, and assess the...
Dengue Antibody-Dependent Enhancement: Knowns and Unknowns, Page 1 of 2
Abstract
Dengue provides the most abundant example in human medicine and the greatest human illness burden caused by the phenomenon of intrinsic antibody-dependent infection enhancement (iADE). In this immunopathological phenomenon infection of monocytes or macrophages using...
Dengue presents a formidable and growing global economic and disease burden, with around half the world's population estimated to be at risk of infection. There is wide variation and substantial uncertainty in current estimates of dengue disease burden and, consequently, on economic burden estimates. Dengue disease varies across time, geography and...
Commercially available diagnostic test kits for detection of dengue virus (DENV) non-structural protein 1 (NS1) and anti-DENV IgM were evaluated for their sensitivity and specificity and other performance characteristics by a diagnostic laboratory network developed by World Health Organization (WHO), the UNICEF/UNDP/World Bank/WHO Special Programme...
Vascular permeability, thrombocytopenia, liver pathology, complement activation and altered hemostasis accompanying a febrile disease are the hallmarks of the dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), a major arthropod-borne viral disease that causes significant morbidity and mortality throughout tropical countries. We studied tissu...
There is an unmet need for a dengue vaccine to further prevent the spread of this disease and contain the growing pandemic. To this end several vaccine companies and academic groups are actively pursuing the development of a tetravalent vaccine to prevent dengue. In the last few years progress has been made in this area, including the first results...
Viremia kinetics directly influence the clinical course and transmission dynamics of DENV, but many aspects of viral dynamics remain unknown. Non-human primates (NHP) have been used as a model system for DENV infection for decades. Here, we identify papers with experimentally-infected NHP and estimate the time to- and duration of viremia as well as...
Sudden increases in disease severity, manifested in Cuba by month-to-month changes in proportion of severe to mild disease and case-fatality rates were reported among secondary dengue virus type 2 (DENV2) infections in 1981 and 1997. A similar phenomenon was described for secondary DENV3 infections in 2001. Year-to-year increases in the proportion...
The envelope (E) protein of dengue virus (DENV) is the major target of neutralizing antibodies (Abs) and vaccine development. Previous studies of human dengue-immune sera reported a significant proportion of anti-E Abs were cross-reactive to all four DENV serotypes and to one or more other flaviviruses, known as group-reactive (GR). Based on the st...
While the benefits of antibody responses are widely known, pathogens are also able to exploit antibodies to facilitate cell entry and potentially alter the cellular response via interactions with Fc receptors. This phenomenon, known as antibody-dependent enhancement (ADE) of disease, is a factor in numerous human and veterinary diseases. It is thou...
A recent clinical trial of a live-attenuated tetravalent chimeric yellow fever-dengue vaccine afforded no protection against disease caused by dengue 2 (DENV-2). This outcome was unexpected as two or more doses of this vaccine had raised broad neutralizing antibody responses. Data from pre-clinical subhuman primate studies revealed that vaccination...
Today, dengue viruses are the most prevalent arthropod-borne viruses in the world. Since the 1960s, numerous reports have identified a second heterologous dengue virus (DENV) infection as a principal risk factor for severe dengue disease (dengue hemorrhagic fever/dengue shock syndrome, DHF/DSS). Modifiers of dengue disease response include the spec...
We address limitantions of precious dengue disease burden using merged data from multiple sources for Mexico
Sensitivity of attack rates to vaccine efficacy.
(PDF)
Background
Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. Wit...
Research into the pathogenesis of dengue fever has exploded over the last half-century, with issues that were considered simple becoming more complex as additional data are found. This has led to the development of a number of controversies that are being studied across the globe and debated in the literature. In this paper, the following six contr...
Recognizing the uniqueness of secondary dengue virus (DENV)-1/3 dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) cases at an interval of 24 years, we sought to estimate DENV infections as well as the ratios between mild disease and DHF/DSS by DENV infection sequence in Playa District (Havana, Cuba) during the 2001-2002 outbreak of dengue vi...
Laurent Coudeville, Jean Lang, and Remy Teyssou are employees of Sanofi-Pasteur (France). Adrienne Guignard, Gerhart Knerer, and Baudoin Standaert are employees of GSK Biologicals (Belgium). Joachim Hombach and Pem Namgyal are staff members of the World Health Organization. This report contains the collective views of an international group of expe...
Introduction Etiology Epidemiology Clinical Findings Diagnosis Treatment Pathogenesis Prevention References
[This corrects the article on p. e1188 in vol. 5.].
Properties of MAbs from donor 033 (Primary DENV3 infection).
(DOC)
Dengue immune human sera used in the present study.
(DOC)
Dengue epidemics in Cuba have repeatedly demonstrated a month-to-month increase in clinical severity during secondary infections. The dengue 2 outbreak that occurred in Santiago de Cuba in 1997 was accompanied by the most severe intraepidemic increase in disease severity reported to date. It was initially proposed that the appearance of neutralizat...
Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhanc...
Japanese encephalitis virus (JEV), a flavivirus maintained in a zoonotic cycle and transmitted by the mosquito Culex tritaeniorhynchus, causes epidemics of encephalitis throughout much of Asia. Resident populations, including short- or long-term visitors to enzootic regions, are at risk of infection and disease. For the past several decades, killed...
Dengue is an arthropod-borne flavivirus that comprises four distinct serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) that constitute an antigenic complex of the genus flavivirus, family Flaviviridae. Infection by one serotype induces life-long immunity against reinfection by the same serotype, but only transient and partial protection against infection w...
Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ∼50 million dengue infections and ∼500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy...
Citations
... Approximately 67,900 JE cases are reported annually and these are associated with about 10,000 deaths (Campbell et al., 2011;Wang and Liang, 2015). While children have traditionally been more susceptible to JE (Halstead et al., 2023), the global widespread use of JE vaccines has led to significant reduction in pediatric cases in many regions. Interestingly, this was accompanied by a noticeable rise in adult JE cases, with some outbreaks having been noted (Wu et al., 2021;Hills et al., 2023). ...
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... 10,14 Acute encephalitis is a severe and potentially life threatening disease, and the fatality rate of encephalitis was found as 24-42% and was highest in children aged 5-9 year age group in developed country with their Intensive care unit (ICU) facility. 15 The death rate was 52% in this study may be due to late referral to this tertiary hospital and lack of treatment facilities including ICU support in the hospital. In Malaysia and Singapore in the period of outbreak in 1998-99 due to Nipha virus infection, out of 265 infected cases, the death rate was 40%. ...
... Neutralizing antibodies prevent the infection, replication, or transmission of the virus, and most, but not all neutralizing antibodies are directed at epitopes within the sialic acid binding site on the head of the HA molecule (HA1) [23,[26][27][28][29]. Under specific circumstances, non-neutralizing cross-reactive IgG antibodies have been associated with enhanced disease [26,[30][31][32][33][34]. In pigs and ferrets, enhanced disease known as vaccine-associated enhanced respiratory disease (VAERD) has been consistently reproduced as a severe lung pathology in IAV challenge trials involving the use of sub-type heterologous killed vaccines [34][35][36]. ...
... A pre-vaccination screening strategy using assays with high specificity (≥98.0%) to avoid erroneous vaccination of individuals without prior DENV infection and high sensitivity (≥95.0%) to detect individuals with a single prior DENV infection has been proposed (14,15). Several serological tests have been reported to determine the DENV serostatus for pre-vaccination screening, including rapid diagnostic tests (RDTs) and ELISAs (16)(17)(18)(19)(20)(21). ...
... Vaccination has been successful in several instances but can fail despite extensive efforts. For example, HIV-1 evades vaccine-induced immune responses [8] and dengue virus infection can be even enhanced by vaccine-induced immune responses [9,10]. In this context of increasing viral threats and lack of effective curative tools, a be er understanding of virus-induced mechanisms that promote infection will reveal potential targets for novel interventions. ...
... However, urban transmission of YFV probably occurred close to the Brazilian border, in Santa Cruz de la Sierra (Bolivia) less than 1� years ago �� . Thus, there is a risk of urbanization of YFV through movements of infected people into cities where �edes aegypti is disseminated 15 . ...
Reference: Emergent arboviruses in Brazil
... COVID-19 vaccines are effective in these people and perhaps reduce the risk of severe disease or death with the standard two-shot regimen (15). However, suboptimal immune response due to relative immune deficiency to the standard regimen is still a concern (16,17). An additional dose may be recommended as part of the extended primary series. ...
... In the Philippines, a Dengvaxia school-based vaccination program was launched in April 2016 among 9-10-year-old children with >830,000 children receiving at least one dose (~420,000 one dose,~49,000 two doses, and~370,000 three doses) (5,(8)(9)(10). After this program was initiated, a DENV nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay (ELISA) was employed in a post-hoc case-control study to determine the baseline DENV serostatus in samples collected 13 months after the first dose of Dengvaxia. ...
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... Доведено, що запалення відіграє важливу роль у патогенезі COVID-19 і може бути важливим фактором прогнозу. Імунна відповідь на респіраторну інфекцію характеризується припливом нейтрофілів до легенів, особливо до альвеол [9]. Постійне вивільнення протизапальних цитокінів може призвести до широкого апоптозу лімфоцитів, що призводить до лімфопенії [1]. ...
... As a result, several reasons are conjured up on why the guidelines should not be observed. [18][19][20][21][22] This study will, therefore, identify individuals' response measures that affect the prevention of COVID-19 infection in the rural areas. ...