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Scott B Halstead

Publications and source records attributed to Scott B Halstead.

17 recordsLinked to original sources
PubMed2005

Dengue virus: molecular basis of cell entry and pathogenesis, 25-27 June 2003, Vienna, Austria.

Multivalent dengue vaccines now in late stage development pose unique vaccine safety challenges in that primary or secondary vaccine failures might place vaccines at risk to antibody-dependent enhanced (ADE) wild-type dengue infections. This conference was organized to address this unique vaccine safety issue. New data were presented on the structure of dengue and other flaviviruses, the cellular receptors of dengue virus for biologically relevant cells, dengue viral cell entry mechanisms and mechanisms underlying in vivo protection, neutralization and enhancement of dengue virus infection. It was concluded that a targeted research program should aim to develop an in vitro test to characterize persons immunized with dengue vaccines as completely or partially protected. Achievement of this aim will require a better understanding of the basic mechanisms by which dengue viruses recognize, attach, enter and infect relevant human cells and how antibodies protect against dengue infections.

Antibodies, Viral↗
PubMed2005

Association between sex, nutritional status, severity of dengue hemorrhagic fever, and immune status in infants with dengue hemorrhagic fever.

The association between sex, nutritional status, and the severity of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), and immune status was investigated in 245 Vietnamese infants with predominantly primary infections with dengue virus. Male and female infants were at equal risk of developing DHF/DSS. However, infants of low height and weight for age were under-represented among DHF/DSS cases compared with 533 healthy baby clinic infant controls. Acute illness phase blood levels of selected cytokines (interferon-gamma and tumor necrosis factor-alpha) and serum levels of antibodies to dengue virus were elevated in the same range in male and female infants with DHF/DSS, as well as in infants with and without malnutrition.

Dengue↗
PubMed2004

Cost-effectiveness of a pediatric dengue vaccine.

To ascertain the economic feasibility of a pediatric tetravalent dengue vaccine, we developed and calibrated a cost-effectiveness model of vaccinating children at 15 months in Southeast (SE) Asia using a societal perspective. We assumed that full immunization would require two doses at prices of US$ 0.50 and US$ 10 per dose in the public and private sectors, respectively. The gross cost per 1000 population (of all ages) of the vaccination program would be US$ 154. Due to projected savings in dengue treatment, the net cost per capita would be only US$ 17 (89% below the gross cost). The cost per disability adjusted life year (DALY) saved by a pediatric vaccine would be US$ 50, making the potential vaccine highly cost-effective. Eventually, vaccination may be able to replace environmental control as a strategy for dengue prevention and be cost saving.

Asia, Southeastern↗
PubMed2004

Dengue hemorrhagic fever in infants: a study of clinical and cytokine profiles.

A prospective study of clinical and cytokine profiles of 107 infants with dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) was conducted. Fever, petechiae on the skin, and hepatomegaly were the most common clinical findings associated with DHF/DSS in infants. DSS occurred in 20.5% of the patients. Hemoconcentration and thrombocytopenia were observed in 91.5% and 92.5% of the patients, respectively. Serologic testing revealed that almost all of the patients (95.3%) had primary dengue virus infections. These data demonstrate that clinical and laboratory findings of DHF/DSS in infants are compatible with the World Health Organization's clinical diagnostic criteria for pediatric DHF. The present study is the first to report evidence of production of cytokines in infants with DHF/DSS and to describe the difference between the cytokine profile of infants with primary dengue virus infections and children with secondary infections. Overproduction of both proinflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha) and anti-inflammatory cytokines (interleukin-10 and -6) may play a role in the pathogenesis of DHF/DSS in infants.

Antibodies, Viral↗
PubMed2003

Biologic properties of dengue viruses following serial passage in primary dog kidney cells: studies at the University of Hawaii.

Serial passage at low dilution of seven different wild-type dengue (DEN) viruses into primary dog kidney (PDK) cell cultures placed selective pressure that resulted in the following changes from parental phenotype: smaller plaques in LLC-MK2 cells, absent plaque formation in green monkey kidney cells, lack of a cytopathic effect in LLC-MK2 cells, shut-off of virus replication at high temperatures (temperature sensitivity), reduced virulence for rhesus monkeys manifested by reduced or absent viremia and/or absence of a secondary-type antibody response following homotypic challenge, and progressive increase in the mean day of death following intracerebral inoculation of sucking mice. Two DEN-1 strains showed most of these changes by the 15th PDK passage. Only one of two DEN-2 strains studied was carried to the 50th PDK passage at the University of Hawaii. For the latter strain, both the temperature of viral replicative shutoff and mouse neurovirulence were reduced. Three DEN-4 strains showed similar late-passage biologic marker changes. The observations made, although not exhaustive, provide laboratory correlates for virus strains that have shown reduced virulence but retained immunogenicity in humans. Candidate human vaccines have been prepared from five of the studied strains: DEN-1 (16007) at PDK 13, DEN-2 (16681 and S-16803) at PDK 50 or above, and DEN-4 (1036 and 341750) at PDK 48 and 20, respectively.

Animals↗
PubMed2002

Effect of dengue-1 antibodies on American dengue-2 viral infection and dengue haemorrhagic fever.

In Iquitos, Peru, no cases of dengue haemorrhagic fever have been recorded in individuals infected with dengue-1 virus followed by American genotype dengue-2 (American dengue-2) virus. We assayed serum samples collected in Iquitos that tested positive for antibodies of monotype dengue-1 and monotype dengue-2 using a plaque reduction neutralisation test to determine their ability to neutralise the infectivity of two dengue-1 viruses, two American dengue-2 viruses, and two Asian dengue-2 viruses. Sera positive for the dengue-1 antibody neutralised dengue-1 viruses and American dengue-2 viruses much more effectively than Asian dengue-2 viruses. Neutralisation of American dengue-2 virus by sera positive for dengue-1 antibodies may account for the absence of dengue haemorrhagic fever in individuals infected with dengue-1 in 1990-91 followed by American dengue-2 virus in 1995 in Iquitos, Peru.

Antibodies, Viral↗
PubMed2002

Effect of age on outcome of secondary dengue 2 infections.

OBJECTIVE: Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) is a growing global health problem. It is not known how age affects the outcome of secondary dengue infections. In an island setting, a large DHF/DSS outbreak in Cuba occurred in 1981. Involved were individuals, 3-40 year old, whose only lifetime dengue exposure was to DEN-1 in 1977 and DEN-2 in 1981. In this report we calculate age-specific DHF/DSS hospitalization and death rates based on secondary DEN 2 infections. METHODS: Published and unpublished hospital and seroepidemiologic data from the 1981 DHF/DSS outbreak were used for the analysis. RESULTS: Children, aged 3 and 4 years, with secondary DEN-2 infections were found to have a high death rate (25.4/10 000 secondary DEN-2 infections). The death rate fell with increasing age, being 15.9-fold lower in the 10-14-year age group. The death rate for children aged 3-14 years was 14.5-fold higher than in young adults aged 15-39 years. The death rate rose somewhat in adults aged 50 years and older. DHF/DSS hospitalization rates showed the same trend as death rates. CONCLUSIONS: Age is an important variable in the outcome of secondary DEN-2 infections. DHF/DSS case fatality and hospitalization rates are highest in young infants and the elderly. The risk that a child will die during a secondary DEN-2 infection is nearly 15-fold higher than the risk in adults.

Adolescent↗
PubMed2002

Dengue.

PURPOSE OF REVIEW: Because efforts to control dengue are flagging, this review focuses on the mechanisms underlying severe disease and on treatment options, good and bad. RECENT FINDINGS: The year 2001 witnessed unprecedented global dengue epidemic activity in the American hemisphere, the Pacific islands and continental Asia. Early diagnosis of dengue is important but what is the value and appropriate use of the tourniquet test? A negative test does not rule out dengue infection, a positive test should be followed by close surveillance for early signs of dengue hemorrhagic fever. Low platelet counts do not predict clinically significant bleeding in dengue. It follows that platelet or blood transfusions should not be administered based upon platelet count alone. Dengue hemorrhagic fever or dengue shock syndrome cases frequently have compensated consumptive coagulopathy that seldom requires treatment. Bleeding is most likely caused by activated platelets resulting from damaged capillary endothelium. Dengue hemorrhagic fever and dengue shock syndrome can be safely treated with just normal saline. Colloids should be immediately given to children presenting with a pulse pressure at or below 10 mmHg. Human leukocyte antigen alleles correlate with both protection and susceptibility to dengue hemorrhagic fever and dengue shock syndrome; studies in Haiti suggest that blacks have a gene providing nearly complete protection against severe dengue illness. SUMMARY: The role that antibodies play in protecting and enhancing dengue infections has been largely ignored. Such studies require definitive knowledge of what cells are infected in human dengue and an understanding of all the early antibody-accessible steps of infection of these target cells.

Dengue↗
PubMed2002

Enhanced severity of secondary dengue-2 infections: death rates in 1981 and 1997 Cuban outbreaks.

OBJECTIVE: To understand the possible effect that length of time has on disease severity with sequential dengue infections. METHODS: Death and hospitalization rates for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) per 10,000 secondary dengue-2 infections were compared in the same age group for two dengue-2 (DEN-2) epidemics in Cuba. The first DEN-2 epidemic affected all of Cuba in 1981; the second one, in 1997, impacted only the city of Santiago de Cuba. The sensitizing infection for DHF/DSS for each of the DEN-2 epidemics was dengue-1 (DEN-1) serotype virus, which was transmitted in 1977-1979, that is, 4 years and 20 years before the two DEN-2 epidemics. Using published seroepidemiological data from the cities of Havana and Santiago de Cuba, we estimated the rates at which persons aged 15-39 years old and those 40 years and older were hospitalized or died of DHF/DSS in Havana and in all of Cuba in 1981 and in just Santiago de Cuba in 1997. RESULTS: Among adults 15-39 years old the death rate per 10,000 secondary DEN-2 infections was 38.5 times as high in Santiago de Cuba in 1997 as in Havana in 1981. As a further indication of the increased severity coming with a longer period between the initial DEN-1 infection and the secondary DEN-2 infection, the case fatality rate for that same age group was 4.7 times as high in Santiago in 1997 as it was in Havana in 1981. CONCLUSION: We found a marked increase in severity with the longer of the two intervals (20 years) between an initial DEN-1 infection and a secondary DEN-2 infection. Such a difference may be due to subtle shifts in causative dengue strains or to changes with the passage of time in the circulating population of human dengue antibodies. These observations have important implications for dengue control, pathogenic mechanisms, and vaccine development.

Adolescent↗
PubMed2002

Dengue hemorrhagic fever in infants: research opportunities ignored.

The age distribution of cases of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) in infants under the age of 1 year are reported from Bangkok, Thailand, and for the first time for Ho Chi Minh City, Vietnam; Yangon, Myanmar; and Surabaya, Indonesia. The four dengue viruses were isolated from Thai infants, all of whom were having a primary dengue infection. Progress studying the immunologically distinct infant DHF/DSS has been limited; most contemporary research has centered on DHF/DSS accompanying secondary dengue infections. In designing research results obtained in studies on a congruent animal model, feline infectious peritonitis virus (FIPV) infections of kittens born to FIPV-immune queens should be considered. Research challenges presented by infant DHF/DSS are discussed.

Age Distribution↗