Search PubMedSearch

Biomedical subjects

C H Hoke

Publications and source records attributed to C H Hoke.

13 recordsLinked to original sources

Hepatitis A in the US Army: epidemiology and vaccine development.

Control of hepatitis A has been an important concern for US military forces in war and peace. Immune serum globulin, although effective, is exceedingly cumbersome to use. The prevalence of antibody against hepatitis A is decreasing in young American soldiers, putting them at risk of hepatitis A during deployment. The US Army has been an active participant in development of hepatitis A vaccine. The first successful cell-culture-derived, formalin-inactivated hepatitis A vaccine was developed at the Walter Reed Army Institute of Research. This prototype vaccine was shown, in 1986, to be safe and immunogenic for humans. Since then we have evaluated the following issues related to the use of inactivated hepatitis A vaccines in military populations. Immunogenicity of vaccine derived from the CLF and HM175 strains; immunogenicity of hepatitis A vaccine given by jet injector; immunogenicity of hepatitis A vaccine when given with hepatitis B vaccine; immunogenicity when given in shortened schedules; safety and immunogenicity in Thai children; and efficacy under field conditions in the tropics. The hepatitis A vaccines which we tested are safe and highly immunogenic. Immunization by jet gun confers immunity equivalent to immunization by needle. Hepatitis A vaccine is equally potent when given with hepatitis B vaccine. Data on rapid immunization schedules and efficacy are under evaluation. We conclude that hepatitis A vaccine is a major improvement in our ability to prevent hepatitis A in soldiers.

Hepatitis A

Laboratory tests and reference reagents employed in studies of inactivated hepatitis A vaccine.

Procedures to evaluate inactivated hepatitis A vaccines in volunteers have been examined. Solid-phase immunoassays were standardized with reference preparations and have been tested to measure antibody response to immunization and antigen content of vaccines. Following immunization, there was a good correlation between antibody response, determined with commercial immunoassays, and neutralization titres, as measured by the radioimmunofocus inhibition test. However, at lower titres of neutralizing antibody, the commercial immunoassay often yielded negative results. To improve the sensitivity of the immunoassay, the serum volume was increased. A fourfold increase of test serum resulted in greater sensitivity, increasing from 54 to 94%, while retaining 100% specificity. Further increases in the volume of test serum resulted in a loss of specificity. In a comparison of neutralization tests, similar titres of postvaccination sera were obtained by using the HM175/18f cytopathic strain of hepatitis A virus in a plaque reduction assay or the HM175 parental virus in the radioimmunofocus inhibition test. Use of the cytopathic virus obviates the need for radioactively labelled serum and reduces the time taken to conduct neutralization tests. The current laboratory procedures can meet the needs of large field trials of inactivated hepatitis A vaccines.

Antigens, Viral

Effect of high-dose dexamethasone on the outcome of acute encephalitis due to Japanese encephalitis virus.

Death due to Japanese encephalitis usually occurs in the first 5 days of hospitalization as a result of deepening coma with respiratory arrest. Death may result from edema-induced increases in intracranial pressure that might be reduced by the administration of steroids. Sixty-five patients presenting in Thailand to four hospitals with a diagnosis of acute Japanese encephalitis were randomized in a double-masked fashion and stratified by initial mental status into a placebo group (saline) or a treatment group (dexamethasone 0.6 mg/kg intravenously as a loading dose followed by 0.2 mg/kg every 6 h for 5 days). Fifty-five of the 65 had confirmed Japanese encephalitis as demonstrated by detection of virus or by Japanese encephalitis virus-specific IgM antibody. Important outcome measures included mortality (24%, treatment group; 27%, control group), days to alert mental status (3.9 vs. 6.2), and neurologic status 3 months after discharge (45% abnormal in each group). No statistically significant benefit of high-dose dexamethasone could be detected.

Acute Disease

Infection of owl monkeys (Aotus trivirgatus) and cynomolgus monkeys (Macaca fascicularis) with hepatitis E virus from Mexico.

Owl and cynomolgus monkeys were inoculated with hepatitis E virus (HEV) to compare disease models and produce antibody and virus. By immune electron microscopy (IEM), all six owl monkeys were shown to have serologic responses manifested by unusually high levels of anti-HEV at 6 months, but only three developed hepatitis. Virus-related antigen in liver (HEV Ag) was detected by immunofluorescence microscopy of biopsies from two of four owl monkeys; one with HEV Ag also had HEV in acute-phase bile (detected by IEM) and feces (detected by infecting another owl monkey). In contrast, cynomolgus monkeys propagated HEV to higher levels and all five had hepatitis. Moderate-to-high levels of HEV Ag correlated with detectable HEV in bile for both species. Thus, the value of using HEV-infected cynomolgus was confirmed. Owl monkeys were shown to be HEV-susceptible and sources of high-level anti-HEV; Sustained anti-HEV in these monkeys may also be useful for understanding immune responses.

Alanine Transaminase

Japanese encephalitis virus in Bangkok: factors influencing vector infections in three suburban communities.

An unexpected outbreak of Japanese encephalitis (JE) in Bangkok in 1985 led us to investigate the vector ecology of urban JE from January 1986 to June 1987 at three suburban sites that displayed a wide range of factors imputed to influence JE transmission. Culex tritaeniorhynchus Giles and Cx. gelidus Theobald, suspected vectors, comprised 71-96% of all mosquitoes collected by CO2-baited CDC traps at the three sites. Mean of mosquito abundance per two trap-nights per month ranged from 28 to 5,728 mosquitoes at the sites of lowest and highest abundance, respectively. Cx. tritaeniorhynchus yielded more JE isolates (n = 16) than Cx. gelidus (n = 7), but the minimum infection rates of the two species (number of JE isolates per 1,000 mosquitoes tested; MIR, 0.17 and 0.47, respectively) were comparable and covaried with vector abundance. Moreover, the proportion of sentinel pigs that had JE antibodies generally increased proportionately with vector abundance at the sites. Vector abundance was high in monsoon (May-October), moderate in transition (March-April and November-December), and low in dry (January-February) seasons. Mosquitoes collected in monsoon seasons yielded 96% of the JE isolates, whereas 4 and 0% of the isolates were obtained from transition and dry season collections, respectively. More pigs seroconverted in monsoon and transition seasons than in dry seasons. Indices of JE transmission activity (vector abundance, pig seroconversions, and MIRs) increased proportionately with rainfall. Despite higher indices at the site of greatest vector abundance than elsewhere, the risk of human infection appeared greatest at the site with moderate vector abundance because of its greatest human population density.

Animals

Infectious Japanese encephalitis virus RNA can be synthesized from in vitro-ligated cDNA templates.

Japanese encephalitis virus (JEV) is a positive-stranded enveloped RNA virus that belongs to the family Flaviviridae. Genomic JEV RNA is approximately 11 kb long and encodes 10 proteins, 3 structural and 7 nonstructural. A full-length cDNA copy of the JEV genome was constructed by in vitro ligation of two cDNA fragments which encode the 5' (nucleotide positions 1 to 5576) and 3' (nucleotide positions 5577 to 10976) halves of the genome. T7 RNA polymerase transcripts of the ligated full-length cDNA template were infectious when transfected into BHK-21 cells. To identify the recombinant virus, a silent mutation was introduced into the clone encoding the 3' half of the genome, which abolished an XbaI site at nucleotide position 9131. Virus recovered by transfection with the transcripts contained this silent mutation, confirming its identity. Recombinant and parent viruses were identical with respect to growth and plaque production in BHK-21 cells, envelope protein expression in C6/36 cells, and neurovirulence and immunogenicity in mice. Repeated attempts to obtain infectious RNA by transcription from full-length JEV genome cDNA templates cloned into plasmid vectors were unsuccessful. Synthesis of infectious JEV RNA from in vitro-ligated JEV cDNA templates will be useful for molecular and genetic studies of flavivirus replication and virulence.

Animals

False-positive Gram-stained smears.

The rate per 1,000 smears showing nonviable Gram-negative bacilli (false-positive smears) increased from a baseline of 10.8 to 38.5 following purchase of new culture-collection devices; the rate decreased to 8.0 following replacement of contaminated culture sets. False-positive reports led to changes in therapy for five patients. In addition to being sterile, commercial culture-collection devices should be certified by the manufacturer as being free of stainable microorganisms or as unsuitable for preparation of Gram-stained smears.

Adolescent

A comparison of a WI-38 vaccine and duck embryo vaccine for preexposure rabies prophylaxis.

Two types of rabies vaccine, WI-38 vaccine (WRV) and Duck Embryo Vaccine (DEV) were compared in rabies preexposure prophylaxis. Once group of veterinary students received four doses of DEV, a second group received four doses of WRV, and a third group received two doses of WRV. Adverse reactions were found to be similar for all three gorups. The antibody responses, however, differed markedly: the mean neutralizing titer after four doses of DEV was 1:75, after four doses of WRV was 1:1517, but was only 1:164 after two doses of WRV. All students who received three or four doses of WRV developed high titers of rabies antibody, making this vaccine very desirable for preexposure prophylaxis.

Adult

Comparison of sevral wild-type influenza viruses in the ferret tracheal organ culture system.

Several strains of wild-type influenza A virus were studied in the ferret tracheal organ culture system. Ciliary activity and viral replication were measured. Ciliary activity was reduced more rapidly by A/Hong Kong/45/68 (H3N2) (A/HK) and A/Victoria/3/75 (H3N2) (A/Vic) than by A/New Jersey/8/76 (Hsw1N1) (A/NJ), A/Scotland/840/74(3HN2) (A/Scot), or A/USSR/90/77 (H1N1) (A/USSR). A/HK, A/Vic, and A/Scot produced titers of virus higher than A/USSR or A/NJ during the first three days after infection. Differences in effects of the five viruses on cilia were not related to history of egg passage. The two strains that destroyed ciliary activity rapidly had caused excess mortality in the United States, whereas the three that destroyed ciliary activity more slowly had not. A relationship may exist between the properties contributing to virulence in humans and the destruction of ciliary activity in vitro in this culture system.

Animals