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Biomedical subjects

J W LeDuc

Publications and source records attributed to J W LeDuc.

At least 37 records · Page 2Linked to original sources

Characterization of Dobrava virus: a Hantavirus from Slovenia, Yugoslavia.

Small mammals were collected in natural foci of hemorrhagic fever with renal syndrome (HFRS) in Slovenia, Yugoslavia, and a hantavirus was isolated from the lungs of an Apodemus flavicol lis captured in Dobrava village. This new isolate, Dobrava virus, was compared with representative strains of the Hantavirus genus by serological and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. It was found by cross immunofluorescent and enzyme-linked immunosorbent assays that antigenic properties of Dobrava virus were different from those of other hantaviruses. The RNA of this virus was successfully amplified with hantavirus genus reactive primer sets by reverse transcriptase polymerase chain reaction (RT-PCR); however, PCR-RFLP analysis of the amplified product was shown to be unique among those of the known hantaviruses, further indicating that Dobrava virus represents a new hantavirus serotype.

Animals↗

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↗

Comparison of hantavirus isolates using a genus-reactive primer pair polymerase chain reaction.

RNA of more than 40 hantavirus isolates, originating from rodents and humans of widely separated geographical areas, was copied to cDNA using reverse transcriptase and amplified by polymerase chain reaction (PCR). A genus-reactive oligonucleotide primer pair, flanking a 365 bp region of the G2 glycoprotein gene, was chosen for genus-reactive PCR. DNA products were digested with 20 restriction endonucleases and cleavage patterns were analysed. For strains of known sequence, the restriction patterns observed were consistent with those predicted from sequence data, demonstrating that the amplified products originated from target virus RNA. Further analyses suggested that all amplified viruses could be easily typed into one of five restriction patterns using only five enzymes. The categories identified by restriction analysis of PCR-amplified cDNA corresponded with serogroups established by plaque-reduction neutralization tests. This method may greatly simplify the identification of new hantavirus isolates.

Base Sequence↗

Risk factors associated with antibodies to leptospires in inner-city residents of Baltimore: a protective role for cats.

Leptospiral antibody prevalence was 16% in residents of Baltimore. Seropositivity was associated with age, gender, race, and bird ownership, reduced the antibody risk associated with age and race from odds ratios (95% confidence interval) of 3.3 (2.0, 5.5) and 3.3 (1.1, 9.3), respectively, to the baseline level. These data establish the high prevalence of leptospiral antibody in Baltimore and suggest a protective role for cats in reducing the risk of human infection.

Adult↗

The role of secretory immunity in hepatitis A virus infection.

Because the role of intestinal immunity remains uncertain in hepatitis A, samples of feces and saliva from infected primates and humans were tested for virus neutralizing activity. Only two of eight owl monkeys infected by the intragastric route developed neutralizing antibody detectable in extracts of feces collected up to 88 days after viral challenge, although serum neutralizing antibody was present in all monkeys by day 33. Similarly, neutralizing antibody was detected in fecal extracts from none of three experimentally infected human volunteers and only 1 of 15 naturally infected humans. The single positive human specimen contained occult blood. Only 2 of 19 saliva samples from naturally infected humans had significant viral neutralizing activity. In contrast, neutralizing antibody to type 2 poliovirus was present in most human fecal or saliva specimens tested. These data suggest that intestinal immunity does not play a significant role in protection against hepatitis A.

Animals↗

Prospective, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin therapy of hemorrhagic fever with renal syndrome.

A prospective, randomized, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin (loading dose of 33 mg/kg, 16 mg/kg every 6 h for 4 days, and 8 mg/kg every 8 h for 3 days) was conducted in 242 patients with serologically confirmed hemorrhagic fever with renal syndrome (HFRS) in the People's Republic of China. Mortality was significantly reduced (sevenfold decrease in risk) among ribavirin-treated patients, when comparisons were adjusted for baseline risk estimators of mortality (P = .01; two-tailed). HFRS typically consists of five consecutive but frequently overlapping clinical phases. Only occurrence of oliguric phase and hemorrhage was associated with severity of clinical disease in the placebo group. Ribavirin therapy also resulted in a significant reduction in the risk of entering the oliguric phase and experiencing hemorrhage. The only ribavirin-related side effect was a well-recognized, fully reversible anemia after completion of therapy.

Anemia, Hemolytic↗

In vivo replication and reversion to wild type of a neutralization-resistant antigenic variant of hepatitis A virus.

Six seronegative owl monkeys were intravenously inoculated with an antigenic variant (S18) of hepatitis A virus that is highly adapted to growth in cell culture and resists neutralization by monoclonal antibodies due to replacement of aspartic acid 70 of capsid protein VP3 with histidine. Each developed hepatitis 22-33 days after inoculation. Virus in feces, serum, and liver was quantified by radioimmunofocus assay. Viremia developed 7-11 days after inoculation, in parallel with fecal shedding of virus, and persisted for a mean of 20.5 days. Although the antigenic variant was recovered from feces or liver of three animals, virus in liver at the time of enzyme elevations was predominantly wild-type antigenic phenotype. Virus was not recovered from liver 96 days after challenge. These studies further define virologic events in hepatitis A and show that in vivo replication of an antigenic variant was restricted compared with that of wild-type virus.

Animals↗

A retrospective analysis of sera collected by the Hemorrhagic Fever Commission during the Korean Conflict.

More than 600 sera from 245 patients with a clinical diagnosis of hemorrhagic fever were preserved by the Hemorrhagic Fever Commission during the Korean Conflict, 1951-1954. These sera were tested for IgM- and IgG-specific antibodies to Hantaan virus by enzyme immunoassay and for hantaviral antigen by immunoassay; one serum from each patient was tested by plaque reduction neutralization using both Hantaan and Seoul viruses. Only 15 patients failed to develop antihantaviral antibodies; most sera contained high titered IgM antibody on admission, and all were IgM-seropositive by day 7 after onset. Attempts to detect hantaviral antigen were unsuccessful. All seropositive patients had highest plaque reduction neutralization titers to Hantaan virus, suggesting that this virus was responsible for the disease seen. These results confirm that hemorrhagic fever of the Korean Conflict was due to Hantaan virus and demonstrate that measurement of specific IgM antibody is the method of choice for diagnosis of acute disease.

Antibodies, Viral↗

Serologic evidence of hantaviral infections within small mammal communities of Baltimore, Maryland: spatial and temporal patterns and host range.

Serologic evidence was used to investigate the spatial and temporal distribution and host range of hantaviruses in small mammal communities in Baltimore, MD. Immunofluorescent antibody (IFA) reactive to a Baltimore rat isolate of Seoul virus was detected in 44% of 404 Norway rats captured at 4 park or residential locations; 21% of 121 meadow voles captured at 4 park locations possessed significant IFA titers to Prospect Hill virus. Evidence from plaque neutralization assay of rodent sera suggested that Seoul virus and Prospect Hill virus circulated concurrently in voles and rats, respectively, at 1 park. No cross infection of virus between these primary reservoir species was observed, as determined by higher specific neutralizing antibody titers to the characteristic virus for each host species. Only 4% of 449 house mice and 1% of 94 white-footed mice captured at the same sites as the primary host species were seropositive to hantaviruses, despite extensive demonstrated overlap in time and space with the primary host species.

Animals↗

Effects of hantaviral infection on survival, growth and fertility in wild rat (Rattus norvegicus) populations of Baltimore, Maryland.

Survival, growth rates, body size and fertility of wild caught Norway rats (Rattus norvegicus), infected and uninfected with a Hantavirus (antigenically related to Seoul virus), were compared. No differences were found in the survival of seronegative versus seropositive rats, as measured by mark-recapture experiments. Growth rates, as measured by weight gain but not by increased body length, were slower in seropositive, sexually mature (greater than 200 g) rats, although no differences in the ultimate body size of infected versus uninfected rats were found. No differences in external measures of sexual maturity, or in embryo counts or testes sizes, were found for infected versus uninfected rats. We conclude that hantaviral infections have little or no impact on demographic processes in Norway rat populations.

Analysis of Variance↗

Association of intraspecific wounding with hantaviral infection in wild rats (Rattus norvegicus).

The potential for hantaviral transmission among wild Norway rats by wounding associated with aggressive interactions was evaluated using a prospective sero-epidemiological study coupled with a mark-release-recapture survey. There was a significant association between an animal's serological status and the presence of wounds. Longitudinal studies of marked and released animals showed seroconversion between captures was associated with wounding between captures more often (33%) than expected by chance, while unwounded animals seroconverted less often (8%) than expected. Typically, less than a 5% difference was found when comparing the incidence of seroconversion with the predicted rate based on wounding and seroprevalence. Infection was highly associated with the onset of sexual maturity and aggression but decoupled from rat age and the length of environmental exposure. Seroconversions occurred at times most associated with aggressive encounters and least associated with amicable behaviours that could lead to aerosol transmission.

Age Factors↗

Aerosol transmission of Hantaan and related viruses to laboratory rats.

Hantaan, Seoul, and Puumala viruses were transmitted to 12-16-week-old female Wistar Rattus norvegicus by inhalation. The rodent infectious dose for each virus by intramuscular inoculation and by inhalation was determined, as was the infectious dose for Vero E-6 cells by direct plaque assay.

Aerosols↗

Isolation of a newly recognized Bunyamwera serogroup virus from a febrile human in Panama.

A virus, strain 86MSP18, was isolated from the acute phase serum of a U.S. soldier with a febrile illness. He was stationed at Fort Sherman in the Republic of Panama when the onset of his illness occurred. A rise in neutralizing antibody to the viral isolate was observed between the patient's acute and convalescent-phase serum samples. Virus strain 86MSP18 has been shown by plaque reduction neutralization to be closely related to but distinct from Cache Valley virus and known subtypes. It appears to be a newly recognized subtype of Cache Valley virus and is believed to be the second isolation of a Cache Valley virus subtype from a human with a febrile illness. The name "Fort Sherman" virus for strain 86MSP18 is proposed.

Animals↗

Epidemiology of nephropathia epidemica in Sweden.

A comprehensive study of nephropathia epidemica (NE), caused by Puumala virus, was conducted in Sweden. Human sera from residents of various regions of Sweden were examined for antibody to Puumala virus, and the incidence of NE was determined. Small mammals were captured at locations throughout Sweden and were examined for antibody to Puumala virus and for antigen. The human serosurvey found the highest prevalence rates and the highest incidence rates in northern Sweden. The bank vole was found to be the most-abundant rodent, as well as the species most frequently positive for antibody. Antibody-positive voles were restricted to the northern two-thirds of the country, an area corresponding to that where most human disease was noted. These results suggest that the bank vole is the principal host of Puumala virus in Sweden and clearly establish the region near 64 degrees N as highly endemic for NE in humans.

Animals↗

Epizootiology of Hantavirus infections in Baltimore: isolation of a virus from Norway rats, and characteristics of infected rat populations.

Rats trapped from 14 locations in Baltimore, Maryland, were shown to have antibody to Hantavirus. Antibody prevalence rates were higher in residential locations than in parks. Infected rats were obtained continuously over a six-year period from 1980-1985 at five locations, indicating the enzootic nature of this infection in urban rats in the United States. Prevalence of antibody and geometric mean titers increased with rat mass and sexual maturity, suggesting that infections in rats are acquired through age-related mechanisms. Three isolates of Hantavirus were obtained from rats. One of these isolates was shown by serologic tests and monoclonal antibody reactivity patterns to be similar, if not identical, to rat virus previously obtained from Philadelphia. The presence of rats in many urban settings and the high prevalence of Hantavirus infection in this species suggest that human exposure to this virus is occurring in the United States, although human disease from this exposure has not been recognized.

Animals↗