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J W LeDuc

Publications and source records attributed to J W LeDuc.

At least 19 recordsLinked to original sources
PubMed1999

Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections.

A passive immunization strategy for treating Ebola virus infections was evaluated using BALB/ c mice, strain 13 guinea pigs, and cynomolgus monkeys. Guinea pigs were completely protected by injection of hyperimmune equine IgG when treatment was initiated early but not after viremia had developed. In contrast, mice were incompletely protected even when treatment was initiated on day 0, the day of virus inoculation. In monkeys treated with one dose of IgG on day 0, onset of illness and viremia was delayed, but all treated animals died. A second dose of IgG on day 5 had no additional beneficial effect. Pretreatment of monkeys delayed onset of viremia and delayed death several additional days. Interferon-alpha2b (2 x 10(7) IU/kg/day) had a similar effect in monkeys, delaying viremia and death by only several days. Effective treatment of Ebola infections may require a combination of drugs that inhibit viral replication in monocyte/macrophage-like cells while reversing the pathologic effects (e.g., coagulopathy) consequent to this replication.

Animals↗
PubMed1999

Prevalence of antibodies to West Nile fever, sandfly fever Sicilian, and sandfly fever Naples viruses in healthy adults in Israel.

BACKGROUND: The arbovirus infections West Nile fever (WNF) and sandfly fever (SFF) are both endemic in the Middle East. Despite the fact that the mosquito and sandfly vectors of these viruses are still found in Israel, SFF has not been reported since 1948, whereas outbreaks of WNF occur periodically. It is suspected that some of the cases of nonspecific febrile illnesses in Israel may in fact be either WNF or SFF. AIM: To determine the extent of past arbovirus infections in subgroups of Israeli soldiers. METHODS: Sera from random samples of three groups of healthy soldiers aged 18-20 (n=273), 21-30 (n=497), and 40-55 years (n=285) were examined for IgG and IgM antibodies to West Nile virus (WNV), sandfly fever Sicilian virus (SFSV), and sandfly fever Naples virus (SFNV), using an ELISA method. RESULTS: The prevalence of antibodies increased with age for all three viruses examined, and ranged from 7.0%, 0, and 2.8%, for WNV, SFSV, AND SFNV, respectively, in soldiers aged 18-20 years, to 41.9%, 23.7%, and 30.8%, in those aged 40-55 years. The percentage of seropositives for IgG who were also IgM positive were 1.0%, 5.9%, and 3.4%, for WNV, SFSV, AND SFNV, respectively. 17.5% of the seropositives for WNV were also positive for SFSV, as compared with 5.7% among the WNV-seronegatives. Among the seropositives for WNV, 23.99% were positive for SFNV, compared with 9.1% of WNV seronegatives. 48.2% of seropositives for SFSV were positive for SFNV, as compared with 8.4% for SFSV-seronegatives. In the age agroup 40-55 years, there were significantly higher prevalence rates in those born in Israel compared with those born abroad. CONCLUSIONS: There is still significant exposure to WNV, SFSV, and SFNV in Israel. Arborviruses are probably responsible for many cases of non-specific febrile illness in this region.

Adolescent↗
PubMed1996

Yellow fever: a decade of reemergence.

Since the 1980s, yellow fever has reemerged across Africa and in South America. The total of 18 735 yellow fever cases and 4522 deaths reported from 1987 to 1991 represents the greatest amount of yellow fever activity reported to the World Health Organization (WHO) for any 5-year period since 1948. There is an excellent vaccine against yellow fever. At present, a high proportion of travelers to at-risk areas are reported to be immunized, reflecting widespread knowledge about the International Health Regulations. In South America, yellow fever remains an occupational hazard for forest workers, who should be immunized. However, Aedes aegypti mosquitoes are now present in urban areas in the Americas (including southern parts of the United States), and there is concern that yellow fever could erupt in explosive outbreaks. In Africa, a large proportion of cases have occurred in children. The WHO, the United Nations Children's Fund (UNICEF), and the World Bank have recommended that 33 African countries at risk for yellow fever add the vaccine to the routine Expanded Programme on Immunization; studies show that this would be highly cost-effective. To date, financing yellow fever vaccine has been a major problem for these countries, which are among the poorest in the world. For this reason, WHO has launched an appeal to raise $70 million for yellow fever control in Africa.

Africa↗
PubMed1996

Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses.

A commercially available immunoglobulin G (IgG) from horses, hyperimmunized to Ebola virus, was evaluated for its ability to protect cynomolgus monkeys against disease following i.m. inoculation with 1 000 PFU Ebola virus (Zaire '95 strain). Six monkeys were treated immediately after infection by i.m. infection of 6.0 ml IgG; these animals developed passive ELISA titers of 1:160 to 1:320 to Ebola, two days afer inoculation. However, the beneficial effects of IgG treatment were limited to a delay in onset of viremia and clinical signs, in comparison with untreated controls. The six IgG recipients had no detectable viremia day 5, in contrast with three virus infected controls whose viremias exceeded 7.0 log10 PFU/ml that day. The controls died on days 6, 6, and 7, while two IgG recipients died day 7 and the remaining 4 died day 8, all with high viremias. These results document that passively acquired antibody can have a beneficial effect in reducing the viral burden in Ebola-infected primates; however, effective treatment of human patients may require antibodies with higher specific activities and more favorable pharmacokinetic properties than the presently available equine IgG.

Animals↗
PubMed1996

WHO program on emerging virus diseases.

Infectious diseases, and especially viral diseases, are important, evolving complex public health problems. Their ultimate prevention and control will increasingly require sophisticated interaction between epidemiologic resources, molecular expertise, and application of modern statistical tools. The integration of epidemiologic and laboratory sciences is central to the success of a coordinated approach to new, emerging and re-emerging infectious diseases, and the WHO is attempting to facilitate and strengthen these resources internationally by focusing on improved surveillance, infrastructure building, applied research, and improved prevention and control strategies. Reference virus laboratories, especially those that deal with exotic virus diseases, will play a key role in implementation of the program, since these laboratories are likely to be called upon to assist in the identification of new, emerging, or re-emerging diseases. Thus, ensuring that these laboratories are well prepared to perform their critical tasks is essential to the ultimate success of the program.

Biometry↗
PubMed1995

Laboratory acquired tick-borne meningoencephalitis: characterisation of virus strains.

BACKGROUND: The handling of tick-borne encephalitis (TBE) virus is potentially hazardous, as indicated by a number of laboratory-acquired infections in the prevaccination era. OBJECTIVES: (1) To reemphasize the hazard of handling TBE virus without being vaccinated by describing the case of a laboratory-acquired full-blown TBE in a microbiologist who isolated the virus from a blood sample. (2) To molecularly characterize the causative virus strain isolated in Slovenia in comparison with the European prototype strain Neudoerfl. STUDY DESIGN: The virological diagnosis of the laboratory infection was established by serology and virus isolation. The virus was characterized by restriction fragment analysis of PCR products of amplified genomic sequences and a panel of monoclonal antibodies reacting with the major envelope protein. RESULTS: The laboratory infection, most probably acquired by aerosol, resulted in a biphasic course of the disease with a severe meningoencephalitis in the second phase. Both by restriction fragment and monoclonal antibody analysis the Slovenian virus strains involved were indistinguishable from the European prototype strain. CONCLUSIONS: This report confirms the potential hazard of handling TBE virus in the laboratory without being vaccinated. The similarity of the virus isolates from Slovenia with the European prototype strain confirms the previously observed homogeneity of TBE virus strains from different European countries.

Journal Article↗
PubMed1994

Isolation of a Puumala-like virus from Mus musculus captured in Yugoslavia and its association with severe hemorrhagic fever with renal syndrome.

An outbreak of severe hemorrhagic fever with renal syndrome (HFRS) occurred in 1988 in Pozarevac, Serbia, Yugoslavia. The disease was diagnosed in 4 children and 1 adult, and 1 of the children died. Rodents were captured from the same area and virus isolation attempted. A hantavirus, POZ-M1, was isolated from lung tissues of hantavirus antigen-positive Mus musculus. Serology and restriction enzyme digestion of polymerase chain reaction-amplified segments from this virus showed that it was a strain of Puumala (PUU) virus, the causative agent of nephropathia epidemica. While Clethrionomys glareolus is the major rodent host for PUU virus, these results suggest that M. musculus may also play an important role in harboring and transmitting PUU-like viruses. The serologic association of this virus with patients with severe HFRS reaffirms that PUU-like viruses may cause severe disease in addition to the generally mild form normally associated with nephropathia epidemica.

Animals↗
PubMed1994

Domestic cases of hemorrhagic fever with renal syndrome in the United States.

Although serologic studies have identified hantaviral infection in the United States, acute disease has not been recognized. This study describes 3 cases of domestically acquired hemorrhagic fever with renal syndrome (HFRS) in the United States. Infection was due to a local strain of Seoul virus (Baltimore rat virus). A review of the clinical features indicated a mild illness characterized by nausea, vomiting, renal and liver failure similar to HFRS described elsewhere for rat-borne viruses. Follow-up of 2 patients identified persistent hypertension and renal disease providing further evidence of an association between past hantaviral infection and hypertensive renal disease.

Antibodies, Viral↗
PubMed1993

Dobrava virus as a new Hantavirus: evidenced by comparative sequence analysis.

Dobrava virus, recently isolated from a yellow-neck mouse (Apodemus flavicollis), captured in a northern Slovenian village where severe cases of hemorrhagic fever with renal syndrome were recognized, was shown by serology and restriction enzyme digestion of PCR-amplified gene segments to be related to previously recognized hantaviruses. To investigate further the relationship of this new isolate to other hantaviruses, a portion of the medium (M) genome segment of Dobrava virus was amplified by PCR and the nucleotide sequence determined. Comparing the nucleotide sequence with the same gene region of other hantaviruses revealed an overall homology of 41.7%. A phylogenetic tree based on pairwise sequence similarity clearly showed that Dobrava virus is genetically distinct, and probably represents a new virus in the genus Hantavirus of the family Bunyaviridae.

Animals↗
PubMed1993

Infection with a ratborne hantavirus in US residents is consistently associated with hypertensive renal disease.

A survey of 8080 subjects was conducted in Baltimore, examining the association between infection with hantaviruses and renal disease. Two groups (N = 6060) with no known risk factors were selected to establish a baseline antibody prevalence. Overall, antibody prevalence was 0.25%. Seroprevalence increased with age, without sex- or race-related differences. Patients with proteinuria showed the same patterns of infection but were more commonly seropositive (1.46%) than the reference group (OR, 3.23; P < .05). Infection among dialysis patients with end-stage renal disease was 2.76%, significantly higher than in the reference group (OR, 5.03; P < .05). In the proteinuria and the dialysis groups, hantavirus infection was consistently associated with a diagnosis of hypertensive renal disease. The association was unrelated to other chronic renal disease diagnoses. Overall, 6.5% of patients with end-stage renal disease due to hypertension were seropositive for a hantavirus. These data suggest that hantavirus infection is associated with hypertensive renal disease.

Adult↗
PubMed1993

Attenuation phenotype of a cell culture-adapted variant of hepatitis A virus (HM175/p16) in susceptible New World owl monkeys.

The virulence of a clonally isolated, cell culture-adapted hepatitis A virus (HM175/p16) was assessed in 4 seronegative owl monkeys inoculated intravenously with 2.8 x 10(4) radioimmunofocus-forming units of virus. The virus was highly attenuated, even though its complete nucleotide sequence contains only 19 mutations from the wild-type genome. Only 3 monkeys developed antibodies to hepatitis A virus (only 2 within 96 days of virus inoculation). One monkey had viremia and significantly elevated serum aminotransferase levels. In this animal, maximum viremia and fecal shedding of virus occurred 30-33 days after inoculation. In contrast, in earlier studies of a related cell culture-adapted but still hepatovirulent virus (HM175/S18), viremia was documented in 6 of 6 animals and peak viremia and fecal shedding of virus occurred 18 or 19 days after intravenous inoculation of about one-tenth as much virus.

Adaptation, Biological↗
PubMed1993

Experimental hepatitis E: pathogenesis in cynomolgus macaques (Macaca fascicularis).

The pathogenesis of experimental hepatitis E has not been thoroughly investigated. The purpose of this study was to more accurately document the events in this disease. Cynomolgus macaques were inoculated intravenously with bile or feces containing hepatitis E virus (HEV). Serum, bile, and liver specimens were evaluated with light microscopy, immune electron microscopy, immunofluorescence microscopy, EIA, and polymerase chain reaction. In the third week, there were histopathologic changes and HEV antigen (HEVAg) in liver, HEV in bile, and alanine aminotransferase (ALT) elevations. Widespread pathologic changes were detected during the fourth week and antibody to HEV (anti-HEV) and peak ALT values in the fifth or sixth week. By the sixth week, HEVAg had disappeared but pathologic changes persisted. This study supports the concept that experimental hepatitis E has an initial phase in which hepatic HEV replication is accompanied by the onset of hepatitis and a later phase in which the appearance of anti-HEV is accompanied by progression of the hepatitis.

Alanine Transaminase↗