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J K Hilliard

Publications and source records attributed to J K Hilliard.

At least 19 recordsLinked to original sources
PubMed2000

Outbreak of Orthoreovirus-induced meningoencephalomyelitis in baboons.

BACKGROUND AND PURPOSE: Spontaneous viral encephalitis is rare in the baboon; yet, during a 13-month period (1993-1994), eight juvenile baboons (Papio cynocephalus spp.) developed acute, progressive nonsuppurative meningoencephalomyelitis caused by an unknown agent. Clinical signs of disease included disorientation and truncal ataxia that rapidly progressed to hemiparesis or paraparesis. Clinicopathologic findings were not remarkable and appreciable gross lesions were not seen at necropsy. Microscopic examination revealed CNS lesions that were characterized by lymphoplasmacytic perivascular cuffing, microglial nodules, demyelination, axonal degeneration, vacuolization, and hemorrhage. Subsequently, a novel syncytium-inducing mammalian orthoreovirus was isolated from the brain tissue of five baboons with clinical signs of infection. METHODS: To confirm the etiologic role of the orthoreovirus, two juvenile baboons were inoculated with the virus, then were monitored for 6 weeks. RESULTS: Lesions similar to those seen in spontaneous cases were found in the CNS, and orthoreovirus was isolated from the brain of both animals. CONCLUSION: Analysis of the outbreak indicated juvenile baboons were most susceptible to disease and the virus had a possible incubation time of 46 to 66 days, but did not indicate a source of the virus or mode of transmission.

Animals↗
PubMed2000

Herpes B-virus specific-pathogen-free breeding colonies of macaques (Macaca mulatta): diagnostic testing before and after elimination of the infection.

BACKGROUND AND PURPOSE: The National Institutes of Health's (NIH) National Center for Research Resources' (NCRR) Division of Comparative Medicine has funded the establishment of specific pathogen-free (SPF) captive macaque colonies. Herpes B-virus (Herpesvirus simiae, Cercopithecine herpesvirus type 1) has been targeted for elimination. Late seroconversion presents the greatest threat to the integrity of SPF colonies. The purpose of the study reported here was to evaluate that threat through detailed investigation of the patterns of seroreactivity and housing histories in one colony. METHODS: From 1990 through 1997, the B-virus Resource Laboratory screened macaques for B-virus, using ELISA or western immunoblot analysis. In 1993, we combined test results and housing histories to verify the seronegative status of one colony. RESULTS: Two groups of latently infected macaques were identified as to time and place of transmission. The infection was eradicated within 3 years (1990-1992), as judged by the absence of true positive seroreactivity in any screened macaques. New infections were not identified in four years of follow-up evaluation. CONCLUSION: With rigorous surveillance, the SPF status of the colony was achieved and maintained.

Animals↗
PubMed1999

B-virus specific-pathogen-free breeding colonies of macaques (Macaca mulatta): retrospective study of seven years of testing.

BACKGROUND AND PURPOSE: National Institutes of Health's Division of Comparative Medicine has sponsored a multi-institutional program for the establishment of specific-pathogen-free (SPF) macaque colonies. B virus (Herpesvirus simiae, Cercopithecine herpesvirus type 1) has been targeted in this surveillance. Participating institutions have established individual timetables for frequency of testing and types of monitoring and husbandry techniques, all with the common goal of producing pathogen-free monkeys for research. The greatest biosecurity threat to the program comes from failure to detect seronegative latent infections, either in first-year macaques or macaques introduced in subsequent years, although these are supposed to operate as closed colonies. METHODS: From January 1990 through December 1996, we screened macaques for B virus, using enzyme-linked immunoabsorbant assay (ELISA) and Western blot analysis. RESULTS: During the first year, 1,097 macaques from six colonies were tested, and 88.4% tested negative for B virus. During the seventh year, 1,843 were tested, of which 99.7% tested negative. Seropositive macaques were detected as late as the seventh year. CONCLUSIONS: An aggressive program to establish an SPF colony of captive breeding macaques can be effective in reducing the risk of B-virus exposure.

Animals↗
PubMed1998

Clinical disease associated with simian agent 8 infection in the baboon.

Simian agent 8 (SA8) is an alphaherpesvirus that was first reported as a spontaneous natural infection in a captive baboon colony in 1988. It was first isolated from an African vervet monkey in 1958 and was classified as a simian agent. Simian agent 8 was later isolated from a baboon rectal swab specimen in 1969 and from an oral lesion in a vervet monkey in 1972. Restriction endonuclease analysis was used to identify the virus as SA8. In a 1-year period, 70 baboons housed in two outside 6-acre breeding corrals developed lesions principally on the genitalia and oral cavity. The incidence was the same for males and females, with recurrence rate, severity of the lesions, and duration for the lesions to resolve being greater in the female baboons. Lesions involving the mouth, tongue, and lips were most commonly observed in the juvenile population. The lesions tended to start as small multiple papules or vesicles, which advanced to large pustular or ulcerative areas. Using an every-other-day treatment regimen consisting of Nolvasan cleaning and procaine penicillin G injections, it took an average of 14 to 21 days for the lesions to resolve totally. Thirty-seven percent of the baboons with herpetic lesions experienced another episode of SA8 infection, usually within 1 year of development of the primary lesion. Several complications have been documented to be associated with SA8 infections. Partial or total vaginal obstruction is most common, leading to impaired breeding performance and pyelonephritis. A vaginal corrective surgical procedure has been developed to allow these females to return to productive breeding status within the colony. Penile urethral obstruction, also causing pyelonephritis, was observed in the male baboons. A case of sciatic neuritis was reported in a baboon that presented with self mutilation of the foot; viral isolation revealed the etiologic agent to be SA8. Four female baboons with chronic SA8 infections went on to develop perineal neoplasms. This is an economically important disease entity in captive baboons because it causes severe morbidity, decreased reproductive performance, and ultimately death in 1% of the baboon colony each year. The baboon is a promising animal model in which to study genital herpes as it relates to disease in human beings.

Alphaherpesvirinae↗
PubMed1995

Herpesvirus papio 2, an SA8-like alpha-herpesvirus of baboons.

Several SA8 isolates obtained from baboons were compared to the prototype SA8 herpesvirus of African green monkeys. SDS-PAGE and restriction enzyme analyses revealed definite differences between green monkey and baboon isolates. DNA and amino acid sequences of the gB, gD and gJ glycoprotein genes exhibited substantial differences in variable regions. For the gB and gD, the amount of amino acid substitutions between SA8 and the baboon viruses was comparable to levels observed between analogous genes of SA8 & B virus or HSV1 & HSV2. Although a high degree of antigenic cross-reactivity was apparent, virus-specific antigenic determinants were also readily detected. Phylogenetic analyses supported separation of the baboon isolates and SA8 as distinct viruses. Taken together these results suggest that although closely related to SA8, the baboon viruses represent a distinct simian alpha-herpesvirus which we propose be designated Herpesvirus papio 2.

Amino Acid Sequence↗
PubMed1995

Guidelines for the prevention and treatment of B-virus infections in exposed persons. The B virus Working Group.

Cercopithecine herpesvirus 1 (B virus), enzootic among monkeys of the genus Macaca, causes minimal morbidity in its natural host. In contrast, human B-virus infection presents as rapidly ascending encephalomyelitis with a fatality rate of approximately 70%. This infection remains an uncommon result of macaque-related injuries, although the increase in the use of macaques for research on simian retrovirus infection and hepatitis has expanded the number of opportunities for human exposure. In response to this situation, Emory University and the Centers for Disease Control and Prevention jointly sponsored a B Virus Working Group to formulate a rational approach to the detection and management of human B-virus infection. The resulting guidelines are presented herein and are based upon information from published cases, unpublished cases managed by working-group members, knowledge of the behavior of herpes simplex virus, and--in the absence of hard data--the collective judgment of the group. Although consensus among the co-authors existed on the major points covered by these guidelines, opinions varied widely regarding specific recommendations.

Animals↗
PubMed1995

Risk of venereal B virus (cercopithecine herpesvirus 1) transmission in rhesus monkeys using molecular epidemiology.

The importance of venereal modes of B virus (cercopithecine herpesvirus 1) transmission was evaluated in 49 rhesus monkeys tested at necropsy. Antibodies to B virus were demonstrated in 19 monkeys, but no active viral shedding was detected in mucosal swabs collected at death. The polymerase chain reaction demonstrated presence of the ICP 18.5 (UL28) gene of B virus in neuronal tissues of 15 monkeys presumed to be latently infected, including 12.8% of trigeminal and 22.9% of lumbosacral ganglia pools. Two monkeys tested positive at both sites. Breeding history was predictive of B virus seropositivity (odds ratio, 1.64; 95% confidence interval, 1.21-2.23; P < .05). The population attributable risk of B virus seropositivity due to breeding was 22.7%, similar to the proportion of monkeys with B virus DNA in neuronal tissues subserving the genital region. Sexual contact is a significant, but not predominant, mode of B virus transmission between monkeys.

Age Factors↗
PubMed1994

Occurrence of human papillomavirus and p53 gene mutations in Kaposi's sarcoma.

Epidemiological evidence indicates that a sexually transmitted agent might be involved in the etiopathogenesis of Kaposi's sarcoma (KS). The prevalence of human papillomaviruses (HPV) in KS has been the focus of several investigations that have reported conflicting data. In addition, mutations of the p53 gene, which are the most frequent genetic changes found in human tumors, are absent in HPV-positive cervical carcinomas leading to the hypothesis that the function of p53 in HPV-positive tumors is inactivated through binding to the E6 viral gene product. Thus, the present study was designed to investigate the presence of HPV and p53 gene mutations in 17 formalin-fixed, paraffin-embedded KS [7 acquired immunodeficiency syndrome-KS (AIDS-KS) and 10 classic KS] specimens. HPV 6 DNA was detected in an AIDS-KS specimen, and HPV 16 DNA was found in 3 classic KS specimens. Heterozygous mutations of the p53 gene were detected in five (24%) KS samples. No p53 mutations were detected in HPV-positive KS. The p53 mutations were mainly transversions (four of five). These data indicate that HPV may contribute to the pathogenesis of some cases of KS and that p53 alteration may represent a key event in the progression of the malignancy.

DNA, Viral↗
PubMed1994

Diagnosis and management of human B virus (Herpesvirus simiae) infections in Michigan.

Three men who had worked at the same animal research facility and had had contact with macaque monkeys were infected with B virus (Herpesvirus simiae). Their clinical presentations varied from self-limited aseptic meningitis syndrome to fulminant encephalomyelitis and death. Patient 1 was treated only after a respiratory arrest and other signs of advanced brain stem dysfunction had occurred. He died 8 days after hospital admission, despite treatment with acyclovir. Patient 2 presented with subtle signs and symptoms of brain stem encephalitis. He received antiviral therapy with intravenous ganciclovir. Patient 3 had a headache without meningismus and was also treated with acyclovir. Both patients 2 and 3 survived and did not have objective sequelae. Viral culturing, ELISA and western blot antibody testing, and magnetic resonance imaging all proved useful in the diagnosis of these patients' conditions.

Acyclovir↗
PubMed1994

B virus-specific pathogen-free (SPF) breeding colonies of macaques: issues, surveillance, and results in 1992.

The NIH's National Center for Research Resources, Comparative Medicine Program has sponsored a multi-institutional program for the establishment of specific pathogen-free (SPF) macaque colonies. Herpes B virus (Cercopithecine herpesvirus I) has been targeted as part of this surveillance. Participating institutions have established individual timetables for frequency of testing, types of monitoring, and husbandry techniques, all with the common goal of producing pathogen-free monkeys for research. From January 1990 through December 1992, we screened animals for evidence of B virus infection, using ELISA and immunoblot to detect humoral antibodies. A total of 984 animals were tested during the first year of the program. At the start of the third year, 631 animals remained in our testing program. Of the 36.9% eliminated for all causes over a 3-year period, B virus screening accounted for 12.1, 1.2, and 0.5% during years 1, 2, and 3, respectively. The greatest threat to the success of the program comes from failure to detect seronegative animals with latent infections, if they do indeed exist, either in first-year animals or animals introduced in subsequent years. The best assurance that a colony is SPF comes from negative results of repeated testing. Introducing new animals into an established SPF colony should be done only after careful screening. Simulations using mathematical models suggest that the best way to detect seronegative animals with latent infections is monthly or bimonthly testing separated by a waiting period. Duration of the waiting period cannot be defined precisely until more is known about the reactivation potential of putative seronegative animals with latent infections.

Animals↗
PubMed1993

Epidemiology of cercopithecine herpesvirus 1 (B virus) infection and shedding in a large breeding cohort of rhesus macaques.

The epidemiology of B virus infection in a large (n = 157) cohort of rhesus macaques at the California Regional Primate Research Center was evaluated prospectively from September 1989 through January 1991 by serial physical examinations, a behavioral substudy (n = 51), and repeated diagnostic testing. Half were B virus antibody-positive at baseline; subsequently, incident cases of infection were documented through serology alone (42) or with virus isolation (5). Eight recurrent infections and a single symptomatic (primary) case were observed. Risk of B virus infection increased as monkeys aged, with few > 3 years old remaining uninfected. Postpubertal monkeys and those entering sexual adolescence (2-3 years) were at greatest risk, although wounding by cagemates and breeding history (for females) were both significant predictors of time to infection. B virus was isolated from oral or conjunctival and genital tissues in equal proportions. Transmission occurred only during the breeding season, possibly coinciding with an elevation in social stressors in the population.

Animals↗
PubMed1993

Rapid detection of B virus (herpesvirus simiae) DNA by polymerase chain reaction.

Rapid diagnosis of B virus (herpesvirus simiae) infection in humans followed by early antiviral treatment is essential for the patient's survival. To improve laboratory diagnosis of B virus infections, a polymerase chain reaction (PCR)-based test using synthetic oligonucleotide primers and probe was developed to detect B virus DNA in clinical samples. After the specificity of the PCR was assessed for detection of several B virus isolates, the method was used to investigate human and monkey specimens, and results were compared with those obtained by viral culture. PCR appeared to be more sensitive than conventional virus isolation and thus of practical use for a rapid identification of B virus infection when conventional viral cultures are negative.

Animals↗
PubMed1993

Infrequent shedding and transmission of herpesvirus simiae from seropositive macaques.

The epizootiologic properties of Herpesvirus simiae (B virus) were studied in singly housed macaques (Macaca mulatta and M. fascicularis) in a biomedical vivarium to determine whether commonly encountered environments and procedures such as quarantine, breeding, Caesarean section, parturition, and social stress induced virus shedding and transmission. Macaques were tested serologically and for infectious virus. Oral, conjunctival, and vaginal swab samples were obtained repeatedly. Virus excretion was not detected during a 7-week quarantine of 32 newly acquired, singly housed animals tested every other week for 6 weeks, and none of 19 seronegative animals from this group seroconverted during 7 weeks in quarantine. No virus shedding was detected in 16 seropositive animals tested weekly for 3 weeks after Caesarean section or normal parturition or in 11 seropositive animals following introduction of new males to animals rooms. One animal seroconverted after repeated breeding of seropositive animals to seronegative partners. Fifty-three singly housed offspring remained seronegative for up to 10 years, even if born to seropositive dams, and only 1 of 86 singly housed animals less than 7 years old was seropositive. These results suggest that shedding of B virus from seropositive macaques is uncommon, when subjected to common laboratory procedures or environments, and that transmission is rare in singly housed animals. These results may be useful in establishing B virus-free colonies of macaques.

Animals↗
PubMed1992

Activation of B virus (Herpesvirus simiae) in chronically immunosuppressed cynomolgus monkeys.

Three of 14 cynomolgus monkeys given the highest dose of an immunosuppressive drug in a 6-month toxicology study developed B virus (Herpesvirus simiae) oral lesions after 3 months of dosing. This necessitated early removal of all high-dose monkeys from the study due to concerns related to B virus. The incidence and severity of parasitic (Oesphagostomum sp.) lesions of the large intestine were also increased in high-dose animals. Both B virus and Oesophagostomum are enzootic in macaques, and the lesions caused by them were considered secondary to chronic immunosuppression caused by the highest dose of the test compound. Evidence of immunosuppression included decreased lymphocyte counts (B-cells; CD2 and CD8 T-cells), histopathologic evidence of lymphoid suppression, and serum-induced inhibition of lymphocyte mitogen responses. Pathogenesis of the B virus was apparently associated with both activation of latent virus as well as transmission of active virus. Approaches for virologic monitoring of primates and for ensuring optimal safety for primate handlers are discussed.

Animals↗
PubMed1990

B virus (Herpesvirus simiae) infection in humans: epidemiologic investigation of a cluster.

A cluster of four cases of symptomatic B virus infection in humans occurred in Pensacola, Florida, in March 1987. Three cases occurred in persons who worked with monkeys at a research facility, and the fourth resulted from apparent autoinoculation through use of a nonprescription skin cream. Contact tracing identified 159 persons who may have been exposed to B virus (21 had been exposed to monkeys at the facility and 138 had been exposed to one or more of the case-patients), but no further cases were identified. Comparisons of restriction endonuclease patterns from B virus isolates linked two of the three cases in monkey handlers to one clinically ill monkey and the other to a second, healthy monkey. Three risk factors for human infection were identified: nonuse of mechanical or chemical restraints for monkeys before handling, nonuse of available protective gear, and direct viral inoculation through the application of a topical medication.

Acute Disease↗
PubMed1990

Ocular histopathologic findings in a case of human herpes B virus infection.

A 37-year-old male laboratory technician who sustained a cutaneous penetrating wound from a rhesus monkey developed a progressive ascending encephalomyelitis due to culture-proven herpes B virus (Herpesvirus simiae) infection. He died 6 weeks after his injury despite acyclovir and ganciclovir treatment that was initiated after central nervous system symptoms developed. Histopathological examination of the patient's left eye revealed a multifocal necrotizing retinitis associated with a vitritis, optic neuritis, and prominent panuveitis. Herpes-type virus was identified in the involved retina by electron microscopy. Postmortem vitreous cultures taken from both eyes and retinal cultures taken from the right eye were positive for herpes B virus. Herpes B virus produces infection and destruction of retinal tissues similar to other herpesviruses. To our knowledge, this case represents the first histopathologic demonstration of herpes B virus infection in a human eye.

Adult↗
PubMed1990

Nonhuman primate bites.

Nonhuman primate (monkey) bites to researchers and attending animal care staff may present problems in patient management. Such inoculations can transmit serious bacterial and viral infections to the human handlers. Significant local and systemic manifestations can subsequently develop following such an injury. Since Herpesvirus simiae (B virus) is enzootic in Asiatic monkeys of the genus Macaca, and since B virus infection in humans is usually fatal, additional prophylactic and therapeutic measures must be taken when persons are bitten by macaque monkeys. Primate bites require early aggressive intervention.

Acyclovir↗