Pet rodents and fatal lymphocytic choriomeningitis in transplant patients.
In April 2005, 4 transplant recipients became ill after receiving organs infected with lymphocytic choriomeningitis virus lymphocytic choriomeningitis virus
A virus of the genus Arenavirus that is the causative agent of lymphocytic choriomeningitis. (LCMV LCMV Lymphocytic Choriomeningitis Virus
LCMV Linearly Constrained Minimum Variance
LCMV Least Cost Matrix Value
LCMV Lightweight Counter-Mortar Radar ); 3 subsequently died. All organs came from a donor who had been exposed to a hamster infected with LCMV. The hamster was traced back through a Rhode Island Rhode Island, island, United States
Rhode Island, island, 15 mi (24 km) long and 5 mi (8 km) wide, S R.I., at the entrance to Narragansett Bay. It is the largest island in the state, with steep cliffs and excellent beaches. pet store to a distribution center in Ohio, and more LCMV-infected hamsters were discovered in both. Rodents from the Ohio facility and its parent facility in Arkansas were tested for the same LCMV strain as the 1 involved in the transplant-associated deaths. Phylogenetic phy·lo·ge·net·ic
1. Of or relating to phylogeny or phylogenetics.
2. Relating to or based on evolutionary development or history. analysis of virus sequences linked the rodents from the Ohio facility to the Rhode Island pet store, the index hamster, and the transplant recipients. This report details the animal trace-back and the supporting laboratory investigations.
Lymphocytic choriomeningitis virus (LCMV) is a rodentborne arenavirus arenavirus /are·na·vi·rus/ (ah-re´nah-vi?rus) any virus of the family Arenaviridae.
Arenavirus /Are·na·vi·rus/ (ah-re´nah-vi?rus endemic in house mice (Mus musculus) worldwide (1-3). Lymphocytic choriomeningitis Lymphocytic Choriomeningitis Definition
Lymphocytic choriomeningitis (LCM) is a viral infection of the membranes surrounding the brain and spinal cord and of the cerebrospinal fluid. (LCM (Liquid Crystal Monitor) A flat panel display that uses the liquid crystal (LCD) technology. See flat panel display. ) in immunocompetent im·mu·no·com·pe·tent
Having the normal bodily capacity to develop an immune response following exposure to an antigen.
im persons usually is a mild, self-limited, viral syndrome or is asymptomatic; aseptic meningitis aseptic meningitis Infectious disease Nonpurulent meningeal inflammation, which is more common in those < age 30 Etiology Viruses, especially Coxsackievirus and echovirus, circumscribed bacterial infections, hemorrhage, neoplasia–eg leukemia and lymphoma, also can occur, but the infection is rarely fatal (4-6). In immunocompromised immunocompromised /im·mu·no·com·pro·mised/ (-kom´pro-mizd) having the immune response attenuated by administration of immunosuppressive drugs, by irradiation, by malnutrition, or by certain disease processes (e.g., cancer). persons, LCM may result in serious systemic infections and death. LCM during pregnancy can cause spontaneous abortion spon·ta·ne·ous abortion
A naturally occurring termination of a pregnancy. Also called miscarriage.
spontaneous abortion or severe birth defects birth defects, abnormalities in physical or mental structure or function that are present at birth. They range from minor to seriously deforming or life-threatening. A major defect of some type occurs in approximately 3% of all births. , including hydrocephalus hydrocephalus (hī'drəsĕf`ələs), also known as water on the brain, developmental (congenital) or acquired condition in which there is an abnormal accumulation of body fluids within the skull. , chorioretinitis, blindness, or psychomotor retardation Psychomotor retardation
Slowed mental and physical processes characteristic of a bipolar depressive episode.
Mentioned in: Bipolar Disorder
psychomotor retardation (7). Congenital LCMV infection is likely greatly underreported as a cause of poor pregnancy outcomes (7). Human infection occurs most commonly through exposure (by direct contact or inhalation of infectious aerosol) to secretions or excretions of infected animals (8). To our knowledge, person-to-person transmission has not been reported, except for transmission from mother to fetus (7) and 1 previous cluster in December 2003 of infection through organ transplantation The transfer of organs such as the kidneys, heart, or liver from one body to another.
The transplantation of human organs has become a common medical procedure. Typical organs transplanted are the kidneys, heart, liver, pancreas, cornea, skin, bones, and lungs. (9,10).
In early April 2005, 4 recipients of solid-organ transplants in 3 hospitals in Rhode Island List of hospitals in Rhode Island (U.S. state), sorted by hospital name.
CDC - Control Data Corporation ), where LCMV was identified as the etiologic agent (10). Viral sequences from the organ recipients were identical to those from a pet hamster acquired by the donor's household 17 days before organ donation (10). Here we report the results of an epidemiologic and environmental investigation to identify the origin of the index hamster and the source of the virus.
Thorough epidemiologic investigations were conducted at the Rhode Island pet store where the index hamster was purchased, the Ohio distribution facility that supplied the pet store, and the primary breeding facility in Arkansas. These investigations focused on interviews; review of invoices, shipping records, and US Department of Agriculture inspection reports; and on-site environmental assessments.
Rodent Sample Collection
All available rodent species known to be competent hosts for LCMV (capable of becoming chronically infected and shedding virus for up to 9 months) (6,11,12) were collected from the remaining rodent stock at the Rhode Island pet store. These species included Syrian hamsters (Mesocricetus auratus Mesocricetus auratus
see cricetus. ), "fancy" mice (M. musculus), and guinea pigs (Cavia porcellus). Although they have not been shown to be competent reservoirs for LCMV, "fancy" rats (Rattus norvegicus) and gerbils (Meriones unguiculatus Meriones unguiculatus
see Mongolian gerbil. ) also were sampled because of their exposure to the infected rodents. Rodents were sampled and euthanized following approved CDC Animal Care and Use Committee protocols.
With a known population size and a LCMV prevalence estimate, the hypergeometric probability distribution Probability distribution
A function that describes all the values a random variable can take and the probability associated with each. Also called a probability function.
probability distribution was used to determine the minimum sample size needed to provide a 95% chance of detecting at least 1 LCMV infected rodent at each site. The LCMV prevalence was estimated to be 4.7% in Ohio and 4.3% in Arkansas. The Ohio prevalence was based on 4 infected of 85 tested at the Rhode Island pet store; the revised prevalence for Arkansas was based on 9 of 211 positives after data from the Ohio samples were incorporated.
The population sizes (Table 1) included only dwarf hamsters and did not distinguish between the Chinese and Roborovsky dwarf hamsters (Cricetulus curtatus and Phodopus roborovskii, respectively). An agreement was reached with the owner in which [approximately equal to] 10% of the total population of 140 Roborovsky's dwarf hamsters was sampled. In this case, the probability of detecting at least 1 positive rodent was 36.5%.
The index hamster, the organ recipients, the animals from the pet store, and rodents from the Ohio and Arkansas facilities were tested for LCMV with a combination of assays that included serology Serology
The division of biological science concerned with antigen-antibody reactions in serum. It properly encompasses any of these reactions, but is often used in a limited sense to denote laboratory diagnostic tests, especially for syphilis. , immunohistochemistry (IHC IHC Immunohistochemistry
IHC Intermountain Health Care
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IHC International Hurricane Center ), reverse transcription-PCR (RT-PCR RT-PCR
reverse transcriptase-polymerase chain reaction. See PCR1. ), TaqMan (Applied Biosystems, Foster City, CA, USA), and virus isolation. Genetic sequences obtained from the respective samples were used in the phylogenetic analysis to identify the LCMV strain and epidemiologic link leading to transplant-associated deaths.
Virus isolation was conducted by using Vero E-6 cells. For blood or serum, 100 [micro]L of sample was used as inoculum inoculum /in·oc·u·lum/ (-ok´u-lum) pl. inoc´ula material used in inoculation.
n. pl. . For tissues, a 10% cell suspension was prepared in a viral support medium (Hank's balanced salt solution with 5% heat-inactivated fetal bovine serum Fetal bovine serum ( or foetal bovine serum) is serum taken from the fetuses of cows. Fetal Bovine Serum (or FBS) is the most widely used serum in the culturing of cells. In some papers the expression foetal calf serum is used. ) and clarified by centrifugation Centrifugation
A mechanical method of separating immiscible liquids or solids from liquids by the application of centrifugal force. This force can be very great, and separations which proceed slowly by gravity can be speeded up enormously in centrifugal . A100-[micro]L aliquot aliquot (al-ee-kwoh) adj. a definite fractional share, usually applied when dividing and distributing a dead person's estate or trust assets. (See: share) of the supernatant supernatant /su·per·na·tant/ (-na´tant) the liquid lying above a layer of precipitated insoluble material.
the liquid lying above a layer of precipitated insoluble material. fluid was used as the inoculum. Flasks were incubated for 1 hour, fed with maintenance medium, and observed for 2 weeks. Cells from flasks were tested for replicating LCMV by immunofluorescent immunofluorescent
having the characteristic of immunofluorescence.
immunofluorescent antibody test
see fluorescence microscopy.
see fluorescence microscopy. antibody assay (IFA Immunofluorescent assay (IFA)
A blood test sometimes used to confirm ELISA results instead of using the Western blotting. In an IFA test, HIV antigen is mixed with a fluorescent compound and then with a sample of the patient's blood. ) on 1 of days 4-7 (depending on supplemental information made available through other testing) and again on day 14. If no reactivity was detected by IFA from days 4 to 7 or on day 14, the flask was considered negative for virus.
Molecular Detection of LCMV in Rodents
Highly sensitive real-time RT-PCR TaqMan assay was performed as described previously (10). RNA RNA: see nucleic acid.
in full ribonucleic acid
One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic isolated from rodent blood, serum specimens, or tissue was subjected to TaqMan real-time assay, and samples with cycle threshold (Ct) values <40 were scored as LCMV-positive. TaqMan-positive specimens were further analyzed by traditional RT-PCR to produce a 232-nt product within the RNA polymerase RNA polymerase
A polymerase that catalyzes the synthesis of RNA from a DNA or RNA template. (L) gene and sequences were obtained by using previously described primers (10). The sequences of LCMV from the transplant recipients, index hamster, and rodents from the Rhode Island pet store and Ohio distribution center were then compared with those obtained for other characterized LCMV strains by using GCG GCG Genetics Computer Group
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GCG Giant-Cell Granuloma Version 11.1.1 (Accelrys, San Diego, CA, USA) and PAUP PAUP Phylogenetic Analysis Using Parsimony (Sinauer Associates Inc., Sunderland, MA, USA). Further evidence of a genetic link between LCMV detected in the rodents and the human cases investigated was obtained by analyzing the viral S RNA segment. A 611-nt S segment PCR PCR polymerase chain reaction.
polymerase chain reaction
Polymerase chain reaction (PCR) product was amplified by using 1-step RT-PCR protocols with a generic primer set (13) capable of amplifying Old World arenaviruses including LCMV. The 1-step RT-PCR was carried out by using the SuperScript Any letter, digit or symbol that appears above the line. For example, 10 to the 9th power is written with the 9 in superscript (109). Contrast with subscript. III One-Step RT-PCR System with Platinum Taq High Fidelity as described by the manufacturer (Invitrogen, Carlsbad, CA, USA).
n. pl. se·rol·o·gies
1. The science that deals with the properties and reactions of serums, especially blood serum.
2. and Immunohistochemical Detection of LCMV in Rodents
An ELISA ELISA (e-li´sah) Enzyme-Linked Immuno-Sorbent Assay; any enzyme immunoassay using an enzyme-labeled immunoreactant and an immunosorbent.
n. was used to evaluate serum samples collected from rodents for immunoglobulin class G (IgG) antibodies that reacted with LCMV antigens produced in Veto E-6 cells. The assay was run as described in Fischer et al. (10), except that a protein A/protein G conjugate conjugate /con·ju·gate/ (kon´jdbobr-gat)
1. paired, or equally coupled; working in unison.
2. a conjugate diameter of the pelvic inlet; used alone usually to denote the true conjugate diameter; see (Immunopure, Pierce Biotechnology Inc., Rockford, IL, USA) was used. A subset of the samples was also tested by IFA, using infected Vero E-6 cells. Immunohistochemical tests were carded out on a variety of tissues from the index hamster (blood, adrenal gland adrenal gland (ədrēn`əl) or suprarenal gland (sprərēn`əl), endocrine gland (see endocrine system) about 2 in. (5. , salivary gland salivary gland
Any of the organs that secrete saliva. Three pairs of major glands secrete saliva into the mouth through distinct ducts: the parotid glands (the largest), between the ear and the back of the lower jaw; the submaxillary glands, along the side of the lower jaw; , pancreas, liver, spleen, kidney, lung, heart, bone marrow, cerebrum cerebrum: see brain.
Largest part of the brain. The two cerebral hemispheres consist of an inner core of myelinated nerve fibres, the white matter, and a heavily convoluted outer cortex of gray matter (see cerebral cortex). , cerebellum cerebellum (sĕr'əbĕl`əm), portion of the brain that coordinates movements of voluntary (skeletal) muscles. It contains about half of the brain's neurons, but these particular nerve cells are so small that the cerebellum accounts for , brain stem, spinal cord spinal cord, the part of the nervous system occupying the hollow interior (vertebral canal) of the series of vertebrae that form the spinal column, technically known as the vertebral column. ) as previously described by Fischer et al. (10).
Rhode Island Traceback Investigation
Physical inspection of the pet store where the donor's hamster was purchased produced no evidence of wild rodent infestation infestation /in·fes·ta·tion/ (-fes-ta´shun) parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. . The store maintained live-capture traps in areas likely to harbor rodents (e.g., near feed bags); the trapping log showed no captures in the preceding 3 months.
Although other rodents had been housed in the same area of the pet store with the index hamster, detailed records were not available and these specific rodents were not identified. Invoices dated from February through March 2005 confirmed that all rodents sold at the pet store had come from the Ohio facility.
Biosecurity in the store was limited, with opportunity for interspecific in·ter·spe·cif·ic
Arising or occurring between species.
interspecific also interspecies
Arising or occurring between species.
Adj. 1. and intraspecific in·tra·spe·cif·ic also in·tra·spe·cies
Arising or occurring within a species: intraspecific competition. cross-infection, particularly due to a lack of employee hand hygiene between handling of individual rodents. As a precautionary measure, all rodents were quarantined at the store and further sales were prohibited by the Rhode Island Department of Health after LCMV was identified in the organ recipients and the index hamster.
A total of 85 animals (55 hamsters, 8 guinea pigs, 10 mice, 7 gerbils, and 5 rats) were sampled from the remaining quarantined rodent stock at the Rhode Island pet store. Of these, 1 guinea pig and 2 hamsters were found positive for LCMV by several methods (Table 2). LCMV antibodies were detected in 1 hamster by IFA, but not ELISA. LCMV isolates were obtained from either blood or kidney and immunohistochemical stains were positive in at least 1 organ in each of the 3 rodents. All 3 rodents were positive for LCMV RNA with the L-gene-specific TaqMan primer/ probe set. The L-gene sequences obtained from these rodents were identical to one another and differed from the index hamster and transplant recipients by only 1 nt (Figure, panel A). Further evidence confirming the presence of viruses of the same genetic lineage in this episode was gathered by RT-PCR amplification of a product from the S segment. The 611-nt S segment sequences of the index hamster and the transplant recipients were 100% identical, thereby reconfirming the previously established genetic link (10). In addition, the S segment sequences obtained from the 2 Rhode Island pet store hamsters were identical, and they differed by only 2 nt from the guinea pig sequence (Figure, panel B). These results indicate the same LCMV virus strain was present in the hamsters and guinea pig in the Rhode Island pet store.
Ohio Traceback Investigation
The Ohio facility served as a distribution/staging area for rodents destined des·tine
tr.v. des·tined, des·tin·ing, des·tines
1. To determine beforehand; preordain: a foolish scheme destined to fail; a film destined to become a classic.
2. for sale in the northeastern United States. Records indicated that it received most of its hamsters from its parent breeding facility in Arkansas. Both facilities, owned by the person, routinely received shipments of rodents from smaller breeders. The Arkansas facility was the largest distributor in North America, with sales to many states.
Breeding operations at the Ohio facility had been suspended in February 2005 by order of the United States Department of Agriculture United States Department of Agriculture (USDA),
n.pr established in 1862, USDA is responsible for the safety of meat, poultry, and egg products. It conducts ongoing research in areas from human nutrition to new crop technologies and also helps ensure open (USDA USDA,
n.pr See United States Department of Agriculture. ) for multiple violations of the Animal Welfare Act (AWA AWA As Well As (internet chat lingo)
AWA Animal Welfare Act
AWA Australian Workplace Agreement
AWA America West Airlines
AWA Anime Weekend Atlanta (Anime convention in Atlanta, GA) ) (14); the suspension included all rodent species other than mice and rats. Interviews and a review of prior USDA facility inspection records indicated ongoing AWA violations and poor biosecurity practices: escaped mice and wild Mus spp. that entered the facility were routinely captured and added to captive breeding captive breeding
mating programs designed for use with animals kept in captivity. See also hand mating. populations; sick rodents shared common airspace with healthy rodents, attending veterinary services were sporadic, rodents were shipped to Ohio without necessary permits and veterinary inspections, and rodents from different sources shared cages for breeding purposes without adequate quarantine practices.
With the assistance of the Ohio Departments of Agriculture and Health, the Ohio facility was quarantined and inspected on July 18, 2005. During this inspection, several examples of poor biosecurity were found: escaped rodents ran free and entered other holding bins; evidence of a wild rodent infestation was found among the feed sacks; and rodents from disparate sources were housed in adjacent racks, with opportunity for large and small particle cross-contamination.
Shipping records were inadequately maintained, making it difficult to accurately account for the individual shipments of rodents. However, hamsters arriving at the Ohio facility from either Arkansas or other outside breeders were placed in tubs labeled with the location of origin and the date of arrival. According to employees at the facility, these hamsters were not mixed with other shipments.
A sample of 126 rodents (116 hamsters, 9 mice, and 1 guinea pig) was collected. This total comprised the statistically necessary 75 (taken from the general population) plus escaped, sick, and dead rodents. Of the specimens examined, 5 hamsters were positive for LCMV by at least 1 method (Table 2): 3 were positive by IFA, but not by ELISA. Three were positive by IHC; these same 3 were LCMV RNA-positive as evidenced by L-segment-specific TaqMan assay. Virus was isolated from kidney tissues of these 3 hamsters, and sequences were obtained from 1 virus isolate. L-segment sequence comparison of the Ohio specimen found exact identity to the Rhode Island pet store hamster virus (Figure, panel A). Additionally, sequences obtained from the 611-nt S segment of the Ohio hamster differed by only 3 nt from the index hamster sequence, thus showing 99.5% identity (Figure, panel B). These sequences were compared to sequences from other previously identified LCMV strains such as the laboratory strains LCMV-Armstrong and WE, and other isolates from clinical material (Table 3). Differences in L-segment sequences in the viruses from the index hamster and pet store/distribution center rodents were <0.5%, while LCMV-Armstrong and WE differed by 18.1% and 13.4%, respectively. Comparison of the S-segment sequences between the index hamster and pet store/distribution center viruses showed <1% difference. LCMV-Armstrong and WE differed by 14.1% and 14.7%, respectively, from the index hamster virus.
Arkansas Traceback Investigation
Several attempts were made to sample the rodents in the Arkansas facility. The initial sample was to include only Syrian hamsters and guinea pigs, but these species were destroyed by the owner when LCMV was found in the Ohio facility. Other remaining rodent species were then sampled as a proxy measure. With the assistance of the Arkansas Department of Health, 450 rodents were sampled, including 125 fancy rats, 125 gerbils, 75 fancy mice, 113 Chinese dwarf hamsters, and 12 Roborovski dwarf hamsters. One fancy rat was IgG positive for LCMV by ELISA. All other test results, including virus isolation, were negative.
This report documents the animal traceback investigation that linked a major pet rodent distribution operation to the recent outbreak of lymphocytic choriomeningitis in 4 organ transplant recipients in Rhode Island and Massachusetts. This investigation demonstrates the ways in which classic epidemiology, laboratory diagnostics, and molecular biology molecular biology, scientific study of the molecular basis of life processes, including cellular respiration, excretion, and reproduction. The term molecular biology was coined in 1938 by Warren Weaver, then director of the natural sciences program at the Rockefeller can complement one another in the investigation of disease clusters. LCMV was not found in the organ donor's tissues; however, the viral isolate from the pet store hamster was sequenced and matched to the sequences of the isolates from the recipients (10). The near-complete sequence match between the virus found in the index hamster and the virus sequenced from the Ohio hamster indicates that the genotypes share a common lineage that is distinct from previously identified strains. It is unlikely that this genotype would be as similar to a genotype found in wild house mice in Rhode Island. Thus, the animal trace-back, coupled with the molecular phylogenetic evidence, supports the hypothesis that the index hamster's infection came from the rodent distribution center in Ohio, rather than from wild M. musculus populations around the home of the donor or pet store.
Sequence and phylogenetic data provided strong support for the presence of the same LCMV lineage in hamsters and guinea pigs in the Rhode Island pet store and the Ohio distribution center and established the epidemiologic link of that particular lineage of LCMV to transplant-associated deaths. Comparison of LCMV genotypes obtained from this investigation with previously identified strains LCMV-Armstrong and WE and other isolates from clinical material found considerable differences (Figure, Table 3). While the differences in S-segment sequences between the index hamster and pet store/distribution center viruses were <1% ([less than or equal to] 3-nt difference), LCMV-Armstrong and WE differed from index hamster sequences by 14.1% (76-nt difference) and 14.7% (86-nt difference), respectively. Similarly, the differences in L-segment sequences in the viruses from the index hamster and pet store/distribution center rodents were <0.5% (3-nt difference), while LCMV-Armstrong and WE differed by 18.1% and 13.4% (41 nt and 30 nt), respectively. These analyses indicate an overall close identity among LCMV strains implicated im·pli·cate
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.
2. in this investigation, and wide differences from previously published sequences of strains Armstrong and WE. This molecular evidence corroborates the epidemiologic data implicating im·pli·cate
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.
2. LCMV transmission within the commercial pet trade.
After the identification of LCMV in the Ohio facility, all states that had received animals from this facility in the previous 5 months were notified. Many potentially infected animals still remained in stores; their disposition was determined by individual states. Actions taken ranged from sale or adoption with an information leaflet or informed consent to issuing stop sale orders on specific rodent species from the Ohio facility.
Upon notification of the Ohio sample test results, the Ohio Department of Agriculture informed the proprietor of the LCMV contamination in his facility and requested that a written plan for decontaminating the facility and a second plan for keeping the facility LCMV-free in the future be provided. The proprietor responded by depopulating the Ohio facility. The quarantine was lifted after the building was disinfected Disinfected
Decreased the number of microorganisms on or in an object.
Mentioned in: Isolation , but the facility was never reopened.
A direct link between the Arkansas and Ohio facilities was established by the discovery of the marked tubs in Ohio. This enabled the Arkansas Departments of Health and Agriculture (Livestock and Poultry) to issue a Joint Quarantine and Inspection Order. However, several days after depopulating the Ohio facility, the proprietor also destroyed all the Syrian hamsters and guinea pigs at the Arkansas facility. Although efforts were made to sample the remaining rodents at the Arkansas facility in an attempt to pinpoint the source of the virus found in Ohio, the owner refused to allow access to the rodents on several occasions and >4 months elapsed e·lapse
intr.v. e·lapsed, e·laps·ing, e·laps·es
To slip by; pass: Weeks elapsed before we could start renovating.
n. between the initial and the ultimately successful attempts to conduct sampling. Virus isolation on all samples was unsuccessful.
Several factors may have contributed to the lack of virus in the Arkansas breeding facility, including the following: 1) the virus was never there, 2) the destruction of the Syrian hamsters and guinea pigs eliminated the virus from the facility, 3) the elapsed time allowed for the removal of infected animals and subsequent decontamination decontamination /de·con·tam·i·na·tion/ (de?kon-tam-i-na´shun) the freeing of a person or object of some contaminating substance, e.g., war gas, radioactive material, etc.
n. of the facility, and 4) a complete replacement of the rodent stock was accomplished within the facility. Although the facility was under quarantine for 3 of the 4 months between the first and last attempts at sampling, only sporadic surveillance of the facility was carried out by a governmental authority. Elimination of the virus from the population did not likely occur naturally because LCMV can chronically infect mice and will lead to persistent colonial transmission (6,11).
Since the time of our investigation, the proprietor's license has been suspended by the USDA for 5 years for violations of the AWA unrelated to this investigation. The Rhode Island pet retailer who sold the index hamster reportedly ceased business relations with the distributor shortly after the infection was linked to his facilities.
To our knowledge, the Rhode Island outbreak represents the first documented case of fatal LCMV infection involving a pet animal (10). In the previous cluster of transplant-related LCMV deaths, no rodent exposure was identified (9). Several rodent species that are sold as pets, including hamsters, mice, and guinea pigs, can be incidental hosts of LCMV. These species become infected through contact with infected wild mice, and can pass the infection to humans. Most human LCMV infections are associated with exposure to wild house mice (6,15); however, several outbreaks have been attributed to laboratory and pet mice and hamsters (5,6,16,17). One example is the 1974 outbreak associated with pet hamsters sold by a single distributor. A total of 181 symptomatic cases (46 requiring hospitalization) in persons with hamster contact were identified in 12 states; no deaths occurred (5). The outbreak was brought under control by voluntary cessation of sale and destruction of the infected breeding stock.
LCMV surveillance should be a primary concern in the pet rodent industry to avoid entry of this virus into pet trade populations. Because of the ubiquitous distribution of the house mouse, eliminating the natural reservoir of LCMV is not practical. Steps can be taken, however, to exclude wild house mice from homes and businesses. Immunocompromised persons and pregnant women should be advised to avoid close contact with all rodents and infested in·fest
tr.v. in·fest·ed, in·fest·ing, in·fests
1. To inhabit or overrun in numbers or quantities large enough to be harmful, threatening, or obnoxious: areas. Educational materials should address the risk from exposure to wild mice as well as pet rodents. The virus is not naturally present in pet rodent species and the ease of transmission of the virus from pet rodents to humans may be greater than from wild mice when one considers the nature of the relationship between pet rodents and their owners (i.e., close physical contact). Therefore, every effort should be made to eliminate the virus from pet populations when it is discovered.
LCMV is already actively excluded from laboratory rodent populations, because the infection can be an occupational hazard occupational hazard n. a danger or risk inherent in certain employments or workplaces, such as deep-sea diving, cutting timber, high-rise steel construction, high-voltage electrical wiring, use of pesticides, painting bridges, and many factories. to laboratory workers who work around infected rodents (5), and because inapparent inapparent
not clearly seen.
infection without clinical signs. infection can interfere with experimental results in rodent studies (18). Economic considerations may prohibit such rigorous biosecurity measures like those used for laboratory animals; however, sentinel surveillance (19), adequate veterinary care, exclusion of wild rodents (20), and good infection control practices can substantially reduce the opportunity for introduction and spread of LCMV and other pet rodent pathogens in commercial pet populations. Efforts to increase such practices within the pet trade are under way. Adherence to regulations that are already in place for obtaining permits and veterinary inspection of commercial rodent populations can also reduce the likelihood of infection and improve animal welfare.
Further efforts to reduce risk for LCM in pet owners are ongoing. Education is critical in preventing LCM and other pet-related infections. Potential pet owners should choose pets appropriate to their household (21). Pregnant women and immunocompromised persons should avoid pet rodents altogether (22). Additionally, pet owners should be advised of the possibility of acquiring zoonotic diseases Zoonotic diseases
Diseases caused by infectious agents that can be transmitted between (or are shared by) animals and humans. This can include transmission through the bite of an insect, such as a mosquito.
Mentioned in: West Nile Virus from any pet and of precautions that should be taken to prevent acquiring pet-related infections such as LCM, tularemia tularemia (tlərē`mēə) or rabbit fever, acute, infectious disease caused by Francisella tularensis (Pasteurella tularensis). (23), salmonellosis salmonellosis (săl'mənĕlō`sĭs), any of a group of infectious diseases caused by intestinal bacteria of the genus Salmonella, (24), and others. Persons can reduce risk for infection from pet rodents by being attentive to proper hand hygiene and environmental cleaning. Additional information on LCMV is available from the CDC website (25).
We wish to acknowledge the following persons and agencies for their contributions to this investigation: James Mills, Herminia Alva, Archer Miller, Thomas Stevens, Michael Bell, Joel Montgomery, Mitesh Patel, Jeannette Guarner, Kimberly Slaughter, Deborah Cannon, Rita Helfand, Joe Foster, Heather Horton; Frank Wilson, Altino McKelvey, Randy Owens, Sherry Langley, Joe Bates Bates , Katherine Lee 1859-1929.
American educator and writer best known for her poem "America the Beautiful," written in 1893 and revised in 1904 and 1911. , Rick Hogan, Reggie Rogers, Gall Kusturin, and other staff in the Arkansas Department of Health and Human Services Noun 1. Department of Health and Human Services - the United States federal department that administers all federal programs dealing with health and welfare; created in 1979
Health and Human Services, HHS ; Jeff Hayes, David Frew, and other staff in the Ohio Departments of Agriculture and Health; Bernadette Juarez, Clara Markin, Randy Coleman, Carl LaLonde, Betty Goldentyer, and additional staff in the US Department of Agriculture Animal and Plant Inspection Service.
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(2.) Childs JE, Glass GE, Korch GW, Ksiazek TG, LeDuc JW. Lymphocytic choriomeningitis virus infection and house mouse (Mus musculus) distribution in urban Baltimore. Am J Trop Med Hyg. 1992;47:27-34.
(3.) Park JY, Peters C J, Rollin PE, Ksiazek TG, Katholi CR, Waites KB, et al. Age distribution of lymphocytic choriomeningitis virus serum antibody in Birmingham, Alabama: evidence of a decreased risk of infection. Am J Trop Med Hyg. 1997;57:37-41.
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(5.) Gregg MB. Recent outbreaks of lymphocytic choriomeningitis in the United States of America UNITED STATES OF AMERICA. The name of this country. The United States, now thirty-one in number, are Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Mississippi, Missouri, New Hampshire, . Bull World Health Organ. 1975;52:549-53.
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(7.) Barton LL, Mets MB, Beauchamp CL. Lymphocytic choriomeningitis virus: emerging fetal teratogen teratogen /ter·a·to·gen/ (ter´ah-to-jen) any agent or factor that induces or increases the incidence of abnormal prenatal development.teratogen´ic
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1. Of or relating to biomedicine.
2. Of, relating to, or involving biological, medical, and physical sciences. laboratories. 4th ed. Washington: US Government Printing Office; 1999.
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Dr Amman is a mammalogist mam·mal·o·gy
The branch of zoology that deals with mammals.
[mamma(l) + -logy.]
mam for the Special Pathogens Branch at CDC in Atlanta, Georgia. His research interests include investigating the ecology of, and relationships between, emerging viruses and their mammalian reservoirs.
Address for correspondence: Brian R. Amman, Centers for Disease Control and Prevention, Mailstop A26, Atlanta, GA 30333, USA; email: firstname.lastname@example.org
Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the U.S. Department of Health and Human Services.
Brian R. Amman, * (1) Boris I. Pavlin, * (1,2) Cesar G. Albarino, * James A. Comer, * Bobbie R. Erickson, * Jennifer B. Oliver, * Tara K. Sealy, * Martin J. Vincent, * Stuart T. Nichol, * Christopher D. Paddock, * Abbigail J. Tumpey, * Kent D. Wagoner, * (3) R. David Glauer, ([dagger]) Kathleen A. Smith, ([double dagger]) Kim A. Winpisinger, ([double dagger]) Melody S. Parsely, ([section]) Phil Wyrick, ([paragraph]) Christopher H. Hannafin, (#) Utpala Bandy bandy /ban·dy/ (band´e) bowed or bent in an outward curve. , ** Sherif she·rif also sha·rif
1. A descendant of the prophet Muhammad through his daughter Fatima.
2. The chief magistrate of Mecca in Ottoman times.
3. A Moroccan prince or ruler. Zaki, * Pierre E. Rollin, * and Thomas G. Ksiazek *
* Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ([dagger]) Ohio Department of Agriculture, Reynoldsburg, Ohio, USA; ([double dagger]) Ohio Department of Health, Columbus, Ohio, USA; ([section]) Arkansas Department of Health and Human Services, Little Rock, Arkansas Little Rock, Arkansas
required military intervention to desegregate schools (1957–1958). [Am. Hist.: Van Doren, 556–557]
See : Bigotry , USA; ([paragraph]) Arkansas Department of Agriculture, Little Rock, Arkansas, USA; (#) Rhode Island Department of Environmental Management, Providence, Rhode Island
“Providence” redirects here. For other uses, see Providence (disambiguation).
Providence is the capital and the most populous city of the U.S. , USA; and ** Rhode Island Department of Public Health, Providence, Rhode Island, USA
(1) These authors contributed equally to this article.
(2) Current affiliation: Johns Hopkins Bloomberg School of Public Health The Johns Hopkins Bloomberg School of Public Health is part of Johns Hopkins University in Baltimore, Maryland, U.S. It was the first institution of its kind in the world.
Founded in 1916 by William H. Welch and John D. , Baltimore, Maryland, USA
(3) Current affiliation: Ithaca College, Ithaca, New York
For other places or objects named Ithaca, see Ithaca (disambiguation). , USA
Table 1. Estimated population sizes and samples taken from 2 rodent distribution facilities Location Species Population size Ohio Syrian hamsters 5,000 Arkansas Fancy rats >10,000 Arkansas Fancy mice 200 Arkansas Gerbils 2,500 Arkansas Dwarf hamsters 3,750 Arkansas Roborovsky dwarf hamster 140 Location Projected Sample prevalence, % size Ohio 5.0 116 Arkansas 3.4 125 Arkansas 3.4 75 Arkansas 3.4 125 Arkansas 3.4 113 * Arkansas 3.4 12 ([dagger]) Location Probability of detecting a positive, % Ohio 99.8 Arkansas 98.7 Arkansas 96.5 Arkansas 98.8 Arkansas 98.1 Arkansas 36.5 * Sample size after removal of 12 Roborovsky hamsters from requested sample size. ([dagger]) Sample size represents an agreed-upon portion of the total population. Table 2. Results of laboratory testing on the index hamster and traceback rodents associated with organ transplantation transmission of LCMV * Rodent ([dagger]) IFA ELISA IHC Index hamster ND Neg Pos Pet store hamster 1 Pos Neg Pos Pet store hamster 2 Neg Neg Pos Pet store guinea pig 1 ND Neg Pos Ohio hamster 1 Pos Neg Pos Ohio Hamster 2 Pos Neg Pos Ohio hamster 3 Pos Neg ND Ohio hamster 4 Neg Neg Pos Ohio hamster 5 Neg Neg Neg RT-PCR/ Virus Sequence Rodent ([dagger]) TagMan isolation (L gene), bp Index hamster Pos Pos 232 Pet store hamster 1 Pos Pos 232 Pet store hamster 2 Pos Pos 232 Pet store guinea pig 1 Pos Pos 232 Ohio hamster 1 Pos Pos 232 Ohio Hamster 2 Pos Pos NA Ohio hamster 3 Neg Neg NA Ohio hamster 4 Pos Pos NA Ohio hamster 5 ND Pos NA * LCMV, lymphocytic choriomeningitis virus; IFA, immunofluorescent antibody assay; IHC, immunohistochemistry; RT-PCR, reverse transcription-PCR; ND, no data; Neg, negative; Pos, positive; NA, no amplification (could not get traditional PCR primers to amplify for sequencing). ([dagger]) The table includes only those rodents that tested positive with [greater than or equal to] 1 test. Table 3. Comparison of nucleotide identity differences among LCMV strains and isolates * State/sample 1 2 3 4 Rhode Island Lung recipient 1 0.0 0.0 0.0 Liver recipient 2 0.0 0.0 0.0 Kidney recipient A 3 0.0 0.0 0.0 Kidney recipient B 4 0.0 0.0 0.0 Donor's hamster 5 0.0 0.0 0.0 0.0 Pet store hamster 1 6 0.3 0.3 0.3 0.3 Pet store hamster 2 7 0.3 0.3 0.3 0.3 Pet store guinea pig 8 0.2 0.2 0.2 0.2 Ohio Distributor hamster 9 0.3 0.3 0.3 0.3 New York WE 10 12.4 12.4 12.4 12.4 Wisconsin Kidney recipients 11 14.4 14.4 14.4 14.4 Missouri Armstrong 12 14.1 14.1 14.1 14.1 California Congenital infection 13 14.7 14.7 14.7 14.7 State/sample 5 6 7 8 Rhode Island Lung recipient 1 0.0 0.4 0.4 0.4 Liver recipient 2 0.0 0.4 0.4 0.4 Kidney recipient A 3 0.0 0.4 0.4 0.4 Kidney recipient B 4 0.0 0.4 0.4 0.4 Donor's hamster 5 0.4 0.4 0.4 Pet store hamster 1 6 0.3 0.0 0.0 Pet store hamster 2 7 0.3 0.0 0.0 Pet store guinea pig 8 0.2 0.2 0.2 Ohio Distributor hamster 9 0.3 0.3 0.3 0.2 New York WE 10 12.4 12.1 12.1 12.3 Wisconsin Kidney recipients 11 14.4 14.4 14.4 14.2 Missouri Armstrong 12 14.1 13.7 13.7 13.9 California Congenital infection 13 14.7 14.4 14.4 14.6 State/sample 9 10 11 Rhode Island Lung recipient 1 0.4 13.4 15.8 Liver recipient 2 0.4 13.4 15.8 Kidney recipient A 3 0.4 13.4 15.8 Kidney recipient B 4 0.4 13.4 15.8 Donor's hamster 5 0.4 13.4 15.8 Pet store hamster 1 6 0.0 12.9 15.3 Pet store hamster 2 7 0.0 12.9 15.3 Pet store guinea pig 8 0.0 12.9 15.3 Ohio Distributor hamster 9 12.9 15.3 New York WE 10 12.3 16.2 Wisconsin Kidney recipients 11 14.4 14.6 Missouri Armstrong 12 14.1 15.2 13.7 California Congenital infection 13 14.7 13.3 14.6 State/sample 12 13 Rhode Island Lung recipient 1 18.1 22.9 Liver recipient 2 18.1 22.9 Kidney recipient A 3 18.1 22.9 Kidney recipient B 4 18.1 22.9 Donor's hamster 5 18.1 22.9 Pet store hamster 1 6 18.5 23.4 Pet store hamster 2 7 18.5 23.4 Pet store guinea pig 8 18.5 23.4 Ohio Distributor hamster 9 18.5 23.4 New York WE 10 18.5 24.1 Wisconsin Kidney recipients 11 19.5 22.5 Missouri Armstrong 12 21.7 California Congenital infection 13 14.4 * LCMV, lymphocytic choriomeningitis virus. The percentage of differences for each pair of sequences was calculated with PAUP as uncorrected distances. Values on the upper diagonal represent differences in the L fragment (232 nt) and values on the lower diagonal represent differences on the S fragment (611 nt).