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Natural history of Sin Nombre virus in western Colorado.

A mark-recapture longitudinal study of immunoglobulin G (IgG) antibody to Sin Nombre virus (SNV) in rodent populations in western Colorado (1994-results summarized to October 1997) indicates the presence of SNV or a closely related hantavirus at two sites. Most rodents (principally deer mice, Peromyscus maniculatus, and pinyon mice, P. truei) did not persist on the trapping webs much beyond 1 month after first capture. Some persisted more than 1 year, which suggests that even a few infected deer mice could serve as transseasonal reservoirs and mechanisms for over-winter virus maintenance. A positive association between wounds and SNV antibody in adult animals at both sites suggests that when infected rodents in certain populations fight with uninfected rodents, virus amplification occurs. At both sites, male rodents comprised a larger percentage of seropositive mice than recaptured mice, which suggests that male mice contribute more to the SNV epizootic cycle than female mice. In deer mice, IgG antibody prevalence fluctuations were positively associated with population fluctuations. The rates of seroconversion, which in deer mice at both sites occurred mostly during late summer and midwinter, were higher than the seroprevalence, which suggests that the longer deer mice live, the greater the probability they will become infected with SNV.

Animals↗

Remote sensing and geographic information systems: charting Sin Nombre virus infections in deer mice.

We tested environmental data from remote sensing and geographic information system maps as indicators of Sin Nombre virus (SNV) infections in deer mouse (Peromyscus maniculatus) populations in the Walker River Basin, Nevada and California. We determined by serologic testing the presence of SNV infections in deer mice from 144 field sites. We used remote sensing and geographic information systems data to characterize the vegetation type and density, elevation, slope, and hydrologic features of each site. The data retroactively predicted infection status of deer mice with up to 80% accuracy. If models of SNV temporal dynamics can be integrated with baseline spatial models, human risk for infection may be assessed with reasonable accuracy.

Animals↗

Sin nombre virus in deer mice captured inside homes, southwestern Montana.

From 1996 through 1999, 35 deer mice (Peromyscus maniculatus) were captured in 25 urban and suburban homes in southwestern Montana. Mice were captured throughout the year except for January; seven mice (20%) from seven (28%) of the homes were seropositive for Sin Nombre virus. The infected mice were mostly adult males captured in the spring and fall.

Animals↗

Hantavirus pulmonary syndrome associated with Monongahela virus, Pennsylvania.

The first two recognized cases of rapidly fatal hantavirus pulmonary syndrome in Pennsylvania occurred within an 8-month period in 1997. Illness in the two patients was confirmed by immunohistochemical techniques on autopsy material. Reverse transcription-polymerase chain reaction analysis of tissue from one patient and environmentally associated Peromyscus leucopus (white-footed mouse) identified the Monongahela virus variant. Physicians should be vigilant for such Monongahela virus-associated cases in the eastern United States and Canada, particularly in the Appalachian region.

Adult↗

Hyperconservation of the N-formyl peptide binding site of M3: evidence that M3 is an old eutherian molecule with conserved recognition of a pathogen-associated molecular pattern.

The mouse MHC class I-b molecule H2-M3 has unique specificity for N-formyl peptides, derived from bacteria (and mitochondria), and is thus a pathogen-associated molecular pattern recognition receptor (PRR). To test whether M3 was selected for this PRR function, we studied M3 sequences from diverse murid species of murine genera Mus, Rattus, Apodemus, Diplothrix, Hybomys, Mastomys, and Tokudaia and of sigmodontine genera Sigmodon and PEROMYSCUS: We found that M3 is highly conserved, and the 10 residues coordinating the N-formyl group are almost invariant. The ratio of nonsynonymous and synonymous substitution rates suggests the Ag recognition site of M3, unlike the Ag recognition site of class I-a molecules, is under strong negative (purifying) selection and has been for at least 50-65 million years. Consistent with this, M3 alpha1alpha2 domains from Rattus norvegicus and Sigmodon hispidus and from the "null" allele H2-M3(b) specifically bound N-formyl peptides. The pattern of nucleotide substitution in M3 suggests M3 arose rapidly from murid I-a precursors by an evolutionary leap ("saltation"), perhaps involving intense selective pressure from bacterial pathogens. Alternatively, M3 arose more slowly but prior to the radiation of eutherian (placental) mammals. Older dates for the emergence of M3, and the accepted antiquity of CD1, suggest that primordial class I MHC molecules could have evolved originally as monomorphic PRR, presenting pathogen-associated molecular patterns. Such MHC PRR molecules could have been preadaptations for the evolution of acquired immunity during the early vertebrate radiation.

Amino Acid Sequence↗

Reservoir hosts of human babesiosis on Nantucket Island.

The host range of Babesia microti was studied on Nantucket Island in order to identify the enzootic reservoir of this human pathogen. White-footed mice (Peromyscus leucopus) were more frequently parasitized than were other indigenous animals. Infection was ubiquitous in locations where deer were abundant. Mice were most frequently parasitemic during spring and summer and adults more frequently than juveniles. Parasitemia, which was rarely intense, was sustained for as long as 4 months. Mice lived as long as 10 months, and juveniles were most abundant during early summer. Prevalence of zoonotic infection, in certain locations, appeared to be inversely correlated with abundance of mice. B. microti was present solely in regions harboring deer.

Animal Population Groups↗

Spirochetes in Ixodes dammini and mammals from Connecticut.

Spirochetes were observed in the midguts of 35% of 147 motile Ixodes dammini from three locations in Lyme and East Haddam, Connecticut. Positive ticks were removed from eastern chipmunks (Tamias striatus), raccoons (Procyon lotor), white-footed mice (Peromyscus leucopus), and a red squirrel (Tamiasciurus hudsonicus). Spirochetes were isolated in fortified Kelly's medium from nine questing or partially engorged I. dammini adults and nymphs and from the bloods of a raccoon and a white-footed mouse. Connecticut isolates from ticks and mammals were serologically indistinguishable from the original Shelter Island, New York strain when cross-tested by immunofluorescence against their mouse antisera. Sera from eight patients diagnosed as having Lyme disease contained antibodies to spirochetes isolated from ticks and mammals. Our finding of serologically and morphologically indistinguishable spirochetes in a raccoon, white-footed mouse and ticks suggests that closely related serotypes are present in wild mammals commonly parasitized by I. dammini, and further supports the claim that a spirochete is involved in the etiology of Lyme disease.

Animals↗

Lyme disease and babesiosis: acaricide focused on potentially infected ticks.

Permethrin-treated cotton, intended as rodent nesting material, was distributed in wooded sites in which the agents of Lyme disease and babesiosis were enzootic, in order to kill immature Ixodes dammini, the ticks that transmit these human pathogens. Such ticks feed most abundantly on white-footed mice (Peromyscus leucopus), apparently the main reservoir hosts of these agents, and tend to concentrate in mouse burrows. Mice captured after permethrin-treated cotton was distributed, were infested by a tenth as many ticks as were those captured in adjacent nontreated sites, a difference that continued throughout the 4-month period of observation. On average, 72% of all mice captured in treated sites were free of ticks, while virtually all mice captured in nontreated sites were infested. Voles (Microtus pennsylvanicus), however, were tick-infested, regardless of site of capture. Laboratory-reared I. dammini failed to attach to mice captured in treated sites, and most such exposed ticks died. Distribution of permethrin-treated cotton appears to be a means for preventing transmission of the pathogens that cause human babesiosis and Lyme disease.

Animals↗

Reservoir competence of white-footed mice for Lyme disease spirochetes.

Using the vector tick, Ixodes dammini, we described the reservoir competence of the white-footed mouse, Peromyscus leucopus, for the Lyme disease spirochete, Borrelia burgdorferi. Nymphal I. dammini were used to infect mammals, and larval ticks were used to diagnose infection (a form of xenodiagnosis). One tick was nearly as efficient as more than 1 in transmitting the spirochete to mice. The duration of the prepatent period was about 1 week. Prevalence of infection approached 100% in ticks that fed as larvae on mice infected 2 or 3 weeks previously. Thereafter, infectivity gradually decreased, but duration exceeded 200 days. Hamsters, too, became infectious for larval I. dammini. This report formally demonstrates the life cycle of B. burgdorferi as it seems to occur in nature. We conclude that the white-footed mouse is a competent reservoir for the Lyme disease spirochete.

Animals↗

Isolation of the causative agent of hantavirus pulmonary syndrome.

Investigation of a recent outbreak of acute respiratory illness in the southwestern United States resulted in the recognition of a new disease, hantavirus pulmonary syndrome (HPS) with high mortality. Different animals and cell lines were used in attempts to isolate the causative agent. A previously unknown hantavirus was passaged in laboratory-bred deer mice, recovered from lung tissues of a deer mouse, Peromyscus maniculatus, and propagated in the E6 clone of Vero cells. Virus antigen was readily detected in the infected cells by an indirect immunofluorescence assay, using convalescent-phase sera from HPS patients. By electron microscopy, the virus was shown to have the typical morphologic features of members of the genus Hantavirus, family Bunyaviridae. Virus sequences corresponded to those previously detected by a nested reverse transcriptase-polymerase chain reaction assay of hantavirus-infected specimens from rodents and humans. This newly recognized virus, the etiologic agent of HPS, has been tentatively named Muerto Canyon virus.

Animals↗

A household-based, case-control study of environmental factors associated with hantavirus pulmonary syndrome in the southwestern United States.

During an outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern United States, trained environmental assessment teams conducted surveys at 17 case-patient homes and matched controls from June through August 1993. Variables related to rodent abundance were quantified and standardized rodent trapping was conducted around and within households. The majority of households were located in pinon-juniper vegetation zones, and there were no significant differences in the type of house in which cases and controls lived. The only environmental factor that distinguished case households from controls was significantly higher small rodent densities (median trap success for case sites = 17.3%, 12.7% for near controls, and 8.3% for far controls). Frequency of hantaviral infection in deer mice (Peromyscus maniculatus) did not vary significantly among households of cases and controls, with a range of 27.5-32.5% antibody-positive. Indices of rodent fecal contamination were slightly higher in case houses. The data indicate that higher rodent densities were associated with households in which HPS cases occurred. Strategies that control rodent numbers and decrease rodent access to dwellings may reduce risk of human infection.

Animals↗

Cocirculation of multiple hantaviruses in Texas, with characterization of the small (S) genome of a previously undescribed virus of cotton rats (Sigmodon hispidus).

An environmental and laboratory investigation was conducted after a fatal childhood case of hantavirus pulmonary syndrome occurred in Deaf Smith County, Texas in May 1995. A trapping campaign was conducted to identify possible rodent carriers. Six species of murid and heteromyid rodents were collected, and at least one hantavirus-seropositive specimen was found in each of the five murid species. Tissues from a selection of 11 seropositive specimens were examined by the polymerase chain reaction (PCR) and sequencing of viral genetic material. The predominant hantavirus was El Moro Canyon virus (ELMCV), which occurred in three of three harvest mice (Reithrodontomys megalotis) and in three of four deer mice (Peromyscus maniculatus) examined. Sin Nombre virus (SNV) was found in one deer mouse and one white-footed mouse (P. leucopus). A seropositive house mouse (Mus musculus) was negative by PCR. Two cotton rats (Sigmodon hispidus) were infected by a virus of novel genotype (Muleshoe virus [MULEV]) that bears closet resemblance to Bayou hantavirus. The sequence of the complete small genomic segment was determined for one MULEV, and high-level expression of its nucleocapsid protein was induced in Escherichia coli. Serologic studies indicated that the most likely etiologic agent in the human infection was SNV.

Adolescent↗

Ecology and demographics of hantavirus infections in rodent populations in the Walker River Basin of Nevada and California.

To study the ecologic correlates of hantavirus in deer mice (Peromyscus maniculatus), we sampled 114 sites in the Walker River Basin of Nevada and California in 1995-1996. Blood samples were tested for antibody to hantavirus, and a subset of samples was also tested for virus RNA by reverse transcription-polymerase chain reaction. Average prevalence of antibody-positive mice was 17%, with heavier males the most likely to be infected. Antibody prevalence varied within repeatedly sampled sites from 0% to 50% over the course of several months, suggesting possible infection cycles. Although there was no linear correlation between deer mouse density and antibody prevalence on sample sites, more complex relationships between density and prevalence appeared likely. Specifically, infections were less likely where rodent densities were lower than a critical threshold value. However, above this value, density had no effect on prevalence.

Age Distribution↗

Black Creek Canal Virus infection in Sigmodon hispidus in southern Florida.

A total of 1,500 small mammals were collected and tested for antibodies cross-reactive to Sin Nombre virus (Hantavirus: Bunyaviridae) at 89 sites in a 1,600 km2 study area of southern Florida. More than 95% of the 123 seropositive animals were cotton rats (Sigmodon hispidus), suggesting infection by Black Creek Canal Virus, although seroreactive Rattus rattus (5 of 294) and Peromyscus gossypinus (1 of 39) also were captured. Crude seroprevalence in S. hispidus was 11%. Seroprevalence increased with body size and was more common in male (18%; n=451) than in female (6%; n=593) cotton rats. Infection within S. hispidus populations was widespread throughout the study area. Prevalence ranged from 0% to 60% at sites where more than five cotton rats were sampled but was not only a function of sample size. Sites with seropositive cotton rats were geographically clustered compared with sites with no seropositive cotton rats. Clustering was not due to the spatial distribution of sites with few animals, season of collection, or sex bias of animals captured at these sites. However, sites with no seropositive animals had an excess of animals in the intermediate size class (60-99 g) and a deficit of the largest and smallest animals. These data suggest that population structure within the habitat mosaic may play a significant role in the spatial distribution of hantavirus infection in local populations of reservoir species.

Animals↗

The incubation period of hantavirus pulmonary syndrome.

In 1993 Sin Nombre virus was recognized as the cause of hantavirus pulmonary syndrome (HPS) and the deer mouse (Peromyscus maniculatus) was identified as the reservoir host. Surveillance by the Centers for Disease Control and Prevention and state health departments includes investigation to determine the likely site(s) and activities that led to infection, an environmental assessment of the home and workplace, and possibly rodent trappings at these sites. As of December 31, 1998, there were 200 confirmed cases from 30 states (43% case-fatality ratio). The national HPS case registry was examined to determine the incubation period of HPS. Review of 11 case-patients with well-defined and isolated exposure to rodents suggests that the incubation period of HPS is 9 to 33 days, with a median of 14-17 days. Case investigations allow a better understanding of the incubation time of HPS and may define high-risk behaviors that can be targeted for intervention.

Adult↗

Enzootic transmission of deer tick virus in New England and Wisconsin sites.

To determine whether rodents that are intensely exposed to the deer tick-transmitted agents of Lyme disease, human granulocytic ehrlichiosis, and human babesiosis are also exposed to deer tick virus (DTV), we assayed serum samples from white-footed mice (Peromyscus leucopus) and meadow voles (Microtus pennsylvanicus) in sites densely infested by deer ticks. To conduct serosurveys, we developed an enzyme-linked immunosorbent assay (ELISA) and Western blot assay by cloning, expressing, and purifying a portion of the DTV envelope glycoprotein (DTV rE) for use as test antigen. Sera from mice and voles trapped in Massachusetts, Rhode Island, and Wisconsin were screened by ELISA for IgG reactive to DTV rE. Samples that were positive or borderline by ELISA were subsequently analyzed by immunoblotting. Samples reactive in both assays were considered to be positive. Three percent of 264 mouse samples collected from sites in Rhode Island, 3.8% of 52 samples from mice trapped in Wisconsin, and 3.9% of 282 samples collected from mice trapped on Nantucket Island, MA were positive. No samples from either Great Island, MA, or voles from any study site were reactive. A reverse transcriptase-polymerase chain reaction yielded molecular evidence of DTV infecting questing adult deer ticks in sites where seroreactive mice were trapped, but not from ticks collected where serologic evidence of virus perpetuation was absent. White-footed mice appear to be exposed to DTV in certain sites where other deer tick-borne agents perpetuate. This virus may be maintained in the same enzootic cycle.

Animals↗

Antibody to sin nombre virus in rodents associated with peridomestic habitats in west central Montana.

Most human cases of hantavirus pulmonary syndrome are acquired in the peridomestic environment, yet studies of the ecology and infection dynamics in the reservoir host, the deer mouse (Peromyscus maniculatus), have focused on sylvan populations. We describe a 2.5-year study of hantavirus infection in rodents associated with peridomestic habitats in west central Montana. Antibodies reactive with Sin Nombre virus (SNV) were found in five species. Overall SNV antibody prevalence was highest among deer mice (25% of individuals tested). As has been demonstrated for sylvan populations, the antibody-positive component of the deer mouse population consisted of a higher proportion of adults and males. However, the prevalence of antibodies to SNV was higher in this study than has been reported in most sylvan studies. The average monthly proportion of deer mouse blood samples with antibodies to SNV ranged from approximately 20% to 25% and was highest in the late spring/early summer. The higher SNV antibody prevalence in peridomestic compared with sylvan settings may be related to behavioral differences and/or potentially longer survival of the virus deposited inside buildings. Peridomestic settings presented higher concentrations of virus and may present a higher risk of human infection than do sylvan settings.

Animals↗

Longitudinal studies of Sin Nombre virus in deer mouse-dominated ecosystems of Montana.

Sin Nombre virus (SNV), hosted by the deer mouse (Peromyscus maniculatus), is the primary etiologic agent of Hantavirus pulmonary syndrome (HPS) in North America. To improve our understanding of the epidemiology of HPS in the western United States, we conducted studies of population dynamics and SNV antibody prevalence in deer mouse populations for 6 years on 12 mark-recapture grids in Montana. Monthly numbers of deer mice ranged from zero to over 170 on 1-hectare grids. SNV antibody prevalence was higher than observed in studies in other parts of the United States, averaging 13% (0% to 50%), and peaking in May or June each year. Antibody-positive mice were older (heavier) (78% of positives were adults versus 52% of negatives) and more likely to be males (61% of positives versus 53.4% of negatives). A higher proportion of antibody-positive deer mice of all age-mass classes had scars than did antibody-negative mice. Month-to-month survivorship of antibody-positive adult mice was similar to that of antibody-negative mice, but survival of young antibody-positive deer mice was lower than antibody-negative deer mice. This is the first study to clearly suggest a detrimental effect of SNV infection on deer mice.

Age Factors↗