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1.  Infections by Leptospira interrogans, Seoul Virus, and Bartonella spp. Among Norway Rats (Rattus norvegicus) from the Urban Slum Environment in Brazil 
Abstract
Norway rats (Rattus norvegicus) are reservoir hosts for zoonotic pathogens that cause significant morbidity and mortality in humans. Studies evaluating the prevalence of zoonotic pathogens in tropical Norway rat populations are rare, and data on co-infection with multiple pathogens are nonexistent. Herein, we describe the prevalence of leptospiral carriage, Seoul virus (SEOV), and Bartonella spp. infection independently, in addition to the rates of co-infection among urban, slum-dwelling Norway rats in Salvador, Brazil, trapped during the rainy season from June to August of 2010. These data were complemented with previously unpublished Leptospira and SEOV prevalence information collected in 1998. Immunofluorescence staining of kidney impressions was used to identify Leptospira interrogans in 2010, whereas isolation was used in 1998, and western blotting was used to detect SEOV antibodies in 2010, whereas enzyme-linked immunosorbent assay (ELISA) was used in 1998: in 2010, Bartonella spp. were isolated from a subsample of rats. The most common pathogen in both years was Leptospira spp. (83%, n=142 in 1998, 63%, n=84 in 2010). SEOV was detected in 18% of individuals in both 1998 and 2010 (n=78 in 1998; n=73 in 2010), and two species of Bartonella were isolated from 5 of 26 rats (19%) tested in 2010. The prevalence of all agents increased significantly with rat mass/age. Acquisition of Leptospira spp. occurred at a younger mass/age than SEOV and Bartonella spp. infection, suggesting differences in the transmission dynamics of these pathogens. These data indicate that Norway rats in Salvador serve as reservoir hosts for all three of these zoonotic pathogens and that the high prevalence of leptospiral carriage in Salvador rats poses a high degree of risk to human health.
doi:10.1089/vbz.2013.1378
PMCID: PMC3880909  PMID: 24359425
Leptospira interrogans; Seoul virus; Bartonella spp.; Norway rats (Rattus norvegicus); Brazil
2.  Influence of Household Rat Infestation on Leptospira Transmission in the Urban Slum Environment 
Background
The Norway rat (Rattus norvegicus) is the principal reservoir for leptospirosis in many urban settings. Few studies have identified markers for rat infestation in slum environments while none have evaluated the association between household rat infestation and Leptospira infection in humans or the use of infestation markers as a predictive model to stratify risk for leptospirosis.
Methodology/Principal Findings
We enrolled a cohort of 2,003 urban slum residents from Salvador, Brazil in 2004, and followed the cohort during four annual serosurveys to identify serologic evidence for Leptospira infection. In 2007, we performed rodent infestation and environmental surveys of 80 case households, in which resided at least one individual with Leptospira infection, and 109 control households. In the case-control study, signs of rodent infestation were identified in 78% and 42% of the households, respectively. Regression modeling identified the presence of R. norvegicus feces (OR, 4.95; 95% CI, 2.13–11.47), rodent burrows (2.80; 1.06–7.36), access to water (2.79; 1.28–6.09), and un-plastered walls (2.71; 1.21–6.04) as independent risk factors associated with Leptospira infection in a household. We developed a predictive model for infection, based on assigning scores to each of the rodent infestation risk factors. Receiver operating characteristic curve analysis found that the prediction score produced a good/excellent fit based on an area under the curve of 0.78 (0.71–0.84).
Conclusions/Significance
Our study found that a high proportion of slum households were infested with R. norvegicus and that rat infestation was significantly associated with the risk of Leptospira infection, indicating that high level transmission occurs among slum households. We developed an easily applicable prediction score based on rat infestation markers, which identified households with highest infection risk. The use of the prediction score in community-based screening may therefore be an effective risk stratification strategy for targeting control measures in slum settings of high leptospirosis transmission.
Author Summary
The Norway rat is an important reservoir for urban leptospirosis, a life-threatening zoonotic disease. In urban settings, leptospirosis transmission occurs primarily in the peri-domiciliary environment of the slums. Rodent control is one of the most frequent strategies to prevent leptospirosis, but the identification of domiciles at higher risk of transmission is challenging. We compared households where an individual with evidence of recent leptospirosis infection resided and households where none of the residents had evidence for infection. Houses with evidence of leptospirosis transmission had higher levels of rodent infestation and environmental conditions related to rodents. We propose a new methodology to easily characterize slum households, based on environmental characteristics, at different levels of risk for leptospirosis transmission. The findings of this study indicate that evaluation for rodent infestation intensity and environmental features may be a feasible strategy for targeting augmented control measures for leptospirosis.
doi:10.1371/journal.pntd.0003338
PMCID: PMC4256176  PMID: 25474580
3.  Urban population genetics of slum-dwelling rats (Rattus norvegicus) in Salvador, Brazil 
Molecular ecology  2013;22(20):10.1111/mec.12455.
Throughout the developing world, urban centers with sprawling slum settlements are rapidly expanding and invading previously forested ecosystems. Slum communities are characterized by untended refuse, open sewers, and overgrown vegetation, which promote rodent infestation. Norway rats (Rattus norvegicus), are reservoirs for epidemic transmission of many zoonotic pathogens of public health importance. Understanding the population ecology of R. norvegicus is essential to formulate effective rodent control strategies, as this knowledge aids estimation of the temporal stability and spatial connectivity of populations. We screened for genetic variation, characterized the population genetic structure, and evaluated the extent and patterns of gene flow in the urban landscape using 17 microsatellite loci in 146 rats from 9 sites in the city of Salvador, Brazil. These sites were divided between three neighborhoods within the city spaced an average of 2.7 km apart. Surprisingly, we detected very little relatedness among animals trapped at the same site and found high levels of genetic diversity, as well as structuring across small geographic distances. Most FST comparisons among sites were statistically significant, including sites <400 m apart. Bayesian analyses grouped the samples in three genetic clusters, each associated with distinct sampling sites from different neighborhoods or valleys within neighborhoods. These data indicate the existence of complex genetic structure in R. norvegicus in Salvador, linked to the heterogeneous urban landscape. Future rodent control measures need to take into account the spatial and temporal linkage of rat populations in Salvador, as revealed by genetic data, to develop informed eradication strategies.
doi:10.1111/mec.12455
PMCID: PMC3864905  PMID: 24118116
population genetics; urban ecology; Rattus norvegicus; rodent control
4.  Avian Host-Selection by Culex pipiens in Experimental Trials 
PLoS ONE  2009;4(11):e7861.
Evidence from field studies suggests that Culex pipiens, the primary mosquito vector of West Nile virus (WNV) in the northeastern and north central United States, feeds preferentially on American robins (Turdus migratorius). To determine the contribution of innate preferences to observed preference patterns in the field, we conducted host preference trials with a known number of adult female C. pipiens in outdoor cages comparing the relative attractiveness of American robins with two common sympatric bird species, European starling, Sternus vulgaris and house sparrow, Passer domesticus. Host seeking C. pipiens were three times more likely to enter robin-baited traps when with the alternate host was a European starling (n = 4 trials; OR = 3.06; CI [1.42–6.46]) and almost twice more likely when the alternative was a house sparrow (n = 8 trials; OR = 1.80; CI = [1.22–2.90]). There was no difference in the probability of trap entry when two robins were offered (n = 8 trials). Logistic regression analysis determined that the age, sex and weight of the birds, the date of the trial, starting-time, temperature, humidity, wind-speed and age of the mosquitoes had no effect on the probability of a choosing a robin over an alternate bird. Findings indicate that preferential feeding by C. pipiens mosquitoes on certain avian hosts is likely to be inherent, and we discuss the implications innate host preferences may have on enzootic WNV transmission.
doi:10.1371/journal.pone.0007861
PMCID: PMC2775674  PMID: 19924251
5.  Risk Factors for Human Infection with Puumala Virus, Southwestern Germany 
Emerging Infectious Diseases  2009;15(7):1032-1039.
Risk factors are available bank vole habitat, abundant vole food supply, high human population density, and warmer climate.
Puumala virus, which causes nephropathia epidemica (NE), is the most prevalent hantavirus in Germany; bank voles serve as the main reservoir. During 2001–2007, most NE cases reported from Germany occurred in the southwestern state of Baden-Württemberg. We investigated the influence of bank vole habitats (beech forest, seed plants), vole food supply (beechnut mast), climate factors (winter and spring temperatures), and human population density on spatial and temporal occurrence of NE cases in Baden-Württemberg. Using Poisson-regression analyses, we found that all these factors influenced disease incidence. Furthermore, an independent trend of increasing incidence predicted that incidence will nearly double each year. The regression model explained 75% of the annual variation in NE incidence. The results suggest that environmental drivers lead to increasing incidence of NE infections in the southern part or even other parts of Germany.
doi:10.3201/eid1507.081413
PMCID: PMC2744254  PMID: 19624917
Hantavirus; climate change; Puumala virus; bank vole; modeling; viruses; zoonoses; Germany; research
6.  Ecologic Factors Associated with West Nile Virus Transmission, Northeastern United States 
Emerging Infectious Diseases  2008;14(10):1539-1545.
Risk for disease was 4 times greater in the least forested counties.
Since 1999, West Nile virus (WNV) disease has affected the northeastern United States. To describe the spatial epidemiology and identify risk factors for disease incidence, we analyzed 8 years (1999–2006) of county-based human WNV disease surveillance data. Among the 56.6 million residents in 8 northeastern states sharing primary enzootic vectors, we found 977 cases. We controlled for population density and potential bias from surveillance and spatial proximity. Analyses demonstrated significant spatial spreading from 1999 through 2004 (p<0.01, r2 = 0.16). A significant trend was apparent among increasingly urban counties; county quartiles with the least (<38%) forest cover had 4.4-fold greater odds (95% confidence interval [CI] 1.4–13.2, p = 0.01) of having above-median disease incidence (>0.75 cases/100,000 residents) than counties with the most (>70%) forest cover. These results quantify urbanization as a risk factor for WNV disease incidence and are consistent with knowledge of vector species in this area.
doi:10.3201/eid1410.071396
PMCID: PMC2609885  PMID: 18826816
West Nile virus; spatial epidemiology; GIS; risk factors; research
7.  Bats: Important Reservoir Hosts of Emerging Viruses 
Clinical Microbiology Reviews  2006;19(3):531-545.
Bats (order Chiroptera, suborders Megachiroptera [“flying foxes”] and Microchiroptera) are abundant, diverse, and geographically widespread. These mammals provide us with resources, but their importance is minimized and many of their populations and species are at risk, even threatened or endangered. Some of their characteristics (food choices, colonial or solitary nature, population structure, ability to fly, seasonal migration and daily movement patterns, torpor and hibernation, life span, roosting behaviors, ability to echolocate, virus susceptibility) make them exquisitely suitable hosts of viruses and other disease agents. Bats of certain species are well recognized as being capable of transmitting rabies virus, but recent observations of outbreaks and epidemics of newly recognized human and livestock diseases caused by viruses transmitted by various megachiropteran and microchiropteran bats have drawn attention anew to these remarkable mammals. This paper summarizes information regarding chiropteran characteristics and information regarding 66 viruses that have been isolated from bats. From these summaries, it is clear that we do not know enough about bat biology; we are doing too little in terms of bat conservation; and there remain a multitude of questions regarding the role of bats in disease emergence.
doi:10.1128/CMR.00017-06
PMCID: PMC1539106  PMID: 16847084
8.  Hantavirus and Arenavirus Antibodies in Persons with Occupational Rodent Exposure, North America 
Emerging Infectious Diseases  2007;13(4):532-538.
Risk for infection was low among those who handled neotomine or sigmodontine rodents on the job.
Rodents are the principal hosts of Sin Nombre virus, 4 other hantaviruses known to cause hantavirus pulmonary syndrome in North America, and the 3 North American arenaviruses. Serum samples from 757 persons who had worked with rodents in North America and handled neotomine or sigmodontine rodents were tested for antibodies against Sin Nombre virus, Whitewater Arroyo virus, Guanarito virus, and lymphocytic choriomeningitis virus. Antibodies against Sin Nombre virus were found in 4 persons, against Whitewater Arroyo virus or Guanarito virus in 2 persons, and against lymphocytic choriomeningitis virus in none. These results suggest that risk for infection with hantaviruses or arenaviruses usually is low in persons whose occupations entail close physical contact with neotomine or sigmodontine rodents in North America.
doi:10.3201/eid1304.061509
PMCID: PMC2725987  PMID: 17553266
Hantavirus; Sin Nombre virus; arenavirus; Bear Canyon virus; Tamiami virus; Whitewater Arroyo virus; lymphocytic choriomeningitis virus; research
9.  A priori prediction of disease invasion dynamics in a novel environment. 
Directly transmitted infectious diseases spread through wildlife populations as travelling waves away from the sites of original introduction. These waves often become distorted through their interaction with environmental and population heterogeneities and by long-distance translocation of infected individuals. Accurate a priori predictions of travelling waves of infection depend upon understanding and quantifying these distorting factors. We assess the effects of anisotropies arising from the orientation of rivers in relation to the direction of disease-front propagation and the damming effect of mountains on disease movement in natural populations. The model successfully predicts the local and large-scale prevaccination spread of raccoon rabies through New York State, based on a previous spatially heterogeneous model of raccoon-rabies invasion across the state of Connecticut. Use of this model provides a rare example of a priori prediction of an epidemic invasion over a naturally heterogeneous landscape. Model predictions matched to data can also be used to evaluate the most likely points of disease introduction. These results have general implications for predicting future pathogen invasions and evaluating potential containment strategies.
PMCID: PMC1691560  PMID: 15002767
10.  Flying Squirrel–associated Typhus, United States 
Emerging Infectious Diseases  2003;9(10):1341-1343.
In March 2002, typhus fever was diagnosed in two patients residing in West Virginia and Georgia. Both patients were hospitalized with severe febrile illnesses, and both had been recently exposed to or had physical contact with flying squirrels or flying squirrel nests. Laboratory results indicated Rickettsia prowazekii infection.
doi:10.3201/eid0910.030278
PMCID: PMC3033063  PMID: 14609478
11.  Skunk and Raccoon Rabies in the Eastern United States: Temporal and Spatial Analysis 
Emerging Infectious Diseases  2003;9(9):1143-1150.
Since 1981, an epizootic of raccoon rabies has spread throughout the eastern United States. A concomitant increase in reported rabies cases in skunks has raised concerns that an independent maintenance cycle of rabies virus in skunks could become established, affecting current strategies of wildlife rabies control programs. Rabies surveillance data from 1981 through 2000 obtained from the health departments of 11 eastern states were used to analyze temporal and spatial characteristics of rabies epizootics in each species. Spatial analysis indicated that epizootics in raccoons and skunks moved in a similar direction from 1990 to 2000. Temporal regression analysis showed that the number of rabid raccoons predicted the number of rabid skunks through time, with a 1-month lag. In areas where the raccoon rabies virus variant is enzootic, spatio-temporal analysis does not provide evidence that this rabies virus variant is currently cycling independently among skunks.
doi:10.3201/eid0909.020608
PMCID: PMC3016792  PMID: 14519253
Rabies; epizootic; raccoon; skunk; wildlife; zoonosis; spatial analysis; eastern United States
13.  Ehrlichia chaffeensis: a Prototypical Emerging Pathogen 
Clinical Microbiology Reviews  2003;16(1):37-64.
Ehrlichia chaffeensis is an obligately intracellular, tick-transmitted bacterium that is maintained in nature in a cycle involving at least one and perhaps several vertebrate reservoir hosts. The moderate to severe disease caused by E. chaffeensis in humans, first identified in 1986 and reported for more than 1,000 patients through 2000, represents a prototypical “emerging infection.” Knowledge of the biology and natural history of E. chaffeensis, and of the epidemiology, clinical features, and laboratory diagnosis of the zoonotic disease it causes (commonly referred to as human monocytic ehrlichiosis [HME]) has expanded considerably in the period since its discovery. In this review, we summarize briefly the current understanding of the microbiology, pathogenesis, and clinical manifestations associated with this pathogen but focus primarily on discussing various ecological factors responsible for the recent recognition of this important and potentially life-threatening tick-borne disease. Perhaps the most pivotal element in the emergence of HME has been the staggering increases in white-tailed deer populations in the eastern United States during the 20th century. This animal serves as a keystone host for all life stages of the principal tick vector (Amblyomma americanum) and is perhaps the most important vertebrate reservoir host for E. chaffeensis. The contributions of other components, including expansion of susceptible human populations, growth and broadening geographical distributions of other potential reservoir species and A. americanum, and improvements in confirmatory diagnostic methods, are also explored.
doi:10.1128/CMR.16.1.37-64.2003
PMCID: PMC145301  PMID: 12525424
15.  Population Dynamics of a Naturally Occurring Heterogeneous Mixture of Borrelia burgdorferi Clones 
Infection and Immunity  1999;67(11):5709-5716.
Two unique isolates of Borrelia burgdorferi, differing in plasmid content and outer surface protein C expression, were cultured on sequential captures of a single free-living Peromyscus leucopus mouse and were examined for differences in transmissibility. Both isolates were transmissible from inoculated C.B-17 mice to larval Ixodes scapularis ticks and, subsequently, from infected nymphal ticks to C3H/HeJ mice. Plasmid and protein analyses suggested that the original isolates were a mixed population of B. burgdorferi, and cloning by limiting dilution resulted in the identification of two clonal groups. In addition to being heterogeneous in plasmid and genomic macrorestriction analyses, the clones varied with respect to the electrophoretic mobilities and antigenicity of their OspC proteins, as shown by their reactivity to a panel of monoclonal antibodies. Plasmid analysis of sequential isolates from C3H mice experimentally infected with the primary isolate or various mixtures of its subclones showed an apparently random fluctuation in clonal dominance in the majority of mice. Surprisingly, mice infected with each subclone were permissive to superinfection with the heterologous subclone, despite the presence of anti-B. burgdorferi antibodies at the time of the secondary challenge. These results show conclusively that mice captured at Lyme disease enzootic sites may be infected by mixed populations of genetically and antigenically distinct B. burgdorferi clones and that these infections can be acquired by coinfection or by sequential infection. The lack of cross-immunization between clones existing within a naturally occurring population may play a role in the maintenance of the genetic heterogeneity of B. burgdorferi in nature.
PMCID: PMC96945  PMID: 10531219
16.  Dusky-Footed Wood Rats (Neotoma fuscipes) as Reservoirs of Granulocytic Ehrlichiae (Rickettsiales: Ehrlichieae) in Northern California 
Journal of Clinical Microbiology  1999;37(10):3323-3327.
Dusky-footed wood rats (Neotoma fuscipes) and Peromyscus sp. mice (P. maniculatus and P. truei) were collected from one site in Placer County, one site in Santa Cruz County, and two sites in Sonoma County in northern California. Serum or plasma samples from 260 rodents were tested for antibodies to the agent of human granulocytic ehrlichiosis. Of these, samples from 25 wood rats (34% of those tested) and 10 (8%) Peromyscus sp. mice were found to be seropositive, but only those from one site. PCR assays targeting the groESL heat shock operon were conducted on all seropositive specimens and a subset of seronegative blood specimens. Ehrlichial DNA was identified in 17 (68%) of the 25 seropositive wood rat blood samples and in 1 of the 10 (10%) Peromyscus sp. specimens. None of 40 seronegative blood samples was PCR positive. Both seropositive and PCR-positive animals were collected during each trapping period. One male tick out of 84 Ixodes pacificus adults collected was PCR positive; samples of Dermacentor occidentalis nymphs and adults were negative. Nucleotide sequences of amplicons from three wood rat blood specimens and from the single PCR-positive tick differed by one and two bases, respectively, from a sequence previously obtained from Ehrlichia equi. At one site in Sonoma County, wood rats had a concurrent high prevalence of seropositivity and PCR positivity, while other sigmodontine rodents collected at the site were only occasionally infected. We suggest that dusky-footed wood rats serve as reservoirs of granulocytic ehrlichial agents in certain areas of northern California. The tick species involved in the transmission of granulocytic ehrlichiae among wood rats remains unknown.
PMCID: PMC85556  PMID: 10488199
17.  Outcome of Diagnostic Tests Using Samples from Patients with Culture-Proven Human Monocytic Ehrlichiosis: Implications for Surveillance 
Journal of Clinical Microbiology  1999;37(9):2997-3000.
We describe the concordance among results from various laboratory tests using samples derived from nine culture-proven cases of human monocytic ehrlichiosis (HME) caused by Ehrlichia chaffeensis. A class-specific indirect immunofluorescence assay for immunoglobulin M (IgM) and IgG, using E. chaffeensis antigen, identified 44 and 33% of the isolation-confirmed HME patients on the basis of samples obtained at initial clinical presentation, respectively; detection of morulae in blood smears was similarly insensitive (22% positive). PCR amplifications of ehrlichial DNA targeting the 16S rRNA gene, the variable-length PCR target gene, and the groESL operon were positive for whole blood specimens obtained from all patients at initial presentation. As most case definitions of HME require a serologic response with compatible illness for a categorization of even probable disease, PCR would have been required to confirm the diagnosis of HME in all nine of these patients without the submission of a convalescent-phase serum sample. These data suggest that many, if not most, cases of HME in patients who present early in the course of the disease may be missed and underscore the limitations of serologically based surveillance systems.
PMCID: PMC85432  PMID: 10449489
18.  Molecular Cloning and Characterization of the Ehrlichia chaffeensis Variable-Length PCR Target: an Antigen-Expressing Gene That Exhibits Interstrain Variation 
Journal of Clinical Microbiology  1999;37(5):1447-1453.
A clone expressing an immunoreactive protein with an apparent molecular mass of 44 kDa was selected from an Ehrlichia chaffeensis Arkansas genomic library by probing with anti-E. chaffeensis hyperimmune mouse ascitic fluid. Nucleotide sequencing revealed an open reading frame (ORF) capable of encoding a 198-amino-acid polypeptide. The ORF contained four imperfect, direct, tandem 90-bp repeats. The nucleotide and deduced amino acid sequences did not show close homologies to entries in the molecular databases. PCR with primers whose sequences matched the sequences flanking the ORF was performed with DNA samples extracted from cell cultures infected with nine different isolates of E. chaffeensis, blood samples from seven patients with monocytic ehrlichiosis, and Amblyomma americanum ticks collected in four different states. The resulting amplicons varied in length, containing three to six repeat units. This gene, designated the variable-length PCR target, is useful for PCR detection of E. chaffeensis and differentiation of isolates.
PMCID: PMC84798  PMID: 10203503
19.  Serologic Testing for Human Granulocytic Ehrlichiosis at a National Referral Center 
Journal of Clinical Microbiology  1999;37(3):558-564.
An indirect immunofluorescence assay (IFA) was used to identify patients with antibodies reactive to the human granulocytic ehrlichiosis (HGE) agent. Serum samples collected from clinically ill individuals were submitted to the Centers for Disease Control and Prevention by physicians via state health departments from throughout the United States and tested against a panel of ehrlichial and rickettsial pathogens. Antibodies reactive to the HGE agent were detected in 142 (8.9%) of 1,602 individuals tested. There were 19 confirmed and 59 probable (n = 78) cases of HGE as defined by seroconversion or a fourfold or higher titer to the HGE agent than to the Ehrlichia chaffeensis antigens. The average age of patients with HGE was 57 years, and males accounted for 53 (68%) of the patients. Cases of HGE occurred in 21 states; 47 (60%) of the cases occurred in Connecticut (n = 14), New York (n = 18), and Wisconsin (n = 15). Onset of HGE was identified from April through December, with cases peaking in June and July. The earliest confirmed cases of HGE occurred in 1987 in Wisconsin and 1988 in Florida. No fatalities were reported among the 78 patients with confirmed or probable HGE. Reactivity to the HGE agent and to either Coxiella burnetii, Rickettsia rickettsii, or Rickettsia typhi was infrequent; however, 74 (52%) of the 142 individuals who were positive for HGE had at least one serum sample that also reacted to the E. chaffeensis antigen. Thirty-four persons with confirmed or probable human monocytic ehrlichiosis due to E. chaffeensis also had antibodies to the HGE agent in at least one serum sample. The specific etiologic agent for 30 patients was not ascribed because of similarity of titers to both ehrlichial antigens. The use of both antigens may be required to correctly diagnose most cases of human ehrlichiosis, especially in geographic regions where both the HGE agent and E. chaffeensis occur.
PMCID: PMC84468  PMID: 9986812
20.  Diagnosis of Human Ehrlichiosis by PCR Assay of Acute-Phase Serum 
A PCR assay of 43 acute-phase serum samples was evaluated as a method for early detection of human granulocytic ehrlichiosis (HGE) and determination of etiology when serologic testing is inconclusive. Sequence-confirmed products of the HGE agent were amplified from three individuals residing or having exposure history in Minnesota or Wisconsin, and similarly confirmed products from Ehrlichia chaffeensis were amplified from three individuals from Florida or Maryland. Etiology, as determined by PCR and serology, was the same whenever there was a fourfold difference between the maximum titers of antibodies to both antigens, indicating that presumptive determination of etiology may be based on fourfold differences in titers. PCR testing determined that E. chaffeensis was the etiologic agent for one individual who had similar titers of antibodies to both agents. PCR assay of acute-phase serum in the absence of whole blood specimens may be a useful method for early detection of human ehrlichiosis and determination of etiology when serologic testing is inconclusive.
PMCID: PMC84159  PMID: 9854059
21.  Serologic Evidence of Infection with Ehrlichia spp. in Wild Rodents (Muridae: Sigmodontinae) in the United States 
Journal of Clinical Microbiology  1998;36(3):695-700.
Rodent (Muridae: Sigmodontinae) blood and sera collected from 14 states were tested for seroreactivity to a cultured isolate of the human granulocytic ehrlichiosis (HGE) agent by using an indirect immunofluorescence assay. Of the 1,240 samples tested, 136 (11%) were found to be reactive at titers of ≥32. Rodents with HGE agent-specific antibodies were found in New York (23% of 491 samples; geometric mean endpoint titer [GMT] = 441), Connecticut (11% of 100 samples; GMT = 481), California (9% of 32 samples; GMT = 323), Colorado (2% of 212 samples; GMT = 256), Florida (7% of 27 samples; GMT = 362), Maryland (7% of 15 samples; titer = 64), New Jersey (4% of 76 samples; titer = 256), and Wisconsin (13% of 8 samples; titer = 128). Samples from Georgia (n = 16), Illinois (n = 27), Nevada (n = 27), North Carolina (n = 52), Ohio (n = 57), and Utah (n = 100) were not reactive. The earliest seroreactive sample was from a Peromyscus leucopus mouse collected in June 1986 in Connecticut, and the majority of the seroreactive samples (68%) were from this species. Samples from other Peromyscus species (P. boylii, P. maniculatus, and P. gossypinus) were also found to be reactive, with a GMT for the genus of 410. Several species of Neotoma woodrats (N. fuscipes, N. lepida, N. albigula, and N. mexicana) from California and Colorado had antibodies that reacted with the HGE agent (genus GMT = 194), suggesting that enzootic cycles of Ehrlichia spp. exist outside of the areas of confirmed human disease. Attempts to amplify and detect ehrlichial DNA from the limited tissues available (n = 40 animals) were unsuccessful. Further studies are needed to determine the identity of the organisms inducing antibody production in these rodent species and to elucidate the epidemiology and public health importance of these agents.
PMCID: PMC104611  PMID: 9508298
22.  Predictive Spatial Dynamics and Strategic Planning for Raccoon Rabies Emergence in Ohio 
PLoS Biology  2005;3(3):e88.
Rabies is an important public health concern in North America because of recent epidemics of a rabies virus variant associated with raccoons. The costs associated with surveillance, diagnostic testing, and post-exposure treatment of humans exposed to rabies have fostered coordinated efforts to control rabies spread by distributing an oral rabies vaccine to wild raccoons. Authorities have tried to contain westward expansion of the epidemic front of raccoon-associated rabies via a vaccine corridor established in counties of eastern Ohio, western Pennsylvania, and West Virginia. Although sporadic cases of rabies have been identified in Ohio since oral rabies vaccine distribution in 1998, the first evidence of a significant breach in this vaccine corridor was not detected until 2004 in Lake County, Ohio. Herein, we forecast the spatial spread of rabies in Ohio from this breach using a stochastic spatial model that was first developed for exploratory data analysis in Connecticut and next used to successfully hind-cast wave-front dynamics of rabies spread across New York. The projections, based on expansion from the Lake County breach, are strongly affected by the spread of rabies by rare, but unpredictable long-distance translocation of rabid raccoons; rabies may traverse central Ohio at a rate 2.5-fold greater than previously analyzed wildlife epidemics. Using prior estimates of the impact of local heterogeneities on wave-front propagation and of the time lag between surveillance-based detection of an initial rabies case to full-blown epidemic, specific regions within the state are identified for vaccine delivery and expanded surveillance effort.
A model predicting that the spread of rabies across Ohio will be much more rapid than elsewhere reveals the power of this approach to pro-actively assist targeted surveillance strategies and vaccine delivery
doi:10.1371/journal.pbio.0030088
PMCID: PMC1054883  PMID: 15737065

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