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The ecology of Colorado tick fever in Rocky Mountain National Park in 1974. II. Infection in small mammals.

Field studies of Colorado tick fever (CTF) in small mammals in Rocky Mountain National Park (RMNP) in 1974 established that Eutamias minimus and Spermophilus lateralis were the most important hosts for CTF virus and were the source of virus for immature stages of the tick vector, Dermacentor andersoni. Other species (Peromyscus maniculatus, Spermophilus richardsonii, Eutamias umbrinus) are secondary hosts. The intensity of viral activity in rodents varied greatly from locality to locality. Highest rodent infection rates were found to occur in the Moraine Park area of RMNP. Lowest infection rates occurred above 3,290 meters in altitude at Rainbow Curve and on the tundra. The prevalence of infection in rodents was constant from April--July (5--6% of animals captured were viremic) and then declined to 1.7--2.5% in August and September coincident with a decline in nymphal tick ectoparasitism. Many animals were captured which were simultaneously viremic and antibody-positive. Under field conditions, neutralizing antibody seroconversion does not always occur.

Animals↗

The ecology of Colorado tick fever in Rocky Mountain National Park in 1974. III. Habitats supporting the virus.

Ecologic studies of small mammals in Rocky Mountain National Park (RMNP) were conducted in 1974 in order to identify the specific habitats within the Lower Montane Forest that support Colorado tick fever (CTF) virus. Data was collected on the abundance and distribution of 4 primary rodent species, tick infestation, CTF virus, and neutralizing antibody prevalence. Rodents were captured along transects crossing different habitats. Open stands of ponderosa pine and shrubs on dry, rocky surfaces were found to be important for maintaining CTF virus.

Animals↗

Detection of Colorado Tick Fever viral RNA in acute human serum samples by a quantitative real-time RT-PCR assay.

A quantitative real-time RT-PCR assay for the detection of Colorado Tick Fever (CTF) viral RNA in human clinical samples is presented. The sensitivity of this assay has been shown to be greater than that of the isolation of virus in Vero cells by standard plaque assay in a direct comparison. The specificity of the CTF quantitative real-time RT-PCR assay was determined by the exclusive detection of CTF viral RNAs when applied to a diverse panel of CTF viral isolates and reference strain agents known to circulate in areas of CTF virus transmission. Lastly, the quantitative real-time RT-PCR assay demonstrated exceptional sensitivity for the detection of CTF viral RNA in acute human serum. The quantitative real-time RT-PCR assay is efficient, sensitive and specific and as such is useful for the detection of CTF viral RNA in the diagnostic or research laboratory.

Colorado Tick Fever↗

Colorado tick fever.

Colorado tick fever, also known as mountain fever and mountain tick fever, is a well-described, viral, tick-borne disease common to the Rocky Mountain region of the United States and Canada. The Rocky Mountain wood tick, Dermacentor andersoni, is the primary vector. The triad of high fever, severe myalgia, and headache is typical, but not specific. Although a self-limited disease in most cases, severe complications may occur. PCR techniques have been developed that allow the diagnosis to be established from the first day of symptoms. Ribavirin may merit consideration in the appropriate clinical setting.

Colorado Tick Fever↗

Ecology of porcupines (Erethizon dorsatum) and Colorado tick fever virus in Rocky Mountain National Park, 1975-1977.

The involvement of porcupines, Erethizon dorsatum (L.), in the ecology of Colorado tick fever (CTF) virus in Rocky Mountain National Park was investigated from 1975 to 1977. Porcupine dens and feeding activity were found mostly on rocky knolls or on south-facing slopes within open stands of the montane coniferous forest, and 20 adult porcupines were trapped or captured by hand at those locations. An average of 24.6 +/- 5.4 adult Dermacentor andersoni Stiles ticks were found per animal (annual range, 17.5-31.4 ticks). The minimum CTF virus infection rate of the ticks removed from porcupines varied from 129 to 257, whereas for questing adult D. andersoni ticks from the same geographic area was 205 in 1976. No virus was isolated from the 20 animals, but 85% had neutralizing antibody against CTF virus. Porcupines utilize the same habitats described for the CTF ecosystem in Rocky Mountain National Park and appear to be an important host for adult D. andersoni.

Animals↗

Detection of Colorado tick fever virus by using reverse transcriptase PCR and application of the technique in laboratory diagnosis.

Colorado tick fever (CTF) virus elicits an acute illness in humans, producing nonspecific flu-like symptoms and a biphasic fever in approximately 50% of patients. The disease is transmitted by the adult Rocky Mountain wood tick (Dermacentor andersoni), and therefore incidence is limited by the habitat and life cycle of that vector. The early symptoms of infection are difficult to distinguish from those of several other agents, especially Rickettsia rickettsii. Serologic testing is usually unable to provide evidence of CTF viral infection during the acute phase because of the late appearance of the various antibodies. Here we report the development and clinical application of a test to diagnose this disease during the acute stages. Oligonucleotide primers to the S2 segment of CTF (Florio) virus were made, and these were used in the amplification of a 528-bp fragment of DNA, transcribed from the double-stranded CTF virus RNA template by reverse transcriptase PCR. RNAs processed from 16 CTF virus isolates yielded similar results when analyzed on agarose gels. These were distinguishable from their antigenic relatives Eyach, S6-14-03, and T5-2092 and from other coltiviruses and an orbivirus but not from the antigenically distinct CTF virus-related isolate 720896. A mouse model demonstrated the utility of this method with whole-blood specimens, and CTF virus was successfully detected in human sera from the initial day of the onset of symptoms to 8 days later. The reverse transcriptase PCR method is a promising tool for the early diagnosis of CTF viral infection, or for ruling out CTF virus as the etiologic agent, in order to facilitate appropriate medical support.

Adult↗

Increasing prevalence of gestational diabetes mellitus (GDM) over time and by birth cohort: Kaiser Permanente of Colorado GDM Screening Program.

OBJECTIVE: The prevalence of gestational diabetes mellitus (GDM) varies in direct proportion with the prevalence of type 2 diabetes in a given population or ethnic group. Given that the number of people with diabetes worldwide is expected to increase at record levels through 2030, we examined temporal trends in GDM among diverse ethnic groups. RESEARCH DESIGN AND METHODS: Kaiser Permanente of Colorado (KPCO) has used a standard protocol to universally screen for GDM since 1994. This report is based on 36,403 KPCO singleton pregnancies occurring between 1994 and 2002 and examines trends in GDM prevalence among women with diverse ethnic backgrounds. RESULTS: The prevalence of GDM among KPCO members doubled from 1994 to 2002 (2.1-4.1%, P < 0.001), with significant increases in all racial/ethnic groups. In logistic regression, year of diagnosis (odds ratio [OR] and 95% CI per 1 year = 1.12 [1.09-1.14]), mother's age (OR per 5 years = 1.7 [1.6-1.8]) and ethnicity other than non-Hispanic white (OR = 2.1 [1.9-2.4]) were all significantly associated with GDM. Birth year remained significant (OR = 1.06, P = 0.006), even after adjusting for prior GDM history. CONCLUSIONS: This study shows that the prevalence of GDM is increasing in a universally screened multiethnic population. The increasing GDM prevalence suggests that the vicious cycle of diabetes in pregnancy initially described among Pima Indians may also be occurring among other U.S. ethnic groups.

Adult↗

Survey for evidence of Colorado tick fever virus outside of the known endemic area in California.

A virus very similar or identical to Colorado tick fever (CTF) virus was recovered from the blood clot of one of 104 black-tailed jack rabbits (Lepus californicus) examined during a survey for various zoonotic agents in mammals and ticks from the University of California, Hopland Field Station, Mendocino County, California, 1974--79. This is the first reported isolation of a CTF-like virus from L. californicus, and only the second time such a virus has been found in northwestern California. Mendocino County is located far outside the known distributional ranges of the most common mammalian hosts of CTF virus and of Dermacentor andersoni, the only proven tick vector for man. The viral isolate is very similar to a CTF-like virus previously recovered from the blood and spleen of a western gray squirrel (Sciurus griseus) from San Luis Obispo County, an area also outside of the previously-known CTF area. Virus was not isolated from 14 additional species of mammals (354 specimens) or from eight species of ticks (4,487 individuals), but CTF-neutralizing antibodies were detected in 28 of 771 (3.6%) sera from seven of 15 mammalian species including significant titers (greater than or equal to 1:8) in two species and one subspecies not previously reported as natural hosts, i.e., brush mouse (Peromyscus boylii), pinyon mouse (P. truei), and Columbian black-tailed deer (Odocoileus hemionus columbianus). CTF indirect immunofluorescent antibodies also were detected in 26 of 129 (20.2%) sera belonging to four of five mammalian species tested. Neutralizing antibodies were found in sera of deer from other localities in Mendocino County, from a deer mouse from Napa County, and from a brush rabbit from Monterey County as well. These findings suggest that a virus identical or similar to CTF virus is widespread in northwestern-westcentral California, and that surveillance for human cases of CTF or a similar disease should be extended to cover this region.

Animals↗

Serologic and molecular diagnosis of Colorado tick fever viral infections.

Molecular and serologic methods usable for the biological diagnosis of Coltivirus infection are reported. We designed a multiplex reverse transcription-polymerase chain reaction system that allowed the simultaneous and specific amplification of three genomic segments from as little as 0.01 plaque-forming units. Another system in the S2 viral segment permitted the differential diagnosis of American and European viral isolates. We also discuss some improvements of previous ELISAs, and the results obtained with paired sera from Colorado tick fever (CTF) virus-infected individuals. Western blot analysis was developed that allowed the detection of antibodies to a 38-kD viral protein in all tested sera. It also enabled the detection of anti-CTF virus antibodies in ELISA-negative sera. Specific IgM antibodies against a synthetic viral peptide could be detected in sera at the acute stage of the infection. Together, these results should permit the diagnosis of Coltivirus infection at any stage of the pathology.

Amino Acid Sequence↗

Immunoperoxidase staining for detection of Colorado tick fever virus, and a study of congenital infection in the mouse.

Indirect immunoperoxidase (IP) staining was evaluated for sensitivity and specificity in detecting Colorado tick fever (CTF) virus antigen in infected cell cultures and infected mouse tissues, and then was applied to a study of congenital CTF infection in mice. The sensitivity of IP staining was comparable to that of immunofluorescence staining in detecting CTF antigen in infected cell cultures. Endogenous peroxidase activity of mouse tissues caused nonspecific reactivity in the IP system, but this could be abolished by treatment with sodium azide and hydrogen peroxide without destroying CTF antigen. Offspring of mice infected with CTF virus during the 2nd week of pregnancy showed a highly significant increase in the incidence of stillbirths and neonatal deaths as compared with offspring of uninfected controls. CTF antigen or virus was demonstrable in only a low proportion (7%) of embryos, ill newborns or stillborns examined, but a high proportion of mice examined at a time when maternal antibody would be lost (6 and 12 weeks) showed CTF antibody, indicating a higher incidence of infection. IP staining showed potential for use in studies of viral pathogenesis in the mouse model.

Animals↗

An overview of Colorado tick fever.

Certain features of Colorado tick fever (CTF) virus and the disease it causes may be relevant to studies on bluetongue virus (BTV), or other orbiviruses. Rapid and easy detection of viral antigen in infected tissues and peripheral blood cells by immunofluorescence staining facilitate diagnosis of the disease. The prolonged (3-4 months) viremia is due to persistent intracellular infection, particularly of erythrocytes, in which the virus is protected from antibody or other host defense mechanisms. This results in more efficient maintenance of the virus cycle in nature, but might lead to adverse effects in the human host. Clues to understanding chronic viral infections or viral immunosuppression might be gained by further research on CTF and other orbiviruses.

Animals↗

The Colorado thyroid disease prevalence study.

CONTEXT: The prevalence of abnormal thyroid function in the United States and the significance of thyroid dysfunction remain controversial. Systemic effects of abnormal thyroid function have not been fully delineated, particularly in cases of mild thyroid failure. Also, the relationship between traditional hypothyroid symptoms and biochemical thyroid function is unclear. OBJECTIVE: To determine the prevalence of abnormal thyroid function and the relationship between (1) abnormal thyroid function and lipid levels and (2) abnormal thyroid function and symptoms using modern and sensitive thyroid tests. DESIGN: Cross-sectional study. PARTICIPANTS: Participants in a statewide health fair in Colorado, 1995 (N = 25 862). MAIN OUTCOME MEASURES: Serum thyrotropin (thyroid-stimulating hormone [TSH]) and total thyroxine (T4) concentrations, serum lipid levels, and responses to a hypothyroid symptoms questionnaire. RESULTS: The prevalence of elevated TSH levels (normal range, 0.3-5.1 mIU/L) in this population was 9.5%, and the prevalence of decreased TSH levels was 2.2%. Forty percent of patients taking thyroid medications had abnormal TSH levels. Lipid levels increased in a graded fashion as thyroid function declined. Also, the mean total cholesterol and low-density lipoprotein cholesterol levels of subjects with TSH values between 5.1 and 10 mIU/L were significantly greater than the corresponding mean lipid levels in euthyroid subjects. Symptoms were reported more often in hypothyroid vs euthyroid individuals, but individual symptom sensitivities were low. CONCLUSIONS: The prevalence of abnormal biochemical thyroid function reported here is substantial and confirms previous reports in smaller populations. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest elevations of TSH corresponded to changes in lipid levels that may affect cardiovascular health. Individual symptoms were not very sensitive, but patients who report multiple thyroid symptoms warrant serum thyroid testing. These results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement.

Adult↗

The prevalence of age-related maculopathy by geographic region and ethnicity. The Colorado-Wisconsin Study of Age-Related Maculopathy.

OBJECTIVES: To determine the prevalence of age-related maculopathy (ARM) in a biethnic population and to determine if there are ethnic and/or geographic differences in the prevalence of ARM. DESIGN: Prevalence data from 2 population-based studies, the San Luis Valley Diabetes Study (n = 1541, ages 21-74 years) and the Beaver Dam Eye Study (n = 3999, ages 43-74 years), were compared. SETTING: Southern Colorado and central Wisconsin. MAIN OUTCOME MEASURE: Color stereoscopic fundus photographs were graded for ARM using the Wisconsin Age-related Maculopathy Grading System. Similar questionnaire, laboratory, and clinical data on potential risk factors were available from both studies. RESULTS: Late-stage ARM was significantly less frequent among Hispanics than non-Hispanic whites (NHW) in Beaver Dam (odds ratio [OR] = 0.07; 95% confidence interval [CI] = 0.01-0.49; Hispanics vs Beaver Dam NHW). The prevalence of any ARM was significantly lower among San Luis Valley NHW (10.4%) than Beaver Dam NHW (14.3%) (OR = 0.67; 95% CI = 0.50-0.91). This prevalence difference was not explained by any of the risk factors examined (smoking, cardiovascular disease, diabetes, alcohol consumption, etc). The 2 NHW groups reported different European heritages. CONCLUSIONS: Late-stage ARM appeared to be rare among Hispanics but there was no ethnic difference in prevalence of any ARM. The 33% difference in risk among NHW by geographic location was not reduced when controlling for possible risk factors or confounders, suggesting that genetic heritage may be an important determinant of risk for ARM.

Adult↗

A successful international child health elective: the University of Colorado Department of Pediatrics' experience.

OBJECTIVES: To describe the organizational features of an international child health elective (ICHE) and to document the diversity of diagnoses observed by residents. DESIGN: Faculty from the Department of Pediatrics, University of Colorado Health Sciences Center, Denver, created a steering committee in 1999 to develop and direct an ICHE, including selecting residents, selecting and organizing sites, and creating objectives and a year-long preparatory curriculum. The elective was piloted in 2000 and repeated in 2002 and 2004. SETTING AND PARTICIPANTS: Residents chose from 4 ICHE sites in Peru and Guatemala, where they observed clinical care in various clinical settings during a 4-week elective. MAIN OUTCOME MEASURES: The ICHE was evaluated via written evaluations by faculty and residents as well as written and oral reports by participating residents. RESULTS: During the 2000 and 2004 electives, residents recorded clinical cases in a data-entry log. Of the patients logged, 18% had illnesses never seen before by the residents and 5.6% had illnesses in advanced stages not previously seen by the residents. Strong reciprocal relationships were created between the department and participating international institutions. Residents reported uniformly that the elective was a valuable element of their training. CONCLUSIONS: Planning and faculty involvement in ICHEs helps to ensure achievement of elective objectives. Well-organized ICHEs have the potential to augment resident education. The experience at our institution demonstrates that ICHEs can provide experience with a variety of medical systems, exposure to diverse pathophysiologic conditions, and opportunities for collaboration with international colleagues.

Colorado↗

Newborn screening for hemoglobinopathies in Colorado. The first 10 years.

In Colorado, newborn screening for hemoglobinopathies by cellulose acetate and citrate agar electrophoresis of dried capillary blood spots was established in 1979. We reviewed the results of screening 528,711 infants through 1988. Forty-seven infants with sickle cell diseases and 27 infants with other hemoglobin diseases were identified. The initial screening failed to detect sickle cell anemia in 4 infants, but the hemoglobinopathy in 3 of these infants was diagnosed correctly by routine retesting of those with suspected sickle cell trait. A total of 47 infants with sickle cell diseases were followed through September 1989. There was no mortality among these infants. The screening test identified 3779 infants (1:140 births) with a suspected hemoglobin trait; confirmatory retesting was obtained in 53%. The results of our experience confirm the value of newborn screening for hemoglobinopathies but suggest that a more sensitive test would improve the program.

Colorado↗

Enamel hypoplasia in ancestral Puebloan populations from southwestern Colorado: I. Permanent Dentition.

Dental enamel hypoplasias are used to examine metabolic disruption experienced during early childhood by ancestral Puebloan (Anasazi) inhabitants of southwestern Colorado. The hypoplasia sample consists of the permanent anterior dentition from 147 individuals from Montezuma County and Mesa Verde National Park. Using the individual as the basis of analysis, the study compares different time periods of occupation of the region with respect to prevalence and timing of hypoplasia occurrence. The frequency of enamel hypoplasia in the combined regional sample is high, affecting 90% of the individuals and 66% of the anterior teeth. The earliest onset of hypoplasia in individuals occurs most commonly at 2.5-3.0 years, and the peak age of enamel disruption in 3.0-3.5 years. There are no significant differences in hypoplasia frequency or timing between males and females or between adults and subadults. The level of childhood stress appears to have increased significantly with time from the Basketmaker III to the Pueblo I and Pueblo II periods, then decreased slightly during the Pueblo III. The differences between the Pueblo I, II, and III periods are not significant. The Pueblo II sample from Yellow Jacket Canyon sites 5MT1 and 5MT3 and the Dolores Pueblo I sample show the highest levels of childhood stress in comparison to other Puebloan populations inhabiting this region prior to A.D.

Adult↗

Brief communication: prehistoric dentistry in the American southwest: a drilled canine from Sky Aerie, Colorado.

A prehistoric Native American mandible from a Fremont site (circa AD 1025) in Colorado has a conical pit in the worn occlusal surface of the lower right canine. Natural causes for this modification are ruled out by the presence of internal striae, a finding confirmed by experimental replication. The canine was artificially drilled before the individual's death and is associated with a periapical abscess. This is one of a very few examples of prehistoric dentistry in the world, and the first from the American Southwest.

Adult↗

Latency analysis in epidemiologic studies of occupational exposures: application to the Colorado Plateau uranium miners cohort.

BACKGROUND: Latency effects are an important factor in assessing the public health implications of an occupational or environmental exposure. Usually, however, latency results as described in the literature are insufficient to answer public health related questions. Alternative approaches to the analysis of latency effects are warranted. METHODS: A general statistical framework for modeling latency effects is described. We then propose bilinear and exponential decay latency models for analyzing latency effects as they have parameters that address questions of public health interest. Methods are described for fitting these models to cohort or case-control data; statistical inference is based on standard likelihood methods. APPLICATION: A latency analysis of radon exposure and lung cancer in the Colorado Plateau uranium miners cohort was performed. We first analyzed the entire cohort and found that the relative risk associated with exposure increases for about 8.5 years and thereafter decreases until it reaches background levels after about 34 years. The hypothesis that the relative risk remains at its peak level is strongly rejected (P < 0.001). Next, we investigated the variation in the latency effects over subsets of the cohort based on attained age, level and rate of exposure, and smoking. Age was the only factor for which effect modification was demonstrated (P = 0.014). We found that the decline in effect is much steeper at older ages (60+ years) than younger. CONCLUSION: The proposed methods can provide much more information about the exposure-disease latency effects than those generally used.

Air Pollutants, Radioactive↗