W. John Pape

West Nile Virus Disease: A Descriptive Study of 228 Patients Hospitalized in a 4-County Region of Colorado in 2003

BACKGROUND Risk factors for complications of West Nile virus disease and prognosis in hospitalized patients are incompletely understood. METHODS Demographic characteristics and data regarding potential risk factors, hospitalization, and dispositions were abstracted from medical records for residents of 4 Colorado counties who were hospitalized in 2003 with West Nile virus disease. Univariate and multivariate analyses were used to identify factors associated with West Nile encephalitis (WNE), limb weakness, or death by comparing factors among persons with the outcome of interest with factors among those without the outcome of interest. RESULTS Medical records of 221 patients were reviewed; 103 had West Nile meningitis, 65 had WNE, and 53 had West Nile fever. Respiratory failure, limb weakness, and cardiac arrhythmia occurred in all groups, with significantly more cases of each in the WNE group. Age, alcohol abuse, and diabetes were associated with WNE. Age and WNE were associated with limb weakness. The mortality rate in the WNE group was 18%; age, immunosuppression, requirement of mechanical ventilation, and history of stroke were associated with death. Only 21% of patients with WNE who survived returned to a prehospitalization level of function. The estimated incidence of West Nile fever cases that required hospitalization was 6.0 cases per 100,000 persons; West Nile fever was associated with arrhythmia, limb weakness, and respiratory failure. CONCLUSIONS Persons with diabetes and a reported history of alcohol abuse and older persons appear to be at increased risk of developing WNE. Patients with WNE who have a history of stroke, who require mechanical ventilation, or who are immunosuppressed appear to be more likely to die. Respiratory failure, limb weakness, and arrhythmia occurred in all 3 categories, but there were significantly more cases of all in the WNE group.

Cases of Cat-Associated Human Plague in the Western US, 1977–1998

Exposure to cats infected with Yersinia pestis is a recently recognized risk for human plague in the US. Twenty-three cases of cat-associated human plague (5 of which were fatal) occurred in 8 western states from 1977 through 1998, which represent 7.7% of the total 297 cases reported in that period. Bites, scratches, or other contact with infectious materials while handling infected cats resulted in 17 cases of bubonic plague, 1 case of primary septicemic plague, and 5 cases of primary pneumonic plague. The 5 fatal cases were associated with misdiagnosis or delays in seeking treatment, which resulted in overwhelming infection and various manifestations of the systemic inflammatory response syndrome. Unlike infections acquired by flea bites, the occurrence of cat-associated human plague did not increase significantly during summer months. Plague epizootics in rodents also were observed less frequently at exposure sites for cases of cat-associated human plague than at exposure sites for other cases. The risk of cat-associated human plague is likely to increase as residential development continues in areas where plague foci exist in the western US. Enhanced awareness is needed for prompt diagnosis and treatment.

Birth Outcomes Following West Nile Virus Infection of Pregnant Women in the United States: 2003-2004

BACKGROUND. Congenital West Nile virus (WNV) infection was first described in a single case in 2002. The proportion of maternal WNV infections resulting in congenital infection and clinical consequences of such infections are unknown. METHODS. In 2003 and 2004, women in the United States who acquired WNV infection during pregnancy were reported to the Centers for Disease Control and Prevention by state health departments. Data on pregnancy outcomes were collected. One of the maternal WNV infections was identified retrospectively after the infant was born. Maternal sera, placenta, umbilical cord tissue, and cord serum were tested for WNV infection by using serologic assays and reverse-transcription polymerase chain reaction. Infant health was assessed at delivery and through 12 months of age. RESULTS. Seventy-seven women infected with WNV during pregnancy were clinically followed in 16 states. A total of 71 women delivered 72 live infants; 4 women had miscarriages, and 2 had elective abortions. Of the 72 live infants, 67 were born at term, and 4 were preterm; gestational age was unknown for 1. Of 55 live infants from whom cord serum was available, 54 tested negative for anti-WNV IgM. One infant born with umbilical hernia and skin tags had anti-WNV IgM in cord serum but not in peripheral serum at age 1 month. An infant who had no anti-WNV IgM in cord blood, but whose mother had WNV illness 6 days prepartum, developed WNV meningitis at age 10 days. Another infant, whose mother had acute WNV illness at delivery, was born with a rash and coarctation of the aorta and had anti-WNV IgM in serum at 1 month of age; cord serum was not available. A fourth infant, whose mother had onset of WNV illness 3 weeks prepartum that was not diagnosed until after delivery, had WNV encephalitis and underlying lissencephaly detected at age 17 days and subsequently died; cord serum was not available. The following major malformations were noted among live-born infants: aortic coarctation (n = 1); cleft palate (n = 1); Down syndrome (n = 1); lissencephaly (n = 1); microcephaly (n = 2); and polydactyly (n = 1). One infant had glycogen storage disease type 1. Abnormal growth was noted in 8 infants. CONCLUSIONS. Of 72 infants followed to date in 2003 and 2004, almost all seemed normal, and none had conclusive laboratory evidence of congenital WNV infection. Three infants had WNV infection that could have been congenitally acquired. Seven infants had major malformations, but only 3 of these had defects that could have been caused by maternal WNV infection based on the timing of the infections and the sensitive developmental period for the specific malformations, and none had any conclusive evidence of WNV etiology. However, the sensitivity and specificity of IgM testing of cord blood to detect congenital WNV infection are currently unknown, and congenital WNV infection among newborns with IgM-negative serology cannot be ruled out. Prospective studies comparing pregnancy outcomes of WNV-infected and -uninfected women are needed to better define the outcomes of WNV infection during pregnancy.

Human Prion Disease and Relative Risk Associated with Chronic Wasting Disease

Colorado death certificate data from 1979 through 2001 show that the risk for Creutzfeldt-Jakob disease did not increase for residents of counties where chronic wasting disease is endemic among deer and elk.

Seasonal Patterns for Entomological Measures of Risk for Exposure to Culex Vectors and West Nile Virus in Relation to Human Disease Cases in Northeastern Colorado

ABSTRACT We examined seasonal patterns for entomological measures of risk for exposure to Culex vectors and West Nile virus (family Flaviviridae, genus Flavivirus, WNV) in relation to human WNV disease cases in a five-county area of northeastern Colorado during 2006–2007. Studies along habitat/ elevation gradients in 2006 showed that the seasonal activity period is shortened and peak numbers occur later in the summer for Culex tarsalis Coquillett females in foothills-montane areas > 1,600 m compared with plains areas <1,600 m in Colorados Front Range. Studies in the plains of northeastern Colorado in 2007 showed that seasonal patterns of abundance for Cx. tarsalis and Culex pipiens L. females differed in that Cx. tarsalis reached peak abundance in early July (mean of 328.9 females per trap night for 18 plains sites), whereas the peak for Cx. pipiens did not occur until late August (mean of 16.4 females per trap night). During June-September in 2007, which was a year of intense WNV activity in Colorado with 578 reported WNV disease cases, we recorded WNV-infected Cx. tarsalis females from 16 of 18 sites in the plains. WNV infection rates in Cx. tarsalis females increased gradually from late June to peak in mid-August (overall maximum likelihood estimate for WNV infection rate of 8.29 per 1,000 females for the plains sites in mid-August). No WNV-infected Culex mosquitoes were recorded from sites > 1,600 m. The vector index for abundance of WNV-infected Cx. tarsalis females for the plains sites combined exceeded 0.50 from mid-July to mid-August, with at least one site exceeding 1.00 from early July to late August. Finally, we found that abundance of Cx. tarsalis females and the vector index for infected females were strongly associated with weekly numbers of WNV disease cases with onset 4–7 wk later (female abundance) or 1–2 wk later (vector index).

Bat ecology and public health surveillance for rabies in an urbanizing region of Colorado

We describe use of Fort Collins, Colorado, and nearby areas by bats in 2001–2005, and link patterns in bat ecology with concurrent public health surveillance for rabies. Our analyses are based on evaluation of summary statistics, and information-theoretic support for results of simple logistic regression. Based on captures in mist nets, the city bat fauna differed from that of the adjacent mountains, and was dominated by big brown bats (Eptesicus fuscus). Species, age, and sex composition of bats submitted for rabies testing locally and along the urbanizing Front Range Corridor were similar to those of the mist-net captures and reflected the annual cycle of reproduction and activity of big brown bats. Few submissions occurred November- March, when these bats hibernated elsewhere. In summer females roosted in buildings in colonies and dominated health samples; fledging of young corresponded to a summer peak in health submissions with no increase in rabies prevalence. Roosting ecology of big brown bats in buildings was similar to that reported for natural sites, including colony size, roost-switching behavior, fidelity to roosts in a small area, and attributes important for roost selection. Attrition in roosts occurred from structural modifications of buildings to exclude colonies by citizens, but without major effects on long-term bat reproduction or survival. Bats foraged in areas set aside for nature conservation. A pattern of lower diversity in urban bat communities with dominance by big brown bats may occur widely in the USA, and is consistent with national public health records for rabies surveillance.

Delayed Mortality in a Cohort of Persons Hospitalized with West Nile Virus Disease in Colorado in 2003

Most mortality associated with West Nile virus (WNV) disease occurs during the acute or early convalescent phases of illness. However, some reports suggest mortality may be elevated for months or longer after acute illness. The objective of this study was to assess the survival of a cohort of patients hospitalized with WNV disease in Colorado in 2003 up to 4 years after illness onset. We calculated age-adjusted standardized mortality ratios (SMRs) to evaluate excess mortality, evaluated reported causes of death in those who died, and analyzed potential covariates of delayed mortality. By 1 year after illness onset, 4% of the 201 patients had died (SMR, 2.7; 95% confidence interval [CI], 1.3-5.2), and 12% had died by 4 years after onset (SMR, 2.0; 95% CI, 1.3-3.0). Among those who had died, the most common immediate and contributory causes of death included pulmonary disease and cardiovascular disease; cancer, hepatic disease, and renal disease were mentioned less frequently. In multivariate analysis, age (hazard ratio [HR], 2.0 per 10-year increase; 95% CI, 1.4-2.7), autoimmune disease (HR, 3.0; 95% CI, 1.1-7.9), ever-use of tobacco (HR, 3.0; 95% CI, 1.3-7.0), encephalitis during acute WNV illness (HR, 2.6; 95% CI, 1.1-6.4), and endotracheal intubation during acute illness (HR 4.8; 95% CI, 1.9-12.1) were found to be independently associated with mortality. Our finding of an approximate twofold increase in mortality for up to 3 years after acute illness reinforces the need for prevention measures against WNV infection among at-risk groups to reduce acute as well as longer-term adverse outcomes.

Spatial Risk Assessments Based on Vector-Borne Disease Epidemiologic Data: Importance of Scale for West Nile Virus Disease in Colorado

We used epidemiologic data for human West Nile virus (WNV) disease in Colorado from 2003 and 2007 to determine 1) the degree to which estimates of vector-borne disease occurrence is influenced by spatial scale of data aggregation (county versus census tract), and 2) the extent of concordance between spatial risk patterns based on case counts versus incidence. Statistical analyses showed that county, compared with census tract, accounted for approximately 50% of the overall variance in WNV disease incidence, and approximately 33% for the subset of cases classified as West Nile neuroinvasive disease. These findings indicate that sub-county scale presentation provides valuable risk information for stakeholders. There was high concordance between spatial patterns of WNV disease incidence and case counts for census tract (83%) but not for county (50%) or zip code (31%). We discuss how these findings impact on practices to develop spatial epidemiologic data for vector-borne diseases and present data to stakeholders.

Irrigated Agriculture is an Important Risk Factor for West Nile Virus Disease in the Hyperendemic Larimer-Boulder-Weld Area of North Central Colorado

ABSTRACT This study focused on two West Nile virus (WNV) disease outbreak years, 2003 and 2007, and included a three-county area (Larimer, Boulder, and Weld) in North Central Colorado that is hyperendemic for WNV disease. We used epidemiological data for reported WNV disease cases at the census tract scale to: 1) elucidate whether WNV disease incidence differs between census tracts classified as having high versus lower human population density (based on a threshold value of 580 persons/km2) and 2) determine associations between WNV disease incidence and habitat types suitable as development sites for the larval stage of Culex mosquito vectors. WNV disease incidence was significantly elevated in census tracts with lower human population density, compared with those with high density of human population, in both 2003 (median per census tract of 223 and 143 cases per 100,000 population, respectively) and 2007 (median per census tract of 46 and 19 cases per 100,000 population). This is most likely related, in large part, to greater percentages of coverage in less densely populated census tracts by habitats suitable as development sites for Culex larvae (open water, developed open space, pasture/hay, cultivated crops, woody wetlands, and emergent herbaceous wetlands) and, especially, for the subset of these habitats made up by irrigated agricultural land (pasture/hay and cultivated crops) that presumably serve as major producers of the locally most important vector of WNV to humans: Culex tarsalis. A series of analyses produced significant positive associations between greater coverage of or shorter distance to irrigated agricultural land and elevated WNV disease incidence. As an exercise to produce data with potential to inform spatial implementation schemes for prevention and control measures within the study area, we mapped the spatial patterns, by census tract, of WNV disease incidence in 2003 and 2007 as well as the locations of census tracts that had either low (<25th percentile) or high (>75th percentile) WNV disease incidence in both outbreak years (relative to the incidence for each year). This revealed substantial changes from 2003 to 2007 in the spatial pattern for census tracts within the study area with high WNV disease incidence and suggests a dynamic and evolving scenario of WNV transmission to humans that needs to be taken into account for prevention and control measures to stay current and represent the most effective use of available resources.