West Nile virus (WNV) is a reemerging pathogen that causes fatal encephalitis in several species, including mouse and human. Recently, we showed that the chemokine receptor CCR5 is critical for survival of mice infected with WNV, acting at the level of leukocyte trafficking to the brain. To test whether this receptor is also protective in man, we determined the frequency of CCR5Δ32, a defective CCR5 allele found predominantly in Caucasians, in two independent cohorts of patients, one from Arizona and the other from Colorado, who had laboratory-confirmed, symptomatic WNV infection. The distribution of CCR5Δ32 in a control population of healthy United States Caucasian random blood donors was in Hardy-Weinberg equilibrium and CCR5Δ32 homozygotes represented 1.0% of the total group (n = 1,318). In contrast, CCR5Δ32 homozygotes represented 4.2% of Caucasians in the Arizona cohort (odds ratios [OR] = 4.4 [95% confidence interval [CI], 1.6–11.8], P = 0.0013) and 8.3% of Caucasians in the Colorado cohort (OR = 9.1 [95% CI, 3.4–24.8], P < 0.0001). CCR5Δ32 homozygosity was significantly associated with fatal outcome in the Arizona cohort (OR = 13.2 [95% CI, 1.9–89.9], P = 0.03). We conclude that CCR5 mediates resistance to symptomatic WNV infection. Because CCR5 is also the major HIV coreceptor, these findings have important implications for the safety of CCR5-blocking agents under development for HIV/AIDS.

West Nile virus (WNV) is a re-emerging pathogen that can cause fatal encephalitis. In mice, susceptibility to WNV has been reported to result from a single point mutation in oas1b, which encodes 2′–5′ oligoadenylate synthetase 1b, a member of the type I interferon-regulated OAS gene family involved in viral RNA degradation. In man, the human ortholog of oas1b appears to be OAS1. The ‘A’ allele at SNP rs10774671 of OAS1 has previously been shown to alter splicing of OAS1 and to be associated with reduced OAS activity in PBMCs. Here we show that the frequency of this hypofunctional allele is increased in both symptomatic and asymptomatic WNV seroconverters (Caucasians from five US centers; total n = 501; OR = 1.6 [95% CI 1.2–2.0], P = 0.0002 in a recessive genetic model). We then directly tested the effect of this SNP on viral replication in a novel ex vivo model of WNV infection in primary human lymphoid tissue. Virus accumulation varied markedly among donors, and was highest for individuals homozygous for the ‘A’ allele (P<0.0001). Together, these data identify OAS1 SNP rs10774671 as a host genetic risk factor for initial infection with WNV in humans.

The causes and frequency of acute paralysis and respiratory failure with West Nile virus (WNV) infection are incompletely understood. During the summer and fall of 2003, we conducted a prospective, population-based study among residents of a 3-county area in Colorado, United States, with developing WNV-associated paralysis. Thirty-two patients with developing paralysis and acute WNV infection were identified. Causes included a poliomyelitislike syndrome in 27 (84%) patients and a Guillain-Barré–like syndrome in 4 (13%); 1 had brachial plexus involvement alone. The incidence of poliomyelitislike syndrome was 3.7/100,000. Twelve patients (38%), including 1 with Guillain-Barré–like syndrome, had acute respiratory failure that required endotracheal intubation. At 4 months, 3 patients with respiratory failure died, 2 remained intubated, 25 showed various degrees of improvement, and 2 were lost to followup. A poliomyelitislike syndrome likely involving spinal anterior horn cells is the most common mechanism of WNV-associated paralysis and is associated with significant short- and long-term illness and death.

Objective: To provide a large, comprehensive evaluation of the CSF findings in patients with serologically confirmed West Nile virus (WNV), CNS disease, and their correlation with outcome. Methods: CSF samples from 334 WNV-infected hospitalized patients were analyzed. Information was available and extracted from the medical records of 250 of these patients, and CSF parameters correlated with clinical and epidemiologic features of disease (e.g., patient age, sex, outcome). Results: Patients with meningitis had a mean of 226 cells/mm 3 , and those with encephalitis had a mean of 227 cells/mm 3 . Three percent of meningitis patients and 5% of encephalitis patients had fewer than 5 cells/mm 3 , and approximately 8% of both groups had more than 500 cells/mm 3 . Patients with meningitis had a mean of 41% neutrophils, and those with encephalitis had 45%. Forty-five percent of meningitis patients and 37% of encephalitis patients had at least 50% neutrophils in their initial CSF specimen. Neither the mean percent neutrophils nor their distribution differed significantly between groups. Forty-seven percent of encephalitis patients and 16% of meningitis patients had CSF protein of 100 mg/dL or greater (p Ͻ 0.01). Although specific CSF parameters, including nucleated cell count and protein concentration, correlated significantly with outcome, multivariate analysis suggested that their total predictive value was modest. Age was an additional predictor of outcome independent of CSF variables in all patients. Conclusions: Serologically confirmed West Nile virus meningitis and encephalitis produce similar degrees of CSF pleocytosis and are frequently associated with substantial CSF neutrophilia. Patients with encephalitis have higher CSF protein concentrations and are more likely to have adverse outcomes, including admission to long-term care facilities or even death after their acute illness. CSF findings were only a modest predictor of disease outcome, with patient age adding important independent prognostic information.

We report 1-year follow-up data from a longitudinal prospective cohort study of patients with West Nile virus–associated paralysis. As in the 4-month follow-up, a variety of recovery patterns were observed, but persistent weakness was frequent. Respiratory involvement was associated with considerable illness and death.

Long-term neurocognitive and functional impairments following West Nile virus (WNV) disease are poorly understood. We assessed quality-of-life indices and neurocognitive performance in a cohort of 54 persons recovering from one of three WNV disease syndromes (fever [WNF], meningitis [WNM], or encephalitis [WNE]) approximately 1.5 years following acute illness. We compared findings between the three syndromic groups; the study cohort and a demographically similar group of 55 controls from a study of chronic fatigue syndrome (CFS); and the study cohort and a 'normative' control population based on cognitive test data. Persistent symptoms, diminished quality of life, and functional impairment were reported by 50% of WNF patients, and 75% each of WNM and WNE patients. Overall, objective neurocognitive performance did not differ significantly between the three syndromic groups, or between the study cohort and the CFS controls or the normative controls. In some neurocognitive subtests, the study cohort scored below the 15th percentile when compared with normative control data. Most persons who returned to independent

Plague is a rare but highly virulent flea-borne zoonotic disease caused by the Gram-negative bacterium Yersinia pestis Yersin. Identifying areas at high risk of human exposure to the etiological agent of plague could provide a useful tool for targeting limited public health resources and reduce the likelihood of misdiagnosis by raising awareness of the disease. We created logistic regression models to identify landscape features associated with areas where humans have acquired plague from 1957 to 2004 in the four-corners region of the United States (Arizona, Colorado, New Mexico, and Utah), and we extrapolated those models within a geographical information system to predict where plague cases are likely to occur within the southwestern United States disease focus. The probability of an area being classified as high-risk plague habitat increased with elevation up to approximately 2300 m and declined as elevation increased thereafter, and declined with distance from key habitat types (e.g., southern Rocky Mountain piñon--juniper [Pinus edulis Engelm. and Juniperus spp.], Colorado plateau piñon--juniper woodland, Rocky Mountain ponderosa pine (Pinus ponderosa P.& C. Lawson var. scopulorum), and southern Rocky Mountain juniper woodland and savanna). The overall accuracy of the model was >82%. Our most conservative model predicted that 14.4% of the four-corners region represented a high risk of peridomestic exposure to Y. pestis.

Identification of methicillin-resistant Staphylococcus aureus (MRSA) from blood cultures usually takes 1 to 2 days following detection in semiautomated blood culture systems. Bloodstream infections with MRSA are associated with significant morbidity and mortality and have a significant impact on healthrelated costs (1, 3). Therefore, early detection of MRSA in blood cultures plays an important role in patient management. A selective and differential medium, CHROMagar MRSA medium (C-MRSA) (Becton Dickinson [BD], Sparks, MD), has been evaluated for identifying MRSA from pure cultures as well as from nasal swab specimens and found to have excellent performance characteristics (5,7,8,12). To determine whether this medium could be useful for rapid identification of MRSA directly from blood cultures, we evaluated the ability of CHROMagar MRSA medium to accurately detect MRSA directly from subcultures of positive blood cultures.The study was performed in the Clinical Microbiology Laboratory at the Hospital of the University of Pennsylvania from May 2005 through January 2006. All blood culture bottles (Bactec Plus aerobic/anaerobic media; BD) containing grampositive cocci in clusters, consistent with staphylococci, were prospectively subcultured to blood agar plates (Trypticase soy agar with 5% sheep blood; BD, Sparks, MD) in addition to C-MRSA and incubated at 35°C without CO 2 for 18 to 24 h before examination. Only the first set of blood cultures containing gram-positive cocci in clusters from a particular patient was included in the study. C-MRSA plates were reincubated for an additional 24 h if there was no growth on the plates. Tube coagulase tests (BD) were performed directly on samples from positive blood culture bottles. Colonies exhibiting the mauve phenotype on C-MRSA were further identified using the catalase test (HUMCO, Texarkana, TX) and the Staphaurex slide test (Remel Europe Ltd., Dartford, Kent, United Kingdom), and susceptibility testing was performed using the Vitek 2 system (GP-61 card; BioMerieux Inc., Hazelwood, MO).One hundred twenty-four MRSA isolates were recovered from blood cultures during the time period (Table 1). C-MRSA detected 121 isolates after 18 to 24 h of incubation (97.6% sensitivity) and 124 after 48 h of incubation (100% sensitivity). Eighty-seven methicillin-susceptible S. aureus (MSSA) isolates were recovered, and none of the MSSA isolates grew on C-MRSA (Table 2). Of 657 coagulase-negative staphylococci (CNS) isolated from blood cultures, 188 did not grow on C-MRSA at 24 or 48 h, 431 grew on C-MRSA at 24 h and 48 h but did not form mauve colonies (i.e., they were colorless), and 31 isolates did not grow after 24 h but appeared as nonmauve colonies at 48 h. Additionally, five CNS isolates grew on C-MRSA along with other bacteria, and all of these were nonmauve colonies. There were two false-positive results. One isolate that grew on C-MRSA and appeared as mauve colonies at 18 to 24 h was identified as Staphylococcus epidermidis. One additional isolate grew on C-MRSA at 48 h, app...