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.
Rabies was undetected in terrestrial wildlife of northern Arizona until 2001, when rabies was diagnosed in 19 rabid skunks in Flagstaff. Laboratory analyses showed causative rabies viruses associated with bats, which indicated cross-species transmission of unprecedented magnitude. Public health infrastructure must be maintained to address emerging zoonotic diseases.
Increasing coccidioidomycosis rates in Arizona may indicate the development of a hypervirulent strain. One hundred and twenty-one clinical Coccidioides spp. isolates were collected over 16 months from Maricopa, Graham, Yuma, and Pima counties in Arizona. The patient age distribution ranged from 9 to 91 years, with a median age of 58 years; 36% were female, and 64% male. All isolates were analyzed by measuring length polymorphisms in nine distinct microsatellite regions. The three microsatellites found to have the greatest discriminatory power for Coccidioides posadasii were: K03 (0.87), GA37 (0.83), and K01 (0.78). The majority of isolates (n=119) were C. posadasii. Duplicate isolates (n=28) from 13 patients showed single strain infections. Phylogenetic analysis of the microsatellite data showed no dominant microsatellite pattern. We conclude that the increase in reported cases of coccidioidomycosis in Arizona is not linked to a dominant, hypervirulent strain of Coccidioides posadasii.
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