RESEARCH Endemic Venezuelan Equine Encephalitis in Nor ther n Peru Patricia V. Aguilar,* Ivorlyne P. Greene,* Lark L. Coffey,* Gladys Medina,*1 Abelardo C. Moncayo,*2 Michael Anishchenko,* George V. Ludwig,† Michael J. Turell,‡ Monica L. O’Guinn,‡ John Lee,‡ Robert B. Tesh,* Douglas M. Watts,† Kevin L. Russell,† Christine Hice,* Stephen Yanoviak,* Amy C. Morrison,§ Terry A. Klein,‡ David J. Dohm,‡ Hilda Guzman,* Amelia P.A. Travassos da Rosa,* Carolina Guevara,† Tadeusz Kochel,† James Olson,† Cesar Cabezas,¶ and Scott C. Weaver* Since Venezuelan equine encephalitis virus (VEEV) was isolated in Peru in 1942, >70 isolates have been obtained from mosquitoes, humans, and sylvatic mammals primarily in the Amazon region. To investigate genetic rela- tionships among the Peru VEEV isolates and between the Peru isolates and other VEEV strains, a fragment of the PE2 gene was amplified and analyzed by single-stranded conformation polymorphism. Representatives of seven genotypes underwent sequencing and phylogenetic analy- sis. The results identified four VEE complex lineages that cocirculate in the Amazon region: subtypes ID (Panama and Colombia/Venezuela genotypes), IIIC, and a new, pro- posed subtype IIID, which was isolated from a febrile human, mosquitoes, and spiny rats. Both ID lineages and the IIID subtype are associated with febrile human illness. Most of the subtype ID isolates belonged to the Panama genotype, but the Colombia/Venezuela genotype, which is phylogenetically related to epizootic strains, also continues to circulate in the Amazon basin. Vemerging mosquito-borne RNA virus in the family enezuelan equine encephalitis virus (VEEV) is an Togaviridae, genus Alphavirus. Since its isolation in 1938, many equine epizootics and epidemics have been reported in Colombia, Venezuela, Trinidad, Peru, Ecuador, Mexico, and the United States, and other countries (1–5); the num- ber of reports of human and equine cases have increased during recent years (6–8). At least 13 distinct subtypes and varieties, including several different species, make up the VEE complex (Table 1). Only subtype I varieties A, B, and C have caused major outbreaks involving hundreds of *University of Texas Medical Branch, Galveston, Texas, USA; †Naval Medical Research Center Detachment, Lima, Peru; ‡U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA; §University of California, Davis, California, USA; and ¶Instituto Nacional de Salud, Lima, Peru thousands of equine and human cases. Subtypes II through VI and subtype I varieties D, E, and F are enzootic, equine- avirulent strains not associated with major equine out- breaks or epidemics, although they do cause human illness, which can be fatal (9,10). In Peru, VEEV was first isolated in the 1940s, when subtype IAB strains caused equine epizootics and epi- demics along the Pacific coast (7,8). Field investigations were later conducted to determine the origin of the IAB strains. Initial ecologic studies in the Amazon region of northeastern Peru (11,12) yielded 11 VEE complex isolates from mosquitoes and sentinel hamsters during 1970 and 1971 in Quistococha, near Iquitos (Figure 1). Antigenic analyses identified 10 isolates as subtype ID VEEV (11) and one strain as subtype IIIC in the VEE complex (12,13). Because these viruses were isolated only from sentinel hamsters and mosquitoes, whether they were human pathogens remained unclear. Not until 1993 through 1995, when VEEV subtype ID was isolated from persons with febrile illness in the Amazon region of Peru (4,14), was there clear evidence that VEEV causes human disease in this region. Two subtype ID strains were isolated from patients in Pantoja in 1994, and 10 other subtype ID strains were obtained from febrile patients in and around the city of Iquitos from 1993 to 1995. Nucleotide sequences and phylogenetic analyses recently performed on Peruvian VEEV isolates indicated that the 1970s VEEV subtype ID mosquito isolates and the 1994 Pantoja human isolates belong to the Colombia/ Venezuela ID genotype, whereas the 1993–1995 Iquitos 1Current affiliation is Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela. 2Current affiliation is Department of Biological Sciences, Ohio Northern University, Ada, Ohio. 880 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 5, May 2004