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West Nile Virus, Venezuela to the Editor: West Nile Virus (WNV; Genus Flavivirus; Family Flaviviridae) Has Been Perpetuating in North America Since 1999 (1)

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West Nile Virus, Venezuela to the Editor: West Nile Virus (WNV; Genus Flavivirus; Family Flaviviridae) Has Been Perpetuating in North America Since 1999 (1) LETTERS West Nile Virus, Venezuela To the Editor: West Nile virus (WNV; genus Flavivirus; family Flaviviridae) has been perpetuating in North America since 1999 (1). However, its status as a self-perpetu- ating pathogen in South America remains uncertain. Infected horses and birds have been reported in vari- ous Caribbean Islands, Mexico, and northern Central America (2,3). In South America, isolated reports of infected dead-end hosts (horses) have come from northern Colombia and Argentina, but they lack evidence for infection in avian amplifying hosts Figure. Temperature and heart rate relationship: scatter plot for patients with dengue fever (4,5). We report serologic evidence of and nondengue febrile illnesses. establishment of WNV in South America. the etiology of dengue-associated 8. Wali JP, Biswas A, Chandra S, Malhotra A, Serum samples from birds and relative bradycardia. Aggarwal P, Handa R, et al. Cardiac horses from 33 locations in involvement in dengue haemorrhagic fever. Venezuela (Online Appendix Table, Int J Cardiol. 1998;64:31–6. Aisha Lateef,* 9. Blatteis CM, Li S, Li Z, Feleder C, Perlik V. available from http://www.cdc.gov/ Dale Andrew Fisher,*† Cytokines, PGE2 and endotoxic fever: a re- EID/content/13/4/651-appT.htm) and Paul Ananth Tambyah,*† assessment. Prostaglandins Other Lipid were screened for immunoglobulin G Mediat. 2005;76:1–18. *National University Hospital, Singapore; (IgG) antibodies against WNV anti- 10. Fink J, Gu F, Vasudevan SG. Role of T and †National University of Singapore, cells, cytokines and antibody in dengue gen by ELISA (6) and confirmed by Singapore fever and dengue haemorrhagic fever. Rev plaque reduction neutralization test Med Virol. 2006;16:263–75. (PRNT) as previously described (7). References The flavivirus generating the IgG Address for correspondence: Paul Ananth 1. Guzman MG, Kouri G. Dengue: an update. response was identified by using the Lancet Infect Dis. 2002;2:33–42. Tambyah, Department of Medicine, National following criteria: 90% inhibition of 2. Fisher D. To the vector borne….mosquito- University of Singapore, 5 Lower Kent Ridge virus in serum diluted at least 1:40 transmitted diseases in Singapore. Rd, Singapore 119074; email: mdcpat@nus. Singapore Med J. 2005;46:596. and 4-fold greater neutralizing anti- edu.sg 3. Wilder-Smith A, Earnest A, Paton NI. Use body titer compared with closely of simple laboratory features to distinguish related flaviviruses. IgG antibody the early stage of severe acute respiratory against flavivirus was detected by syndrome from dengue fever. Clin Infect Dis. 2004;39:1818–23. ELISA in 14 of 576 resident birds, 4. Guzman MG, Kouri G. Dengue diagnosis, including 5 Turdus leucomelas, 3 advances and challenges. Int J Infect Dis. Gallus gallus (captive), 2 Campylor- 2004;8:69–80. hamphus trochilirostris, and 1 each of 5. Ostergaard L, Huniche B, Andersen PL. Relative bradycardia in infectious diseases. Elaenia flavogaster, Coereba flaveo- J Infect. 1996;33:185–91. la, Thraupis palmarum, and Anisog- 6. Cunha BA. The diagnostic significance of nathus flavinucha. relative bradycardia in infectious disease. WNV was confirmed as the etio- Clin Microbiol Infect. 2000;6:633–4. 7. Khongphatthanayothin A, Suesaowalak M, logic agent of infection in 5 adult Muangmingsook S, Bhattarakosol P, birds (3 T. leucomelas [pale-breasted Pancharoen C. Hemodynamic profiles of thrush], 1 C. flaveola [bananaquit], patients with dengue hemorrhagic fever and 1 G. gallus [domestic chicken] during toxic stage: an echocardiographic study. Intensive Care Med. 2003;29:570–4. with the earliest collection date in February 2006); virus neutralization Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 4, April 2007 651 LETTERS titers ranged from 80 to 320. One infection of dead-end hosts, e.g., hors- not been detected in Venezuela, this serum sample cross-reacted with es. This is the first report of WNV flavivirus is prevalent in Brazil, Peru, other flaviviruses tested, with equiva- infection in South American birds and French Guyana, Trinidad, and lent titers to WNV, Saint Louis definitive establishment of the virus Colombia. Our study demonstrated encephalitis virus (SLEV), and Ilheus in South America. widespread distribution of ILHV in virus (ILHV) and was thus considered We observed varying WNV sero- Venezuela. Other South American fla- infected with an undetermined fla- prevalence rates in birds and horses viviruses, such as Bussuquara, vivirus. Seven serum samples were across regions in Venezuela (Figure). Cacipacore, and Iguape, and as yet negative (antibody titers <20), and 1 These differences reflect the focal and undiscovered viruses may also circu- sample was not tested because of stochastic nature of arbovirus trans- late in Venezuela. insufficient sample volume. mission, which depends upon many We encourage those involved in Antibody against flavivirus was ecologic factors. One possible expla- the public and animal health systems detected by ELISA in 141 of 791 hors- nation for the greater seroprevalence in Venezuela to consider zoonotic fla- es, and 34 (4.3%) were confirmed pos- in the central and eastern llanos viviruses in the differential diagnoses itive for WNV infection by PRNT; (savannahs) and valley regions, com- of human and equine cases of viral titers ≥640 occurred in half of pared with the coastal western region encephalitis and to consider ecologic these horses. The earliest collection of Zulia State (p<0.0001, by surveillance for zoonotic flaviviruses date for a WNV-positive horse was Pearson’s χ2 test) would be virus in mosquito and vertebrate host popu- February 2004 and the most recent introduction by migrating birds by an lations. We recommend monitoring was May 2006. Specific WNV-reac- eastern migration route. blood and organ donations for fla- tive equine serum samples were dis- Existence of several closely relat- vivirus infections. Our study sheds tributed in valley regions (prevalence ed flaviviruses in the American trop- light on flavivirus distribution in 1.3%), savannah grasslands (2.4%), ics (8–10) may convey cross-protec- Venezuela. However, nothing else is the western region of Zulia (0.4%) and tion in animals (e.g., ILHV and known about the ecology of zoonotic the Central Lake Basin (0.3%). A total SLEV) or humans (dengue viruses, flaviviruses in this country. Such of 46 (5.8%) equine serum samples yellow fever virus), thereby potential- knowledge will be essential for were positive for neutralizing antibody ly diminishing disease caused by a designing effective surveillance and to SLEV, and 8 (1.0%) samples were newly introduced flavivirus such as control should these viruses be shown positive for neutralizing antibodies to WNV. Although ILHV infection has to cause human illnesses. ILHV. Forty-nine samples neutralized at least 2 of the 3 viruses and were classified as undetermined flavivirus- es. Serum samples from 2 horses were negative in neutralization assays; 2 others were not tested because of insufficient sample volume. Detection of WNV-infected resi- dent birds provides strong evidence of the establishment, rather than impor- tation, of WNV in South America. We hypothesize that ornithophilic mos- quitoes (such as some Culex spp.), which are present in the area in con- sistently high numbers, acquired the virus through hematophagous feeding on recently infected, migrating birds. Once introduced to local mosquitoes, virus is amplified among susceptible resident birds fed upon by ornitho- Figure. West Nile virus (WNV) collection sites in Venezuela, indicated by number (see philic mosquitoes. This pattern allows online Appendix Table). Symbols represent results of tests for specific antibodies to WNV perpetuation and subsequent estab- in serum samples of birds and horses (viral titers in a 90% plaque reduction neutralization test >40 and a 4-fold differential inhibition in a neutralization assay to WNV compared with lishment of virus in a continuous other related flaviviruses). Source: Instituto Geográfico de Venezuela Simón Bolivar, transmission cycle, as opposed to Caracas. 652 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 13, No. 4, April 2007 LETTERS Acknowledgments Agrícolas, Maracay, Venezuela; ‡‡Instituto Novel Extended- We dedicate this work to the late Oswaldo Cruz, Rio de Janeiro, Brazil; Andrew Spielman, our coauthor and §§Centers for Disease Control and spectrum Prevention, San Juan, Puerto Rico, USA; β beloved mentor. We thank J. Rivero, I. ¶¶Universidad del Zulia, Maracaibo, -Lactamase in Pérez, M. Méndez, I. Matheus, M. Aguiar Venezuela; ##Ministerio de Salud Insalud, Shigella sonnei de Bracho, I. Carreño, J.M. Hernández, A. Carabobo, Venezuela; ***Centers for Nagy, A. Suarez, N. Moncada, M. Disease Control and Prevention, Fort To the Editor: A 38-year-old Kilpatrick, E. Rodriguez, E. Marquez, E. Collins, Colorado, USA; and ††† Harvard French man with a history of chronic School of Public Health, Boston, Marian, B. Hernández; C. Rivero-Blanco, Massachusetts, USA juvenile arthritis was referred to the M. Azar, J. Rodriguez, H. Montañez, F. Necker-Enfants Malades University Alfonzo, and G. Rangel for their contribu- References hospital (Paris, France) with a dysen- tions to this study; and the Centro de teric syndrome. The patient had Investigaciones Biomédicas, Universidad 1. Hayes EB, Komar N, Nasci RS, returned the day before from a 1- Montgomery SP, O’Leary DR. Campbell de Carabobo and the Cell Culture Core of GL Epidemiology and transmission dynam- month stay in Port-au-Prince, Haiti, Wadsworth Center, New York State ics of West Nile virus disease. Emerg Infect where he spent most of his time in Health Department, for their support. We Dis. 2005;11:1167–73. close contact with young children also thank ProFauna and the National 2. Komar N, Clark GG. West Nile virus activ- from an orphanage, most of whom ity in Latin America and the Caribbean. Institute of Parks in Venezuela for permis- Rev Panam Salud Publica. 2006;19:112–7. had diarrhea. Clinical examination at sion to obtain mosquito and bird samples. 3. Morales-Betoulle ME, Morales H, Blitvich admission showed fever (39°C), BJ, Powers AM, Davis EA, Klein R, et al.
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