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Estudios Serológicos Preliminares De Virus Una Y Mayaro (Alphavirus

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Estudios Serológicos Preliminares De Virus Una Y Mayaro (Alphavirus Articulo original Estudios serológicos de Virus Una y Mayaro (Alphavirus), en humanos de la localidad de Orán, Salta Argentina. Autores: Jean, A.1; Farías, A.1; Cacace, M.2; Pisano, B. 1; Konigheim, B. 1; Aguilar, J.1; Spinsanti, L.1; Contigiani, M1. 1 Instituto de Virología “Dr. J. M. Vanella”, Facultad de Ciencias Médicas – Universidad Nacional de Córdoba, Córdoba, Argentina. 2Hospital San Vicente de Paul-San Ramón de la Nueva Orán- Salta, Argentina. *Autor: Jean Ana Noelia Instituto de Virología “Dr. J. M. Vanella” Facultad de Ciencias Médicas Universidad Nacional de Córdoba. Córdoba, Argentina. Enfermera Gordillo Gómez s/n Ciudad Universitaria CP: 5016, Córdoba, Argentina. [email protected] 1 RESUMEN Los virus Una (UNAV) y Mayaro (MAYV) se encuentran ampliamente distribuidos en América del Sur, donde han sido detectados en mosquitos y en hospedadores vertebrados (humanos, caballos y aves). Estudios serológicos han detectado infección por UNAV en aves, equinos y humanos en Argentina, pero su distribución y riesgo como patógeno no se conoce. MAYV ha sido asociado a enfermedad febril, similar a Dengue, con producción de rash y artralgias en regiones tropicales de América del sur. Hasta el presente no se conoce la situación de este virus en nuestro país. El objetivo del estudio fue detectar la presencia de anticuerpos neutralizantes contra UNAV y MAYV en sueros humanos de la localidad de San Ramón de la Nueva Orán, Salta, Argentina. Se obtuvo una prevalencia de anticuerpos neutralizantes para UNAV de 3.2% (9/281), mientras que no se detectaron muestras positivas para MAYV. Estos resultados constituyen el primer reporte de infección en humanos por UNAV en la ciudad de San Ramón de la Nueva Orán, destacándose así la necesidad de profundizar el estudio de infecciones febriles negativas para Dengue a fin de poder conocer el rol del UNAV como agente patógeno. PALABRAS CLAVES: UNAV, MAYV, Prevalencia, Orán, Argentina. 2 INTRODUCCION Los virus Una (UNAV) y Mayaro (MAYV) pertenecen al complejo antigénico Semliki forest, género Alphavirus, familia Togaviridae 1.Se encuentran ampliamente distribuidos en América del sur, donde han sido detectados en mosquitos y en hospedadores vertebrados (humanos, caballos y aves) 2. UNAV ampliamente distribuido en zonas tropicales y subtropicales de América Central y Sur 3 no ha sido asociado a ningún tipo específico de enfermedad en humanos. En Argentina se han aislado dos cepas de este virus (Cba An979 y Cba An995) a partir de un equino febril y otro muerto en la provincia de Córdoba 4, donde además fueron detectados anticuerpos en aves y equinos 3, 5. MAYV, antigénicamente relacionado a UNAV, produce una enfermedad febril benigna y autolimitada 2.Casos por este virus han sido documentados en países limítrofes a Argentina como en Bolivia y Brasil 2, 6, 7. Hasta el presente no se conoce la situación de nuestro país frente a la presencia de este virus. Por otra parte estos virus poseen relación antigénica con virus Chikungunya, detectándose, recientemente, 3 casos importados en Brasil, situación que alertó a los servicios de salud de dicho país frente al posible establecimiento endémico de este nuevo virus exótico en nuestro continente 8. Por esta razón, resulta importante conocer la distribución y endemicidad de MAYV y UNAV en nuestro país ante la necesidad de realizar un diagnóstico diferencial de enfermedades febriles similares a las que producen Dengue (DENV) y/o Chikungunya. El objetivo de este trabajo fue determinar la presencia de anticuerpos neutralizantes para UNAV y MAYV en sueros humanos con serología negativa para DENV, pertenecientes a la localidad de San Ramón de la nueva Orán, Salta, Argentina. 3 MATERIALES Y METODOS Área de Estudio: Corresponde a la ciudad de San Ramón de la Nueva Orán, 23°08′ Sur 64°20′ Oeste en la provincia de Salta, Argentina. El clima es subtropical con estación seca. Muestras: Se analizaron 281 muestras colectadas en el año 2009 correspondientes a sueros de pacientes con síndrome febril indiferenciado y serología negativa para DENV. Dichas muestras correspondieron a pacientes de ambos sexos con un rango etáreo de 0-85 años que asistieron al hospital San Vicente de Paul (Orán, Salta). Ningún paciente reportó historia previa de viajes a las zonas endémicas de los virus en estudio. Virus: se utilizaron las cepas UNAV Cba An 979 y MAYV Be Ar 20290. Las suspensiones virales para la técnica de neutralización fueron preparadas a partir de cerebros de ratón lactante infectados al 10% (peso/volumen) en medio esencial mínimo, con sales de Earle y L-glutamina, 10% de suero fetal bovino y antibiótico, centrifugada a 10000 rpm durante 30 minutos. Prueba serológica: se utilizó la prueba de neutralización de unidades formadoras de placas (ufp) en cultivo de células Vero (riñón de mono verde africano) bajo agarosa9. En la prueba de tamizaje se utilizó la dilución 1:10 de cada suero y se consideraron positivos aquellos sueros que neutralizaban el 80% de las ufp incluidas en la prueba. Los sueros que resultaron positivos en el tamizaje se titularon por la misma técnica a partir de la dilución 1:10 utilizando diluciones seriadas factor 2. Software para análisis estadístico: Info-stat Profesional 2.0. 4 RESULTADOS Del total de muestras analizadas, 57% eran mujeres y 43% hombres. Sólo 9 muestras resultaron positivas para UNAV, lo que representa una prevalencia del 3.2%. Los títulos de anticuerpos neutralizantes de las muestras positivas se muestran en la Tabla 1. Ninguno de los sueros resultó positivo para MAYV. Los análisis estadísticos demostraron que no existía dependencia entre los casos positivos y la edad del paciente (P-valor >0.05). TABLA 1: Títulos de anticuerpos neutralizantes (AcNT) en sueros positivos para UNAV. MUESTRA EDAD (años) TITULO DE AcNT 1 50 1/20 2 76 1/20 3 57 1/40 4 43 1/80 5 68 1/20 6 37 1/40 7 38 1/20 8 1 1/20 9 27 1/20 5 DISCUSIÓN Estos resultados constituyen el primer reporte de circulación en humanos por UNAV en la ciudad de San Ramón de la Nueva Orán, con una prevalencia y títulos de anticuerpos neutralizantes similares a los encontrados en humanos de la ciudad de Córdoba 10 y en monos de la región norte de nuestro país 11. En este estudio la detección de anticuerpos en un individuo de 1 año de edad (Tabla 1) podría estar indicando circulación reciente de UNAV. Por otro lado, no se pudo implicar a este virus como agente etiológico de la sintomatología febril debido a que el hallazgo de anticuerpos en una única muestra de suero no permite el diagnóstico confirmatorio. Para esto sería necesario una segunda muestra de suero o la detección de anticuerpos tipo IgM indicadores de infección reciente. No se evidenció la presencia de anticuerpos para MAYV a diferencia de lo encontrado en el país limítrofe Bolivia, donde se conoce que existe la circulación de este arbovirus 12. Si bien estos resultados contribuyen al conocimiento de la distribución del UNAV y MAYV en Argentina, sería importante profundizar el estudio de infecciones febriles negativas para DENV a fin de poder conocer la verdadera implicancia del UNAV en estos casos. 6 REFERENCIAS: 1. Griffin, DE. Alphavirus. En: Fields Virology (Two Volumes) 4th Edition by Bernard N. Fields (Ed), Peter M., MD Howley (Ed), Diane E., Ph.D. Griffin (Ed), Robert A., Ph.D. Lamb (Ed), Malcolm A., MD Martin (Ed), Bernard Roizman (Ed), Stephen E., MD Straus (Ed), David M., Ph.D. Knipe (Ed) By Lippincott Williams & Wilkins Publishers. 2001.30:745-785. 2. Contigiani, MS; Díaz, LA. Togaviroses:Encefalites e outras Doenças En: Doenças Transmitidas e Causadas por Artrópodes. Brisola Marcondes, C. Atheneu(Ed), Sao Pablo. 2009.3: 27-47. 3. Sabattini, MS; Avilés,G; Monath, TP. Historical, epidemiological and ecological aspects of arboviruses in Argentina: Togaviridae, Alphavirus. En: Travassos Da Rosa, A.P.A.; Vasconcelos P.F.C. y Travassos Da Rosa, J.F.S., ed. An overview of Arbovirology in Brazil and neighbouring countries. Belém, Instituto Evandro Chagas, 1998. 135-153. 4. Gonzalez, LE; Sabattini, MS; Vanella, JM y Bianchini, NR - Primer Aislamiento en la República Argentina de arbovirus Grupo A, pertenecientes al Complejo Mayaro-Una. Validez del Aislamiento. En: Terceras Sesiones Científicas de Biología, Rosario, 1965. Resumen 78. 5. Sabattini, MS; Shope, RE y Vanella, JM - Estudio serológico de arbovirus en la Provincia de Córdoba, Argentina. Amer. J. Trop. Med. HYG, 1965. 14:1073-1078. 6. Torres, J; Russell, L; Vasquez, C; B; Salas, R y Watts D. Family Cluster of Mayaro Fever, Venezuela. Emerging infectious diseases. 2004. 10: 1304–1306. 7. Coimbra,T; Santos, C; Suzuki, A; Petrella, S; Bisordi, I; Nagamori, A; Marti, A; Santos ,R; Fialho, D; Lavigne, S; Buzzar ,M; Rocco. Mayaro virus: imported cases of 7 human infection in São Paulo State, Brazil. Revista do Instituto de Medicina Tropical Sao Paulo. 2007. 49: 221-224. 8. Gomes Cavalcanti de Albuquerque,I; Marandino,R; Pimentel Mendonça ,A; Ribeiro Nogueira, R; Da Costa Vasconcelos, F; Rodrigues Guerra, L; Castro Brandão, B; Pimentel Mendonça, A; Ribeiro Aguiar, G; Martinez de Bacco, P. Chikungunya virus infection: report of the first case diagnosed in Rio de Janeiro, Brazil. Revista da Sociedade Brasileira de Medicina Tropical. 2012.45: 128-129. 9. Early E, Peralta P, Johnson KM. A plaque neutralization method for arboviruses. Proc Soc Exp Biol. 1967. 25: 741-747. 10. Díaz, LA; Spinsanti, LI; Almiron, WR; Contigiani, MS. UNA virus: first report of human infection in Argentina. Rev. Inst. Med Trop. 2003. 45: 109-110. 11. Díaz, LA; Díaz, M; Almirón, W; Contigian, M. Infection by UNA virus (Alphavirus; Togaviridae) and risk factor analysis in black howler monkeys (Alouatta caraya) from Paraguay and Argentina. Transactions of the Royal Society of Tropical Medicine and Hygiene.
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