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Virus heartland: una nueva y emergente encefalitis transmitida por garrapatas.

Heartland virus: a novel and emerging tick-borne encephalitis

El Virus Heartland (HRTV) es un Bunyaviridae, Phlebovirus que ha surgido recientemente en los Estados Unidos y China como el agente causal de una enfermedad humana caracterizada por trombocitopenia y leucopenia. Parece ser que el HRTV ha sido reportado en China, Japon y Corea. Recientemente se reporto el primer caso fatal de la enfermedad HRTV en un residente de 80 aos de edad de Tennessee (1).

Las garrapatas Amblyomma americanum y Dermacentor variabilis han sido implicadas como vectores de HRTV in EEUU. La amplificacion de huespedes vertebrados asociados con el mantenimiento enzootico del HRTV ha sido estudiada en Missouri. Se identificaron anticuerpos neutralizantes a HRTV en mapaches (42.6%), caballos (17.4%), venado cola blanca (14.3%), perros (7.7%) y zarigueyas (3.8%). No se encontraron anticuerpos en aves. La alta seroprevalencia asociada con abundancia local de venados cola blanca y mapaches demostro que estas especies pueden ser huespedes amplificadores. Experimentos para aislar el HRTV a partir de sueros y garrapatas no han sido exitosos (2).

En 2012, en fincas de Missouri, se recolectaron 56.428 garrapatas Amblyomma americanum y Dermacentor variabilis. Mediante el uso de RT-PCR (reaccion en cadena de la polimerasa con retrotranscriptasa inversa), varios grupos de ninfas de A. americanum fueron positivos, en 8 grupos se detectaron virus viables. Datos de la secuencia de la proteina no estructural del segmento pequeo demostro que las cepas de garrapatas y cepas humanas son muy similares, con un >97.6% de identidad en las secuencias (3).

Este fue el primer estudio para aislar HRTV de las garrapatas y al parecer estan implicas como vectores potenciales. Amblyomma americanum es posible que se infecte al alimentarse de los huespedes viremicos durante la etapa larval y la transmision a los seres humanos se produce durante la primavera y principios del verano cuando las ninfas son abundantes y estan activas buscando un huesped (3).

En una encuesta de seroprevalencia realizada en Minnesota, EE.UU, en muestras de sangre de animales domesticos para determinar anticuerpos para HRTV. Los anticuerpos contra nucleoproteinas del virus fueron encontrados en un 10%-18% de las muestras provenientes de ganado, ovejas, cabras, ciervos y alces en el condado de Minnesota (4).

La mayoria de los pacientes con HRTV presentan fiebre, trombocitopenia, leucopenia fatiga, anorexia, dolor de cabeza, nauseas, mialgia y artralgia. Una enfermedad clinicamente compatible con HRTV ha sido definida con fiebre ([mayor que o igual a] 38.0[grados]C), leucopenia (globulos blancos recuento <4.500 celulas/[mm.sup.3]; rango normal = 4.50012.000 celulas/[mm.sup.3]) y trombocitopenia (recuento de plaquetas < 150.000/[mm.sup.3]; rango normal = 150.000400.000/[mm.sup.3]) y sin una explicacion clinica diferente a HRTV. Los medicos en Colombia y Latinoamerica deben reconocer el virus de Heartland en pacientes que presentan fiebre, leucopenia y trombocitopenia y que han resultado negativos para la infecciones por Ehrlichia, Anaplasma y Babesia o no han respondido a la terapia con doxiciclina (5).

Recientemente hubo un informe del primer caso fatal de la enfermedad HRTV en un residente de Tennessee de 80-aos de edad. El paciente fue ingresado a la clinica con fiebre, confusion, leucopenia, trombocitopenia, hemorragia y desarrollo de insuficiencia multiorganica. El paciente fallecio en el hospital 15 dias despues y muestras provenientes de la autopsia fueron probadas para diversos agentes patogenos como parte de una evaluacion de una muerte inexplicable. Se detectaron antigenos HRTV post mortem en el bazo y los ganglios linfaticos por inmunohistoquimica y HRTV se detecto en la sangre pre mortem por RT-PCR y el virus se aislo en cultivo celular (6).

Debido HRTV es un virus emergente, el diagnostico de laboratorio todavia es incipiente, sin embargo, el diagnostico en Colombia y Latinoamerica es extremadamente dificil. Sin embargo, la deteccion de ARN viral mediante RT-PCR en sangre o tejido se puede llevar a cabo, por tanto, un aumento de [amyor que o igual a] 4 de titulos de anticuerpos por PRNT en muestras de suero en convalecientes se puede llevar a cabo (5).

Al igual que otros virus, no existe una vacuna o medicamento que este disponible para prevenir o tratar la enfermedad de virus Heartland. Dado que es posible que el virus sea transmitido por garrapatas infectadas u otros artropodos, la prevencion depende del uso de repelentes de insectos, el uso de mangas largas, pantalones y la realizacion de controles de garrapatas despues de pasar tiempo al aire libre (5).

En Colombia, especialmente en los tropicos, hay una fuerte evidencia de Amblyomma sp y Dermacentor por lo tanto, es probable que HRTV este circulando. Los casos fatales en EE.UU. demuestran que la infeccion HRTV puede causar una enfermedad grave y la muerte. En Colombia, la poblacion de garrapatas es endemica y afecta a los animales y a las personas, la difusion de la HRTV en Colombia probablemente sea debido a las condiciones geoclimaticas favorables (7).

Por ultimo, los virus transmitidos por garrapatas que causan enfermedades en humanos pertenecen principalmente a 3 familias: Bunyaviridae, Flaviviridae, y Reoviridae, en Latinoamerica no sabemos acerca de estas enfermedades transmitidas por vectores por lo que es necesario llevar a cabo varios estudios para establecer la prevalencia de aquellos virus en los vectores y los seres humanos.

Heartland virus (HRTV) is a Bunyaviridae, phlebovirus that it has recently emerged as the causative agent of human disease characterized by thrombocytopenia and leukopenia in the United States and China. It seems to be the HRTV has been also reported in China, Japan and Korea. Recently the first fatal case of HRTV disease in an 80-year-old Tennessee resident was reported (1).

Amblyomma americanum and Dermacentor variabilis ticks have been involved as a vector of HRTV in USA. The vertebrates amplification hosts associated with enzootic maintenance of the HRTV have been studied in Missouri. Neutralizing antibodies to HRTV in raccoons (42.6%), horses (17.4%), white-tailed deer (14.3%), dogs (7.7%) and opossums (3.8%) were identified. No antibodies were found in birds. The high seroprevalence associated with local abundance of white-tailed deer and raccoons demonstrated these species may be an amplification hosts. Virus isolation experiments from sera and ticks to detect HRTV virus were unsuccessful (2).

In 2012 in Missouri farms, 56.428 ticks of Amblyomma americanum and Dermacentor variabilis were collected. By using RT-PCR (reverse transcription-polymerase chain reaction), several nymphs pools of A. americanum were positive, 8 pools yielded viable viruses. Sequence data from the nonstructural protein of the small segment demonstrates that tick strains and human strains are very similar, >97.6% sequence identity (3).

This was the first study to isolate HRTV from ticks and they seem to be implicating as potential vectors. Amblyomma americanum possible to becomes infected by feeding on viremic hosts during the larval stage, and transmission to humans occurs during the spring and early summer when nymphs are abundant and actively host seeking (3).

A seroprevalence survey performed in Minnesota, USA, tested blood samples from domestic animals to determine antibodies to HRTV. Antibodies against virus nucleoproteins in 10%18% of samples from cattle, sheep, goats, deer, and elk in Minnesota counties were found (4).

Most patients with HRTV show fever, thrombocytopenia, leukopenia fatigue, anorexia, headache, nausea, myalgia, or arthralgia. A clinically compatible disease have been defined as fever ([greater than or equal to] 38.0[degrees]C), leukopenia (white blood cell count < 4.500 cells/[mm.sup.3]; normal range = 4.500-12.000 cells/[mm.sup.3]), and thrombocytopenia (platelet count <150.000/[mm.sup.3]; normal range =150.000-400.000/ [mm.sup.3]) without a more probably clinical explanation. Physicians in Colombia and Latin America should recognize Heartland virus testing in patients who show fever, leukopenia, and thrombocytopenia without more likely evidence and who have tested negative for Ehrlichia, Anaplasma and Babesia infection or have not responded to doxycycline therapy (5).

Recently, there was a report of the first fatal case of HRTV disease in an 80-year-old Tennessee resident. The patient was admitted at the clinic with fever, confusion, leukopenia, and thrombocytopenia and developed multiorgan failure and hemorrhage. The patient died on hospital day 15, and autopsy specimens were tested for various pathogens as part of an unexplained death evaluation. HRTV antigens were detected in postmortem spleen and lymph nodes by immunohistochemistry, and HRTV was detected in premortem blood by RT-PCR and the virus was isolated in cell culture (6).

Because HRTV is an emerging virus, laboratory diagnosis is incipient yet, the diagnosis in Colombia and Latin America is extremely difficult. However, detection of viral RNA by RT-PCR on blood or tissue can be carry out, hence a [greater than or equal to] 4-fold rise antibody titers by PRNT in acute and convalescent serum specimens can be carry out (5).

Like other viruses, no vaccine or medication is available to prevent or treat Heartland virus disease. Because the virus possible is transmitted through infected ticks or other arthropods, prevention depends on using insect repellents, wearing long sleeves and pants and performing tick checks after spending time outdoors (5).

In Colombia especially in the tropics, there are strong evidence of Amblyomma sp and Dermacentor ticks thus, it is likely that HRTV is circulating. The fatal cases in USA demonstrate that HRTV infection can cause severe disease and death. In Colombia, tick's population are endemic affecting animals and people, the dissemination of the HRTV in Colombia is likely because the favourable geoclimatic conditions (7).

Finally, tick-borne viruses that cause diseases in humans mainly belong to 3 families: Bunyaviridae, Flaviviridae, and Reoviridae, we actually in Latin America do not know about this vector borne disease, it is necessary to carry out several surveys to establish the prevalence of those viruses in the vectors and humans as well.

Salim Mattar V. Ph.D.

Marco Gonzalez T. M.Sc.

REFERENCES

(1.) Bosco-Lauth AM, Panella NA, Root JJ, Gidlewski T, Lash RR, Harmon JR, Burkhalter KL, Godsey MS, Savage HM, Nicholson WL, Komar N, Brault AC. Serological Investigation of Heartland Virus (Bunyaviridae: Phlebovirus) Exposure in Wild and Domestic Animals Adjacent to Human Case Sites in Missouri 2012-2013. Am J Trop Med Hyg. 2015; 92:1163-1167.

(2.) Bosco-Lauth AM, Panella NA, Root JJ, Gidlewski T, Lash RR, Harmon JR, et al. Serological investigation of heartland virus (Bunyaviridae: Phlebovirus) exposure in wild and domestic animals adjacent to human case sites in Missouri 2012-2013. Am J Trop Med Hyg 2015; 92(6):1163-7. doi: 10.4269/ajtmh.14-0702.

(3.) Savage HM1, Godsey MS Jr, Lambert A, Panella NA, Burkhalter KL, Harmon JR, et al. First detection of heartland virus (Bunyaviridae: Phlebovirus) from field collected arthropods. Am J Trop Med Hyg. 2013; 89(3):445-52. doi: 10.4269/ajtmh.13-0209.

(4.) Xing Z, Schefers J, Schwabenlander M, Jiao Y, Liang M, Qi X, et al. Novel bunyavirus in domestic and captive farmed animals, Minnesota, USA. Emerg Infect Dis. 2013; 19(9):1487-9. doi: 10.3201/eid1909.130165.

(5.) Pastula DM, Turabelidze G, Yates KF, Jones TF, Lambert AJ, Panella Al. Notes from the field: Heartland virus disease--United States, 2012-2013. MMWR Morb Mortal Wkly Rep. 2014 Mar 28;63(12):270-1.

(6.) Muehlenbachs A, Fata CR, Lambert AJ, Paddock CD, Velez JO, Blau DM. Heartland virusassociated death in Tennessee. Clin Infect Dis. 2014; 59(6):845-50. doi: 10.1093/cid/ciu434.

(7.) Miranda J, Portillo A, Oteo JA, Mattar S. Rickettsia sp. Strain Colombianensi (Rickettsiales: Rickettsiaceae): A New Proposed Rickettsia Detected in Amblyomma dissimile (Acari: Ixodidae) From Iguanas and Free-Living Larvae Ticks From Vegetation. J Med Entomol 2012; 49(4):960-965. DOI: http://dx.doi. org/10.1603/ME11195.
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Title Annotation:EDITORIAL
Author:Mattar V., Salim; Gonzalez T., Marco
Publication:Revista MVZ (Medicina Veterinaria y Zootecnia)
Date:Jan 1, 2016
Words:1974
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