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Endemic Severe Fever with Thrombocytopenia Syndrome, Vietnam.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne virus (genus Phlebovirus, family Phenuiviridae) that can cause a mild to severe febrile illness similar to hemorrhagic fever (1). Phleboviruses have been found in the Americas, Asia, Africa, and the Mediterranean region. For example, Heartland virus (HRTV), another tickborne phlebovirus, was identified in northwestern Missouri, USA, in 2009 (2). Malsoor virus, a new bat phlebovirus closely related to SFTSV and HRTV, was identified in western India, and a phlebovirus similar to SFTSV and HRTV was isolated from ticks in Australia (3,4).

Severe fever with thrombocytopenia syndrome (SFTS) illness was first confirmed in China in 2009. It was retrospectively identified in South Korea in 2010 and the western regions of Japan in 2013 (1,5,6). SFTS is characterized by acute high fever, thrombocytopenia, leukopenia, elevated serum hepatic enzymes, gastrointestinal symptoms, and multiorgan failure and has a death rate of 16.2%-30% (1,6,7). Atypical signs and symptoms and asymptomatic infections also have been identified (5,8). Most SFTSV infections occur through Haemaphysalis longicornis ticks, although SFTSV transmission can also occur through close contact with an infected patient (8).

To investigate evidence of SFTSV infections in Vietnam, we collected serum samples from 80 patients with acute febrile illnesses admitted to Hue University Hospital (Hue, Vietnam) during October 1, 2017-March 31, 2018. The Institutional Review Board of Hue University Hospital approved the study.

For the molecular diagnosis of SFTSV, we extracted RNA from stored patient serum using a QIAamp Viral RNA Mini Kit (QIAGEN, https://www.qiagen.com) and performed real-time reverse transcription PCR (rRT-PCR) to amplify the partial small (S) segment of the viral RNA from the stored serum and confirm SFTSV infection (9). rRT-PCR showed 2 positive results, from the stored serum of 2 patients with thrombocytopenia who had been seen at Hue University Hospital during 2017 and who had no history of travel to SFTSV-endemic countries, such as China, South Korea, and Japan. We also detected IgM in the serum of 1 of these patients (Appendix Table, https://wwwnc.cdc. gov/EID/article/25/5/18-1463-App1.pdf) (8).

On October 29, 2017, a 29-year-old woman (Hue 06-Vietnam-10-2017) was hospitalized at Hue University Hospital because of headache, vomiting, and gum bleeding. She lived in Hue City and was unaware of having received an insect bite. Her temperature was 38[degrees]C, and blood tests showed leukopenia (leukocyte count 1,900 cells/gL [reference 4,000-10,000 cells/gL]), thrombocytopenia (platelet count 125 x 103/gL [reference 150-450 x 103/gL]), and a low hematocrit level (34.3% [reference 36%-44%]). The patient fully recovered without other complications after 5 days.

On November 2, 2017, a 27-year-old man (Hue 13-Vietnam-11-2017) was hospitalized at Hue University Hospital because of headache and fatigue. He had had dengue fever at 8 years of age. Blood tests showed thrombocytopenia (platelet count 14 x [10.sup.3]/gL), normal leukocyte count (7,410 cells/gL), mildly elevated aspartate aminotransferase (84 IU/L [reference 8-38 IU/L]), elevated alanine aminotransferase (98 IU/L [reference 4-44 IU/L]), and mildly elevated hematocrit (47.6% [reference 36%-44%]). He fully recovered without other complications after 7 days.

We sequenced rRT-PCR products from the stored serum samples using a BigDye Terminator Cycle Sequencing kit (Applied Biosystems, http://www.thermofisher. com). We performed phylogenetic analysis of the partial S segment sequences with MEGA6 (https://www.megasoftware.net) and constructed phylogenetic trees using the maximum-likelihood method, which confirmed SFTSV infection (Appendix Figure).

We confirmed 2 SFTSV infections in Hue in 2017 by amplifying the partial S segment of the viral RNA in stored serum from patients with thrombocytopenia; elevated levels of serum hepatic enzymes, including aspartate aminotransferase and alanine aminotransferase; and gastrointestinal symptoms, such as vomiting. The signs and symptoms were milder than the major signs and symptoms of SFTS, which has a high death rate.

H. longicornis, Amblyomma testudinarium, and Ixodes nipponensis ticks are vectors of SFTSV, and A. testudinarium has been found in Vietnam. Migratory birds are known to be long-distance carriers of virus-bearing ticks (10). Therefore, virus-bearing A. testudinarium ticks and migratory birds may play a role in dispersing SFTSV to Vietnam (10).

This study expands the understanding of the distribution of SFTSV in Southeast Asia and suggests that SFTSV may have a much wider global distribution than previously thought. The 2 patients reported here had relatively mild illness, and 1 did not have leukopenia. Therefore, further epidemiologic and clinical research is needed to clarify the epidemiology, geographic distribution, and transmission dynamics of SFTSV in Vietnam and other areas of Southeast Asia. This subject deserves further discussion and might warrant changes in the background description of the disease (5,8).

Acknowledgments

We thank L. Bakkensen for providing comments on this paper.

This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF), funded by the South Korean government (grant no. NRF-2016M3A9B6021161), and a grant from the Korean Health Technology R&D Project of the Ministry of Health and Welfare, South Korea (grant no. HI15C2891).

Dr. Tran is a professor at the Department of Infectious Diseases, Hue University Hospital and Hue University of Medicine and Pharmacy, Hue, Vietnam. His research interest is infectious diseases.

References

(1.) Yu XJ, Liang MF, Zhang SY, Liu Y, Li JD, Sun YL, et al. Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med. 2011;364:1523-32. http://dx.doi.org/ 10.1056/NEJMoa1010095

(2.) McMullan LK, Folk SM, Kelly AJ, MacNeil A, Goldsmith CS, Metcalfe MG, et al. A new phlebovirus associated with severe febrile illness in Missouri. N Engl J Med. 2012;367:834-41. http://dx.doi.org/10.1056/NEJMoa1203378

(3.) Mourya DT, Yadav PD, Basu A, Shete A, Patil DY, Zawar D, et al. Malsoor virus, a novel bat phlebovirus, is closely related to severe fever with thrombocytopenia syndrome virus and Heartland virus. J Virol. 2014;88:3605-9. http://dx.doi.org/10.1128/JVI.02617-13

(4.) Wang J, Selleck P, Yu M, Ha W, Rootes C, Gales R, et al. Novel phlebovirus with zoonotic potential isolated from ticks, Australia. Emerg Infect Dis. 2014;20:1040-3. http://dx.doi.org/10.3201/ eid2006.140003

(5.) Kim YR, Yun Y, Bae SG, Park D, Kim S, Lee JM, et al. Severe tever with thrombocytopenia syndrome virus infection, South Korea, 2010. Emerg Infect Dis. 2018;24:2103-5. http://dx.doi.org/10.3201/eid2411.170756

(6.) Takahashi T, Maeda K, Suzuki T, Ishido A, Shigeoka T, Tominaga T, et al. The first identification and retrospective study of severe fever with thrombocytopenia syndrome in Japan. J Infect Dis. 2014;209:816-27. http://dx.doi.org/10.1093/infdis/jit603

(7.) Li H, Lu QB, Xing B, Zhang SF, Liu K, Du J, et al. Epidemiological and clinical features of laboratory-diagnosed severe fever with thrombocytopenia syndrome in China, 2011-17: a prospective observational study. Lancet Infect Dis. 2018;18:1127-37. http://dx.doi.org/10.1016/S1473-3099(18)30293-7

(8.) Yoo JR, Heo ST, Park D, Kim H, Fukuma A, Fukushi S, et al. Family cluster analysis of severe fever with thrombocytopenia syndrome virus infection in Korea. Am J Trop Med Hyg. 2016;95:1351-7. http://dx.doi.org/10.4269/ajtmh.16-0527

(9.) Zhang YZ, He YW, Dai YA, Xiong Y, Zheng H, Zhou DJ, et al. Hemorrhagic fever caused by a novel bunyavirus in China: pathogenesis and correlates of fatal outcome. Clin Infect Dis. 2012;54:527-33. http://dx.doi.org/10.1093/cid/cir804

(10.) Yun Y, Heo ST, Kim G, Hewson R, Kim H, Park D, et al. Phylogenetic analysis of severe fever with thrombocytopenia syndrome virus in South Korea and migratory bird routes between China, South Korea, and Japan. Am J Trop Med Hyg. 2015; 93:468-74. http://dx.doi.org/10.4269/ajtmh.15-0047

Address for correspondence: Keun Hwa Lee, Jeju National University College of Medicine, Department of Microbiology and Immunology, 15, Aran 13-gil, Jeju 63241, South Korea; email: yomust7@jejunu.ac.kr

Author affiliations: The Hue University Hospital and Hue University of Medicine and Pharmacy, Hue, Vietnam (X.C. Tran, L.V. An, N.T.P. Thao, P.K.C. Man); Ewha Womans University, Seoul, South Korea (Y. Yun); The Kyung Hee University, Seoul (S.-H. Kim); The Jeju National University College of Medicine, Jeju, South Korea (J.R. Yoo, S.T. Heo, K.H. Lee); Seoul National University College of Medicine, Seoul (N.-H. Cho)

DOI: https://doi.org/10.3201/eid2505.181463
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Title Annotation:RESEARCH LETTERS
Author:Tran, Xuan Chuong; Yun, Yeojun; Van An, Le; Kim, So-Hee; Thao, Nguyen T. Phuong; Man, Phan Kim C.; Y
Publication:Emerging Infectious Diseases
Geographic Code:9JAPA
Date:May 1, 2019
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