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Volume 26, Number 1—January 2020
Research Letter

Hantavirus Pulmonary Syndrome in Traveler Returning from Nepal to Spain

Elena Sulleiro1, Maria Luisa Aznar1, Núria Serre-Delcor, Fernando Salvador, Adrian Sanchez-Montalvá, Mateu Espasa, Daniel Molina, Fernando de Ory, M. Paz Sanchez-Seco, Israel Molina, Candido Diaz-Lagares, Miguel J. Martinez, Tomàs Pumarola, and Inés OliveiraComments to Author 
Author affiliations: Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain (E. Sulleiro, M.L. Aznar, N. Serre-Delcor, F. Salvador, A. Sanchez-Montalvá, M. Espasa, D. Molina, I. Molina, C. Diaz-Lagares, T. Pumarola, I. Oliveira); Instituto de Salud Carlos III, Majadahonda, Spain (F. de Ory, M.P. Sanchez-Seco); Hospital Clínic, Barcelona (M.J. Martinez)

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Abstract

Most human hantavirus infections occur in Asia, but some cases have been described in Europe in travelers returning from Asia. We describe a case of hantavirus pulmonary syndrome in a previously healthy traveler occurring shortly after he returned to Spain from Nepal. Serologic tests suggested a Puumala virus–like infection.

More than 24 pathogenic hantaviruses that are known to be pathogenic to humans have been identified worldwide (1). The diseases these viruses have caused have been traditionally divided into 2 major clinical syndromes: hemorrhagic fever with renal syndrome (HFRS) in Europe, Asia, and Africa, and hantavirus pulmonary syndrome (HPS; sometimes referred to as hantavirus cardiopulmonary syndrome) in the Americas (2). We describe a life-threatening hantavirus infection in a patient with respiratory failure returning to Spain from Nepal.

In October 2017, a 28-year-old man sought care at the outpatient clinic of Drassanes Tropical Medicine Unit at Hospital Vall d’Hebrón, Barcelona, Spain, on day 2 after onset of symptoms. He had recently returned from a 5-week trip to Nepal (Appendix), during which he stayed at basic hostels, where sounds of rats or mice were audible. The patient reported onset of fever, malaise, weakness, headache, arthromyalgia, and abdominal pain during his flight back to Spain. Medical examination revealed only fever (38.2°C) and a mild diffuse macular rash on his trunk. Laboratory tests showed thrombocytopenia (platelets 125 × 109/L) and mild liver enzyme elevation (alanine aminotransferase 127 IU/L, aspartate aminotransferase 81 IU/L); results of tests for various pathogens, including hantavirus, were negative (Table).

The patient returned home, but on day 4, he incurred a head wound after a fall caused by dizziness, requiring treatment at the Vall d’Hebrón Hospital emergency department; he was discharged on day 5 in stable condition and with normal chest radiograph results. On day 6, he was readmitted for dyspnea; within 12 hours, respiratory failure developed, requiring admission to the intensive care unit with high-flow nasal cannula oxygen therapy and vasoactive support. Results of new chest radiograph revealed bilateral pleural effusion and extensive alveolar edema. Electrocardiogram results showed no abnormality, but echocardiogram results showed mild ventricular dysfunction (left ventricular ejection fraction 50%) without evidence of pericardial effusion.

The patient required respiratory and vasoactive support in the intensive care unit for 5 days; he was transferred to a regular room 7 days after admission. At that point, 12 days after symptom onset, repeat testing showed positive results for hantavirus IgM (weak positive) and IgG (Table). The diagnosis was established as HPS, as defined by the US Centers for Disease Control and Prevention (CDC) classification (3). The patient was discharged to his home 2 days later. Repeat test results on day 22 after symptom onset remained positive for hantavirus IgM and IgG. A month after discharge, the patient still reported a mild dyspnea and fatigue. Pulmonary function tests showed no abnormality. Intolerance to exercise lasted for 2 months after discharge. One year later, he is fully recovered without sequelae.

The course of this patient was as classically described for HPS: an initial prodromal phase with influenza-like symptoms, followed by a rapid progression to abrupt onset of respiratory failure (3). Elevated levels of C-reactive protein and lactate dehydrogenase were found soon after symptom onset (Table), as described in the literature (4). Results of coagulation, cardiac enzyme, and renal function tests were normal throughout hospitalization, but proteinuria and microhematuria were not evaluated.

Once the hantavirus diagnosis was established, we contacted the patient’s trip partner, who accompanied him during the first 2 weeks in Nepal. He was asymptomatic; results of a serologic test (ELISA) performed 7 weeks after his return was negative for hantavirus IgM and IgG.

Little is known about the incidence of hantavirus infections in Nepal. Thottapalayam virus, a genetically distant virus from other Old World hantaviruses, has been detected in the Asian house shrew (Suncus murinus) (5); no human cases of infection with this virus have been reported. However, serologic evidence of hantavirus infection in patients with fever of unknown origin has been reported in Nepal (6). Serum and urine samples from our patient tested negative by an in-house nested reverse transcription PCR (RT-PCR) targeting the small segment of the viral genome for detection of New World and Old World hantaviruses. Viral RNA is rarely found in blood more than a few days after onset of fever, and similar negative results in RT-PCR have been previously reported (79). Alternatively, the infection may have been caused by a genetically different hantavirus not detected by the in-house hantavirus RT-PCR. Furthermore, the serum sample was frozen and thawed several times, which may have degraded the RNA.

The pattern of serologic findings able to confirm only a transitory presence of Puumala virus (PUUV) IgG suggest a cross-reaction with an unknown hantavirus, because the known PUUV reservoir, the Myodes glareolus bank vole, is absent from Nepal and India. The PUUV IgG and IgM seroconversion and the classical HPS manifestation (3) are highly reminiscent of 2 fatal HFRS/HPS cases previously described in South India (8,9) that were also PUUV immunoblot positive.

Hantaviruses are emerging zoonotic pathogens and, although recognition of the infection in humans has greatly improved worldwide during the past decade, many cases probably remain undiagnosed. This case highlights the importance of clinical suspicion of hantavirus infection in travelers, even in countries where no cases have been previously reported.

Dr. Sulleiro is a microbiologist in the Department of Microbiology, Vall d’Hebron University Hospital, PROSICS Barcelona. Her primary research interests are Chagas disease and arbovirus. Dr. Aznar is a physician working in the Tropical Medicine Unit Drassanes-Vall d`Hebron Infectious Diseases Department, Vall d’Hebron University Hospital, PROSICS Barcelona. Her primary research interests are tropical medicine and tuberculosis.

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Acknowledgment

We thank the patient, who provided written, informed consent for publication of this case.

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References

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  3. Centers for Disease Control and Prevention. Hantavirus pulmonary syndrome (HPS) 2015 case definition. 2015 [cited 2019 Oct 11]. https://wwwn.cdc.gov/nndss/conditions/hantavirus-pulmonary-syndrome/case-definition/2015
  4. Clement  J, LeDuc  JW, McElhinney  LM, Reynes  J-M, Van Ranst  M, Calisher  CH. Clinical characteristics of ratborne Seoul hantavirus disease. Emerg Infect Dis. 2019;25:3878. DOIPubMed
  5. Kang  HJ, Kosoy  MY, Shrestha  SK, Shrestha  MP, Pavlin  JA, Gibbons  RV, et al. Short report: Genetic diversity of Thottapalayam virus, a Hantavirus harbored by the Asian house shrew (Suncus murinus) in Nepal. Am J Trop Med Hyg. 2011;85:5405. DOIPubMed
  6. Thompson  CN, Blacksell  SD, Paris  DH, Arjyal  A, Karkey  A, Dongol  S, et al. Undifferentiated febrile illness in Kathmandu, Nepal. Am J Trop Med Hyg. 2015;92:8758. DOIPubMed
  7. Sunil-Chandra  NP, Clement  J, Maes  P, DE Silva  HJ, VAN Esbroeck  M, VAN Ranst  M. Concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized in Sri Lanka: implications for a potentially worldwide underestimated problem - ERRATUM. Epidemiol Infect. 2015;143:2094. DOIPubMed
  8. Clement  J, Maes  P, Muthusethupathi  M, Nainan  G, Van Ranst  M. Hantavirus in India: a new deadly disease with an as yet unknown hantavirus strain. Acta Clin Belg. 2008;64:171.
  9. Clement  J, Maes  P, Muthusethupathi  M, Nainan  G, van Ranst  M. First evidence of fatal hantavirus nephropathy in India, mimicking leptospirosis. Nephrol Dial Transplant. 2006;21:8267. DOIPubMed

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Table

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Suggested citation for this article: Sulleiro E, Aznar ML, Serre-Delcor N, Salvador F, Sanchez-Montalvá A, Espasa M, et al. Hantavirus pulmonary syndrome in traveler returning from Nepal to Spain. Emerg Infect Dis. 2020 Jan [date cited]. https://doi.org/10.3201/eid2601.181685

DOI: 10.3201/eid2601.181685

Original Publication Date: 11/1/2019

1These authors contributed equally to this article.

Table of Contents – Volume 26, Number 1—January 2020

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Inés Oliveira, Vall d’Hebron University Hospital, Infectious Diseases Department, PROSICS Barcelona, Barcelona, Spain

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Page created: November 01, 2019
Page updated: November 01, 2019
Page reviewed: November 01, 2019
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
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