jueves, 25 de septiembre de 2014

Ahead of Print -Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels - Volume 20, Number 12—December 2014 - Emerging Infectious Disease journal - CDC

full-text ►

Ahead of Print -Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels - Volume 20, Number 12—December 2014 - Emerging Infectious Disease journal - CDC



CDC - Centers for Disease Control and Prevention - CDC 24/7: Saving Lives. Protecting People.™

Volume 20, Number 12—December 2014

Research

Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels

Danielle R. Adney, Neeltje van Doremalen, Vienna R. Brown, Trenton Bushmaker, Dana Scott, Emmie de Wit, Richard A. Bowen1Comments to Author , and Vincent J. Munster1
Author affiliations: Colorado State University, Fort Collins, Colorado, USA; (D.R. Adney, V.R. Brown, R.A. Bowen);National Institutes of Health, Hamilton, Montana, USA (N. van Doremalen, T. Bushmaker, D. Scott, E. de Wit, V.J. Munster)

Abstract

In 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the Middle East. Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Here we provide experimental support for camels as a reservoir for MERS-CoV. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. Clinical signs of the MERS-CoV infection were benign, but each of the camels shed large quantities of virus from the upper respiratory tract. We detected infectious virus in nasal secretions through 7 days postinoculation, and viral RNA up to 35 days postinoculation. The pattern of shedding and propensity for the upper respiratory tract infection in dromedary camels may help explain the lack of systemic illness among naturally infected camels and the means of efficient camel-to-camel and camel-to-human transmission.
The Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 related to a fatal human case of pneumonia in Saudi Arabia (1). Currently, >800 cases of MERS have been identified, and the estimated case-fatality rate is ≈35% (2). Most cases have been identified on the Arabian Peninsula, but several travel-associated cases have been reported (24). Human-to-human transmission has been reported, predominantly among persons in health care facilities and households; the rate of human infection by zoonotic transmission from a reservoir source is currently not known (46).
The close phylogenetic relationship of human MERS-CoV isolates with those obtained from bats initially suggested a direct link between the emergence of MERS-CoV and a putative natural reservoir (79). Anecdotal reports mentioned contact of MERS-CoV–infected patients with camels and goats, suggesting that livestock might be the intermediate reservoir host for MERS-CoV (4,1012). Serologic studies revealed widespread prevalence of MERS-CoV–specific antibodies in dromedary camels from several countries that reported MERS cases (4,1319). Further, MERS-CoV RNA was detected in nasal swab samples obtained from 3 camels on a farm linked to 2 human MERS-CoV cases, and the virus was isolated from nasal swab samples from dromedary camels in Qatar (14). MERS-CoV isolation and subsequent full genome sequencing directly linked a dromedary camel and a fatal MERS-CoV case in a person in Saudi Arabia (20,21). Despite these associations, the role of camels as a primary reservoir for MERS-CoV is still debated (22,23). Here we report on the experimental inoculation of 3 camels with a human isolate of MERS-CoV.

Ms. Adney is a graduate student at Colorado State University in Fort Collins, Colorado. Her research focus is on the pathogenesis of emerging infectious diseases.

Acknowledgments

We thank Bart Haagmans and Ron Fouchier, for providing MERS-CoV (isolate hCoV-EMC/2012); Tina Thomas, Dan Long, and Rebecca Rosenke for histopathologic examination; and Anita Mora and Ryan Kissinger for figure preparation.
This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Animal Models Core at Colorado State University. D.R.A. was supported through the Infectious Disease: Translational Research Training Program at Colorado State University.
All animal work in this study was approved by the Institutional Animal Care and Use Committee of Colorado State University and was performed in compliance with recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institute of Health.

References

  1. Zaki AMvan Boheemen SBestebroer TMOsterhaus ADFouchier RAIsolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.N Engl J Med2012;367:181420 . DOIPubMed
  2. World Health Organization. Global Alert and Response. Middle East respiratory syndrome coronavirus (MERS-CoV) – update; 2014 June [cited 30 Jun 2014]. http://www.who.int/csr/don/2014_06_16_mers/en/
  3. Puzelli SAzzi ASantini MGDi Martino AFacchini MCastrucci MRInvestigation of an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Florence, Italy, May to June 2013. Euro Surveill2013;18:20564 .PubMed
  4. Milne-Price SMiazgowicz KLMunster VJ. The emergence of the Middle East respiratory syndrome coronavirus. Pathog Dis. 2014;71:121–36.
  5. Assiri AMcGeer APerl TMPrice CSAl Rabeeah AACummings DAHospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med2013;369:40716DOIPubMed
  6. Memish ZAAl-Tawfiq JAAssiri AHospital-associated Middle East respiratory syndrome coronavirus infections. N Engl J Med2013;369:17612.DOIPubMed
  7. van Boheemen Sde Graaf MLauber CBestebroer TMRaj VSZaki AMGenomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. MBio2012;3:e00473012 . DOIPubMed
  8. Memish ZAMishra NOlival KJFagbo SFKapoor VEpstein JHMiddle East respiratory syndrome coronavirus in bats, Saudi Arabia. Emerg Infect Dis2013;19:181923DOIPubMed
  9. Graham RLDonaldson EFBaric RSA decade after SARS: strategies for controlling emerging coronaviruses. Nat Rev Microbiol2013;11:83648.DOIPubMed
  10. Albarrak AMStephens GMHewson RMemish ZARecovery from severe novel coronavirus infection. Saudi Med J2012;33:12659 .PubMed
  11. Buchholz UMuller MANitsche ASanewski AWevering NBauer-Balci TContact investigation of a case of human novel coronavirus infection treated in a German hospital, October-November 2012. Euro Surveill2013;18:20406 .PubMed
  12. Drosten CSeilmaier MCorman VMHartmann WScheible GSack SClinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection. Lancet Infect Dis2013;13:74551DOIPubMed
  13. Reusken CBHaagmans BLMuller MAGutierrez CGodeke GJMeyer BMiddle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet Infect Dis2013;13:85966DOIPubMed
  14. Haagmans BLAl Dhahiry SHSReusken CBEMRaj VSGaliano MMyers RMiddle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis2014;14:1405DOIPubMed
  15. Reusken CBAbabneh MRaj VSMeyer BEljarah AAbutarbush SMiddle East respiratory syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan, June to September 2013. Euro Surveill2013;18:20662 .PubMed
  16. Meyer BMuller MACorman VMReusken CBRitz DGodeke GJAntibodies against MERS coronavirus in dromedary camels, United Arab Emirates, 2003 and 2013. Emerg Infect Dis2014;20:5529DOIPubMed
  17. Nowotny NKolodziejek JMiddle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels, Oman, 2013. Euro Surveill.2014;19:20781 .PubMed
  18. Alagaili ANBriese TMishra NKapoor VSameroff SCde Wit EMiddle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. MBiol. 2014; e00884-14.
  19. Hemida MGPerera RAWang PAlhammadi MASiu LYLi MMiddle East respiratory syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013. Euro Surveill2013;18:20659 .PubMed
  20. Memish ZACotten MMeyer BWatson SJAlsahafi AJAl Rabeeah AAHuman infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerg Infect Dis2014;20:10125DOIPubMed
  21. Azhar EIEl-Kafrawy SAFarraj SAHassan AMAl-Saeed MSHashem AMEvidence for camel-to-human transmission of MERS coronavirus. N Engl J Med2014;370:2499505DOIPubMed
  22. Samara EMAbdoun KAConcerns about misinterpretation of recent scientific data implicating dromedary camels in epidemiology of Middle East respiratory syndrome (MERS). MBio2014;5:e0143014DOIPubMed
  23. Alagaili ANBriese TKaresh WBDaszak PLipkin WIReply to “Concerns about misinterpretation of recent scientific data implicating dromedary camels in epidemiology of Middle East respiratory syndrome (MERS).”MBio2014;5DOIPubMed
  24. Corman VMMuller MACostabel UTimm JBinger TMeyer BAssays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Euro Surveill2012;17:20334 .PubMed
  25. de Wit ERasmussen ALFalzarano DBushmaker TFeldmann FBrining DLMiddle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques. Proc Natl Acad Sci U S A2013;110:16598603DOIPubMed
  26. Nemeth NMBowen RADynamics of passive immunity to West Nile virus in domestic chickens (Gallus gallus domesticus). Am J Trop Med Hyg.2007;76:3107 .PubMed
  27. Alexandersen SKobinger GPSoule GWernery UMiddle East respiratory syndrome coronavirus antibody reactors among camels in Dubai, United Arab Emirates, in 2005. Transbound Emerg Dis2014;61:1058DOIPubMed
  28. Hemida MGChu DKPoon LLPerera RAAlhammadi MANg H-YMERS coronavirus in dromedary camel herd, Saudi Arabia. Emerg Infect Dis.2014;20:12314DOIPubMed
  29. Briese TMishra NJain KZalmout ISJabado OJKaresh WBMiddle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia. MBio2014;5:e0114614.DOIPubMed

Figures

Table

Suggested citation for this article: Adney DR, van Doremalen N, Brown VR, Bushmaker T, Scott D, de Wit E, et al. Replication and shedding of MERS-CoV in upper respiratory tract of inoculated dromedary camels. Emerg Infect Dis. 2014 Dec [date cited]. http://dx.doi.org/10.3201/eid2012.141280
DOI: 10.3201/eid2012.141280
1These senior authors contributed equally to this article.

No hay comentarios:

Publicar un comentario