Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 21, Number 1—January 2015
Synopsis

Health Care Response to CCHF in US Soldier and Nosocomial Transmission to Health Care Providers, Germany, 2009

Nicholas G. CongerComments to Author , Kristopher M. Paolino, Erik C. Osborn, Janice M. Rusnak, Stephan Günther, Jane Pool, Pierre E. Rollin, Patrick F. Allan, Jonas Schmidt-Chanasit, Toni Rieger, and Mark G. Kortepeter1
Author affiliations: Landstuhl Regional Medical Center, Landstuhl, Germany (N.G. Conger, E.C. Osborn, J. Pool, P.F. Allan); Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (K.M. Paolino); Force Health Protection, Fort Detrick, Maryland, USA (J.M. Rusnak); Bernard Nocht Institute, Hamburg, Germany (S. Günther, J. Schmidt-Chanasit, T. Rieger); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (P. Rollin); Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA (M.G. Kortepeter)

Main Article

Table 1

Results of laboratory testing and regimen for ribavirin treatment for a US soldier with CCHF, Germany, 2009*

Treatment/test or procedure Day after symptom onset, date
Reference range
Day 6, Sep 11 Day 7, Sep 12 Day 8, Sep 13 Day 9, Sep 14 Day 10, Sep 15 Day 11, Sep 16
Ribavirin treatment†
Oral
IV
IV
IV
IV
None
NA
Test/procedure
RT-PCR, RNA copies/mL‡ 1.2 × 109 ND 6 × 109 ND 3 × 108 ND NA
Dialysis ND ND Renal Renal/hep Renal/hep Renal NA
CCHF culture§ + ND ND ND ND ND
IgM/IgG¶ −/− ND −/− ND +/+ ND
Hemoglobin, g/dL 12.8 7.7 9.1 11.9 9.9 8.5 13.2–17.1
Hematocrit, % 35.3 21.6 25.4 33.5 27.7 23.7 38–50
Leukocyte count, × 103/μL 9.6 8.8 4.9 4.0 3.4 3.5 3.5–10.5
Platelets, × 103/μL 14,000 68,000 62,000 93,000 126,000 77,000 151–356
Creatinine, mg/dL 7.8 8.7 5.1 2.7 1.4 0.9 0.8–1.5
BUN, mg/dL 67 72 32 8 2 <2 8–26
Sodium, mmol/L 140 146 143 142 141 147 137–145
Potassium, mmol/L 4.7 5.2 4.0 5.0 4.3 3.4 3.6–5.1
Bicarbonate, mmol/L 20 12 19 18 28 33 22–31
Chloride, mmol/L 110 102 98 103 100 101 101–111
Lactate, mmol/L 3.0 14.9 17.8 8.7 7.7 7.4 0.7–2.1
Glucose, mg/dL 92 187 93 68 82 89 74–106
AST, U/L 1,472 3,957 11,295 9,628 9,061 5,967 15–41
ALT, U/L 411 1,838 2,854 2,151 1,805 1,122 17–63
LDH, IU/L 756 ND ND ND ND ND 98–192
Alkaline phos, UL 186 123 163 202 254 354 38–126
Bilirubin
Total, mg/dL 1.8 5.8 6.7 8.1 9.2 10.4 0.2–1.3
Direct, mg/dL 1.1 ND 3.3 3.2 3.0 3.0 0.1–0.3
aPTT, s 106.9 89.8 56.6 59.3 67.4 52.7 28.2–40.3
Prothrombin time, s 21.8 22.4 22.3 14.9 19.7 24 11.9–15.1
Fibrinogen, mg/dL 143 190 238 156 153 111 168–407
D-dimer, µg/dL 20 ND ND ND ND ND <5
Albumin, g/dL 2.8 2.8 3.7 4.2 4.7 4.8 3.5–5.0
CPK, U/L 1,437 1,528 1,889 3,008 4,728 4,973 55–170
Myoglobin, ng/mL 1,226.5 ND ND ND ND ND 17.4–105.7
Other
Malaria smear −** ** ** ** ** ** NA
Bacterial cultures# −** ** ** ** ** ** NA
Radiology
X-ray/CT, chest ND Moderate to severe pulmonary edema and atelectesis ND ND ND ND NA
CT, abdomen ND Ascites, gallbladder edema ND ND ND ND NA
Cytokines
Interleukin
10, pg/mL †† 515 ND 1,498 ND 904 ND <7
6, pg/mL †† 1,530 ND >3,023 ND 2,439 ND <15
IFN-γ, pg/mL †† 59 ND 390 ND 125 ND <15
TNF-α, pg/mL †† 77 ND 56 ND 100 ND <15
Growth factors
PLGF, pg/mL †† 203 ND 64 ND 81 ND <25
sVEGF-R1, pg/mL †† 2,930 ND 13,903 ND 13,308 ND <180

*aPTT, activated partial thromboplastin time; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CCHF, Crimean–Congo hemorrhagic fever; CPK, creatine phosphokinase; CT, computerized tomography; hep, hepatic; IFN-γ, interferon γ; IV, intravenously; LDH, lactate dehydrogenase; NA, not applicable; ND, not determined; phos, phosphatase; PLGF, placental growth factor; RT-PCR, reverse transcription PCR; sVEGF-R1, soluble vascular endothelial growth factor receptor 1; TNF-α, tumor necrosis factor α; −, negative; +, positive.
†On day 6, an initial 4-g loading dose (LD) of oral ribavirin was administered via nasogastric tube, followed by 1,200 mg 6 h later. On day 7, a partial LD of 22 mg/kg was administered IV (because of 60% bioavailability of oral ribavirin and poor absorption with gastrointestinal bleeding) followed by 16-mg/kg doses every 6 h (per dose-reduction protocol). Beginning day 9, 14 mg/kg was administered every 6 h, with an extension of the dosing interval to every 8 h on day 10 because of severe renal failure (only a minimal amount of drug is removed through dialysis) (3).
‡Real-time RT-PCR for virus quantification and Nairovirus spp.–specific gel-based RT-PCR coupled with PCR product sequencing to confirm the diagnosis (6,7).
§CCHF culture of blood and urine (virus was isolated on Vero cells and sequenced) (8).
¶CCHF-specific IgM/IgG by indirect immunofluorescence assay using CCHF virus–infected cells; assay performed at Bernard Nocht Institute, Hamburg, Germany.
#Culture of blood, urine, and sputum samples.
**Malaria smear and culture results were not specifically obtained on day 6; multiple cultures were performed.
††Testing for cytokines and vascular endothelial growth factors and their soluble receptors of blood were performed in the Biosafety Level 4 facility of Bernard Nocht Institute by using Quantikine Immunoassays (R&D Systems Europe, Abingdon, UK), according to the manufacturer’s instructions.

Main Article

References
  1. Bente  DA, Forrester  NL, Watts  DM, McAuley  AJ, Whitehouse  CA. Crimean–Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity. Antiviral Res. 2013;100:15989. DOIPubMed
  2. Erby  A. Crimean–Congo hemorrhagic fever virus. In: Dongyou Liu, editor. Manual of security sensitive microbes and toxins. Boca Raton (FL): CRC Press; 2014. p. 37–52.
  3. Rusnak  JM. Experience with ribavirin for treatment and postexposure prophylaxis of hemorrhagic fever viruses: Crimean Congo hemorrhagic fever, Lassa fever, and hantavirus [cited 2014 Sep 15]. http://www.absa.org/abj/abj/111602Rusnak.pdf
  4. Swanepoel  R, Gill  DE, Shepherd  AJ, Leman  PA, Mynhardt  JH, Harvey  S. The clinical pathology of Crimean–Congo hemorrhagic fever. Rev Infect Dis. 1989;11:S794800. DOIPubMed
  5. Karti  SS, Odabasi  Z, Korten  V, Yilmaz  M, Sonmez  M, Caylan  R, Crimean–Congo hemorrhagic fever in Turkey. Emerg Infect Dis. 2004;10:137984. DOIPubMed
  6. Wölfel  R, Paweska  JT, Petersen  N, Grobbelaar  AA, Leman  PA, Hewson  R, Virus detection and monitoring of viral load in Crimean–Congo hemorrhagic fever virus patients. Emerg Infect Dis. 2007;13:1097100. DOIPubMed
  7. Lambert  AJ, Lanciotti  RS. Consensus amplification and novel multiplex sequencing method for S segment species identification of 47 viruses of the Orthobunyavirus, Phlebovirus, and Nairovirus genera of the family Bunyaviridae. J Clin Microbiol. 2009;47:2398404. DOIPubMed
  8. Olschläger  S, Gabriel  M, Schmidt-Chanasit  J, Meyer  M, Osborn  E, Conger  NG, Complete sequence and phylogenetic characterisation of Crimean-Congo hemorrhagic fever virus from Afghanistan. J Clin Virol. 2011;50:902. DOIPubMed
  9. Centers for Disease Control and Prevention (CDC). Interim guidance for managing patients with suspected viral hemorrhagic fever in US Hospitals; 2005 19 May [cited 2014 Sept 11]. http://www.cdc.gov/HAI/pdfs/bbp/VHFinterimGuidance05_19_05.pdf.
  10. World Health Organization. Application for inclusion of ribavirin in the WHO model list of essential medicines [2010 Sep 15]. http://archives.who.int/eml/expcom/expcom15/applications/newmed/ribaravin/ribavirin.pdf
  11. Khan  AS, Maupin  GO, Rollin  PE, Noor  AM, Shurie  HHM, Shalabi  AGA, An outbreak of Crimean–Congo hemorrhagic fever in the United Arab Emirates, 1994–1995. Am J Trop Med Hyg. 1997;57:51925 .PubMed
  12. Burney  MI, Ghafoor  A, Saleen  M, Webb  PA, Casals  J. Nosocomial outbreak of viral hemorrhagic fever caused by Crimean hemorrhagic fever–Congo virus in Pakistan, January 1976. Am J Trop Med Hyg. 1980;29:9417 .PubMed
  13. Amorosa  V, MacNeil  A, McConnell  R, Patel  A, Dillon  KE, Hamilton  K, Imported Lassa fever, Pennsylvania, USA, 2010. Emerg Infect Dis. 2010;16:1598600. DOIPubMed
  14. Jauréguiberry  S, Tattevin  P, Tarantola  A, Legay  F, Tall  A, Nabeth  P, Imported Crimean–Congo hemorrhagic fever. J Clin Microbiol. 2005;43:49057. DOIPubMed
  15. Barry  M, Russi  M, Armstrong  L, Geller  D, Tesh  R, Dembry  L, Treatment of a laboratory-acquired Sabia virus infection. N Engl J Med. 1995;333:2946. DOIPubMed
  16. Timen  A, Koopmans  MP, Vossen  AC, van Doornum  GJ, Gunther  S, van den Berkmortel  F, Response to imported case of Marburg hemorrhagic fever, the Netherlands. Emerg Infect Dis. 2009;15:11715. DOIPubMed
  17. World Health Organization. Global alert and response (GAR). Ebola virus disease, West – update. 2014 Jul 27[cited 4 Aug 2014]. http://www.who.int/csr/don/2014_07_27_ebola/en/
  18. Bhagat  CI, Lewer  M, Prins  A, Beilby  JP. Effects of heating plasma at 56 degrees C for 30 min and at 60 degrees C for 60 min on routine biochemistry analytes. Ann Clin Biochem. 2000;37:8024. DOIPubMed
  19. Bodur  H, Akinci  E, Onguru  P, Carhan  A, Uyar  Y, Tanrici  A, Detection of Crimean–Congo hemorrhagic fever virus genome in saliva and urine. Int J Infect Dis. 2010;14:e2479. DOIPubMed
  20. Thomas  S, Thomson  G, Dowall  S, Bruce  C, Cook  N, Easterbrook  L, Review of Crimean Congo hemorrhagic fever infection in Kosova in 2008 and 2009: prolonged viremias and virus detected in urine by PCR. Vector Borne Zoonotic Dis. 2012;12:8004. DOIPubMed
  21. Keshtkar-Jahromi  M, Sajadi  MM, Ansari  H, Mardani  M, Holakouie-Naieni  K. Crimean–Congo hemorrhagic fever in Iran. Antiviral Res. 2013;100:208. DOIPubMed
  22. Bodur  H, Akinci  E, Ascioglu  S, Onguru  P, Uyar  Y. Subclinical infection with Crimean–Congo hemorrhagic fever virus, Turkey. Emerg Infect Dis. 2012;18:6402. DOIPubMed
  23. Ozturk  B, Tutuncu  E, Kuscu  F, Gurbuz  Y, Sencan  I, Tuzun  H. Evaluation of factors predictive of the prognosis in Crimean–Congo hemorrhagic fever: new suggestions. Int J Infect Dis. 2012;16:e8993. DOIPubMed
  24. Hatipoglu  CA, Bulut  C, Yetkin  MA, Ertem  GT, Erdinc  FS, Kilic  EI, Evaluation of clinical and laboratory predictors of fatality in patients with Crimean–Congo haemorrhagic fever in a tertiary care hospital in Turkey. Scand J Infect Dis. 2010;42:51621. DOIPubMed
  25. Çevik  MA, Erbay  A, Bodur  H, Gulderen  E, Bastug  A, Kubar  A, Clinical and laboratory features of Crimean–Congo hemorrhagic fever: predictors of fatality. Int J Infect Dis. 2008;12:3749. DOIPubMed
  26. Ozbey  SB, Kader  C, Erbay  A, Ergonul  O. Early use of ribavirin is beneficial in Crimean–Congo hemorrhagic fever. Vector Borne Zoonotic Dis. 2014;14:3002. DOIPubMed
  27. Onguru  P, Dagdas  S, Bodur  H, Yilmaz  M, Akinci  E, Eren  S, Coagulopathy parameters in patients with Crimean–Congo hemorrhagic fever and its relation with mortality. J Clin Lab Anal. 2010;24:1636. DOIPubMed
  28. Saksida  A, Duh  D, Wraber  B, Dedushaj  I, Ahmeti  S, Avsic-Zupanc  T. Interacting roles of immune mechanisms and viral load in the pathogenesis of Crimean–Congo hemorrhagic fever. Clin Vaccine Immunol. 2010;17:108693. DOIPubMed
  29. Connolly-Andersen  AM, Moll  G, Andersson  C, Akerström  S, Karlberg  H, Douagi  I, Crimean–Congo hemorrhagic fever virus activates endothelial cells. J Virol. 2011;85:776674. DOIPubMed
  30. Weber  F, Mirazimi  A. Interferon and cytokine responses to Crimean Congo hemorrhagic fever virus; an emerging and neglected viral zoonosis. Cytokine Growth Factor Rev. 2008;19:395404. DOIPubMed
  31. Ergonul  O, Tuncbilek  S, Baykam  N, Celikbas  A, Dokuzoguz  B. Evaluation of serum levels of interleukin (IL)-6, IL-10 and tumor necrosis factor-α in patients with Crimean–Congo hemorrhagic fever. J Infect Dis. 2006;193:9414. DOIPubMed
  32. Papa  A, Bino  S, Velo  E, Harxhi  A, Kota  M, Antoniadis  A. Cytokine levels in Crimean–Congo hemorrhagic fever. J Clin Virol. 2006;36:2726. DOIPubMed
  33. Ozturk  B, Kuscu  F, Tutuncu  E, Sencan  I, Gurbuz  Y, Tuzan  H. Evaluation of the association of serum levels of hyaluronic acid, sICAM-1, sVCAM-1, and VEGF-A with mortality and prognosis in patients with Crimean–Congo hemorrhagic fever. J Clin Virol. 2010;47:1159. DOIPubMed
  34. Peyrefitte  CN, Perret  M, Garcia  S, Rodriguez  R, Bagnaud  A, Lacote  S, Differential activation profiles of Crimean–Congo hemorrhagic fever virus– and Dugbe virus–infected antigen-presenting cells. J Gen Virol. 2010;91:18998. DOIPubMed
  35. Bodur  H, Akinci  E, Onguru  P, Uyar  Y, Basturk  B, Gozel  MG, Evidence of vascular endothelial damage in Crimean–Congo hemorrhagic fever. Int J Infect Dis. 2010;14:e7047. DOIPubMed
  36. Bakir  M, Bakir  S, Sari  I, Celik  VK, Gozel  MG, Engin  A. Evaluation of the relationship between serum levels of VEGF and sVEGFR1 with mortality and prognosis in patients with Crimean–Congo hemorrhagic fever. J Med Virol. 2013;85:1794801. DOIPubMed
  37. van Paassen  J, Bauer  MP, Arbous  MS, Visser  LG, Schmidt-Chanasit  J, Schilling  S, Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever. Lancet Infect Dis. 2012;12:63542. DOIPubMed
  38. Andersson  I, Lundkvist  A, Haller  O, Mirazimi  A. Type I interferon inhibits Crimean–Congo hemorrhagic fever virus in human target cells. J Med Virol. 2006;78:21622. DOIPubMed
  39. Andersson  I, Karlberg  H, Mousari-Jazi  M, Martinez-Sobrido  L, Wever  F, Mirazimi  A. Crimean–Congo hemorrhagic fever virus delays activation of the innate immune response. J Med Virol. 2008;80:1397404. DOIPubMed
  40. Oestereich  L, Rieger  T, Neumann  M, Bernreuther  C, Lehmann  M, Krasemann  S, Evaluation of antiviral efficacy of ribavirin, arbidol, and T-705 (favipiravir) in a mouse model for Crimean–Congo hemorrhagic fever. PLoS Negl Trop Dis. 2014;8:e2804. DOIPubMed

Main Article

1Preliminary results from this study were presented at the Annual Meeting of the Armed Forces Infectious Disease Society; May 23, 2010, San Antonio, Texas, USA; NATO Biomedical Advisory; May 27, 2010, Munich, Germany; and Asian Pacific Military Medicine Conference, May 3, 2011, Sydney, New South Wales, Australia.

Page created: December 17, 2014
Page updated: December 17, 2014
Page reviewed: December 17, 2014
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.
file_external