Research Open Access
Like 0



Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne disease in Africa, Asia, the Balkan peninsula, the south-east of Europe and the Middle East, with mortality rates of 3–30%. Transmission can also occur through contact with infected animals or humans.


This observational, prospective case series aimed to investigate detectable viral genomic RNA in whole-body fluids and antibody dynamics in consecutive daily samples of patients diagnosed with CCHF until discharge from hospital.


We tested 18 patients and 824 swabs and sera with RT-PCR and 125 serum samples serologically.


The longest duration until clearance of viral RNA was 18 days from serum collection and 18, 15, 13, 19 and 17 days, respectively, from nasal, oral, genital (urethral or vaginal) and faecal swab, and urine. In seven patients, viral load decreased in serum at the same time as it increased in urine or persisted at the same logarithmic values. Despite clearance in serum, viral RNA was detected in faeces and genital swabs in two and three patients, respectively. Viral clearance from body fluids occurred earlier than from serum in eight patients on ribavirin treatment. The shortest seroconversion time was 3 days after symptom onset for IgM and IgG. Seroconversion of IgG occurred until Day 14 of symptoms.


We report persistence of viral RNA in urine, faeces and genital swabs despite serum clearance. This may indicate a need for extending isolation precautions, re-evaluating discharge criteria and transmission risk after discharge, and considering oral swabs as a less invasive diagnostic alternative.


Article metrics loading...

Loading full text...

Full text loading...



  1. Bente DA, Forrester NL, Watts DM, McAuley AJ, Whitehouse CA, Bray M. Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity. Antiviral Res. 2013;100(1):159-89.  https://doi.org/10.1016/j.antiviral.2013.07.006  PMID: 23906741 
  2. Gargili A, Estrada-Peña A, Spengler JR, Lukashev A, Nuttall PA, Bente DA. The role of ticks in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus: A review of published field and laboratory studies. Antiviral Res. 2017;144:93-119.  https://doi.org/10.1016/j.antiviral.2017.05.010  PMID: 28579441 
  3. Ergönül O. Crimean-Congo haemorrhagic fever. Lancet Infect Dis. 2006;6(4):203-14.  https://doi.org/10.1016/S1473-3099(06)70435-2  PMID: 16554245 
  4. Ergonul O. Crimean-Congo hemorrhagic fever virus: new outbreaks, new discoveries. Curr Opin Virol. 2012;2(2):215-20.  https://doi.org/10.1016/j.coviro.2012.03.001  PMID: 22482717 
  5. European Centre for Disease Prevention and Control (ECDC). Rapid risk assessment: Crimean–Congo haemorrhagic fever in Spain – 9 September 2016. Stockholm: ECDC; 2016. Available from: https://www.ecdc.europa.eu/en/publications-data/rapid-risk-assessment-crimean-congo-haemorrhagic-fever-spain-9-september-2016
  6. European Centre for Disease Prevention and Control (ECDC). Communicable disease threats report, 12-18 August 2018, week 33. Stockholm: ECDC; 2018. Available from: https://ecdc.europa.eu/en/publications-data/communicable-disease-threats-report-12-18-august-2018-week-33
  7. Kırım Kongo Kanamalı Ateşi (KKKA). [Crimean Congo Hemorrhagic Fever (CCHF)]. Ankara: Public Health General Directorate of Turkey. [Accessed: 19 Nov 2019]. Turkish. Available from: https://hsgm.saglik.gov.tr/tr/zoonotikvektorel-kkka/zoonotikvektorel-kkka-istatistik
  8. Spengler JR, Bente DA, Bray M, Burt F, Hewson R, Korukluoglu G, et al. Second international conference on Crimean-Congo hemorrhagic fever. Antiviral Res. 2018;150:137-47.  https://doi.org/10.1016/j.antiviral.2017.11.019  PMID: 29199036 
  9. Pshenichnaya NY, Sydenko IS, Klinovaya EP, Romanova EB, Zhuravlev AS. Possible sexual transmission of Crimean-Congo hemorrhagic fever. Int J Infect Dis. 2016;45:109-11.  https://doi.org/10.1016/j.ijid.2016.02.1008  PMID: 26972040 
  10. Ergonul O, Battal I. Potential sexual transmission of Crimean-Congo hemorrhagic fever infection. Jpn J Infect Dis. 2014;67(2):137-8.  https://doi.org/10.7883/yoken.67.137  PMID: 24647261 
  11. Gürbüz Y, Sencan I, Oztürk B, Tütüncü E. A case of nosocomial transmission of Crimean-Congo hemorrhagic fever from patient to patient. Int J Infect Dis. 2009;13(3):e105-7.  https://doi.org/10.1016/j.ijid.2008.08.002  PMID: 18948048 
  12. Zeller H. Chapter 18: Laboratory diagnosis of Crimean Congo Hemorrhagic Fever pp: 233-240. In: Ergonul O, Whitehouse C (eds) Crimean Congo Hemorrhagic Fever. A Global Perspective. 2007, Springer, Dordrecht, The Netherlands.
  13. Ergunay K, Kocak Tufan Z, Bulut C, Kinikli S, Demiröz AP, Ozkul A. Antibody responses and viral load in patients with Crimean-Congo hemorrhagic fever: a comprehensive analysis during the early stages of the infection. Diagn Microbiol Infect Dis. 2014;79(1):31-6.  https://doi.org/10.1016/j.diagmicrobio.2013.12.015  PMID: 24630756 
  14. Burt FJ, Leman PA, Abbott JC, Swanepoel R. Serodiagnosis of Crimean-Congo haemorrhagic fever. Epidemiol Infect. 1994;113(3):551-62.  https://doi.org/10.1017/S0950268800068576  PMID: 7995364 
  15. Centers for Disiease Control and Prevention (CDC). Type and Duration of Precautions Recommended for Selected Infections and Conditions. Atlanta: CDC. [Accessed: 19 Nov 2019]. Available from: https://www.cdc.gov/infectioncontrol/guidelines/isolation/appendix/type-duration-precautions.html#C
  16. Fletcher TE, Gulzhan A, Ahmeti S, Al-Abri SS, Asik Z, Atilla A, et al. Infection prevention and control practice for Crimean-Congo hemorrhagic fever-A multi-center cross-sectional survey in Eurasia. PLoS One. 2017;12(9):e0182315.  https://doi.org/10.1371/journal.pone.0182315  PMID: 28886039 
  17. Leblebicioglu H, Sunbul M, Bodur H, Ozaras R; Crimean–Congo Haemorrhagic Fever Research Network of Turkey (CCRNT). Discharge criteria for Crimean-Congo haemorrhagic fever in endemic areas. J Infect. 2016;S0163-4453(16)00026-8.
  18. Precautions to Prevent Transmission of Infectious Agents. Atlanta: CDC. [19 Nov 2019]. Available from: https://www.cdc.gov/infectioncontrol/guidelines/isolation/precautions.html
  19. Yagci-Caglayik D, Bayrakdar F, Menemenlioglu D, Korukluoglu G, Ozkul A. Performance of a commercial and in-house real time RT-PCR assays for CCHFV diagnosis. 1st International Conference on Crimean-Congo Hemorrhagic Fever. 13-14 February 2015, Thessaloniki, Greece.
  20. Dokuzoguz B, Celikbas AK, Gök ŞE, Baykam N, Eroglu MN, Ergönül Ö. Severity scoring index for Crimean-Congo hemorrhagic fever and the impact of ribavirin and corticosteroids on fatality. Clin Infect Dis. 2013;57(9):1270-4.  https://doi.org/10.1093/cid/cit527  PMID: 23946218 
  21. Bodur H, Akinci E, Ongürü P, Carhan A, Uyar Y, Tanrici A, et al. Detection of Crimean-Congo hemorrhagic fever virus genome in saliva and urine. Int J Infect Dis. 2010;14(3):e247-9.  https://doi.org/10.1016/j.ijid.2009.04.018  PMID: 19656706 
  22. Thomas S, Thomson G, Dowall S, Bruce C, Cook N, Easterbrook L, et al. 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(9):800-4.  https://doi.org/10.1089/vbz.2011.0776  PMID: 22925025 
  23. Hasanoğlu I, Guner R, Carhan A, Kocak Tufan Z, Yagci-Caglayik D, Guven T, et al. Crucial parameter of the outcome in Crimean Congo hemorrhagic fever: Viral load. J Clin Virol. 2016;75:42-6.  https://doi.org/10.1016/j.jcv.2015.12.006  PMID: 26780111 
  24. Pshenichnaya NY, Nenadskaya SA. Probable Crimean-Congo hemorrhagic fever virus transmission occurred after aerosol-generating medical procedures in Russia: nosocomial cluster. Int J Infect Dis. 2015;33:120-2.  https://doi.org/10.1016/j.ijid.2014.12.047  PMID: 25576827 
  25. Barbosa CM, Di Paola N, Cunha MP, Rodrigues-Jesus MJ, Araujo DB, Silveira VB, et al. Yellow fever virus RNA in urine and semen of convalescent patient, Brazil. Emerg Infect Dis. 2018;24(1):176-8.  https://doi.org/10.3201/eid2401.171310  PMID: 29058663 
  26. Van den Bossche D, Cnops L, Van Esbroeck M. Recovery of dengue virus from urine samples by real-time RT-PCR. Eur J Clin Microbiol Infect Dis. 2015;34(7):1361-7.  https://doi.org/10.1007/s10096-015-2359-0  PMID: 25794553 
  27. Musso D, Gubler DJ. Zika Virus. Clin Microbiol Rev. 2016;29(3):487-524.  https://doi.org/10.1128/CMR.00072-15  PMID: 27029595 
  28. Nagy A, Bán E, Nagy O, Ferenczi E, Farkas Á, Bányai K, et al. Detection and sequencing of West Nile virus RNA from human urine and serum samples during the 2014 seasonal period. Arch Virol. 2016;161(7):1797-806.  https://doi.org/10.1007/s00705-016-2844-5  PMID: 27038827 
  29. Deveci K, Uysal EB, Kaya A, Sancakdar E, Alkan F. Evaluation of renal involvement in children with Crimean-Congo hemorrhagic fever. Jpn J Infect Dis. 2013;66(6):493-6.  https://doi.org/10.7883/yoken.66.493  PMID: 24270136 
  30. Haddock E, Feldmann F, Hawman DW, Zivcec M, Hanley PW, Saturday G, et al. A cynomolgus macaque model for Crimean-Congo haemorrhagic fever. Nat Microbiol. 2018;3(5):556-62.  https://doi.org/10.1038/s41564-018-0141-7  PMID: 29632370 
  31. Leblebicioglu H, Sunbul M, Guner R, Bodur H, Bulut C, Duygu F, et al. Healthcare-associated Crimean-Congo haemorrhagic fever in Turkey, 2002-2014: a multicentre retrospective cross-sectional study. Clin Microbiol Infect. 2016;22(4):387.e1-4.  https://doi.org/10.1016/j.cmi.2015.11.024  PMID: 26806137 
  32. Naderi HR, Sarvghad MR, Bojdy A, Hadizadeh MR, Sadeghi R, Sheybani F. Nosocomial outbreak of Crimean-Congo haemorrhagic fever. Epidemiol Infect. 2011;139(6):862-6.  https://doi.org/10.1017/S0950268810002001  PMID: 20800007 
  33. Kreuels B, Wichmann D, Emmerich P, Schmidt-Chanasit J, de Heer G, Kluge S, et al. A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med. 2014;371(25):2394-401.  https://doi.org/10.1056/NEJMoa1411677  PMID: 25337633 

Data & Media loading...

Supplementary data

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error