Skip to main content
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2007:245–269. doi: 10.1007/978-1-4020-6106-6_19

Treatment of Crimean-Congo Hemorrhagic Fever

Onder Ergonul 3, Ali Mirazimi 4, Dimiter S Dimitrov 5
Editors: Onder Ergonul1, Chris A Whitehouse2
PMCID: PMC7119965

Abstract

Ribavirin is a synthetic purine nucleoside analog with a modified base and D-ribose sugar, also known as virazol, first synthesized by Sidwell and colleagues in 1972 [43, 49] (Fig. 19-1). It is of particular interest, because it was the first synthetic nucleoside to exhibit broad spectrum antiviral activity, and it is one of few antiviral drugs in clinical use effective against agents other than HIV and herpesviruses [43]. It inhibits the replication of a wide range of RNA and DNA viruses in vitro, including orthomyxo, paramyxo, arena, bunya, flavi, herpes, adeno, pox, and retroviruses [49]. In current clinical practice, ribavirin is commonly used for certain viral infections (Table 19-1). Most notably, it is used in combination with interferon-α for treatment of HCV infection [66]. Ribavirin aerosol is used for treatment of pediatric infection by respiratory syncytial virus [19]. It is the only antiviral drug that could be also used in viral hemorrhagic fever syndromes. Besides Crimean- Congo hemorrhagic fever (CCHF), it is used in Lassa fever [70]. Viruses in the Bunyaviridae family are generally sensitive to ribavirin [92]. A prospective, randomized, double-blind, placebo-controlled trial of 242 patients with serologically confirmed Hantaan virus in the People’s Republic of China found a sevenfold decrease in mortality among ribavirin-treated patients [54], other studies did not confirm these benefits. Ribavirin was found to be effective against CCHF virus (CCHFV) in vitro [99, 104].

Keywords: Respiratory Syncytial Virus, Disseminate Intravascular Coagulation, Disseminate Intravascular Coagulation, Hemorrhagic Fever, Hemorrhagic Fever With Renal Syndrome

Contributor Information

Onder Ergonul, Email: onderergonul@yahoo.com.

Chris A. Whitehouse, Email: chris.whitehouse@amedd.army.mil.

Onder Ergonul, Email: onderergonul@yahoo.com.

Ali Mirazimi, Email: ali.mirazimi@smi.ki.se.

Dimiter S. Dimitrov, Email: dimitrov@ncifcrf.gov.

References

  • 1.Altaf A, Luby S, Ahmed AJ, Zaidi N, Khan AJ, Mirza S, McCormick J, Fisher-Hoch S. Outbreak of Crimean-Congo haemorrhagic fever in Quetta, Pakistan: contact tracing and risk assessment. Trop Med Int Health. 1998;3:878–882. doi: 10.1046/j.1365-3156.1998.00318.x. [DOI] [PubMed] [Google Scholar]
  • 2.Anderson SL, Carton JM, Lou J, Xing L, Rubin BY. Interfero-induced guanylate binding protein–1 (GBP–1) mediates an antiviral effect against vesicular stomatitis virus and encephalomyocarditis virus. Virology. 1999;256:8–14. doi: 10.1006/viro.1999.9614. [DOI] [PubMed] [Google Scholar]
  • 3.Andersson I, Bladh L, Mousavi-Jazi M, Magnusson KE, Lundkvist A, Haller O, Mirazimi A. Human MxA protein inhibits the replication of Crimean-Congo hemorrhagic fever virus. J Virol. 2004;78:4323–4329. doi: 10.1128/JVI.78.8.4323-4329.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.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;78:216–222. doi: 10.1002/jmv.20530. [DOI] [PubMed] [Google Scholar]
  • 5.Andrei G, De Clercq E. Inhibitory effect of selected antiviral compounds on arenavirus replication in vitro. Antiviral Res. 1990;14:287–299. doi: 10.1016/0166-3542(90)90009-V. [DOI] [PubMed] [Google Scholar]
  • 6.Andrei G, De Clercq E. Molecular approaches for the treatment of hemorrhagic fever virus infections. Antiviral Res. 1993;22:45–75. doi: 10.1016/0166-3542(93)90085-W. [DOI] [PubMed] [Google Scholar]
  • 7.Asper M, Sternsdorf T, Hass M, Drosten C, Rhode A, Schmitz H, Gunther S. Inhibition of different Lassa virus strains by alpha and gamma interferons and comparison with a less pathogenic arenavirus. J Virol. 2004;78:3162–3169. doi: 10.1128/JVI.78.6.3162-3169.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Baba M, Nakajima M, Schols D, Pauwels R, Balzarini J, De Clercq E. Pentosan polysulfate, a sulfated oligosaccharide, is a potent and selective anti-HIV agent in vitro. Antiviral Res. 1988;9:335–343. doi: 10.1016/0166-3542(88)90035-6. [DOI] [PubMed] [Google Scholar]
  • 9.Baba M, Pauwels R, Balzarini J, Arnout J, Desmyter J, De Clercq E. Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro. Proc Natl Acad Sci USA. 1988;85:6132–6136. doi: 10.1073/pnas.85.16.6132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Baba M, Snoeck R, Pauwels R, de Clercq E. Sulfated polysaccharides are potent and selective inhibitors of various enveloped viruses, including herpes simplex virus, cytomegalovirus, vesicular stomatitis virus, and human immunodeficiency virus. Antimicrob Agents Chemother. 1988;32:1742–1745. doi: 10.1128/aac.32.11.1742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Bakir M, Ugurlu M, Dokuzoguz B, Bodur H, Tasyaran MA, Vahaboglu H. Crimean-Congo haemorrhagic fever outbreak in Middle Anatolia: a multicentre study of clinical features and outcome measures. J Med Microbiol. 2005;54:385–389. doi: 10.1099/jmm.0.45865-0. [DOI] [PubMed] [Google Scholar]
  • 12.Bekisz J, Schmeisser H, Hernandez J, Goldman ND, Zoon KC. Human interferons alpha, beta and omega. Growth Factors. 2004;22:243–251. doi: 10.1080/08977190400000833. [DOI] [PubMed] [Google Scholar]
  • 13.Bertolotti-Ciarlet A, Smith J, Strecker K, Paragas J, Altamura LA, McFalls JM, Frias-Staheli N, Garcia-Sastre A, Schmaljohn CS, Doms RW. Cellular localization and antigenic characterization of Crimean-Congo hemorrhagic fever virus glycoproteins. J Virol. 2005;79:6152–6161. doi: 10.1128/JVI.79.10.6152-6161.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Borish LC, Steinke JW. 2. Cytokines and chemokines. J Allergy Clin Immunol. 2003;111:S460–475. doi: 10.1067/mai.2003.108. [DOI] [PubMed] [Google Scholar]
  • 15.Bradbury J. RNA interference: new drugs on the horizon. Drug Discov Today. 2005;10:1266–1267. doi: 10.1016/S1359-6446(05)03615-9. [DOI] [PubMed] [Google Scholar]
  • 16.Casadevall A. Passive antibody administration (immediate immunity) as a specific defense against biological weapons. Emerg Infect Dis. 2002;8:833–841. doi: 10.3201/eid0808.010516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Chiou HE, Liu CL, Buttrey MJ, Kuo HP, Liu HW, Kuo HT, Lu YT. Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: experience in two medical centers. Chest. 2005;128:263–272. doi: 10.1378/chest.128.1.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Clemens MJ. Interferons and apoptosis. J Interferon Cytokine Res. 2003;23:277–292. doi: 10.1089/107999003766628124. [DOI] [PubMed] [Google Scholar]
  • 19.Cooper AC, Banasiak NC, Allen PJ. Management and prevention strategies for respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a review of evidence-based practice interventions. Pediatr Nurs. 2003;29:452–456. [PubMed] [Google Scholar]
  • 20.De Clercq E. Interferon: ten stories in one. A short review of some of the highlights in the history of an almost quinquagenarian. Acta Microbiol Immunol Hung. 2005;52:273–289. doi: 10.1556/AMicr.52.2005.2.6. [DOI] [PubMed] [Google Scholar]
  • 21.Veer MJ, Holko M, Walker E, Der S, Paranjape JM, Silverman RH, Williams BR. Functional classification of interferon-stimulated genes identified using microarrays. J Leukoc Biol. 2001;69:912–920. [PubMed] [Google Scholar]
  • 22.Der SD, Zhou A, Williams BR, Silverman RH. Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci USA. 1998;95:15623–15628. doi: 10.1073/pnas.95.26.15623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Diamond MS, Harris E. Interferon inhibits dengue virus infection by preventing translation of viral RNA through a PKR-independent mechanism. Virology. 2001;289:297–311. doi: 10.1006/viro.2001.1114. [DOI] [PubMed] [Google Scholar]
  • 24.Dimitrov DS. Virus entry: molecular mechanisms and biomedical applications. Nat Rev Microbiol. 2004;2:109–122. doi: 10.1038/nrmicro817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Dusheiko G, Main J, Thomas H, Reichard O, Lee C, Dhillon A, Rassam S, Fryden A, Reesink H, Bassendine M, Norkrans G, Cuypers T, Lelie N, Telfer P, Watson J, Weegink C, Sillikens P, Weiland O. Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study. J Hepatol. 1996;25:591–598. doi: 10.1016/S0168-8278(96)80225-X. [DOI] [PubMed] [Google Scholar]
  • 26.Ergonul O, Celikbas A, Dokuzoguz B, Eren S, Baykam N, Esener H. Characteristics of patients with Crimean-Congo hemorrhagic fever in a recent outbreak in Turkey and impact of oral ribavirin therapy. Clin Infect Dis. 2004;39:284–287. doi: 10.1086/422000. [DOI] [PubMed] [Google Scholar]
  • 27.Ergonul O. Crimean-Congo haemorrhagic fever. Lancet Infect Dis. 2006;6:203–214. doi: 10.1016/S1473-3099(06)70435-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Ergonul O, Celikbas A, Baykam N, Eren S, Dokuzoguz B. Analysis of risk-factors among patients with Crimean-Congo haemorrhagic fever virus infection: severity criteria revisited. Clin Microbiol Infect. 2006;12:551–554. doi: 10.1111/j.1469-0691.2006.01445.x. [DOI] [PubMed] [Google Scholar]
  • 29.Ergonul O, Tuncbilek S, Baykam N, Celikbas A, Dokuzoguz B. Evaluation of serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha in patients with Crimean-Congo hemorrhagic fever. J Infect Dis. 2006;193:941–944. doi: 10.1086/500836. [DOI] [PubMed] [Google Scholar]
  • 30.Espert L, Degols G, Gongora C, Blondel D, Williams BR, Silverman RH, Mechti N. ISG20, a new interferon-induced RNase specific for single-stranded RNA, defines an alternative antiviral pathway against RNA genomic viruses. J Biol Chem. 2003;278:16151–16158. doi: 10.1074/jbc.M209628200. [DOI] [PubMed] [Google Scholar]
  • 31.Espert L, Rey C, Gonzalez L, Degols G, Chelbi-Alix MK, Mechti N, Gongora C. The exonuclease ISG20 is directly induced by synthetic dsRNA via NF-kappaB and IRF1 activation. Oncogene. 2004;23:4636–4640. doi: 10.1038/sj.onc.1207586. [DOI] [PubMed] [Google Scholar]
  • 32.Espert L, Degols G, Lin YL, Vincent T, Benkirane M, Mechti N. Interferon-induced exonuclease ISG20 exhibits an antiviral activity against human immunodeficiency virus type 1. J Gen Virol. 2005;86:2221–2229. doi: 10.1099/vir.0.81074-0. [DOI] [PubMed] [Google Scholar]
  • 33.Fisher-Hoch SP, Khan JA, Rehman S, Mirza S, Khurshid M, McCormick JB. Crimean Congo-haemorrhagic fever treated with oral ribavirin. Lancet. 1995;346:472–475. doi: 10.1016/S0140-6736(95)91323-8. [DOI] [PubMed] [Google Scholar]
  • 34.Flick R, Flick K, Feldmann H, Elgh F. Reverse genetics for Crimean-Congo hemorrhagic fever virus. J Virol. 2003;77:5997–6006. doi: 10.1128/JVI.77.10.5997-6006.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Franchini M, Lippi G, Manzato F. Recent acquisitions in the pathophysiology,diagnosis and treatment of disseminated intravascular coagulation. Thromb J. 2006;4:4. doi: 10.1186/1477-9560-4-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Frese M, Kochs G, Meier-Dieter U, Siebler J, Haller O. Human MxA protein inhibits tick-borne Thogoto virus but not Dhori virus. J Virol. 1995;69:3904–3909. doi: 10.1128/jvi.69.6.3904-3909.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Frese M, Kochs G, Feldmann H, Hertkorn C, Haller O. Inhibition of bunyaviruses, phleboviruses, and hantaviruses by human MxA protein. J Virol. 1996;70:915–923. doi: 10.1128/jvi.70.2.915-923.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Frese M, Pietschmann T, Moradpour D, Haller O, Bartenschlager R. Interferon-alpha inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway. J Gen Virol. 2001;82:723–733. doi: 10.1099/0022-1317-82-4-723. [DOI] [PubMed] [Google Scholar]
  • 39.Garcia KC, Teyton L, Wilson IA. Structural basis of T cell recognition. Annu Rev Immunol. 1999;17:369–397. doi: 10.1146/annurev.immunol.17.1.369. [DOI] [PubMed] [Google Scholar]
  • 40.Garcia S, Chinikar S, Coudrier D, Billecocq A, Hooshmand B, Crance JM, Garin D, Bouloy M. Evaluation of a Crimean-Congo hemorrhagic fever virus recombinant antigen expressed by Semliki Forest suicide virus for IgM and IgG antibody detection in human and animal sera collected in Iran. J Clin Virol. 2006;32:154–159. doi: 10.1016/j.jcv.2005.02.016. [DOI] [PubMed] [Google Scholar]
  • 41.Gonzalez JP, Wilson ML, Cornet JP, Camicas JL. Host-passage-induced phenotypic changes in Crimean-Congo haemorrhagic fever virus. Res Virol. 1995;146:131–140. doi: 10.1016/0923-2516(96)81082-X. [DOI] [PubMed] [Google Scholar]
  • 42.Gonzalez JP, Camicas JL, Cornet JP, Wilson ML. Biological and clinical responses of West African sheep to Crimean-Congo haemorrhagic fever virus experimental infection. Res Virol. 1998;149:445–455. doi: 10.1016/S0923-2516(99)80013-2. [DOI] [PubMed] [Google Scholar]
  • 43.Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006;16:37–48. doi: 10.1002/rmv.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Gresser I. Wherefore interferon? J Leukoc Biol. 1997;61:567–574. doi: 10.1002/jlb.61.5.567. [DOI] [PubMed] [Google Scholar]
  • 45.Griffin DE. Immune responses to RNA-virus infections of the CNS. Nat Rev Immunol. 2003;3:493–502. doi: 10.1038/nri1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Haferkamp S, Fernando L, Schwarz TF, Feldmann H, Flick R. Intracellular localization of Crimean-Congo Hemorrhagic Fever (CCHF) virus glycoproteins. Virol J. 2005;2:42. doi: 10.1186/1743-422X-2-42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Haller O, Frese M, Kochs G. Mx proteins: mediators of innate resistance to RNA viruses. Rev Sci Tech. 1998;17:220–230. doi: 10.20506/rst.17.1.1084. [DOI] [PubMed] [Google Scholar]
  • 48.Haller O, Kochs G, Weber F. The interferon response circuit: Induction and suppression by pathogenic viruses. Virology. 2006;344:119–130. doi: 10.1016/j.virol.2005.09.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Hayden FG. Antiviral Agents. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman's. Mc Graw Hill, New York: The Pharmacological Basis of Therapeutics; 2006. pp. 1265–1267. [Google Scholar]
  • 50.Heagy W, Crumpacker C, Lopez PA, Finberg RW. Inhibition of immune functions by antiviral drugs. J Clin Invest. 1991;87:1916–1924. doi: 10.1172/JCI115217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Hoogstraal H. The epidemiology of tick-borne Crimean-Congo hemorrhagic fever in Asia, Europe, and Africa. J Med Entomol. 1979;15:307–417. doi: 10.1093/jmedent/15.4.307. [DOI] [PubMed] [Google Scholar]
  • 52.Horisberger MA. Interferons, Mx genes, and resistance to influenza virus. Am J Respir Crit Care Med. 1995;152:S67–71. doi: 10.1164/ajrccm/152.4_Pt_2.S67. [DOI] [PubMed] [Google Scholar]
  • 53.Huggins JW. Prospects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral drug. Rev Infect Dis. 1989;11(4):S750–761. doi: 10.1093/clinids/11.supplement_4.s750. [DOI] [PubMed] [Google Scholar]
  • 54.Huggins JW, Hsiang CM, Cosgriff TM, Guang MY, Smith JI, Wu ZO, LeDuc JW, Zheng ZM, Meegan JM, Wang QN, et al. Prospective, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin therapy of hemorrhagic fever with renal syndrome. J Infect Dis. 1991;164:1119–1127. doi: 10.1093/infdis/164.6.1119. [DOI] [PubMed] [Google Scholar]
  • 55.Hui DJ, Bhasker CR, Merrick WC, Sen GC. Viral stress-inducible protein p56 inhibits translation by blocking the interaction of eIF3 with the ternary complex eIF2.GTP.Met-tRNAi. J Biol Chem. 2003;278:39477–39482. doi: 10.1074/jbc.M305038200. [DOI] [PubMed] [Google Scholar]
  • 56.Hui DJ, Terenzi F, Merrick WC, Sen GC. Mouse p56 blocks a distinct function of eukaryotic initiation factor 3 in translation initiation. J Biol Chem. 2005;280:3433–3440. doi: 10.1074/jbc.M406700200. [DOI] [PubMed] [Google Scholar]
  • 57.Hultgren C, Milich DR, Weiland O, Sallberg M. The antiviral compound ribavirin modulates the T helper (Th) 1/Th2 subset balance in hepatitis B and C virus-specific immune responses. J Gen Virol. 1998;79(10):2381–2391. doi: 10.1099/0022-1317-79-10-2381. [DOI] [PubMed] [Google Scholar]
  • 58.Isaacs A, Lindenmann J. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957;147:258–267. doi: 10.1098/rspb.1957.0048. [DOI] [PubMed] [Google Scholar]
  • 59.Isaacs A, Lindenmann J, Valentine RC. Virus interference. II. Some properties of interferon. Proc R Soc Lond B Biol Sci. 1957;147:268–273. doi: 10.1098/rspb.1957.0049. [DOI] [PubMed] [Google Scholar]
  • 60.Jabbari A, Besharat S, Abbasi A, Moradi A, Kalavi K. Crimean-Congo hemorrhagic fever: case series from a medical center in Golestan province, Northeast of Iran (2004) Indian J Med Sci. 2006;60:327–329. doi: 10.4103/0019-5359.26609. [DOI] [PubMed] [Google Scholar]
  • 61.Janeway CA, Jr., Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216. doi: 10.1146/annurev.immunol.20.083001.084359. [DOI] [PubMed] [Google Scholar]
  • 62.Kinsella E, Martin SG, Grolla A, Czub M, Feldmann H, Flick R. Sequence determination of the Crimean-Congo hemorrhagic fever virus L segment. Virology. 2004;321:23–28. doi: 10.1016/j.virol.2003.09.046. [DOI] [PubMed] [Google Scholar]
  • 63.Knowles SR, Phillips EJ, Dresser L, Matukas L. Common adverse events associated with the use of ribavirin for severe acute respiratory syndrome in Canada. Clin Infect Dis. 2003;37:1139–1142. doi: 10.1086/378304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Kochs G, Janzen C, Hohenberg H, Haller O. Antivirally active MxA protein sequesters La Crosse virus nucleocapsid protein into perinuclear complexes. Proc Natl Acad Sci USA. 2002;99:3153–3158. doi: 10.1073/pnas.052430399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Leroy M, Pire G, Baise E, Desmecht D. Expression of the interferon-alpha/beta-inducible bovine Mx1 dynamin interferes with replication of rabies virus. Neurobiol Dis. 2005;21:515–521. doi: 10.1016/j.nbd.2005.08.015. [DOI] [PubMed] [Google Scholar]
  • 66.Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005;352:2609–2617. doi: 10.1056/NEJMoa042608. [DOI] [PubMed] [Google Scholar]
  • 67.Mardani M, Jahromi MK, Naieni KH, Zeinali M. The efficacy of oral ribavirin in the treatment of Crimean-Congo hemorrhagic fever in Iran. Clin Infect Dis. 2003;36:1613–1618. doi: 10.1086/375058. [DOI] [PubMed] [Google Scholar]
  • 68.Marquez VE, Lim MI, Treanor SP, Plowman J, Priest MA, Markovac A, Khan MS, Kaskar B, Driscoll JS. Cyclopentenylcytosine. A carbocyclic nucleoside with antitumor and antiviral properties. J Med Chem. 1988;31:1687–1694. doi: 10.1021/jm00117a004. [DOI] [PubMed] [Google Scholar]
  • 69.Mazza JJ. Manual of Clinical Hematology. Philadelphia: Lippincott Williams & Wilkins; 2002. [Google Scholar]
  • 70.McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM, Elliott LH, Belmont-Williams R. Lassa fever. Effective therapy with ribavirin. N Engl J Med. 1986;314:20–26. doi: 10.1056/NEJM198601023140104. [DOI] [PubMed] [Google Scholar]
  • 71.Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996;17:138–146. doi: 10.1016/0167-5699(96)80606-2. [DOI] [PubMed] [Google Scholar]
  • 72.Moulard M, Phogat SK, Shu Y, Labrijn AF, Xiao X, Binley JM, Zhang MY, Sidorov IA, Broder CC, Robinson J, Parren PW, Burton DR, Dimitrov DS. Broadly cross-reactive HIV–1–neutralizing human monoclonal Fab selected for binding to gp120–CD4–CCR5 complexes. Proc Natl Acad Sci USA. 2002;99:6913–6918. doi: 10.1073/pnas.102562599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Nabeth P, Cheikh DO, Lo B, Faye O, Vall IO, Niang M, Wague B, Diop D, Diallo M, Diallo B, Diop OM, Simon F. Crimean-Congo hemorrhagic fever, Mauritania. Emerg Infect Dis. 2004;10:2143–2149. doi: 10.3201/eid1012.040535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.Ozkurt Z, Kiki I, Erol S, Erdem F, Yilmaz N, Parlak M, Gundogdu M, Tasyaran MA. Crimean-Congo hemorrhagic fever in Eastern Turkey: clinical features, risk factors and efficacy of ribavirin therapy. J Infect. 2006;52:207–215. doi: 10.1016/j.jinf.2005.05.003. [DOI] [PubMed] [Google Scholar]
  • 75.Padlan EA. Anatomy of the antibody molecule. Mol Immunol. 1994;31:169–217. doi: 10.1016/0161-5890(94)90001-9. [DOI] [PubMed] [Google Scholar]
  • 76.Page T, Connor JD. The metabolism of ribavirin in erythrocytes and nucleated cells. Int J Biochem. 1990;22:379–383. doi: 10.1016/0020-711X(90)90140-X. [DOI] [PubMed] [Google Scholar]
  • 77.Papa A, Bino S, Llagami A, Brahimaj B, Papadimitriou E, Pavlidou V, Velo E, Cahani G, Hajdini M, Pilaca A, Harxhi A, Antoniadis A. Crimean-Congo hemorrhagic fever in Albania, 2001. Eur J Clin Microbiol Infect Dis. 2002;21:603–606. doi: 10.1007/s10096-002-0770-9. [DOI] [PubMed] [Google Scholar]
  • 78.Papa A, Bozovi B, Pavlidou V, Papadimitriou E, Pelemis M, Antoniadis A. Genetic detection and isolation of Crimean-Congo hemorrhagic fever virus, Kosovo, Yugoslavia. Emerg Infect Dis. 2002;8:852–854. doi: 10.3201/eid0801.010087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79.Perrota PL, Pisciotto PT, Snyder EL. Platelets and Related Products. In: Hillyer CD, Silberstein LE, Ness PM, Anderson KC, Roush KS, editors. Blood Banking and Transfusion Medicine. Philadelphia: Churchill Livingstone; 2003. pp. 181–205. [Google Scholar]
  • 80.Regad T, Chelbi-Alix MK. Role and fate of PML nuclear bodies in response to interferon and viral infections. Oncogene. 2001;20:7274–7286. doi: 10.1038/sj.onc.1204854. [DOI] [PubMed] [Google Scholar]
  • 81.Reichelt M, Stertz S, Krijnse-Locker J, Haller O, Kochs G. Missorting of LaCrosse virus nucleocapsid protein by the interferon-induced MxA GTPase involves smooth ER membranes. Traffic. 2004;5:772–784. doi: 10.1111/j.1600-0854.2004.00219.x. [DOI] [PubMed] [Google Scholar]
  • 82.Rubinstein M, Dinarello CA, Oppenheim JJ, Hertzog P. Recent advances in cytokines, cytokine receptors and signal transduction. Cytokine Growth Factor Rev. 1998;9:175–181. doi: 10.1016/S1359-6101(98)00006-9. [DOI] [PubMed] [Google Scholar]
  • 83.Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev. 2001;14:778–809. doi: 10.1128/CMR.14.4.778-809.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84.Sanchez AJ, Vincent MJ, Nichol ST. Characterization of the glycoproteins of Crimean-Congo hemorrhagic fever virus. J Virol. 2002;76:7263–7275. doi: 10.1128/JVI.76.14.7263-7275.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.Sanchez AJ, Vincent MJ, Erickson BR, Nichol ST. Crimean-Congo hemorrhagic fever virus glycoprotein precursor is cleaved by Furin-like and SKI–1 proteases to generate a novel 38–kilodalton glycoprotein. J Virol. 2006;80:514–525. doi: 10.1128/JVI.80.1.514-525.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Sasaki N, Matsui A, Momoi M, Tsuda F, Okamoto H. Loss of circulating hepatitis C virus in children who developed a persistent carrier state after mother-to-baby transmission. Pediatr Res. 1997;42:263–267. doi: 10.1203/00006450-199709000-00003. [DOI] [PubMed] [Google Scholar]
  • 87.Sen GC. Viruses and interferons. Annu Rev Microbiol. 2001;55:255–281. doi: 10.1146/annurev.micro.55.1.255. [DOI] [PubMed] [Google Scholar]
  • 88.Shepherd AJ, Swanepoel R, Leman PA. Antibody response in Crimean-Congo hemorrhagic fever. Rev Infect Dis. 1989;11(4):S801–806. doi: 10.1093/clinids/11.supplement_4.s801. [DOI] [PubMed] [Google Scholar]
  • 89.Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK. Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1, 2, 4-triazole-3-carboxamide. Science. 1972;177:705–706. doi: 10.1126/science.177.4050.705. [DOI] [PubMed] [Google Scholar]
  • 90.Sidwell RW, Huffman JH, Smee DF, Gilbert J, Gessaman A, Pease A, Warren RP, Huggins J, Kende M. Potential role of immunomodulators for treatment of phlebovirus infections of animals. Ann N Y Acad Sci. 1992;653:344–355. doi: 10.1111/j.1749-6632.1992.tb19661.x. [DOI] [PubMed] [Google Scholar]
  • 91.Sidwell RW, Huffman JH, Barnard DL, Smee DF, Warren RP, Chirigos MA, Kende M, Huggins J. Antiviral and immunomodulating inhibitors of experimentally-induced Punta Toro virus infections. Antiviral Res. 1994;25:105–122. doi: 10.1016/0166-3542(94)90100-7. [DOI] [PubMed] [Google Scholar]
  • 92.Sidwell RW, Smee DF. Viruses of the Bunya– and Togaviridae families: potential as bioterrorism agents and means of control. Antiviral Res. 2003;57:101–111. doi: 10.1016/S0166-3542(02)00203-6. [DOI] [PubMed] [Google Scholar]
  • 93.Silverman RH. Fascination with 2–5A-dependent RNase: a unique enzyme that functions in interferon action. J Interferon Res. 1994;14:101–104. doi: 10.1089/jir.1994.14.101. [DOI] [PubMed] [Google Scholar]
  • 94.Suleiman MN, Muscat-Baron JM, Harries JR, Satti AG, Platt GS, Bowen ET, Simpson DI. Congo/Crimean haemorrhagic fever in Dubai. An outbreak at the Rashid Hospital. Lancet. 1980;2:939–941. [PubMed] [Google Scholar]
  • 95.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(4):S794–800. doi: 10.1093/clinids/11.supplement_4.s794. [DOI] [PubMed] [Google Scholar]
  • 96.Sweeney MJ, Gerzon K, Harris PN, Holmes RE, Poore GA, Williams RH. Experimental antitumor activity and preclinical toxicology of mycophenolic acid. Cancer Res. 1972;32:1795–1802. [PubMed] [Google Scholar]
  • 97.Tam RC, Lau JY, Hong Z. Mechanisms of action of ribavirin in antiviral therapies. Antivir Chem Chemother. 2001;12:261–272. doi: 10.1177/095632020101200501. [DOI] [PubMed] [Google Scholar]
  • 98.Tatar A, Ozkurt Z, Kiki I. Genotoxic effect of ribavirin in patients with Crimean-Congo hemorrhagic fever. Jpn J Infect Dis. 2005;58:313–315. [PubMed] [Google Scholar]
  • 99.Tignor GH, Hanham CA. Ribavirin efficacy in an in vivo model of Crimean-Congo hemorrhagic fever virus (CCHF) infection. Antiviral Res. 1993;22:309–325. doi: 10.1016/0166-3542(93)90040-P. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 100.Tosi MF. Innate immune responses to infection. J Allergy Clin Immunol. 2005;116:241–249. doi: 10.1016/j.jaci.2005.05.036. [DOI] [PubMed] [Google Scholar]
  • 101.Vandenbroucke JP. When are observational studies as credible as randomised trials? Lancet. 2004;363:1728–1731. doi: 10.1016/S0140-6736(04)16261-2. [DOI] [PubMed] [Google Scholar]
  • 102.Vassilenko SM, Vassilev TL, Bozadjiev LG, Bineva IL, Kazarov GZ. Specific intravenous immunoglobulin for Crimean-Congo haemorrhagic fever. Lancet. 1990;335:791–792. doi: 10.1016/0140-6736(90)90906-L. [DOI] [PubMed] [Google Scholar]
  • 103.Vincent MJ, Sanchez AJ, Erickson BR, Basak A, Chretien M, Seidah NG, Nichol ST. Crimean-Congo hemorrhagic fever virus glycoprotein proteolytic processing by subtilase SKI–1. J Virol. 2003;77:8640–8649. doi: 10.1128/JVI.77.16.8640-8649.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 104.Watts DM, Ussery MA, Nash D, Peters CJ. Inhibition of Crimean-Congo hemorrhagic fever viral infectivity yields in vitro by ribavirin. Am J Trop Med Hyg. 1989;41:581–585. doi: 10.4269/ajtmh.1989.41.581. [DOI] [PubMed] [Google Scholar]
  • 105.Williams BR. PKR; a sentinel kinase for cellular stress. Oncogene. 1999;18:6112–6120. doi: 10.1038/sj.onc.1203127. [DOI] [PubMed] [Google Scholar]
  • 106.Wilson ML, Gonzalez JP, Cornet JP, Camicas JL. Transmission of Crimean-Congo haemorrhagic fever virus from experimentally infected sheep to Hyalomma truncatum ticks. Res Virol. 1991;142:395–404. doi: 10.1016/0923-2516(91)90007-P. [DOI] [PubMed] [Google Scholar]
  • 107.Young KC, Lindsay KL, Lee KJ, Liu WC, He JW, Milstein SL, Lai MM. Identification of a ribavirin-resistant NS5B mutation of hepatitis C virus during ribavirin monotherapy. Hepatol (Baltimore, MD) 2003;38:869–878. doi: 10.1053/jhep.2003.50445. [DOI] [PubMed] [Google Scholar]
  • 108.Zeerleder S, Hack CE, Wuillemin WA. Disseminated intravascular coagulation in sepsis. Chest. 2005;128:2864–2875. doi: 10.1378/chest.128.4.2864. [DOI] [PubMed] [Google Scholar]
  • 109.Zhang MY, Shu Y, Phogat S, Xiao X, Cham F, Bouma P, Choudhary A, Feng YR, Sanz I, Rybak S, Broder CC, Quinnan GV, Evans T, Dimitrov DS. Broadly cross-reactive HIV neutralizing human monoclonal antibody Fab selected by sequential antigen panning of a phage display library. J Immunol Methods. 2003;283:17–25. doi: 10.1016/j.jim.2003.07.003. [DOI] [PubMed] [Google Scholar]
  • 110.Zhang MY, Shu Y, Rudolph D, Prabakaran P, Labrijn AF, Zwick MB, Lal RB, Dimitrov DS. Improved breadth and potency of an HIV-1-neutralizing human single-chain antibody by random mutagenesis and sequential antigen panning. J Mol Biol. 2004;335:209–219. doi: 10.1016/j.jmb.2003.09.055. [DOI] [PubMed] [Google Scholar]
  • 111.Zhang MY, Shu Y, Sidorov I, Dimitrov DS. Identification of a novel CD4i human monoclonal antibody Fab that neutralizes HIV–1 primary isolates from different clades. Antiviral Res. 2004;61:161–164. doi: 10.1016/j.antiviral.2003.09.009. [DOI] [PubMed] [Google Scholar]
  • 112.Zhang MY, Xiao X, Sidorov IA, Choudhry V, Cham F, Zhang PF, Bouma P, Zwick M, Choudhary A, Montefiori DC, Broder CC, Burton DR, Quinnan GV, Jr., Dimitrov DS. Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody. J Virol. 2004;78:9233–9242. doi: 10.1128/JVI.78.17.9233-9242.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Crimean-Congo Hemorrhagic Fever are provided here courtesy of Nature Publishing Group

RESOURCES