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International Journal of Infectious Diseases (2009) 13, 380—386 http://intl.elsevierhealth.com/journals/ijid The epidemiology of Crimean-Congo hemorrhagic fever in Turkey, 2002—2007§ Gul Ruhsar Yilmaz a,*, Turan Buzgan a, Hasan Irmak a, Ahmet Safran a, Ramazan Uzun a, Mustafa Aydin Cevik b, Mehmet Ali Torunoglu a a b Ministry of Health, General Directorate of Primary Health Care, Mithatpasa Cad. 3, 06434 Sihhiye, Ankara, Turkey Ankara Numune Training and Research Hospital, Ankara, Turkey Received 23 March 2008; received in revised form 30 June 2008; accepted 11 July 2008 Corresponding Editor: William Cameron, Ottawa, Canada KEYWORDS Crimean-Congo hemorrhagic fever; Epidemiology; Turkey Summary Background: Crimean-Congo hemorrhagic fever (CCHF) is a serious disease caused by the CCHF virus of the Bunyaviridae family. The disease has been reported in 30 countries in Africa, Asia, Eastern Europe, and the Middle East. It has been present in Turkey since 2002. In this study we present and discuss the epidemiological features, clinical and laboratory findings, treatment, and outcome of cases diagnosed with CCHF between 2002 and 2007 from the surveillance results of the Turkish Ministry of Health (MoH). Methods: According to the surveillance system of the MoH, data for patients with clinical, laboratory, and epidemiological findings compatible with CCHF are recorded on case reporting forms. These forms are submitted to the General Directorate of Primary Health Care of the MoH by the city health directorates. All the surveillance data regarding CCHF were recorded on a database (SSPS 11.0) established in the Communicable Diseases Department of the MoH. Results: According to the surveillance reports of the Turkish MoH, between 2002 and 2007, 1820 CCHF cases occurred (150 in 2002—2003, 249 in 2004, 266 in 2005, 438 in 2006, and 717 in 2007). The crude fatality rate was calculated to be 5% (92/1820). Two thirds of the CCHF cases were reported from five cities located in the Mid-Eastern Anatolia region; 69.4% of the cases were from rural areas. The male to female ratio was 1.13:1. Of all the reported cases, 68.9% had a history of tick-bite or tick contact and 84.1% were seen in the months of May, June, and July. Of 1820 CCHF cases, three (0.16%) were nosocomial infections. Conclusions: CCHF appears to be a seasonal problem in the Mid-Eastern Anatolia region of Turkey. The possible risk factors for transmission and the clinical and laboratory findings of patients with a diagnosis of CCHF were found to be similar to those reported in the literature. The mean fatality rate for Turkey is lower than the rate reported for other series from other parts of the world. # 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. § In memory of Mustafa Aydin Cevik for all his support and guidance. * Corresponding author. Tel.: +90 312 5851390; fax: +90 312 4322994. E-mail address: [email protected] (G.R. Yilmaz). 1201-9712/$36.00 # 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2008.07.021 The epidemiology of CCHF in Turkey, 2002-2007 Introduction Crimean-Congo hemorrhagic fever (CCHF) is a viral infection caused by a tick bite or transmitted through the blood or body fluids of domestic animals or CCHF patients. It was first seen in the Crimean Peninsula in 1940. Today, it is found in 30 countries located in Africa, Asia, Eastern Europe, and the Middle East. Despite the incidence of CCHF in Bulgaria, Russia, Iran, and Iraq, countries neighboring Turkey, no case of CCHF was reported from Turkey until 2002.1—4 Following a regional epidemic in Turkey in 2003, the disease was determined to be CCHF by laboratory confirmation, and several reports have now been published.5—17 When considering the number of CCHF cases reported to date worldwide,18 the highest number has been reported in Turkey. In this study, the epidemiological features, clinical and laboratory findings, treatment, and outcome of cases diagnosed with CCHF between 2002 and 2007 obtained from the surveillance results of the Turkish Ministry of Health (MoH) are discussed. Materials and methods Outbreak history Turkey has a population of 70 million, and there are no reports of CCHF occurring before 2002. In the spring and summer of 2002, the first cases with clinical and laboratory findings compatible with CCHF were reported from the city of Tokat, located in the Middle Anatolia-Black sea region of Turkey. In the spring and summer of 2003, cases with similar clinical and laboratory findings were reported from Tokat and its neighboring cities of Yozgat, Sivas, etc. In the same year, a scientific commission set up by Turkish MoH described the cases and developed a case report form, before the diagnosis of the disease was established. The MoH demanded that the approach to such cases be in compliance with these case descriptions. In 2003, serum samples were found positive for the disease by the National Reference Center for Arbovirus and Viral Hemorrhagic Fevers, Pasteur Institute, Lyon, France. CCHF surveillance system of the Turkish Ministry of Health CCHF has been listed as a notifiable disease since December 2003. In that year, the MoH ordered through a declaration that all suspected cases of CCHF with specific clinical findings compatible with the disease should be referred to a secondary healthcare center by the primary care centers, and that notification of the case should come from the secondary care center. The MoH has described the centers that can treat patients according to their severity of disease, case definitions, and referral criteria. Treatment options, isolation measures, suggestions for disinfection, and the approach in handling the deceased were published in a small pamphlet and sent to all health centers. Patient data, including clinical, laboratory, and epidemiological findings compatible with CCHF, are recorded on MoH surveillance forms. These forms, along with serum samples 381 obtained from suspected cases (the first sample), are submitted to the General Directorate of Primary Health Care, Department of Communicable Diseases and Refik Saydam Hygiene Center, Virology Laboratory of the MoH by the city health directorates. It is required that all patients diagnosed with CCHF based on case definition criteria be followed in hospitals. The centers are also directed to collect a second sample of blood from individuals with a prediagnosis or definitive diagnosis of CCHF in the second week of the disease or upon discharge, and to send these samples to the MoH. Based on the notification system, epidemiological data were collected starting from 2004 using the standard case reporting forms developed by the CCHF scientific committee. All the surveillance data were recorded on a database (SSPS 11.0) established in the Communicable Diseases Department of the MoH. In the case of missing patient information, contact was established with the city health directorates and the information was obtained. Case definition Among the cases with epidemiological risk factors and clinical and laboratory findings compatible with CCHF, those with confirmed CCHF virus RNA in blood or body fluid samples by reverse transcriptase-polymerase chain reaction (RT-PCR) evaluation or IgM and/or IgG positivity by ELISA were defined as confirmed CCHF cases. Risk factors and findings compatible with CCHF were defined as follows: (1) epidemiological risk factors: tick-bite or tick contact, involvement in animal husbandry or farmer, contact with the body fluid of a CCHF patient or working at a laboratory, and individuals with similar complaints in the proximity of a CCHF patient; (2) clinical findings: fever, hemorrhage, headache of acute onset, myalgia/arthralgia, lethargy, nausea/vomiting, and abdominal pain/diarrhea; (3) laboratory findings: thrombocytopenia (platelet count <150 109/l) and/or leukopenia (white blood cell count <4 109/l) and elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine phosphokinase (CK). Laboratory tests Between 2002 and 2004, patient serum samples were collected and sent via the Refik Saydam Hygiene Center to the National Reference Center for Arbovirus and Viral Hemorrhagic Fevers, Pasteur Institute, Lyon, France and the National Center for Infectious Diseases (NCID), Special Pathogen Branch of the Division of Viral and Rickettsial Disease (DVRD), CDC, Atlanta, USA. Between 2005 and 2007, serum samples were studied by the virology laboratory of Refik Saydam Hygiene Center. Patient serum samples were tested for anti-CCHF IgM and IgG antibodies by ELISA. CCHF virus RNA was investigated by RT-PCR, and direct sequence analysis was performed in these centers. Statistical analyses Statistical analyses were performed using SPSS 11.0 package program (SPSS Inc., Chicago, IL, USA). The Chi-square test was used. 382 G.R. Yilmaz et al. Results Between 2002 and 2007, a total of 1820 CCHF cases occurred (150 in 2002—2003, 249 in 2004, 266 in 2005, 438 in 2006, and 717 in 2007); 92 of these cases resulted in mortality. The mean fatality rate was 5% (4.5—6.2%). Because the case report form was only prepared in 2003 and the patient demographic data only collected from 2004, the tables presented in this report do not contain the data for 2002—2003. Of the CCHF cases, 53% were male and 47% were female. The mean age of the patients was 44 years Table 1 (range 1—92 years). Evaluation of the age distribution of the patients showed that fewer patients were aged under 10 years or over 80 years. The distribution of patients according to occupation showed that most were homemakers (36.4%), followed by farmers (34.1%), and those working in the animal husbandry sector (6.6%). The disease was most common in the months of June and July (Table 1). Of the CCHF cases, 68.9% had a history of tick-bite or tick contact and 61.7% had a history of close contact with animals. One case was a baby who was infected through breastfeeding (Table 2). Fatigue, fever, myalgia, and headache The epidemiological characteristics of patients with a diagnosis of Crimean-Congo hemorrhagic fever. Gender Male Female Age groups (years) 0—9 10—19 20—29 30—39 40—49 50—59 60—69 70—79 80—89 90—99 Location of residence Village Town City center Occupation Undeclared Farmer Homemaker Student or government worker Worker Working in animal husbandry or as a shepherd Unemployed Child Other, retired, butcher Healthcare workera Month of disease incidence March April May June July August September October Total 2004, n (%) 2005, n (%) 2006, n (%) 2007, n (%) Total, n (%) 131 (52.6) 118 (47.4) 130 (48.9) 136 (51.1) 249 (56.8) 189 (43.2) 375 (52.3) 342 (47.7) 885 (53.0) 785 (47.0) 25 102 85 96 108 128 106 56 10 1 59 210 206 230 268 285 254 136 20 2 5 29 32 30 44 39 48 21 0 1 (2.0) (11.6) (12.9) (12.0) (17.7) (15.7) (19.3) (8.4) (0.0) (0.4) 14 25 35 38 35 48 39 30 2 0 (5.3) (9.4) (13.1) (14.3) (13.1) (18.0) (14.7) (11.3) (0.8) (0.0) 15 54 54 66 81 70 61 29 8 0 (3.4) (12.3) (12.3) (15.1) (18.5) (16.0) (13.9) (6.6) (1.8) (0.0) (3.5) (14.2) (11.9) (13.4) (15.1) (17.9) (14.8) (7.8) (1.4) (0.1) (3.5) (12.6) (12.3) (13.8) (16.0) (17.1) (15.2) (8.1) (1.2) (0.1) 183 (73.5) 48 (19.3) 18 (7.2) 185 (69.5) 50 (18.8) 31 (11.7) 298 (68.0) 97 (22.1) 43 (9.8) 493 (68.8) 154 (21.5) 70 (9.7) 15 85 105 11 3 14 (6.0) (34.1) (42.2) (4.4) (1.2) (5.6) 7 85 115 14 2 14 (2.6) (32.0) (43.2) (5.3) (0.8) (5.3) 46 165 140 31 2 24 (10.5) (37.7) (32.0) (7.1) (0.5) (5.5) 65 234 248 41 10 59 (9.1) (32.6) (34.6) (5.7) (1.4) (8.2) 133 569 608 97 17 111 (8.0) (34.1) (36.4) (5.8) (1.0) (6.6) (3.2) (0.4) (2.8) (0.0) 7 15 5 2 (2.6) (5.6) (1.9) (0.8) 17 5 6 2 (3.9) (1.1) (1.4) (0.5) 15 16 27 2 (2.1) (2.2) (3.8) (0.3) 47 37 45 6 (2.8) (2.2) (2.7) (0.4) 8 1 7 0 2 8 37 66 105 28 2 1 249 (0.8) (3.2) (14.9) (26.5) (42.2) (11.2) (0.8) (0.4) (100.0) 0 10 40 72 99 36 4 5 266 (0.0) (3.8) (15.0) (27.1) (37.2) (13.5) (1.5) (1.9) (100.0) 4 31 56 183 128 35 1 0 438 (0.9) (7.1) (12.8) (41.8) (29.2) (8.0) (0.2) (0.0) (100.0) 3 27 150 259 210 53 15 0 717 (0.4) (3.8) (20.9) (36.1) (29.3) (7.4) (2.1) (0.0) (100.0) 1159 (69.4) 349 (20.9) 162 (9.7) 9 76 283 580 542 152 22 6 1670 (0.5) (4.6) (16.9) (34.7) (32.5) (9.1) (1.3) (0.4) (100.0) a In 2005, a nurse and healthcare technician contracted the disease by contamination via blood and body fluids. Both cases recovered. In 2006, a nurse contracted the disease by contact and died; the other case was a healthcare worker who had a history of tick-bite, thus, there was no nosocomial infection. In 2007, neither of the two healthcare workers had a history of contact with a CCHF patient; one had a history of tick-bite and the other had a history of living in rural areas. To sum up, starting from 2004, three nosocomial infection cases were reported to the MoH. The epidemiology of CCHF in Turkey, 2002-2007 383 Table 2 Possible risk factors for transmission and clinical and laboratory findings in patients with a diagnosis of Crimean-Congo hemorrhagic fever. Possible risk factors for transmission Tick-bite or tick contact Close contact with animals Contact with animal blood, tissue, or body fluids Contact with the body fluid of a CCHF patient or working at a laboratory a Individuals with similar complaints in the proximity of a CCHF patient 2004 (N = 249) n (%) 2005 (N = 266) n (%) 2006 (N = 438) n (%) 2007 (N = 717) n (%) Total (N = 1670) n (%) 137 (55.0) 140 (56.2) 32 (12.9) 169 (63.5) 177 (66 .5) 13 (4.9) 309 (70.5) 282 (64.4) 65 (14.8) 535 (74.6) 432 (60.3) 55 (7.7) 1150 (68.9) 1031 (61.7) 165 (9.9) 2 (0.8) 3 (1.1) 1 (0.2) 0 (0) 6 (0.4) 16 (6.4) 11 (4.1) 16 (3.7) 10 (1.4) 53 (3.2) Clinical findings Fever Headache Myalgia Fatigue Nausea Vomiting Abdominal pain Diarrhea Hemorrhagic findings b 221 185 196 239 193 142 120 91 93 (88.8) (74.3) (78.7) (96.0) (77.5) (57.0) (48.2) (36.5) (37.3) 230 164 167 253 161 112 79 79 90 (86.5) (61.7) (62.8) (95.1) (60.5) (42.1) (29.7) (29.7) (33.8) 396 300 318 399 274 196 138 98 106 (90.4) (68.5) (72.6) (91.1) (62.6) (44.7) (31.5) (22.4) (24.2) 646 489 483 651 452 266 212 146 95 (90.1) (68.2) (67.4) (90.8) (63.0) (37.1) (29.6) (20.4) (13.2) 1493 1138 1164 1542 1080 716 549 414 384 (89.4) (68.1) (69.7) (92.3) (64.7) (42.9) (32.9) (24.8) (23.0) Laboratory findings Leukopenia Thrombocytopenia Elevated AST and ALT Elevated LDH Elevated CK 221 239 226 202 183 (88.8) (96.0) (90.8) (81.1) (73.5) 236 249 235 219 189 (88.7) (93.6) (88.3) (82.3) (71.1) 387(88.4) 397 (90.6) 365 (83.3) 325 (74.2) 291 (66.4) 640 672 608 520 437 (89.3) (93.7) (84.8) (72.5) (60.9) 1484 1557 1434 1266 1100 (88.9) (93.2) (85.9) (75.8) (65.9) CCHF, Crimean-Congo hemorrhagic fever; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase; CK, creatine phosphokinase. a Three of six cases were healthcare workers with nosocomial infections, two cases were siblings, and one case was the breastfed baby of a nursing mother with a diagnosis of CCHF. b p < 0.05. were the most common clinical findings. Hemorrhagic findings were detected in 23.0% of the patients. IgM seropositivity was 65.1% in first blood samples and 86.4% in second blood samples. RT-PCR positivity was 45.3% in first blood samples and 24.7% in second blood samples. According to the case reporting forms, oral ribavirin treatment was applied in 67.9% of the CCHF cases in 2004. This rate was 21.8% in 2005, 16.2% in 2006, and 11.8% in 2007 (Table 3). Discussion In Turkey, the first cases with findings compatible with CCHF were reported to the Turkish MoH from the city of Tokat in 2002.16 In 2003, the disease was determined to be CCHF by laboratory confirmation. In 2004, the total number of cases was 249, which increased to 266 in 2005, 438 in 2006, and 717 in 2007. The gradual increase in the number of cases over the latter two years may have been associated with regional dispersion of the disease as well as increased awareness of healthcare personnel and the public about the disease. These data show that Turkey has become the country with the highest number of CCHF cases among those countries that report CCHF cases annually. Despite reports of the disease from the neighboring countries of Iran (mostly from the areas closer to the Pakistani border), Russia, and Bulgaria, the number of reported cases from these countries is much smaller than that reported from Turkey.1—3 The mean fatality rate for Turkey is about 5%. This rate has not changed over the years and is lower than the rate reported for other series from other parts of the world. The lower fatality rate in Turkey compared to the rates reported by other countries may be due to a better surveillance system, which facilitates the detection of cases with mild to moderate clinical findings, and the relatively better treatment facilities. In the regions where the disease is endemic, diagnosis of cases with mild clinical findings due to education and increased awareness of the healthcare personnel and public may have contributed to the low fatality rate. In addition, the CCHF strain determined in our country is significantly homologous with the strain detected in Russia and Kosovo (the old Yugoslavia).5 In CCHF cases caused by similar strains, the fatality rate has been found to be lower than those of other regions.19,20 384 Table 3 G.R. Yilmaz et al. The prognosis and treatment of patients with a diagnosis of Crimean-Congo hemorrhagic fever. 2004 (N = 249) n (%) 2005 (N = 266) n (%) 2006 (N = 438) n (%) 2007 (N = 717) n (%) Total (N = 1670) n (%) Outcome Cured Died 236 (94.8) 13 (5.2) 253 (95.1) 13 (4.9) 411 (93.8) 27 (6.2) 684 (95.4) 33 (4.6) 1584 (94.9) 86 (5.1) Treatment Ribavirin Supportive Untreated No data 169 37 14 29 58 106 2 100 71 94 0 273 85 615 4 13 (67.9) (14.9) (5.6) (11.6) (21.8) (39.8) (0.8) (37.6) The majority of cases in our country were from 15 cities in Kelkit Canyon and its environs, particularly the cities of Tokat, Sivas, Yozgat, Çorum, and Erzurum from which two thirds of cases were reported (Figure 1). With these characteristics, the disease is in an endemic state that is limited to a certain region. This has been associated with factors such as climatic features (temperature, humidity, etc.), geographical conditions, flora and wild life, the Figure 1 2007. (16.2) (21.5) (0) (62.3) (11.8) (85.8) (0.6) (1.8) 383 852 20 415 (22.9) (51.0) (1.2) (24.9) animal husbandry sector, and increased contact with animals and ticks.21 In a study by Tonbak et al. from our country, 47% of the tick species collected from domestic animals were Rhipicephalus bursa and 46% were Hyalomma marginatum marginatum. In the same study CCHF was detected in 9.09% of the R. bursa pool and 3.22% of the H. m. marginatum pool.9 Both tick species play a role in CCHF transmission.22 Incidence rates (number of cases/100 000) of Crimean-Congo hemorrhagic fever in the cities with the highest prevalence, The epidemiology of CCHF in Turkey, 2002-2007 Evaluation of the epidemiological characteristics of 1670 cases (2004—2007) showed that the female to male ratio was similar. The disease is common in the rural areas of the region and in the actively working age group. Nearly two thirds of the patients were farmers and homemakers in the rural areas. In Turkey, the population defined as homemakers in rural areas is made up of active workers in the agricultural and animal husbandry sectors. The occupations at risk for CCHF have primarily been those that are engaged in animal husbandry and farming, which involve the risk of contact with ticks.8,23—26 The incidence rate of the disease among healthcare workers is very low in Turkey. The number of cases with nosocomial CCHF infection has been limited to three. This might have been due to high compliance of healthcare workers in the region with the established standard measures and isolation methods for protection from the disease. In Turkey, the disease occurs between the months of March and October with peak levels in June and July. Nearly 70% of the cases were reported in the months of June and July, which are the months of intensive work for those working in agriculture and the animal husbandry sector. In the earlier years, the peak number of cases occurred in July; however, in the last two years (2006 and 2007) this peak occurred in June. This may be associated with earlier activation of the tick population due to global warming. Evaluation of transmission routes has shown that nearly 70% of cases had a history of tick contact. Strikingly, the same rate was found in those with a history of close contact with animals and/or animal blood or body tissue. As is known, infection progresses asymptomatically in domestic animals such as sheep, goats, and cattle, and close contact with animals in the viremic stage has been established in the literature as one of the transmission routes.22,27,28 In our country, the primary route of transmission in cases with no history of tick contact is close contact with animals. Contact with a patient’s blood or excretions is another route of transmission. In the literature, epidemics by this transmission route have been reported.29—31 In Turkey, there have been six reported cases, three in healthcare workers, two in siblings, and one in a breastfed baby of a nursing mother with CCHF; all had a history of contact with a CCHF patient. Evaluation of clinical findings showed that the most common symptoms were fatigue, fever, myalgia, and headache. The most common symptoms reported in the literature have been fever, fatigue, headache, loss of appetite, and myalgia.3,8,22,32,33 In the cases from our country, hemorrhagic findings were detected in almost a quarter of cases. The rate of cases with hemorrhagic findings has gradually decreased over the years ( p < 0.05; Table 2), and this may be attributed to diagnosis of cases with mild to moderately severe findings due to increased awareness of healthcare personnel and patients about the disease. Primary laboratory findings in patients diagnosed with CCHF are thrombocytopenia, leukopenia, and increased levels of transaminases.1,7,8,22,27 In the cases from our country, thrombocytopenia was the most common laboratory finding (in 93.2% of cases). This was followed by leukopenia (88.9%) and elevated levels of transaminase (85.9%). Ribavirin treatment was started in nearly one third of the patients with data for treatment options on their reporting forms. Despite some missing data, ribavirin use for treatment 385 purposes has gradually decreased over the years. Currently, there are no Food and Drug Administration approved antiviral agents for the treatment of CCHF.22 Ribavirin has been shown to inhibit in vitro viral replication.18,34 In Turkey, it has been in use in clinical practice by some centers for treatment purposes. The treatment efficacy of ribavirin in CCHF remains unclear. Nevertheless, the literature reveals studies reporting its efficiency in treatment and prophylaxis.31,35—38 Some studies from our country have reported a decreased mortality rate among severe cases who were given oral ribavirin treatment, while other studies have reported that ribavirin has no effects on mortality.6,8,39 CCHF remains a seasonal problem in the Mid-Eastern Anatolia region of Turkey. The Turkish Ministry of Health has been conducting studies on the reporting, diagnosis, and treatment of the disease. We believe that the data collected in Turkey on CCHF will significantly contribute to the literature. Conflict of interest: No conflict of interest to declare. References 1. Papa A, Christova I, Papadimitriou E, Antoniadis A. CrimeanCongo hemorrhagic fever in Bulgaria. Emerg Infect Dis 2004;10: 1465—7. 2. ProMED-mail (Program of the International Society for Infectious Diseases). Crimean-Congo hemorrhagic fever Kazakhstan, Russia; 2007. Available at: http://www.radiomayak.ru/doc. html?id=25314&cid= (accessed July 2007). 3. Alavi-Naini R, Moghtaderib A, Koohpayeha HR, Sharifi-Mooda B, Naderia M, Metanata M, et al. Crimean-Congo hemorrhagic fever in Southeast of Iran. J Infect 2006;52:378—82. 4. Al-Tikriti SK, Al-Ani F, Jurji FJ, Tantawi H, Al-Moslih M, Al-Janabi N, et al. Congo/Crimean haemorrhagic fever in Iraq. Bull World Health Organ 1981;59:85—90. 5. Karti SS, Odabasi Z, Korten V, Yilmaz M, Sonmez M, Caylan R, et al. Crimean-Congo hemorrhagic fever in Turkey. Emerg Infect Dis 2004;10:1379—84. 6. 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—7. 7. Bakir M, Ugurlu M, Dokuzoguz B, Bodur H, Tasyaran MA, Vahaboglu H, the Turkish CCHF Study Group. Crimean-Congo haemorrhagic fever outbreak in Middle Anatolia: a multicentre study of clinical features and outcome measures. J Med Microbiol 2005;54:385—9. 8. Ozkurt Z, Kiki I, Erol S, Erdem F, Yilmaz N, Parlak M, et al. Crimean-Congo hemorrhagic fever in Eastern Turkey: clinical features, risk factors and efficacy of ribavirin therapy. J Infect 2006;52:207—15. 9. Tonbak S, Aktas M, Altay K, Azkur AK, Kalkan A, Bolat Y, et al. Crimean-Congo hemorrhagic fever virus: genetic analysis and tick survey in Turkey. J Clin Microbiol 2006;44:4120—4. 10. 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—4. 11. Ergonul O, Tuncbilek S, Baykam N, Celikbas A, Dokuzoguz B. Evaluation of serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-a in patients with Crimean-Congo hemorrhagic fever. J Infect Dis 2006;193:941—4. 12. 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