INTRODUCTION — Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease transmitted by ticks and characterized by fever and hemorrhage [1,2]. It was first described in Soviet soldiers in the Crimea in 1944 and was named Crimean fever. In 1956, the virus was isolated from a child with similar symptoms and was named Congo virus [3]. The causative agent of both illnesses was shown to be the same virus, which was subsequently termed CCHF virus [4]. CCHF infects a range of animals; humans are the only known host that develops disease.
EPIDEMIOLOGY — CCHF is an emerging infectious disease given the expanding distribution of its main vector, ticks of the genus Hyalomma. Each year, more than 1000 human cases are reported from southeastern Europe and western Asia [5-7]. The primary means of transmission to humans is via tick bites.
Geography and season — CCHF is endemic in parts of Africa, the Middle East, Asia, and southeastern Europe [5,6,8]. CCHF virus (CCHFV) has been observed in over 30 countries, including in Africa (Democratic Republic of Congo, South Africa, Nigeria, Senegal, Uganda, Tanzania, Mauritania, Kenya), Asia (Pakistan, Afghanistan, Tajikistan, Uzbekistan, Kazakhstan, China), the Middle East (Iran, Iraq, United Arab Emirates, Saudi Arabia, Oman), and southeastern Europe (the Russian Federation, Bulgaria, Albania, Kosovo, Turkey, Greece, and Spain) (figure 1) [5,8-11]. Emergence of CCHF in India was reported in 2011 [12], and CCHF in Spain was first reported in 2016 [8,13]. Between 1998 and 2013, CCHF occurred most frequently in Turkey, Russia, Iran, Pakistan, and Afghanistan [7,14].
In the Northern Hemisphere, transmission of CCHFV is common between May and September, with a peak incidence in June and July [15]. In Pakistan, CCHF has biannual peaks between March and May and between August and October [16]. In Turkey, there is peak transmission in early summer months and a strong association with living at altitude greater than 836.5 m [17]. Seasonal transmission at moderate altitudes, typically around 1000 m, has been reported in other studies, presumably reflecting optimum conditions for tick populations [18,19].
Ticks — CCHFV is primarily transmitted via hard-bodied Hyalomma ticks of the family Ixodes, particularly Hyalomma marginatum [20]. The geography of CCHF infection reflects the distribution of Hyalomma ticks, which have a northern geographic limit of 48° north latitude [21]. CCHFV has also been isolated from Rhipicephalus, Boophilus, and Dermacentor spp, which may also transmit the virus [22].
The most common viral reservoirs are domestic livestock (sheep, goat, cattle, and pig), which are infected by adult ticks. Larvae and nymphs tend to feed on rodents, hares, hedgehogs, and ground-dwelling birds, which serve as amplifying hosts for the virus [2]. Hyalomma ticks have a two-year life cycle (figure 2), and blood meals are required for development at each life cycle stage. Ticks can remain attached for 2 to 13 days; after completion of feeding, the ticks detach from the host and begin to search for new hosts. The virus begins to multiply within 36 hours of attachment [23]; it does not have the ability to survive outside the host but may persist in infected body fluids such as blood, stool, or vomit.
Ticks survive most readily in relatively warm, dry habitats. Tick density increases markedly following a preceding mild winter and in the setting of diminished rainfall; these conditions are associated with increased numbers of human CCHF cases [24,25].
Changing tick habitats and elimination of usual host animals may lead to an increase in the spread of tick-borne disease [26]. Environmental factors associated with CCHF infection include livestock grazing at the edge of forests and presence of scrub and herbaceous vegetation [27,28]. (See 'Disease emergence' below.)
Disease emergence — The incidence of CCHF appears to be increasing. Possible causes of CCHF outbreaks include changing agricultural practices, climate change [29-31], movement of domestic animals [31-33], migrating birds [34,35], increasing numbers of susceptible animals, and increasing tick populations [5,9]. Changing agriculture practices such as deforestation and irrigation projects may be associated with increased contact with vectors [22,32]. Conversely, reducing agricultural activities may be associated with increases in wildlife and numbers of ticks in a particular area; subsequent utilization of such areas for farming may be associated with CCHF outbreaks [3,36]. Increased diagnostic awareness may also play a role in the apparent increased incidence [12].
Transmission — CCHF is transmitted via ticks, direct contact with blood or other bodily fluids of infected animals, nosocomial transmission, and vertical transmission.
CCHF is most commonly transmitted via tick bites or crushing ticks with bare fingers. Ticks can attach to all sites of the human body, including the trunk, extremities, and head and neck [37]; H. marginatum commonly attaches to the trunk [38].
Transmission can also occur via direct contact with blood or other bodily fluids of livestock; abattoir workers and farmers are at increased risk for infection [2,39-41]. In a large epidemiologic study including more than 1800 cases of CCHF, 69 percent of patients reported a history of tick bite or tick contact, 62 percent reported close contact with animals, and 10 percent had history of direct contact with animal body fluids or tissue [15].
The risk of community-based transmission to close contacts and relatives of patients with CCHF is low [42-44]. Relatives and caregivers should avoid direct contact with infected patients and their blood/bodily fluids, wear gloves and protective clothes, and wash hands regularly. Personal items such as razors or toothbrushes should not be shared.
Nosocomial transmission of CCHFV has been described [45-47]. The risk is highest during later stages of disease, which are associated with higher viral loads as well as diarrhea, vomiting, and hemorrhage [48]. Direct contact with blood and body fluids, needle-stick injuries, and splash exposures are common causes of nosocomial transmission [48-51]. Health care personnel are also at risk of infection during aerosol-generating procedures [52,53]. Transmission between patients sharing the same hospital room has occurred, likely due to contact with infected blood or body fluids [54]. (See 'Infection control' below.)
Vertical (mother-to-child) transmission of CCHFV has been described; in such cases, fetal prognosis may be guarded [55,56]. Thus far, breastfeeding has not been associated with CCHFV transmission [57]. The role of sexual transmission is uncertain [58,59]; CCHF with epididymoorchitis has been described [60] as has detection of CCHFV in urine [61,62].
The risk of laboratory exposure to CCHFV while processing blood samples is low if routine laboratory procedures are followed [48].
Risk groups — Individuals at risk for CCHFV infection include agricultural workers, individuals in rural areas engaged in animal husbandry, abattoir workers, veterinarians, leather factory workers in areas with high tick density, campers and hikers, hunters, soldiers, health care workers, and travelers to endemic areas (particularly in the setting of exposure to farming and slaughtering) [2,39,53,63-69].
In high-risk populations, the seroprevalence of CCHFV infection is 10 to 14 percent [70-72]. Independent risk factors for seropositivity include history of tick bite, manually removing ticks from animals, animal husbandry or farming, age >60 years, and residence in a rural area [70-73]. Data are insufficient regarding the risk of CCHFV infection in immunocompromised hosts.
VIROLOGY — CCHF virus (CCHFV) is a member of the Nairovirus genus within the family Bunyaviridae, which contains negative-stranded, enveloped RNA viruses. The genome of CCHFV has three segments, which are small (S), medium (M), and large (L). Based on the CCHFV S-segment sequences, CCHFV strains have seven clades in different geographical locations [9,74-78]. All Balkan strains are clustered in the same branch [79], and they are closely related to Turkish and southwestern Russian strains [9]. Detection of several viral variants and differences in clade distribution have been demonstrated over time [80], and cross-border movements of livestock may have contributed to the insertion of new clades into countries and spread of the disease [81]. Wild birds have also been shown to have the capacity to carry ticks containing CCHFV to different geographic areas [34].
CLINICAL MANIFESTATIONS — The spectrum of clinical manifestations ranges from subclinical illness (88 percent) to acute infection with hemorrhage and multiorgan failure [15,70]. The incubation period ranges from 1 to 13 days; it correlates with viral load and the type of transmission. The incubation period following tick bite is typically one to three days; the incubation period following contact with blood and body fluids is typically three to seven days [82,83]. Relatively short incubation periods have been described in cases due to nosocomial infection during later stages of disease, which are associated with high viral loads as well as diarrhea, vomiting, and hemorrhage [48,84].
Clinical manifestations of CCHF include sudden onset of fever, headache, malaise, myalgia, sore throat, dizziness, conjunctivitis, photophobia, abdominal pain, nausea, and vomiting [1,15,85,86]. One case series including more than 1600 patients with CCHF reported frequency of clinical manifestations as follows: fever (89 percent), headache (68 percent), myalgia (70 percent), fatigue (92 percent), nausea (65 percent), vomiting (43 percent), diarrhea (25 percent), and hemorrhage (23 percent) [15]. Rales are generally associated with pulmonary hemorrhage [87]. Ocular findings include subconjunctival and retinal hemorrhage, which may occur in the absence of visual complaints [88]. Other clinical findings include tachycardia, hepatomegaly, lymphadenopathy, and confusion.
The initial period of nonspecific symptoms generally lasts up to seven days and is followed by either recovery or progression to severe disease [89]. The convalescence period in recovering patients generally lasts up to four weeks with no long-term sequelae.
In severe cases, hemorrhagic manifestations are observed; these include petechiae (picture 1), ecchymoses (picture 2 and picture 3), epistaxis, and gum bleeding (picture 4). Pulmonary hemorrhage, intra-abdominal bleeding, hematuria, melena, and vaginal bleeding (heavy menstrual bleeding or early menstrual bleeding) can also occur. Severe disease is thought to be due to an exaggerated proinflammatory cytokine response ("cytokine storm"), causing endothelial cell activation and increased vascular permeability, resulting in hypotension, shock, multiple organ failure, and death [90-94].
Laboratory findings may include thrombocytopenia, leukopenia, hyperbilirubinemia with elevated transaminases, and prolongation of international normalized ratio, prothrombin time, and activated partial thromboplastin time [15,95]. Anemia is observed in some cases. In the setting of multiorgan failure, elevated blood urea nitrogen, creatinine, and creatine phosphokinase may be present. Patients with disseminated intravascular coagulation have decreased fibrinogen levels and increased fibrin-degradation products [46].
DIAGNOSIS — The diagnosis of CCHF should be suspected in patients presenting with fever and bleeding who have relevant geographic and epidemiologic risk factors (including exposure to an endemic region within the previous two weeks in addition to known tick bite and/or contact with animal tissue or body fluids). (See 'Epidemiology' above.)
Diagnostic tools include detection of CCHF virus (CCHFV) RNA by reverse-transcriptase polymerase chain reaction (RT-PCR) and specific immunoglobulin (Ig)M and IgG by enzyme-linked immunosorbent assay. In endemic areas, diagnostic testing may be limited to reference laboratories. If available, RT-PCR is preferred; this test allows rapid and accurate diagnosis of CCHFV with high sensitivity and specificity [96-98]. Specific IgM and IgG antibodies are detectable five days from the onset of symptoms [99], and IgG antibodies can remain detectable for at least five years [2]. Specific IgM positivity in a single sample indicates current infection, and seroconversion or fourfold rise of CCHFV IgG antibody levels in paired sera confirm recent or current infection [2].
CCHFV can be cultured in cell culture; this requires biosafety level 4 laboratories and is only used for research purposes.
DIFFERENTIAL DIAGNOSIS — The differential diagnosis depends on the geographic region and includes:
●Other viral hemorrhagic fevers – Other viruses capable of causing hemorrhagic fever include dengue, Ebola, Marburg, Lassa, and yellow fever. These illnesses can all cause severe multiorgan system illness accompanied by hemorrhage. The diseases may be distinguished based on relevant epidemiologic exposure and polymerase chain reaction or serologic testing. (See "Dengue virus infection: Clinical manifestations and diagnosis" and "Clinical manifestations and diagnosis of Ebola virus disease" and "Marburg virus" and "Yellow fever: Epidemiology, clinical manifestations, and diagnosis" and "Lassa fever".)
●Malaria – Clinical manifestations of malaria include fever, chills, malaise, fatigue, diaphoresis, headache, cough, anorexia, nausea, vomiting, abdominal pain, diarrhea, arthralgias, and myalgias. The diagnosis is established by microscopy or rapid diagnostic testing. (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children" and "Laboratory tools for diagnosis of malaria".)
●Rickettsial infection – Certain rickettsial infections (such as scrub typhus, African tick bite fever) may begin insidiously or abruptly; most patients develop high fever, headache, and myalgias, and an eschar or rash may develop in a subset of patients. The diagnosis is confirmed via serology. (See "Scrub typhus: Clinical features and diagnosis" and "Other spotted fever group rickettsial infections".)
●Q fever – Acute Q fever most commonly presents as a flu-like illness, pneumonia, or hepatitis, typically in association with animal exposure. The diagnosis is established via serology. (See "Clinical manifestations and diagnosis of Q fever".)
●Brucellosis – Acute brucellosis usually consists of fever, night sweats, arthralgias, myalgias, low back pain, and weight loss as well as weakness, fatigue, malaise, headache, dizziness, depression, and anorexia; it is transmitted via unpasteurized dairy products from infected animals. The diagnosis is established via culture or serology. (See "Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)
●Leptospirosis – Leptospirosis presents with the abrupt onset of fever, rigors, myalgias, and headache; conjunctival suffusion is an important sign. The diagnosis is established by serologic testing. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)
●Relapsing fever – Clinical manifestations of relapsing fever include acute febrile episodes punctuated by an intervening afebrile period; headache, neck stiffness, arthralgia, myalgia, and nausea may accompany the fever. The diagnosis is established by blood smear. (See "Clinical features, diagnosis, and management of relapsing fever".)
●Viral hepatitis – Clinical manifestations of viral hepatitis include jaundice, hepatomegaly, and elevated aminotransferases; the diagnosis is established via serology. (See "Hepatitis A virus infection in adults: Epidemiology, clinical manifestations, and diagnosis" and "Hepatitis B virus: Clinical manifestations and natural history" and "Hepatitis B virus: Screening and diagnosis" and "Screening and diagnosis of chronic hepatitis C virus infection".)
●Meningococcemia – Clinical manifestations of meningococcemia include fever, nausea, vomiting, headache, myalgias, and petechial rash. The diagnosis consists of isolation of Neisseria meningitidis by culture from a usually sterile body fluid, such as blood or cerebrospinal fluid. (See "Clinical manifestations of meningococcal infection" and "Diagnosis of meningococcal infection".)
In addition, noninfectious entities in the differential diagnosis include:
●Idiopathic thrombocytopenic purpura (ITP) – Clinical manifestations of ITP include bleeding (petechiae, epistaxis, purpura, and/or severe hemorrhage) and thrombocytopenia. The diagnosis is made following elimination of other potential causes of thrombocytopenia. (See "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis".)
●Acute leukemia – Clinical manifestations of acute leukemia may include signs and symptoms of anemia (eg, shortness of breath, dyspnea on exertion, pallor), excess bleeding or bruising, and infection. The diagnosis is established via bone marrow biopsy. (See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia".)
TREATMENT — There is no proven antiviral treatment for CCHF infection. Ribavirin has been studied in vitro, in animal models, and in some patients [100-104]; it has not been shown to reduce viral load or mortality in humans [85,105-110], and its clinical efficacy is controversial [85,107,111-114]. In addition, most of the studies evaluating the effectiveness of ribavirin are limited by methodology flaws [115]; further study is needed [114].
Management of CCHF consists of supportive care; in severe cases, blood product replacement is warranted [116]. Patients with CCHF should be managed in a health care center with appropriate facilities for diagnosis, treatment, and prevention of disease, including isolation precautions. (See 'Infection control' below.)
Data are insufficient to support routine use of steroids, intravenous immunoglobulin, or plasma exchange [116-119]. Use of hyperimmunoglobulin (which is prepared from the plasma of donors with antibody against CCHF) requires further study. Hyperimmunoglobulin can decrease viral load via direct neutralization, although viral strain variability may be an important determination in the use of this therapy [120].
Supportive care — Supportive treatment is essential for management of CCHF [116]. Careful attention should be paid to fluid balance and electrolytes. Mechanical ventilation, hemodialysis, vasopressor, and inotropic agents may be needed. Acetaminophen may be used for fever and pain management; ibuprofen and aspirin should be avoided as these agents can adversely affect normal clotting.
Platelet transfusion is warranted to maintain platelet count >50,000/mm3 in the setting of bleeding and for patients with platelet count <20,000/mm3 in the absence of bleeding [121]. The need for blood transfusion should be assessed based on the hemoglobin level as well as the general clinical status. Unnecessary interventional procedures should be avoided to minimize risk of bleeding.
In nonsevere cases, symptoms usually resolve in 7 to 10 days. In the absence of bleeding, transaminases and platelet counts tend to return to normal levels after 5 to 10 days.
Infection control
Precautions — Infection control precautions (including standard, contact, and droplet precautions) should be implemented to prevent nosocomial transmission of CCHF [9,122]. Patients with suspected or confirmed CCHF should be treated in isolation rooms [123]; if this is not possible, cohorting of patients is appropriate. The number of health care personnel entering patient rooms should be minimized. (See "Infection prevention: Precautions for preventing transmission of infection".)
Health care worker training about CCHF transmission, exposure prevention, hand hygiene, and use of personal protective equipment is essential [122,124]. Contact precautions include appropriate personal protective equipment (an impervious gown, gloves, mask, and eye/face protection) [122]. Respiratory protection (N95 mask or FFP3 respirator) is required during aerosol-generating procedures. Shoe covers are warranted when there is significant environmental contamination. It is essential to remove and dispose of personal protective equipment safely when leaving patient rooms [53,123,125].
Using "safe-sharps" systems help prevent needle-stick injuries. Principles of safe phlebotomy should be adhered to, and needles must not be recapped. All sharps and needles should be disposed of in hard containers and at the point of use.
Precautions may be discontinued for patients with no signs and symptoms of disease for at least three days, with a platelet count >50,000/mm3 and normal coagulation tests (international normalized ratio, prothrombin time, and activated partial thromboplastin time). If possible, a negative blood polymerase chain reaction for viral hemorrhagic fever should also be documented [126,127].
Postexposure management — The exposed individual should undergo a two-week period of monitoring for symptoms or signs of CCHF, including daily temperature measurement and weekly assessment of complete blood count measurement; no quarantine is required [82,128]. Development of a febrile illness during the monitoring period should prompt diagnostic testing. (See 'Diagnosis' above.)
The role of ribavirin for prevention of clinical illness when given as postexposure prophylaxis is uncertain [49,51,53,129,130]; further study is needed.
Environmental cleaning — CCHF virus (CCHFV) can be inactivated by disinfectants including 1% sodium hypochlorite (household bleach), 70% alcohol, 2% glutaraldehyde, hydrogen peroxide, and peracetic acid, and the virus is susceptible to high temperature at 56°C (133°F) for 30 minutes or 60°C (140°F) for 15 minutes. Areas contaminated with CCHFV can be disinfected with an approved hospital disinfectant or bleach [128]. Housekeeping staff should use personal protective equipment when cleaning.
PROGNOSIS — The mortality rate varies among countries and ranges from 2 to 80 percent [9,131-133]. Mortality rates in endemic countries are approximately 4 to 20 percent [7,134-138]. Most patients with CCHF live in rural areas and may have limited or delayed access to health care facilities, which may be associated with adverse outcomes.
CCHF is a notifiable disease in Turkey and Iran, and both countries have active surveillance and detection systems. Between 2002 and 2015, 9787 cases were reported to the Ministry of Health in Turkey, with a mortality rate of 4.8 percent [136]. The case-fatality rate is higher in nosocomial cases, probably due to high viral inoculum [125,139,140].
Independent predictors of mortality include presence of hemorrhage (particularly gastrointestinal bleeding and hematuria) [141], impaired consciousness [39,141], central nervous system involvement, diarrhea [142], splenomegaly [39], thrombocytopenia [141], leukocytosis, increased alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase [142,143], and decreased fibrinogen levels with a prolonged activated partial thromboplastin time [141-143]. In addition, CCHFV RNA level >107 copies/mL is an important indicator for mortality (positive predictive value 80 percent, sensitivity 89 percent, specificity 93 percent) [144,145].
Severity scoring systems have been developed based on these factors [143,146-148]; further prospective studies are needed.
PREVENTION — Prevention consists of avoiding tick exposure and avoiding contact with animal bodily fluids. Issues related to prevention of nosocomial transmission are discussed above. (See 'Infection control' above.)
Residents of and travelers to endemic areas should be educated regarding personal protection measures to avoid tick bites [69,82]. Wearing light-colored clothing allows easy detection of ticks, and tucking shirts into pants and pants into socks is helpful to minimize exposure. The use of a 20 to 30% N,N-diethyl-m-toluamide (DEET) repellant for skin provides some protection, and permethrin-treated clothes also help to prevent tick bites. Grassy areas should be avoided in warm seasons when ticks are most active. Ticks should not be handled with bare hands and should not be crushed or squeezed. Skin and clothes should be examined regularly for presence of ticks, and attached ticks should be removed with tweezers. Following tick removal, the skin should be cleaned with antiseptic. (See "Prevention of arthropod and insect bites: Repellents and other measures".)
Control of CCHF in animals is difficult. Restricted areas should be established for slaughtering. To reduce the risk of human infection during slaughtering, animals should be quarantined for 14 days before slaughtering [149]. Quarantine could also be applied to imported cattle [150].
Acaricides are effective against ticks in livestock and should be applied to animals prior to entering slaughterhouses. All butchers and slaughters should be educated for preventive measures [149]. Impervious protective clothes and gloves should be worn during slaughtering, butchering, and handling of animals [2].
There is no approved vaccine for use in humans or animals. An inactivated suckling mouse brain–derived vaccine developed for CCHF is used in Bulgaria; it is given in three doses with a booster dose after five years and affords variable protection [151]. Virus-neutralizing activity of this vaccine is low, and repeated doses are necessary to achieve adequate neutralizing antibody levels [152]. Another vaccine based on CCHF virus glycoproteins is under development [153,154]; further study is needed.
SUMMARY
●Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease transmitted by ticks and characterized by fever and hemorrhage. CCHF is endemic in parts of Africa, the Middle East, Asia, and southeastern Europe (figure 1). In the Northern hemisphere, transmission of CCHF virus (CCHFV) is common between May and September; ticks survive most readily in relatively warm, dry habitats. (See 'Introduction' above and 'Epidemiology' above.)
●CCHFV is most commonly transmitted via ticks or direct contact with bodily fluids of infected animals; nosocomial transmission can also occur. Individuals in rural endemic areas working in animal husbandry are at highest risk for infection. The incubation period following tick bite is typically one to three days; the incubation period following contact with blood and body fluids is typically three to seven days. (See 'Transmission' above and 'Clinical manifestations' above.)
●Clinical manifestations of CCHF include sudden onset of fever, headache, malaise, myalgia, sore throat, dizziness, conjunctivitis, photophobia, abdominal pain, nausea, and vomiting. In severe cases, hemorrhagic manifestations (petechiae, ecchymoses, epistaxis, and gum bleeding) are observed. Laboratory findings include thrombocytopenia, leukopenia, hyperbilirubinemia with elevated transaminases, and prolongation of prothrombin time and partial thromboplastin time. (See 'Clinical manifestations' above.)
●The diagnosis of CCHF should be suspected in patients presenting with fever and bleeding who have relevant geographic and epidemiologic risk factors. Diagnostic tools include detection of CCHFV RNA by reverse-transcriptase polymerase chain reaction (RT-PCR) and serology. If available, RT-PCR is preferred. Specific immunoglobulin (Ig)M and IgG antibodies are detectable five days from the onset of symptoms. (See 'Diagnosis' above.)
●Management of CCHF consists of supportive care; in severe cases, blood product replacement is warranted. Careful attention should be paid to fluid balance and electrolytes. Mechanical ventilation, hemodialysis, vasopressor, and inotropic agents may be needed. Acetaminophen may be used for fever and pain management; ibuprofen and aspirin should be avoided as these agents can adversely affect normal clotting. (See 'Treatment' above.)
●Patients with CCHF should be managed in a health care center with appropriate facilities for management and prevention of infection. Infection control precautions (including standard, contact, and droplet precautions) must be implemented to prevent nosocomial transmission. (See 'Infection control' above.)
●Prevention of CCHF consists of avoiding tick exposure and avoiding contact with animal bodily fluids. (See 'Prevention' above.)
1 : A nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part I. Clinical features.
2 : Crimean-Congo hemorrhagic fever.
3 : The epidemiology of tick-borne Crimean-Congo hemorrhagic fever in Asia, Europe, and Africa.
4 : Congo virus: a hitherto undescribed virus occurring in Africa. I. Human isolations--clinical notes.
5 : The impact of Crimean-Congo hemorrhagic fever virus on public health.
6 : Crimean-Congo hemorrhagic fever: risk for emergence of new endemic foci in Europe?
7 : Crimean-Congo hemorrhagic fever: A neglected infectious disease with potential nosocomial infection threat.
8 : Autochthonous Crimean-Congo Hemorrhagic Fever in Spain.
9 : Crimean-Congo haemorrhagic fever in Eurasia.
10 : Recent advances in research on Crimean-Congo hemorrhagic fever.
11 : Notes from the Field: Crimean-Congo Hemorrhagic Fever Outbreak - Central Uganda, August-September 2017.
12 : Crimean Congo hemorrhagic fever: requires vigilance and not panic.
13 : First outbreak of Crimean-Congo haemorrhagic fever in western Europe kills one man in Spain.
14 : Crimean-Congo hemorrhagic fever infections reported by ProMED.
15 : The epidemiology of Crimean-Congo hemorrhagic fever in Turkey, 2002-2007.
16 : Bi-annual surge of Crimean-Congo haemorrhagic fever (CCHF): a five-year experience.
17 : The geographic distribution of cases of Crimean-Congo hemorrhagic fever: Kastamonu, Turkey.
18 : Crimean-Congo hemorrhagic fever cases in the eastern Black Sea region of Turkey: Demographic, geographic, climatic, and clinical characteristics
19 : Epidemiologic features and risk factors of Crimean-Congo hemorrhagic fever in Samsun province, Turkey.
20 : Evolution of Crimean-Congo Hemorrhagic Fever virus.
21 : Emergence of Crimean-Congo haemorrhagic fever in Greece.
22 : Changing patterns of tickborne diseases in modern society.
23 : Crimean-Congo haemorrhagic fever virus replication in adult Hyalomma truncatum and Amblyomma variegatum ticks.
24 : Variable strength of forest stand attributes and weather conditions on the questing activity of Ixodes ricinus ticks over years in managed forests.
25 : Effects of climate change on ticks and tick-borne diseases in europe.
26 : Guineafowl, ticks and Crimean-Congo hemorrhagic fever in Turkey: the perfect storm?
27 : The trend towards habitat fragmentation is the key factor driving the spread of Crimean-Congo haemorrhagic fever.
28 : Modeling the spatial distribution of crimean-congo hemorrhagic fever outbreaks in Turkey.
29 : Impact of climate trends on tick-borne pathogen transmission.
30 : Global warming may increase the incidence and geographic range of Crimean-Congo Hemorrhagic Fever.
31 : Crimean-congo hemorrhagic fever virus in ticks from imported livestock, Egypt.
32 : Possible drivers of Crimean-Congo hemorrhagic fever virus transmission in Kosova.
33 : Crimean-Congo hemorrhagic fever in Southeast of Iran.
34 : Role of migratory birds in spreading Crimean-Congo hemorrhagic fever, Turkey.
35 : Emergence of Crimean-Congo hemorrhagic fever.
36 : Drivers, dynamics, and control of emerging vector-borne zoonotic diseases.
37 : Tick attachment sites.
38 : Preferences of different tick species for human hosts in Turkey.
39 : Crimean-Congo haemorrhagic fever outbreak in Middle Anatolia: a multicentre study of clinical features and outcome measures.
40 : Crimean-Congo haemorrhagic fever in ostriches: A public health risk for countries of the European Union?
41 : Crimean-Congo hemorrhagic fever: experience at a tertiary care hospital in Karachi, Pakistan.
42 : Crimean-Congo haemorrhagic fever cases in Turkey.
43 : Investigation of Crimean-Congo hemorrhagic fever virus transmission from patients to relatives: a prospective contact tracing study.
44 : The risk of transmission of Crimean-Congo hemorrhagic fever virus from human cases to first-degree relatives.
45 : Nosocomial outbreak of viral hemorrhagic fever caused by Crimean Hemorrhagic fever-Congo virus in Pakistan, January 1976.
46 : A nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part III. Clinical pathology and pathogenesis.
47 : Crimean-Congo haemorrhagic fever and secondary bacteraemia in Turkey.
48 : Healthcare-associated Crimean-Congo haemorrhagic fever in Turkey, 2002-2014: a multicentre retrospective cross-sectional study.
49 : Is ribavirin prophylaxis effective for nosocomial transmission of Crimean-Congo hemorrhagic fever?
50 : Short report: Crimean-Congo hemorrhagic fever outbreak in Rawalpindi, Pakistan, February 2002.
51 : A nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part IV. Preventive and prophylactic measures.
52 : Probable Crimean-Congo hemorrhagic fever virus transmission occurred after aerosol-generating medical procedures in Russia: nosocomial cluster.
53 : Health care response to CCHF in US soldier and nosocomial transmission to health care providers, Germany, 2009.
54 : A case of nosocomial transmission of Crimean-Congo hemorrhagic fever from patient to patient.
55 : Favorable outcomes for both mother and baby are possible in pregnant women with Crimean-Congo hemorrhagic fever disease: a case series and literature review.
56 : Pregnancy and Crimean-Congo haemorrhagic fever.
57 : Breastfeeding in Crimean-Congo haemorrhagic fever.
58 : Potential sexual transmission of Crimean-Congo hemorrhagic fever infection.
59 : Possible sexual transmission of Crimean-Congo hemorrhagic fever.
60 : Crimean-Congo haemorrhagic fever presenting as epididymo-orchitis.
61 : Detection of Crimean-Congo hemorrhagic fever virus genome in saliva and urine.
62 : Review of Crimean Congo hemorrhagic fever infection in Kosova in 2008 and 2009: prolonged viremias and virus detected in urine by PCR.
63 : Sequencing and phylogenetic characterisation of a fatal Crimean - Congo haemorrhagic fever case imported into the United Kingdom, October 2012.
64 : Non-fatal case of Crimean-Congo haemorrhagic fever imported into the United Kingdom (ex Bulgaria), June 2014.
65 : [Two cases of Crimean-Congo haemorrhagic fever (CCHF) in two tourists in Senegal in 2004].
66 : Clinical features of Crimean-Congo haemorrhagic fever in the United Arab Emirates.
67 : A preliminary report on Crimean-Congo haemorrhagic fever in Turkey, March - June 2008.
68 : Travellers and viral haemorrhagic fevers: what are the risks?
69 : Crimean-Congo haemorrhagic fever in travellers: A systematic review.
70 : Subclinical infections with Crimean-Congo hemorrhagic fever virus, Turkey.
71 : Crimean-Congo hemorrhagic fever virus in high-risk population, Turkey.
72 : The seroprevalance of Crimean-Congo haemorrhagic fever in people living in the same environment with Crimean-Congo haemorrhagic fever patients in an endemic region in Turkey.
73 : Seroprevalence of Crimean-Congo hemorrhagic fever virus, Bulgaria.
74 : Bayesian phylogeography of Crimean-Congo hemorrhagic fever virus in Europe.
75 : New circulating genomic variant of Crimean-Congo hemorrhagic fever virus in Iran.
76 : Crimean-Congo hemorrhagic fever virus genomics and global diversity.
77 : Molecular epidemiology of African and Asian Crimean-Congo haemorrhagic fever isolates.
78 : Towards an understanding of the migration of Crimean-Congo hemorrhagic fever virus.
79 : Crimean-Congo hemorrhagic fever in Bulgaria.
80 : Prevalence of Crimean-Congo hemorrhagic fever virus in healthy population, livestock and ticks in Kosovo.
81 : Relationship between Crimean-Congo hemorrhagic fever virus strains circulating in Iran and Turkey: possibilities for transborder transmission.
82 : Crimean-Congo hemorrhagic fever.
83 : Human Crimean-Congo hemorrhagic fever, Sénégal.
84 : Fatal nosocomial spread of Crimean-Congo hemorrhagic fever with very short incubation period.
85 : Efficacy of oral ribavirin treatment in Crimean-Congo haemorrhagic fever: a quasi-experimental study from Turkey.
86 : Epidemiologic and clinical features of Crimean-Congo hemorrhagic fever in southern Africa.
87 : Evaluation of respiratory findings in Crimean-Congo hemorrhagic fever.
88 : Ocular findings in patients with Crimean-Congo hemorrhagic fever.
89 : Crimean-Congo hemorrhagic fever.
90 : Pathogenesis of Crimean-Congo hemorrhagic fever.
91 : Evidence of vascular endothelial damage in Crimean-Congo hemorrhagic fever.
92 : Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity.
93 : Hemorrhagic fever virus-induced changes in hemostasis and vascular biology.
94 : Cytokine levels in Crimean-Congo hemorrhagic fever.
95 : Coagulopathy parameters in patients with Crimean-Congo hemorrhagic fever and its relation with mortality.
96 : Rapid and quantitative detection of Crimean-Congo hemorrhagic fever virus by one-step real-time reverse transcriptase-PCR.
97 : Novel one-step real-time RT-PCR assay for rapid and specific diagnosis of Crimean-Congo hemorrhagic fever encountered in the Balkans.
98 : Development of a real-time RT-PCR assay for the detection of Crimean-Congo hemorrhagic fever virus.
99 : [Evaluation of PCR and ELISA-IgM results in the laboratory diagnosis of Crimean-Congo haemorrhagic fever cases in 2008 in Turkey].
100 : Inhibition of Crimean-Congo hemorrhagic fever viral infectivity yields in vitro by ribavirin.
101 : Ribavirin efficacy in an in vivo model of Crimean-Congo hemorrhagic fever virus (CCHF) infection.
102 : Pathogenesis and immune response of Crimean-Congo hemorrhagic fever virus in a STAT-1 knockout mouse model.
103 : Evaluation of antiviral efficacy of ribavirin, arbidol, and T-705 (favipiravir) in a mouse model for Crimean-Congo hemorrhagic fever.
104 : Ribavirin Had Demonstrable Effects on the Crimean-Congo Hemorrhagic Fever Virus (CCHFV) Population and Load in a Patient With CCHF Infection.
105 : Effect of oral ribavirin treatment on the viral load and disease progression in Crimean-Congo hemorrhagic fever.
106 : A preliminary study to evaluate the effect of intravenous ribavirin treatment on survival rates in Crimean-Congo hemorrhagic fever.
107 : The efficacy of ribavirin in the treatment of Crimean-Congo hemorrhagic fever in Eastern Black Sea region in Turkey.
108 : Crimean-Congo hemorrhagic fever in Eastern Turkey: clinical features, risk factors and efficacy of ribavirin therapy.
109 : The role of ribavirin in the therapy of Crimean-Congo hemorrhagic fever: early use is promising.
110 : Ribavirin for Crimean-Congo hemorrhagic fever: systematic review and meta-analysis.
111 : Ribavirin is not effective against Crimean-Congo hemorrhagic fever: observations from the Turkish experience.
112 : The efficacy of oral ribavirin in the treatment of crimean-congo hemorrhagic fever in Iran.
113 : Ribavirin for patients with Crimean-Congo haemorrhagic fever: a systematic review and meta-analysis.
114 : Ribavirin for treating Crimean Congo haemorrhagic fever.
115 : The efficacy of ribavirin in Crimean-Congo hemorrhagic fever--randomized trials are urgently needed.
116 : Case management and supportive treatment for patients with Crimean-Congo hemorrhagic fever.
117 : Efficacy of high-dose methylprednisolone in patients with Crimean-Congo haemorrhagic fever and severe thrombocytopenia.
118 : A case of Crimean-Congo haemorrhagic fever successfully treated with therapeutic plasma exchange and ribavirin.
119 : Double filtration plasmapheresis for a case of Crimean-Congo hemorrhagic fever.
120 : Prompt administration of Crimean-Congo hemorrhagic fever (CCHF) virus hyperimmunoglobulin in patients diagnosed with CCHF and viral load monitorization by reverse transcriptase-PCR.
121 : Guidelines for the use of platelet transfusions.
122 : Recommended precaution procedures protect healthcare workers from Crimean-Congo hemorrhagic fever virus.
123 : Ebola and other viral haemorrhagic fevers.
124 : Crimean-Congo hemorrhagic fever: prevention and control limitations in a resource-poor country.
125 : Crimean-Congo hemorrhagic fever outbreak in Rawalpindi, Pakistan, February 2002: contact tracing and risk assessment.
126 : Crimean-Congo hemorrhagic fever outbreak in Rawalpindi, Pakistan, February 2002: contact tracing and risk assessment.
127 : Discharge criteria for Crimean-Congo haemorrhagic fever in endemic areas.
128 : Update: management of patients with suspected viral hemorrhagic fever--United States.
129 : Treatment and prophylaxis with ribavirin for Crimean-Congo Hemorrhagic Fever--is it effective?
130 : Crimean-Congo hemorrhagic fever among health care workers, Turkey.
131 : Clinical and epidemiologic features of Crimean-Congo hemorrhagic fever among children and adolescents from southeastern Iran.
132 : Crimean-Congo hemorrhagic fever in children.
133 : Crimean-Congo haemorrhagic fever among children in north-eastern Turkey.
134 : Current situation of Crimean-Congo hemorrhagic fever in Southeastern Europe and neighboring countries: a public health risk for the European Union?
135 : Crimean-Congo hemorrhagic fever in Iran.
136 : Crimean-Congo hemorrhagic fever in Turkey: Current status and future challenges.
137 : Crimean-Congo haemorrhagic fever virus in Kazakhstan (1948-2013).
138 : Crimean-Congo Haemorrhagic Fever: Breaking the chain of transmission.
139 : Outbreak of Crimean-Congo haemorrhagic fever in Quetta, Pakistan: contact tracing and risk assessment.
140 : Crimean-Congo hemorrhagic fever in Iran and neighboring countries.
141 : Clinical and laboratory features of Crimean-Congo hemorrhagic fever: predictors of fatality.
142 : Evaluation of clinical and laboratory predictors of fatality in patients with Crimean-Congo haemorrhagic fever in a tertiary care hospital in Turkey.
143 : The clinical pathology of Crimean-Congo hemorrhagic fever.
144 : Viral load as a predictor of outcome in Crimean-Congo hemorrhagic fever.
145 : Viral load as predictor of Crimean-Congo hemorrhagic fever outcome.
146 : Severity scoring index for Crimean-Congo hemorrhagic fever and the impact of ribavirin and corticosteroids on fatality.
147 : Validation of a severity grading score (SGS) system for predicting the course of disease and mortality in patients with Crimean-Congo hemorrhagic fever (CCHF).
148 : Association Between Severity Grading Score And Acute Phase Reactants In Patients With Crimean Congo Hemorrhagic Fever.
149 : Consensus report: Preventive measures for Crimean-Congo Hemorrhagic Fever during Eid-al-Adha festival.
150 : Current status of Crimean-Congo haemorrhagic fever in the World Health Organization Eastern Mediterranean Region: issues, challenges, and future directions.
151 : The Bulgarian vaccine Crimean-Congo haemorrhagic fever virus strain.
152 : Healthy individuals' immune response to the Bulgarian Crimean-Congo hemorrhagic fever virus vaccine.
153 : A novel vaccine against Crimean-Congo Haemorrhagic Fever protects 100% of animals against lethal challenge in a mouse model.
154 : A Crimean-Congo hemorrhagic fever (CCHF) viral vaccine expressing nucleoprotein is immunogenic but fails to confer protection against lethal disease.