crimean - congo hemorrhagic fever ( cchf ) is an arthropod - borne viral infection that infects domestic and wild animals and can be transmitted to humans via several routes . the causative agent of cchf is an rna virus of the genus nairovirus belonging to the bunyaviridae family of viruses ( 1 ) . over several decades , serious outbreaks with high case - fatality rates have been reported from different parts of the world , including the middle east ( 2 - 6 ) . cchf is becoming a global problem , and more cases are expected to be diagnosed as the disease becomes endemic to more areas due to movement of livestock , changes in hunting activities and agricultural practices ( 7 ) . a real threat exists to health care workers managing patients with cchf and causing nosocomial outbreaks , which may have high fatality rates ( 8) . another concern is related to the potential use of the virus as a weapon of bioterrorism , given the limited availability of diagnostic laboratory services with biosafety level 4 facilities ( 9 ) . cchf is not endemic to uae ; however , two documented limited outbreaks occurred in 1979 and 1994 and were associated with high mortality rates among infected health care workers ( 10 , 11 ) . here , on october 28 , 2010 , a previously healthy 24-year - old male butcher working in dubai abattoir complained of fever , headache , and right lower quadrant abdominal pain , which was managed symptomatically in a private clinic , and he was discharged home . two days later , he developed vomiting and non - bloody loose motions with generalized abdominal pain . he was admitted to another private hospital in dubai for workup as a case of acute abdomen . investigations on october 30 , 2010 , revealed the following : white blood cells ( wbc ) 11.8  10/l ( 87.9% neutrophils ) , hemoglobin ( hb ) 15.1 g / dl , platelets ( plt ) 145  10/l , creatinine 1.2 mg / dl , bilirubin 0.6 mg / dl , urine red blood cells ( rbc ) 10 - 15 , ast 196 u / l , inr 1.7 , ggt 55 chest x - ray was normal , and abdominal ultrasound showed a small right renal stone . on november 1 , 2010 , his condition deteriorated and he developed hematemesis and melena with worsening abdominal pain and continuous high spikes of temperature . repeated labs were as follows : wbc 5.96  10/l ( 88.2% neutrophils ) , hb 14.3 g / dl , plt 35  10/l . he was referred to our hospital for further evaluation and management of his fever , severe thrombocytopenia , and acute gastrointestinal bleeding . at the time of admission to our hospital , the patient was febrile ( 38.3c ) , his pulse rate was 120/minutes , and bp was 90/60 mmhg . investigations revealed wbc 14.1 ( neutrophilia with bandemia ) , hb 14.2 g / dl , plt 8  10/l , d - dimer 5.3 , urea 55 mg / dl , esr 120 mm in the first hour , ldh 3086 u / l , alt 72 u / l , pt 32.4 seconds , ptt 159.8 seconds , inr 3.34 , urine rbc 20 - 25 . the initial differential diagnosis included tauleremia , leptospirosis , and severe community - acquired bacterial infection , and accordingly he was started on levofloxacin , ceftriaxone , and gentamicin . a presumptive diagnosis of viral hemorrhagic fever ( most likely cchf ) was also entertained in view of his occupation , and a loading dose of intravenous ribavirin therapy was given a few hours later . the patient was transferred to a single room for isolation with barrier nursing , and strict infection - control measures were adopted to minimize the number of medical staff members in contact with the patient and eliminate exposure to the patient s body fluids . the patient s condition continued to deteriorate , and he developed respiratory compromise requiring mechanical ventilation . despite all supportive measures , maximum inotropic support , and iv ribavirin therapy , the patient died on november 4 , 2010 , due to severe dic and circulatory failure . a sample of the patient s blood and ticks collected from the abattoir were sent to a regional reference laboratory in saudi arabia , and polymerase chain reaction ( pcr ) testing for crimean - congo virus was positive for both samples . around 140 health care workers ( physicians , nurses , and laboratory staff ) came into variable degrees of contact with the patient or his body fluids during his admission to our hospital . they were classified into five groups according to their degree of contact : group 1 ( high risk ) : percutaneous contact with blood ( needle - sharp sticks or patient s blood contact with broken skin or mucosa ) : nil group 2 : patient s blood contact to unbroken skin : 3 group 3 : patient s body fluid contact to unbroken skin : 2 group 4 : physical contact with the patient without exchange of fluids : 32 group 5 : close proximity to the patient ( 1 m ) without physical contact : 103 concerned staff members were requested to measure their temperature twice daily and to report to the emergency room if they developed any febrile illness ( t > 38.3c ) or mucocutaneous bleeding . staff members in groups 1 and 2 were also counseled regarding post - exposure prophylactic ribavirin therapy . all individuals preferred close follow - up with an infectious disease specialist , and nobody received ribavirin therapy . in addition to health care workers , the patient s roommates , work colleagues , and close family members were contacted and interviewed and were advised to report to our hospital immediately in case they developed fever , loose motions , or bleeding . all were followed for 21 days post - exposure to the index case , and none of the medical staff in our hospital or the referring hospital nor any of his close contacts developed symptoms suggestive of acquiring the infection . it should be noted that no serological testing was carried out to document subclinical infection . another previously healthy young male ( 33 years old ) presented to a private hospital in dubai on november 23 , 2010 , with 5 days history of high - grade temperature , vomiting , and loose motions . on the day of admission , he developed hematemesis and melena . clinically , he was febrile , hypotensive , and tachycardic , with a generalized petechial rash . importantly , the patient was in dubai abattoir during the hajj holidays , a few days prior to the start of his illness . laboratory investigations revealed the following results : wbc 4.29  10/l , hb 17 g / dl , plt 40  10/l ( dropped to 26  10/l within a few hours of admission ) , creatinine 2.1 mg / dl , na 138 mmol / l , k 5.3 mmol / l , inr 1.947 , d - dimer > 20 . cchf was highly suspected in this case , and he was resuscitated and shifted to icu and mechanically ventilated , with a loading dose of intravenous ribavirin started immediately . a few hours later , he passed a large amount of fresh blood per rectum , his general condition worsened with uncontrolled circulatory collapse , and he died on the day of admission , 7 days after the start of illness . the patient s blood sample was sent to the same regional hospital for cchf viral pcr testing , and the results were confirmatory for cchf by pcr . similar infection - control measures were taken as in index case 1 , and no medical staff in our hospital or the referring hospital developed clinical infection . his wife and three children were also contacted , and they , too , did not develop the illness clinically . on october 28 , 2010 , a previously healthy 24-year - old male butcher working in dubai abattoir complained of fever , headache , and right lower quadrant abdominal pain , which was managed symptomatically in a private clinic , and he was discharged home . two days later , he developed vomiting and non - bloody loose motions with generalized abdominal pain . he was admitted to another private hospital in dubai for workup as a case of acute abdomen . investigations on october 30 , 2010 , revealed the following : white blood cells ( wbc ) 11.8  10/l ( 87.9% neutrophils ) , hemoglobin ( hb ) 15.1 g / dl , platelets ( plt ) 145  10/l , creatinine 1.2 mg / dl , bilirubin 0.6 mg / dl , urine red blood cells ( rbc ) 10 - 15 , ast 196 u / l , inr 1.7 , ggt 55 chest x - ray was normal , and abdominal ultrasound showed a small right renal stone . on november 1 , 2010 , his condition deteriorated and he developed hematemesis and melena with worsening abdominal pain and continuous high spikes of temperature . repeated labs were as follows : wbc 5.96  10/l ( 88.2% neutrophils ) , hb 14.3 g / dl , plt 35  10/l . he was referred to our hospital for further evaluation and management of his fever , severe thrombocytopenia , and acute gastrointestinal bleeding . at the time of admission to our hospital , the patient was febrile ( 38.3c ) , his pulse rate was 120/minutes , and bp was 90/60 mmhg . investigations revealed wbc 14.1 ( neutrophilia with bandemia ) , hb 14.2 g / dl , plt 8  10/l , d - dimer 5.3 , urea 55 mg / dl , esr 120 mm in the first hour , ldh 3086 u / l , alt 72 u / l , pt 32.4 seconds , ptt 159.8 seconds , inr 3.34 , urine rbc 20 - 25 . the initial differential diagnosis included tauleremia , leptospirosis , and severe community - acquired bacterial infection , and accordingly he was started on levofloxacin , ceftriaxone , and gentamicin . a presumptive diagnosis of viral hemorrhagic fever ( most likely cchf ) was also entertained in view of his occupation , and a loading dose of intravenous ribavirin therapy was given a few hours later . the patient was transferred to a single room for isolation with barrier nursing , and strict infection - control measures were adopted to minimize the number of medical staff members in contact with the patient and eliminate exposure to the patient s body fluids . the patient s condition continued to deteriorate , and he developed respiratory compromise requiring mechanical ventilation . despite all supportive measures , maximum inotropic support , and iv ribavirin therapy , the patient died on november 4 , 2010 , due to severe dic and circulatory failure . a sample of the patient s blood and ticks collected from the abattoir were sent to a regional reference laboratory in saudi arabia , and polymerase chain reaction ( pcr ) testing for crimean - congo virus was positive for both samples . around 140 health care workers ( physicians , nurses , and laboratory staff ) came into variable degrees of contact with the patient or his body fluids during his admission to our hospital . they were classified into five groups according to their degree of contact : group 1 ( high risk ) : percutaneous contact with blood ( needle - sharp sticks or patient s blood contact with broken skin or mucosa ) : nil group 2 : patient s blood contact to unbroken skin : 3 group 3 : patient s body fluid contact to unbroken skin : 2 group 4 : physical contact with the patient without exchange of fluids : 32 group 5 : close proximity to the patient ( 1 m ) without physical contact : 103 concerned staff members were requested to measure their temperature twice daily and to report to the emergency room if they developed any febrile illness ( t > 38.3c ) or mucocutaneous bleeding . staff members in groups 1 and 2 were also counseled regarding post - exposure prophylactic ribavirin therapy . all individuals preferred close follow - up with an infectious disease specialist , and nobody received ribavirin therapy . in addition to health care workers , the patient s roommates , work colleagues , and close family members were contacted and interviewed and were advised to report to our hospital immediately in case they developed fever , loose motions , or bleeding . all were followed for 21 days post - exposure to the index case , and none of the medical staff in our hospital or the referring hospital nor any of his close contacts developed symptoms suggestive of acquiring the infection . it should be noted that no serological testing was carried out to document subclinical infection . another previously healthy young male ( 33 years old ) presented to a private hospital in dubai on november 23 , 2010 , with 5 days history of high - grade temperature , vomiting , and loose motions . on the day of admission , he developed hematemesis and melena . clinically , he was febrile , hypotensive , and tachycardic , with a generalized petechial rash . importantly , the patient was in dubai abattoir during the hajj holidays , a few days prior to the start of his illness . laboratory investigations revealed the following results : wbc 4.29  10/l , hb 17 g / dl , plt 40  10/l ( dropped to 26  10/l within a few hours of admission ) , creatinine 2.1 mg / dl , na 138 mmol / l , k 5.3 mmol / l , inr 1.947 , d - dimer > 20 . chest x - ray was normal , and abdominal ultrasound revealed minimal ascites . cchf was highly suspected in this case , and he was resuscitated and shifted to icu and mechanically ventilated , with a loading dose of intravenous ribavirin started immediately . a few hours later , he passed a large amount of fresh blood per rectum , his general condition worsened with uncontrolled circulatory collapse , and he died on the day of admission , 7 days after the start of illness . the patient s blood sample was sent to the same regional hospital for cchf viral pcr testing , and the results were confirmatory for cchf by pcr . similar infection - control measures were taken as in index case 1 , and no medical staff in our hospital or the referring hospital developed clinical infection . his wife and three children were also contacted , and they , too , did not develop the illness clinically . cchf is not endemic in uae , and only sporadic cases with limited nosocomial outbreaks have been reported , including one from this hospital . regionally , the disease has been reported in oman , ksa , kuwait , iran , pakistan , india , and iraq ( 13 - 24 ) . in nonendemic gulf countries , the risk of acquiring human infection the risk seems to be greatest during hajj season , when hundreds of thousands of cattle are imported to the region for the ceremonial sacrifice . following initial infection by tick bite or contact with body fluids of an infected animal or human , four different phases of illness are recognized , as described first by hoogstraal in 1979 and subsequently by others ( 25 - 28 ) . not all patients pass through the same phases , depending on the severity of their illness and their response to therapy . our patient in case 1 initially presented to a private hospital in phase 2 ( pre - hemorrhagic ) , which progressed to phase 3 ( hemorrhagic ) , while the patient in case 2 came in the hemorrhagic phase with persistent fever and circulatory collapse . laboratory and imaging findings in this disease depend on the stage in which the patient presents . in the hemorrhagic phase , hepatic transaminases are elevated , and figures in the thousands can be seen with severe hepatic necrosis . found that age , male gender , high platelet levels , and high alt , ast , wbc , and ptt values and decrease in these values during follow - up are all indicative of a poor prognosis ( 12 ) . lactate dehydrogenase and creatinine kinases are nonspecifically elevated and have also been shown to be associated with poor outcome . ardalan et al . reported a case of cchf presenting as thrombotic microangiopathy and acute renal failure ( 29 ) . pulmonary manifestations of cchf include pleural effusion with or without hemothorax , diffuse alveolar hemorrhage , and ards ( 30 - 32 ) . engin et al . conducted a prospective study on 44 confirmed cases of cchf and found that patients with severe infection had lower left ventricular ejection fraction , higher systolic pulmonary artery pressure , and more frequent pericardial effusion compared with nonsevere cases and concluded that severe and fatal cchf cases have impaired cardiac functions , which could be linked to increased fatality in severe infections ( 33 ) . abdominal ultrasound can show ascites or organomegaly , as seen in our patient in case 2 . as highlighted above , the hallmark of cchf is bleeding diathesis resulting from vascular endothelial injury , which in turns leads to prolonged bleeding time , pt , aptt , elevated fibrinogen degradation products , and decreased fibrinogen ( 34 ) . in both cases discussed here , inr was raised at the beginning of presentation although higher in case 2 and later progressed to dic . the confirmation of cchf infection relies on antibody detection by elisa , antigen detection , virus isolation and pcr tests . these tests should be performed in high biosafety - level laboratories . both of our cases were confirmed by pcr in a reference laboratory . management of human cases with cchf has two main objectives : managing index case(s ) and preventing human - human transmission . active management of infected patients mostly relies on optimal supportive measures and restoration of a normal coagulation profile , depending on the severity of the infection . data on the efficacy of ribavirin therapy in treating cchf is conflicting , and there is no consensus nor clear guidelines on its role in the management of confirmed or suspected cases of cchf . to date , it is the only available option to treat viral hemorrhagic fevers , such as cchf , hantavirus , and lassa fever , although it is not yet approved by the fda for the management of cchf . several studies have examined oral or iv ribavirin therapy during different stages of the illness and have shown variable results in terms of efficacy and mortality ( 35 - 38 ) . having that said , the authors of two recent meta - analyses of data on ribavirin therapy in managing cchf concluded that there is no strong evidence supporting the use of the drug to reduce mortality among infected patients ( 39 , 40 ) . accordingly , we can make no clear recommendations on the efficacy or optimal dose of oral or iv ribavirin therapy for the management of cchf . in our studied cases , preventing human - human transmission is very important in this disease , especially among health care workers in nonendemic countries , who may not suspect the disease early in its course . the risk of transmission is highest during the hemorrhagic phase via incidental needle - stick injuries or exposure to infected body fluids through broken skin . microbiology laboratory personnel could be at risk when handling infected material without proper infection - control measures . to control nosocomial infections , it is important to take precautions ; barrier nursing , hand washing , and use of surgical masks and gloves are mandatory and effective in controlling infection when managing a suspected case ( 41 ) . a debatable question is whether to give oral ribavirin prophylaxis to those who come into contact with confirmed cchf patients or highly suspicious cases . this is not an easy question to answer , as we lack strong data on the efficacy of oral ribavirin in preventing secondary cases of cchf , who should receive post - exposure prophylactic therapy , and the optimal dose and duration of prophylaxis . current recommendations suggest administration of oral ribavirin therapy to people with close contact to the index cases , particularly if exposed to body fluids or tissue . they should be followed closely and asked to report immediately if they develop any febrile illness . if the clinical suspicion of acquiring a secondary infection is high , then post - exposure prophylaxis is recommended with 200 mg ribavirin orally twice daily for 5 - 14 days ( 42 , 43 ) . cchf is not endemic to uae and other gulf countries , and both cases described above occurred as a result of importing cattle with infected ticks . in nonendemic countries , a high level of suspicion is required in patients with fever , low platelets , and hemorrhagic tendencies . health care providers and preventive medicine practitioners need to be aware of this serious and potentially lethal imported zoonotic illness and should use proper infection - control measures to prevent the spread of such fatal cases in the future , especially during the hajj season . cchf is not endemic to uae and other gulf countries , and both cases described above occurred as a result of importing cattle with infected ticks . in nonendemic countries , a high level of suspicion is required in patients with fever , low platelets , and hemorrhagic tendencies . health care providers and preventive medicine practitioners need to be aware of this serious and potentially lethal imported zoonotic illness and should use proper infection - control measures to prevent the spread of such fatal cases in the future , especially during the hajj season .
introductioncrimean - congo hemorrhagic fever ( cchf ) is a severe infectious disease that is not endemic in the united arab emirates ( uae).case presentationwe report two cases of confirmed cchf diagnosed in dubai , uae , during hajj season 2010 . 
 both patients presented with an acute history of high - grade fever , skin rash , and hematemesis.conclusionsin spite of maximal supportive measures and intravenous ribavirin therapy , both patients died within a few days from start of illness . 
 more than 250 health care workers came into variable degrees of contact with the index cases , and none of them developed signs or symptoms suggestive of acquiring the illness . 
 health care workers from nonendemic regions should be aware of zoonotic hemorrhagic fevers imported via infected cattle and ticks and be able to diagnose and properly manage suspected cases in a timely manner . 
 in addition , proper infection - control measures should be undertaken to prevent nosocomial spread of infection .