Crimean-Congo Hemorrhagic Fever Virus for Clinicians-Diagnosis, Clinical Management, and Therapeutics.

Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread tickborne viral infection worldwide and has a fatality rate of up to 62%. Despite its widespread range and high fatality rate, no vaccines or treatments are currently approved by regulatory agencies in the United States or Europe. Supportive treatment remains the standard of care, but the use of antiviral medications developed for other viral infections have been considered. We reviewed published literature to summarize the main aspects of CCHFV infection in humans. We provide an overview of diagnostic testing and management and medical countermeasures, including investigational vaccines and limited therapeutics. CCHFV continues to pose a public health threat because of its wide geographic distribution, potential to spread to new regions, propensity for genetic variability, potential for severe and fatal illness, and limited medical countermeasures for prophylaxis and treatment. Clinicians should become familiar with available diagnostic and management tools for CCHFV infections in humans.

Big Epidemic of Small City: Crimean-Congo Hemorrhagic Fever.

Objective: Crimean-Congo hemorrhagic fever (CCHF) is the most common tick-borne viral hemorrhagic fever in our country and the world. While investigating the etiology of fever, tick contact should be questioned, especially in rural areas, and CCHF should be remembered. This study aimed to review the characteristics of the cases detected in Bayburt, one of the cities where CCHF is endemic. Methods: A total of 100 patients aged 16 years and older who were diagnosed with CCHF in our clinic between April 2020 and October 2022 were included in the study. Demographic, epidemiological, and clinical characteristics, treatments, and prognoses of the patients were reviewed retrospectively through the hospital automation system and CCHF information system of The Ministry of Health. Results: Sixty one (61%) of the patients included in the study were male, and their primary age (± standard deviation) was 50.4±15.7. 77% of the patients engaged in farming and or animal husbandry, and 71% were living in rural areas. The highest number of cases was in June and July. 63% of the patients had a history of a tick bite. At the first presentation, there were complaints of fatigue (95%), generalized body pain (84%), headache (67%), and fever (65%), in order of frequency. Ribavirin was started in 52 (52%) patients. One patient admitted in the late period died, and 99 patients were discharged with good recovery. Conclusion: CCHF is an important public health problem that has been causing seasonal epidemics in our country for nearly two decades. Although sporadic cases have been reported from almost every region, the disease is endemic in some areas. Since signs and symptoms are not specific, the disease can be easily missed when tick contact is not questioned. Therefore CCHF should be considered in patients presenting with fever and thrombocytopenia in rural areas, especially in the spring and summer months.

CD8+ T-cells target the Crimean-Congo haemorrhagic fever virus Gc protein to control the infection in wild-type mice.

BACKGROUND: Crimean-Congo haemorrhagic fever (CCHF) is a serious viral hemorrhagic fever caused by the CCHF virus (CCHFV). Spread by the bites of infected ticks or handling of viremic livestock, human disease is characterized by a non-specific febrile illness that can rapidly progress to fatal hemorrhagic disease. No vaccines or antivirals are available. Case fatality rates can vary but can be higher than 30%, although sub-clinical infections are often unrecognized and unreported. Yet, while most humans infected with CCHFV will survive the infection, often with little-to-no symptoms, the host responses that control the infection are unknown. METHODS: Here we investigated the role of cellular immunity in control of CCHFV infection in an immunocompetent mouse model. FINDINGS: We found that CD8+ T-cells are crucial for efficient control of the acute infection and rapidly acquired CCHFV-specific antiviral effector functions such as production of antiviral cytokines and degranulating in response to CCHFV peptides. We further identified the minimal CD8+ T-cell epitopes in the viral Gc proteins and that infection of mice lacking IFNγ resulted in worsened disease and higher viral loads. INTERPRETATION: Together our data suggest that CD8+ T-cells are important for control of acute CCHFV infection likely through production of antiviral cytokines. FUNDING: This work was supported by the Intramural Research Program of the NIH.

Cytokine release syndrome in Crimean-Congo hemorrhagic fever: can IL-1 receptor antagonist levels be a guide in its treatment?

OBJECTIVE: Crimean-Congo Hemorrhagic Fever (CCHF) is a potentially fatal zoonotic viral disease involving fever and hemorrhage. Our aim was to investigate the relationship between interleukin (IL)-1 and IL-1 receptor antagonist (RA) levels in patients with CCHF and the course of the disease and mortality, as well as to contribute to the literature at a time when new therapeutic protocols are being investigated. PATIENTS AND METHODS: Sixty-one patients with CCHF were admitted to our hospital's infectious diseases ward between March and September 2022, and 40 healthy people were included in the control group in our study. The patients were divided into mild/moderate (n=35) and severe (n=26) CCHF groups depending on the clinical course. The patients with CCHF were also divided into surviving and exitus groups. IL-1 and IL-1RA levels were measured from blood specimens using the ELISA method. RESULTS: Significant elevation in IL-1 and IL-1RA levels was observed in CCHF cases with a severe manifestation compared to those with moderate disease. Both patient groups' IL-1 and IL-1RA levels were also significantly higher than those of the control group. In addition, IL-1 and IL-1RA levels were significantly higher among the exitus patients compared to the surviving CCHF patients. The laboratory values of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine phosphokinase (CK), platelet count, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were also significantly higher among the patients with severe manifestations compared to the moderate severity patient group, and in the exitus patients compared to the survivors. However, platelet count and fibrinogen levels were lower in the patients with a severe manifestation compared to the moderate severity group and in the exitus patients compared to the survivors. White blood cells (WBC) were higher in exitus patients than in survivors. CONCLUSIONS: IL-1 and IL-1RA levels were elevated in all the CCHF patients, while the higher values in patients with a fatal course suggest that the inflammatory process is very severe and that IL-1 receptor antagonists may be needed in the treatment.

Crimean-Congo haemorrhagic fever virus.

Crimean-Congo haemorrhagic fever (CCHF) is a severe tick-borne illness with a wide geographical distribution and case fatality rates of 30% or higher. Caused by infection with the CCHF virus (CCHFV), cases are reported throughout Africa, the Middle East, Asia and southern and eastern Europe. The expanding range of the Hyalomma tick vector is placing new populations at risk for CCHF, and no licensed vaccines or specific antivirals exist to treat CCHF. Furthermore, despite cases of CCHF being reported annually, the host and viral determinants of CCHFV pathogenesis are poorly understood. CCHFV can productively infect a multitude of animal species, yet only humans develop a severe illness. Within human populations, subclinical infections are underappreciated and may represent a substantial proportion of clinical outcomes. Compared with other members of the Bunyavirales order, CCHFV has a more complex genomic organization, with many viral proteins having unclear functions in viral pathogenesis. In recent years, improved animal models have led to increased insights into CCHFV pathogenesis, and several antivirals and vaccines for CCHFV have shown robust efficacy in preclinical models. Translation of these insights and candidate therapeutics to the clinic will hopefully reduce the morbidity and mortality caused by CCHFV.

Investigating the effect of ribavirin treatment on genetic mutations in Crimean-Congo haemorrhagic fever virus (CCHFV) through next-generation sequencing.

Crimean-Congo haemorrhagic fever (CCHF) is the most widespread tick-borne viral haemorrhagic fever affecting humans, and yet a licensed drug against the virus (CCHFV) is still not available. While several studies have suggested the efficacy of ribavirin against CCHFV, current literature remains inconclusive. In this study, we have utilised next-generation sequencing to investigate the mutagenic effect of ribavirin on the CCHFV genome during clinical disease. Samples collected from CCHF patients receiving ribavirin treatment or supportive care only at Sivas Cumhuriyet University Hospital, Turkey, were analysed. By comparing the frequency of mutations in each group, we found little evidence of an overall mutagenic effect. This suggests that ribavirin, administered at the acute stages of CCHFV infection (at the World Health Organization-recommended dose) is unable to induce lethal mutagenesis that would cause an extinction event in the CCHFV population and reduce viremia.

Distribution pattern of Crimean-Congo Hemorrhagic Fever in Asia and the Middle East.

Crimean-Congo Hemorrhagic Fever (CCHF) is one of the most important vector-borne diseases of zoonotic potential that can be acquired following the bite of the Hyalomma species of ticks. It is a highly prevalent disease in Asia and the Middle East. The risk factors of this disease are contact with infected tissue, blood, patient, or livestock in the acute viremic phase, infected tick bites, or the manual removal of ticks. The disease is clinically described as progressive hemorrhages, fever, and pain in musculature. Biochemical tests reveal elevated levels of creatinine phosphokinase, alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase. Clotting time is prolonged in pro-thrombin tests, and pathogenesis is mostly related to the disruption of the epithelium during viral replication and indirectly by secreting cytotoxic molecules. These molecules cause endothelial activation and result in the loss of function. Supportive therapy is given through blood or plasma infusions to treat or manage the patients. According to the most advanced studies, CCHF can be treated by Ribavirin, which is an antiviral drug that shows excellent results in preventing the disease. Health-care staff are more prone to infection. The hemorrhagic phase represents a high risk for accidental exposures. This literature review presents a comprehensive overview of the viral epidemiology, zoonotic perspectives, and significant risk factors of CCHF in various Middle East and Asian countries. Furthermore, the pathophysiology and preventive strategies of CCHF have also been discussed as well as legislation and policies regarding public outreach programs, research, and development aimed at infection prevention and control that are required at a global level.

Changing Disease Course of Crimean-Congo Hemorrhagic Fever in Children, Turkey.

Crimean-Congo hemorrhagic fever (CCHF), endemic in certain regions of the world, is listed as a priority disease with pandemic potential. Since CCHF was first identified in Turkey, children have been known to experience milder disease than adults. However, during the COVID-19 pandemic, we observed an unusually severe disease course, including hemophagocytic lymphohistiocytosis (HLH). We examined cytokine/chemokine profiles of 9/12 case-patients compared with healthy controls at 3 time intervals. Interferon pathway-related cytokines/chemokines, including interleukin (IL) 18, macrophage inflammatory protein 3α, and IL-33, were elevated, but tumor necrosis factor-α, IL-6, CXCL8 (formerly IL-8), and cytokines acting through C-C chemokine receptor 2 and CCR5 were lower among case-patients than controls. Interferon pathway activation and cytokines/chemokines acting through CCR2 and CCR5 improved health results among children with severe CCHF. Children can experience severe CCHF, including HLH, and HLH secondary to CCHF can be successfully treated with intravenous immunoglobulin and steroid therapy.

A screen of FDA-approved drugs with minigenome identified tigecycline as an antiviral targeting nucleoprotein of Crimean-Congo hemorrhagic fever virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to the genus Orthonairovirus and is the causative agent of a viral hemorrhagic disease with a case fatality rate of 30%. However, limited studies have been conducted to explore antiviral compounds specific to CCHFV. In this study, we developed a minigenome system of orthonairoviruses, CCHFV and Hazara virus to analyze viral replication and screened an FDA-approved compound library. The transfection of the minigenome components induced marked increase in luciferase expression, indicating the sufficient replication and translation of reporter RNA. Compound library screening identified 14 candidate compounds that significantly decreased luciferase activity. Some of the compounds also inhibited the replication of the infectious Hazara virus. The mechanism of inhibition by tigecycline was further analyzed, and a decrease in the interaction between the viral N protein and RNA by tigecycline was observed. This work provides a basis for validation using animal models and the design of chemical derivatives with stronger activity in future studies on the development of an antiviral against CCHFV.

In vitro and in vivo efficacy of a novel nucleoside analog H44 against Crimean-Congo hemorrhagic fever virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus that causes fever, hemorrhage, and multi-organ failure, with an average fatality rate of ∼40% in humans. Currently, there are no available vaccines or drugs for the treatment of Crimean-Congo hemorrhagic fever (CCHF). Favipiravir (T-705), a nucleoside analog, protects against CCHFV infection in animal models. Here, we evaluated the anti-CCHFV efficacy of several nucleoside analogs, including some well-known compounds such as remdesivir (GS-5734), EIDD-1931 and its prodrug molnupiravir (EIDD-2801), as well as a novel T-705-derived compound H44. T-705, H44, and EIDD-1931 inhibited CCHFV infection in vitro while GS-5734 had no inhibitory effect. All three nucleoside analogs functioned at the "post-entry" stage of virus infection. However, EIDD-2801 failed to protect type I interferon receptor knockout (IFNAR)-/- mice from CCHFV infection. H44, similar to T-705, conferred 100% protection to IFNAR-/- mice against lethal CCHFV challenge, even with delayed administration. This study provided in vitro and in vivo data regarding the anti-CCHFV efficacy of different nucleosides and identified a novel compound, H44, as a promising drug candidate for the treatment of CCHFV infection in vivo.

Vaginal bleeding as a sign of Crimean-Congo hemorrhagic fever infection: a case report.

BACKGROUND: Crimean-Congo hemorrhagic fever is a severe vector-borne viral hemorrhagic fever with considerable mortality in humans. This disease is endemic in Afghanistan, and its incidence rate has rapidly increased in recent years. This infection can cause a broad range of hemorrhage manifestations including epistaxis, petechial or purpuric rashes, hematemesis, and melena; however, vaginal bleeding is also reported as a rare manifestation. CASE PRESENTATION: We report the case of a previously healthy 30-year-old Afghan female of shepherding occupation, with a sudden onset of fever, generalized body pain, epistaxis, and vaginal bleeding. She was admitted to the hospital after 7 days of symptom manifestation, with predominant signs being high fever, vaginal bleeding, and elevated liver enzymes. The serological test result for Crimean-Congo hemorrhagic fever was positive. She was treated with oral ribavirin and discharged with normal parameters. CONCLUSIONS: People in high-risk professions in endemic areas should be informed that vaginal bleeding is a serious symptom and requires immediate action and, therefore, might be attributed to nongynecologic disorders.

Crimean-Congo Hemorrhagic Fever Virus: Current Advances and Future Prospects of Antiviral Strategies.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widespread, tick-borne pathogen that causes Crimean-Congo hemorrhagic fever (CCHF) with high morbidity and mortality. CCHFV is transmitted to humans through tick bites or direct contact with patients or infected animals with viremia. Currently, climate change and globalization have increased the transmission risk of this biosafety level (BSL)-4 virus. The treatment options of CCHFV infection remain limited and there is no FDA-approved vaccine or specific antivirals, which urges the identification of potential therapeutic targets and the design of CCHF therapies with greater effort. In this article, we discuss the current progress and some future directions in the development of antiviral strategies against CCHFV.

[Evaluation of Efficacy of Ribavirin on Laboratory Test and Severity Score in Crimean-Congo Hemorrhagic Fever in Children]. / Çocuklarda Kirim-Kongo Kanamali Atesinde Ribavirinin Laboratuvar Testi ve Siddet Skoru Üzerindeki Etkinliginin Degerlendirilmesi.

Crimean-Congo hemorrhagic fever (CCHF) is endemic in Tokat province. It is observed in all age groups. The case fatality rate varies 20-30% in hospitalized patients and 0-5% among children. Ribavirin use and supportive measures are the main treatment modalities, but the effects of ribavirin in CCHF are controversial. Most of the studies investigating the effectiveness of ribavirin are done by comparing the initial and the final laboratory values. The purpose of this study was to evaluate the effects of oral ribavirin use in children with CCHF by using all the clinical and laboratory findings and to investigate the presence of unnoticed results. In the study, the data of 67 patients under 19 years old who were hospitalized and followed up with a diagnosis of CCHF during 2012-2020 epidemic period were retrospectively analyzed. Epidemiological and demographic characteristics, clinical and laboratory data were retrieved from the patient files. We implemented a linear mixed-effects model to assess the effects of the ribavirin, taking into account the repeated measures of the data. Ribavirin was given to 33 (49.2%) of the patients. 54 (80.6%) of the patients were male, 13 (19.4%) were female, 52 (77.6%) of the patients were living in rural areas and 15 (22.4%) were living in urban areas. The mean age was 15.1 (median= 15.5, range= 8-18) years in patients who did not receive ribavirin, and 15.2 (median= 15, range= 11-18) years in ribavirin administered patients. At the time of admission 63 (94%) of the patients had fever, 60 (89.6%) had fatigue, 38 (56.7%) had rash, 48 (71.6%) had myalgia, 30 (44.8%) had headache, 25 (37.3%) had abdominal pain, 30 (44.8%) had vomiting, 21 (31.8%) had diarrhea, 29 (43.3%) had drowsiness, 29 (43.3%) had bleeding in the mucosa and 27 (40.3%) had petechiae. Drowsiness and mucosal bleeding rates were significantly higher in patients who received ribavirin (p<0.05). The time from tick bite to hospital admission was 4.85 (median= 4.5, range= 2-9) days in patients who did not receive ribavirin, and 4.64 (median= 5, range= 2-9) days in ribavirin administered patients. The mean length of the hospital stay in patients who did not receive ribavirin was 6.68 (median= 7, range= 4-10) days, while it was 7.45 (median= 8, range= 3-13) days in those treated with ribavirin. Linear-mixed effect test results showed that ribavirin decreased hemoglobin (Hb) (95% GA= -0.12/-0.02), suppressed white blood cell count (WBC) (95% GA= -0.15/-0.02) and absolute lymphocyte count (ALC) (95% GA= -0.12/0.05), and decreased alanine aminotransferase (ALT) (95% GA= -9.32/-1.49), lactate dehydrogenase (LDH) (95% GA= -25.06/-2.36) and severity score index (95% GA= -0.28/-0.004). As a result, ribavirin suppressed Hb, WBC and ALC levels in children with CCHF, but decreased liver enzymes and severity score much faster in the elapsed time.

Knowledge, attitude and perceptions about Crimean Congo Haemorrhagic Fever (CCHF) among occupationally high-risk healthcare professionals of Pakistan.

BACKGROUND: Crimean Congo Haemorrhagic Fever (CCHF), a tropically neglected infectious disease caused by Nairovirus, is endemic in low middle-income countries like Pakistan. Emergency health care professionals (HCPs) are at risk of contracting nosocomial transmission of CCHF. We, therefore, aim to analyze the knowledge, attitudes, and perceptions (KAP) of at-risk physicians, nurses, and pharmacists in Pakistan and the factors associated with good KAP. METHOD: A validated questionnaire (Cronbach's alpha 0.71) was used to collect data from HCPs in two CCHF endemic metropolitan cities of Pakistan by employing a cross-sectional study design. For data analysis percentages, chi-square test and Spearman correlation were applied by using SPSS version 22. RESULTS: Of the 478 participants, 56% (n = 268) were physicians, 37.4% (n = 179) were nurses, and 6.5% (n = 31) were pharmacists. The proportion of HCPs with good knowledge, attitude, and perception scores was 54.3%, 81, and 69%, respectively. Being a physician, having more work experience, having a higher age, working in tertiary care settings, were key factors for higher knowledge (p < 0.001). The correlation coefficient showed significant positive correlation between attitude- perception (r = 0.560, p < 0.001). CONCLUSION: We have observed average knowledge of HCPs. Therefore, we recommend time to time education campaigns and workshops in highly endemic CCHF regions to be launched by health ministries and HCPs, in particular nurses, encouraged to follow authentic academic sources of information to prevent nosocomial transmission.

Case Report: A Rare Case of Crimean-Congo Hemorrhagic Fever Associated with Epididymo-Orchitis.

Crimean-Congo hemorrhagic fever (CCHF) is an acute infectious disease that affects multiple organ systems and is characterized by extensive ecchymosis, internal hemorrhage, and hepatic dysfunction. The reported case fatality rate varies between 8% and 80%. It is frequently transmitted by Hyalomma ticks, which are endemic in the Northeast Anatolia region of Turkey in spring and summer. Our patient presented from an endemic area with fever, malaise, joint pain, and scrotal pain following a tick bite, and real-time PCR analysis of venous blood was positive for CCHF. Based on Doppler ultrasound performed because of the patient's scrotal pain, he was diagnosed as having epididymo-orchitis, which was considered secondary to CCHF after ruling out other etiologies and resolved with scrotal elevation and anti-inflammatory treatment. Being a very rare complication, this report aimed to document this case of CCHF-associated epididymo-orchitis in the literature.

Efficacy of favipiravir (T-705) against Crimean-Congo hemorrhagic fever virus infection in cynomolgus macaques.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus found throughout Eastern Europe, Africa, the Middle East and Asia. It is spread through bites from infected ticks, animal husbandry and can also be acquired in the healthcare setting during care of infected patients. In humans, CCHFV can cause a sudden onset of a non-specific febrile illness that can rapidly progress to severe hemorrhagic manifestations. Currently, there is no widely available vaccine and although ribavirin has been suggested for the treatment of CCHFV, clinical efficacy in both animal models and humans is inconsistent suggesting more potent antivirals are needed for CCHFV. Favipiravir is approved in Japan for the treatment of influenza virus infections and has shown promise against other highly pathogenic RNA viruses including CCHFV with demonstrated efficacy in the type I interferon deficient mouse model. In this report we utilized the cynomolgus macaque model to evaluate the efficacy of once- and twice-daily favipiravir treatment against CCHFV infection. We found that favipiravir treatment suppressed viremia and viral shedding when treatment was initiated 24 h post-infection and viral burdens in key tissues trended lower in favipiravir-treated animals. Our data indicate that favipiravir has efficacy against CCHFV in vivo in a non-human primate model of infection.

[A Case of Simultaneous Acute Lymphoblastic Leukemia Diagnosis with Crimean-Congo Hemorrhagic Fever]. / Kirim-Kongo Kanamali Atesi ile Es Zamanli Akut Lenfoblastik Lösemi Tanisi Alan Olgu.

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease that can be presented with fever, fatigue, generalized joint/body pain, diarrhea and bleeding in various parts of the body. The risk of developing a severe fatal disease in humans, the possibility of being infected with aerosols and the risk of being used as a biological weapon make the disease still an important health problem all over the world as there is no a specific treatment and vaccine that has proven effective againt the virus today. The pathogenesis of the disease is not known, but vascular endothelial damage is prominent. Therefore, it progresses with thrombocytopenia, anemia, leukopenia and this hematological findings can be confused with hematological malignancies. Acute lymphoblastic leukemia (ALL) is a malignancy included in differential diagnoses and occurs as a result of mutations occuring at a stage of differentiation in the lymphoid precursor cells in the bone marrow. In this study, we present a case of ALL who was diagnosed with CCHF simultaneously. A 43-year old female patient who works in the library and does not have a chronic disease other than asthma and thyroid disorder, has admitted to our hospital with the complaints of intermittent fever, weakness, generalized joint and body pain for about 3 weeks. She had fever and the physical examination revealed bilateral cervical and right postauricular lymphadenopathies. Her aspartate aminotransferase: 77 U/L, alanine aminotransferase: 117 U/L, lactate dehydrogenase: 616 U/L, hemoglobin: 8.27 g/dl, leukocyte count: 15.690/mm3 , neutrophil count: 550/mm3 (%3.5), lymphocyte count: 6690/mm3 (%42.6), platelet count: 102.100/mm3 , C-reactive protein: 163.6 mg/L was detected and the patient was hospitalized on 5 August 2019 for further examination and treatment. Considering that the patient may have viral infection in the foreground the requested test results were detected as; anti-CMV IgM negative, anti-CMV IgG positive, anti-toxoplasma IgM negative, anti-toxoplasma IgG positive, anti-rubella IgM negative, anti-rubella IgG positive, HBsAg negative, anti-HBc IgM negative, antiHBs positive, anti-HAV IgM negative, anti-HAV IgG positive, anti-HCV negative, anti-HIV negative, EpsteinBarr virus (EBV) VCA IgM negative, EBV VCA IgG positive, EBV EBNA IgG positive. Brucella Rose Bengal and Coombs tube agglutination was found be negative. As the cytopenia of the patient deepened, the patient was accepted to have neutropenic fever and it was planned to start piperacillin-tazobactam 4 x 4.5 g/day and two units of erythrocyte replacement therapy. When the patient's history was questioned again, it was learned that she had a tick on her neck about three weeks ago and she had removed the tick herself; 4-5 days later she had the complaints of fever and flu like symptoms and also diarrhea complaints lasting for 3-4 days. Considering the current anamnesis and laboratory findings, the patient was thought to have CCHF and the patient was isolated. The serum sample taken from patient with an initial diagnosis of CCHF and sent to Department of Microbiology Reference Laboratory Public Health Agency of Turkey. The patient was referred to the Antalya Training and Research Hospital. The patient's CCHF serum result was positive. Ribavirin treatment was not initiated in the patient who was accepted to be in the convalescence period, piperacillin-tazobactam 4 x 4.5 g/day treatment was continued and supportive treatment was given. In the follow-up, as the patient's neutropenia, thrombocytopenia and lymphocytopenia still continuing, she was transferred to hematology clinic for malignancy examination and bone marrow biopsy performed by hematology and B cell ALL was diagnosed. She was accepted to be convalescent in terms of CCHF and chemotherapy was started for ALL treatment by hematology. The patient is still being followed up by the hematology clinic and allogenic hematopoietic stem cell tranplantation is planned for the patient. As a result, CCHF is a disease that can be confused with many differential diagnosis. With this case, it is aimed to draw attention to the diagnostic difficulties of CCHF and ALL and to be the first case in the literature.

Monitoring Crimean-Congo haemorrhagic fever virus RNA shedding in body secretions and serological status in hospitalised patients, Turkey, 2015.

IntroductionCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne disease in Africa, Asia, the Balkan peninsula, the south-east of Europe and the Middle East, with mortality rates of 3-30%. Transmission can also occur through contact with infected animals or humans.AimThis observational, prospective case series aimed to investigate detectable viral genomic RNA in whole-body fluids and antibody dynamics in consecutive daily samples of patients diagnosed with CCHF until discharge from hospital.MethodsWe tested 18 patients and 824 swabs and sera with RT-PCR and 125 serum samples serologically.ResultsThe longest duration until clearance of viral RNA was 18 days from serum collection and 18, 15, 13, 19 and 17 days, respectively, from nasal, oral, genital (urethral or vaginal) and faecal swab, and urine. In seven patients, viral load decreased in serum at the same time as it increased in urine or persisted at the same logarithmic values. Despite clearance in serum, viral RNA was detected in faeces and genital swabs in two and three patients, respectively. Viral clearance from body fluids occurred earlier than from serum in eight patients on ribavirin treatment. The shortest seroconversion time was 3 days after symptom onset for IgM and IgG. Seroconversion of IgG occurred until Day 14 of symptoms.ConclusionWe report persistence of viral RNA in urine, faeces and genital swabs despite serum clearance. This may indicate a need for extending isolation precautions, re-evaluating discharge criteria and transmission risk after discharge, and considering oral swabs as a less invasive diagnostic alternative.