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.

Case Management of Imported Crimean-Congo Hemorrhagic Fever, Senegal, July 2023.

We report an imported Crimean-Congo hemorrhagic fever case in Senegal. The patient received PCR confirmation of virus infection 10 days after symptom onset. We identified 46 patient contacts in Senegal; 87.7% were healthcare professionals. Strengthening border crossing and community surveillance systems can help reduce the risks of infectious disease transmission.

Therapeutic plasma exchange for envenomation: Is it reasonable?

BACKGROUND AND OBJECTIVES: The incidence of poisoning due to snakebite and Crimean Congo Hemorrhagic Fever (CCHF), referred to as 'envenomation', varies according to the region, and many deaths occur every year. Therapeutic plasma exchange (TPE) is a method of extracorporeal blood purification that clears toxins and virus load from the circulation. Therefore, its use has been increasing recently in envenomation cases. However, there are a limited number of studies on poisoning due to snakebite and CCHF. In the present study, we share our TPE experience retrospectively in patients diagnosed with poisoning due to snakebite and CCHF between 2010 and 2019. MATERIALS AND METHODS: A total of 26 patiens, including 20 patients with poisoning due to snakebite and 6 CCHF patients were treated with TPE. Demographic data, clinical status, and outcomes of patients were recorded. Routine biochemical and hematologic laboratory parameters were analyzed before and after TPE. TPE was performed by using centrifugation technology via a central venous catheter. Fresh frozen plasma was used as replacement fluid. RESULTS: An average of 3.95 (1-11) apheresis sessions were applied to patients poisoned due to snakebite, and 19 patients (95 %) were discharged in an average of 8.3 (1-17) days without any complications. None of the patients enrolled in the study lost their limbs. Only one patient died due to disseminated intravascular coagulopathy. Six patients with CCHF who received 5 sessions of TPE on average were discharged successfully after an average of 6.5 days. No adverse events or complications were observed in any patient after TPE. CONCLUSIONS: TPE is a good alternative and a reliable method in treating envenomation cases who are refractory to supportive measures. TPE should be performed without delay in cases of poisoning due to snakebite and CCHF.

Crimean-Congo hemorrhagic fever: A pediatric case responding to plasmapheresis treatment.

Crimean-Congo hemorrhagic fever (CCHF) is a life-threatening tick-borne viral infection. The most important step in the treatment of CCHF is supportive therapy. Ribavirin is the recommended antiviral agent for infected patients. We present a case of a child who presented to our pediatric intensive care unit due to CCHF and was treated with plasmapheresis and ribavirin. A previously healthy seven-month-old male infant presented to the emergency room with a fever of 39.5 °C, nosebleed, cough, vomiting, and weakness. We decided to apply plasmapheresis treatment due to multiple organ failure associated with thrombocytopenia, acute liver failure, and a family history of death from the disease. Plasmapheresis was performed in three sessions. By the sixth day of his admission to the intensive care unit, the patient's clinical condition had improved and his laboratory values had returned to normal, so he was transferred to the infectious diseases service in stable condition.

Evaluation of neutrophil to lymphocyte ratio in predicting the prognosis of Crimean-Congo haemorrhagic fever.

Crimean-Congo haemorrhagic fever (CCHF) is a severe form of haemorrhagic fever identified in parts of Africa, Asia, Eastern Europe and the Middle East. CCHF continues to be a justifiable cause of concern for people in rural areas where the disease is endemic. A total of 151 patients, diagnosed with CCHF, were evaluated retrospectively. The demographic characteristics of these patients and the relationship between the neutrophil-lymphocyte ratio (NLR) at admission and survival were examined. There were 21 (13.9%) deaths. There was no relationship between age, gender and mortality, but elevated neutrophil-lymphocyte ratio (NLR) on admission was statistically associated with mortality. NLR is a laboratory marker that can be studied even in medical centres with limited facilities and may be helpful in predicting the clinical course of the disease.

Efficacy of therapeutic plasma exchange in patients with Crimean-Congo hemorrhagic fever.

OBJECTIVE: To examine the efficacy of therapeutic plasma exchange (TPE) in patients critically ill with Crimean-Congo hemorrhagic fever (CCHF). METHODS: Patients with CCHF received supportive treatment (ST) or TPE. After laboratory and clinical evaluations, the patients were divided into mild, moderate, and severe CCHF groups according to the severity score index (SSI). To assess the efficacy of TPE, the incubation period, time of admission to hospital, hospitalization duration, mortality rate and times to recovery of the platelet count and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were compared between patients receiving ST and TPE. RESULT: A total of 119 confirmed CCHF cases was analyzed. The median SSIs were 7 in the TPE group and 5 in the ST group. The SSI stages, median incubation times and admission times were similar in the two groups. However, the duration of hospitalization was longer in the TPE group. The overall mortality rates were 9% (3 of 33 patients) in the TPE group and 16% (5 of 31 patients) in the ST group; the difference was significant. The platelet count recovered after a median of 6 (4-7) days in the ST group. CONCLUSION: The mortality rate was lower in the TPE group than in the ST group, but the duration of hospitalization and the time to platelet recovery were longer in the TPE group than in the ST group. TPE did not contribute significantly to the prognosis of patients with intermediate-severity CCHF. However, TPE might be efficacious in patients with severe CCHF.

Crimean-Congo hemorrhagic fever: An update.

Crimean-Congo hemorrhagic fever (CCHF) is a severe form of hemorrhagic fever caused by a virus of the genus Nairovirus. The amplifying hosts are various mammal species that remain asymptomatic. Humans are infected by tick bites or contact with animal blood. CCHF has a broad geographic distribution and is endemic in Africa, Asia (in particular the Middle East) and South East Europe. This area has expanded in recent years with two indigenous cases reported in Spain in 2016 and 2018. The incubation period is short with the onset of symptoms in generally less than a week. The initial symptoms are common to other infectious syndromes with fever, headache, myalgia and gastrointestinal symptoms. The hemorrhagic syndrome occurs during a second phase with sometimes major bleeding in and from the mucous membranes and the skin. Strict barrier precautionary measures are required to prevent secondary and nosocomial spread. CCHF may be documented by PCR detection of the virus genome during the first days after the onset of illness, and then by serological testing for IgM antibodies as from the 2nd week after infection. Patient management is mainly based on supportive care. Despite a few encouraging retrospective reports, there is no confirmed evidence that supports the use of ribavirin for curative treatment. Nevertheless, the World Health Organization continues to recommend the use of ribavirin to treat CCHF, considering the limited medical risk related to short-term treatment. The prescription of ribavirin should however be encouraged post-exposure for medical professionals, to prevent secondary infection.

Aeromedical Transfer of Patients with Viral Hemorrhagic Fever.

For >40 years, the British Royal Air Force has maintained an aeromedical evacuation facility, the Deployable Air Isolator Team (DAIT), to transport patients with possible or confirmed highly infectious diseases to the United Kingdom. Since 2012, the DAIT, a joint Department of Health and Ministry of Defence asset, has successfully transferred 1 case-patient with Crimean-Congo hemorrhagic fever, 5 case-patients with Ebola virus disease, and 5 case-patients with high-risk Ebola virus exposure. Currently, no UK-published guidelines exist on how to transfer such patients. Here we describe the DAIT procedures from collection at point of illness or exposure to delivery into a dedicated specialist center. We provide illustrations of the challenges faced and, where appropriate, the enhancements made to the process over time.

Recent advances in understanding Crimean-Congo hemorrhagic fever virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus and the cause of hemorrhagic disease in Africa, Southern and Eastern Europe, the Middle East, India and Asia. Recent emergence of CCHFV into Spain indicates that the geographic range of this virus is expanding and the presence of its tick vector in several countries without reported disease suggest that CCHFV will continue to spread. Research into CCHFV was historically limited by a lack of suitable animal models and tools to study viral pathogenesis. However, in the past few years the toolset for studying CCHFV has expanded with small animal and non-human primate models for CCHFV being developed along with a reverse genetics system that allows for investigation of viral determinants of disease. These tools have been utilized to understand how CCHFV antagonizes host restriction factors and to develop novel vaccine candidates that may help limit the substantial morbidity and mortality in humans caused by CCHFV.

Second International Conference on Crimean-Congo Hemorrhagic Fever.

The Second International Conference on Crimean-Congo Hemorrhagic Fever (CCHF) was held in Thessaloniki, Greece, from September 10-13, 2017, and brought together international public health professionals, clinicians, ecologists, and basic laboratory researchers. Nearly 100 participants, representing 24 countries and the World Health Organization (WHO), were in attendance. Meeting sessions covered the epidemiology of CCHF in humans; ticks and virus-tick interactions; wild and domestic animal hosts; molecular virology; taxonomic classification; pathogenesis and animal models; clinical aspects and diagnosis; clinical management and clinical trials; and disease prevention in humans. The concluding session focused on recent WHO recommendations for public health measures and future research. This report summarizes lectures by the invited speakers and highlights advances in the field.

Therapeutic management of Crimean-Congo haemorrhagic fever. / Manejo terapéutico de la fiebre hemorrágica de Crimea-Congo.

Crimean-Congo haemorrhagic fever has been reported in more than 30 countries in Africa, Asia, the Middle East and Eastern Europe, with an increasing incidence in recent years, especially in Europe. Because no specific treatments have demonstrated efficacy, supportive treatment is essential, as well as the provision of a centre with the appropriate means to guarantee the safety of its healthcare professionals. Laboratory monitoring of thrombocytopenia, severe coagulopathy or liver failure is of critical importance. Patients with Crimean-Congo haemorrhagic fever should be admitted to High Level Isolation Units where appropriate biocontainment procedures can prevent nosocomial transmission through infected fluids or accidents with contaminated material. In case of high-risk exposures, early administration of ribavirin should be considered.

THE RELATIONSHIP BETWEEN CRIMEAN-CONGO HEMORRHAGIC FEVER AND CLIMATE: DOES CLIMATE AFFECT THE NUMBER OF PATIENTS?

- Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonosis. The incidence of zoonotic diseases has been shown to be affected by climatic factors. In this study, we evaluated patients endemic to the CCHF region and examined the relationship between the number of patients and climatic properties of the region where they lived. The study included 548 CCHF patients. Along with the patient demographic and clinical characteristics, we recorded temperature, humidity and precipitation in the places where they lived at the time of their admission to the hospital. In addition to temperature, humidity and precipitation at the time of patient admission, these values were assessed at one month and three months prior to admission. The relationship between the number of patients and the above-mentioned values was examined. Humidity at the time of and one month prior to hospital admission, and precipitation three months prior to hospital admission were found to affect the number of patients admitted to the hospital for CCHF. In conclusion, climate appeared to affect the number of CCHF patients. We believe that the number of patients presenting to the hospital with CCHF could be predicted by taking into account climatic properties of the places where CCHF has been recorded, along with undertaking necessary measures.

Hemorrhagic fever of bunyavirus etiology: disease models and progress towards new therapies.

A growing number of bunyaviruses are known to cause viral hemorrhagic fever (VHF), a severe febrile illness which can progress to hypovolemic shock and multi-organ failure and is characterized by hematologic abnormalities and vascular leak. At present, there are no approved vaccines or antiviral therapies to effectively prevent or treat VHF caused by pathogenic bunyaviruses. Advances in the modeling of bunyaviral infections have facilitated efforts towards the development of novel post-exposure prophylactic and therapeutic countermeasures, several of which may some day be approved for human use. Here, we review recent progress in animal models of severe bunyaviral infections essential to this mission, as well as promising antivirals and biologicals that are at various stages of the development process.

Clinical severity in forecasting platelet to lymphocyte ratio in Crimean-Congo hemorrhagic fever patients.

Crimean-Congo hemorrhagic fever (CCHF) is a life-threatening disease that develops as a result of infection by a member of the Nairovirus genus of the Bunyaviridae family, and its initial symptoms are not specific. In patients with severe clinical progression, in particular, the neutrophil rate is high, whereas lymphocyte and monocyte levels are low. A total of 149 patients, in whom the diagnosis was confirmed with reverse transcriptase PCR, were included in the study. In order to compare patient clinical progression severity, we divided the patients into two groups. For group 1, Çevik's severity score was used. The patients who had a platelet/lymphocyte ratio (PLR) <41 constituted group 2. Of 149 patients, 20 (13.4 %) were determined as group 1 (Çevik's classification) and 38 (25.5 %) were determined as group 2 (PLR <41). Of 11 deaths, 4 (36.4 %) patients were from group 1 and 7 (63.6 %) were from group 2. This is the first study to our knowledge to analyse the relationship between severity and PLR in patients with CCHF. PLR is a simple laboratory test that can aid in determining the prognosis of individuals with this disease.

[A case of brucellosis and Crimean-Congo hemorrhagic fever coinfection in an endemic area]. / Endemik bir bölgede bruselloz ve Kirim Kongo kanamali atesi koenfeksiyonu olgusu.

Brucellosis, a zoonotic disease which is especially seen in developing countries is still an important public health problem worldwide. Crimean-Congo hemorrhagic fever (CCHF) is another zoonotic disease that transmits to humans by infected tick bites as well as exposure to blood or tissue from infected animals. Both of the diseases are common among persons who live in rural areas and deal with animal husbandry. Since brucellosis usually presents with non-specific clinical symptoms and may easily be confused with many other diseases, the diagnosis of those infections could be delayed or misdiagnosed. In this report, a case of coinfection of brucellosis and CCHF has been presented to emphasize the possibility of association of these infections. A 70-year-old female patient with a history of dealing with animal husbandry in a rural area admitted to our hospital with the complaints of fever, malaise, generalized body and joint pains, and headache. Her complaints had progressed within the past two days. She also reported nausea, vomiting, abdominal pain and bloody diarrhea. She denied any history of tick bites. Her physical examination was significant for the presence of 38.8°C fever, increased bowel sounds and splenomegaly. Laboratory analysis revealed leukopenia, thrombocytopenia and high levels of liver enzymes. The patient was admitted to our service with the prediagnosis of CCHF. Serum sample was sent to the Department of Microbiology Reference Laboratory at Public Health Agency of Turkey for CCHF testing. During patient's hospitalization in service, more detailed history was confronted and it was learned that she had fatigue, loss of appetite, sweating, joint pain, and intermittent fever complaints were continuing within a month and received various antibiotic treatments. The tests for brucellosis were conducted and positive results for Brucella Rose Bengal test, tube agglutination (1/160 titers) and immune capture test with Coombs (1/320 titers) were determined. The tests performed in the reference laboratory revealed CCHF virus-specific IgM positivity by immunofluorescence assay and viral RNA positivity by real-time polymerase chain reaction. Two blood cultures remained sterile during hospitalization, this situation was considered to be the cause of antibiotic usage in the last month. Doxycycline and rifampicin therapy were initiated for brucellosis, and close monitoring with supportive therapy for CCHF. On the second day of admission, the patient was transfused with 5 units random platelets and 2 units fresh frozen plasma due to dramatic decline of platelet count (37.000/mm(3)). Early clinical response to brucellosis therapy was confirmed with resolution of fever and improved blood counts and the treatment was completed in eight weeks on an outpatient basis. No other problems were encountered during follow-ups after completion of treatment. According to accessible literature search, coinfection of brucellosis and CCHF has not been reported previously. In conclusion, as our country is endemic for both brucellosis and CCHF, it is important to consider both infections in the differential diagnosis. Physicians should keep in mind that, likewise in our case, coinfection of brucellosis and CCHF can be detected.

Direct healthcare costs for patients hospitalized with Crimean-Congo haemorrhagic fever can be predicted by a clinical illness severity scoring system.

Crimean-Congo hemorrhagic fever (CCHF) is endemic in Turkey, with peak incidence of hospital admissions in the summer months. The aim of this pilot study was to evaluate the role of the severity grading score (SGS) in predicting length of hospital stay, laboratory usage, need for blood products, and hence total costs of patients. Thirty-five patients admitted to one specialist center in Turkey in 2013 and 2014 with PCR-proven CCHF. The mean (SD) age was 55 (±14) and 63% of the patients were male, with 8 (22.9%) mortality. Patients were classified by SGS into three groups with mortality as follows: low risk (0/19); intermediate (6/14); and high (2/2). The direct hospital cost of these admissions was at least $41 740 with median (range) of $1210 ($97-$13 054) per patient. There was a significant difference between low-risk and combined (intermediate-high) risk groups as 635 (97-1500) and 2264.5 (154-13 054), respectively (p = 0.012). In conclusion, a clinical grading score can be used to predict illness severity and to predict associated health care costs.