Crimean-congo Hemorrhagic Fever
Disease Details
Family Health Simplified
- Description
- Crimean-Congo hemorrhagic fever is a viral zoonotic disease characterized by sudden onset of fever, muscle aches, and bleeding, transmitted through tick bites or contact with infected animal blood or tissues.
- Type
- Crimean-Congo hemorrhagic fever (CCHF) is a viral disease. Its genetic material is RNA, and it belongs to the Nairoviridae family, genus Orthonairovirus. The virus is transmitted to humans primarily through tick bites or contact with blood or tissues from infected livestock. Human-to-human transmission can also occur via direct contact with infectious blood or bodily fluids.
- Signs And Symptoms
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The clinical illness associated with CCHFV (the CCHF virus) is a severe form of hemorrhagic fever. Following infection by a tick bite, the incubation period is typically two to three days but can last as long as nine days, while the incubation period following contact with infected blood or tissues is usually five to six days with a documented maximum of 13 days. The onset of symptoms ushering in the pre-hemorrhagic phase is sudden, with fever, myalgia (muscle ache), dizziness, neck pain and stiffness, backache, headache, sore eyes and photophobia (sensitivity to light). Typical symptoms include nausea, vomiting (which may progress to severe bleeding and can be fatal if not treated), diarrhea, abdominal pain and sore throat early in the acute infection phase, followed by sharp mood swings, agitations and confusion. After several days, agitation may be replaced by sleepiness, depression and lassitude, and the abdominal pain may localize to the upper right quadrant, with detectable liver enlargement. As the illness progresses into the hemorrhagic phase, large areas of severe bruising, severe nosebleeds, and uncontrolled bleeding at injection sites can be seen, beginning on about the fourth day of illness and lasting for about two weeks. Other clinical signs include tachycardia (fast heart rate), lymphadenopathy (enlarged lymph nodes), and a petechiae (a rash caused by bleeding into the skin) on internal mucosal surfaces, such as in the mouth and throat, and on the skin. The petechiae may give way to larger rashes called ecchymoses, and other haemorrhagic phenomena. There is usually evidence of hepatitis, and severely ill patients may experience rapid kidney deterioration, liver failure or pulmonary failure after the fifth day of illness.
In documented outbreaks of CCHF, fatality rates in hospitalized patients have ranged from 9% to as high as 70%, though the WHO notes a typical range of 10–40%, with death often occurring in the second week of illness. In patients who recover, improvement generally begins on the ninth or tenth day after the onset of illness. The long-term effects of CCHF infection have not been studied well enough in survivors to determine whether or not specific complications exist. However, recovery is slow. - Prognosis
- Crimean-Congo hemorrhagic fever (CCHF) has a varied prognosis, depending on several factors such as the severity of the disease and the timing of treatment. The overall fatality rate for CCHF ranges between 10% and 40%. Early detection and supportive care can improve outcomes.
- Onset
- The onset of Crimean-Congo Hemorrhagic Fever (CCHF) typically includes sudden symptoms such as high fever, headache, back pain, joint pain, stomach pain, and vomiting. This is often followed by symptoms such as jaundice, mood swings, and petechiae, which are red spots caused by bleeding under the skin. The initial symptoms generally appear within 1 to 3 days of being bitten by a tick or coming into contact with infected blood, but can take up to 9 days in some cases.
- Prevalence
- Crimean-Congo hemorrhagic fever (CCHF) is most commonly found in Africa, the Balkans, the Middle East, and Asia. The prevalence can vary significantly by region and time of year, often correlating with tick activity and livestock movements. Human cases are relatively rare but can occur following tick bites or contact with infected animal blood or tissues. There are no definitive global prevalence statistics due to underreporting and variability in surveillance.
- Epidemiology
- CCHF occurs most frequently among agricultural workers, following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock, and medical personnel through contact with the body fluids of infected persons.
- Intractability
- Crimean-Congo hemorrhagic fever is potentially intractable due to the lack of highly effective antiviral treatments and the severe nature of the disease. Management primarily involves supportive care, and the use of ribavirin, an antiviral, has shown some benefits but is not universally effective. Mortality rates can be high, especially in severe cases.
- Disease Severity
- Crimean-Congo hemorrhagic fever (CCHF) can be a severe and potentially fatal disease. The severity can range from mild symptoms to severe hemorrhagic manifestations and multiorgan failure. The mortality rate varies but can be as high as 40%.
- Healthcare Professionals
- Disease Ontology ID - DOID:12287
- Pathophysiology
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Crimean-Congo Hemorrhagic Fever (CCHF) is caused by the Crimean-Congo hemorrhagic fever virus (CCHFV) belonging to the Nairovirus genus of the Bunyaviridae family. The pathophysiology involves several key steps:
1. **Transmission**: CCHFV is primarily transmitted to humans through bites from infected ticks (Hyalomma species), contact with blood or tissues from infected livestock, or human-to-human transmission via blood or bodily fluids.
2. **Viral Entry and Replication**: Once the virus enters the bloodstream, it infects endothelial cells, monocytes, macrophages, and hepatocytes. The virus uses these cells to replicate and disseminate throughout the host's body.
3. **Immune Response and Cytokine Storm**: The infection triggers a robust immune response, including the release of pro-inflammatory cytokines. An excessive immune response, or "cytokine storm," can contribute to disease severity.
4. **Endothelial Damage and Hemorrhage**: CCHFV induces apoptosis (programmed cell death) in infected endothelial cells, leading to increased vascular permeability, capillary leakage, and widespread tissue damage. This endothelial damage is a significant factor in the hemorrhagic manifestations of the disease.
5. **Coagulopathy**: The virus can impair the host's coagulation system, causing disseminated intravascular coagulation (DIC) and leading to organ failure and hemorrhage.
6. **Multiorgan Failure**: Severe cases can progress to multiple organ failure due to a combination of direct viral damage, widespread inflammatory response, and coagulopathy.
These combined mechanisms result in the severe clinical manifestations of CCHF, such as high fever, severe bleeding, liver dysfunction, and shock, which can lead to high mortality rates if untreated. - Carrier Status
- Crimean-Congo hemorrhagic fever (CCHF) is primarily transmitted through bites of infected Hyalomma ticks or through contact with blood or tissues from infected livestock. Hyalomma ticks are the main carriers of the virus. Humans can also become infected through direct contact with the blood or bodily fluids of infected individuals, particularly in healthcare settings without adequate infection control measures.
- Mechanism
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Crimean-Congo hemorrhagic fever (CCHF) is caused by the Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the Nairoviridae family. The mechanism of the disease involves several stages:
1. **Entry and Replication**: CCHFV typically enters the human body through tick bites or contact with infected animal blood or tissues. The virus binds to host cell surface receptors, possibly involving cell surface proteoglycans and low-density lipoprotein receptor-related proteins. After entry via endocytosis, the viral RNA genome is released into the cytoplasm, where it hijacks the host's machinery to replicate and produce proteins.
2. **Immune Evasion and Host Response**: CCHFV can evade the host immune system by inhibiting the interferon response, which is crucial for antiviral defense. The viral non-structural proteins (NSs) and other factors interfere with the signaling pathways, reducing the efficacy of the host’s innate immune response.
3. **Viral Assembly and Release**: Newly formed viral particles are assembled within the host cell and then transported to the cell membrane, where they are released to infect new cells, propagating the infection.
### Molecular Mechanisms:
1. **Viral Proteins**:
- **Gn and Gc Glycoproteins**: These surface proteins are critical for viral attachment and entry into host cells.
- **L Protein (RNA-dependent RNA polymerase)**: This enzyme is essential for viral RNA replication and transcription.
- **N Protein (Nucleoprotein)**: Binds to viral RNA, protecting it and playing a role in replication and assembly.
2. **Interferon Antagonism**:
- **NSs Protein**: This non-structural protein inhibits the host's interferon response, helping the virus evade immune detection.
- **Other Viral Factors**: Some studies suggest additional viral proteins may interfere with the host's immune signaling pathways.
3. **Host Cell Damage**: The extensive viral replication and immune response can lead to widespread cell damage and vascular leakage, contributing to hemorrhagic symptoms, tissue necrosis, and multi-organ failure.
4. **Apoptosis and Cytokine Storm**: The virus can induce apoptosis (programmed cell death) in infected cells and provoke a cytokine storm, leading to an excessive inflammatory response. This contributes to severe symptoms and potentially fatal outcomes.
Understanding these molecular mechanisms is critical for developing targeted therapies and effective vaccines against CCHFV. - Treatment
- Treatment is mostly supportive. Ribavirin has shown some efficacy in vitro and has been used by mouth during outbreaks, but there is uncertain evidence to support its use, and this medication can cause serious side effects including hemolytic anemia and liver damage.As of 2011 the use of Immunoglobulin preparations has remained unproven and antibody engineering, which raised hopes for monoclonal antibody therapy, has remained in its infancy.
- Compassionate Use Treatment
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Crimean-Congo hemorrhagic fever (CCHF) is a severe viral disease with limited treatment options. The primary supportive treatment often involves managing symptoms and preventing complications. Experimental treatments and compassionate use options may include:
1. **Ribavirin**: This antiviral drug has been used off-label and on a compassionate use basis for CCHF. Some studies suggest it may reduce mortality if administered early in the course of the disease, although definitive clinical trial evidence is limited.
2. **Convalescent Plasma**: Using plasma from recovered CCHF patients has been considered, as it contains antibodies against the virus. This approach is experimental and used in some severe cases under compassionate use protocols.
3. **Favipiravir**: This antiviral, primarily used against other viral infections, is being explored as a potential treatment for CCHF, but clinical data is limited.
4. **Supportive Care**: Ensuring patients receive optimal supportive care in intensive care units—including maintaining fluid and electrolyte balance, managing blood pressure, and providing transfusions if necessary—is crucial.
Experimental and compassionate use treatments are typically pursued when standard supportive care is insufficient, and their use is often determined by the severity of the case and availability of these drugs. - Lifestyle Recommendations
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To reduce the risk of Crimean-Congo Hemorrhagic Fever (CCHF), consider the following lifestyle recommendations:
1. **Avoid Tick Bites**:
- Wear protective clothing, such as long sleeves and pants.
- Use tick repellents on exposed skin and clothing.
- Check for ticks regularly and remove them promptly.
2. **Safe Agricultural Practices**:
- Limit exposure to livestock and animal blood, particularly in regions where CCHF is endemic.
- Use protective equipment, like gloves and goggles, when handling animals or animal products.
3. **Healthcare Precautions**:
- Health workers should use standard infection control practices when handling suspected CCHF patients, including the use of personal protective equipment.
4. **Travel Precautions**:
- Be aware of CCHF endemic areas and take preventive measures if traveling to those regions.
5. **Educate and Inform**:
- Stay informed about outbreaks and follow public health advisories in affected areas.
Implementing these practices can significantly reduce the risk of contracting Crimean-Congo Hemorrhagic Fever. - Medication
- There are no specific antiviral medications approved for Crimean-Congo hemorrhagic fever. However, treatment primarily focuses on supportive care to manage symptoms and maintain vital functions. In some cases, Ribavirin, an antiviral drug, may be used off-label based on limited evidence suggesting potential benefits. Additionally, efforts are often made to ensure proper hydration, electrolyte balance, and blood pressure stabilization, along with careful monitoring for hemorrhagic complications.
- Repurposable Drugs
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Repurposable drugs that have been explored for Crimean-Congo Hemorrhagic Fever (CCHF) include:
1. **Ribavirin**: An antiviral drug traditionally used for hepatitis C, which has shown some effectiveness against CCHF in clinical and observational studies.
2. **Favipiravir**: Typically used for influenza, it has potential antiviral activity against a broad spectrum of RNA viruses, including the CCHF virus.
3. **Monoclonal Antibodies**: Targeting specific proteins of the CCHF virus, though still largely in experimental stages.
These drugs are not specifically approved for CCHF but have shown promise in various studies. Always consult healthcare professionals for the most appropriate treatment options. - Metabolites
- Metabolites for Crimean-Congo Hemorrhagic Fever (CCHF) have not been detailed in the information provided. Typically, in infectious diseases like CCHF, specific viral and host metabolites could be involved in the disease process, but detailed profiling often requires extensive biochemical analysis. Primary diagnostic methods for CCHF focus on detecting the virus itself, using techniques such as RT-PCR, serology, and viral culture.
- Nutraceuticals
- There is currently no established evidence that nutraceuticals or nanotechnology-based treatments are effective for Crimean-Congo Hemorrhagic Fever (CCHF). CCHF is a viral hemorrhagic fever caused by the Nairovirus, primarily transmitted through tick bites or contact with infected animal blood or tissues. Effective management typically includes supportive care, antiviral treatments like ribavirin, and prevention measures such as tick control and using personal protective equipment.
- Peptides
- Peptides have been investigated in the context of Crimean-Congo Hemorrhagic Fever (CCHF) for their potential roles in diagnostics, therapeutics, and vaccine development. Specifically, peptides can be used to identify and neutralize viral proteins, aiding in the design of antiviral drugs and improving immune responses against the virus. Nanotechnology can further enhance these applications by enabling targeted delivery systems, enhancing the stability of peptide-based drugs, and improving diagnostic sensitivity through nanoparticle-based assays.