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Hemorrhagic Fever With Renal Syndrome

Disease Details

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Description: Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease caused by hantaviruses, characterized by fever, hemorrhage, and acute kidney failure.
Type: Hemorrhagic fever with renal syndrome (HFRS) is a type of viral hemorrhagic fever. It is not transmitted genetically; rather, it is an infectious disease transmitted through contact with the urine, feces, or saliva of infected rodent hosts, specifically rodents from the family Muridae.
Signs And Symptoms: Symptoms of HFRS usually develop within one to two weeks after exposure to infectious material, but in rare cases, they may take up to eight weeks to develop. In Nephropathia epidemica, the incubation period is three weeks. Initial symptoms begin suddenly and include intense headaches, back and abdominal pain, fever, chills, nausea, and blurred vision. Individuals may have flushing of the face, inflammation or redness of the eyes, or a rash. Later symptoms can include low blood pressure, acute shock, vascular leakage, and acute kidney failure, which can cause severe fluid overload.
The severity of the disease varies depending upon the virus causing the infection. Hantaan and Dobrava virus infections usually cause severe symptoms, while Seoul, Saaremaa, and Puumala virus infections are usually more moderate. Complete recovery can take weeks or months.The course of the illness can be split into five phases:

Febrile phase
Symptoms include redness of cheeks and nose, fever, chills, sweaty palms, diarrhea, malaise, headaches, nausea, abdominal and back pain, respiratory problems such as the ones common in the influenza virus, as well as gastro-intestinal problems. These symptoms normally occur for three to seven days and arise about two to three weeks after exposure.Hypotensive phase
This occurs when the blood platelet levels drop and symptoms can lead to tachycardia and hypoxemia. This phase can last for two days.Oliguric phase
This phase lasts for three to seven days and is characterised by the onset of renal failure and proteinuria.Diuretic phase
This is characterized by diuresis of three to six litres per day, which can last for a couple of days up to weeks.Convalescent phase
This is normally when recovery occurs and symptoms begin to improve.This syndrome can also be fatal. In some cases, it has been known to cause permanent renal failure.
Prognosis: For Hemorrhagic Fever with Renal Syndrome (HFRS), the prognosis varies based on the severity of the infection and timely medical intervention. Generally, the disease can present in mild, moderate, or severe forms. The mild form has a good prognosis, with most patients recovering fully. In contrast, severe forms can lead to significant complications, including acute kidney injury and hemorrhage, which can be fatal if not managed properly. Early diagnosis and supportive care significantly improve outcomes, reducing the mortality rate in treated settings to between 1-15%.
Onset: The onset of Hemorrhagic Fever with Renal Syndrome (HFRS) typically begins with nonspecific symptoms such as fever, chills, headache, and muscle aches. These symptoms can appear suddenly and usually start about 1 to 2 weeks after exposure to the virus. The disease can progress through several phases, including febrile, hypotensive, oliguric, diuretic, and convalescent phases.
Prevalence: Hemorrhagic fever with renal syndrome (HFRS) is most prevalent in Asia and parts of Europe. It is particularly common in China, Korea, Russia, and some Balkan countries. The disease is caused by hantaviruses, which are carried by rodents and can be transmitted to humans through contact with rodent urine, droppings, or saliva. The prevalence can vary widely based on rodent population densities and human exposure levels.
Epidemiology: HFRS is primarily a Eurasian disease, whereas HPS appears to be confined to the Americas. The geography is directly related to the indigenous rodent hosts and the viruses that coevolved with them.Although fatal in a small percentage of cases, nephropathia epidemica is generally milder than the HFRS that is caused by hantaviruses in other parts of the world.
Intractability: Hemorrhagic fever with renal syndrome (HFRS) can be challenging to manage but is not necessarily intractable. The disease is caused by hantaviruses and can vary in severity. Management typically includes supportive care, such as maintaining fluid and electrolyte balance, managing blood pressure, and, in severe cases, providing renal replacement therapy like dialysis. Early diagnosis and appropriate medical care can improve outcomes. While there is no specific antiviral treatment widely available for HFRS, supportive medical care significantly impacts recovery.
Disease Severity: Hemorrhagic fever with renal syndrome (HFRS) varies in severity among infected individuals, ranging from mild to severe forms. Mild cases may present with flu-like symptoms, while severe cases can lead to hemorrhagic manifestations, acute kidney injury, and potentially be fatal. The disease severity depends on factors such as the hantavirus type, patient health, and promptness of supportive care. Overall, severe cases require intensive medical attention and carry a significant risk of serious complications.
Healthcare Professionals: Disease Ontology ID - DOID:11266
Pathophysiology: Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses, which are transmitted through contact with the urine, droppings, or saliva of infected rodents. The pathophysiology involves several key steps:

1. **Viral Entry and Early Infection**: The virus enters the body through the respiratory tract and infects endothelial cells, which line blood vessels.

2. **Immune Response and Cytokine Release**: The immune system responds to the infection, leading to the release of cytokines and inflammatory mediators. This inflammatory response contributes to increased vascular permeability.

3. **Endothelial Dysfunction**: The virus causes direct damage to endothelial cells and disrupts the endothelial barrier, leading to plasma leakage and hypotension.

4. **Hemorrhage and Kidney Damage**: Increased vascular permeability and capillary leakage result in hemorrhage and subsequent damage to organs, including the kidneys. The kidneys may suffer from acute tubular necrosis and interstitial nephritis.

5. **Renal Involvement**: The hallmark of HFRS is kidney dysfunction, which manifests as oliguria (reduced urine output), proteinuria (excessive protein in the urine), and, in severe cases, acute kidney injury.

The multi-system involvement and the interplay between viral replication, immune response, and endothelial damage contribute to the clinical manifestations of hemorrhagic fever with renal syndrome.
Carrier Status: Hemorrhagic fever with renal syndrome (HFRS) is primarily carried by rodents. The disease is caused by hantaviruses, which are found in the urine, droppings, and saliva of infected rodents. Humans typically become infected through inhalation of aerosolized virus particles from rodent excreta.
Mechanism: Hemorrhagic fever with renal syndrome (HFRS) is primarily caused by hantaviruses. The disease mechanism involves vascular endothelial damage leading to hemorrhage and renal dysfunction.

**Mechanism:**
1. **Transmission and Entry:** Hantaviruses are transmitted to humans primarily through aerosolized particles from rodent excreta. The virus enters the human body via the respiratory tract and targets endothelial cells lining blood vessels.
2. **Endothelial Cell Infection:** The virus infects and replicates in endothelial cells, causing increased permeability and leading to plasma leakage.
3. **Immune Response:** Infected endothelial cells trigger a strong immune response, including cytokine release, which can exacerbate vascular permeability and tissue damage.
4. **Hemorrhage and Renal Damage:** The disruption of endothelial barrier function results in hemorrhaging. The kidneys are particularly affected, leading to renal failure due to impaired capillary functions.

**Molecular Mechanisms:**
1. **Virus Receptors:** Hantaviruses utilize integrins (like β3 and β1 integrins) as receptors to facilitate entry into endothelial cells.
2. **Host Cell Manipulation:** Upon entry, hantaviruses manipulate host cell machinery to hinder apoptosis and promote viral replication.
3. **Cytokine Storm:** The infected endothelial cells produce various cytokines (e.g., TNF-α, IL-6) which contribute to systemic inflammation and increased vascular permeability.
4. **Complement Activation:** The activation of the complement system further damages endothelial cells and exacerbates vascular leakage.
5. **Platelet Dysfunction:** Hantavirus interaction with platelets may impair normal clotting mechanisms, increasing the risk of hemorrhage.

Understanding these mechanisms provides insight into potential therapeutic targets and interventions for HFRS.
Treatment: There is no cure for HFRS. Treatment involves supportive therapy including renal dialysis. Treatment with ribavirin in China and Korea, administered within seven days of onset of fever, resulted in a reduced mortality as well as shortened course of illness.
Compassionate Use Treatment: Hemorrhagic fever with renal syndrome (HFRS) is a viral disease caused by hantaviruses. The mainstay of management involves supportive care, but experimental or compassionate use treatments have garnered interest:

1. **Ribavirin**: An antiviral drug that has shown efficacy in some clinical trials for reducing the severity and duration of HFRS when administered early in the disease course.

2. **Favipiravir (T-705)**: An antiviral drug investigated for various viral infections that has shown promise in experimental settings against hantavirus.

3. **Plasma Exchange and Hemofiltration**: Used in severe cases to manage complications such as renal failure, although not a curative treatment.

4. **Immunomodulatory Therapies**: Such as corticosteroids, have been considered to mitigate immune-mediated damage during advanced disease stages. However, their benefit remains unclear and requires further research.

Experimental treatments ideally occur within the scope of clinical trials to ensure safety and efficacy.
Lifestyle Recommendations: For individuals affected by Hemorrhagic Fever with Renal Syndrome (HFRS), here are some lifestyle recommendations to aid in recovery and prevent further complications:

1. **Rest and Hydration**: Ensure adequate rest and stay well-hydrated to support kidney function and overall recovery.

2. **Balanced Diet**: Follow a nutritious diet rich in fruits, vegetables, lean proteins, and whole grains to boost the immune system and promote healing.

3. **Avoid Strenuous Activities**: Reduce physical exertion to avoid undue stress on the body, especially the kidneys.

4. **Monitor Health**: Regularly check vital signs and kidney function as advised by a healthcare provider.

5. **Medication Adherence**: Take all prescribed medications on schedule and avoid any non-prescribed treatments without consultation.

6. **Prevent Infection**: Maintain good hygiene to avoid secondary infections, and follow any specific guidelines to prevent new infections.

7. **Recognize Symptoms**: Be aware of worsening symptoms like increased abdominal pain or decreased urine output and seek medical attention when necessary.

8. **Rodent Control**: Since HFRS is often transmitted through exposure to rodent excreta, maintain a clean living environment and take measures to prevent rodent infestations.

These lifestyle adjustments support recovery and help manage symptoms associated with HFRS. Always follow medical advice provided by healthcare professionals.
Medication: There is no specific antiviral medication approved for hemorrhagic fever with renal syndrome (HFRS). Supportive treatment is the main approach, which includes maintaining fluid and electrolyte balance, renal function support (such as dialysis if necessary), and managing bleeding and blood pressure. In severe cases, ribavirin, an antiviral drug, has been used off-label with some reported success in reducing severity and mortality. Early medical intervention is crucial.
Repurposable Drugs: For hemorrhagic fever with renal syndrome (HFRS), repurposable drugs such as ribavirin, an antiviral medication originally used for treating hepatitis C, have shown some efficacy. Additionally, supportive care, including managing fluid and electrolyte balance and renal function maintenance, plays a crucial role in treatment. However, always consult with a healthcare provider for the most appropriate treatment options.
Metabolites: Hemorrhagic Fever with Renal Syndrome (HFRS) is primarily caused by hantaviruses. While specific metabolomic studies on HFRS may be limited, key metabolic changes associated with viral infections can include alterations in amino acids, lipids, and energy metabolism. Significant metabolites may include:

1. Amino acids such as glutamine and arginine.
2. Lipid metabolites including fatty acids.
3. Biomarkers related to oxidative stress and inflammation, like malondialdehyde.

These metabolic changes can reflect the body's response to infection and the ensuing renal and systemic damage. Further targeted metabolomic studies would be needed to detail the specific metabolites unique to HFRS.
Nutraceuticals: Currently, there are no specific nutraceuticals recommended for the prevention or treatment of hemorrhagic fever with renal syndrome (HFRS). Treatment primarily focuses on supportive care, including maintaining fluid and electrolyte balance, managing blood pressure, and dialysis if necessary.
Peptides: Hemorrhagic fever with renal syndrome (HFRS) is associated with hantaviruses. There is research on peptide-based therapeutics aimed at neutralizing the virus or modulating the immune response. Peptides can be designed to interfere with viral entry or replication and may serve as potential treatments. However, development and clinical testing of such therapies are ongoing, and no peptide-based treatments for HFRS are currently approved for widespread clinical use.