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Marburg Hemorrhagic Fever

Disease Details

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Description: Marburg hemorrhagic fever is a severe and often fatal illness caused by the Marburg virus, characterized by sudden onset of fever, chills, headache, and myalgia followed by severe hemorrhaging.
Type: Marburg hemorrhagic fever is caused by the Marburg virus, which is a member of the Filoviridae family. The type of genetic transmission for this virus is via RNA.
Signs And Symptoms: The most detailed study on the frequency, onset, and duration of MVD clinical signs and symptoms was performed during the 1998–2000 mixed MARV/RAVV disease outbreak. A skin rash, red or purple spots (e.g. petechiae or purpura), bruises, and hematomas (especially around needle injection sites) are typical hemorrhagic manifestations. However, contrary to popular belief, hemorrhage does not lead to hypovolemia and is not the cause of death (total blood loss is minimal except during labor). Instead, death occurs due to multiple organ dysfunction syndrome (MODS) due to fluid redistribution, hypotension, disseminated intravascular coagulation, and focal tissue necroses.Clinical phases of Marburg hemorrhagic fever's presentation are described below. Note that phases overlap due to variability between cases.

Incubation: 2–21 days, averaging 5–9 days.
Generalization Phase: Day 1 up to Day 5 from the onset of clinical symptoms. MHF presents with a high fever 104 °F (~40˚C) and a sudden, severe headache, with accompanying chills, fatigue, nausea, vomiting, diarrhea, pharyngitis, maculopapular rash, abdominal pain, conjunctivitis, and malaise.
Early Organ Phase: Day 5 up to Day 13. Symptoms include prostration, dyspnea, edema, conjunctival injection, viral exanthema, and CNS symptoms, including encephalitis, confusion, delirium, apathy, and aggression. Hemorrhagic symptoms typically occur late and herald the end of the early organ phase, leading either to eventual recovery or worsening and death. Symptoms include bloody stools, ecchymoses, blood leakage from venipuncture sites, mucosal and visceral hemorrhaging, and possibly hematemesis.
Late Organ Phase: Day 13 up to Day 21+. Symptoms bifurcate into two constellations for survivors and fatal cases. Survivors will enter a convalescence phase, experiencing myalgia, fibromyalgia, hepatitis, asthenia, ocular symptoms, and psychosis. Fatal cases continue to deteriorate, experiencing continued fever, obtundation, coma, convulsions, diffuse coagulopathy, metabolic disturbances, shock and death, with death typically occurring between days 8 and 16.
Prognosis: Although supportive care can improve survival chances, marburg virus disease is fatal in the majority of cases. As of 2023 the case fatality rate was assessed to be 61.9%.
Onset: Marburg hemorrhagic fever has a sudden onset. Symptoms typically appear abruptly 2 to 21 days after exposure to the Marburg virus.
Prevalence: The incidence of Marburg hemorrhagic fever is extremely rare. Outbreaks have occurred infrequently and sporadically in parts of Africa, particularly in countries like Uganda, Angola, and the Democratic Republic of the Congo. Due to its rarity, there is no significant widespread prevalence.
Epidemiology: Marburg hemorrhagic fever is a severe, often fatal illness caused by the Marburg virus. Here's a brief overview of its epidemiology:

- **Geographical Distribution**: Primarily occurs in parts of Africa, with outbreaks reported in countries such as Uganda, Kenya, the Democratic Republic of the Congo, and Angola.
- **Reservoir**: The natural reservoir is the African fruit bat, Rousettus aegyptiacus.
- **Transmission**: Human infection occurs through direct contact with the body fluids of infected animals or individuals, or contaminated surfaces.
- **Incidence**: Outbreaks are sporadic and relatively rare but have a high case-fatality rate, often above 80%.
- **Affected Population**: Primarily affects people who have direct contact with fruit bats or who are caregivers for infected individuals, including healthcare workers.
Intractability: Marburg Hemorrhagic Fever is considered highly challenging to manage due to its severity, high mortality rate, and the lack of specific antiviral treatments. While supportive care can improve outcomes, the disease itself remains difficult to treat effectively.
Disease Severity: **Marburg Hemorrhagic Fever (MHF)**

- **Disease Severity:** Marburg Hemorrhagic Fever is a severe and often fatal illness in humans. It is characterized by sudden onset of high fever, severe headache, muscle pain, and, within a few days, severe hemorrhaging and multi-organ dysfunction. The case-fatality rate can be as high as 88%, depending on the outbreak and quality of care.

- **Nan:** No specific information available.
Healthcare Professionals: Disease Ontology ID - DOID:4327
Pathophysiology: **Pathophysiology:**

Marburg hemorrhagic fever (MHF) is caused by the Marburg virus, a member of the Filoviridae family. Following infection, the virus primarily targets endothelial cells, monocytes, and macrophages. The infection triggers a cascade of events leading to:

1. **Viral Replication**: The virus replicates rapidly within host cells, causing cell lysis and widespread tissue destruction.
2. **Immune Response**: The infection prompts an aggressive immune response, releasing pro-inflammatory cytokines and chemokines. This can result in a "cytokine storm," which exacerbates tissue damage.
3. **Endothelial Damage**: The virus directly infects endothelial cells lining blood vessels, causing cell death and leading to increased vascular permeability.
4. **Hemorrhage and Coagulopathy**: Vascular damage, along with the dysregulation of coagulation pathways, can result in severe hemorrhage, disseminated intravascular coagulation (DIC), and multi-organ failure.
5. **Systemic Involvement**: The combined effect of the viral cytopathic effect and immune-mediated damage can lead to multiple organ dysfunctions, including liver, kidney, and central nervous system involvement.

Nan is not associated with the pathophysiology of Marburg hemorrhagic fever, as it appears to be an unrelated or incorrect term.
Carrier Status: Marburg hemorrhagic fever is not associated with a carrier state in humans. The primary hosts are fruit bats, specifically the Egyptian fruit bat (Rousettus aegyptiacus). Humans typically become infected through contact with these bats or their excretions, and person-to-person transmission can occur through direct contact with bodily fluids of infected individuals.

"Nan" generally stands for "not a number" and is not applicable for carrier status in the context of infectious diseases.
Mechanism: Marburg hemorrhagic fever is caused by the Marburg virus, a filovirus similar to the Ebola virus. The disease's mechanism involves the virus entering the host through mucosal surfaces or broken skin. Once inside, the Marburg virus targets and infects various cell types, including dendritic cells, macrophages, and monocytes, leading to an impaired immune response.

### Molecular Mechanisms:
1. **Viral Entry**: The Marburg virus glycoprotein (GP) facilitates attachment to host cell receptors, followed by endocytosis and fusion with the host cell membrane, allowing viral RNA to enter the cytoplasm.
2. **Replication**: The RNA genome is transcribed and replicated using the host's cellular machinery, producing viral mRNA and new viral genomes.
3. **Protein Synthesis**: Viral proteins are synthesized in the cytoplasm and on the endoplasmic reticulum, assisting in assembly and maturation of new virions.
4. **Immune Evasion**: Marburg virus suppresses the host immune response by interfering with the function of interferons and other critical signaling molecules, mitigating the antiviral response.
5. **Cytokine Storm**: Infected cells release excessive inflammatory cytokines, leading to a "cytokine storm," causing widespread tissue damage and contributing to the hemorrhagic symptoms.
6. **Endothelial Damage**: The virus can infect endothelial cells, leading to increased vascular permeability and hemorrhaging due to the breakdown of vascular integrity.

These molecular events collectively lead to severe disease characterized by high fever, multi-organ failure, and significant internal bleeding.
Treatment: There is currently no effective marburgvirus-specific therapy for MVD. Treatment is primarily supportive in nature and includes minimizing invasive procedures, balancing fluids and electrolytes to counter dehydration, administration of anticoagulants early in infection to prevent or control disseminated intravascular coagulation, administration of procoagulants late in infection to control hemorrhaging, maintaining oxygen levels, pain management, and administration of antibiotics or antifungals to treat secondary infections.
Compassionate Use Treatment: Marburg hemorrhagic fever (MHF) is a severe and often fatal illness. Currently, no specific antiviral treatment has been approved for MHF. However, several experimental treatments and compassionate use therapies have been explored:

1. **Favipiravir**: An antiviral drug that has shown some promise in reducing viral replication in laboratory settings.

2. **Remdesivir**: Another antiviral that has been tested against Marburg virus in preclinical studies.

3. **ZMapp and Other Monoclonal Antibodies**: These have been studied for their effectiveness against related hemorrhagic fevers like Ebola, and similar approaches are being researched for Marburg.

4. **Convalescent Serum**: Plasma from recovered patients, which contains antibodies against the virus, may be used in an attempt to boost the immune response.

5. **Vaccines under Development**: While primarily preventative, some vaccines being developed could potentially be used in post-exposure scenarios.

These treatments are not officially approved for Marburg and are considered experimental, often available only through clinical trials or compassionate use protocols.
Lifestyle Recommendations: Lifestyle recommendations to reduce the risk of Marburg hemorrhagic fever include the following:

1. **Avoid Caves and Mines**: Avoid visiting caves or mines that might be inhabited by Rousettus bats, which are known to be natural hosts of the Marburg virus.
2. **Use Protective Gear**: If you are in a region where outbreaks have occurred, wear protective clothing like gloves and masks, especially if you are involved in health care or handling animals.
3. **Practice Good Hygiene**: Wash hands frequently with soap and water or use alcohol-based hand sanitizers, particularly after being in contact with sick individuals or animals.
4. **Safe Burial Practices**: If you need to handle deceased individuals who may have been infected, follow strict protocols to prevent exposure, such as using protective gear and ensuring proper burial practices.
5. **Avoid Contact with Infected Individuals**: Avoid direct contact with the blood or bodily fluids of people who are sick with Marburg hemorrhagic fever.
6. **Disinfect and Clean**: Ensure that all surfaces, medical equipment, and environments that might be contaminated are properly disinfected and cleaned.
7. **Seek Medical Attention Promptly**: If you suspect that you or someone else is infected, seek medical attention immediately to get appropriate treatment and reduce the risk of spreading the virus.

Following these recommendations can help reduce the risk of contracting Marburg hemorrhagic fever and limit its spread.
Medication: Currently, there is no specific antiviral medication approved for Marburg hemorrhagic fever. Treatment primarily involves supportive care, which includes maintaining hydration, providing oxygen, managing blood pressure, replacing lost blood and clotting factors, and treating any complicating infections. Experimental treatments and therapies, such as monoclonal antibodies and antiviral drugs, are being researched but are not yet widely available.
Repurposable Drugs: There are no officially approved treatments specifically for Marburg hemorrhagic fever at this time. Some repurposable drugs and treatments that have been explored include:

1. **Favipiravir:** An antiviral drug initially developed to treat influenza, showing potential in experimental treatments against the virus.
2. **Remdesivir:** Another antiviral initially developed for Ebola, which has shown some effectiveness in treating Marburg virus in laboratory settings.
3. **Monoclonal antibodies:** Such as the ones developed for Ebola, which may be cross-reactive and provide therapeutic benefits against Marburg virus.

These drugs are still under investigation and would require more clinical trials to establish their efficacy and safety for Marburg hemorrhagic fever.
Metabolites: Marburg hemorrhagic fever is caused by the Marburg virus, which belongs to the Filoviridae family. Regarding metabolites specific to Marburg hemorrhagic fever, there is limited detailed information. However, the disease causes systemic disruptions and can lead to significant metabolic disturbances, such as elevated liver enzymes, alterations in electrolytes, and changes in blood coagulation parameters. These indicate liver dysfunction and hemorrhagic manifestations.
Nutraceuticals: There are no specific nutraceuticals documented or validated for the prevention or treatment of Marburg hemorrhagic fever. Management primarily involves supportive care, including rehydration, maintenance of electrolyte balance, and treatment of specific symptoms.
Peptides: Marburg hemorrhagic fever (Marburg HF) is a severe, often fatal illness caused by the Marburg virus. While there is limited specific information on peptides directly associated with Marburg HF, peptides in the context of viral infections can be relevant for therapeutic and diagnostic purposes. Research into antiviral peptides, which can inhibit virus entry or replication, is ongoing. Additionally, peptides derived from viral proteins can be used as antigens in vaccine development or in diagnostic assays to detect immune responses.

In the case of Marburg HF and other viral hemorrhagic fevers, the development and study of such peptides are crucial due to the lack of widely available treatments and vaccines. Researchers are exploring various peptides that can neutralize the virus or elicit a strong immune response to provide protection or improve diagnostic accuracy.