"Ebola Virus"

 

Ebola virus (EBOV) is a highly virulent pathogen that causes Ebola virus disease (EVD), a severe hemorrhagic fever with high mortality rates. It belongs to the Filoviridae family and is classified under the genus Ebolavirus. The virus has caused multiple outbreaks, primarily in sub-Saharan Africa, and remains a significant public health concern.

1. Virology & Structure

  • Ebola virus is a negative-sense, single-stranded RNA virus (~19 kb genome).
  • It has a filamentous structure (up to 14,000 nm long, ~80 nm in diameter).
  • The viral genome encodes seven structural proteins:
    1. Nucleoprotein (NP) – Encapsidates RNA for replication.
    2. Viral protein 35 (VP35) – Inhibits the host immune response.
    3. Viral protein 40 (VP40) – Essential for virion assembly.
    4. Glycoprotein (GP) – Mediates host cell entry.
    5. Viral protein 30 (VP30) – Regulates transcription.
    6. Viral protein 24 (VP24) – Antagonizes interferon signaling.
    7. RNA-dependent RNA polymerase (L protein) – Essential for viral replication.

2. Pathogenesis & Mechanism of Infection

Entry & Replication

  • The virus enters host cells through macropinocytosis, mediated by the GP protein.
  • It binds to Niemann-Pick C1 (NPC1), a key endosomal receptor.
  • The viral genome is released, and replication occurs in the cytoplasm.

Immune Evasion

  • VP35 and VP24 suppress interferon (IFN) responses.
  • Ebola disrupts dendritic cells, preventing effective immune activation.
  • It induces massive cytokine storms, leading to widespread inflammation.

Tissue Destruction & Hemorrhagic Features

  • Endothelial damage → causes vascular leakage, shock, and hemorrhages.
  • Liver failure → impairs clotting, contributing to hemorrhagic symptoms.
  • Lymphocyte apoptosis → leads to severe immunosuppression.

3. Symptoms & Clinical Presentation

  • Incubation period: 2–21 days (average ~8–10 days).
  • Early Symptoms (nonspecific, flu-like):
    • High fever
    • Fatigue, muscle pain
    • Headache, sore throat
  • Progressive Symptoms:
    • Severe vomiting, diarrhea → leads to dehydration.
    • Hemorrhagic manifestations: internal/external bleeding, hematemesis, epistaxis.
    • Multi-organ failure, septic shock.

4. Diagnosis

  • RT-PCR (Reverse Transcription Polymerase Chain Reaction) – Gold standard for viral RNA detection.
  • ELISA (Enzyme-Linked Immunosorbent Assay) – Detects viral antigens or antibodies.
  • Viral culture – Performed in high-containment biosafety labs.

5. Transmission

  • Human-to-human transmission:
    • Direct contact with bodily fluids (blood, saliva, vomit, urine, sweat, semen, breast milk).
    • Contaminated objects (needles, medical equipment).
    • Sexual transmission (virus can persist in semen for months).
  • Zoonotic reservoir:
    • Likely fruit bats (Pteropodidae family).
    • Transmission via infected animals (apes, monkeys, pigs).

6. Treatment & Vaccination

Supportive Care

  • Fluid resuscitation (IV fluids, electrolytes).
  • Oxygen therapy & blood pressure management.
  • Anticoagulants/Coagulation therapy (depending on phase).
  • Organ support (dialysis, ventilation if needed).

Antiviral Therapies

  • Monoclonal antibodies:
    • Inmazeb (REGN-EB3) – Three-antibody cocktail.
    • Ansuvimab (mAb114) – Single monoclonal antibody.
  • RNA-based therapies:
    • Remdesivir (experimental).
  • Convalescent plasma (historically used but limited efficacy).

Vaccination

  • rVSV-ZEBOV (Ervebo) – Highly effective single-dose vaccine.
  • Ad26.ZEBOV/MVA-BN-Filo – Two-dose regimen for outbreak prevention.

7. Epidemiology & Outbreaks

  • First identified: 1976, simultaneous outbreaks in Sudan and Zaire (now DRC).
  • Largest outbreak: 2014–2016 West Africa Epidemic (~28,000 cases, 11,000 deaths).
  • Recent outbreaks:
    • 2018–2020 DRC outbreak – Introduced widespread vaccination.
    • 2022 Uganda outbreak (Sudan strain, not covered by rVSV-ZEBOV).

8. Prevention & Future Research

  • Quarantine & isolation protocols in outbreaks.
  • Rapid diagnostic tools to detect early infections.
  • New antivirals targeting viral replication and immune evasion.
  • Long-term immunity & post-infection complications research.

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