Ebola primer, v2.0

Epidemiology

• The current outbreak in Guinea, Liberia, and Sierra Leone is the largest ever recorded, with approximately 14,000 cases to date. Mortality rates in African treatment units exceed 60%.
• The natural reservoir of the virus (a filovirus) is suspected to be fruit-eating bats.
• Transmission occurs via contact with infected human body fluids (blood, saliva, sweat, vomitus, stool, semen, breast milk, and tears). Most transmission events are associated with direct contact with blood and body fluids. Transmission via indirect contact (i.e., fomites) can occur but appears to be uncommon.
• Nosocomial transmission is a key driver of outbreaks. Healthcare workers are at high risk for infection.
• Transmission has not been demonstrated from individuals who are in the asymptomatic incubation period. Even in the early stages of symptomatic disease, risk of transmission appears to be very low. As the disease progresses, infectivity increases. Infectivity is highly positively correlated with the patient's viral load.

Clinical

• The incubation period is 2-21 days (usually 5-7 days).
• The illness is characterized by onset of fever, chills, myalgias and malaise. This is followed in a few days by GI symptoms (nausea, vomiting, profuse diarrhea and abdominal pain), and headache. GI fluid losses can be as high as 10 L/day. Relative bradycardia is common.
• Hemorrhagic symptoms usually occur at the peak of illness and include maculopapular rash, petechiae, bruising, and bleeding from venipuncture sites. Gross bleeding from the GI and GU tracts is usually only seen in dying patients. Of note, overt bleeding has been uncommon in the current outbreak.
• The late stage of disease is manifested by cytokine storm, multiple organ dysfunction syndrome, shock, capillary leak syndrome, seizures, delerium, coma, bleeding and anuria.
• Laboratory findings include azotemia, leukopenia, thrombocytopenia, elevated transaminases, severe electrolyte abnormalities, proteinuria, and markers of DIC. Bilirubin is typically normal.
• Spontaneous abortion occurs at high rates in pregnant women and mortality rates are higher in pregnant women.
• Age is associated with mortality (highest survival rates are seen in those <21 years old).
• Mean time from onset of symptoms to death in African treated cases is 10 days.
• In survivors, the convalescent phase is long.
• Ebola viral disease should be suspected in a patient with a history of travel to an outbreak area who has fever or other associated symptoms, though other infections (e.g., malaria, typhoid fever) must also be considered.

Diagnostic Testing 

• Diagnostic testing focuses on PCR, which may be negative in the early stages of infection.
• In the United States, most testing is currently performed in public health laboratories. 
• A commercially available PCR assay (by Biofire Defense) with a 1 hour turn around time was given an Emergency Use Authorization by the FDA on 10/25/14.
• Viral load in serum increases as the disease progresses and may be as high as 10 billion/mL at the time of death.
• Viral load mirrors clinical response and when undetectable establishes that the patient is no longer infectious and can be released from isolation.
• Viral load at the time of presentation predicts mortality (VL <100,000 associated with 33% mortality, whereas >10 million was associated with 94% mortality in data from Sierra Leone). 

Treatment

• Treatment is focused on aggressive supportive care, particularly fluid and electrolyte management. Antiemetics and antimotility agents should be used to reduce GI fluid losses. 
• Hyperimmune serum from recovered patients has been used in the United States.
• No approved antiviral therapy is currently available. 
• Experimental therapies include brincidofovir (by Chimerix), monoclonal antibody (ZMapp by Mapp Biopharmacuetical), and TKM-Ebola (small interfering RNAs by Tekmira).
• Corticosteroids, nonsteroidal anti-inflammatory drugs, and aspirin are contraindicated. 
• Early treatment in developed countries appears to be effective.

Resources:

• CDC Ebola site
• WHO Ebola site
• New England Journal of Medicine Ebola publications

Photo: Frederick Murphy, CDC.