Ebola Viral Disease (EVD)

Essentials of Diagnosis

• Early stage EVD presents as a nonspecific febrile illness

• Later stage EVD typically includes severe gastrointestinal symptoms, followed by neurologic ones and hypovolemic shock

• Hemorrhagic manifestations occur late in course

• Uveitis is prominent ocular finding

• Travel and contact history from an Ebola-affected country raise suspicion

• Diagnosis is confirmed by detection of virus with a real-time polymerase chain reaction

General Considerations

• The first Ebola outbreak occurred in 1976 as a simultaneous epidemic in the Democratic Republic of Congo and South Sudan

• The number of EVD cases spread rapidly; there are at least 10 affected countries, especially Guinea, Liberia, and Sierra Leone. Many cases and deaths in these countries occurred among health care workers.

• As of November 2019, 3298 probable and confirmed cases (and 2197 deaths) were reported from 28 health zones in the Democratic Republic of Congo, including 163 cases among health care workers

• Countries with effective viral containment include Sierra Leone, Liberia and Guinea. Outbreaks in the Democratic Republic of Congo have been reported as of 2018.

• Four species cause human disease

  • Species: Zaire ebolavirus; virus: Ebola virus (EBOV)

  • Species: Sudan ebolavirus; virus: Sudan virus

  • Species: Taï Forest ebolavirus; virus: Taï Forest virus (TAFV)

  • Species: Bundibugyo ebolavirus; virus: Bundibugyo virus

• Transmission

  • Occurs from direct contact with infected body fluids

  • No evidence supporting airborne transmission

  • However, the virus aerosolizes, meaning that certain settings such as health facilities carry additional risk

  • Virus must enter the body via mucous membranes, nonintact skin, sexual intercourse (virus has been detected in semen up to 9 months after recovery from infection), breastfeeding, or needlestick

  • Prior to symptoms, Ebola is not transmitted

• Ebola has a 2- to 21-day incubation period (average is 8–10 days)

Symptoms and Signs

• Early stage EVD

  • Headache

  • Weakness

  • Dizziness

  • Fever

  • Malaise, fatigue

  • Myalgia, arthralgia

• Later stage EVD (after 3–5 days)

  • Abdominal pain, severe nausea, vomiting, and diarrhea accompanying the febrile illness

  • Encephalitis is commonly observed and includes

    • Confusion

    • Slowed cognition

    • Agitation

    • Occasional seizures

  • Hypovolemic shock develops in most patients

  • However, hemorrhagic manifestations (gastrointestinal bleeding, diffuse mucosal bleeding, conjunctival bleeding) develop in only 1–5% of patients

  • Respiratory symptoms (ie, cough) are not typical, although interstitial pneumonia and respiratory failure are reported

Differential Diagnosis

• Varies with the stage of illness

• Early stage EVD

  • Malaria, typhoid, and other viral illnesses

  • Viral hepatitis

  • Toxins

  • Leptospirosis

  • Rickettsial diseases

• In later stage EVD

  • Bacterial, viral, and parasitic illnesses, including cholera

  • In children, rotavirus infection, which can present with severe gastroenteritis and shock

  • Encephalitis must be differentiated from the confusion associated with acute kidney injury and other neurologic manifestations

• As nonspecific symptoms progress to a severe systemic inflammatory response, coagulopathy with evidence of platelet dysfunction and DIC often develops

• IgM antibodies and IgG antibody response on real-time polymerase chain reaction

• Low platelet count

• Leukopenia

• Transaminitis (AST greater than ALT)

• Hypoalbuminemia

• Electrolytes imbalance

• Increased serum creatinine level

• Elevated blood urea nitrogen, AST, and creatinine upon presentation are associated with higher mortality

• There are no approved medications for the treatment of EVD

• Administration of convalescent plasma does not result in improved survival

• Supportive

• Intravenous fluids can reduce the mortality rates to < 50%

• Invasive or noninvasive mechanical ventilation and continuous renal replacement therapy are necessary in many cases

• Patients typically receive empiric antimalarial agents and broad-spectrum antibiotics

• Two antivirals used in the EVD outbreak

  • ZMapp

    • A combination of three chimeric monoclonal antibodies against Zaire ebolavirus

    • Safe and well tolerated

    • However, the PREVAIL II study failed to establish efficacy due to low enrollment numbers

  • REGN-EB3

    • Another combination of three monoclonal antibodies against Zaire ebolavirus

    • Given as a single dose

    • Does not require freezing

    • Shows efficacy in nonhuman primates, including reduction in mortality

• Remdesivir and favipiravir

  • High likelihood of efficacy for both agents against EVD if given within 3–4 days of infection

  • Efficacy of remdesivir is theoretically 100% while that for favipiravir is 60%

Complications

• Hypovolemic shock

• Multiorgan failure

• Rhabdomyolysis

• Coinfections with malaria or bacteria, or both

• Musculoskeletal pain; headache; auditory symptoms (including hearing loss); and ocular symptoms, including uveitis, may develop postinfection

• EVD survivors exhibit high rates of neuropsychological long-term sequelae including

  • Depression

  • Anxiety

  • Posttraumatic stress disorder

Prevention

• Disinfection, hygiene, sanitation, and isolation

• The experimental recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing Zaire ebolavirus (ZEBOV) glycoprotein

  • Found to be highly effective in disease prevention after 10 days from receiving the vaccine

  • Side effects of the vaccine include

    • Fever

    • Myalgia

    • Chills

    • Fatigue

    • Headaches

    • Oligoarthritis

  • Showed promising results in phase III clinical trials (most study participants had persistent antibody levels at 1 year)

• The WHO recommends that men avoid sexual activity or use barrier protection during intercourse for 12 months from onset of symptoms or until their semen tests negative twice for Ebola virus

Prognosis

• Mortality rates are about 70% in endemic areas

• Pregnancy is a risk factor for severe illness and death; in the 2014–2016 outbreak, the average maternal mortality was 86%

• Immunosuppressed patients had shorter incubation time, rapid progression of disease, and poor outcomes

• A higher baseline viral load was strong predictor of mortality

• In general, poor overall medical care confers a poor prognosis

• Among survivors, protective antibodies persist for at least 10 years

When to Admit

• Persons living in or returning from a country with high rates of Ebola transmission should be monitored for 21 days

• They should be admitted to a healthcare facility when symptoms meeting the WHO case definition of a suspected EVD case develop; for example,

  • Any person suffering from a fever (or history of fever) and having had contact with suspected, probable or confirmed Ebola case;

  • Any person with a fever (or history of fever) and at least three of the following symptoms:

    • Headaches

    • Vomiting

    • Anorexia/loss of appetite

    • Diarrhea

    • Lethargy

    • Stomach pain

    • Aching muscles or joints

    • Difficulty swallowing

    • Breathing difficulties

    • Hiccups

  • Any person with inexplicable bleeding