Medical Grand Rounds

Ebola virus: Questions, answers, and more questions

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ABSTRACTEbola virus causes a hemorrhagic fever with a high case-fatality rate. Treatment remains supportive although a variety of specific treatments are still in the early stages of investigation. This report reviews the clinical virology of Ebola virus, the reported proposed treatments, and the current outbreak.


  • Ebola virus is spread by contact with body fluids, with no evidence to date that it is airborne.
  • Ebola virus is likely maintained in a reservoir of small animals, possibly bats.
  • The incubation period is about 5 to 7 days, during which the patient is not infectious.
  • Symptoms begin abruptly, with fever, chills, and general malaise, which in some patients leads to weakness, severe headache, myalgia, nausea, vomiting, diarrhea, and abdominal pain.
  • Once the disease is symptomatic, patients have high levels of virus in the blood and other body fluids and are therefore infectious.
  • Survivors show improvement in the second week of illness, during which viremia resolves and virus-specific antibodies appear.



A 50-year-old man who returned from a business trip to Nigeria 24 days ago presents with complaints of the sudden onset of fever, diarrhea, myalgia, and headache. He reports 10 bowel movements per day and has seen bloody stools.

During his trip he flew in to Murtala Muhammed International Airport in Lagos, ate meals only in his hotel, and attended meetings in Lagos central business district. He had no exposure to animals, mosquitoes, ticks, or sick people, and no sexual activity. After returning home, he felt well for the first 3 weeks.

The patient has a history of hypertension. He does not smoke, drink alcohol, or use injection drugs. He is married, works with commercial banks and financial institutions, and lives in Cleveland, OH.

On physical examination his temperature is 100.0˚F (37.8˚C), pulse 98, respirations 15, blood pressure 105/70 mm Hg, and weight 78 kg (172 lb). He appears comfortable but is a little diaphoretic. His abdomen is tender to palpation in the epigastrium and slightly to the right; he has no signs of peritonitis. His skin is without rash, bleeding, or bruising. The remainder of the examination is normal.

His white blood cell count is 17 × 109/L, hemoglobin 15 g/dL, hematocrit 41%, and platelet count 172 × 109/L. His sodium level is 126 mmol/L, potassium 3.8 mmol/L, chloride 95 mmol/L, carbon dioxide 20 mmol/L, blood urea nitrogen 11 mg/dL, creatinine 0.7 mg/dL, and glucose 130 mg/dL. His aminotransferase and alkaline phosphatase levels are normal.

Could this patient have Ebola virus disease?

With Ebola virus disease on the rise in West Africa, physicians who encounter patients like this one need to include it in the differential diagnosis. Because the disease is new, many questions are raised for which we as yet have no answers. Here, I will review what we know and do not know in an effort to remove some of the fear and uncertainty.


Ebola virus disease is a severe hemorrhagic fever caused by negative-sense single-stranded RNA viruses classified by the International Committee on Taxonomy of Viruses as belonging to the genus Ebolavirus in the family Filoviridae. Filoviruses get their name from the Latin filum, or thread-like structure.

The family Filoviridae was discovered in 1967 after inadvertent importation of infected monkeys from Uganda into Yugoslavia and Marburg, Germany. Outbreaks of severe illness occurred in workers at a vaccine plant who came into direct contact with the animals by killing them, removing their kidneys, or preparing primary cell cultures for polio vaccine production.

Ebola virus was discovered in 1976 by Peter Piot, who was working at the Institute of Tropical Medicine in Antwerp, Belgium. The blood of a Belgian woman who had been working in what is now the Democratic Republic of the Congo (formerly Zaire) had been sent to the institute; she and Mabalo Lokela, a school headmaster and the first recorded victim of Ebola virus, had been working near Yambuku, about 96 km from the Ebola River.

Before the 2014 outbreak, all known outbreaks had caused fewer than 2,400 cases across a dozen African countries over 3 decades.

Five species of Ebola virus

The genus Ebolavirus contains five species, each associated with a consistent case-fatality rate and a more or less well-identified endemic area.1

Zaire ebolavirus was recognized in 1976; it has caused multiple outbreaks, with high case-fatality rates.

Sudan ebolavirus was seen first in the 1970s; it has a 50% case-fatality rate.

Tai Forest ebolavirus has been found in only one person, an ethologist working with deceased chimpanzees.

Bundibugyo ebolavirus emerged in 2007 and has a 30% case-fatality rate.

Reston ebolavirus is maintained in an animal reservoir in the Philippines and is not found in Africa. It caused an outbreak of lethal infection in macaques imported into the United States in 1989. There is evidence that Reston ebolavirus can cause asymptomatic infection in humans. None of the caretakers of the macaques became ill, nor did farmers working with infected pigs, although both groups seroconverted.

A reservoir in bats?

A reservoir in nonhuman primates was initially suspected. However, studies subsequently showed that monkeys are susceptible to rapidly lethal filoviral disease, precluding any role as a host for persistent viral infection. It is likely that Ebola virus is maintained in small animals that serve as a source of infection for both humans and wild primates. A prominent suspect is fruit bats, which are consumed in soup in West Africa.

Transmission is person-to-person or nosocomial

Ebola virus is transmitted by direct contact with body fluids such as blood, urine, sweat, vomitus, semen, and breast milk. Filoviruses can initiate infection via ingestion, inhalation (although probably not Ebola), or passage through breaks in the skin. Droplet inoculation into the mouth or eyes has been shown to result from inadvertent transfer of virus from contaminated hands. Patients transmit the virus while febrile and through later stages of disease, as well as postmortem through contact with the body during funeral preparations. The virus has been isolated in semen for as many as 61 days after illness onset.

One primary human case generates only one to three secondary cases on average, but the case-fatality rate is high

Ebola virus can also be spread nosocomially. In 1976, a 44-year-old teacher sought care for fever at the Yambuku Mission Hospital. He was given parenteral chloroquine as empiric treatment for presumed malaria, which was routine for all febrile patients. However, he had unrecognized Ebola virus infection. Moreover, syringes were rinsed in the same pan of water and reused, which spread the infection to nearly 100 people, all of whom developed fulminant Ebola virus disease and died. Infection then spread to family caregivers, the hospital staff, and those who prepared the bodies for burial.

Nosocomial transmission was also responsible for an outbreak of Lake Victoria Marburg virus in Uige Province in northern Angola in 2005, with 374 putative cases and 329 deaths. When teams from Médecins Sans Frontières started setting up the Marburg ward, there were five patients with hemorrhagic fever in a makeshift isolation room in the hospital, together with corpses that the hospital staff had been too afraid to remove. Healers found in many rural African communities were administering injections in homes or in makeshift clinics with reused needles or syringes.2

There is no evidence that filoviruses are carried by mosquitoes or other biting arthropods. Also, the risk of transmission via fomites appears to be low when currently recommended infection-control guidelines for the viral hemorrhagic fevers are followed.3 One primary human case generates only one to three secondary cases on average.

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