All about Ebola
Ebola and Marburg hemorrhagic fevers are acute diseases that often lead to severe illness and death in both humans and nonhuman primates. The diseases typically affect multiple organs in the body and are often accompanied by hemorrhage (bleeding). The illnesses are caused by filoviruses, the only two known members of the virus family Filoviridae.
Marburg hemorrhagic fever was first recognized in 1967, when laboratory workers in Germany and Yugoslavia developed a hemorrhagic illness after handling tissue from green monkeys. The outbreak resulted in 31 infections and 7 deaths. Researchers later identified the cause as a never-before-seen filovirus, termed “Marburg” after one of the outbreak locations.
Eleven years later, Ebola virus was identified when two outbreaks of hemorrhagic fever occurred in northern Zaire (now the Democratic Republic of Congo) and southern Sudan. The causes of the outbreaks were identified as two different species of another novel filovirus, called “Ebola” after a river in northern Zaire. Both species proved to be highly lethal, as 90 percent of the Zairian cases and 50 percent of the Sudanese cases resulted in death.
There are five species of Ebola virus, named for the locations in which they were first recognized. Four of the five subtypes have caused disease in humans: Ebola-Zaire, Ebola-Sudan/Gulu, Ebola-Ivory Coast, and Ebola-Bundibugyo. The fifth, Ebola-Reston, has caused disease in nonhuman primates (gorillas, chimpanzees, and monkeys) but not in humans.
Filoviruses are believed to be zoonotic, meaning they are transmitted to humans by animals. The natural reservoirs, or animal hosts, of Ebola and Marburg viruses are not known. The viruses can replicate, or reproduce, in certain types of bats native to the areas where the viruses are found, so some researchers think that these bats could be the natural reservoirs.
Once the virus has been transmitted to a human, it can then be spread through person-to-person contact. People can be exposed to Ebola and Marburg viruses from direct contact with the blood or secretions of an infected person.
Nosocomial transmission, or the spread of disease within a healthcare setting, also occurs, making the use of protective clothing and the disposal of needles and syringes crucial to preventing the spread of infection.
Symptoms of Ebola hemorrhagic fever usually appear 2 to 21 days after exposure to the virus. Symptoms include fever, headache, joint and muscle aches, sore throat, and weakness followed by diarrhea, vomiting, and stomach pain. Other symptoms, including rash, red eyes, hiccups, and internal and external bleeding, may also occur.
Symptoms of Marburg hemorrhagic fever appear 5 to 10 days after exposure to the virus. Symptoms appear suddenly and include fever, chills, headache, and muscle aches. Infected people may also develop a red rash usually on the chest, back, or stomach. Nausea, vomiting, chest pain, a sore throat, abdominal pain, and diarrhea may appear. Symptoms become increasingly severe and may include severe weight loss, delirium, shock, liver failure, and external bleeding.
Diagnosis of Ebola and Marburg hemorrhagic fevers can be difficult because early symptoms are often similar to other infectious diseases, such as malaria and typhoid fever.
If they suspect Ebola or Marburg infection, healthcare providers will isolate infected patients. Laboratory tests can confirm infection within a few days of the onset of symptoms.
Treatment and Prevention
There are no specific drugs to treat Ebola or Marburg hemorrhagic fevers. If hospitalized, ill people can be given supportive care such as intravenous fluids.
The molecular events that affect disease transmission and human response to Ebola and Marburg viruses are poorly understood. Researchers in NIAID’s Division of Intramural Research and Vaccine Research Center as well as NIAID-supported scientists at external institutions are studying all aspects of Ebola and Marburg viruses and how they cause disease. This includes seeking better ways to diagnose and treat Ebola and Marburg fevers, and using applied research to develop diagnostics, vaccines, and therapeutics.
Ebola Vaccine Research
The Vaccine Research Center (VRC) has developed an Ebola vaccine candidate in collaboration with Okairos, a Swiss-Italian biotech company recently acquired by GSK. The investigational vaccine, which was designed by VRC scientists, contains no infectious Ebola virus material. It is a chimpanzee adenovirus vector vaccine into which two Ebola genes have been inserted. This is a non-replicating viral vector, which means the vaccine enters a cell, delivers the gene inserts and does not replicate further. The gene inserts express a protein to which the body makes an immune response. The investigational vaccine has recently shown promise in a primate model. The VRC vaccine will enter into a phase 1 clinical trial, which could start enrollment as early as fall 2014, pending approval by the FDA. The VRC is also in discussions with governmental and non-governmental partners regarding options for advancing this candidate beyond Phase I clinical evaluation.
Additionally, NIAID’s Division of Microbiology and Infectious Diseases is supporting the Crucell biopharmaceutical company’s development of a multivalent Ebola/Marburg vaccine using recombinant adenovirus vector platforms. A Phase I clinical trial is planned for late 2015 or early 2016. NIAID is also funding Profectus Biosciences to develop and test a recombinant vesicular stomatitis virus vectored vaccine against Ebolavirus. The vaccine is currently in preclinical testing to determine the most promising constructs.
Investigators from NIAID’s Division of Intramural Research and Thomas Jefferson University are collaborating to develop a candidate Ebola vaccine based on the established rabies virus vaccine that has demonstrated protection against rabies and Ebola infection in animals. This research team is pursuing an inactivated version of this vaccine for human and veterinary use and a live vaccine for use in wildlife in Africa to help prevent the transmission of Ebolavirus from animals to humans.
Ebola Therapeutics Research
NIAID is supporting a number of projects designed to develop Ebola treatments. For example, NIAID supported Mapp Biopharmaceutical, Inc., in its development of a monoclonal antibody “cocktail” called MB-2003, which prevents Ebolavirus infection in mice and non-human primates when administered as post-exposure prophylaxis within one to two days of Ebolavirus infection. Additionally, NIAID currently is funding development of an optimized anti-Ebola monoclonal antibody product, zMapp, which has superior efficacy compared to earlier cocktails. The zMapp, which is partially derived from MB-2003, is a cocktail of three antibodies against Ebola.
In addition, NIAID is funding BioCryst Pharmaceuticals to develop and test BCX4430, a novel nucleoside with broad spectrum antiviral activity including against Ebolavirus. To date, BCX4430 has shown efficacy in animal infection models for Ebola and Marburg viruses. A Phase I trial is expected to begin in late 2014 or early 2015. NIAID also is supporting other monoclonal antibody-based broadly-protective filovirus immunotherapeutics.
Ebola Diagnostics Research
NIAID is also supporting the development of improved diagnostics for Ebolavirus infection. For example, NIAID is funding a Lassa fever recombinant antigen diagnostic that could be modified to detect Ebolavirus infection. NIAID also is supporting development of multiplex diagnostics, microfluidics-based diagnostics and optofluidic-based diagnostics for Ebola.