Ebola Virus
21. Reservoir
Bats are considered the most likely natural reservoir of the Ebola virus (EBOV); plants, arthropods, and birds have also been considered. Bats were known to reside in the cotton factory in which the first cases for the 1976 and 1979 outbreaks were employed, and they have also been implicated in Marburg virus infections in 1975 and 1980.Of 24 plant species and 19 vertebrate species experimentally inoculated with EBOV, only bats became infected. The absence of clinical signs in these bats is characteristic of a reservoir species. In a 2002?2003 survey of 1,030 animals including 679 bats from Gabon and the Republic of the Congo, 13 fruit bats were found to contain EBOV RNA fragments. As of 2005, three types of fruit bats (Hypsignathus monstrosus, Epomops franqueti, and Myonycteris torquata) have been identified as being in contact with EBOV. They are now suspected to represent the EBOV reservoir hosts.Antibodies against Ebola Zaire and Reston viruses have been found in fruit bats in Bangladesh, thus identifying potential virus hosts and signs of the filoviruses in Asia.
22. Replication
The ebolavirus life cycle begins with virion attachment to specific cell surface receptors, followed by fusion of the virion envelope with cellular membranes and the concomitant release of the virus nucleocapsid into the cytosol. The viral RNA polymerase, encoded by the L gene, partially uncoats the nucleocapsid and transcribes the genes into positive strand mRNAs, which are then translated into structural and nonstructural proteins. Ebolavirus RNA polymerase (L) binds to a single promoter located at the 3 end of the genome. Transcription either terminates after a gene or continues to the next gene downstream. This means that genes close to the 3 end of the genome are transcribed in the greatest abundance, whereas those toward the 5 end are least likely to be transcribed. The gene order is, therefore, a simple but effective form of transcriptional regulation. The most abundant protein produced is the nucleoprotein, whose concentration in the cell determines when L switches from gene transcription to genome replication. Replication results in full length, positive strand antigenomes that are, in turn, transcribed into negative strand virus progeny genome copy. Newly synthesized structural proteins and genomes self assemble and accumulate near the inside of the cell membrane. Virions bud off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles then infect other cells to repeat the cycle.The Ebola Virus genetics are difficult to study due to its virulent nature.
23. Classification
The genera Ebolavirus and Marburgvirus were originally classified as the species of the now obsolete Filovirus genus. In March 1998, the Vertebrate Virus Subcommittee proposed in the International Committee on Taxonomy of Viruses (ICTV) to change the Filovirus genus to the Filoviridae family with two specific genera: Ebola like viruses and Marburg like viruses. This proposal was implemented in Washington, DC, on April 2001 and in Paris on July 2002. In 2000, another proposal was made in Washington, D.C., to change the like viruses to virus resulting in todays Ebolavirus and Marburgvirus.Rates of genetic change are 100 times slower than influenza A in humans, but on the same magnitude as those of hepatitis B. Extrapolating backwards using these rates indicates that Ebolavirus and Marburgvirus diverged several thousand years ago. However, paleoviruses (genomic fossils) of filoviruses (Filoviridae) found in mammals indicate that the family itself is at least tens of millions of years old. Fossilized viruses that are closely related to ebolaviruses have been found in the genome of the Chinese hamster.
24. Differential diagnosis
The symptoms of EVD are similar to those of Marburg virus disease.It can also easily be confused with many other diseases common in Equatorial Africa such as other viral hemorrhagic fevers, falciparum malaria, typhoid fever, shigellosis, rickettsial diseases such as typhus, cholera, gram negative septicemia, borreliosis such as relapsing fever or EHEC enteritis. Other infectious diseases that should be included in the differential diagnosis include the following: leptospirosis, scrub typhus, plague, Q fever, candidiasis, histoplasmosis, trypanosomiasis, visceral leishmaniasis, hemorrhagic smallpox, measles, and fulminant viral hepatitis.[citation needed] Non infectious diseases that can be confused with EVD are acute promyelocytic leukemia, hemolytic uremic syndrome, snake envenomation, clotting factor deficiencies platelet disorders, thrombotic thrombocytopenic purpura, hereditary hemorrhagic telangiectasia, Kawasaki disease, and even warfarin poisoning.
25. Behavioral changes
Ebola viruses are contagious, with prevention predominantly involving behavior changes, proper full body personal protective equipment, and disinfection. Techniques to avoid infection involve not contacting infected blood or secretions, including from those who are dead. This involves suspecting and diagnosing the disease early and using standard precautions for all patients in the healthcare setting. Recommended measures when caring for those who are infected include isolating them, sterilizing equipment, and wearing protective clothing including masks, gloves, gowns and goggles. Hand washing is important but can be difficult in areas where there is not even enough water for drinking.
26. Quarantine
Quarantine, also known as enforced isolation, is usually effective in decreasing spread.Governments often quarantine areas where the disease is occurring or individuals who may be infected. In the United States the law allows quarantine of those infected with Ebola. The lack of roads and transportation may help slow the disease in Africa. During the 2014 outbreak Liberia closed schools.
27. Vaccine
No vaccine is currently available for humans. The most promising candidates are DNA vaccines or vaccines derived from adenoviruses, vesicular stomatitis Indiana virus (VSIV) or filovirus like particles (VLPs) because these candidates could protect nonhuman primates from ebolavirus induced disease. DNA vaccines, adenovirus based vaccines, and VSIV based vaccines have entered clinical trials.
Vaccines have protected nonhuman primates. Immunization takes six months, which impedes the counter epidemic use of the vaccines. Searching for a quicker onset of effectiveness, in 2003 a vaccine using an adenoviral (ADV) vector carrying the Ebola spike protein was tested on crab eating macaques. Twenty eight days later they were challenged with the virus and remained resistant. A vaccine based on attenuated recombinant vesicular stomatitis virus (VSV) vector carrying either the Ebola glycoprotein or the Marburg glycoprotein in 2005 protected nonhuman primates, opening clinical trials in humans.The study by October completed the first human trial, over three months giving three vaccinations safely inducing an immune response. Individuals for a year were followed, and, in 2006, a study testing a faster acting, single shot vaccine began; this new study was completed in 2008. Trying the vaccine on a strain of Ebola that more resembles one that infects humans is the next step.
28. Treatment
No ebolavirus specific treatment exists. Treatment is primarily supportive in nature and includes minimizing invasive procedures, balancing fluids and electrolytes to counter dehydration, administration of anticoagulants early in infection to prevent or control disseminated intravascular coagulation, administration of procoagulants late in infection to control bleeding, maintaining oxygen levels, pain management, and the use of medications to treat bacterial or fungal secondary infections.Early treatment may increase the chance of survival. A number of experimental treatments are being studied.
29. Research
Favipiravir looks like it may be useful in a mouse model of the disease. Estrogen receptor drugs used to treat infertility and breast cancer (clomiphene and toremifene) inhibit the progress of Ebola virus in infected mice. Ninety percent of the mice treated with clomiphene and fifty percent of those treated with toremifene survived the tests. Given their oral availability and history of human use, these drugs would be candidates for treating Ebola virus infection in remote geographical locations, either on their own or together with other antiviral drugs.
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