16. Ebola Virus Disease anja.boehme.pdf
the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny
particles then infect other cells to repeat the cycle.
Endothelial cells, mononuclear phagocytes, and hepatocytes are the main targets of infection. After
infection, in a secreted glycoprotein (sGP) the Ebola virus glycoprotein (GP) is synthesized. Ebola
replication overwhelms protein synthesis of infected cells and host immune defenses. The GP forms
a trimeric complex, which binds the virus to the endothelial cells lining the interior surface of blood
vessels. The sGP forms a dimeric protein which interferes with the signaling of neutrophils, a type
of white blood cell, which allows the virus to evade the immune system by inhibiting early steps of
neutrophil activation. These white blood cells also serve as carriers to transport the virus throughout
the entire body to places such as the lymph nodes, liver, lungs, and spleen. The presence of viral
particles and cell damage resulting from budding causes the release of cytokines (specifically TNFα, IL-6, IL-8, etc.), which are the signaling molecules for fever and inflammation. The cytopathic effect,
from infection in the endothelial cells, results in a loss of vascular integrity. This loss in vascular
integrity is furthered with synthesis of GP, which reduces specific integrins responsible for cell
adhesion to the inter-cellular structure, and damage to the liver, which leads to coagulopathy.
EVD is clinically indistinguishable from Marburg virus disease (MVD), and it can also easily be
confused with many other diseases prevalent 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 ought to be included in the differential
diagnosis include leptospirosis, scrub typhus, plague, Q
fever, candidiasis, histoplasmosis, trypanosomiasis, visceral leishmaniasis,
hemorrhagic smallpox, measles, and fulminant viral hepatitis. 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 intoxication.
The most important indicator that may lead to the suspicion of EVD at clinical examination is
the medical history of the patient, in particular the travel and occupational history (which countries
were visited?) and the patient's exposure to wildlife (exposure to bats, bat excrement, nonhuman
primates?). EVD can be confirmed by isolation of ebolaviruses from or by detection of ebolavirus
antigen or genomic or subgenomic RNAs in patient blood or serum samples during the acute phase of
EVD. Ebolavirus isolation is usually performed by inoculation of grivet kidney epithelial Vero E6 or
MA-104 cell cultures or by inoculation of human adrenal carcinoma SW-13 cells, all of which react to
infection with characteristic cytopathic effects. Filovirions can easily be visualized and identified in cell
culture by electron microscopy due to their unique filamentous shapes, but electron microscopy
cannot differentiate the various filoviruses alone despite some overall length
differences. Immunofluorescence assays are used to confirm ebolavirus presence in cell cultures.
During an outbreak, virus isolation and electron microscopy are most often not feasible options. The
most common diagnostic methods are therefore RT-PCR in conjunction with antigen-capture
ELISA which can be performed in field or mobile hospitals and laboratories. Indirect
immunofluorescence assays (IFAs) are not used for diagnosis of EVD in the field anymore.
A researcher working with the Ebola virus while wearing a biosafety level 4 positive pressure suit to
Ebolaviruses are highly infectious as well as contagious.
As an outbreak of ebola progresses, bodily fluids from diarrhea, vomiting, and bleeding represent a
hazard. Due to lack of proper equipment and hygienic practices, large-scale epidemics occur mostly
in poor, isolated areas without modern hospitals or well-educated medical staff. Many areas where
the infectious reservoir exists have just these characteristics. In such environments, all that can be
done is to immediately cease all needle-sharing or use without adequate sterilization procedures,