Ebola Virus Disease - Diagnosis

Diagnosis

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.