8. Pathogenesis of the disease

Though the natural reservoir of Ebola virus is unknown, bats are the main primary reservoirs along with some non-human primates such as monkeys, baboons, chimpanzees and gorillas known to transmit the virus to humans through contact with the animals or their body fluids such as sweat, blood, urine, and other secretions or other infectious objects. Ebola virus can persist on objects in a dried state for several hours and can persist in body fluids for several days [28, 33]. Once humans get in contact with the virus, it enters the body through mucous membranes following abrasions or cuts and adheres to cell membranes. Following attachment on cell membrane, it penetrates, uncoating its membrane and replicates it RNA which then expresses its constituent proteins and reassembled to a matured virus that is release from the cell. It gets into the circulatory system infecting monocytes, dendritic cells and macrophages and subsequently spread in the lymphatic system infecting lymphocytes and other organs such as the spleen, liver, kidney, etc. [34]. This has been confirmed in in vitro studies where macrophages largely infected by Ebola virus produce high amounts of viral particles which are delivered to various organs such as the lymph nodes, liver, spleen, endothelium, adrenal gland, kidney and pancreas [35, 36].

The infected cells as well as lymphocytes becomes destroyed releasing inflammatory substances such as interleukins (interleukin-2 and -10), interferons (interferons-alpha and -gamma), tumour necrosis factor etc. which destroys the vascular and endothelial system increasing vascular permeability. Peripheral smears of infected persons have shown atypical or death lymphocytes which are suggested to result from apoptosis triggered by inflammatory mediators released from viral infected target cells and/or from viral glycoprotein secretions [36].

The destruction of the microvascular tissues changes vascular permeability, cause cellular necrosis and activate clotting factors thereby leading to coagulopathy, hypotensive shock and possibly death [37]. Also, impairment of endothelial and platelet cells alter fluid and electrolyte balance disrupting the body's homeostasis [38]. Virus induced shock is due to elevated increase in nitric oxide production which leads to damage of the vascular system altering the blood pressure [39]. Also, these hypotensive shock may also result from platelet-derived agents such as thrombin following the damaged of endothelial cells. Theses clotting factors can disseminate into various organs causing intravascular coagulation [40].

One of the possible mechanisms the virus is able to persist in the body is through its ability to evade the immune system by destroying immune cells such as lymphocytes, natural killer cells, phagocytes as well as impairment of the action of dendritic cells [41].
