9. Clinical manifestation

human to human via the respiratory route [31]. The type of contact among individuals can

High risk Percutaneous, needle stick or mucosal exposure to virus-contaminated blood, bodily fluids, tissues or laboratory specimens in severely ill or known positive patients.

Casual contact with a feverish, ambulant, self-caring patient. Examples: sharing a sitting area or

protection) with a patient who is coughing or vomiting, has nose bleeds or who has diarrhoea.

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

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

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

from viral infected target cells and/or from viral glycoprotein secretions [36].

influence the risk of transmission of Ebola virus disease as shown in Table 1 [32].

public transportation; receptionist tasks.

Table 1. Risk of Ebola virus transmission and its association with the level of contact.

Low risk Close face-to-face contact with a feverish and ambulant patient. Example: physical examination, measuring temperature and blood pressures. Moderate risk Close face-to-face contact without appropriate personal protective equipment (including eye

8. Pathogenesis of the disease

Type of contact

134 Current Topics in Tropical Emerging Diseases and Travel Medicine

Levels of risk of transmission

Very low or no recognized risk

gland, kidney and pancreas [35, 36].

Once an individual gets infected with Ebola virus, it can persist in the body for a few days with no clinical manifestation. Thus, the incubation period ranges from 2 to 21 days with an average between 4 and 10 days. After this incubation period, an acute infection emerges which starts to portray clinical manifestations. The illness commences with symptoms of flu-like syndrome which includes a sudden onset of high fever, chills and myalgia. This early infection can affect the gastrointestinal system causing anorexia, vomiting, nausea, diarrhoea, abdominal pain, as well as the respiratory system causing cough, chest pain and dyspnea. Also, the vascular system can be affected leading to hypotension, oedema as well as neurologic system causing headache and coma [42, 43]. Though the periodical manifestation of Ebola virus varies among individuals, generally, these clinical features can be categorized into four phases as suggested by Suresh and Dashrath [44].

Phase 1 - Influenza-like syndrome: The onset of the infection commences with non-specific signs or symptoms such as high fever, nausea, headache, sore throat, arthralgia, and myalgia.

Phase 2 - Acute phase: A persistent acute fever emerges along with headache and intense fatigue within 1–6 days which is not responsive to antibiotics or antimalarial drugs. This is usually followed by gastrointestinal obstructions such as abdominal pain, diarrhoea, vomiting, etc.

Phase 3 - Pseudo-remission: After the acute phase, a false recovery phase emerges by days 7–8 where the patient feels better showing some signs of recovery such as gain of appetite. In some patients, this phase may eventually lead to total recovery and survival of the disease.

Phase 4 - Aggravation phase: By day 9, the health status gets worsen in most individuals presenting respiratory disorders such as cough, dyspnea, hiccups, throat and chest pain as well as cardiovascular distress and hypovolemic shock. Also, rask may develop on the skin as well as petechiae.

During the infection, laboratory investigations show high levels of aminotransferase, and marked lymphocytopenia, and thrombocytopenia in patients' blood [45]. More so, bleeding usually occurs in the gastrointestinal tract and may be expressed as petechiae, melena, conjunctival haemorrhage, easy bruising, haematuria, or intraperitoneal bleeding. Also, mucous membrane bleeding as well as excessive clot formation and failure of venipuncture sites are evident during infection. Progression of these symptoms over a period of time may lead to dehydration, confusion, stupor, hypotension and failure of multiple organs culminating to fulminant shock and eventually death which occurs between the 6 and 16 days of illness [46, 47]. However, a few patients may survive and recovery from the infection gradually presenting arthralgia and fatigue.

feasible in Africa as most local health settings lack or do not have sufficient or adequate laboratory facilities for such molecular techniques. Another major challenge is the high cost for the molecular diagnostic tests (RT-PCR, ELISA). The cost per sample may cost between \$50 to \$100 which may not be affordable by majority of individuals in developing countries especially in endemic areas including West Africa, Sub-Saharan Africa and central East Africa. More so, though these molecular diagnostic tools are very reliable, analyses take about 2–6 h, which is too long for such acute infection. As such, there is considerable need for rapid diagnostic tests which can take just a few minutes for detection. Also, cell culture on vero E6 African monkey kidney cells which is a traditional gold standard test requires biosafety level 4 (BSL-4) containment, thus, restricts its use for routine diagnosis. More so, the test can last for

Ebola Virus Disease: Progress So Far in the Management of the Disease

http://dx.doi.org/10.5772/intechopen.79053

137

up to 5 days from the moment of viral inoculation to microscopic visualization [55].

diagnostic tool is not readily available.

10.1. Rapid diagnostic test for Ebola virus disease

An immunochromatographic assay may be suitable for such effective and prompt diagnosis. In 1995, a colorimetric assay was developed by Dr. Sherif Zaki of the CDC for the identification of Ebola virus in skin biopsies preserved in formalin [56]. However in recent years, this

Following the 2014, outbreak in West Africa, several field trials on rapid diagnostic tests (RDTs) are ongoing and a few RDT kits have been approved by U.S. Food and drug Administration (FDA) and WHO on Emergency Use Authorization (EUA) status. These RDT kits are lateral flow immunoassays (LFIs) which basically detects viral protein antigens circulating in blood. Three of the recently approved RDTs include ReEBOV Antigen Rapid Test kit,

The ReEBOV Antigen Rapid Test kit by Corgenix, Inc. was the first LFI for EVD to receive emergency use authorization (EUA) status from both FDA and WHO) [58, 59]. This chromatographic dipstick immunoassay kit is a RDT that detects the Ebola virus VP40 matrix protein of three species which includes EBOV, SUDV, and BDBV in whole blood, plasma or serum. Following a finger prick, a drop of blood is applied directly unto the nitrocellulose test strip. The nitrocellulose strip is then deepened into a tube containing reaction buffer which initiates the movement of the sample along the test strip by capillary action. The presence of VP40 in the sample leads to the formation of an immune complex between the VP40 matrix protein antigen and gold-labelled anti-antibodies against VP40 which is subsequently deposited along the strip boundary of anti-VP40 producing a pink-red line that is visible between 15 to 25 min after the analysis. Validation study for the performance of ReEBOV RDT conducted in Sierra Leone on venipuncture blood showed a 100% sensitivity and 92% specificity when compared with results obtained from RealStar Filovirus Screen RT-PCR kit by Altona Diagnostics [58]. The second RDT kit that has received approval from WHO and FDA on EUA status is the OraQuick Ebola Rapid Antigen Test manufactured by OraSure Technologies, Inc. [60, 61]. Just like the ReEBOV Antigen Rapid Test kit, this RDT kit detects VP40 matrix protein of EBOV, SUDV, and BDBV species with similar assay procedure. In addition to the use of whole blood, this kit also makes use of cadaveric oral fluid which is collected using an oral mucosa swab for the detection of Ebola virus. Similarly as ReEBOV RDT, the presence of Ebola virus antigens is

OraQuick Ebola Rapid Antigen Test and SD Q Line Ebola Zaire Ag test [57].
