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Paper Abstract

Ebola Virus disease

Overview

Ebola or the Ebola virus disease is a highly contagious disease caused by the Ebola virus. The Ebola virus is an enveloped single-stranded RNA virus belonging to the genera of Filoviruses. There are six species of the Ebola virus, out of which the Zaire Ebola virus has caused the most devastation, resulting in multi-organ failure and homeostatic imbalance in infected patients. The Ebola virus disease occurs in both primates and humans. In humans, it is caused by four Ebola virus species, namely Zaire virus, Sudan virus, Taï Forest virus, and Bundibugyo virus. It can infect people of all ages (from infants to the elderly). EVD was earlier known as Ebola hemorrhagic fever or EHF, but in 2014 it was renamed EVD as it is not just a febrile illness. The transmission of EVD is both zoonotic (animals to humans) and anthroponotic (humans to humans). In zoonotic transmission, humans become infected by physical contact with infected animals or meat. Human-to-human transmission can occur via contact with blood and/or body fluids from infected humans. The virus can cause an infected person to bleed, leading to hemorrhagic shock. The multiple organ failure in the Ebola virus disease can also result in death. The Ebola infection usually may become noticeable within 3 weeks. The infected patients are not contagious until apparent symptoms begin to manifest.

Clinical presentation

The symptoms of EVD become apparent, rapidly between 2 to 21 days of infection. The major early symptoms of EVD are fever, muscle pain, fatigue, sore throat, and headache. Subsequent symptoms include vomiting, diarrhea, skin rash, symptoms of impaired kidney and liver functions, low platelet count as well as both internal and external bleeding. EVD begins typically as a febrile illness of non-specific nature followed by gastrointestinal symptoms such as abdominal pain and diarrhea. In patients with high viral loads, with a dysregulated immune response, the disease progresses to fatal complicated multiple organ dysfunction syndromes. Whereas the patients usually with lower viral loads, have a lesser magnitude of disease severity and progression, as well as organ dysfunction. Consequently, these patients develop strong immune responses leading to clearance of the virus and subsequent attainment of resolution.

Global scenario

The Ebola virus has since become the factor for severe febrile illness and sporadic human disease outbreaks in Equatorial African countries. The outbreak of 2014-16 hit three countries namely Sierra Leone, Guinea, and Liberia, simultaneously, which was documented as the longest duration of the outbreak with the maximum number of infections and a relatively high fatality rate.  In the first quarter of 2014, an Ebola virus variant called EBOV Makona was for the first time identified in Guinea, subsequently, it crossed borders. Moreover, it was the first outbreak affecting several cases in densely populated areas of urban regions including the capitals of these countries. Subsequently, EVD affected the United States along with Europe. In Western Africa, the Ebola virus disease sporadic outbreaks in the recent decade were a global public health threat. According to WHO-reported statistics, around 40% of gross mortality due to EVD was recorded in December 2013. Thus, overall, by 2020, approximately 33,604 Ebola virus infections in humans have occurred, consisting of 14,742 deceased cases.

Diagnosis

Laboratory-based diagnosis proves to be of utmost importance for the confirmation of EVD. The laboratory diagnosis has a huge role to play in the rapid response to outbreaks. There are three ways of detecting the Ebola virus in suspected patients. These include serological tests that evaluate host antibodies generated against the virus, antigen-based tests that detect viral proteins, and molecular tests that detect viral RNA sequences. However, to date, none of the tests have proven to demonstrate the ability to detect the Ebola virus before the onset of symptoms in patients. Serological detection of antibodies was done by IFAT or indirect immunofluorescence antibody testing earlier, but currently, IgG/IgM antibody detection is done by ELISAs or enzyme-linked immunosorbent assays. The use of a rapid antigen detection test is further recommended under field settings. The advantage is early detection using antigen-based methods as detectable antigen exists in nearly all EVD patients by the third day of illness. In addition, sophisticated molecular detection techniques such as conventional reverse-transcriptase polymerase chain reaction (RT-PCR), as well as real-time reverse transcription-PCR techniques have now gained much popularity and efficiency regarding sensitivity and specificity. Real-time RT-PCR performed on blood samples has turned out to be the standard testing method for diagnosis of acute cases of EVD in the setting of an outbreak, while real-time RT-PCR on saliva samples has turned out to be the standard for postmortem testing.

Management

Supportive care for an infected person includes rehydration with oral or intravenous fluids as well as treatment with symptomatic therapy. Patient isolation and proper care of both patients and caregivers are of utmost priority. Good outbreak control measures depend on the implementation of a regimen of interventions; involving case management, contact tracing, and surveillance, along with a good laboratory service, safe burials, and social mobilization. Two monoclonal antibodies namely Inmazeb and Ebanga were approved in both children and adults for the treatment of Ebola virus infection, especially Zaire Ebola virus species by the US Food and Drug Administration (FDA) in late 2020. In addition, vaccines are always protective gear against any infectious diseases. In late 2020, the vaccine Ervebo was approved by US FDA and World Health Organization for use in persons 18 years or older in gaining protection against the Zaire Ebola virus. Another set of two vaccines namely Zabdeno and Mvabea were granted and recommended marketing authorization by the European Medicines Agency in May 2020. Due to the extent of mortality and affected health workers in the past episodes of EVD outbreaks, concerns from all corners of the world have been raised to investigate extensively precautionary measures, early diagnostics, and therapeutics for the disease. Also, there is a potential arena of treatments regarding blood products, immune therapies, and drug therapies, which are currently being evaluated and these areas need to be addressed on an immediate basis in the future.

Quality of life

The infection and its related spread among both, close acquaintances and healthcare workers are a major concern regarding maintaining the quality of life of the patients. Thus, early goal-directed resuscitation and other supportive care measures, such as the provision of enteral nutrition or tube feeding and prevention of nosocomial infections, stress ulcers, skin breakdown as well as deep venous thrombosis (coagulation of blood in the circulatory system) are pivotal parameters to enhance the quality of life and survival rate. Social isolation of patients and proper assessment of prognosis along with evaluating the healthcare workers’ quality of life is required for the management of the disease.

Collaborators

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