An Overview on Ebola Virus Disease

 

Akshay R. Yadav*, Shrinivas K. Mohite

Department of Pharmaceutical Chemistry, Rajarambapu College of Pharmacy,

Kasegaon, Sangli, Maharashtra, India-415404.

 

ABSTRACT:

Ebolaviruses belongs to the family of Filoviridae in the order of Mononegavirales. The genome is a single, negative polarity strand of RNA. EBOV is one of the most virulent pathogens among viral haemorrhagic fevers, with case fatality rates of up to 90% reported. Mortality is the result of multi-organ failure and serious bleeding complications. By 18 September 2014, the WHO reported 5,335 cases (confirmed, suspected and probable) with 2,622 deaths, resulting in a case fatality rate of around 50%. There are no approved medications or vaccines available for EVD until today; supporting care is the pillar of therapy. There are, however, a number of therapeutic approaches along the way that could have a real impact on the control and prevention of this global threat. This review aims to provide clinicians with an overview of EVD with emphasis on epidemiology, clinical manifestations and options for treatment.

 

 

 

INTRODUCTION:

In March 2014, the World Health Organization (WHO) announced a major outbreak of Ebola in the western African nations of Guinea, Liberia and Sierra Leone¹. The 2014 ZEBOV-caused EVD outbreak in West Africa is the longest, largest, most lethal, and most complex in history. There were 22,859 EVD cases as of 11 February 2015, with a total of 9,162 deaths. According to the average estimate of previous episodes in 36 years (1976-2012), there are currently over ten times the total number of cases of infection and over six times the total number of deaths, 2,232 infected people and 1,503 deaths².

 

Morphologically, the viral particles, when viewed under an electron microscope, look like long stretched filaments with certain particles appearing to curve into an form close to number 6. The genus Ebolavirus currently consists of five species: EBOV, Sudan ebolavirus (SUDV), Tai forest ebolavirus (TAFV), Bundibugyo ebolavirus (BDBV) and Reston ebolavirus (RESTV), respectively³. RESTV is found non-pathogenic to humans⁴. The genus is named after the first recorded outbreak that occurred in Yambuku village near the Ebola river in Zaire (now Democratic Republic of Congo). Many EVD outbreaks have occurred since, often of EBOV and SUDV⁵.

 

Epidemiology:

Ebola virus disease is a zoonotic disease and any epidemic in the human population starts with an entry from an animal inventory, i.e. due to hunting, direct interaction with infected animals, capture of bush meat⁶. A main cause of infection is direct contact with a sick person, or where there is infectious infection at the highest level, or when the patient uses infected products. Body fluids and secretions are primarily blood, saliva, urine, vomit, feces, and semen. Within the skin, filoviruses reach the host through mucosal surfaces, breaks and abrasions in the skin⁷.

 

Symptoms:

Symptoms typically start with sudden flu-like symptoms such as rapid onset of fever, mayopathy, and headache that are soon accompanied by bloody vomiting and diarrhea, nausea and vomiting, anorexia, body weakness, abdominal pain, arthralgia, back pain, oral cavity mucosal redness, dysphasia, conjunctivitis, rash on the body⁸. Some days later the first signs may start bleeding through the eyes, nose or mouth five to seven days later. A hemorrhagic rash may develop, which also bleeds, on the whole body. For most patients too, muscle pain and pharynx swelling occur⁹. In the current outbreak, west Africa registered the most common signs and symptoms from the symptom-onset to the time. The case was: fever (87%), fatigue (76%), vomiting (68%), diarrhea (66%), and loss of appetite (65%). The condition was observed. Only 18 percent of patients reported unexplained bleeding, most of them blood in stools (about 6%)¹⁰.

 

Diagnosis:

When Ebola virus is suspected in person, travel history and work history, along with exposure to wildlife, are important factors to consider with respect to further diagnostic efforts¹¹.

 

Nonspecific laboratory testing:

Low platelet count; initial decreased white blood cell count accompanied by increased blood cell count; elevated levels of liver enzymes alanine-aminotransferase (ALT) and aminotransferase aspartate (AST); and blood clots abnormalities often associated with disseminated intravascular coagulation (DIC) such as a prolonged prothrombin time, partial thromboplastin time, and bleeding time¹².

 

Specific laboratory testing:

The isolation of the virus and detection of antibodies to the virus in a person's blood confirms the diagnosis of EvD. The viruses are best used for early stages of disease as well as for the detection of the virus in human such as cell cultures, the detection by polymerase chain reaction (PCR) of viral RNA and the detection of the enzyme-related immunosorbent assay (ELISA)¹³. In later stages of the disease and in the recoverer, antibodies against the virus detection is most effective. Two days after symptoms start, IgM antibodies are detectable, and IgG antibodies 6 to18 days after symptom onset may be detected¹⁴.

 

Differential diagnosis:

Other tropical infectious diseases, such as influenza, measles, typhoid, leptospirosis, relapsing fever, anthrax, typhoid, non typhoid salmonellosis, dengue fiver, dengue fever, yellow fever, meningococcal Septicemia, and various types of encephalitis which are prevalent in these countries may be similar to early symptoms¹⁵. The differential diagnosis is also associated with non-infectious hemorrhage syndrome, such as acute leukemia, lupus erythematosus, idiopathic thrombocytopenic purpura, and hemolytic uremic syndrome¹⁶.

 

Treatment of Ebola Virus Infections:

The main strategies used currently for treatment of EVD are the care of patients by maintaining fluid and acid-base balance and the treatment of secondary infections, thus ensuring symptomatic and supportive care. There are currently no licensed EVD therapies.

 

Supportive Care of EVD Patients:

Ebola virus disease, characterized by muscle pain, fatigue, diarrhea and vomiting, is a febrile acute illness. Supportive EVD patients treatment is intended to restore the balance of body fluid and electrolytes otherwise lost in the digestive tract. The amount lost by severe diarrhea is compensated by oral or intravenous fluid in patients. It is also considered necessary to restore the levels of potassium, magnesium or calcium ion in blood. To reduce the severity of these symptoms, the management of symptoms of disease is necessary. The administration of antiemetics, such as metoclopramide and ondansetron, treat nausea and vomiting. The use of antidiarrheal substances such as loperamide is used to treat diarrhea. Pain is regulated by the use of acetaminophene or one of the analgesic opioids. Antibacterial agents are often used to avoid the translocation of bacteria from the gastrointestinal tract in infected patients¹⁷.

 

Polymerase Inhibitors:

Several inhibitors of viral polymerase were confirmed to have Ebola virus efficacy. BCX4430 is an adenosine synthetic analog that inhibits the termination of RNA polymerase. This compound was previously used in the intramusculary treatment of mouse models for the protection from Ebola virus and Marburg virus infection. After 48 hours of viral infection, Cynomolgus macaques have also been protected from Marburg Virus¹⁸.

 

Inhibitors of Virus Entry and Fusion:

The first step in Ebola virus infection is the fusion of viral and host cell membranes. Potential candidates for developing new drugs against the Ebola virus are viral fusion-inhibiting molecules and the entry into target cells. A high-performance in-vitro test with a 1536-well plate was recently developed to screen the molecular drugs approved by the Food and Drug Administration (FDA). The test led to the identification of 53 compounds which exhibited a virus-like particles inhibitory effect. The majority of these drugs have already been licensed to use as anti-cancer agents (e.g., vinblastine, vinorelbine, vinristine) and anti-depressants (e.g., Maprotiline and Clomipramine) (i.e., vinblastine and vincristine). In another in vitro assay for repurposing FDA-approved drugs¹⁹.

 

Convalescent Plasma and Monoclonal Antibodies:

Patients who survived with EVD infections immediately protect infected patients using convalescent plasma. In 1995 Borisevich et al. tried to use immunoglobulin isolated from equine hyperimmune serum to guard against EVD hamadryas (papio hamadryas). In the tests conducted in Hamadryas baboons, immunoglobulin provided up to 100 % protection against EVD. In a different study, EVD titer immune plasma was taken from immune sheep and goats and tested on experimentally infected guinea pigs. Prophylaxis was reported within 48 hours of the infection. As a possible therapy of EVD, the World Health Organisation (WHO) considers the use of whole or plasma convalescent blood from survivors. Treatment for transfusion is seen as an economical way of life-saving infected patients, with a predicted lower mortality rate from the use of recovery plasma than that for entire blood. Transfusion therapy High neutralizing antibodies transfusions can provide protection from various viral infections²⁰.

 

Therapeutic Approach to EVD:

No specific compounds have currently been approved for EVD therapy. The management of EVD depends on the replacement of fluid and diarrhoeal-loss electrolytes and on the severity of the symptoms of disease, such as diarrhoea and muscle pain. The current therapeutic approach to EVD has focused on implementing various strategies such as the use of plasma convalescent and monoclonal anticorps as well as testing compounds which prevent the injection and fusion of Ebola virus into target cells or have inhibitory viral polymerase enzymes. The 2014 outbreak of Ebola has also increased the pace to develop an efficient Ebola vaccine. The following sections focus on current efforts to develop Ebola therapy and promising clinical trial vaccine platforms²¹.

 

CONCLUSION:

Ebolavirus diseases (EVD) is a painful reminder everywhere as an outbreak which can be a risk. In the most affected countries, the Global Health Security Agenda aims to strengthen public health systems in order to eliminate spreads before emergencies. Drought, stupor, confusion, hypotension, multi-organs failure, leading to shock and eventual death, progressed symptoms over time. Preclinical screening for different candidates for the vaccine is also ongoing. It's been hypothesized that macrophage infection is one of the causes of hemorrhage growth. Recurrent Ebola outbreaks during 2014 call for urgency in the development of new medicines and therapeutic strategies. Locals where humans live in close contact with wild animals, which can serve as reservoirs for viruses, make EVD management especially at risk and pose the most difficult challenge to defend against infection. Strategic utilization of the best drugs and therapies currently available is therefore, in our opinion, the best approach for controlling and preventing the Ebola infection in such populations until better strategies and vaccines can be developed.

 

ACKNOWLEDGEMENT:

I express my sincere thanks to Vice-principal Prof. Dr. S. K. Mohite for providing me all necessary facilities and valuable guidance extended to me.

 

REFERENCES:

1.      Karunakar T, Kumar E, Naresh K, Sriram R. A review on Ebola virus. Int J Pharmacother. 2013;3(2): 55-59.

2.      Johnson KM, Lange JV, Webb PA, Murphy FA. Isolation and partial characterisation of a new virus causing acute haemorrhagic fever in Zaire. Lancet. 1977;1: 569-71.

3.      Le GB, Formenty P, Wyers M, Gounon P, Walker F, Boesch C. Isolation and partial characterisation of a new strain of Ebola virus. Lancet. 1995;345: 1271-1274.

4.      Gire SK, Goba A, Andersen KG, et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Sci. 2014;345: 1369-1372.

5.      Bausch DG, Bangura J, Garry RF, et al. A tribute to Sheik Humarr Khan and all the healthcare workers in West Africa who have sacrificed in the fight against Ebola virus disease: Mae we hush. Antiviral Res. 2014;111C:33-35.

6.      Hartman AL, Towner JS, Nichol ST. Ebola and Marburg hemorrhagic fever. Clin Lab Med. 2010;30: 161-177.

7.      McElroy AK, Erickson BR, Flietstra TD, et al. Ebola hemorrhagic Fever: novel biomarker correlates of clinical outcome. J Infect Dis. 2014;210: 558-566.

8.      Baize S, Pannetier D, Oestereich L. Emergence of Zaire Ebola Virus Disease in Guinea – Preliminary Report. N Engl J Med. 2014;371: 1418-1425.

9.      Leroy EM, Gonzalez JP, Baize S. Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa. Clin Microbiol Infect. 2011;17: 964-976.

10.   Takada A, Feldmann H, Ksiazek TG, Kawaoka Y. Antibody-dependent enhancement of Ebola virus infection. J Virol. 2003;77: 7539-7544.

11.   Van Gorp EC, Setiati TE, Mairuhu AT. Impaired fibrinolysis in the pathogenesis of dengue hemorrhagic fever. J Med Virol. 2002;67: 549-554.

12.   Jahrling PB, Geisbert TW, Geisbert JB, et al. Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections. J Infect Dis. 1999;179: 224-234.

13.   Warren TK, Wells J, Panchal RG. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature. 2014;508: 402-405.

14.   Leirs H, Mills JN, Krebs JW, et al. Search for the Ebola virus reservoir in Kikwit, Democratic Republic of the Congo: reflections on a vertebrate collection. J Infect Dis. 1999;179: 155-163.

15.   Kreuels B, Wichmann D, Emmerich P, Schmidt-Chanasit J, de Heer G, Kluge S, Sow A, Renne T, Gunther S, Lohse AW. A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med. 2014;371(25):2394–2401.

16.   Connor MJ Jr, Kraft C, Mehta AK, Varkey JB, Lyon GM, Crozier I, Stroher U, Ribner BS, Franch HA. Successful delivery of RRT in Ebola virus disease. J Am Soc Nephrol. 2015;26(1): 31–37.

17.   Gignoux E, Azman AS, de Smet M, Azuma P, Massaquoi M, Job D, Tiffany A, Petrucci R, Sterk E, Potet J. Effect of Artesunate-Amodiaquine on mortality related to Ebola virus disease. N Engl J Med. 2016; 374(1): 23–32.

18.   Dufour-Gaume F, Delaune D, Martinaud C, Sailliol A. Early and repeated use of plasma for the management of Ebola patients: reflection around a case. Transfus Clin Biol. 2017;24(1):5–8.

19.   Madrid PB, Chopra S, Manger ID, Gilfillan L, Keepers TR, Shurtleff AC, Green CE, Iyer LV, Dilks HH, Davey RA. A systematic screen of FDA-approved drugs for inhibitors of biological threat agents. PLoS One. 2013;8(4):605-609.

20.   Liu G, WongG, Su S, BiY, Plummer F, GaoGF, KobingerG, Qiu X. Clinical evaluation ofEbola virusdisease therapeutics. Trends Mol Med. 2017;23(9):820-830.

 

 

Received on 08.06.2020         Modified on 07.07.2020

Accepted on 25.07.2020       ©A&V Publications All right reserved