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The health disaster caused by the outbreak of the ebola virus in zaire

Nature and History of Ebola Virus: An Overview, Arch Neurosci. Ebola virus is infamous due to its reputation in hemorrhagic fever disease outbreaks in various countries of the world including West Africa. The current paper briefly discussed the history of Ebola virus along with its origin, geographical distribution, structure, replication, reservoirs, hosts, pathogenicity, viral entry mechanism, mode of action, epidemiology, viral transmission, disease symptoms, diagnostic strategies, clinical applications, medication and protective measures to create awareness among people.

Before 2014, approximately the total loss of 1500 lives was recorded out of 2400 recognized cases, since the first discovery of Ebola virus in 1976. But the ongoing West African outbreak is the largest Ebola virus disease outbreak in the history, world health organization WHO reported a total of 28,599 cases observed and 11,289 deaths from this outbreak by 10 November 2015. Despite the known severity of Ebola outbreaks, no effective vaccine or therapeutic drug is developed so far because of the RNA coded nature of this virus, but many candidate vaccines are going on trial basis.

Lethal and infectious nature of this virus requires the effective diagnostic methods. Scientists working in this field should be cooperative and committed to combat this natural disaster effectively. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4. Introduction About 1500 species of infectious organisms are known to be pathogenic to humans, including 217 viruses and prions 12.

The ongoing multinational Ebola outbreak posed a serious threat to the countries of West Africa and beyond due to its unprecedented magnitude. Ebola is an enveloped virus that belongs to the family Filoviridae. It includes five species of Ebola and a strain of Marburg virus, which cause hemorrhagic fever in humans and also in nonhuman primates.

The term viral hemorrhagic fever refers to a variety of viral diseases characterized by bleeding and fever in humans. Almost similar severe outbreaks of hemorrhagic fever with high fatality rate occurred in the provinces of Zaire and Sudan. Although the causing agents were identical and similar in morphology to Marburg virus strain isolated from South Africa in 1975 and Germany in 1967 and was named Ebola virus, the electron microscopy and serological studies showed that the involved viruses were closely related 6.

Ebola virus is mostly thrived in West and Black Africa where it has caused large outbreaks with high mortality rates. In spite of such severity of Ebola outbreaks, no affective vaccine or therapeutic drug is developed yet for clinical purposes.

Ebola virus disease

This strain is considered as not being pathogenic for humans but causes hemorrhagic fever in experimentally infected animals 89.

It is said that the current outbreak of Ebola virus disease in West Africa found its roots from a single zoonotic transmission event by a two year old boy in Meliandou, Guinea 10. Hosts Natural reservoir for Ebola is not confirmed yet. However researchers suspect the fruit bats as the most probable candidate species. Three different bat types are found to carry this virus without being affected that suggested them as a primary natural reservoir for Ebola viruses 11. However infectious Ebola viruses have never been characterized from any fruit bat species except small amount of viral RNA fragments of Zaire Ebola virus around endemic areas 12 - 14.

Birds, plants, and arthropods are also regarded as possible reservoirs of this virus.

  1. Reducing the risk of possible sexual transmission, based on further analysis of ongoing research and consideration by the WHO Advisory Group on the Ebola Virus Disease Response, WHO recommends that male survivors of Ebola virus disease practice safe sex and hygiene for 12 months from onset of symptoms or until their semen tests negative twice for Ebola virus.
  2. Relapse-symptomatic illness in someone who has recovered from EVD due to increased replication of the virus in a specific site is a rare event, but has been documented.
  3. Having tested negative, survivors can safely resume normal sexual practices without fear of Ebola virus transmission.
  4. The observed mutational rate of Ebola virus is 2.

On the other hand several strains of filovirus are detected through enzyme-linked immunosorbent assay ELISA from the serum of migratory fruit bats Eidolon helvum in Zambia 14. Insectivorous free-tailed bats Mops condylurus may be the potential source of African outbreak since it survived experimental infections, and index case may be infected by playing near the housing colony of these bats 10.

  • About 731 nucleotides from the 5' end and 472 nucleotides from the 3' end are enough for viral genome replication though not for infection;
  • A ring vaccination protocol was chosen for the trial, where some of the rings are vaccinated shortly after a case is detected, and other rings are vaccinated after a delay of 3 weeks;
  • Introduction About 1500 species of infectious organisms are known to be pathogenic to humans, including 217 viruses and prions 1 , 2;
  • Persistent virus in people recovering from Ebola virus disease Ebola virus is known to persist in immune-privileged sites in some people who have recovered from Ebola virus disease.

Phylogenetic and sequencing evidence revealed that filovirus-like elements integrated in the genomes of bats, shrews, tenrecs, rodents and marsupials. This shows that the mammal-filovirus association is ancient which resulted in gene production RNA or protein 16.

Other three proteins are glycoprotein GPVP24 and VP40 are associated with viral membrane to form the filamentous virions 1920. Expression of the virion-associated proteins VP24 and VP35 led to assembly of nucleocapsids by transmission of electron microscopy and showed that it is involved in the assembly of EBOV nucleocapsids 21. The matrix protein VP24 is also involved in the regulatory process of viral genome replication and transcription 22.

About 731 nucleotides from the 5' end and 472 nucleotides from the 3' end are enough for viral genome replication though not for infection. As Ebola virus is RNA coded, therefore it was found to mutate very rapidly within the host and reservoir population. The observed mutational rate of Ebola virus is 2. That is why it is very difficult to develop vaccine against Ebola virus.

The diameter of cylinders is approximately 80 nm and the length may be 14000 nm having a spike like virally encoded glycoprotein GP of 7 - 10 nm long projects from its surface of lipid bilayer 23. The overall shape of virions varies considerably ranging from simple cylinders to branches, loops and reverse direction.

However, the characteristic threadlike structure is a more general shape of filoviruses Figure 1. Structure and the Genome of Ebola Virus 24 5. For viral fusion, viruses mostly exploit the endocytic routes and through that, they access cytoplasm by macropinosomes, caveolae and clathrin-coated vesicles pathways.

The EBOV also exploits several molecules such as a variety of different C-type lectins to entry the host cells 26. EBOV proteins interact with various host proteins for virus replication. EBOV-GP is synthesized as single-chain precursors and further transferred co-translationally into the lumen of the endoplasmic reticulum to form trimmers 38.

Entry of the virus is pH dependent and also associated with the cleavage of GP by proteases 40. Cleavage produced three cleavage fragments, with masses of 23, 19, and 4 kDa 41. A 19-kDa core subunit triggers GP to bind endosomal receptors and potentiates GP to undergo subsequent fusion-relevant conformational changes 4243.

The GP1 subunit is responsible for receptor binding while GP2 subunit anchors the glycoprotein into the viral membrane. The first 300 residues of GP1 subunit are conserved but the remaining residues are variable. The variable region of GP1 that is C-terminal, contains several O-linked glycosylation sites and is known as the mucin domain 4445. The structure of GP2 by X-ray crystallography revealed that GP2 contains a central triple stranded coiled coil followed by a disulfide-bonded loop.

  1. Ebola virus is infamous due to its reputation in hemorrhagic fever disease outbreaks in various countries of the world including West Africa. Historical Outbreaks and the Studied Cases Ebola virus disseminates in Black Africa, where it often drives large outbreaks of acute hemorrhagic fever with high fatality rate 55.
  2. Health-care workers have frequently been infected while treating patients with suspected or confirmed EVD.
  3. However researchers suspect the fruit bats as the most probable candidate species. As Ebola virus is RNA coded, therefore it was found to mutate very rapidly within the host and reservoir population.
  4. In women who have been infected while pregnant, the virus persists in the placenta, amniotic fluid and fetus.

GP2 could bridge two membranes to initiate membrane fusion 46. Thetrimeric crystal structure of surface glycoprotein GP is also required to initiate attachment and fusion of viral and host membranes that further bind to a neutralizing antibody, KZ52, in humans 42. Human lysosomal cholesterol transporter Niemann-Pick C1 NPC1 fulfills a cardinal property of viral receptors and binds specifically to viral GP 3031.

EBOV-GP is the main viral determinant of the Ebola virus pathogenicity that induces cytotoxic effects in human endothelial cells 47. GP contains a mucin-like domain involved in massive endothelial cell loss within 24 hours and resulted in increased vascular permeability into explanted human or porcine blood vessels.

The mucin-like domain of GP was required for this effect and indicated that it was the viral determinant of Ebola pathogenicity 47. These filoviruses maintain glycoprotein glycosylation to protect against antibody neutralization and proteases at the expense of efficient entry 3. Infection and Mode of Action of Ebola Virus 36 8. Disease and Symptoms Ebola virus has an incubation period of 2 to 21 days and during these days infected patients develop flu-like symptoms such as fever, headache, reduced appetite, vomiting, abdominal pain, vascular dysfunction, diarrhea and fatigue.

Fever remains higher than 38.

Sexual transmission

These conditions are followed by vomiting, abdominal pain and sometimes chest pain and shortness of breath may occur. Severe and fatal stages are accompanied by bleeding from small infections, hemorrhagic diathesis, reduced adaptive immune responses, shock, coagulation disorders and eventual multiple-organ failure occur in this disease 5051. The fatal outcome is also associated with the aberrant innate immune responses due to massive intravascular B- and T-lymphocyte apoptosis that induced profound suppression of adaptive immunity in experimentally infected animals and humans 5152.

Recovery may start 7 to 14 days after the first symptom 52. Death often occurs due to decreased blood pressure because of severe bleeding and loss of body fluid 53.

Those who survive have many ongoing problems such as liver inflammation, muscular and joint pain, decreased hearing, weight loss and weakness. Recovered patient can no longer transfer the virus 54. Epidemiology and Transmission of Ebola High numbers of Ebola virus particles can be found in sweat glands of the human skin indicating that transmission may occur through direct contact but viral entry in the body is still unclear.

Archives of Neuroscience

Human-to-human transmission mainly occurs via contact with the body fluids of the infected person during the treatment reusing unsterilized medical devices and traditional funeral practicing, kissing, touching and washing the body 55. Airborne mode of transmission between primates including humans is not observed yet either in natural conditions or in laboratories.

The transmissibility of Ebolavirus is generally highest in the clinical course of infection unlike other viruses 56. This virus may reach any place in the world with no time through modern transportation. Investigation suggested that environmental factors are also associated with transmission of Ebola virus disease EVD particularly to the drier conditions at the end of the rainy season and may enhance transmission of Ebola virus from its cryptic reservoir to humans 56.

Historical Outbreaks and the Studied Cases Ebola virus disseminates in Black Africa, where it often drives large outbreaks of acute hemorrhagic fever with high fatality rate 55. The first case of filovirus hemorrhagic fever was reported in 1967 in Germany and the former Yugoslavia, and the causative agent was identified as Marburg virus. After that, 12 similar cases of hemorrhagic fever were described in 1976 from outbreaks in two neighboring locations: This strain caused three more epidemics in the areas of Nezara, Sudan in 1979 57.

An unknown causative agent was isolated from patients in both outbreaks and named Ebola virus after a small river in northwestern DRC. Later it was identified that this newly discovered virus had the same aspect of Ebola hemorrhagic fever as the other two Ebola strains 59. In 1994 an epidemic was primarily reported as a yellow fever outbreak in 44 cases with 28 deaths in Gabon.

Later studies suggested that it was due to Ebola virus attack.

Gabon was attacked twice by Ebola virus in 1996. The first outbreak began in February and out of the 37 cases 21 died.

Transmission

The second epidemic was from July to December and 40 deaths were reported among the 52 identified cases 60. Ebola hemorrhagic fever was re-emerged in 1995 in Kikwit, Democratic Republic of the Congo. Isolates obtained from the samplings confirmed the presence of Zaire Ebola Virus ZEBOV ; viruses that caused severe hemorrhagic fever outbreak among the people of Kikwit, Democratic Republic of the Congo in 1995 and 231 people died out of 300 affected people.

Similar isolates were also observed during an outbreak of this fever in cynomolgus macaques in Texas, Alice and the Philippines in 1996 4661. With a total number of about 430 cases reported in Uganda in 2000-2001, this Ebola virus outbreak is considered as the largest epidemic described to date. A novel strain of Ebola virus named Bundibugyo ebolavirus was identified during an outbreak of viral fever in Bundibugyo district of western Uganda and later on in equatorial regions of Africa in 2007-2008.

The Bundibugyo Ebola virus outbreak caused a lower proportion of deaths than did the Sudan Ebola virus outbreak in Gulu and Sudan. Uganda ministry of health UMOH declared deaths of 39 persons in this outbreak in Bundibugyo district 62. Before 2014, approximately more than 2400 people were infected, along with more than 1500 recorded deaths in the past four decades since its first discovery in 1976 in the areas of Zaire and Sudan 64.

From December 2013 to September 2014, a total of 2296 deaths were reported out of 4507 confirmed and probable cases of Ebola virus from five countries of West Africa i e, Guinea, Nigeria, Senegal, Liberia, and Sierra Leone 65. The largest outbreak is the ongoing epidemic in some specific areas of West Africa including main targets of Guinea and Sierra Leone. WHO reported a total of 28,599 cases observed and 11,289 deaths from this outbreak by 10 November 2015 66.

There were about 24 outbreaks of EVD, but only seven involved more than 100 cases.