03 August 2012

Ebola strikes in Uganda! Are we prepared?
- The Ugandan Ministry of Health has reported an outbreak of Ebola hemorrhagic fever in the Kibaale District of western Uganda. As of July 31, there have been 38 cases and 16 deaths. Five cases have been laboratory confirmed. Travelers are not particularly susceptible to Ebola Hemorrhagic Fever (HF). However it is advisable not to come in close contact with suspected cases as this heightens the possibility of contamination. There is currently no vaccine for it. So, exercise judicious inter-personal communications. Confirmed cases of Ebola HF have been reported in the Democratic Republic of the Congo, Gabon, Sudan, the Ivory Coast, Uganda, and the Republic of the Congo.

- Now, what is Ebola again? It is a deadly virus that causes severe hemorrhagic fever, which has seen several outbreaks in Africa over the years. Let us quickly review the makings of a virus and how they act in host systems.Vruses consist basically of nucleic acid surrounded by one or more proteins. Some have an outer-membrane envelope. Since they only contain a nucleic acid and a protein, their nucleic acids can’t produce the vital enzymes necessary for the metabolism of protein, carbohydrate and lipids necessary for high-energy phosphates. They need to inhabit living cells to obtain the necessary elements of a living organism in order for the virus itself to multiply. That means they are parasites. The fusion of viral proteins with cell membranes is a crucial step in viral infection.

- In the Filoviridae family of viruses, order of Mononegavirales, comes Ebola, ranking among the largest known viruses with variable length (as long as 14 000 nanometers).  It is a negative-strand RNA virus. In the host cells, they go through a fast lytic replication. The virions are characterized by a single negative-strand RNA genome, the RNA serving as a framework for at least seven polypeptides, a glycoprotein, a polymerase, a nucleoprotein and least four other undesignated proteins. Except for influenza virus, which transcribes its mRNAs and anti-genomic RNAs in the cell’s nucleus, negative-strand RNA viruses replicate entirely in the cytoplasm. All Negative-strand RNA viruses, including influenza viruses, assemble in the cytoplasm. Their capsid symmetry is helical. (There are two main classes  of  virus structures: helical and icosahedral symmetry.) Current understanding demonstrates that Ebola Virus Disease is caused by four of five viruses classified in the genus Ebolavirus, family Filoviridae, order Mononegavirales: Bundibugyo virus, Ebola (Zaire) virus, Ebola (Sudan virus), and Taï Forest virus also known as Côte d'Ivoire Ebolavirus discovered in Africa, in 1994 . The fifth virus, Reston virus, is thought not to be pathogenic for humans and first discovered during an outbreak of simian hemorrhagic fever virus (SHFV) in crab-eating macaques in 1989. The cynomolgus monkeys had been shipped from the Philippines (where the virus has also infected pigs) to a location in the U.S.. No humans were affected and no illness ensued.

- There are Asian filoviridae, as well as African filoviridae. There is apparently close identity at the glycoprotein level among Asian filoviruses, but not African filoviruses. Primary infection due to Filoviridae is very rare. The first appearance of this pathogen was in Marburg, hence the name Marburg virus, a genetically unique zoonotic (that is, animal-borne) RNA virus of the filovirus family which has caused outbreaks in Marburg, when cases of hemorrhagic fever occurred simultaneously in laboratories in Marburg and Frankfurt, Germany and in Belgrade, Yugoslavia (now Serbia) The virus was first recognized in 1967. The virus that was isolated from these cases had an unusual,looped and branched filamentous form (hence the name, filovirus). The first people infected had been exposed to African green monkeys or their tissues. Thirty-one people became ill; they included laboratory workers as well as several medical personnel and family members who had cared for them. There were 7 deaths among the reported cases. The current Ebola (Sudan) hemorrhagic fever variety was first isolated in 1976, apparently among health workers in a mission hospital. A large outbreak of the Ebola (Zaire) strain took place in the Democratic Republic of Congo which resulted in 315 cases with a high mortality rate of around 80 percent. A fourth of the total people affected were healthcare workers in a hospital, with eventual secondary spread in the community. The five species of Ebola virus are the only other known members of the filoviridae family.

- In August 2000, Ebola (Sudan) re-emerged in Uganda leading to a large epidemic which resulted in 400 or so cases, and which seemed to have ended in January of the following year. On November 24, 2007, the Uganda Ministry of Health confirmed an outbreak of Ebolavirus in the Bundibugyo District. This, scientists confirmed, was the fifth type of Ebola virus. While the main mode of transmission is person to person, contact with body secretions is the contamination factor. Droplet or casual contact are not the usual modes of transmission. However, because of its lethal nature, Ebola is a candidate for bioterrorism or germ warfare. However, for this purpose, it has to be bioengineered further.

  -Ebola virus virion. Created by CDC microbiologist Cynthia Goldsmith, 
   this colorized transmission electron micrograph (TEM) revealed some 
   of the ultrastructural morphology displayed by an Ebola virus virion.
   Source: Public Health Image Library, #10816

- The incubation period, ranges from about a week or so, to three weeks. Abrupt fever with chills, severe headache, muscle pains, malaise, arthralgia, conjunctivitis are the usual signs and symptoms at the onset. There is also occurrence of sore throat and a papular rash (which may later desquamate). Three days after onset, there are gastro-intestinal manifestations of diarrhea and vomiting. At the end of the week of onset, signs of hepatic disease ensue, which are detected by markedly elevated aspartate transaminase (AST). Jaundice is not a feature. Bilirubin is not elevated and alanine transaminase (ALT) is disproportionately low. Ebola-specific IgG rises in survivors, while in fatal cases there is no IgG and hardly any IgM. Bleeding is prominent as demonstrated by petechiae, hemorrhagic effusions and copious bleeding from syringe needle puncture sites. The most notable outcome is hypotensive shock. 

-The virus particles seem to be drawn to reticulo-endothelial cells. During the last five days of life, there is DNA fragmentation in blood leukocytes and protein in the nuclear substance indicates intravascular apoptosis. Fatal cases show high titers of virus and extensive dissemination of the latter in tissues. If an individual who has come in close contact with infected patients, or contaminated material, begins to develop fever and malaise, an antigen-capture enzyme-linked immunosorbent assay (ELISA) testing, IgM ELISA, polymerase chain reaction (PCR), and virus isolation can be used to diagnose a case of Ebola HF within a few days of the onset of symptoms. If a person with previous contact with a suspected Ebola HF case, travels to his home country, or to another location, it is highly recommended that he perform the aforementioned tests. If positive, isolate the individual and inform local health authorities.

- Since the reservoir of Ebola is unknown, precautions are difficult to promote, or warnings announced to the public, that is, aside from avoidance of close contact with patients, and meticulous hygiene. Avoid contact with animals. Hence, health workers dealing with patients with suspicious, abrupt fevers with the aforementioned signs and symptoms should exercise extreme care with potentially contaminated material, used syringes, soiled dressings and excreta. There is no standard treatment.  For the affected individual, only intensive care support is the management of choice. Isolation of the patient is essential. Airline personnel are advised to be observant of any suspicious passengers presenting with fever and severe malaise. Again, health authorities must be notified without delay. Human vaccines are in the making.
-For further information, kindly visit the Centers for Disease Control website.
Well, that wraps it up for now.  Stay tuned for developments.

-Fernando Yaakov Lalana, M.D.

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