Abstract
The announcement for the successful global smallpox eradication by the World Health Organization was made in 1980. The effect of the elimination was that the worldwide vaccination process was discontinued. The gradual discontinuation exposes humans to the re-emergence of smallpox either intentionally or accidentally considering the massive number of people not vaccinated in the world and that variola virus, which is the causative agent, still exists in some laboratories. Considering the high mortality rate and the potential danger it presents, one must understand its biochemical features and molecular mechanism.
Introduction
One must understand the molecular and biochemical basis of smallpox and how it was eradicated, considering the possibility of re-emergence. First, an understanding of its clinical features based on history is essential. The mortality rate of the virus is between 1% to greater than 97% in Variola minor and hemorrhagic cases respectively (Thèves et al., 2014). It starts with an incubation period of between eight to fourteen days. After that, the patient experiences shivering, high fever, and arthralgia. A maculopapular rash follows this phase, and on the third day, they produce blisters followed by pustules that are infected on the seventh day. The patient is then ushered into the drying phase on the tenth to twelfth days if they survive characterized by the falling off of the scabs, leaving permanent scars. As for the hemorrhagic cases, the patients died after 24 hours, characterized by bleeding of the skin or mucous membrane. Therefore, an infected person could either recover or die, and in case of a recovery, they acquired lifelong immunity. There is no existing record of a successful treatment trial.
(Weiss & Esparza, 2015)
Biochemical Features
Since the resulting rash is the principal pathological feature of the virus, earlier studies show that several changes led to the lesion feature. First, capillaries dilation in the corium papillae was accompanied by endothelium lining swelling and histiocytes and lymphocytes infiltration. Afterward, there was a progression of the signs to the epidermis where the cells enlarged and underwent vacuolization at the center of the epidermal layer (Thèves et al., 2014). The proliferation of the Malpighian layer cells also resulted in the whole epithelial layer thickening. The process extended to middle layer adjacent cells resulting in extreme edema, which led to cell membranes rupture and vesicle formation. The septum found in the vesicles was because of the remains of the cells that were not annihilated.
Progression of the process led to the disappearance of the septa in the vesicles, thereby allowing the entry of polymorphonuclear leukocytes from the dermis into the vesicles leading to pustule production. Afterward, there was an absorption of the pustule fluid leading to the drying up of its contents and the formation of a cavity. The epithelial cells around the cavity area developed under the exudates residual mass. Consequently, the creation of scab was due to the presence of leukocytes, degenerated epithelial cells, and debris (Weiss & Esparza, 2015). The cause of the pockmarks left by the pustules was due to granulation tissue formation and sebaceous glands annihilation. Even though the pockmarks occurred in the entire body, most happened in the face since it, together with the scalp, has the most significant number of sebaceous glands.
Also, lesions were found in the mucous membranes of different organs such as the larynx, pharynx, upper part of the esophagus, and the mouth. Damage to the epithelial layers of the organs brought about the production of the excretions of the oropharyngeal that were highly contagious. While the skin has an impermeable keratin layer giving the skin a waterproof characteristic, a similar layer is not present in the above organs, thereby explaining the highly contagious excretions (Thèves et al., 2014). However, lesions were not reported in other organs of the body from previous research. However, there are reports of the liver and heart occasionally exhibiting small hemorrhages. Also, hemorrhagic smallpox though rare, was characterized by the occurrence of hemorrhages beneath the pleura, pericardium, and pericardium serosa. Lastly, the virus was also marked by bleeding in some organs such as the uterus, liver, kidney, lungs, bladder, and occasional bleeding in the bone marrow.
Molecular Mechanism
Research on understanding the molecular mechanism of the virus is complicated by the fact that it only occurs in humans. However, the development of new vaccines and antivirals are useful lies in first understanding the molecular mechanism of the virus. During an epidemic, the virus has a mutation potential that can speed up any outbreak or make it last longer. In 1940, the absence of RNA and the presence of DNA in the virus was established. This achievement was followed by the demonstration that the DNA was double-stranded, and it was composed of about 36% cytosine and guanine in 1962 (Thèves et al., 2014). It was not possible to distinguish the orthopoxviruses based on their structure. One unique feature of this DNA virus in comparison to other DNA viruses is that its replication occurs in the cytoplasm of the host cell as opposed to the nucleus.
The viruses were replicated in the host cells cytoplasm and consequently transcribed with the help of RNA replicase, which copies the DNA sequence of the virus into an RNA sequence. Therefore, to help in the transcription and translation of its genetic material in the host cell, the outer protective layer of the virion is lost. In the process, some of the virions contained in the cytoplasm are enveloped since the virions in themselves are inert (Weiss & Esparza, 2015). The envelope is made of polypeptides that are specific to the virus and include hemagglutinin. Afterward, the viruses are released from the host cells in the form of enveloped virions. However, not all virion particles are enclosed as only a few acquire the envelope. Those that are not enveloped are released after the host cells have gone through a disruption.
The natural way of contracting the virus was through aerosols droplets dropping on the respiratory mucosa or the oropharyngeal. However, the dosage of virions required for the virus to be infectious remained unknown. Early multiplication of the virus occurred in the regional lymph nodes, distant lymph nodes, bone marrow, and spleen following the early infection of the macrophages cells allowing the virus to migrate further through the local lymphatic channels. During this stage of infection targeting the upper respiratory tract and oropharynx, the patients were mainly asymptomatic (Thèves et al., 2014). Also, the presence of the virus in the cells led to viremia, which provided the virus with access to the rest of the body even as the virions remained localized in the dermis through small vessels. Consequently, the macrophages that had the virus infection could migrate into the epidermis and, in turn, infecting basal layer cells that were nearby. Afterward, necrosis and edema occurred, leading to a dermis split, and the polymorphonuclear leukocytes migrated into the developing vesicles lumen bringing about a pustular.
Therefore, the orthopoxviruses genome has a central region containing sequences that are highly conserved. It is from this region that most genes taking part in transcription, replication, and repair of the DNA, virus protein structure modifications, and biosynthesis of the mRNA are located (Weiss & Esparza, 2015). As for the terminal regions of the genome, they vary and determine the properties linked to a particular species, the immunomodulatory protein genes of the virus, and its strain. The virus is unique in the sense that it relates to some genes that encode proteins that adeptly adjusts the various defense systems of the organism that has hosted it.
Diagnosis
During diagnosis, the only difficulty in diagnosing smallpox was chickenpox since both were characterized by skin lesions and were transmitted through skin lesions contact or respiratory secretions. However, the appearance of the lesions and the clinical course of the diseases helped in distinguishing them (Melamed et al., 2018). It was easy to diagnose smallpox using rash distribution and presentation. However, the diagnosis had to be confirmed through a laboratory test to identify the particular DNA sequence of the virus.
Clinical Management
The clinical management of the virus required preventive measures for pre-exposure, infection control measures for post-exposure and post-exposure therapy. For instance, one of the measures by most states in the United States required the vaccination of children before they start schooling. The eradication of the virus is linked to vaccination as opposed to treatment. However, such vaccinations stopped in 1972. Therefore, the current world population, especially those below the age of 45, is exposed and highly susceptible to a smallpox outbreak (Melamed et al., 2018). Even though the CDC and WHO have some vaccines, they are insignificant in comparison to the current world population.
Conclusion
Considering the smallpox virus has been placed in category A of bioweapons due to the possibility of its use or the use of a pathogenic virus in bioterrorism and bio-warfare, the world must be adequately prepared for any eventuality. A category A bioweapon is one whose dissemination and transmission from one subject to another is easy, as seen in the biochemical features and molecular mechanism of the virus. Notwithstanding its eradication in 1980, further studies on the biochemical characteristics and molecular mechanism of the virus are essential in ensuring the world is better prepared in case of an emergency.