Structure and Pathogenesis of Small Pox Virus

Classification

Genome: Linear double-stranded DNA

Family: Poxviridea

subfamily: Chordopoxvirinae

genus: orthopoxvirus

species: variola

Structure

The smallpox virus is a large, brick-shaped with size measuring 300-400*230nm. It is the double-stranded DNA (dsDNA) virus that serologically cross-reacts with other members of the poxvirus family. The member of the virus includes ectromelia, cowpox, monkeypox, vaccinia, and camelpox. Smallpox virus is also known as variola virus and unlike other DNA viruses, the variola virus gets multiplies in the cytoplasm of parasitized host cells.

Viruses have a complex symmetry that is it is of neither icosahedral nor helical. The external surface of smallpox virus consists of ridges. Its structure has a core which is of dumble shaped.

Core- It has the large viral genome of dsDNA with 130-375 kb. Core also contains many enzymes including transcriptional system.

DNA-It consists of inverted terminal repeats of variable length. Two strands are connected at the ends by terminal repeats sequences.

Virion- It contains more than 100 polypeptides and known to be infective form

Human beings are naturally infected by variola virus and do not exist in a carrier state. Experimentally infected cynomolgus macaques (Macaca fascicularis) develop ordinary or hemorrhagic variola, which depends on upon the size of the inoculums. The smallpox virus is most stable at low temperatures, which can survive in the environment for a short period along with low humidity. Smallpox is spread most efficiently by means of inhalation and sometimes also less efficiently by means of direct contact with pustular or scabs material from skin lesions.

Transmission

Mostly this virus gets entrance in the human body through portal entry such as mucus membranes of upper respiratory tract (URT) or inoculation on the skin. Also through excretions from mouth and nose, rather than scabs, are the most important sources of virus.

Pathogenesis

As the virus get transmit through a different site in a human body, firstly, primary replication of virus occur at the site of inoculation. Then gradually replication occur at regional lymph nodes, and finally to the deeper lymph nodes. This replication causes the transient viremia condition which is also known to be primary viremia. It is the condition where the virus gets transmit to the blood. Then finally it causes the infection of Reticulo Endothelial System (RES) which includes spleen, bone marrow, and other lymph nodes infection. Infection still continues leading towards secondary multiplication in those cells, which is known to be secondary, more intense viremia. The pathogenesis ends with showing the clinical disease with sign and symptoms.

Symptoms

There are two major forms of smallpox virus:

1. variola major
2. variola minor

Clinically, prodromal phase begins 1-4 days before the onset of rash and includes fever over 101F and at least one of these symptoms: Headache, backbone pain, chills, vomiting, abdominal pain etc.

The presence of classic smallpox lesions; firm, round, deep- seated vesicles or pustles and also the appearance of lesions on the palms of the hands and soles of the feet.

Types of smallpox

The two most common types of smallpox are namely major and minor. These types of variola greatly differ in their mortality rates (30% vs 1%, respectively). All outbreaks of smallpox in Asia and most in Africa were due to variola major during the 20^TH century. Among minor and major, variola major was the predominant endemic strain throughout the world, and by the end of the 18th century, it was responsible for approximately 400,000 deaths a year in Europe. Variola minor was endemic in some countries in Europe, North America, South America, and many parts of Africa. Blindness was common mostly in the patients who recovered from this disease and as well as disfiguring scars were nearly universal.

Four subtypes of Variola major smallpox are Ordinary smallpox, Modified smallpox, Flat smallpox and Hemorrhagic smallpox.

• Ordinary smallpox is the most common form. It accounts for 90% or more of smallpox cases

• Modified smallpox is a mild form that occurs in previously vaccinated persons

• Flat smallpox is also known as malignant smallpox. It is a severe variety of smallpox in which lesions do not project above the skin surface.
• Hemorrhagic smallpox is also known as fulminant smallpox which is rare, very severe, highly fatal variety of smallpox. On this case, hemorrhages develop in the skin and mucous membranes.

Variola minor was previously found mainly in South Africa, South America, Europe, and Australia. This type is less common and also much less virulent.

Other types of smallpox include are variola sine eruptione, a pulmonary form of smallpox, a pharyngeal form of smallpox and influenza-like a form of smallpox. Among these, the pharyngeal and influenza-like forms are relatively mild, usually, affect individuals who have been previously immunized, and do not cause mortality.

• Variola sine eruptione is known to be variola sine exanthema which is another less common form of smallpox.
• Pulmonary form of smallpox has been described in individuals with little or no smallpox immunity. It is notified by severe symptoms, cyanosis, and bilateral infiltrates; the mortality rate of this type is undetermined.
• A pharyngeal form of smallpox mostly presents with a spotty enanthem over the soft palate, uvula, and pharynx. This type develops in immunized individuals.
• Influenza-like a form of smallpox rarely results in a rash.

Lab diagnosis

In most cases, clinical diagnosis is sufficient. Lab diagnosis is done in the following order;

Specimens:

Vesicular or pustular fluids, scabs, scrapings of skin lesions, blood, tonsillar swabs etc.

Isolation and identification of virus

The virus is isolated by inoculation of potential specimens into a chorioallantoic membrane of the chick embryo. After 2-3 days of incubation, small variola pox can be seen. The definitive identification of the virus is also made by immunofluorescence assay.

The virus can also be identified by electron microscopy, Polymerase chain reaction, and serological tests.

Immunity

Immunological response by both cell mediated and antibody mediated is high in variola infection. Infection provides long last immunity.

Cellular immunity and antibody-mediated immunity are elicited in response to smallpox infection. During the first week of infection by this virus, neutralizing antibodies can be detected from it whereas second to third weeks, hemagglutination-inhibition and complement-fixation antibodies are found. Neutralizing antibodies detected have the capacity to persist for many years or decades after clinical illness, whereas levels of hemagglutination-inhibition and complement-fixation antibodies generally decrease within a year of infection.

Cell-mediated immunity likely plays an important role in controlling disease; virus-specific cytotoxic T cells are believed to limit viral spread by causing lysis of infected cells in the reticuloendothelial system and the skin and they are detectable in lymphoid organs as early as 4 days after infection .

Treatment

There is no effective treatment other than management of symptoms:

• Adequate fluid intake
• Alleviation of pain and fever
• Keeping skin lesions clean to prevent bacterial infections

Immunoglobulin therapy is available in case of variola major.

Antiviral Drug: Cidofovir

Vaccination

Edward Jenner (1796) developed a vaccine against smallpox which was traditionally given using bifurcated needles. (15 times, 1 time/3sec)

Features of Eradication

• Effective vaccine (provides lifelong immunity)
• Only one stable serotype
• No animal reservoir
• No persistent infection

REFERENCE

Cheesbrough, M. Medical Laboratory Manual for Tropical Countries. Vol. Vol 2. ELBS London, 2007.

Tille, P.Diagnostic Microbiology.13th. Elsevier, 2014.

D, Grenwood, Slack RCB and Peutherer J. Medical Microbiology. Dunclude Livingstone: ELBS, 2001.