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Monday, October 22, 2007

Smallpox

Compiled and Summarized by Anthony
Smallpox (also known by the Latin names Variola or Variola vera) is a contagious disease unique to humans. Smallpox is caused by either of two virus variants named Variola major and Variola minor. The deadlier form, V. major, has a mortality rate of 30–35%, while V. minor causes a milder form of disease called alastrim and kills ~1% of its victims. Long-term side-effects for survivors include the characteristic skin scars. Occasional side effects include blindness due to corneal ulcerations and infertility in male survivors.

Smallpox killed an estimated 60 million Europeans, including five reigning European monarchs, in the 18th century alone. Up to 30% of those infected, including 80% of the children under 5 years of age, died from the disease, and one third of the survivors became blind.

Smallpox was responsible for an estimated 300–500 million deaths in the 20th century. As recently as 1967, the World Health Organization (WHO) estimated that 15 million people contracted the disease and that two million died in that year. After successful vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in 1979. To this day, smallpox is the only human infectious disease to have been completely eradicated from nature.

Signs and Symptoms

People who have contracted smallpox initially develop such symptoms as fever, body aches, headache, chills, and, particularly, backache. Over half of people with smallpox experience chills and vomiting. About 15% become confused.

A rash appears 48-72 hours after the initial symptoms and turns into virus-filled sores, which later scab over. The process can take up to 2 weeks.

Just after the rash appears, the virus is highly contagious as it moves into the mucous membranes. The body sheds the cells, and virus particles are released, coughed, or sneezed into the environment. The infected person can be infectious for up to 3 weeks (until the scabs fall off the rash). Live virus can be present in the scabs. After the scabs or crusts fall off (in 2-4 weeks), a depression or light-skinned scar remains.

Early in the course of the disease, the rash and pus-filled sores can easily be mistaken for chickenpox. Lesions occur first in the mouth and spread to the face, then to the forearms and hands, and finally to the lower limbs and trunk. In contrast, rash from chickenpox progresses from the arms and legs to the trunk and rarely forms in the armpits, palms, soles, and elbow areas.

Causative Agent

Variola major and Variola minor

Mode of Transmission

The most frequent mode of transmission was person-to-person, spread through direct deposit of infective droplets onto the nasal, oral, or pharyngeal mucosal membranes, or the alveoli of the lungs from close, face-to-face contact with an infectious person. Indirect spread (i.e., not requiring face-to-face contact with an infectious person) through fine-particle aerosols or a fomite containing the virus was less common.

Diagnosis

Initial diagnosis of smallpox is most likely based on a history and physical examination findings.

The doctor may take a throat swab to make the diagnosis of smallpox. A sample from a freshly opened pustule may also be useful in diagnosis. For suspected cases of hemorrhagic smallpox, the doctor may sample fluid from a spinal tap (lumbar puncture). Under certain conditions, cytoplasmic inclusion bodies (also known as Guarnieri bodies) may be visible within the cells. This is also evidence of smallpox infection.

Technicians isolate the variola virus in labs with only the highest biosafety levels (Biosafety level IV). The CDC in Atlanta and the US Army Medical Research Institute of Infectious Diseases (USAMRIID) at Ft. Detrick, Maryland, are the only laboratories in the US with these capabilities right now.

The doctor sends the possible smallpox sample using special means. Viral cultures, polymerase chain reaction (PCR), and/or enzyme-linked immunoabsorbent assay (ELISA) may be undertaken to make a definitive diagnosis once the sample arrives at the lab.

Even one case of smallpox is considered an international public health emergency, and public health officials must be notified of a possible case of smallpox immediately.

Incubation Period

The incubation period between contraction and the first obvious symptoms of the disease is around 12 days. In the initial growth phase the virus seems to move from cell to cell, but around the 12th day, lysis of many infected cells occurs and the virus is found in the bloodstream in large numbers.

Pathogenesis

· The portal of entry for variola virus is usually through the oropharyngeal or respiratory mucosa; variola virus can also enter through the skin, and rarely, through the conjunctiva or placenta (see References: Fenner 1988: Chapters 1 and 3).

· The virus migrates rapidly to regional lymph nodes.

· Asymptomatic viremia occurs on the 3rd or 4th day after infection, with further dissemination of the virus to spleen, bone marrow, and other lymph nodes.

· Secondary viremia occurs by the 8th to 12th day after initial infection; this is followed by onset of fever and toxemia.

· The virus localizes in small blood vessels of the dermis and oropharyngeal mucosa, leading to initial onset of the enanthem and exanthem, at which point (about day 14) the patient becomes infectious. The spleen, lymph nodes, kidneys, liver, bone marrow, and other viscera also may contain large amounts of virus (see References: Breman 2002).

· The development and evolution of skin lesions involves the following steps:


  • Dilatation of the capillaries in the papillary layer of the dermis occurs initially, followed by swelling of the endothelial cells in the vessel walls. Perivascular cuffing with lymphocytes, plasma cells, and macrophages can be seen.
  • Lesions then develop in the epidermis, where the cells become swollen and vacuolated; characteristic B-type inclusion bodies can be found in the cytoplasm.
  • The cells increase in size and the cell membranes rupture, leading to vesicular lesions.
  • Pustulation results from the migration of polymorphonuclear cells into the vesicle.
  • The contents of the pustule gradually become desiccated, leading to crusting or scabbing of the lesions.
  • Re-epithilialization and scarring occur as the lesions heal.

Death most commonly results from overwhelming toxemia, probably associated with circulating immune complexes.

Pathophysiology

Smallpox is most efficiently spread via the respiratory system, although contact with infected skin or fomites also may transmit the disease. The variola virus multiplies in the reticuloendothelial system, and it is clinically silent for approximately 12 days (range, 7-17 d). Viremia then proceeds to the prodromal phase (range, 2-4 d), which is characterized by the sudden onset of fever, severe headache, pharyngitis, nausea, backache, and malaise. During the later part of the prodromal phase, an enanthem may be appreciated on the palate, the tongue, and the pharynx. The virus then enters the skin; this event marks the beginning of the rash phase of the disease.

The skin findings begin on the face and spread centrifugally. Most lesions are in the same stage of development at any given time. Characteristic lesions start as macules and then develop into papules, pustules, and crusts over a period of approximately 17 days. The virus is readily found on the skin, in the oropharynx, and in the reticuloendothelial system throughout the rash phase (a highly infectious period from the appearance of enanthema until day 10 of the rash). Overwhelming toxemia has been the usual cause of death, and typical cases of smallpox had a mortality rate of 30%. The rarer hemorrhagic and flat-type forms of the disease were nearly universally fatal.

Both cellular immunity and humoral immunity are elicited in response to variola infection. Neutralizing antibodies can be detected during the first week of clinical illness, whereas hemagglutination-inhibition and complement-fixation antibodies are found in the second to third weeks. Neutralizing antibodies persist for many years or decades after infection, whereas levels of hemagglutination-inhibition and complement-fixation antibodies generally decrease within a year. Cell-mediated immunity likely plays an important role in controlling disease; virus-specific cytotoxic T cells are detectable in lymphoid organs as early as 4 days after infection. These cytotoxic T cells are believed to limit viral spread by causing lysis of infected cells in the reticuloendothelial system and the skin.

The relative importance of the cellular immune response against smallpox has been demonstrated in animals. Studies show that mice with defective T cells are able to generate normal humoral responses to a viral challenge, yet they die when exposed to orthopoxvirus concentrations that are sublethal in healthy mice. Studies in rodents and sheep have demonstrated memory in the form of virus-specific, cytotoxic lymphocyte immune responses that occur long after the initial variola infection.

Prevention

Vaccination is the most effective means of preventing smallpox infection. Vaccination can even be administered up to 4 or 5 days after a person is exposed to the virus. This practice may not completely prevent disease, but probably it will result in a significantly less severe case of the illness.

How the vaccination is given: The inoculation is injected with a special 2-pronged needle dipped into the vaccine solution. The needle is then used to prick the skin (usually of the upper arm) 15 times. The pricked spot becomes sore afterward. A red, itchy bump develops in 3-4 days, becomes a pus-filled blister, and begins to drain. During the second week, the blister dries up, and the scab that forms eventually falls off, leaving a small scar. The vaccination site should be kept covered with a bandage and the person with the sore should not touch it.

Treatment

In the hospital's emergency department, a suspected smallpox victim is isolated. All emergency medical services and hospital personnel exposed to someone with smallpox require quarantine and vaccination if they have not been previously vaccinated.

Quarantine: The infected person and anyone who has come into contact with the infected person for up to 17 days prior to illness (including the treating doctor and nursing staff) may be required to remain in isolation until a definite diagnosis is made. If the suspected case is indeed smallpox, these individuals will have to remain in isolation for at least 17 days to ensure that they are not also infected with the virus.


  • The most likely scenario of a smallpox outbreak is from a terrorist attack. Given the highly infectious nature of the organism, researchers estimate that 1 infected person can infect up to 20 new contacts during the infectious stage of the illness. If 1 infected person appears at a hospital, it is assumed that a more people have been infected.
  • Because of the medical, legal, and social implications of quarantine and isolation, coordinated involvement at the federal, state, and local levels is mandatory. In reality, strict quarantine of a large segment of the population is probably not possible.
  • Infectious disease specialists are consulted, along with state, federal, and local health authorities.

Treatment: Medical treatment for smallpox eases its symptoms. This includes replacing fluid lost from fever and skin breakdown. Antibiotics may be needed for secondary skin infections. The infected person is kept in isolation for 17 days or until the scabs fall off.


  • Experiments testing new antiviral medications are in progress, but it will be some time before they produce results. Vaccinations and postexposure interventions are the mainstays of treatment.

Complications

· Morbidity was commonly associated with smallpox.

· Most patients (65-80%) recovering from infection had cutaneous scarring, which was made worse if secondary bacterial infections developed during the course of the disease.

· Other complications included the following:


  • Bronchopneumonia
  • Keratitis
  • Corneal ulceration
  • Blindness (1% of cases)
  • Arthritis (2% of cases)
  • Osteomyelitis
  • Orchitis
  • Encephalitis (<1% of cases)

References

http://www.wikipedia.org
Source for primary information.

http://www.fda.gov
Served as extra reference and source.

http://www.emedicine.com
Served as secondary information source.

http://www.emedicinehealth.com
Served as main source.

http://www.cidrap.umn.edu
Served as extra reference.

If you find an error, please inform us.

2 comments:

Anonymous said...

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