Smallpox was an infectious
disease caused by one of two virus variants, Variola major and Variola
minor. The last naturally occurring case was diagnosed in October 1977, and
the World Health Organization (WHO) certified the global eradication of the
disease in 1980. The risk of death following contracting the disease was about
30%, with higher rates among babies. Often those who survived had extensive scarring
of their skin, and some were left blind.
The initial symptoms of the disease
included fever and vomiting. This was followed by formation of sores in the
mouth and a skin rash. Over a number of days the skin rash turned into
characteristic fluid-filled bumps with a dent in the center. The bumps then scabbed
over and fell off, leaving scars. The disease was spread between people or via contaminated
objects. Prevention was by the smallpox
vaccine. Once the disease had
developed, certain antiviral medication may have helped.
The origin of smallpox is unknown. The
earliest evidence of the disease dates to the 3rd century BCE in Egyptian
mummies. The disease historically occurred in outbreaks. In 18th-century
Europe, it is estimated 400,000 people per year died from the disease, and
one-third of the cases resulted in blindness. These deaths included four
reigning monarchs and a queen consort. Smallpox is estimated to have killed up to 300 million people
in the 20th century and around 500 million people in the last 100 years of its
existence. As recently as 1967, 15
million cases occurred a year.
Edward Jenner discovered in 1798 that vaccination
could prevent smallpox. In 1967, the WHO intensified efforts to eliminate the
disease. Smallpox is one of two infectious diseases to have been eradicated,
the other being rinderpest in 2011. The term "smallpox" was first
used in Britain in the early 16th century to distinguish the disease from syphilis,
which was then known as the "great pox". Other historical names for
the disease include pox, speckled monster, and red plague
Transmission of Smallpox
Transmission occurred through inhalation
of airborne Variola virus, usually droplets expressed from the oral,
nasal, or pharyngeal mucosa of an infected person. It was transmitted from one
person to another primarily through prolonged face-to-face contact with an
infected person, usually within a distance of 1.8 m (6 feet), but could
also be spread through direct contact with infected bodily fluids or
contaminated objects (fomites) such as bedding or clothing. Rarely, smallpox
was spread by virus carried in the air in enclosed settings such as buildings,
buses, and trains. The virus can cross the placenta, but the incidence of congenital
smallpox was relatively low. Smallpox was not notably infectious in the prodromal
period and viral shedding was usually delayed until the appearance of the rash,
which was often accompanied by lesions in the mouth and pharynx. The virus can
be transmitted throughout the course of the illness, but this happened most
frequently during the first week of the rash, when most of the skin lesions
were intact. Infectivity waned in 7 to 10 days when scabs formed over the
lesions, but the infected person was contagious until the last smallpox scab
fell off.
Smallpox was highly contagious, but
generally spread more slowly and less widely than some other viral diseases,
perhaps because transmission required close contact and occurred after the
onset of the rash. The overall rate of infection was also affected by the short
duration of the infectious stage. In temperate areas, the number of smallpox
infections was highest during the winter and spring. In tropical areas,
seasonal variation was less evident and the disease was present throughout the
year. Age distribution of smallpox infections depended on acquired immunity. Vaccination
immunity declined over time and was probably lost within thirty years. Smallpox
was not known to be transmitted by insects or animals and there was no asymptomatic
carrier state.
Diagnosis of Smallpox
The clinical definition of smallpox is
an illness with acute onset of fever equal to or greater than 38.3 °C
(101 °F) followed by a rash characterized by firm, deep seated vesicles or
pustules in the same stage of development without other apparent cause. When a
clinical case was observed, smallpox was confirmed using laboratory tests.
Microscopically, poxviruses produce
characteristic cytoplasmic inclusions, the most important of which are known as
Guarnieri bodies, and are the sites of viral replication. Guarnieri bodies are
readily identified in skin biopsies stained with hematoxylin and eosin, and
appear as pink blobs. They are found in virtually all poxvirus infections but
the absence of Guarnieri bodies could not be used to rule out smallpox. The
diagnosis of an orthopoxvirus infection can also be made rapidly by electron
microscopic examination of pustular fluid or scabs. All orthopoxviruses exhibit
identical brick-shaped virions by electron microscopy. If particles with the
characteristic morphology of herpesviruses are seen this will eliminate
smallpox and other orthopoxvirus infections.
Definitive laboratory identification of Variola
virus involved growing the virus on chorioallantoic membrane (part of a
chicken embryo) and examining the resulting pock lesions under defined
temperature conditions. Strains were characterized by polymerase chain reaction
(PCR) and restriction fragment length polymorphism (RFLP) analysis. Serologic
tests and enzyme linked immunosorbent assays (ELISA), which measured Variola
virus-specific immunoglobulin and antigen were also developed to assist in
the diagnosis of infection.
Chickenpox was commonly confused with
smallpox in the immediate post-eradication era. Chickenpox and smallpox could
be distinguished by several methods. Unlike smallpox, chickenpox does not
usually affect the palms and soles. Additionally, chickenpox pustules are of
varying size due to variations in the timing of pustule eruption: smallpox
pustules are all very nearly the same size since the viral effect progresses
more uniformly. A variety of laboratory methods were available for detecting
chickenpox in evaluation of suspected smallpox cases.
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