Postvaccinal encephalitis
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Postvaccinal encephalitis (PVE) is postvaccinal complication which was associated with
vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
with
vaccinia virus ''Vaccinia virus'' (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the ...
during worldwide smallpox eradication campaign. With mortality ranging between 25 – 30% and lifelong consequences between 16 – 30% it was one of the most severe adverse events associated with this vaccination. The mechanism of its underlying condition is unknown.


Symptoms and signs

PVE symptoms start to appear between 8th and 14th day after vaccination. Amongst the first are fever, headache, confusion and nausea. With passing time
lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
,
seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
, short and long term memory dysfunctions, localized paralysis,
hemiplegia Hemiparesis, or unilateral paresis, is weakness of one entire side of the body ('' hemi-'' means "half"). Hemiplegia is, in its most severe form, complete paralysis of half of the body. Hemiparesis and hemiplegia can be caused by different medic ...
,
polyneuritis Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
and
convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
s. In extreme cases PVE can lead to
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
and death. Among the several forms of viral brain inflammation are rabies, polio, and two types transmitted by the mosquito: equine encephalitis in its various forms and St. Louis encephalitis. The latter two have appeared in epidemic form in the United States and are characterized by high fever, prolonged coma (which is responsible for the disease being known as a "sleeping sickness"), and convulsions sometimes followed by death. Encephalitis that results as a complication of another systemic infection is known as parainfectious encephalitis and can follow such diseases as measles (rubeola), influenza, and scarlet fever. The AIDS virus also infects the brain and produces dementia in a predictably progressive pattern. Although no specific treatment can destroy the virus once the disease has become established, many types of encephalitis can be prevented by immunization.


Histology

Inflammatory extra-adventitial lesions are found not only in the brain but in the spinal cord as well. Lesions might be uniform in acute phase or disseminated in subacute phase. Unlike in cases of
encephalitis lethargica Encephalitis lethargica is an atypical form of encephalitis. Also known as "sleeping sickness" or "sleepy sickness" (distinct from tsetse fly-transmitted sleeping sickness), it was first described in 1917 by neurologist Constantin von Economo a ...
the main damage is found in white brain matter. Meninges are infiltrated with
T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s, plasmatic cells and phagocytic cells. Polymorfonuclear cells were found only in severe lesions. Apart from cellular infiltrate in perivascular space there is a tissue rarefication in spaces close to damaged blood vessels. Accumulated small nuclei are found in places of such rarefication. Strong demyelination with rapid clearance of degraded
myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...
is also observed in cases of PVE. Tissue damage leads to
necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
in the end.


Treatment

Vaccinia immunoglobulin was given to patients with PVE. But some significant effects of this treatment were observed only if given before PVE developed. That is why only supportive treatment was given to patients with PVE to attenuate symptoms.


Incidence

Vaccination with vaccinia virus was accompanied with a spectrum of adverse events. Some of them lethal. Generally accepted number of deaths after vaccination with live vaccine is one per one million vaccinations. But during the eradication campaign, more than one vaccination strain was used and these strains differed significantly in causing adverse events. The incidence of PVE was between 44.9 cases per one million vaccinations with Bern strain used in western Europe to 2.9 cases per one million vaccinations with NYCBH strain used in the US. Number of deaths directly connected to PVE also differed from strain to strain. With 11 deaths per one million vaccinations with the Bern strain to 1.2 deaths per one million vaccinations with the NYCBH strain. PVE incidence also depended on the age of the vaccinated person. That is why in the US children up to one year of age and in Europe children up to three years of age were excluded from vaccination.


History

Complications with the central neural system after smallpox vaccination were observed for the first time right after the vaccination begun. The first diagnosed case of PVE was in 1905. In times of the smallpox eradication campaign, when PVE was a serious problem, there were no tools for identification of the immune mechanism behind PVE available. Considering the fact that modern smallpox vaccines are much safer and only chosen personnel are vaccinated, PVE is no longer in the centre of attention. Nevertheless, for its similarity with acute disseminated encephalomyelitis (ADEM), which is also postvaccinal adverse reaction (observed for example after anti
hepatitis A Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop them ...
or B virus vaccination), PVE is considered to be of autoimmune nature. There is no final proof of PVE being caused directly by vaccine virus replication in neural tissues.


References

{{DEFAULTSORT:Postvaccinal encephalitis History of medicine Inflammations Rare diseases Viral encephalitis Rare infectious diseases Unsolved problems in neuroscience