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It takes 5 to 15 days after the bite of an infected mosquito to develop symptoms of LACV disease. Symptoms include nausea, headache, vomiting in milder cases and seizures, coma, paralysis and permanent brain damage in severe cases.
LAC encephalitis initially presents as a nonspecific summertime illness with fever, headache, nausea, vomiting and lethargy. Severe disease occurs most commonly in children under the age of 16 and is characterized by seizures, coma, paralysis, and a variety of neurological sequelae after recovery. Death from LAC encephalitis occurs in less than 1% of clinical cases. In many clinical settings, pediatric cases presenting with CNS involvement are routinely screened for herpes or enteroviral causes. Since there is no specific treatment for LAC encephalitis, physicians often do not request the tests required to specifically identify LAC virus, and the cases are reported as aseptic meningitis or viral encephalitis of unknown cause.
As with many infections, the very young, the very old and the immunocompromised are at a higher risk of developing severe symptoms.
The virus can infect the brain (encephalitis), the meninges (meningitis) or both (meningoencephalitis).
In general, mortality is 1% to 2%, with deaths occurring 5 to 7 days after the onset of neurologic signs.
In dogs, the disease also manifests as a neurological disorder with signs varying from tremors to seizures and death.
In ruminants, neurological disease is also present, and animals may refuse to eat, appear lethargic, and also develop respiratory signs.
The majority of infections result in mild illness, including fever and headache. When infection is more severe the person may experience headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, occasional convulsions and spastic paralysis. Fatality ranges from . Aged people are more likely to have a fatal infection.
Most individuals with HSE show a decrease in their level of consciousness and an altered mental state presenting as confusion, and changes in personality. Increased numbers of white blood cells can be found in patient's cerebrospinal fluid, without the presence of pathogenic bacteria and fungi. Patients typically have a fever and may have seizures. The electrical activity of the brain changes as the disease progresses, first showing abnormalities in one temporal lobe of the brain, which spread to the other temporal lobe 7–10 days later. Imaging by CT or MRI shows characteristic changes in the temporal lobes (see Figure). Definite diagnosis requires testing of the cerebrospinal fluid (CSF) by a lumbar puncture (spinal tap) for presence of the virus. The testing takes several days to perform, and patients with suspected Herpes encephalitis should be treated with acyclovir immediately while waiting for test results.
Viral encephalitis is a type of encephalitis caused by a virus.
It is unclear if anticonvulsants used in people with viral encephalitis would prevent seizures.
Herpesviral encephalitis is encephalitis due to herpes simplex virus.
Herpes simplex encephalitis (HSE) is a viral infection of the human central nervous system. It is estimated to affect at least 1 in 500,000 individuals per year and some studies suggest an incidence rate of 5.9 cases per 100,000 live births. The majority of cases of herpes encephalitis are caused by herpes simplex virus-1 (HSV-1), the same virus that causes cold sores. 57% of American adults are infected with HSV-1, which is spread through droplets, casual contact, and sometimes sexual contact, though most infected people never have cold sores. About 10% of cases of herpes encephalitis are due to HSV-2, which is typically spread through sexual contact. About 1 in 3 cases of HSE result from primary HSV-1 infection, predominantly occurring in individuals under the age of 18; 2 in 3 cases occur in seropositive persons, few of whom have history of recurrent orofacial herpes. Approximately 50% of individuals who develop HSE are over 50 years of age.
Saint Louis encephalitis is a disease caused by the mosquito borne Saint Louis encephalitis virus. Saint Louis encephalitis virus is related to Japanese encephalitis virus and is a member of the Flaviviridae subgroup. This disease mainly affects the United States. Occasional cases have been reported from Canada and Mexico.
Adult patients with encephalitis present with acute onset of fever, headache, confusion, and sometimes seizures. Younger children or infants may present irritability, poor appetite and fever.
Neurological examinations usually reveal a drowsy or confused patient. Stiff neck, due to the irritation of the meninges covering the brain, indicates that the patient has either meningitis or meningoencephalitis.
Japanese encephalitis (JE) is an infection of the brain caused by the Japanese encephalitis virus (JEV). While most infections result in little or no symptoms, occasional inflammation of the brain occurs. In these cases symptoms may include headache, vomiting, fever, confusion, and seizures. This occurs about 5 to 15 days after infection.
JEV is generally spread by mosquitoes, specifically those of the "Culex" type. Pigs and wild birds serve as a reservoir for the virus. The disease mostly occurs outside of cities. Diagnosis is based on blood or cerebrospinal fluid testing.
Prevention is generally with the Japanese encephalitis vaccine, which is both safe and effective. Other measures include avoiding mosquito bites. Once infected there is no specific treatment, with care being supportive. This is generally carried out in hospital. Permanent problems occur in up to half of people who recover from encephalopathy.
The disease occurs in Southeast Asia and the Western Pacific. About 3 billion people live in areas where the disease occurs. About 68,000 symptomatic cases occur a year with about 17,000 deaths. Often cases occur in outbreaks. The disease was first described in 1871.
Encephalitis lethargica is identified by high fever, headache, delayed physical response, and lethargy. Individuals can exhibit upper body weakness, muscular pains, and tremors, though the cause of encephalitis lethargica is not currently known. From 1917 to 1928, an epidemic of encephalitis lethargica occurred worldwide.
La Crosse encephalitis is an encephalitis caused by an arbovirus (the La Crosse virus) which has a mosquito vector ("Ochlerotatus triseriatus" synonym "Aedes" "triseriatus").
La Crosse encephalitis virus (LACV) is one of a group of mosquito-transmitted viruses that can cause encephalitis, or inflammation of the brain. LAC encephalitis is rare; in the United States, about 80–100 LACV disease cases are reported each year, although it is believed to be under-reported due to minimal symptoms experienced by many of those affected.
Tick-borne encephalitis (TBE) is a viral infectious disease involving the central nervous system. The disease most often manifests as meningitis, encephalitis, or meningoencephalitis. Although TBE is most commonly recognized as a neurological disorder, mild fever can also occur. Long-lasting or permanent neuropsychiatric consequences are observed in 10 to 20% of infected patients.
The number of reported cases has been increasing in most countries.
The tick-borne encephalitis virus is known to infect a range of hosts including ruminants, birds, rodents, carnivores, horses, and humans. The disease can also be spread from animals to humans, with ruminants and dogs providing the principal source of infection for humans.
TBE, like Lyme disease, is one of the many tick-borne diseases.
Japanese encephalitis is diagnosed by commercially available tests detecting JE virus-specific IgM antibodies in serum and /or cerebrospinal fluid, for example by IgM capture ELISA.
JE virus IgM antibodies are usually detectable 3 to 8 days after onset of illness and persist for 30 to 90 days, but longer persistence has been documented. Therefore, positive IgM antibodies occasionally may reflect a past infection or vaccination. Serum collected within 10 days of illness onset may not have detectable IgM, and the test should be repeated on a convalescent sample. For patients with JE virus IgM antibodies, confirmatory neutralizing antibody testing should be performed.
Confirmatory testing in the US is only available at CDC and a few specialized reference laboratories. In fatal cases, nucleic acid amplification, and virus culture of autopsy tissues can be useful. Viral antigen can be shown in tissues by indirect fluorescent antibody staining.
Types of encephalitis in humans include:
- Arbovirus encephalitis
- La Crosse encephalitis
- Enterovirus
- California encephalitis virus
- Japanese encephalitis
- St. Louis encephalitis
- Eastern equine encephalitis virus
- Western equine encephalitis virus
- Venezuelan equine encephalitis virus
- Murray Valley encephalitis virus
- Tick-borne meningoencephalitis
- Powassan encephalitis
- West Nile virus
- Herpes simplex
- Human herpesvirus 6
- Varicella zoster virus
- Rabies
- HIV
- H5N1 encephalitis
- Nipah virus encephalitis
- Lymphocytic choriomeningitis, which also causes encephalitis
About 95% of symptomatic cases report joint pain. This is typically symmetrical and with acute onset, affecting the fingers, toes, ankles, wrists, back, knees and elbows. Fatigue occurs in 90% and fever, myalgia and headache occur in 50–60%.
A rash occurs in 50% of patients and is widespread and maculopapular. Lymphadenopathy occurs commonly; sore throat and coryza less frequently. Diarrhea is rare. About 50% of people report needing time off work with the acute illness. If the rash is unnoticed, these symptoms are quite easily mistaken for more common illnesses like influenza or the common cold. Recovery from the flu symptoms is expected within a month, but, because the virus currently cannot be removed once infection has occurred secondary symptoms of joint and muscle inflammation, pain and stiffness can last for many years.
Less common manifestations include splenomegaly, hematuria and glomerulonephritis. Headache, neck stiffness, and photophobia may occur. There have been three case reports suggesting meningitis or encephalitis.
Reports from the 1980s and 1990s suggested RRV infection was associated with arthralgia, fatigue and depression lasting for years. More recent prospective studies have reported a steady improvement in symptoms over the first few months, with 15–66% of patients having ongoing arthralgia at 3 months. Arthralgias have resolved in the majority by 5–7 months. The incidence of chronic fatigue is 12% at 6 months and 9% at 12 months, similar to Epstein-Barr virus and Q fever. The only significant predictor of the likelihood of developing chronic symptoms is the severity of the acute illness itself. No other aspects of the patient's medical or psychiatric history have been found to be predictive. However, in those with the most persisting symptoms (12 months or more), comorbid rheumatologic conditions and/or depression are frequently observed .
Epstein–Barr can cause infectious mononucleosis, also known as 'glandular fever', 'mono' and 'Pfeiffer's disease'. Infectious mononucleosis is caused when a person is first exposed to the virus during or after adolescence. It is predominantly found in the developing world, and most children in the developing world are found to have already been infected by around 18 months of age. Infection of children can occur when adults mouth feed or pre-chew food before giving it to the child. EBV antibody tests turn up almost universally positive. In the United States roughly half of five-year-olds have been infected.
The strongest evidence linking EBV and cancer formation is found in Burkitt's lymphoma
and nasopharyngeal carcinoma. Additionally, it has been postulated to be a trigger for a subset of chronic fatigue syndrome patients as well as multiple sclerosis and other autoimmune diseases.
Burkitt's lymphoma is a type of Non-Hodgkin's lymphoma and is most common in equatorial Africa and is co-existent with the presence of malaria. Malaria infection causes reduced immune surveillance of B cells immortalized by EBV, resulting in an excessive number of B cells and an increased likelihood of an unchecked mutation. Repeated mutations can lead to loss of cell-cycle control, causing excessive proliferation observed as Burkitt's lymphoma. Burkitt's lymphoma commonly affects the jaw bone, forming a huge tumor mass. It responds quickly to chemotherapy treatment, namely cyclophosphamide, but recurrence is common.
Other B cell lymphomas arise in immunocompromised patients such as those with AIDS or who have undergone organ transplantation with associated immunosuppression (Post-Transplant Lymphoproliferative Disorder (PTLPD)). Smooth muscle tumors are also associated with the virus in malignant patients.
Nasopharyngeal carcinoma is a cancer found in the upper respiratory tract, most commonly in the nasopharynx, and is linked to the EBV virus. It is found predominantly in Southern China and Africa, due to both genetic and environmental factors. It is much more common in people of Chinese ancestry (genetic), but is also linked to the Chinese diet of a high amount of smoked fish, which contain nitrosamines, well known carcinogens (environmental).
Before puberty, the disease typically only produces flu-like symptoms, if any at all. When found, symptoms tend to be similar to those of common throat infections (mild pharyngitis, with or without tonsillitis).
In adolescence and young adulthood, the disease presents with a characteristic triad:
- Fever – usually lasting 14 days; often mild
- Sore throat – usually severe for 3–5 days, before resolving in the next 7–10 days.
- Swollen glands – mobile; usually located around the back of the neck (posterior cervical lymph nodes) and sometimes throughout the body.
Another major symptom is feeling tired. Headaches are common, and abdominal pains with nausea or vomiting sometimes also occur. Symptoms most often disappear after about 2–4 weeks. However, fatigue and a general feeling of being unwell (malaise) may sometimes last for months. Fatigue lasts more than one month in an estimated 28% of cases. Mild fever, swollen neck glands and body aches may also persist beyond 4 weeks. Most people are able to resume their usual activities within 2–3 months.
The most prominent sign of the disease is often the pharyngitis, which is frequently accompanied by enlarged tonsils with pus—an exudate similar to that seen in cases of strep throat. In about 50% of cases, small reddish-purple spots called petechiae can be seen on the roof of the mouth. Palatal enanthem can also occur, but is relatively uncommon.
Spleen enlargement is common in the second and third weeks, although this may not be apparent on physical examination. Rarely the spleen may rupture. There may also be some enlargement of the liver. Jaundice occurs only occasionally.
A small minority of people spontaneously present a rash, usually on the arms or trunk, which can be macular (morbilliform) or papular. Almost all people given amoxicillin or ampicillin eventually develop a generalized, itchy maculopapular rash, which however does not imply that the person will have adverse reactions to penicillins again in the future. Occasional cases of erythema nodosum and erythema multiforme have been reported.
Viral cardiomyopathy occurs when viral infections cause myocarditis with a resulting thickening of the myocardium and dilation of the ventricles. These viruses include Coxsackie B and adenovirus, echoviruses, influenza H1N1, Epstein-Barr virus, rubella (German measles virus), varicella (chickenpox virus), mumps, measles, parvoviruses, yellow fever, dengue fever, polio, rabies and the viruses that cause hepatitis A and C.
An oncovirus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin.
It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the Retinoblastoma protein.
The World Health Organization's International Agency for Research on Cancer estimated that in 2002, infection caused 17.8% of human cancers, with 11.9% caused by one of seven viruses. These cancers might be easily prevented through vaccination (e.g., papillomavirus vaccines), diagnosed with simple blood tests, and treated with less-toxic antiviral compounds.
A subclinical infection (sometimes called a preinfection) is an infection that, being , is nearly or completely asymptomatic (no signs or symptoms). A subclinically infected person is thus an asymptomatic carrier of a microbe, intestinal parasite, or virus that usually is a pathogen causing illness, at least in some individuals. Many pathogens spread by being silently carried in this way by some of their host population. Such infections occur both in humans and nonhuman animals. An example of an asymptomatic infection is a mild common cold that is not noticed by the infected individual. Since subclinical infections often occur without eventual overt sign, their existence is only identified by microbiological culture or DNA techniques such as polymerase chain reaction.
An individual may only develop signs of an infection after a period of subclinical infection, a duration that is called the incubation period. This is the case, for example, for subclinical sexually transmitted diseases such as AIDS and genital warts. Individuals with such subclinical infections, and those that never develop overt illness, creates a reserve of individuals that can transmit an infectious agent to infect other individuals. Because such cases of infections do not come to clinical attention, health statistics can often fail to measure the true prevalence of an infection in a population, and this prevents the accurate modeling of its infectious transmission.
Differential diagnosis may include:
- Opsoclonus-myoclonus-ataxia syndrome
- Miller-Fisher syndrome
- Meningoencephalitis
- Cerebral abscess
- Tumor
- Hydrocephalus
- Inner-ear Disease
- Acute Vestibulitis
- Acute Labyrinthitis