You are in: eMedicine Specialties > Infectious Diseases > MEDICAL TOPICS Venezuelan EncephalitisArticle Last Updated: Feb 17, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Iris Reyes, MD, Advisory Dean; Director of Quality Improvement, Associate Professor, Department of Emergency Medicine, University of Pennsylvania Iris Reyes is a member of the following medical societies: American College of Emergency Physicians Coauthor(s): William H Shoff, MD, DTM&H, Director, PENN Travel Medicine, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania; Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania; Director of Education and Research, PENN Travel Medicine Editors: Martin J Wood, MD †, Former Consulting Staff, Department of Infection and Tropical Medicine, Birmingham Heartlands Hospital, UK; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; John L Brusch, MD, FACP, Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance; Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital; Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital Author and Editor Disclosure Synonyms and related keywords: Venezuelan encephalitis, Venezuelan equine encephalitis, VEE, encephalomyelitis, peste loca INTRODUCTIONSection 2 of 10
  BackgroundVenezuelan equine encephalitis (VEE) is an acute viral disease characterized by fever, chills, headache, nausea, vomiting, lumbosacral pain, and myalgia, which may progress to encephalitis. VEE is a significant cause of disease in the Americas. Epidemics involving tens of thousands of humans and hundreds of thousands of equines have been reported. Although predominantly a disease found in South and Central America, the disease has spread to the United States. In 1938, the disease was first recognized in Venezuela. In 1943, the first descriptions of VEE infection in humans were reported from laboratories where equine isolates were being characterized. Researchers determined that these infections were acquired from aerosolized virus. In 1952, the first naturally acquired human illness was reported from Colombia, while the first reported natural human infection in the United States was not documented until 1968. A 1995 outbreak in Colombia and Venezuela affected an estimated 75,000 humans; 3000 people developed neurologic complications, and 300 fatalities occurred. Of the estimated 50,000 equines infected, 8% died of the disease. This was the first major epidemic of VEE in 22 years. The combination of unvaccinated horses and a record high level of rainfall leading to an increase in the mosquito population is suspected to have led to the extensive transmission of the virus. Major outbreaks involving humans have been associated with VEE subtype I, varieties AB and C. The IA and IB strains are considered genetically indistinguishable and, thus, are classified as IAB. While these epizootic strains are virulent for both equines and humans, the enzootic VEE virus serotypes ID, IE, and IIIA can cause illness in humans but not equines. Mosquitos typically transmit the enzootic strains designated ID through F and II through VI among small mammals. The mammals, usually rodents, show few adverse effects from the virus infection. VEE is highly infectious by the aerosol route, and numerous laboratory infections have occurred. PathophysiologyAlphaviruses are limited in their geographic spread primarily by the presence of an appropriate competent arthropod vector. At least 10 mosquito species, including Aedes, Culex, Psorophora, Mansonia, and Deinocerites species, have been identified as probable epidemic vectors, with different mosquito vectors possessing varying levels of efficiency. The mosquito vector becomes infected after biting a viremic equine host. Humans can develop a viremia significant enough to infect mosquitos, but humans never have been directly implicated in epidemic transmission. Although VEE virus can be demonstrated in human throat swabs, human-to-human transmission never has been demonstrated. For approximately 1 week, the virus replicates in the midgut epithelium of the mosquito. The virus then is disseminated to other organs, including the hemolymph and salivary glands. Spread to humans occurs when the infected mosquito deposits the virus in the skin of a naïve host while feeding. Viremia and a febrile response mark the initial phase of infection, during which the virus replicates in extraneural tissues. Sites of human replication remain unclear, but, in equines and laboratory rodents, the sites include skeletal muscle, lymphoid, and hematopoietic tissues. This may lead to relative lymphopenia, neutropenia, and thrombocytopenia. Circulating virus gains access to the CNS via the blood stream or perhaps via the olfactory apparatus. Neuronal infection with VEE is associated with the onset of acute encephalitis and cell death by apoptosis. FrequencyUnited StatesOutbreaks of VEE in the United States have been rare. From 1969-1972, a major outbreak of VEE involving much of Central America spread to Texas. Approximately 1500 horses died of VEE in Texas, and several hundred humans were infected. Western and eastern equine encephalitis alphaviruses are those most associated with a similar infection in the United States. A strain nonvirulent to equines (subtype 1D and 1E) has caused sporadic infection in Central America and Florida. The mosquito vector and the rodents that live in tropical swamps and forests maintain these strains of VEE viruses. InternationalIn 1938, VEE was first isolated from brains of infected horses during an epidemic in Venezuela. VEE continues to occur most commonly in Central and South America. Tens of thousands of humans and hundreds of thousands of equine infections have resulted from periodic epidemics in these areas. Spread tends to occur to areas contiguous to the site of the outbreak. Mortality/MorbidityNonneurologic infections are self-limited, and complete recovery generally occurs within several weeks of onset. The overall fatality rate is less than 1%. Neurologic manifestations occur at a rate of 4-14% in children ( <1% in adults), with a case fatality rate of 20%. RaceNo racial predilection exists. SexNo sex predilection exists. AgeVEE occurs in all age groups, but children are more likely to develop fatal encephalitis. CLINICALSection 3 of 10
HistoryInapparent VEE infections are rare. VEE infection presents with influenzalike symptoms approximately 1-6 days after infection.
Physical
Causes
DIFFERENTIALSSection 4 of 10
Arenaviruses Coxsackieviruses Cytomegalovirus Dengue Fever Echoviruses Hepatitis, Viral Herpes Simplex Infectious Mononucleosis Influenza Leptospirosis Listeria Monocytogenes Lyme Disease Malaria Meningitis Meningococcal Infections Meningococcemia Naegleria Infection Norwalk Virus Picornavirus-Overview Q Fever St. Louis Encephalitis West Nile Encephalitis Yellow Fever
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| Drug Name | Phenytoin (Dilantin) |
|---|---|
| Description | Used for seizures. May act in motor cortex where it may inhibit spread of seizure activity. Activity of brain stem centers responsible for tonic phase of grand mal seizures also may be inhibited. Dose should be individualized. Administer larger dose before retiring if dose cannot be divided equally. |
| Adult Dose | Loading: 15-20 mg/kg PO/IV once or divided doses, followed by 100-150 mg per dose at 30-min intervals Initial: 100 mg (125 mg susp) IV/PO tid Maintenance: 300-400 mg/d PO/IV divided tid or qd/bid if using ER; increase to 600 mg/d (625 mg/d susp) may be necessary; not to exceed 1500 mg/d Rate of infusion must not exceed 50 mg/min to avoid hypotension and arrhythmia |
| Pediatric Dose | Loading: 15-20 mg/kg PO/IV once or divided doses Initial: 5 mg/kg/d PO/IV divided bid/tid Maintenance: 4-8 mg/kg PO/IV divided bid/tid >6 years: May require minimum adult dose (300 mg/d); not to exceed 300 mg/d |
| Contraindications | Documented hypersensitivity; hypotension; second- and third-degree AV block |
| Interactions | Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase phenytoin toxicity; phenytoin effects may decrease when taken concurrently with barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate; phenytoin may decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, and valproic acid |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Perform blood counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if a skin rash appears and do not resume use if rash is exfoliative, bullous, or purpuric; rapid IV infusion may result in death from cardiac arrest, marked by QRS widening; caution in acute intermittent porphyria and diabetes (may elevate blood sugars); discontinue use if hepatic dysfunction occurs |
| Drug Name | Carbamazepine (Tegretol) |
|---|---|
| Description | Used for seizures. Indicated for complex partial seizures and trigeminal neuralgia. May block posttetanic potentiation by reducing summation of temporal stimulation. Following a therapeutic response, may reduce dose to minimum effective level or discontinue treatment at least once q3mo. |
| Adult Dose | 200 mg PO bid (100 mg PO qid susp); increase at weekly intervals by no more than 200 mg/d tid/qid (bid with ER) until best response obtained; not to exceed 1600 mg/d |
| Pediatric Dose | <6 years: 10-20 mg/kg/d PO bid/tid (qid susp), increase weekly to achieve optimal clinical response tid/qid; not to exceed 100 mg/d 6-12 years: 100 mg PO bid (50 mg qid susp), increase gradually every wk by adding 100 mg/d PO divided tid/qid (bid with ER) until best response is obtained; not to exceed 1000 mg/d >12 years: Administer as in adults; not to exceed 1000 mg/d in children aged 12-15 y or 1200 mg/d if >15 y |
| Contraindications | Documented hypersensitivity; history of bone marrow depression; administration of MAOIs within last 14 d |
| Interactions | Serum levels may increase significantly within 30 d of danazol coadministration (avoid whenever possible); do not coadminister with MAOIs; cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; carbamazepine may decrease primidone and phenobarbital levels (their coadministration may increase carbamazepine levels) |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Do not use to relieve minor aches or pains; caution with increased intraocular pressure; obtain CBCs and serum iron baseline levels prior to treatment, during first 2 mo, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness |
Venezuelan Encephalitis excerpt
Article Last Updated: Feb 17, 2006
