West Nile viral encephalitis: a case study.
Subject: Virus diseases (Care and treatment)
Virus diseases (Case studies)
Encephalitis, Viral (Care and treatment)
Encephalitis, Viral (Case studies)
Author: Morgan, Rhonda
Pub Date: 08/01/2004
Publication: Name: Journal of Neuroscience Nursing Publisher: American Association of Neuroscience Nurses Audience: Professional Format: Magazine/Journal Subject: Health care industry Copyright: COPYRIGHT 2004 American Association of Neuroscience Nurses ISSN: 0888-0395
Issue: Date: August, 2004 Source Volume: 36 Source Issue: 4
Accession Number: 121074975
Full Text: Abstract: West Nile virus (WNV) has recently emerged as a significant and increasingly frequent etiology of encephalitis in this country. Even though WNV has been in the limelight of the national news media and in the public arena, recognition of WNV encephalitis is frequently not overtly apparent. The reason for this is that WNV infection can present a variety of symptoms along a continuum of severity. Awareness of the symptoms of WNV infection and the measures to prevent disease spread are important factors that will shape future management o/the disease, as well as the extent of outbreaks facing the population.

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Ted is a 67-year-old male with no significant past medical history, except for occasional migraine headaches. He is married, has two grown children, and is retired from the Air Force. He does not smoke and does not use alcohol. He has no regular exercise program, but does try to eat healthy. On July 15, Ted awoke with pain in his chin and jaw that radiated to his left ear. The next day, he visited his physician, as the pain had become more intense. He described the pain as severe, sharp, and constant. His physician could find no etiology for the facial pain, and convinced it was likely a dental problem, he advised Ted to see his dentist.

Since the pain remained constant with unremitting intensity, Ted saw his dentist the next day. He was prescribed amoxycillin for a likely developing dental abscess and was to return in 1 week for definitive treatment. When he returned to his dentist 1 week later, the pain had somewhat subsided, and no evidence of a dental abscess could be found either radiographically or clinically.

Two days later Ted embarked upon a 1,500-mile car trip across the country to attend a family reunion. His condition worsened while traveling, and he presented to an emergency department en route with a fever of 104.2 [degrees] F and worsening pain in the left side of his face and jaw. He was diagnosed with strep throat and prescribed antibiotics. After resting for 1 day in a hotel, Ted felt well enough to continue the trip to his destination, even though the pain and fever persisted, and now Ted complained of overall weakness.

Upon arriving at his destination, the home of relatives, Ted was not improved. He continued to have fever, and he described shooting pains in his face, accompanied by pain in his back and legs. He was brought to the emergency room by family members for the fever pain, and dizziness. He was treated for viral syndrome and discharged with amitriptyline, oxycodone, and meclizine. Throughout the following evening, Ted developed nausea, the fever increased, and his mental status declined. His family noticed mild confusion, particularly with timing of events and short-term memory. He also developed a rash on his lower legs, both axillae and over his shoulders. Ted's family brought him back to the emergency department because of persistent fever, worsening mental status, and the inability to keep down his food.

Upon this third visit to an emergency department, Ted was found to be in obvious discomfort, mildly confused, but oriented to person and place. He had no history of trauma or seizures and demonstrated no photophobia. He had no nuchal rigidity, but did experience left-sided neck pain upon rotation. Pupils were equal and briskly reactive to light. Tympanic membranes were clear bilaterally, and his oropharynx and nasopharynx were dry without erythema and exudates. He had coarse basilar crackles in the right lung, but the left lung was clear. Neurological exam revealed cranial nerves II-XII were grossly intact; sensation was equal bilaterally in upper and lower extremities. Muscle strength was 5/5 in all extremities. Deep tendon reflexes were 2+ in both upper and lower extremities. Vital signs were as follows: temperature 102.8[degrees]F, pulse 98 bpm, normal sinus rhythm, blood pressure 136/79 mm Hg, respiratory rate 24/min, and weight 96 kg.

Laboratory studies were as follows: urine: protein 30, ketones 15; WBC 5.4 with 18% bands, 16% lymphs, platelets 141,000; Hgb/Hct:14.1gm/dL/42.3%, ALT = 122U/L; and AST = 89U/L. His chest X ray showed bilateral basilar focal atelectasis.

During the 2 hours in the emergency department, while awaiting laboratory and X-ray results, Ted became more confused, failed to recognize family members, and ceased to follow commands. A computed tomography (CT) scan of the brain was done, which was normal. A lumbar puncture was performed with the following results: protein 101, glucose 89, nucleated cells 960, segs 78. The cerebrospinal fluid (CSF) was slightly cloudy, but colorless.

Ted was admitted with the medical diagnosis of meningitis and dehydration. With the hospital being at high census, Ted was kept in the emergency department for the night awaiting a monitored bed in a respiratory isolation room. He was started on intravenous (IV) normal saline at 150 ml/hr, clear liquids as tolerated, vancomycin 2 grams IV q 12 hours, ceftriaxone 2 grams IV q 12 hours, and metoclopramide 10 mg q 3 hours as needed for nausea.

Upon further questioning about recent history, Ted's wife recalled he had a large mosquito bite on his left ear before leaving home 2 weeks earlier. Based on this information, blood was drawn for West Nile Virus (WNV) studies and sent for analysis.

Ted was received in the medical intensive care unit (ICU) the following morning. Upon admission to the ICU, Ted was moving all extremities spontaneously, did not open his eyes to voice or pain, and did not follow commands or recognize family members. Vital signs were as follows: temperature 102.6 [degrees] F, pulse 116 bpm, respiratory rate 36/min, and blood pressure 118/67 mm Hg. A fine red rash was noted on both lower extremities, upper chest, axillae, and shoulders. His breathing was rapid, shallow, and labored. An arterial blood gas sample yielded the following results: pH 7.47, pa[O.sub.2] 64 mm Hg, paC[O.sub.2] 29 mm Hg, HC[O.sub.3] 23 mEq. He experienced increasing respiratory distress with crackles and wheezing in both lung fields. A repeat chest X ray revealed bilateral pulmonary edema. A pulmonary consult was ordered, and Ted was electively intubated and placed on mechanical ventilation due to clinical respiratory failure and inability to control his airway. Positive pressure volume limited mechanical ventilation in assist-control mode with a rate of 20/min, fraction of inspired oxygen (FI[O.sub.2]) of 50%, tidal volume (VT) of 650 ml, and positive end-expiratory pressure (PEEP) of +8 cm [H.sub.2]O were employed to manage his respiratory failure. Ted's pulmonary status continued to worsen over the next 3 days, with increased airway pressures, decreased pulmonary compliance, and increased oxygen requirements. His chest X ray, as well as clinical evidence, indicated adult respiratory distress syndrome (ARDS). The oxygen concentration were increased to 65% and PEEP was increased to +12 cm [H.sub.2]O.

Over the next 7 days, Ted remained neurologically unresponsive, mechanically ventilated, and received sedation with lorazepam and morphine to achieve comfort and maintain ventilator synchrony. His mental status did not improve even during short periods of time off sedation. Supportive care consisted of enteral feedings via gastric tube, kinetic therapy; prophylaxis for deep vein thrombosis, and fever management. Family members were present most of the time and were involved in Ted's care. His wife and sister assisted in turning, positioning, bathing, and massaging his hands and feet. His family members were offered frequent updates and counseled about measures for self-care.

By day 10, Ted had made significant improvement and was responsive to voice and able to follow simple commands. His ARDS was improving, with decreasing airway pressures and adequate oxygenation on an FI[O.sub.2] of 30%, as well as an improved chest X ray. Continuous positive airway pressure (CPAP) trials were begun with the goal of extubation within the next 24 hours. Lab studies of serum IgM, lgG, and titers for WNV, which were drawn 8 days earlier, returned positive.

On day 11, Ted was sleepy but arousable, followed commands, and had tolerated daytime CPAP trials well. He had periods of agitation and self-extubated on the evening of day 11, but maintained appropriate oxygen saturation levels and denied dyspnea.

On day 12, Ted's pulmonary status was stable, with a forceful cough and oxygen saturation of 98% on 3L of oxygen by nasal cannula. He was moderately confused and lethargic, but followed commands. He was transferred to a step-down unit. Ted's gastric tube was removed, and clear liquids by mouth were begun and tolerated well. Even though he experienced periods of agitation, restlessness, and profound muscle weakness, Ted was able to stand and move to a chair with assistance.

On day 13, Ted was transferred to a medical floor for a 2-day stay before being discharged to a rehabilitation hospital for convalescence. At the time of discharge to a rehabilitation facility, Ted experienced significant muscle weakness and periods of restlessness and agitation, but was oriented to person and place. After spending 2 weeks in the rehabilitation facility, he was discharged to the home of relatives for several weeks before returning to his own home.

Epidemiology

WNV is an arbovirus, transmitted by the Culex pipiens mosquito (arthropod vector) from a bird (non-human primary vertebrae host), which is frequently the American crow, then to the human (alternate) host via a mosquito bite. First recognized in the United States in 1999, WNV was initially identified in the West Nile district of Uganda in 1937 (Asnis, Conetta, Waldman, & Teixeira, 2001). The WNV causes diffuse disintegration of nerve cells, followed by inflammation and necrosis of both gray and white matter in the central and peripheral nervous systems.

Outbreaks of WNV blossomed in South Africa in 1974, in Romania in 1996, in Russia in 1999, and in New York City in the summer of 1999, where large numbers of bird deaths were reported, primarily involving the American crow, but also some exotic birds at the Queens and Bronx Zoos. Numerous patients were admitted to New York City hospitals in 1999 with encephalitis, among whom there were 62 cases of confirmed WNV and 7 deaths (Asnis et al., 2001). The following year, in 2000, there were 21 cases and 2 deaths, and in 2001, there were 66 cases and 9 deaths in the United States. In 2002, there were 4,156 human cases and 284 deaths in the United States. As of September 3, 2003, 1,856 human cases of WNV and 37 deaths were reported by the CDC in this country (Center for Disease Control and Prevention [CDC], 2003). Colorado leads the 50 states in numbers of WNV infection, both in reported cases, 635, and deaths, 6 (CDC).

As of July 14, 2003, every blood bank in the United States began screening donated blood for WNV (CDC, 2003). The new method allows blood banks to destroy potentially infectious blood before it is given to anyone. To reduce the number of donations from potentially infected people, blood banks will refuse to accept blood from people with recent fever and headaches. Potential blood donors with a medical diagnosis of West Nile viral illness that includes compatible illness history and laboratory results should not be allowed to donate blood for at least 28 days from the start of their symptoms or until 14 days after they recover, whichever date is later (CDC).

Clinical Features

Most WNV infections are mild and often clinically unapparent. Approximately 20% of those infected report a mild febrile illness (Hinson, 2001). The incubation period is thought to range from 3 to 14 days, and symptoms generally last 3 to 6 days. Viremia peaks 1-2 days before symptoms begin. Usually manifest as a febrile illness of sudden onset, WNV infection is often accompanied by malaise, headache, anorexia, nausea and vomiting, eye pain, myalgia, erythematous rash, and lymphadenopathy. Approximately 1 in 150 infections will result in severe neurological disease, as was evident in Ted's case (CDC, 2003). The common manifestations of severe disease are fever, weakness, gastrointestinal symptoms, change in mental status, seizures, maculopapular or morbilliform rash involving the neck, trunk, arms or legs (as was seen with Ted), flaccid paralysis, ataxia, extrapyramidal signs, cranial nerve abnormalities, myelitis, optic neuritis, and nuchal rigidity. Although not observed in recent outbreaks, myocarditis, pancreatitis, and fulminant hepatitis have been described. Encephalitis is more commonly reported than meningitis in WNV infection. The most significant risk factor for developing severe neurological disease with WNV is advanced age (Hinson, 2001).

Clinical Suspicion

Diagnosis of WNV is based on a high index of suspicion and obtaining specific antibody laboratory tests. WNV or other arboviral diseases, such as St. Louis encephalitis, should be considered in any adult older than 50 years who develops unexplained encephalitis or meningitis in the summer or early fall. The local presence of WNV enzootic activity or incidence of human cases should further raise suspicion. Surveillance studies show that nonhuman vertebrae deaths, especially birds, coincide with WNV in humans. Obtaining a recent travel history--as was evidenced in Ted's case--is also important. Year-round transmission of WNV is possible in some warmer climates; therefore it should be considered in all persons with unexplained encephalitis and meningitis.

Diagnostic Testing and Reporting

The most efficient diagnostic method for WNV infection is detection of IgM antibody to WNV in serum collected within 8-14 days of illness onset or CSF collected within 8 days of illness onset using the IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA; Huang, Chatterjee, & Grady 1999). As IgM does not cross the blood-brain barrier, IgM antibody in CSF strongly suggests central nervous system infection. Polymerase chain reaction (PCR) can also be performed on the CSF. Those who have been recently vaccinated against or recently infected with related flaviviruses (yellow fever, Japanese encephalitis, dengue) may have false positive WNV MACELISA results. WNV encephalitis is on the list of designated nationally notifiable arboviral encephalitides. The timely identification of persons with acute WNV infection has significant public health implications, such avoidance of blood transfusion and organ donation transmission of the disease, and will likely shape the public health response to reduce the risk of additional human infections.

Laboratory Findings

Among patients in recent outbreaks, the following commonalities were found in diagnostic testing:

* Total leukocyte counts in peripheral blood were mostly normal or elevated with lymphocytopenia and anemia also present.

* Hyponatremia was sometimes present, particularly in patients with encephalitis.

* CSF showed pleocytosis, usually with a predominance of lymphocytes. Protein was universally elevated. Glucose was normal.

* CT of brain usually did not show evidence of acute disease, but in about one-third of patients, magnetic resonance imaging showed enhancement of the leptomeninges, the periventricular areas, or both.

Ted's lab results were, for the most part, congruent with these findings. His WBC was normal, but did show slight lymphocytopenia. However, he was not anemic. The CSF analysis revealed elevated protein, pleocytosis, and normal glucose levels. The CT of his brain was normal.

Treatment

Treatment is supportive, involving hospitalization, IV fluids, respiratory support, and prevention of secondary infections for those with severe disease such as Ted. Ribavirin in high doses and interferon alpha-2b have been found to have some activity against WNV in vitro, but no controlled studies have been completed on the use of these or other medications in the management of WNV encephalitis. Potential complications of the disease include decreased level of consciousness, irritability, muscle weakness, respiratory complications, immobility, and nutritional risks. Ted demonstrated all these complications, with the gravest being markedly decreased level of consciousness and profound respiratory distress.

Expected Outcomes

Signs and symptoms of mild disease generally last a few days. However, signs and symptoms of severe disease may last several weeks, and some neurological effects may be permanent. Children recover faster than adults. Myalgias and muscle weakness can persist for an extended period of time. The mortality rate in the New York City outbreak of 1999 was 12% of hospitalized patients (Asnis et al., 2001). Sequelae of WNV encephalitis continue to be studied.

Ted suffered severe disease from WNV infection, and at the time of this writing, 6 weeks after symptom onset, he still experiences muscle weakness, restlessness, and slow response times. His family states that when he is fully awake, his mental status is becoming more normal.

Prevention

At this time there is no human vaccine for WNV. Personal protective measures include remaining indoors at dawn and dusk, which are peak mosquito-biting times for many species of mosquitoes, and wearing long-sleeved shirts, long pants, and socks when outdoors. The use of an insect repellent containing 25%-30% DEET on exposed skin areas and spraying directly on clothing so that mosquitoes will not be carried indoors is helpful (www.cdc.gov). Repellents containing DEET should not be applied to skin under clothing. DEET-containing repellents should not be used on infants and young children due to side effects. Standing water around homes and lawns should be drained. Screens over doors and windows should be tight-fitting and in good repair. Dead birds may be a sign that WNV is circulating between birds and mosquitoes in an area. As more than 130 species of birds are known to have been infected with WNV, dead birds should be reported to local health departments. Awareness and vigilance regarding the presentation, symptoms, management, and prevention of WNV encephalitis is of paramount importance in reducing the incidence and morbidity caused by this viral infection.

Summary

WNV infection is an evolving disease, taking on a variety of clinical manifestations and often presenting with a confounding set of signs and symptoms. Because of this perplexing symptomatology, diagnosis and treatment are often delayed. Ongoing study continues to define the long-term effects and neurological sequelae of WNV infection. As we observe this disease evolution and encounter those affected, we must not lose sight of the fact that reported cases of WNV infection are likely a microcosm of the actual extent of the infectivity in the United States. A high index of suspicion and early detection of WNV infection will not only benefit those with the disease, but also positively affect measures for controlling the disease and preventing its spread.

References

Asnis, D., Conetta, R., Waldman, G., & Teixeira, A. (2001). The West Nile virus encephalitis outbreak in the United States. Annals of the New York Academy of Sciences 951, 161-171.

Centers for Disease Control and Prevention [CDC]. (2003). Division of vector-borne infective diseases. Retrieved September 3, 2003, from www.cdc.gov.ncidol/dvbid/westnile/qaoverview.html

Hinson, V., & Ryor, W. (2001), Update on viral encephalitis. Current Opinion in Neurology, 14(3) 369-374.

Huang, C., Chatterjee, M. & Grady, L. (1999). Diagnosis of viral infections of the central nervous system. New England Journal of Medicine, 340(6), 483-484.

Questions or comments about this article may be directed to Rhonda Morgan, MSN RN CEN CNRN, by phone at 423/224-6249 or by e-mail at rhonda_m_morgan@wellmont.org. She is a clinical nurse specialist in neuro-intensive care at Wellmont Holston Valley Medical Center Kingsport, TN.
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