West Nile Virus Infection in Older Adults
Mr. D is a 75-year-old Caucasian man who sought care after experiencing a one-day history of fever and generalized weakness. He stated that he began to feel unwell after a day of gardening. He reported mild intermittent headache and generalized malaise with no stiff neck. He denied having a sore throat, with no cough and no dyspnea. He had no urinary symptoms earlier, but the morning of his visit he reported having some dysuria. There was no pertinent travel history of environmental exposure. The patient, a WWII veteran, has lived with his long-term girlfriend in southern Louisiana for the past 30 years. He has a medical history that is significant for coronary artery disease with myocardial infarction and had a prior coronary artery bypass graft in 1996. He had a mild cerebrovascular accident in 1999 with no significant residual symptoms. Subsequently, he had an episode of seizure in 2000, which was well controlled with felbamate. He also has a history of hypertension, hyperlipidemia, and benign prostate hypertrophy. He does not smoke or use alcohol. Vital signs were taken, indicating the following: blood pressure 123/76 mm Hg; pulse 90 beats per minute; respiratory rate 22; and temperature 103.1 degrees F. Additional physical examination revealed coarse breath sounds from both lung fields. Laboratory results indicated normal electrolytes, liver enzymes, coagulation studies, and urinalysis. Blood urea nitrogen (BUN) and creatinine levels were slightly elevated at 32 mg/dL and 1.5 mg/dL, respectively. A complete blood count showed normal hemoglobin and hemocrit with a white cell count of 5.3x103/µL with 89% neutrophils, 9% lymphocytes, and 2% monocytes. Platelet count was 130x103/µL. Erythrocyte sedimentation rate was 22 mm/h. C-reactive protein was 2.5 mg/L. Cardiac enzymes were negative. Thyroid function tests were normal. Chest x-ray showed no acute pulmonary infiltrates, and electrocardiogram revealed normal sinus rhythm of 100 beats per minute with left ventricular hypertrophy. Blood/urine/sputum cultures were obtained, as well as additional tests for West Nile virus (WNV). Mr. D was treated empirically with broad-spectrum antibiotics, intravenous fluid, and an antipyogenic. The next hospital day, the patient’s high fever persisted at 102 degrees F with rigor, and he developed shortness of breath. A computed tomographic angiography of the chest was performed and ruled out pulmonary embolism. An ultrasound of the bilateral lower extremities revealed no deep venous thrombosis. Tests for rheumatoid factor, ehrlichiosis, HIV, and antistreptolysin O were negative, as was a skin test for tuberculosis. The patient’s fever persisted daily, with a maximal temperature of 103 degrees F for the next few days with fluctuating mental status. He became drowsier and more lethargic with minimal response to commands. A magnetic resonance imaging of the brain showed some enhancement in the meninges of the brain, with otherwise unremarkable findings. A lumbar puncture was performed. Mr. D had normal open pressure with elevated protein and normal glucose from cerebrospinal fluid (CSF). There was predominantly lymphocytic pleocytosis in the CSF, and testing for herpes simplex and WNV from the CSF were submitted. Acyclovir was added to cover for possible herpes encephalitis. All of the blood and urine cultures were negative. The initial serum WNV serology on day 5 was negative, but was positive with repeat testing from CSF and blood on day 20.
West Nile virus is an emerging mosquito-transmitted encephalitis virus, with its first North American case recognized in 1999.1 The virus spread rapidly, with initial cases reported along the Atlantic seaboard. The highest concentration of cases was in the upper Midwest and the South, such as in Louisiana, where the case presented here occurred. Current cases have been reported throughout most of the continental United States.2,3 Outbreaks tend to occur in late summer and early fall. In most healthy adults, WNV infection is asymptomatic or causes a mild flu-like syndrome, characterized by vague constitutional symptoms and fever that occur after an initial incubation period ranging from 3 days to 2 weeks. In a small minority of infected patients, WNV infection results in meningoencephalitis, which may be accompanied by a neurological syndrome that can include aseptic meningitis, encephalitis, and neuromuscular paralysis.4-6
Clinical manifestations of WNV infection are heavily age-dependent. The acute febrile syndrome occurs most often in the young, whereas frank encephalitis occurs more in the elderly, such as the case presented here. The risk factors for developing WNV encephalitis include diabetes, alcohol abuse, advanced age, and possible genetic factors.7 Advanced age plays a very significant role, as evidenced in the 2002 Chicago-area outbreak: the incidence of WNV encephalitis was less than 5 cases per 100,000 among 45-59–year-olds; triple that in 60-74–years-olds; and more than 30 per 100,000 among individuals age 75 years and older.8 The diagnosis of WNV infection relies on a high index of suspicion coupled with appropriately timed serological testing. Infection with WNV or other parvovirus should be considered in adults presenting with unexplained fever and neurological symptoms who live in, or have traveled to, appropriate geographic regions such as the upper Midwest of the United States in late summer or early fall. In the southern United States, WNV can be transmitted from June to November.2
While the majority of human WNV transmission occurs from mosquito bites, other modes of transmission have been reported, including transplacental, or through blood product transfusion and solid organ transplantation.3,9 The most common and preferred diagnostic test is the immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (ELISA), which can be performed on serum or CSF sample. The presence of the antibody in CSF is highly suggestive of a neurological infection.10 In hospitalized patients, IgM antibodies to WNV have been isolated within eight days of symptom onset in 95% of serum specimens.11 Because this assay may not be positive at initial patient presentation, as demonstrated in the present case, serological testing should be repeated when there is a high clinical suspicion for WNV infection to avoid misdiagnosis and unnecessary antibiotics usage.
Currently, the treatment for WNV infection is supportive because specific antiviral therapy is not available for most causative entities. The efficacy of corticosteroids is not established, and other therapeutic options such as interferon-alpha 2b and immunoglobulin have not proven to be effective. The prognosis is always guarded, especially at the extremes of age. Advanced age and diabetes were the most significant risk factors for death.1 Mortality may be much higher among patients admitted to the Intensive Care Unit (ICU), especially for those requiring mechanical ventilation.10
Outcome of the Case Patient
Mr. D’s antibiotics and antiviral agents were stopped after confirmed serum and CSF testing were positive for WNV. He was admitted to the ICU for hypotension spells and was given IV fluids and antipyogenic medication, and symptomatic support care. Fortunately, he did not require intubation for respiratory support. Gradually, he was able to be moved to the step-down unit and continued to improve until fully recovered in four weeks. The patient has been continually followed up at the clinic with no consequence and lives independently with his girlfriend.
The authors report no relevant financial relationships.
Dr. Bi is Staff Physician, Qilu Hospital, Jinan, China; Mr. Liu is a Neuroscience student at Emory University, Atlanta, GA; and Dr. Liu is Staff Physician, Freedman Clinic of Internal Medicine, Alexandria, LA.
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