Laboratory Studies
The diagnosis of enteroviral infection is most often based on the clinician's assessment of the patient in conjunction with seasonal outbreaks, known exposure risks, geographic locations, and age groups. Ancillary laboratory test results aid the physician in supportive care of the patient and eliminate other potentially harmful and treatable bacterial illnesses. Diagnostic testing plays a role in enteroviral infections. As newer methods have demonstrated increased sensitivities, determining viral etiologies of aseptic meningitis and neonatal sepsis has resulted in improved patient care.
Cell culture, serology, and polymerase chain reaction (PCR) laboratory testing can diagnostically isolate enteroviral infections. Enteroviruses are found in stool, the pharynx, blood, and cerebral spinal fluid (CSF). Blood cultures and serology are of questionable use because the viral levels may be undetectable by the time symptoms have appeared. Pharyngeal viral levels remain present from 2 days to 2 weeks after the infection. Stool isolation of enteroviruses is not specific to acute infections because viral stool shedding persists for as long as 3 months after the infection.
Historically, the criterion standard of isolation has been cell cultures; however, clinical evidence is proving PCR tests to be both more sensitive and more efficient. Tissue cultures take approximately 3-8 days to grow the enterovirus, and the identification of the subtype requires even more time. Overall, low cell culture sensitivity rates of 65-75% have been repeatedly demonstrated in enteroviral meningitis.
Another method, serologic testing, uses multiple titers to identify a pattern of rising antibody levels over a 2-week to 4-week period. A single level of enteroviral antibodies can be present in a healthy patient; therefore, monitoring the serology to identify a 4-fold increase in levels is needed. Identifying the specific subtype and monitoring the antibody levels are labor intensive. Furthermore, waiting for periods of 2-4 weeks for tissue results is not useful in improving patient care.
In contrast, the reverse transcriptase PCR testing is designed to detect a common genetic area in the enteroviral subtypes. The results are available in 24 hours, making detection more sensitive (95%), more specific (97%), and more time efficient. Both Chonmaitree et al in 1982 and Singer et al in 1980 demonstrated the positive outcomes of viral detection in aseptic meningitis, yielding shortened hospital stay and antibiotic course. [29, 30]
Recent studies have demonstrated the efficacy and increased sensitivity of using the PCR technique to isolate CSF enterovirus. PCR testing may also play a pivotal role in identifying epidemiological outbreaks of infections.
In 1997, Ahmed et al demonstrated 100% sensitivity and 90% specificity using PCR CSF assays in conjunction with viral cultures to detect enteroviral meningitis in infants younger than 3 months. [31]
Poliomyelitis can be isolated from stool, nasopharyngeal mucosa, and CSF. Stool specimens have the greatest yield for polio. Antibody serology titers demonstrate a 4-fold rise and must be acquired at early onset of illness. If positive, samples must be sent to the CDC.
Ancillary laboratory tests may also be helpful in treating patients. CBC count results vary, demonstrating a WBC count within the reference range or demonstrating a mild elevation of WBCs with neutrophilia or leukocytosis.
A basic chemistry panel is only useful in patients with extreme lethargy or dehydration and is used to eliminate possible diagnosis of electrolyte imbalances. Erythrocyte sedimentation rate is a nonspecific test, and the results should be elevated in any inflammatory process, including enteroviral infections.
Urinalysis is a part of the sepsis workup in neonates and young children to eliminate bacterial infections. Also, blood and urine cultures should be obtained. In addition, measure cardiac enzymes.
Other Tests
Imaging studies
Chest radiographs should be obtained as part of the neonatal sepsis workup and in cases of pleurodynia. Radiographic findings are normal in patients with pleurodynia.
Obtain echocardiograms in patients with suspected cardiac involvement.
Electrocardiography
Obtain an electrocardiogram (ECG) in suspected cases of pericarditis. The ECG results can be normal, can be nonspecific, or can have changes common to all causes of pericarditis.
Lumbar puncture
Lumbar puncture is the most important test in meningitis. Send CSF for cell count with differential, protein, glucose, Gram stain, and bacterial cultures. Send extra fluid for PCR testing and viral cell cultures.
CSF fluid demonstrates aseptic meningitis in patients with polio and nonpolio virus. Importantly, some patients may not demonstrate pleocytosis, so the PCR results should be sought. One study showed 18% of enteroviral meningitis cases did not demonstrate CSF pleocytosis. [32] Another series has shown pleocytosis in patients with sepsis-like features but no clinical features of meningitis. [23] The protein level can be within the reference range or mildly elevated (80-100 mg/100 mL). The glucose level is within the reference range.
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Erosions on the base of the tongue.
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A red halo surrounds several vesicles on the finger flexures and palms.
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Small linear vesicle on the thumb.
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Vesicle on the dorsal hand of a young adult.
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Calf blisters from coxsackievirus A6 as seen in atypical hand-foot-mouth disease. Courtesy of Elsevier (Feder HM Jr, Bennett N, Modlin JF. Atypical hand, foot, and mouth disease: a vesiculobullous eruption caused by Coxsackie virus A6. Lancet Infect Dis. Jan 2014;14(1):83-6).
