How is Enterovirus Contracted, Diagnosed and Treated?
Contracting enterovirus can actually be quite easy. Since Enteroviruses are small, highly contagious viruses made of ribonucleic acid (RNA) and protein, they are passed from person to person either through direct touch or indirect means, like through a sneeze or cough, much like a cold is passed from one to another. Other ways of transmission are in secretions from the mouth, eye, nose or blister fluid, or from human waste (oral-fecal transmission through contact with contaminated water i.e. swimming in lake or river, drinking contaminated water). The average incubation period is 3-10 days.
Enterovirus Diagnosis and Testing:
Diagnosis of Enterovirus Infections is not that simple. Since it can masquerade as many common conditions during early onset, diagnosis often occurs when the virus has progressed to a severe or deadly state. The prolonged nature of an infection or an aforementioned complications arise with the initial infection should lead to further investigation.
Although many hospitals and some doctor’s offices can test ill patients to see if they have an enterovirus infection, most cannot do specific testing to determine the type of enterovirus. Specific lab tests on specimens from a person’s nose and throat, or special tests on blood or spinal fluid and MRI findings have been used to diagnose conditions linked to enterovirus.
After the acute phase of an infection, enteroviruses can disappear from the blood and cerebrospinal fluid completely, but can remain in organs and other tissues. This makes it difficult to diagnose enterovirus infections without a biopsy, and even then, the tests are limited.
Clinical Tests, Non-clinical Tests, Other Tests and Studies
Listed in this section are clinical laboratory tests for acute enterovirus infections, clinical laboratory tests for persistent enterovirus infections, imaging tests and other tests. These are provided to assist those infected or potentially infected with testing options to discuss with their physician.
After explanations of the tests, there is a section of bulleted notes from renowned infectious disease physician Dr. John Chia to assist with diagnosis.
Clinical laboratory tests for acute enterovirus infections
Serology - Serological examination can reveal an increase in antibodies to enteroviruses neutralizing antibody level to enteroviruses between the acute and convalescent phases of illness. This diagnostic modality can only identify coxsackie B1-6 and Echo 6, 7, 9, 11, and 30. The other known enteroviruses cannot be identified with this test. A negative serological test does not necessarily mean the absence of enterovirus.
Viral isolation - This is the criterion standard for diagnosing enterovirus infections. The virus can be isolated from cerebrospinal fluid, blood, or feces, depending on the site affected, and the yield is increased if multiple sites are sampled. The serotype of enteroviruses isolated by this method can be identified with neutralizing assays using type-specific antisera by the CDC or by VP1 gene sequencing.
Reverse transcription-Polymerase Chain Reaction (RT-PCR) - This test is highly sensitive and specific for detecting enterovirus RNA in cerebral spinal fluid specimens, with a sensitivity of 100% reported by some studies and specificity of 97%. This test of a nasopharyngeal swab taken from patients with colds helped identify the viruses in EV D68 outbreak. PCR provides rapid results. PCR testing of the blood can only identify the virus in 30% of chronic fatigue syndrome/myalgia encephalomyelitis patients.
Cardiac enzyme levels and troponin 1 - These levels may be elevated in persons with myopericarditis, indicating myocardial damage like inflammation or damage to the heart muscle.
Cerebrospinal fluid analysis - The cerebrospinal fluid profile of patients with aseptic meningitis reveals a mildly elevated white blood cell count. Glucose levels are normal or mildly decreased, while the protein level is normal or slightly increased.
Reverse Transcriptase-Polymerase Chain Reaction (RT- PCR) - This test is designed to detect a common genetic area of most of the enteroviruses. The results could be available in 24 hours, making detection more sensitive (95%), more specific (97%), and more time efficient. This test is approved for diagnosing enterovirus meningitis. For other body fluids such as the stool, respiratory secretions and blood, the yield is less certain. (This the same as the PCR, 3rd paragraph of this section).
Clinical laboratory tests for chronic enterovirus infections
Immunohistochemistry (IHC) - This technique is the most useful in analyzing organ biopsies or autopsy sections. In this procedure, tissues are stained with an EV monoclonal antibody to determine if the viral protein is expressed at the time of the biopsy.
Biopsies of the organs where patients have symptoms are very helpful in making a diagnosis of persistent enterovirus infection. Brain, heart, and muscles are often involved with persistent enterovirus infections, but biopsies of these organs are not likely to be done. The stomach is the most common place where enteroviruses usually go in view of the respiratoy and gastrointestinal routes of virus transmission. Enterovirus protein, or RNA, and defective viruses have been found in the stomach biopsies of patients from endoscopy procedures. Enterovirus protein has also been demonstrated in the nasal and sinus tissue, throat, thyroid, heart and brain of patients.
It is important to note that a biopsy is often taken during an endoscopy and that biopsies are typically preserved in paraffin for years in the pathology department where the procedure was performed. These can be requested in order to perform this test. This test can be ordered from EV Med Research.
Micro-neutralization test - Persistently elevated antibody levels for one or more enteroviruses over years can suggest a chronic enterovirus infection. The Micro-neutralization test is a very sensitive, specific test and only 11 enteroviruses, coxsackie B1-6 and echoviruses 6, 7, 9, 11, and 30 can be tested using this method. Titers of 1:160-320 and higher are good indicators of current infection.
It is important to note that only one commercial laboratory in the United States is recommended for this test: Associate Regional University Pathologist Laboratory (ARUP), Salt Lake City, Utah. These tests can be ordered directly from ARUP or ordered through LabCorp. If ordered through LabCorp, write on the form to specifically state this is a virus neutralization test to send this test to ARUP.
For more information:
Reverse transcription-Polymerase Chain Reaction (RT-PCR) - The PCR test is not considered sensitive for chronic enterovirus infections. Since viruses are cleared quickly from the blood stream, the chance of finding viral gene or RNA in the blood by the PCR technique is low. With special techniques and repeated testing, enterovirus RNA can be found in close to thirty percent of whole blood samples taken from chronically infected EV patients.
For Immunohistochemistry stain requests, please do not send samples to the foundation.
EV Med Research
25332 Narbonne Ave. #170
Lomita, CA, 90717
Click here for the request form
Chest radiography - In patients with myopericarditis, the chest radiograph may reveal cardiomegaly secondary to pericardial effusion or cardiac dilation. In pleurodynia, chest radiograph findings are normal since this is an infection of the chest/abdominal muscle.
Echocardiography - For patients with myocarditis or pericarditis, transient wall motion abnormalities or pericardial effusion may be revealed with echocardiography. Severe cases can reveal acute ventricular dilation and reduced ejection fraction. This is a much sensitive test for the diagnosis of the disease.
ECG - Nonspecific ST-T changes may be observed in persons with myopericarditis. Severe disease may cause Q waves, ventricular tachyarrhythmia, and heart block. ECG findings may demonstrate evolution through several stages of myopericarditis, as follows:
Stage I - Diffuse ST elevation with PR depression
Stage II - Normalization of ST and PR segments
Stage III - Deep symmetric inversion of T waves
Stage IV - May revert to normal or permanent T-wave inversions
Electroencephalography - This test may be useful for evaluating the extent and severity of illness in patients with encephalitis.
Ophthalmic slit-lamp examination - In persons with Acute Hemorrhagic Conjunctivitis (AHC), corneal erosions may be visualized using a fluorescein stain. Enterovirus 70 and coxsackievirus A24 can be recovered from conjunctival swabs during the first 3 days of infection.
Advice from doctors from Dr. John Chia to aid in the diagnosis of both acute and chronic enterovirus infections:
Most of the acute enterovirus infections, even in the case of poliovirus infections, are asymptomatic (no sickness.)
The diagnosis of acute symptomatic infection is usually suspected and empirically diagnosed based on the physician's assessment of the patient along with outbreaks of other cases in the community, known exposure risks, geographic locations (next to a river and lake) and age groups.
Ulcerations of the mouth (stomatitis), especially over the lining of the cheeks, tongue ulcers, blisters of the soft palate or the roof of the mouth (herpangina) are helpful signs of acute enterovirus infection.
Pediatricians can often diagnose enterovirus infections in young children since they are trained to recognize these infections.
All "flu-like illnesses" are not the same, and can be caused by a number of infectious agents. With effective influenza vaccination, the numbers of influenza cases have decreased dramatically. Most of the respiratory infections in the winter or summer are not due to influenza but other respiratory viruses or Mycoplasma. Whereas acute influenza symptoms rarely last more than one week, acute enterovirus infections often last much longer than one or two weeks.
Acute enterovirus infection can present with respiratory and/or gastrointestinal symptoms if the same symptoms recur every month.
Diagnostic testing plays a role in acute enterovirus 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 (growth of the actual virus), serology (antibody testing of the blood), and polymerase chain reaction (PCR, a special viral gene test) can confirm acute enterovirus infections. Enteroviruses are found in the stool, the pharynx, blood, and the cerebrospinal fluid.
In the past, the standard of virus isolation has been cell cultures, but cultures take approximately 3-8 days to grow the enterovirus, and the identification of the particular type of enterovirus is usually not done for a long time afterwards.
Virus isolation from blood is not very helpful 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.
Another method, serologic testing, uses two blood samples to identify a rise of antibody levels over a 2- to 4-week period. A single level of enterovirus antibodies can be present in a healthy patient; therefore, monitoring the serology to identify a 4-fold increase in levels is needed. We can only identify 11 of the 60+ Human enterovirus serotypes by this method. 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 of most of the enteroviruses. The results could be available in 24 hours, making detection more sensitive (95%), more specific (97%), and more time efficient. FDA has approved this test for diagnosing enterovirus meningitis. For other body fluids (stool, respiratory secretions and blood), the yield is less certain.
Measure cardiac and muscle enzymes in a patient with heart and muscle symptoms. Enteroviruses are the usual pathogen of the heart and skeletal muscles. Other viruses can affect the heart.