A six year old boy was brought in to the Emergency Department by his worried parents because he was drowsy and had been complaining of a headache. His parents were concerned that he might have meningitis. He was seen urgently by the paediatricians who noted the boy also had a fever. As meningitis was the most serious possible diagnosis a set of bloods were taken to look for evidence of infection and a lumbar puncture was performed. As soon as the lumbar puncture had been done the boy was started on antibiotics (IV Ceftriaxone) for possible bacterial meningitis whilst waiting for the results of the lumbar puncture and other tests including a urine and blood cultures.
The lumbar puncture showed a raised white blood cell count, 90% of which were lymphocytes, a normal glucose in ratio to serum glucose and a slightly raised protein. Although this was consistent with a diagnosis of viral meningitis the paediatricians were reluctant to stop the Ceftriaxone “just in case it was something else!” It isn’t going to be because the CSF is lymphocytic and has a normal glucose but it’s often harder to stop antibiotics than it is to start them. It should be possible to diagnose viral meningitis from the CSF white blood cell count, glucose and protein with over 99% accuracy, without needing any further tests, especially as these are expensive (each individual viral PCR costs about £50) and there is no specific treatment for any of the viral causes of meningitis anyway.
If the boy had bacterial meningitis the CSF would contain neutrophil polymorphs, have a low glucose and a very high protein, antibiotics are essential as the infection is life-threatening.
The doctors still wanted a viral PCR which was arranged and later that day the CSF was shown to contain Parechovirus, a viral cause of meningitis. “Meningitis, meningitis, meningitis…” is that an echo or a par-echo-virus? The parents (and the doctors) were reassured that this was definitely viral meningitis and that their son would soon be feeling better. The Ceftriaxone was stopped and as he was feeling a bit better the following day the boy was allowed to go home.
If the boy had bacterial meningitis the CSF would contain neutrophil polymorphs, have a low glucose and a very high protein, antibiotics are essential as the infection is life-threatening.
The doctors still wanted a viral PCR which was arranged and later that day the CSF was shown to contain Parechovirus, a viral cause of meningitis. “Meningitis, meningitis, meningitis…” is that an echo or a par-echo-virus? The parents (and the doctors) were reassured that this was definitely viral meningitis and that their son would soon be feeling better. The Ceftriaxone was stopped and as he was feeling a bit better the following day the boy was allowed to go home.
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Clinical presentation
The parechoviruses are very similar to the enteroviruses however they are just different enough genetically to be classified as separate types of virus within the whole picornavirus family. The two viruses cause the same types of clinical condition and are transmitted in the same ways. It is impossible to distinguish them clinically.
Parechovirus and Enterovirus infections can present in a number of different ways with more than one symptom from the list below:
In my experience I see Enterovirus and Parechovirus meningitis in 2 main groups of patients, children and adults who have close contact with children (usually their own!). I guess it’s pretty obvious that children get virus infections; they have usually not been exposed to these viruses before and their hand hygiene is often not very good! The adult cases, I see, have almost invariably had contact with children, with either flu-like or gastrointestinal symptoms, in the week preceding the onset of their own infection. The adult often also reports a flu-like prodromal period (early symptoms and signs of an illness) before they became more unwell.
The dangerous exception
It is impossible to distinguish parechoviruses and enteroviruses clinically except in the context of poliomyelitis which is characteristically distinct causing flaccid paralysis (either a limb or more extensive) which can be permanent. We routinely vaccinate children in the UK and the WHO have made the worldwide eradication of poliomyelitis one of their major priorities. They are yet to achieve this but they continue to try.
How are enteroviruses and parechoviruses detected?
There are 14 different serotypes of parechovirus and over a 100 different serotypes of enterovirus. There were originally 72 enterovirus serotypes but modern techniques, such as PCR, have led to detection of new serotypes. In fact PCR has revolutionised the detection of these viruses in clinical specimens.
When I started in microbiology in 2001 detection was through either isolation in cell culture or visualization using an electron microscope. Both techniques were fiddly, time consuming (days to weeks) and required a huge amount of expertise. Nowadays there are commercial kits that will detect the presence of enteroviruses in CSF, throat swabs and stool samples within a couple of hours. They might be expensive but they give doctors the confidence to stop antibiotics and send patients home from hospital earlier, and also allow doctors to isolate neonates with viral sepsis much more rapidly in order to protect other babies.
What is the treatment of Enterovirus or Parechovirus infection?
Enterovirus and Parechovirus infections are usually self-limiting except in neonates and the immunosuppressed. YES… even meningitis and encephalitis with these microorganisms is self-limiting. Supportive care with adequate hydration and antipyretics may be required. At present there is no specific treatment for these viruses.
Infection control
Hand hygiene is the most important method of preventing transmission of these viruses. Alcohol hand gels are NOT as effective as soap and water. Transmission of the viruses occurs via droplets from the upper respiratory tract for the first 3 weeks of infection and via the faecal-oral route for up to 8 weeks. The most infectious period is the first 2 weeks. The incubation period is approximately 5 days.
Past infection provides only serotype specific immunity therefore given the number of different serotypes further infections are common. Because neonates are particularly at risk of severe and life-threatening infections neonates with enteroviruses or parechoviruses must be strictly isolated and gloves and gowns should be used when there is a risk of contact with body fluids. I would also go as far as saying that, if possible, neonates with an Enterovirus and Parechovirus infection should have a dedicated nurse.
So, not all meningitis is life-threatening. Over 50% are caused by the enteroviruses and parechoviruses and are self-limiting. However, it’s still frightening for patients, parents and their doctors; therefore ANTIBIOTICS SHOULD ALWAYS BE GIVEN until viral meningitis is diagnosed. Rapid PCR tests to help confirm the diagnosis of viral meningitis are really useful in facilitating the stopping of unnecessary antibiotics, reassuring the patient that antibiotics have no effect on viruses and that the symptoms will resolve and therefore the patient can be discharged safely.
The parechoviruses are very similar to the enteroviruses however they are just different enough genetically to be classified as separate types of virus within the whole picornavirus family. The two viruses cause the same types of clinical condition and are transmitted in the same ways. It is impossible to distinguish them clinically.
Parechovirus and Enterovirus infections can present in a number of different ways with more than one symptom from the list below:
- Fever
- Headache
- Nausea
- Vomiting
- Diarrhoea
- Conjunctivitis
- Pharyngitis
- Maculopapular rashes
- Meningoencephalitis – more than 50% of all meningitis is caused by enteroviruses (90% in infants)
- Neonatal sepsis - including features of pneumonia, hepatitis, myocarditis and necrotising enterocolitis
- Flaccid paralysis (only caused by Poliovirus, an enterovirus, which is very rare in most of the World including the UK, see below)
In my experience I see Enterovirus and Parechovirus meningitis in 2 main groups of patients, children and adults who have close contact with children (usually their own!). I guess it’s pretty obvious that children get virus infections; they have usually not been exposed to these viruses before and their hand hygiene is often not very good! The adult cases, I see, have almost invariably had contact with children, with either flu-like or gastrointestinal symptoms, in the week preceding the onset of their own infection. The adult often also reports a flu-like prodromal period (early symptoms and signs of an illness) before they became more unwell.
The dangerous exception
It is impossible to distinguish parechoviruses and enteroviruses clinically except in the context of poliomyelitis which is characteristically distinct causing flaccid paralysis (either a limb or more extensive) which can be permanent. We routinely vaccinate children in the UK and the WHO have made the worldwide eradication of poliomyelitis one of their major priorities. They are yet to achieve this but they continue to try.
How are enteroviruses and parechoviruses detected?
There are 14 different serotypes of parechovirus and over a 100 different serotypes of enterovirus. There were originally 72 enterovirus serotypes but modern techniques, such as PCR, have led to detection of new serotypes. In fact PCR has revolutionised the detection of these viruses in clinical specimens.
When I started in microbiology in 2001 detection was through either isolation in cell culture or visualization using an electron microscope. Both techniques were fiddly, time consuming (days to weeks) and required a huge amount of expertise. Nowadays there are commercial kits that will detect the presence of enteroviruses in CSF, throat swabs and stool samples within a couple of hours. They might be expensive but they give doctors the confidence to stop antibiotics and send patients home from hospital earlier, and also allow doctors to isolate neonates with viral sepsis much more rapidly in order to protect other babies.
What is the treatment of Enterovirus or Parechovirus infection?
Enterovirus and Parechovirus infections are usually self-limiting except in neonates and the immunosuppressed. YES… even meningitis and encephalitis with these microorganisms is self-limiting. Supportive care with adequate hydration and antipyretics may be required. At present there is no specific treatment for these viruses.
Infection control
Hand hygiene is the most important method of preventing transmission of these viruses. Alcohol hand gels are NOT as effective as soap and water. Transmission of the viruses occurs via droplets from the upper respiratory tract for the first 3 weeks of infection and via the faecal-oral route for up to 8 weeks. The most infectious period is the first 2 weeks. The incubation period is approximately 5 days.
Past infection provides only serotype specific immunity therefore given the number of different serotypes further infections are common. Because neonates are particularly at risk of severe and life-threatening infections neonates with enteroviruses or parechoviruses must be strictly isolated and gloves and gowns should be used when there is a risk of contact with body fluids. I would also go as far as saying that, if possible, neonates with an Enterovirus and Parechovirus infection should have a dedicated nurse.
So, not all meningitis is life-threatening. Over 50% are caused by the enteroviruses and parechoviruses and are self-limiting. However, it’s still frightening for patients, parents and their doctors; therefore ANTIBIOTICS SHOULD ALWAYS BE GIVEN until viral meningitis is diagnosed. Rapid PCR tests to help confirm the diagnosis of viral meningitis are really useful in facilitating the stopping of unnecessary antibiotics, reassuring the patient that antibiotics have no effect on viruses and that the symptoms will resolve and therefore the patient can be discharged safely.
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