Emerging non-polio enteroviruses
Neglected and emerging human pathogens

Enteroviruses can cause severe infections and can occur in large outbreaks. Especially young children are vulnerable. These viruses cause a wide variety of diseases, with aseptic meningitis being the most common in both adults and children. Non-polio enterovirus infections are not notifiable in most countries.

Enteroviruses affect more than a billion of people worldwide each year but exactly how many people are infected each year is unknown. Some may be asymptomatic and screening for these diseases is not routinely performed. With yearly increasing numbers, these viruses uncover an urgent need for better screening to improve child health in many low resource countries.

1

BILLION

New infections per year

/

<1

%

Severe disease

/

?

PEOPLE

Dead per year

What causes Enteroviral diseases

Enteroviruses are a group of viruses that cause a number of illnesses which are usually mild febrile illness, mild respiratory illness like the common cold and may be causing some of the acute diarrheal outbreaks. They can however occasionally lead to severe disease. Their main route of transmission is fecal-oral.

On the basis of their pathologies, enteroviruses were originally classified into four groups, polioviruses, Coxsackie A viruses, Coxsackie B viruses and echoviruses.

Enteroviruses isolated more recently are named with a system of consecutive numbers based on the VP1 capsid region of the genome. Enterovirus serotypes are not exclusively associated with particular disease syndromes, but sometimes have a propensity to cause particular symptoms.

Echovirus serotypes are frequently reported to be responsible for meningitis, but also are responsible for most enterovirus infections. Among coxsackieviruses, the leading serotypes associated with central nervous system diseases are B1 to B6, A7 and A9.

Image: Coxsackievirus A16

Acute hemorrhagic conjunctivitis, a highly contagious infection characterized by eye pain, eyelid swelling, and subconjunctival haemorrhage has been associated with enterovirus 70 and coxsackievirus A24. Enterovirus 71 has been associated with major outbreaks of hand, foot and mouth disease with concurrent fatal encephalitis among very young children. 

Historically, poliomyelitis was the most significant disease caused by an enterovirus. While wild-polio viruses have mainly been eradicated, an alarmingly large number of non-polio cases are being reported annually, with the number increasing each year.

Where are Enteroviruses found

Enteroviruses are found world-wide. Enterovirus A types EV-A71, EV-A6, EV-A16, and EV-A10 are the most commonly found types in East Asia, and Southeast Asia. Enterovirus B is found most commonly in Western Asia, Europe, Africa, South America, Southern Asia and Oceania. Most of the data available is from countries who are actively suppressing polio, which may make any attempt to map them inaccurate.

Climate and socio-economic factors likely contributors to the geographic distribution of different types. Many enteroviruses are transmitted through the oral-fecal route. Poor sanitary conditions and overcrowding are important factors driving epidemics related to these viruses.

Image: Geographic Distribution of Enteroviruses - Brown et al (2020)

What are the symptoms of Enteroviral infections

Enteroviruses cause a wide range of symptoms, from rashes in small children, to summer colds, to encephalitis, to blurred vision, to pericarditis. They also have a great range in presentation and seriousness. 

  • Nonspecific febrile illness is the most common presentation of enterovirus infection. Other than fever, symptoms include muscle pain, sore throat, gastrointestinal distress/abdominal discomfort, and headache. In newborns the picture may be that of sepsis and can be severe and life-threatening.
  • Poliomyelitis primarily via the fecal-oral route, affects the central nervous system and causes muscle weakness.
  • Polio-like syndrome found in children who tested positive for enterovirus 68.
  • Aseptic meningitis in children. The symptoms are diverse and non-specific with possibility of vomiting, headaches, firm neck pain.
  • Acute hemorrhagic conjunctivitis can be caused by enteroviruses.
  • Acute flaccid paralysis is one of the most serious conditions attributed to enterovirus B.
  • Bornholm disease or epidemic pleurodynia is characterized by severe paroxysmal pain in the chest and abdomen, along with fever, and sometimes nausea, headache, and emesis.
  • Pericarditis and/or myocarditis are typically caused by enteroviruses; symptoms consist of fever with dyspnea and chest pain.
  • Arrhythmias, heart failure, and myocardial infarction have also been reported.
  • Herpangina is caused by Coxsackie A virus, and causes a vesicular rash in the oral cavity and on the pharynx, along with high fever, sore throat, malaise, and often dysphagia, loss of appetite, back pain, and headache. It is also self-limiting, with symptoms typically ending in 3–4 days.
  • Hand, foot and mouth disease is a childhood illness most commonly caused by infection by Coxsackie A virus or EV71.
  • Encephalitis is rare manifestation of enterovirus infection. When it occurs, the most frequent enterovirus found to be causing it is echovirus 9.
  • Myocarditis is characterized by inflammation of the myocardium (cardiac muscle cells). Over the last couple of decades, numerous culprits have been identified as playing a role in myocarditis pathogenesis in addition to the enterovirus, which at first was the most commonly implicated virus in this pathology. One of the most common enteroviruses found to be responsible for causing Myocarditis is the Coxsackie B3 virus.
  • Possibly chronic fatigue syndrome. Acute respiratory or gastrointestinal infections associated with enterovirus may be a factor in this disease.

How can Enteroviral infections be prevented

Most enteroviruses are spread through the faecal-oral route, which is why environmental sanitation plays a vital role in preventing transmission. Good hygiene practices, such as frequent hand-washing, are essential to reducing the risk of becoming infected.

Some enteroviruses can be prevented with vaccines:

  • Polio vaccines are vaccines used to prevent poliomyelitis. Two types are used: an inactivated poliovirus given by injection and a weakened poliovirus given by mouth. A potential, adverse effect of the oral vaccine is its ability to recombine to a form that causes neurological infection and paralysis. It does not affect the person who was originally vaccinated but can allow spread of polio in areas with poor sanitation and low vaccination coverage.
  • For hand foot and mouth disease a vaccine is available in China for the EV71 virus.

How are Enteroviral infections diagnosed

Most infections are usually diagnosed based on symptoms. However this is a highly unreliable way to identify these complex disease presentations. Enteroviruses can be detected by Polymerase chain reaction (PCR) tests, such as the ones made available by the WoIDM. Use of these molecular tests offers several potential advantages. While the results are fast and the test have high sensitivity, they also allow to type the virus and enable detection of viruses that cannot be typed with other serological tests.

How are Enteroviral infections treated

There is no specific treatment for non-polio enterovirus infection. People with mild illness typically only need to treat their symptoms.

Some illnesses caused by non-polio enteroviruses can be severe enough to require hospitalization. Also here, supportive treatment is used based on symptoms. There are no specific antiviral drugs for enteroviruses.

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