Coxsackie Virus

Coxsackieviruses, part of the Enterovirus genus within the Picornaviridae family, are RNA viruses that can lead to a range of diseases, from mild infections to severe conditions affecting the heart, central nervous system, and other organs. 

What is Coxsackievirus?

Coxsackieviruses, classified within the Enterovirus genus of the Picornaviridae family, are non-enveloped RNA viruses that can cause a wide range of diseases. Based on pathogenicity, they are divided into two groups: Group A and Group B.

Both groups of coxsackieviruses can cause nonspecific febrile illnesses and aseptic meningitis, and both are associated with central nervous system diseases. 

Group A Coxsackievirus

Group A coxsackieviruses primarily affect the skin and mucous membranes, leading to conditions such as hand-foot-and-mouth disease (HFMD), herpangina, and acute hemorrhagic conjunctivitis. 

Notably, coxsackievirus A16 (CVA16) is a major cause of HFMD, with outbreaks often occurring in children. 

While CVA16 typically causes mild symptoms, severe complications such as aseptic meningitis and myocarditis have been reported, especially when co-infection with other enteroviruses like enterovirus 71 (EV71) occurs.

Additionally, CVA16 has been linked to a rare condition called acute flaccid myelitis (AFM), which affects the spinal cord and causes muscle weakness. 

An emerging concern is coxsackievirus A6 (CVA6), which became a significant cause of HFMD during an outbreak in Finland in 2008. While CVA16 and EV71 were traditionally linked to HFMD, CVA6 was identified as a key pathogen, with cases presenting with typical HFMD symptoms as well as unusual complications like onychomadesis (nail shedding). 

Understanding the evolving nature of coxsackievirus infections is important in identifying them; CVA6 is now considered an important pathogen to monitor, particularly during HFMD outbreaks.

Group B Coxsackievirus

Group B coxsackieviruses, including serotypes CVB1-CVB6, tend to target deeper tissues such as the heart, pancreas, and liver, causing conditions like myocarditis, pericarditis, pleurodynia (Bornholm disease), and hepatitis. 

CVB infections are also associated with severe outcomes such as neonatal systemic disease and have been implicated in the development of insulin-dependent diabetes. Coxsackievirus Group B is a major cause of viral myocarditis, especially in neonates and younger children.

Group B viruses are also recognized as a cause of aseptic meningitis, but their primary impact is on the organs mentioned above.

Coxsackie Virus Transmission Routes

 Coxsackieviruses are primarily transmitted through the fecal-oral route, which means that the virus spreads via contact with contaminated surfaces or food. 

The virus can also spread through respiratory droplets, making it highly contagious, particularly in close-contact settings like daycare centers and hospitals.

Common Clinical Manifestations of Coxsackie Virus

Coxsackie virus manifestations may depend on the viral strain and the organs affected. 

Hand, Foot, and Mouth Disease (HFMD)

This is the most common manifestation of CVA infections, characterized by fever, painful sores in the mouth, and a rash on the hands and feet. This condition is typically caused by CVA16 and EV-A71.

Herpangina

This infection, caused by CVA, leads to painful sores in the back of the throat, often seen in young children. It can be caused by Coxsackie viruses and Enterovirus 71.

Acute Hemorrhagic Conjunctivitis

This eye infection, caused by both CVA and CVB, results in redness, swelling, and bleeding in the conjunctiva.

Myocarditis and Pericarditis

CVB infections can cause inflammation of the heart muscle or the sac surrounding the heart. These conditions can be severe, particularly in young adults.

Pleurodynia (Bornholm Disease)

CVB is the primary cause of pleurodynia, which involves sudden sharp chest pain that may mimic a heart attack.

Meningitis

Both CVA and CVB can lead to inflammation of the membranes surrounding the brain and spinal cord, which can manifest as fever, headache, and neck stiffness.

Who Should Get Tested for Coxsackievirus?

Coxsackievirus testing is primarily indicated for patients presenting with characteristic symptoms that are suggestive of infection. 

These include oral sores combined with a rash (HFMD), painful throat lesions (herpangina), eye redness and swelling (acute hemorrhagic conjunctivitis), chest pain (pleurodynia), or symptoms of meningitis (fever, headache, and stiff neck). 

Testing is also critical in outbreak scenarios to confirm diagnoses and prevent viral spread.

Testing for Coxsackievirus

Coxsackievirus infection is typically diagnosed through polymerase chain reaction (PCR), which offers high sensitivity and fast results. Virus isolation in cell culture is an alternative but slower and less sensitive method.

Samples are commonly taken from stool, rectal swabs, or the oropharynx early in the disease. 

Serological tests, including neutralizing antibody titers, can also be used but are less reliable and harder to interpret.

For aseptic meningitis, diagnosis requires cerebrospinal fluid (CSF) analysis, showing lymphocytic predominance, normal-to-decreased glucose, and slightly elevated protein. 

PCR of CSF has a sensitivity of 66-90%, while cell culture is less commonly used. Routine CSF PCR can shorten hospital stays and reduce antibiotic use.

Encephalitis diagnosis involves CSF evaluation, which typically shows similar findings to aseptic meningitis. Electroencephalography (EEG) may help in cases of nonconvulsive seizures.

For myopericarditis, diagnosis is based on positive PCR from oropharyngeal or fecal samples or serological testing.

For acute hemorrhagic conjunctivitis (AHC), diagnosis is made through conjunctival swabs, scrapings, or exudate, with rising antibody titers used for confirmation.

What Does a Positive Coxsackievirus Test Mean?

A positive test for Coxsackievirus confirms that the virus is likely the cause of the patient’s symptoms. 

Some tests may also be able to identify specific serotypes, such as CVA16 or CVB3, which can provide valuable information for epidemiological tracking and understanding clinical outcomes. 

However, it’s important to interpret test results in conjunction with the patient’s symptoms and clinical history. For instance, a patient with HFMD symptoms and a positive CVA16 test supports the diagnosis, while a positive CVB result might be more likely in cases of myocarditis or pleurodynia.

What Does a Negative Coxsackievirus Test Mean?

A negative Coxsackievirus test means that the virus is not detected, but this does not necessarily exclude the infection, as the viral load may be too low for detection or may not be present in the tested sample. 

It's also important to consider other possible diagnoses. A negative result does not rule out other infections or conditions with similar clinical presentations, such as bacterial infections or other viral illnesses like enteroviruses or herpes.