Coxsackie virus is an RNA virus, belongs to the family of Picornaviridae and genus enterovirus. The viruses are transmitted primarily via the fecal-oral route and the respiratory droplets. Coxsackie viruses are of two types group A and group B viruses . Group A coxsackie viruses are associated with infection of the skin and mucous membrane, acute hemorrhagic conjunctivitis and the hand, foot, and mouth (HFM) disease . Group B are responsible for the infection of the heart, pleura, pancreas and liver casing pleurodynia, myocarditis, pericarditis and hepatitis accordingly . Both types of viruses have the sign symptoms of febrile illness, skin rashes and upper respiratory tract disease. Coxsackie viruses are one of the leading causes of aseptic meningitis. Coxsackie viruses are among the leading causes of aseptic meningitis. Recent studies have been shown the significant association between the insulin-dependent diabetes (IDDM) the type-B Coxsackie virus infection . Coxsackie virus infections have worldwide distribution. The infection occurs in all age groups but young children, infant and immune compromised groups are at high risk for the complications.
Most Coxsackie virus infections are mild and self-limiting. The patient may be presented with common cold, sore throat and characteristic rashes on the palms, soles, inside the mouth, tongue, gums and cheek, known as hand-foot-mouth disease (HFMD), more common in children under 10 years . The diagnosis of coxsackie virus infection is typically clinical. Usually no treatment is required for mild infection because of the ability of the body immune system to destroy the viruses. Patient with severe signs and symptoms treatment are supportive . Hand hygiene, Environmental hygiene and creating public awareness are the key steps for the prevention and control of this viral infection. Efforts are continuing to search for a vaccine against Coxsackie virus infection.
Coxsackie viruses belong to the family of Picornaviridae and genus of Enterovirus. Enteroviruses are the commonest and important human pathogens usually occur in children but also
occur in adults . It causes blister-like rash involving the hands, foot and mouth for this reason named as Hand, foot, mouth Disease (HFMD) and it also causes diseases of muscles, lungs and heart . Coxsackie viruses are divided into group A and group B viruses. Type A viruses cause herpangina (sores in the throat) and hand, foot, and mouth disease. Type B viruses cause epidemic pleurodynia, and inflammation in the chest. The virus was first isolated in 1948-49 by Dr. Gilbert Dalldorf, working as a scientist in the New York State Department of Health in Coxsackie viruses are distributed worldwide, predominant in summer season with sporadic cases are found all the year round [7,8] (Figure 1) Panel A shows the organization of the Coxsackie viruses genome, including its nucleotides. 2A and 3C are viral proteinases which is responsible for the cleavage of the polyprotein encoded for by the genome. 3D is the RNA-dependent RNA polymerase (RdRP). 2B, 2C, and 3A are core viral proteins. The genome also codes for 4 capsid proteins, VP4, VP1, VP2, and VP3 that form an icosahedral capsid . Panel B shows the structure of the virion which is non-enveloped, spherical, about 30 nm in diameter, T=pseudo 3 icosahedra capsid surrounding
the naked RNA genome. The virus causes initially fever, anorexia,
sore throat and cough. After the initial phase small blisters like
rashes develop which are itchy in nature usually on the palms
of the hand and soles of the feet and the buttocks and genitals
may be involved [10,11]. Some are suffering from conjunctivitis
.The patients are most contagious for a week after the symptoms
begin but may take for several weeks. In majority cases HMFD
are self-limited, so usually no treatment is required .
Coxsackievirus infections have worldwide distribution and
seasonality in areas of higher latitude. Neonates and immune
compromised individuals are at higher risk. An infected
person may spread the viruses through close personal contact,
by coughing or sneezing, contact with feces or contact with
contaminated objects and surfaces .
Most of coxsackie viruses infections are asymptomatic
or cause mild nonspecific febrile illnesses. It is common for
the Coxsackie virus to cause a febrile upper respiratory tract
infection with sore throat with or without a runny nose. Skin
rashes are other clinical findings which may not appear until
the infection has started to get better. The rash itself is not
contagious, resemble a light sunburn appearance. Sometimes the
rashes appeared like a small, tender blisters on the palms, soles
of the feet, and inside the mouth including the tongue, gums, and
the cheek. This condition is known as hand-foot-mouth disease
(HFMD) (Figure 2) and is caused by group A coxsackie virus .
The mild case usually resolves on its own. This infection
usually transmitted through respiratory droplets or stool
exposure or the blister fluids . The clinical syndrome
presents with fever, sore throat, and small, tender blisters inside
the mouth is called herpangina, more common in summer and
is usually found among children 3-10 years of age . The
infection may cause swollen eyelids and red hemorrhagic spots with burning pain in the conjunctiva clinically known as acute
hemorrhagic conjunctivitis (AHC) usually spreads to the other
eye as well . Group B Coxsackie viruses may cause viral
meningitis also known as “aseptic meningitis” because routine
cultures of the spinal fluid show no bacterial growth. Patients
with aseptic meningitis presents with a complain of a headache,
fever with mild neck stiffness with or without rash in adults. In
children, they show change in personality or lethargy or febrile
In some rare occasions patient may suffers from temporary
muscle weakness in their limbs or even partial paralysis. Patients
also may complain for sudden onset of sharp chest pain which
gets worse when taking a deep breath due to inflammation of
the muscles of chest. This condition is called as Pleurodynia
and is self-limiting . A very serious complication caused by
coxsackie virus infection is myopericarditis may vary from mild
to severe form characterized by shortness of breath, chest pain,
fatigue, and leg swelling. This condition is more common young,
active adults . Coxsackievirus infection may be transmitted
from mother to neonate during pregnancy at the time of delivery
as the infant comes into contact with the mother’s secretions.
Severely affected infants become unresponsive and may have
myopericarditis, heart failure, pneumonia, hepatitis or liver
failure, diarrhea that may cause severe dehydration in infants
associated with life-threatening or fatal outcomes. Neonates are
at risk for severe infection associated with neurologic signs .
The diagnosis of coxsackievirus infection is typically
clinical, because the association of acute fever and rash is highly
predictive in areas where the disease is endemic . Isolation
of the virus in cell culture the specific diagnosis. Samples from
stool, oropharynx or rectal swabs are usually collected. To rule
out aseptic meningitis and encephalitis cerebrospinal fluid (CSF)
evaluation are required. The virus can be isolated via cell culture
(sensitivity, 30-35%) or PCR (sensitivity, 66-90%) .
In most of case epidemic hand-foot-and-mouth disease
(HFMD) viral infections are caused by coxsackievirus A16, A6, or
enterovirus 71. Besides this, sporadic cases with coxsackievirus
infections are associated with types A4-A7, A9, A10, B1-B3, and
B5 . Coxsackie viruses infections are transmitted primarily via
the fecal-oral route, respiratory droplets and fomites. Initially
the viruses replicate in buccal and ileal mucosa. After the initial
infection the virus can be detected in the respiratory tract up
to 3 weeks and in feces up to 8 weeks. The viruses replicate in
the sub mucosal lymph nodes within 24 hours and disseminate
to the reticuloendothelial system. In severe cases dissemination
occurs to target organs following a secondary viremia .
(Figure 3) Enteroviruses are transmitted primarily through
the fecal-oral route or fomite. Then the viruses replicate in the
mucosa of the oropharynx, small intestine and the lymphoid tissue (tonsils, Peyer’s patches of the intestinal mucosa followed
by shed into the feces. This time may be taken months after the
Within 7 days the level of the neutralizing antibody increase
and the virus is eliminated. However one study showed that the
neutralizing antibody may not correlated with disease severity
These preventive measures are aimed against transmission
of the infectious agents. These precautions are focused on all
blood, body fluids including saliva and coughed up material,
secretions, excretions such as wound drainage, urine and stool
but not sweat, non-intact skin and mucous membrane have the
probability of spreading the infection. Recommendations for
Standard Precautions have been taken from several guidelines
published by HICPAC/CDC, the IDSA, and the World Health
Some preventive measures under Standard Precautions are:
a. Hand hygiene: Hand hygiene in appropriate times is
effective in both healthcare and no healthcare such as school,
daycare centers and dormitories, guest rooms, hallways etc.
settings. Hand washing can be done with plain soap and water or
soap containing an antiseptic agent or waterless alcohol-based
hand rub containing at least 60% alcohol [28,29].
b. Use of Gloves: Gloves are not alternatives for hand
hygiene. It is an additional requirement to prevent contact with
blood, body fluids, secretions, excretions, non-intact skin and
mucous membrane. Immediately after removal of gloves we
should wash our hand properly.
c. Respiratory hygiene: All respiratory secretions are
considered potentially infectious. The following precautions are
required to take into action:
To cover the mouth and nose with tissues during
coughing and sneezing,
Immediately disposal of the tissues followed by hand
Vulnerable groups such as children, weakened immune
status, and elderly are required to keep at least 3-
6 feet (1-2 meters) away from the infected person.
In a public or crowded place people with weakened
immune status are required to wear masks.
d. Blood and body fluid precautions: The following
measures are required to take:
Family member are needed to avoid sharing personal
items such as toothpaste, razors, cloths etc.
To restrict the entrance of an individual with open skin
Isolation of the infected patient.
e. Practice for safe infection: The caregivers should
follow the following precautions:
For medication single-dose vials are always preferred
A single person is required for monitoring the
medication vials, insulin pens and figerstick device.
Needles are required to be disposed separately in a
The housekeeping staff should practice caution during
cleaning the linens and clearing the rooms .
f. Environmental Hygiene: Bacteria and viruses can
survive for long times on environmental surface. So it is required
to clean by removal of dirt and contaminated surface scrubbing
with a detergent followed by rinsing with water .
g. Precautions for Highly Immune-compromised
Patients : To reduce the airborne transmission at home following
measures can be undertaken [27,31] :
To reduce dust overload it is required to maintain
the heating, ventilation, and air conditioning (HVAC) device
To avoid exposure to construction sites or the outdoors
on windy days.
To wear special type of mask such as N95 respirator
during travelling to and from the hospital.
To avoid carpeting which is a major source retained
If carpeting essential it is required to use a highefficiency
particulate air (HEPA)-filtered vacuum for clean the
area regularly in the absence of the patient.
In common areas it is required to avoid the use of
humidifiers and or dehumidifiers.
In the room avoid keeping potted plants or fresh
Supportive medical care can be offered on an outpatient
basis. Any complications may require inpatient management.
For aseptic meningitis medication with emteroviral capsidstabilizing
drug such as Pleconaril, shown to reduce the
symptoms. Antibiotics may be useful until bacterial meningitis
is ruled out . In case of myopericarditis medication with
carvedilol, a non-selective beta-blocker has shown to decrease
the replication of the virus in a murine model but this has not
been evaluated in humans . Patient suffering from epidemic
pleurodynia has been shown to recover completely within 1
week after taking analgesics, narcotics and heating pads for their
medical therapy .
Usually the prognosis is very good for Coxsackie virus infection.
Although key advances have been made in understanding the
biologic aspects and pathogenesis of Coxsackie virus infections
but still there are some questions critical to the development of
targeted and preventive strategies. Patients should be reassured
that it is a self-limiting illness that usually does not require any
antibiotics for the treatment. Creating awareness among the
patient as well as the general people for good hygiene practices
to avoid transmission is necessary.