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Coxsackie B is a group of six
serotypes A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the ep ...
of
coxsackievirus Coxsackieviruses are a few related enteroviruses that belong to the ''Picornaviridae'' family of nonenveloped, linear, positive-sense single-stranded RNA viruses, as well as its genus ''Enterovirus'', which also includes poliovirus and echovir ...
(CVB1-CVB6), a
pathogenic In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ger ...
enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal). Serologic ...
, that trigger illness ranging from gastrointestinal distress to full-fledged
pericarditis Pericarditis is inflammation of the pericardium, the fibrous sac surrounding the heart. Symptoms typically include sudden onset of sharp chest pain, which may also be felt in the shoulders, neck, or back. The pain is typically less severe when sit ...
and
myocarditis Myocarditis, also known as inflammatory cardiomyopathy, is an acquired cardiomyopathy due to inflammation of the heart muscle. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. Th ...
(
coxsackievirus-induced cardiomyopathy Coxsackieviruses-induced cardiomyopathy are positive-stranded RNA viruses in picornavirus family and the genus enterovirus, acute enterovirus infections such as Coxsackievirus B3 have been identified as the cause of virally induced acute myocar ...
). The genome of Coxsackie B virus consists of approximately 7,400 base pairs.


Geographic distribution

The various members of the Coxsackie B group were discovered almost entirely in the United States, appearing originally in
Connecticut Connecticut () is the southernmost state in the New England region of the Northeastern United States. It is bordered by Rhode Island to the east, Massachusetts to the north, New York (state), New York to the west, and Long Island Sound to the ...
,
Ohio Ohio () is a U.S. state, state in the Midwestern United States, Midwestern region of the United States. Of the List of states and territories of the United States, fifty U.S. states, it is the List of U.S. states and territories by area, 34th-l ...
,
New York New York most commonly refers to: * New York City, the most populous city in the United States, located in the state of New York * New York (state), a state in the northeastern United States New York may also refer to: Film and television * '' ...
, and
Kentucky Kentucky ( , ), officially the Commonwealth of Kentucky, is a state in the Southeastern region of the United States and one of the states of the Upper South. It borders Illinois, Indiana, and Ohio to the north; West Virginia and Virginia ...
, although a sixth member of the group has been found in the
Philippines The Philippines (; fil, Pilipinas, links=no), officially the Republic of the Philippines ( fil, Republika ng Pilipinas, links=no), * bik, Republika kan Filipinas * ceb, Republika sa Pilipinas * cbk, República de Filipinas * hil, Republ ...
. However, all six serotypes have a global distribution and are a relatively common cause of gastrointestinal upset. The name reflects the first isolation from Coxsackie, New York.


Transmission

Infections are most commonly spread by the oral-fecal route, emphasizing the importance of good hygiene, especially hand-washing. Oral-oral and respiratory droplets can also be means of transmission.


Epidemiology

Coxsackie B infections have been reported to account for nearly a quarter of all
enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal). Serologic ...
infections. Nearly half of all reported cases of Coxsackie B infections occur before the age of five. For the CBV1 serotype, two-thirds of
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
reported infections in the United States were for children under one year of age.


Symptoms

Symptoms of infection with viruses in the Coxsackie B grouping include
fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
,
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
,
sore throat Sore throat, also known as throat pain, is pain or irritation of the throat. Usually, causes of sore throat include * viral infections * group A streptococcal infection (GAS) bacterial infection * pharyngitis (inflammation of the throat) * to ...
, gastrointestinal distress, extreme
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
as well as
chest The thorax or chest is a part of the anatomy of humans, mammals, and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main divisions of the crea ...
and muscle pain. It can also lead to spasms in arms and legs. This presentation is known as pleurodynia or
Bornholm disease Bornholm disease, also known as epidemic pleurodynia, is a condition characterized by myositis of the abdomen or chest caused by the Coxsackie B virus or other viruses. The myositis manifests as an intermittent stabbing pain in the musculature that ...
in many areas. Patients with chest pain should see a doctor immediately—in some cases, viruses in the Coxsackie B family progress to myocarditis or pericarditis, which can result in permanent heart damage or death. Coxsackie B virus infection may also induce aseptic meningitis. As a group, they are the most common cause of unexpected sudden death, and may account for up to 50% of such cases. The incubation period for the Coxsackie B viruses ranges from 2 to 6 days, and illness may last for up to 6 months in extreme cases, but may resolve as quickly as two days. Infection usually occurs between the months of May and June, but do not show symptoms until October in temperate Northern Hemisphere regions. People should ideally spend 1 month resting during the height of infection. Another cause of this virus is from a dirty wound from an accident.


Diagnosis

Enterovirus infection is diagnosed mainly via
serological Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mic ...
tests such as
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
and from
cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This tec ...
. Because the same level and type of care is given regardless of type of Coxsackie B infection, it is mostly unnecessary for treatment purposes to diagnose which virus is causing the symptoms in question, though it may be epidemiologically useful.


Pathology

Coxsackie B infections usually do not cause serious disease, although for newborns in the first 1–2 weeks of life, Coxsackie B infections can easily be fatal. The pancreas is a frequent target, which can cause
pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic p ...
. Coxsackie B3 (CB3) infections are the most common enterovirus cause of
myocarditis Myocarditis, also known as inflammatory cardiomyopathy, is an acquired cardiomyopathy due to inflammation of the heart muscle. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. Th ...
and
sudden cardiac death Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
. CB3 infection causes
ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ...
pathology in the heart, leading to
ventricular arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adult ...
. Studies in mice suggest that CB3 enters cells by means of toll-like receptor 4. Both CB3 and CB4 exploit cellular
autophagy Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
to promote replication.


Diabetes

The B4 Coxsackie viruses (CB4) serotype was suggested to be a possible cause of
diabetes mellitus type 1 Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...
(T1D). An
autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
response to Coxsackie virus B infection upon the
islets of Langerhans The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of ...
may be a cause of T1D. Other research implicates strains B1, A4, A2 and A16 in the destruction of
beta cells Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dim ...
, with some suggestion that strains B3 and B6 may have protective effects via immunological cross-protection.


Treatment and Prevention

, there is no well-accepted treatment for the Coxsackie B group of viruses.
Palliative care Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...
is available, however, and patients with chest pain or stiffness of the neck should be examined for signs of cardiac or
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
involvement, respectively. Some measure of prevention can usually be achieved by basic sanitation on the part of food-service workers, though the viruses are highly contagious. Care should be taken in washing ones hands and in cleaning the body after swimming. In the event of Coxsackie-induced myocarditis or pericarditis,
anti-inflammatories Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as op ...
can be given to reduce damage to the heart muscle.


Persistent Coxsackie B virus (non-cytolytic infection)

Enteroviruses are usually only capable of acute infections that are rapidly cleared by the adaptive immune response. However, mutations which enterovirus B serotypes such as coxsackievirus B and
echovirus Echovirus is a polyphyletic group of viruses associated with enteric disease in humans. The name is derived from "enteric cytopathic human orphan virus". These viruses were originally not associated with disease, but many have since been identif ...
acquire in the host during the acute phase can transform these viruses into the non-cytolytic form (also known as non-cytopathic or defective enterovirus). This form is a mutated quasispecies of enterovirus which is capable of causing persistent infection in human tissues, and such infections have been found in chronic myocarditis or
dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Co ...
. In these persistent infections, viral RNA is present at very low levels and some researchers believe it is just a fading remnant of the acute infection although others think it may have pathological effects.


References

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