Coxsackievirus

LEARNING OBJECTIVES1. Enumerate the viruses causing aseptic meningitis2. Describe the important characteristics & virulence factor of Coxackie and echoviruses and their clinical significance3. Enumerate the diseases caused by coxackie viruses & echoviruses4. Describe the pathogenicity and lab diagnosis of coxackie viruses & echoviruses

Aseptic causes of MeningitisViruses that cause meningitis include 1. Enteroviruses (Coxasckie & Echo viruses)2. Mumps3. Herpesvirus, including Epstein-Barr virus,

herpes simplex viruses, varicella-zoster virus (which also causes chicken pox and shingles), measles, and influenza4. arboviruses ( spread through mosquitoes

and other insects) 5. In rare cases LCMV (lymphocytic choriomeningitis virus), which is spread by rodents, can cause viral meningitis

Enteroviruses

Virus family Serotypes

Polio 1-3

Coxsackie A 1-22, 24

Coxsackie B 1-6EchovirusEnteric, cytopathic, human, orphan 1-9, 11-27, 29-34

Hepatitis A Enterovirus 72

Other Enteroviruses  68-71 

• Kayla Nicole Clingerman of Woollum, KY was tragically taken from us at the age of 6 from Viral Meningitis.

October 13, 1997 - October 11, 2004

• This is a picture of Seven month old Olivia Grace Hamilton at Cayuga Lake in 2004. Viral Meningitis. tragically took her life.

Introduction

• Late summer or early fall…It’s not yet cold or flu season, but your child is sick. Consider coxsackie virus.

• It’s often the culprit when parents leave a doctor’s appointment without knowing what disease their child has.

Definition • Coxsackie viruses, a family of enteroviruses. These

viruses share in common that they infect the human intestines (and stool), but they can cause symptoms throughout the body.

• Coxsackie viruses are typical enteroviruses, with a diameter of 28 nm.

Common biological properties

• 24-30nm• spherical• naked, icosahedral• +ssRNA• multiply in the cytoplasm • Resistance

– resistant -- ether, acid (tolerate pH3-5)– sensitive -- drying, heat and UV– survive for a long period in water and sewage

• spherical,20-30nm.

• Icosahedral symmetry,

• non-enveloped.

• Capsid:VP1-VP4

• +ssRNA.

Features of coxsackievirus infection in man

• Coxsackievirus A 1-24• Asptic meningitis

• Febrile illness• Herpangina

• Hand-foot-and-mouth disease• Coxsackievirus B 1-6

• Neonatal disease• Myocarditis, hepatitis

• Meningitis

COXSACKIE VIRUSESThey produce a variety of ill nesses in human beings, including aseptic meningitis, herpangina, pleurodynia, hand, foot, and mouth disease, myo- and pericarditis, common colds, and possibly diabetes.

Coxsackie viruses have been divided into 2 groups, A and B, having different pathogenic potentials for mice. Coxsackie B viruses are the most commonly identified causative agents of viral heart disease in humans.

Group A viruses produce widespread myositis in the skeletal muscles of newborn mice, resulting in flaccid paralysis without other observable lesions.

Group B viruses may produce focal myositis, encephalitis, and, most typically, necrotizing steatitis involving mainly fetal fat lobules.

Pathogenesis of enterovirus infection

Rhino,echo,coxsackie,polio

Replication in oropharynx

Primary viremia

Target Tissue

Secondary viremia

Skin Muscle Brain Meninges Liver

Echo

Coxsackie

A

Echo

Coxsackie

A, B

Polio

Coxsackie

Echo

Polio

Coxsackie

Echo

Coxsackie

Pathogenic mechanism

• CV are characterized by their ability to cause CPE in tissue culture and by their capacity to initiate acute disease by inducing apoptosis within targeted organs in vivo. So,these viruses are considered highly cytolytic.

• CV can establish persistence in susceptible cells, indicating that a regulatory mechanism may exist to shut off viral protein synthesis and replication under certain situations.

To cell

• Basically, the virus confuses the body's defence system.• First, the body detects the presence of an enemy using its

antigen recognition system. The virus, meanwhile, may mimic the protein structure of the heart muscle, and sometimes, may even interact and alter the antigenic configuration there.

• Second, the body's defence system reads the signals wrongly. It deploys killer white cells to attack the enemy. The white cells do two things. One, it fires virus-seeking missiles called antibodies to neutralise Coxsackie B and removes it. Two, the white cells also attack the wrong target: the heart. the white cells attack one of its own life support systems.

To defence system

Immunity • Serum IgA is very important to resist

absorption and replication of virus in alimentery tract.

• Neutralizing Ab in serum can prevent the diffusion of virus,which can last for several years,even all the life.

• .

Incubation • The incubation period (the time between

infection and the onset of symptoms) for most coxackie virus infections is about 2 to 10 days

Transmission• Coxsackieviruses are present both in the stool

and in the respiratory secretions

Fecal-oral transmissionDroplet transmissionContact transmission

symptoms• Hand-foot-and-mouth disease mainly affecting young children • Rash. • Nonspecific fever, headache • Herpangina. • Respiratory Infection. • Gastrointestinal Infection.

Herpangina:

There is an abrupt onset of fever, sore throat, anorexia, dysphagia, vomiting, or abdominal pain. The pharynx is usually hyperaemic, and characteristic discrete vesicles occur on the anterior pillars of the fauces, the palate, uvula, tonsils, or tongue. The illness is self-limited and most frequent in small children.

Summer Minor Illnesses:

It occur during the summer or fall and are without distinctive features.

Pleurodynia (Epidemic Myalgia, Bornholm Disease): by group B viruses--- Fever, malaise, head ache, and anorexia. chest pain (substernal), is intensified by movement, Abdominal pain occurs in approximately half of cases, and in children this may be the chief complaint.

Aseptic Meningitis and Mild Paresis:

Fever, malaise, headache, nausea, and abdominal pain are common early symptoms. Signs of meningeal irritation, stiff neck or back, and vomiting may appear 1-2 days later.

Neonatal Disease: Neonatal disease may be caused by group B coxsackieviruses. with lethargy, feeding difficulty, and vomiting, with or without fever.

Colds: A number of the enteroviruses have been associated with common colds; among these are coxsackieviruses A10, A21, A24, and B3.

Hand, Foot, and Mouth Disease:

The syndrome is characterized by oral and pharyngeal ulcerations and a vesicular rash of the palms and soles that may spread to the arms and legs

Hand-foot-and-mouth disease

Exanthems – Rubelliform rashes

Hand-foot-and-mouth disease

• rash

conjunctivitis Herpangina

• Meningitis

Viral myocarditis

Duration • The duration usually varies, depending on the

specific type. • Coxsackie fever often asymptoms, a child's

temperature may return to normal within 24 hours, although the average fever lasts 3 to 4 days. In pleurodynia, fever and muscle pain usually last 1 to 2 days, and in herpangina, symptoms generally last 3 to 6 days.

Myocardiopathy: Coxsackie virus B infections are increasingly recognized as a cause of primary myocardial disease in adults as well as children.

Acute Hemorrhagic Conjunctivitis: Coxsackievirus A24 is one of the agents that can cause this disease (see below).

Diabetes Mellitus: Serologic studies suggest an association of diabetes of abrupt onset with past infection by Coxsackievirus B4 and perhaps other members of the B group.

Diagnose

• Diagnosis is made based on the history and physical exam

• Lab tests are available test stool or fluids from the back of the throat• Serum test for specific Ab • PCR for viral nucleic acid

Treatment• Antibiotics do not help with coxsackievirus

infections • Plenty of fluids is useful• Acetaminophen (such as Tylenol) may be

given to relieve any minor aches and pains • Most children with a simple coxsackie

infection recover completely after a few days at home.

ECHOVIRUSESThe echoviruses (enteric cytopathogenic human orphan viruses) are grouped together because they infect the human enteric tract and because they can be recovered from humans only by inoculation of certain tissue cultures.

Over 30 serotypes are known, but not all cause human illness. Aseptic meningitis, febrile illnesses with or without rash, common colds, and acute hemorrhagic conjunctivitis are among the diseases caused by echoviruses.

Important Characteristics• Echoviruses are typical enteroviruses

measuring 24-30 nm.

• Not produce diseases in sucking mice, rabbits, or monkeys;

• Cause aseptic meningitis, infantile diarrhea, • Monkey kidney and human embryonated

kidney cell culture