General Characteristics and Epidemiology
General features of Coxsackievirus
- Family: Picornaviridae
- Genus: Enterovirus
- RNA virus:
- Single stranded
- Positive sense
- Functions as mRNA
- Diameter: approximately 30 nm
- Icosahedral symmetry
- Lacks a lipid envelope
- Acid-stable viruses
Clinically relevant species
Coxsackie group A virus (23 serotypes):
- Hand, foot, and mouth disease (HFMD)
- Acute hemorrhagic conjunctivitis
Coxsackie group B virus (6 serotypes):
- Neonatal disease
Both groups can cause:
- Upper respiratory tract infection
- Aseptic meningitis
- Worldwide distribution
- More common in summer
- Affects men and women equally
- Occurs in all age groups, but more common in infants and young children
Humans are the only reservoir.
- Fecal-oral route
- Respiratory aerosols
- Oral entry of the virus → replication in the submucosal lymphatic tissue of the pharynx and intestine
- Spread to regional lymph nodes → replication
- Asymptomatic viremia → reticuloendothelial system and organs:
- Lungs and pleura
- Skin and mucous membranes
- Replication at these locations → cell death and inflammation → clinical manifestations
Coxsackie group A viruses are the principal cause of this self-limiting disease.
- Vesicular lesions with surrounding erythema of the:
- Soft palate
- Lesions evolve into shallow ulcers before healing.
Hand, foot, and mouth disease
Hand, foot, and mouth disease is a mild, self-limiting disease caused by the coxsackie group A virus.
- Mouth pain
- Oral enanthem:
- Initially erythematous macules
- Progresses to vesicles with surrounding erythema
- Eventual rupture → superficial ulcers with grey-yellow base
- Most commonly involve the tongue and buccal mucosa
- Appearance may be:
- Not painful or pruritic
- Hands (palms)
- Feet (soles)
- Appearance may be:
|Condition||Coxsackie group||Signs and symptoms|
|Acute hemorrhagic conjunctivitis||A|
|Epidemic pleurodynia (Bornholm disease)||B|
|Exanthem||A and B|
|Aseptic meningitis||A and B|
|Encephalitis||A and B|
|Flu-like symptoms||A and B|
Diagnosis and Management
The diagnosis is usually made clinically. The following may be performed if the diagnosis is uncertain or in the case of severe disease:
- Viral culture
- Serology has limited value.
Most coxsackievirus infections are self-limiting, and management is largely supportive.
- Analgesics for pain:
- Unproven therapeutic options for severe disease or immunocompromised patients:
- IV immunoglobulin (IVIG)
- Rarely used
- Not FDA approved
- Minimize contact with infected individuals.
Comparison of Enteroviruses
The following table summarizes the characteristics and diseases associated with different enteroviruses:
URI: upper respiratory tract infection
- Respiratory syncytial virus infection: an infection of the lower respiratory tract caused by an enveloped ssRNA virus. The infection presents with fever, cough, wheezing, tachypnea, and crackles. The diagnosis is made clinically. Management is supportive.
- Rhinovirus infection: an infection caused by an acid-labile, positive-sense RNA virus of the Picornaviridae family. As the rhinovirus is inactivated by gastric acid, it can only affect the nasal mucosa and conjunctiva and cause edema of subepithelial tissues. A rhinovirus infection presents as a “common cold” with mild upper respiratory symptoms. Diagnosis is clinical, and the disease is typically minor and self-limiting. Management is supportive.
- Infectious mononucleosis: a disease caused by the EBV, which is characterized by fever, fatigue, lymphadenopathy, and pharyngitis. Complications can include viral meningitis and myocarditis. The diagnosis is based on clinical features and testing, such as a positive heterophile antibody test or serology. Management is supportive.
- Bacterial meningitis: an acute infection of the meninges. Patients present with headache, fever, nuchal rigidity, and rapid clinical deterioration. A lumbar puncture is performed to make the diagnosis. Unlike the findings of aseptic meningitis, CSF analysis will show a turbid fluid having low glucose levels and a high WBC count with neutrophil predominance. Gram stain and culture are used to identify the causative bacteria. Treatment includes antibiotics and corticosteroids.
- Adenovirus infection: an infection caused by a non-enveloped double-stranded DNA virus, which typically causes mild respiratory infections, though conjunctivitis, atypical pneumonia, gastroenteritis, meningoencephalitis, and myocarditis can also occur. The diagnosis is typically clinical, but PCR testing may be performed for severe disease. Management is supportive.
- West Nile virus infection: an infection caused by Flavivirus. The majority of patients will be asymptomatic or have headaches, myalgias and arthralgias, vomiting, diarrhea, or a rash. Some patients develop encephalitis, meningitis, or flaccid paralysis. The diagnosis can be made with serology, PCR, and viral cultures. Management is supportive.
- Lyme disease: a tick-borne infection caused by the gram-negative spirochete, Borrelia burgdorferi. The presentation of Lyme disease can vary depending on the stage of the disease and may include the characteristic erythema migrans rash. Neurological, cardiac, ocular, and joint manifestations are also common in later stages. Diagnosis of Lyme disease relies on clinical findings and tick exposure, and is supported by serological testing. Antibiotics are used for treatment.
- Ehrlichiosis and anaplasmosis: tick-borne infections caused by Ehrlichia chaffeensis and Anaplasmosis phagocytophilum, respectively. Symptoms of ehrlichiosis and anaplasmosis include fever, headache, and malaise. Disseminated intravascular coagulation, multiorgan failure, and coma can also occur with severe disease. Diagnosis is made using PCR. Treatment of both diseases is with doxycycline.
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