Picornaviruses Notes

NOTES NOTES PICORNAVIRUSES MICROBE OVERVIEW ▪ Have small, cytoplasmic, single-stranded, linear, positive-polarity RNA Taxonomy ▪ Family Picornaviridae; 35 genera (e.g. Enterovirus, Apthovirus, Cardiovirus, Rhinovirus, Hepatovirus) Morphology ▪ Non-enveloped ▪ Icosahedral capsid ▪ Diameter ▫ 27–30nm(smallest of RNA viruses) ▪ Genome length ▫ About 2500nm Transmission ▪ Hosts: humans, birds, vertebrates OSMOSIS.ORG 487

COXSACKIEVIRUS osms.it/coxsackievirus PATHOLOGY & CAUSES SIGNS & SYMPTOMS HFMD (hand, foot and mouth disease) ▪ Clinical syndrome characterized by oral enanthem; maculopapular/vesicular rash of hands, feet ▫ Common exanthem in children and adults ▫ Most commonly caused by coxsackie A virus HFMD ▪ Mouth, throat pain ▫ Young children may refuse to eat ▪ Mild fever ▪ Lethargy ▪ Oral enanthem: on tongue, buccal mucosa ▫ Erythematous macules → vesicles with halo of erythema ▪ Exanthem: macular, maculopapular, vesicular; nonpruritic, usually not painful ▫ Involves hands (including palms), feet (including soles), buttocks, legs, arms ▫ Palmer and plantar desquamation 1–3 weeks after presentation Herpangina ▪ Benign clinical syndrome characterized by fever, papulo-vesiculo-ulcerative oral enanthem ▫ Most commonly caused by coxsackie A virus ▪ Transmission person to person via oralfecal route or respiratory aerosols → incubation for 3–5 days → virus replicates in the submucosal lymphoid tissue of pharynx or lower intestine → spread to regional lymph nodes (minor viremia) → dissemination throughout the body → major viremia RISK FACTORS ▪ Age ▫ Most common in children <10 years ▪ Season ▫ Spring, summer, autumn ▪ Poor hygiene Herpangina ▪ Acute onset with high fever; may present with febrile seizure ▪ Anorexia, emesis, irritability common in young children ▪ Malaise, headache, sore throat, dysphagia, abdominal pain ▪ Papulovesicular lesions in throat ▪ Additional findings ▫ Neck stiffness, positive Kernig sign, cervical adenitis COMPLICATIONS ▪ ▪ ▪ ▪ ▪ ▪ Reduced oral intake → dehydration Rhombencephalitis Acute flaccid paralysis Aseptic meningitis Myocarditis Pancreatitis Figure 89.1 Characteristic mouth lesions of hand, foot and mouth disease. 488 OSMOSIS.ORG

Chapter 89 Picornaviruses DIAGNOSIS LAB RESULTS ▪ Throat, stool, vesicular fluid samples for cell culture/polymerase chain reaction (PCR) TREATMENT MEDICATIONS ▪ Analgesia, fluids ▪ No specific antiviral therapy OTHER INTERVENTIONS ▪ Treat complications (e.g. neurological, cardiovascular) Prevention ▪ Infection control practices ▫ Hand hygiene; isolate hospitalized individuals; contact precautions Figure 89.2 Characteristic mouth lesions of hand, foot and mouth disease. HEPATITIS A VIRUS osms.it/hepatitis-a-virus PATHOLOGY & CAUSES ▪ Hepatitis A virus (HAV) → hepatitis A infection ▪ Reservoir ▫ Humans ▪ Transmission ▫ Oral-fecal route ▪ Infection of hepatocyte by HAV → replication hepatocyte cytoplasm→ hepatocellular damage → HAV-specific CD8+ T lymphocytes, natural killer cells destroy infected hepatocytes → host’s immune response to HAV → hepatic injury ▪ Infection usually self-limiting (does not become chronic); results in life-long immunity (IgG antibodies) RISK FACTORS ▪ Poor sanitation ▪ Limited access to clean water ▪ Travel to low resource countries COMPLICATIONS ▪ Cholestatic hepatitis: characterized by prolonged jaundice ▪ Relapsing hepatitis: symptoms relapse after acute illness ▪ Autoimmune hepatitis: chronic hepatitis, characterized by hyperglobulinemia SIGNS & SYMPTOMS ▪ Usually self-limiting; fulminant hepatic failure rare ▪ Incubation period ▫ 28 days (average) ▪ Symptoms ▫ Nausea, vomiting, anorexia, fever, malaise, abdominal pain OSMOSIS.ORG 489

▪ Signs ▫ Dark urine, pale stools, jaundice (peaks within two weeks of infection), pruritus, scleral icterus, hepatosplenomegaly DIAGNOSIS LAB RESULTS ▪ Elevated serum aminotransferase levels may indicate diagnosis ▪ Established diagnosis by detection of serum IgM anti-HAV antibodies ▫ Serum IgG antibodies in absence of anti-HAV IgM indicates previous infection/vaccination TREATMENT Prevention ▪ Hepatitis A vaccination ▪ Immune globulin; passive immunization indicated for ▫ Immunocompromised individuals (unable to amount immune response to HAV vaccine) ▫ < 12 months, > 40 years ▫ Individuals with chronic liver disease ▫ Allergy to hepatitis A vaccine OTHER INTERVENTIONS Prevention ▪ Infection control practices ▫ Handwashing; avoid tap water, raw foods in poorly-sanitized areas MEDICATIONS ▪ Medications known to cause liver damage should be avoided/used with caution POLIOMYELITIS (POLIO) osms.it/poliomyelitis PATHOLOGY & CAUSES ▪ Infectious disease caused by poliovirus ▪ Characterized by (rare but devastating) cases of muscle weakness, permanent paralysis ▫ Most infections remain asymptomatic ▫ Some experience minor symptoms (e.g. fever, sore throat, headache) ▫ Some may recover from muscle paralysis ▪ Natural host ▫ Humans ▪ Transmitted by fecal-oral route; less commonly via respiratory droplets ▫ Asymptomatic, infected persons may shed virus ▪ Pathogenesis ▫ Oral entry → poliovirus infects cells 490 OSMOSIS.ORG of mouth, nose, throat → spread to lymphatics → primary replication in tissue of gastrointestinal tract and oropharynx → primary (minor) viremia → invasion of the central nervous system → replication in motor neurons of spinal cord, brain stem, or motor cortex → destruction of motor neurons → secondary (major) viremia and paralysis RISK FACTORS ▪ Unvaccinated status ▪ Travel to countries endemic for poliovirus COMPLICATIONS ▪ Post-polio syndrome ▫ Slowly developing muscle weakness similar to initial infection ▪ Bulbar poliomyelitis

Chapter 89 Picornaviruses ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▫ Infection of brain stem; may lead to drooling, aspiration pneumonia, respiratory muscle paralysis Skeletal malformations due to muscle paresis, paralysis Equinus foot (club foot) Stunted growth Osteoporosis, bone fractures Urinary tract infections, kidney stones Paralytic ileusv Myocarditis, cor pulmonale Acute flaccid paralysis ▪ Complete paralysis; spinal, bulbar, bulbospinal ▪ Quadriplegia/respiratory failure ▪ Reflexes absent ▪ Sensation intact SIGNS & SYMPTOMS Minor illness/minor viremia ▪ Abortive poliomyelitis ▫ Nausea ▫ Vomiting ▫ Abdominal pain ▫ Constipation ▫ Diarrhea ▫ Sore throat ▫ Mild fever ▫ Coryza Major illness/major viremia ▪ Involvement of central nervous system (CNS) ▪ Nonparalytic aseptic meningitis ▪ Headache ▪ Neck, back, abdominal, extremity pain ▪ Fever ▪ Vomiting ▪ Lethargy ▪ Irritability Paralytic disease ▪ Varies from one muscle to muscle group ▪ Reduced tone; often asymmetric ▪ Affects proximal muscles > distal muscles ▪ Affects legs > arms ▪ Worsens over 2–3 days Figure 89.3 An individual with atrophy of the mucles of the right leg caused by polio. DIAGNOSIS ▪ Acute-onset flaccid paralysis LAB RESULTS ▪ PCR detection of poliovirus RNA from cerebrospinal fluid; cerebrospinal fluid (CSF) may also show ↑ leukocytes, ↑ protein ▪ Alternative ▫ Detection by poliovirus isolation, culture (from throat secretions); comparison of viral titers in acute, convalescent sera OSMOSIS.ORG 491

TREATMENT MEDICATIONS Antiviral therapy ▪ Role remains uncertain Prevention ▪ Passive immunization: gamma globulin; reduces infected individuals’ disease severity ▪ Inactivated poliovirus vaccine ▫ Given in high-income countries ▫ Cannot revert to paralytic form ▪ Live attenuated oral poliovirus vaccine ▫ Inexpensive, easy to administer; given in countries where virus endemic ▫ Risk: attenuated virus reverting to paralysis-causing form OTHER INTERVENTIONS ▪ Physical therapy; respiratory failure → mechanical ventilation ▪ No effective treatment for restoring motor neuron function Figure 89.4 An individual with polio inside an iron lung, which provided mechanical ventilation by creating negative pressure. RHINOVIRUS osms.it/rhinovirus → host inflammatory response to virus → elaboration of inflammatory mediators, recruitment of polymorphonuclear leukocytes → symptoms → illness lasts about 1–2 weeks PATHOLOGY & CAUSES ▪ The causative agent of most common colds ▪ > 100 serotypes ▪ Most frequent human infectious disease, preferentially infecting the upper respiratory tract ▪ Usually causes mild, self-limiting disease, with increased incidence in early autumn (September–November) and in Spring (March–May) ▪ Predisposes to other infections ▫ Otitis media in children, community acquired pneumonia ▪ Potential to infect the lower respiratory tract → exacerbation of asthma, chronic bronchitis ▪ Inoculation of the nose or conjunctiva → intracellular adhesion molecule-1 (ICAM1) attachment → incubation (2–4 days) 492 OSMOSIS.ORG Transmission ▪ Airborne droplet nuclei/aerosols (from sneezing, coughing) ▪ Droplet transmission ▪ Direct contact (e.g. hand contact → rubbing eyes, nasal mucosa) ▪ Fomites RISK FACTORS ▪ ▪ ▪ ▪ ▪ Fatigue (insufficient sleep) Psychological stress Work in daycare/schools Smoking Underlying chronic disease

Chapter 89 Picornaviruses COMPLICATIONS ▪ ▪ ▪ ▪ Sinusitis Lower respiratory tract disease Asthma exacerbations Acute otitis media SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪ Cough Coryza Rhinorrhea (clear/purulent) Sore throat Myalgia Fatigue, malaise Headache Anorexia Fever DIAGNOSIS DIAGNOSTIC IMAGING ▪ Lower respiratory tract infection → chest radiograph OTHER DIAGNOSTICS ▪ Nasal cavity examination: swollen, erythematous nasal turbinates TREATMENT MEDICATIONS ▪ Analgesics ▫ Relieve headache, ear pain, myalgia ▫ E.g. acetaminophen, nonsteroidal antiinflammatory drugs ▪ Antihistamine/decongestant combinations ▪ Cough suppressants OTHER INTERVENTIONS ▪ Zinc supplements at initial infection may reduce duration OSMOSIS.ORG 493