Childhood Viruses Flashcards
Viruses of childhood (causing viremia)
Measles Virus Mumps Virus Rubella Virus Parvovirus B19 Varicella zoster
Why are vaccines against Measles, Mumps, and Rubella so effective?
- Natural infection protects against re-infection and disease
- Each virus has only a single antigenic type - key to vaccine effectiveness
- Each virus has a systemic replication phase prior to infecting target organ where symptoms develop - antibodies developed as a result of immunization can limit or block virus at this stage
- Humans are the only known host
Cilnical consequences of measles virus infection
Measles - cough, conjunctivitis, coryza, photophobia, Koplik spots
Atypical Measles - more intense rash, petechiae, purpura
Postmeasles encephalitis - acute onset of headache, confusion, vomiting
Subacute sclerosing panencephalitis - CNS manifestations
Which complication of the measles virus is the most likely to cause death in children?
Pneumonia
Measles, mumps, rubella vaccine (MMR)
Live attenuated viruses given as combination
- 12-15 months and 4-6 years
Induce strong long lasting antibody response - prevents infection of target organ
Measles is particularly endemic in ______
Kenya
Between 2000 and 2010, measles deaths has decrease __%
74
Mumps clinical syndromes
Infections often asymptomatic
Parotitis - almost always bilateral and accompanied by fever
Swelling of other glands
CNS involvement
Disease mechanisms of Mumps virus
1) Virus infects epithelial cells of respiratory tract
2) Virus spreads systemically by viremia
3) Infection of parotid gland, testes, and central nervous system
4) Principal symptom is swelling of parotid glands caused by inflammation
5) Cell mediated immunity is essential for control of infection and responsible for causing some of the symptoms - antibody is not sufficient because virus spreads from cell to cell
Effective live attenuated vaccine (Mumps)
Humans only host
Only one serotype
Lifelong immunity
Rubella German Measles (characteristics)
- Is a togavirus
- Only infects humans
- Has only one serotype
- Does not cause readily detectable cytopathologic effects
- Can cause asymptomatic infections
Clinical diseases caused by rubella virus
Children:
Adults:
Neonates younger than 20 weeks:
Children: Mild rash disease
Adults: More severe disease with arthritis or arthralgia
Neonates younger than 20 weeks: congenital defects
Prominent Clinical Fingings in Congenital Rubella Syndrome
Cataracts and other ocular defects Heart defects Deafness Intrauterine growth retardation Failure to thrive
Parvovirus B19 (characteristics)
- Singe stranded DNA virus
- Icosahedral, non enveloped
- Replicates in nucleus
- Dependent on host DNA replication functions
Bocavirus (Parvovirus)
A newly discovered parvovirus responsible for respiratory and gastrointestinal tract infections
Parvovirus B19
Infection:
Receptor:
Replication:
Infection: infects actively replicating red blood cell progenitors in blood marrow
Receptor: Blood group P antigen (globoside) - expressed on mature erythrocytes
Replication: Uses cellular DNA polymerase to replicate
Parvovirus time course of infection
0-5 days: Incubation
5-14 days: Lytic, infection phase
21-28 days: Noninfectious immunologic phase
Parvovirus B19 clinical features
Usually causes clinically inapparent infection
Clinically apparent disease: Erythema infectiosum (Fifth disease)
- Bright red cheeks
- Maculopapular rash
- Circulating immune complexes, do not fix complement, but cause rash, arthralgia and arthritis
Complications of Pavrvovirus B19 infection
Causes anemia due to reduced cell number and reduced hemoglobin
In chronic hemolytic anemia patients virus causes aplastic crisis due to destruction of red cell progenitors
When transmitted to the fetus (ventricle): Can cause still births, generalized edema, anemia, congestive heart failure
Rotavirus (Reo) and Norovirus (Calici) Transmission
Fecal oral transmission
Replication in GI tract
Gastroenteritis, Diarrhea, Vomiting
Most common cause of severe diarrheal illness requiring hospitalization in infants and young children
Rotavirus
Rotavirus - “wheel”
Genome and characteristics
11 double stranded RNA segments encoding 12 genes
No envelope - three layer capsid
Multiple antigenic groups (A-E)
Group A - most common cause of human disease
Great diversity of antigenicity - multiple serotypes
Co-infection can lead to reassortment of segments (mutation rate 1000X higher than DNA viruses)
Antigens and proteins on Rotavirus molecule
VP4 neutralization antigen (P serotype - 28)
VP7 neutralization antigen (G serotype - 19)
VP6 subgroup antigen (A-E)
Non-structural proteins (NSPs)
NSP4 - acts as enterotoxin
Mechanisms by which rotaviruses cause diarrhea
1) infection of initial cell by luminal virus leads to entry, uncoating, transcription and translation of viral proteins
2) Intracellular NSP4 induces release of Ca2+ from internal stores - primarily the ER increasing internal calcium
3) NSP4 produced by the infection disrupts tight junctions allowing paracellular flow of water and electrolytes
4) Increase in calcium also disrupts the microvillar cytoskeleton - stimulates enteric nervous system which induces Cl- secretion
Rotavirus Vaccines
RotaTeq:
Rotarix:
RotaTeq:
- Approved by the FDA in 2006
- Live attenuated vaccine, humans - bovine reassortant, mixture of 5 different virus types
- Given 3 times orally between ages 2, 4 and 6 months
Rotarix:
- Approved by FDA in 2008
- Live attenuated single human strain, based on most prevalent circulating strain globally
- Given 2 times orally at about 2 and 4 months
Considerations for Rotavirus Vaccines
- Vaccine related intussusception
- Possible reversion to virulent strain
- Viremia - side effects
- Shedding of virus by vaccine recipients
- Immunosuppressed children
Norovirus
Discovery:
Symptoms:
Discovery: Discovered in 1972 in an Ohio outbreak
Symptoms: Major cause of acute gastroenteritis in school-aged children and adults
Norovirus illness is most common in ______
Winter
Norovirus Epidemiology Low infectious dose: Prolonged asymptomatic shedding: Stability: Substantial strain diversity: Lack of lasting immunity:
Low infectious dose: person to person spread, secondary spread
Prolonged asymptomatic shedding: Increased risk for secondary spread regarding food handlers
Stability: Difficult to eliminate from contaminated water - virus maintained in ice and steamed oysters
Substantial strain diversity: Requires composite diagnostics
Lack of lasting immunity: Childhood infection does not protect from disease in adulthood
Targets for the design of antiviral therapies (for norovirus)
Pro - viral protease
Pol - viral polymerase (RNA dependent)
Enteroviruses
Coxsackie virus
Echovirus
Clinical syndromes associated with major enterovirus groups
Paralytic disease
Encephalitis, meningitis
Respiratory tract infections
Undifferentiated fever
Which month has the highest incidence of enterovirus cases
August
Viral meningitis occurs mostly in children younger than age __
5
Meningitis
Common symptoms in infants:
Common symptoms in adults:
Common symptoms in infants: - fever - irritability - poor eating - hard to awaken Common symptoms in adults: - Headache - fever, chills - nausea, vomiting - stiff neck - sensitivity to light
Coxsackie A viruses - Hand foot and mouth disease
Symptoms:
Mild fever Sore throat Fatigue Loss of appetite Vesicular lesions
