Viral infections in childhood Flashcards
describe the structure of a virion
- nucleic acid
- protein coat - which is called the capsid
- might or might not have a envelope
- nucleocapsid = combination of DNA/RNA with repeating structures of capsomeres
what is a nucelocapsid
= combination of DNA/RNA with repeating structures of capsomeres
what are the different types of viruses
DNA
RNA
- Double-stranded DNA
- (Single-stranded DNA in parvovirus)
- Single-stranded RNA (+ or – polarity)
- (Double-stranded RNA in reoviruses)
what virus has single stranded DNA
- single stranded DNA in parvovirus
what virus has double stranded RNA
= reovirus
how is most viral diagnosis made
- by PCR
what are viruses
- these are obligate intracellular parasites meaning that they are completely dependent on the cellular machinery
what are the steps in the viral life cycle
ATTACHMENT
ENTRY
UNCOATING
SYNTHESIS OF VIRAL COMPONENTS
ASSEMBLY AND RELEASE
describe how viral attachement happens
Binding sites on the virus
Receptors (+/- co-receptors) on plasma membrane of cell
what is cell tropism
“Cell tropism” – determines what cell the virus can get into
what does it mean if the cell is permissive
- this means it has all the right intracellular components required by the virus to replicate
- in order for the virus to be able to replicate and survive it has to enter a permissive cell
describe how the virus enters the cell
- Takes from seconds to several minutes
- Enveloped viruses undergo membrane fusion with the cell membrane
- May undergo receptor-mediated endocytosis
where does uncoating of the virus take place
Endosome (receptor-mediated endocytosis) – due to low pH and lysosomal enzymes
Cytosol
Nuclear membrane
what happens once uncoating of the virus has taken place
- the virus can synthesis more copies of itself
how does synthesis of viral components take place
Requires viral mRNA to enable viral polypeptides and nucleic acid to be synthesized by cell machinery
DNA viruses that enter the nucleus can use only cellular enzymes
All other viruses must synthesize their viral mRNA
May carry their own enzymes (eg RNA polymerase, reverse transcriptase
describe how positive and negative polarity RNA viruses can synthesise there viral components and the difference between them
Positive polarity means it already has its RNA to be activated as messenger RNA to be translated and make more virions
Negative polarity – has opposite compoesnation of RNA it needs to make virons, therefore RNA polymerase is needed to mke positive polarity RNA which can be processed by the cell
how does the virus release from the cell
- cell lysis - if this happens this can kill the cell which might not be a good thing for the virus in the long term
- budding (without cell death)
several thousands of …
Several thousand viral particles can be produced per cell
name some DNA enveloped viruses
Herpes viruses
- Herpes simplex
- Varicella zoster
- CMV
- Epstein-Barr
- HHV 6/7/8
Hepatitis B
Poxviruses
name herpes viruses
Herpes simplex Varicella zoster CMV Epstein-Barr HHV 6/7/8
name some non-enveloped DNA viruses
Papillomavirus
Adenovirus
Parvovirus (ssDNA)
- spell out PAP, cervical smar for papillomarvirus
what do all enveloped viruses typically cause
- typically cause a rash type illness
How does herpes simplex virus present in the adult
- get herpes labials
- cold sore
- herpetic whitlow
how does Herpes simplex virus present in neonates
Disseminated HSV
- Sepsis-like syndrome
- Hepatitis, coagulopathy
HSV encephalitis
- Fever, seizures
- Haemorrhagic infarction of white matter and cortex
How do you treat disseminated HSV
- IV Aciclovir
what are the two HSV presentations in neonates
Disseminated HSV
HSV encephalitis
describe what virals are like in early life
Often more severe disease – immature antiviral immunity can cause this
More likely to become chronic
Prolonged shedding of the infection - don’t clear the infection as quickly for example CMV can take months or years for the immune system can bring this under control
What is immunity like in early life
- Has evolved to protect babies against extracellular pathogens (bacteria and fungi) which can be rapidly fatal
- Consequence is that antiviral immunity is less well developed in early life
describe the characteristics of cytomegalovirus
- self-limiting illness
- sometimes presents like a mononucleosis like illness such as EBV
- severe disease in immunosuppressed
what is the most comments congenital infection in developed countries
- CMV
what is the main symptoms that CMV can cause
- sensorineural hearing loss
How do you treat CMV
For babies with symptomatic disease:
- IV ganciclovir (requires a central line) or oral valganciclovir (pro-drug of ganciclovir) – inhibits DNA synthesis
What can treatment of CMV reduce
6 months of treatment reduces hearing loss and improves neurodevelopment
what are the problems with the treatment of CMV
- Neutropenia,
- thrombocytopenia
- IV access
- Long term fertility/malignancy risk
what are the symptoms of CMV
- sensioruneal deafness
- calcification in the brain
- hydrocephalus
- extra medullary haemopoitesis
- hepatosplenomeagly
what people is varicella zoster virus severe in
Severe in immunosuppressed
- Steroid treatment
- Chemotherapy
what can varicella zoster virus cause to happen
- can have complications especially in secondary bacterial infection such as staphylcocous and streptococcus that can get in the lesions
what can chicken pox cause to happen in adults
- more server disease - if the host has a robust immune response this can cause pathology this is what happens to adults as they have a more robust immune system than children
- pneumonitis
- particular serve in pregnancy women
what are the symptoms of varicella zoster virus
- rash - lasts 4-5 days
- once the lesions have crusted over they are no longer transmittable
what is the goldilocks effect
need an immune response that is:
- not too small - severest disease such as neonatal HSV
- not too big - immunopathology e.g adult VZV
- just right
what are the symptoms of EBV in early life versus older children
Usually asymptomatic in early life Infectious mononucleosis (glandular fever), typically 15-25 yrs old
what does EBV stand for
Epstein-Barr virus
how does EBV spread
- spread by salvia
EBV presents differently depending on …
geography
what does EBV cause in Africa
- Burkitt’s lymphoma
- EBV infection at early age
- Plus chronic immunosuppression due to endemic malaria
how does EBV effect host immunity
Lymphoma in children and adults with advanced HIV disease - people who are immunuosupressed can get an advanced tumour that is driven by EBV
Post-transplant lymphoproliferative disease
what is HHV 6 and 7 cause
Roseola infantum
when do people have roseola infantum
Also known as exanthem subitum
Common between 6mo-2yrs of age
what are the symptoms of Roseola infantum
Sudden onset of high fever, lasts few days then suddenly stops, rash appears
Hep B - how does the age of the infection effect how long you have then infection
- if you are born with the infection then you are likely to have chronic infection
- as you get older there is a lesser chance that you get chronic HepB
How does the chances of getting symptoms vary with age in Hep B
- as you get older you are more likely to present with symptoms even though you won’t get chronic HepB whereas if you are younger you might not present with symptoms but you have chronic HepB
what are the consequences of chronic Hep B infection
Cirrhosis
Hepatocellular carcinoma
how is hepatitis B passed from mother to child
- chronic Hep B can be passed down to the baby
- want to intervene around the time of brith, the E antigen is found in the virus and this tells us about how infectious, if you are E antigen positive then the virus is dividing more rapidly and therefore the risk of transmission is higher
How do you reduce the risk of transmission at birth
- give Hep B virus vaccine at birth and then at 1 month of age
- and HBIG as well (hepatitis B immunoglobulin)
what increases your risk of transmission in Hep b
eAg-negative 10-20%
eAg-positive 90%
- being eAg positive - this is because the virus is dividing more rapidly if it has this therefore there is a higher risk of transmission
what does poxvirus cause
smallpox
molluscum contagiosum
how was small pox eradicated
Routine vaccination
Isolation of cases lead to outbreak control
what are the factors of small pox that aided eradication
Severe disease, easy to identify
Slow spread, poor transmissibility
No carrier state, no animal reservoirs
Easy vaccine to produce and distribute
What is molluscs contagiosum
- this is often found in most areas such as in the groin and axilla
- spread by direct contact or fomites
- mild but can persist fore several years
what is a cause of cervcial cancer
Papillomavirus
what are the serotypes of HPV that can cause cancer
HPV 16 and 18
what does HPV stand for
human Papillomavirus
what HPV serotypes lead to genital warts
HPV 6 and 11
what vaccinations are given for HPV
Old:
Cervarix vaccine, bivalent (16, 18)
Current:
Gardasil vaccine, quadrivalent (6, 11, 16, 18)
–given at age 12-13 years
what can adenovirus cause
URTI / pneumonia
Conjunctivitis
Diarrhoea
Disseminated disease in immunocompromised hosts
when is parvovirus not susceptible
- people who do not express the group P antigen are not susceptible as they cannot be infected
Who is highly susceptible to parvovirus
- have haematological problems such as sickle cells disease which can lead to an aplastic crisis
- parvovirus can replicates in rapidly dividing cell which occurs in people who have haematological problems
What are the symptoms of parovirus B19
Asymptomatic
‘Slapped cheek’ syndrome
Arthropathy (adults) - present with disabling arthritis
Aplastic crisis
Fetal loss in pregnant women
What are important RNA enveloped virus
Measles, mumps, rubella
RSV, influenza, parainfluenza
Hepatitis C
HIV
- MMR, RSV, influenza, parainfluenza - respiratory in presentation
- Hepatisis C, HIV - blood infections
What are non enveloped RNA viruses
Rotavirus
Enteroviruses (includes polio)
Hepatitis A
- broadly cause enteric infections and gut infections
what is the incubation period for measles
7-14 days
what are the original symptoms of measles
and then what happens after 2 days and then 2 days after
Fever
Cough
Conjunctivitis
Miserable
then after 2 days get kopek spots
then after another 2 days a rash develops - usually starts behind the ear and spread downwards
where does the measles rash usually start
- behind the ear and spread downwards
what are complications of measles
Rare complication
Often in children who were infected at young age (<2 yrs)
Present years later with neurodegenerative disease
and they have developed Subacute sclerosing pan-encephalitis (SSPE)
what are the symptoms of rubella
- Fever
- occipital lymphadenopathy
- Mild rash
what are the symptoms of congenital rubella
EYES: cataracts, micro-ophthalmia, glaucoma
EARS: sensorineural deafness
HEART: pulm artery stenosis, VSD
- Low birth weight, rash, microcephaly
what are the three typical congenial infections that we test for
- rubella
- CMV
- toxoplasmosis
what is bronchiolitis caused by
Viral infection of infants (70% RSV)
what is bronchitis
Inflammation of bronchioles
How does bronchiolitis present
- cough
- respiratory distress
- wheeze
who can bronchiolitis be severe in
- preterm
- congenital heart disease
What is the treatment for bronchiolitis
Palivizumab (monoclonal Ab) for RSV prophylaxis - given monthly as an injection to high risk babies which prevents them from getting RSV infection
How is Hepatitis c treated
- direct antiviral agent’s (DAAs) in past few years
- 8-12 weeks treatment course with greater than a 95% cure
- little experience in children yet
children below the age of 3 years will….
Many children below 3 years of age will spontaneously clear infection and no indication for treatment at young ages
why is there little transmission of hepatitis C in children
- lower risk of mother to child transmission, approximately 5%
what type of virus is HIV
retrovirus
how do you prevent mother to child transmission of HIV
- NII
- AZT
- Dural ART
- HAART = 1% transmission rate - can have a normal vaginal delivery
HIV infection is more…
severe in infants than adults
describe HIV in infants
- Higher viral loss
- rapid progression
- more likely to develop diarrhoea
- wasting
there are fewer drugs for …
HIV in infants
- toxicity
- long term costs
what are the symptoms of rotavirus
Fever
vomiting
watery diarrhoea
what vaccines can now be used for rotavirus
RotaTeq
RotaRix (included in UK schedule since 2013
When was the rotavirus vaccine introduced
2013
how is the rotavirus vaccine given
Oral vaccines are easier to give in mass immunization campaigns
what is the rotavirus given
2 and 3 months of age
why does the oral rotavirus work less well in areas such as Africa and Asia
- due to the gut problems (enteropathy)
what viral infections lead to latency
CMV, EBV, VZV
what viruses can be chronic
Hepatitis B
what virus is more server and less serve in children
- HSV more severe
- VZV less serve
what viruses can be transmitted from mother to child
hepatitis B, HIV
what viruses can cause cancer
papilloma, EBV, hep B
