Viruses Flashcards
What is good about ELISA?
Remember in low incidence setting most positives are false positives
Excellent sensitivity but more limited specificity
Technically simpler, automatable and objective readout
Western Blot Assay pros and cons?
Limited sensitivity but excellent specificity
Interpretation of results leads to subjective element
Often requires multiple bands to be positive
Antigen detection Assay pros and Cons?
Amenable to multiple point of care formats
Can be very robust
Element of subjectivity in reading result
PCR assays pros and cons?
Very good sensitivity and specificity
Assay can be over sensitive
Sampling error can occur
Needs sophisticated equipment
Isothermal amplification now possible
What is wrong with crude antigen tests?
False positive rates higher
Where do you need to test a specificity and sensitivity
In endemic areas
Negatives need to come from an endemic area
What does IgG 4 positive mean?
It means active disease
IgG
How long are you immune positive for following infection?
Antibodies last several years
When are you trichinella positive?
Not when you are symptomatic
Only have antibodies later on
Where is hep A and who is infected?
It’s worldwide, more common in LMIC
In LMIC most children >90% have been infected before the age of 10
How is hep A transmitted?
Faecal-oral, contaminated food or water
Person to person contact
How does hep A present in adults? Phases
Incubate 14-28 days
Prodromal phase lasts 7 days and includes fever, malaise, anorexia, nausea, vomiting and abdo pain
Icteric Phase: Jaundice, clerical icterus, dark urine and pale stools
How does hep A present in children?
Usually asymptomatic
Lab abnormalities in hep A?
Elevation of ALT>AST (>1000)
Elevation of serum bilirubin and ALP (Up to 400)
ALT and AST rise precedes bilirubin elevation and peaks 1 month after exposure
Hyperbilirubinaemia peaks 7-10 days
What is the general clinical course of hep A?
Usually self-limiting
Rarely causes chronic disease
What are the unusual cx of hep A?
Acute hepatic failure
Relapsing hepatitis
Prolonged cholestasis
Autoimmune hepatitis
What are some of the extra-hepatic manifestations?
Arthralgias, arthritis, Rash, immune complex disease
What antibody becomes positive first?
IgM, lasts several weeks or months
IgG increases later, but provides lifelong protection
How do you diagnose Hep A?
Acute infection: IgM anti-HAV
Total anti HAV antibodies measures both IgG and IgM, therefore cannot tell difference between acute and chronic
What is treatment and prevention of hep A?
Supportive therapy for tx
Vaccine for prevention: Inactivated HAV, 2 doses
A live attenuated vaccine which is 1 dose is available in some countries
What do you do for post-exposure prophylaxsis of hep A?
HAV vaccine or immunoglobulin within 2 weeks of exposure
How many genotypes of HEV?
4 genotypes that affect humans (HEV1-HEV4)
Where is HEV1 and HEV2 found?
LMIC such as Africa and Asia, some outbreaks in Mexico
Where is HEV3 and HEV4 found?
More higher income countries, China especially
What is reservoir for HEV1 and 2 vs HEV3 and HEV4?
Humans for HEV1 and 2
Mainly swines in HEV3 and HEV4
What is tx of HEV1 and HEV2?
Contamination of drinking water supplies with human faeces
Iatrogenic
What is tx of HEV3 and HEV4?
Consumption of contaminated animal meat or contact with infected animals
Iatrogenic
How is HEV transmitted?
Large waterborne transmission with HEV-1 and HEV-2
Zoonotic transmission of HEV 3 and HEV 4
What are the clinical manifestations of hep E?
Incubate for 2-6 weeks
Get Acute Icteric hepatitis: occurs in 5-30% of cases, more commonly assoc with HEV1 and 2
lasts 2-6 weeks, Prodromal phase of 7 days
What are the extra-hepatic manifestations of hep E?
GBS, encephalitis and myelitis
Renal cx such as IgA nephropathy, membranoproliferative glomerulonephritis, cryglobulinaemia
What is the clinical course of Hep E?
In immunocompetent patients HEV usually resolves spontaneously
Chronic infection occurs more common with HEV 3 and HEV4, this is mainly in immunocompromised patients
Pregnant women get higher risk of symptomatic disease and acute liver failure with HEV1 and HEV2
How do you Dx acute hep E? chronic hep E?
Detection of anti-HEV IgM
Chronic HEV infection- detect HEV RNA in serum
Tx of Hep E?
Most immunocompetent individuals do not require antivirals
Ribavirin can lead to faster recovery times but is CI in pregnancy
How do you prevent hep E?
Boil and chlorinate water
Heat food >2 mins
Screen blood banks
Recombinant vaccine only available in China
What genotype os responsible for most HCV infections?
Genotype 1 accounts for 44% of all HCV infections
Genotype 3: More common in LMIC especially south Asia
Genotype 4: North Africa and Middle East
How is HCV transmitted?
Medical procedures
Tattoing
IVDU
Needlstick injuries
Mother to child and sexual transmission is possible, HIV infection increases risk of HCV transmission
What is the acute course of HCV?
Not typically clinically apparent
Fulminant hepatitis is rare
How does chronic HCV present?
Majority of patients develop chronic hep C (75-80%)
DEtect HCV RNA after 12 weeks
Common symptoms are fatigue, weight loss and joint pains, RUQ discomfort
75% develop extra-hepatic manifestations
Some examples of extra-hepatic hep c?
Vasculitis
T2DM
Thyroid disease
Eye disease
How do you Dx HCV?
Anti-HCV antibodies emerge within 12 weeks of infection
HCV RNA detects early and chronic infection
What do you check if positive anti HCV antibodies?
detect HCV RNA
Diagnosed with chronic heo C if HCV RNA remains positive for 6 months
Tx of HCV? Who are priority groups
Interferon free DAA are the first line therapy
All adults with acute or chronic HCV
Priority groups: substantial fibrosis, cirrhosis, high risk populations, patients with extra hepatic manifestations, liver transplant patients
What is defined as cure from Hep C?
Sustained virologic response at 12 weeks after end of therapy
What do you need to assess for before starting tx in Hep C?
Assess for liver fibrosis with non-invasive testing
What is tx in patients without cirrhosis vs cirrhosis?
Without cirrhosis: sofosbuvir/velapastir usually 12 weeks or sofosbuvir/daclatsavir 12 weeks
With cirrhosis: sofostbuvir/daclatsavir 24 weeks
What are the major forms of influenza that infect humans?
Two major types– A and B
What are the main reservoirs of A type of influenza?
Ducks, pigs, cats, whales
genetic drift vs shit?
Genetic drift– the more immunity in the community, the faster the mutation of the virus
Genetic shift– from zoonotic to humans
What four subtypes of influenza cause disease?
H1N1
H1N2
H2N2
H3N2
Usually only one type circulates actively
What flu viruses are worst in young children?
B viruses
Where does influenza morbitidy and mortality shows periodicity?
In temperate regions, not tropical!
What are some of the rare complications of influenza?
Viral Pneumonia and ARDs
Encephalopathy
Pericarditis
Rhabdomyolysis
GBS
Who is presentation of flu not obvious in?
Typically older people do not develop a fever
Infants often present with GI symptoms
What diseases coincide with peak of influenza?
IHD
Diabetes
Stroke
How does influenza link to strep Pneumoniae?
Strips the cilia on the epithelium
Much worse infection with S Pneumoniae
What do you need antibodies to protect from?
Enteroviruses
Pneumococcus
Meningococcus
Giardia
What are the classes of antivirals?
1) M2 ion channel blockers such as amatidine and rimantidinie. Need to start fast, but high levels of resistance, resitant to one, will be resitant to the other. Significant toxicity, especially in elderly.
2) Neuroaminidase inhibitors, do not get class resistant. Such as oseltamavir.
3) Polymerase acidic endonuclease drugs such as baloxavir
What are most vaccines based on? Other than live attenuated
A haemoglutination response
What are some of the issues with egg based vaccines?
Delays in adapting strains to eggs
Issues with scale up in the event of pandemic
Side effects such as GBS
Can probably give vaccines to kids that are allergic to eggs
Which vaccines work best in which groups of people?
LAIV work best in healthy young adults
Split vaccines work least well in elderly
What does finding HBsAg and HBeAg mean in serology?
Highly virulent
What is the clinical picture of HBV?
Only small % develop clinical symptoms acutely which is just general hepatitis picture
Who is at highest risk of chronic hep B?
90% of infants <1yr
How is chronic hep B defined?
Presence of HBsAg on 2 occasions measured at 6 months apart
What is the risk of chronic hep B?
25% will go on to develop cirrhosis
Of these, some will go on to develop HCC
Some people directly develop HCC without cirrhosis
Interpret these results:
HBsAg positive
Anti HBs negative
Anti HBC positive
HBV DNA detected
Hepatitis B infection is HBsAg present for more than 6 months, then this is chronic
In acute infection Anti HBc is in the form IgM
What is the window period of hep B?
24-30 weeks
HBsAg and anti HBsAg is negative
Only thing that is positive is Anti HBc IgM
What is APRI? what is the cut off for cirrhosis?
Aspartate amino transferase to platelet ratio index
If More than 2 means cirrhosis
Who do you treat for Hep B?
If cirrhosis present, treat ALL patients and treat lifelong
If cirrhosis not present, take into account age- older than 30? Look at ALT and HBV DNA
Who can you stop tx in Hep B in?
Patients who have been on therapy for a year
If LFTs normal, viral load undetectable and HBeAg converted to anti-HBe
Tx of Hep B?
Tenofovir or Entecavir
For kids entecavir
Alternative is Pegylated interferon for 1yr, but SE profile include bone marrow toxicity
How do you tx pregnant women with Hep B?
Tenofovir recommended at 30-32 weeks until 3 months post partum to reduce risk of VT
Recommended in women with HBV DNA>20,000
C-Section not recommended
What is defined as cure?
Virologic cure:
• Eradication of HBV DNA from blood and liver
• Continued positive anti-HBc with or without anti-HBs
• Unattainable at present
Functional cure:
• HBsAg loss
• Undetectable levels of HBV DNA in peripheral blood
• Sustained indefinitely after a finite course of therapy
Partial cure:
• Detectable HBsAg
• Low (<2000 IU/mL) to undetectable level of HBV DNA
• Maintained indefinitely after treatment is stopped
How do you prevent Hep B? What is acquired immunity defined as?
Recombinant vaccine
3 dose series
Administer first dose within 24hrs of birth
Acquired immunity is individuals with anti-HBs levels >10
Why does hep D coinfect with Hep B?
It has to envelope itself with Hep B surface antigen
Hep D has no envelope and no enzymes itself
What is the most frequent route of transmission of hep D?
Is parenteral typically IVDU
How does Hep D infect someone?
Either at the exact same time as Hep B, cotransmission
Typically this will present with more acute infection as have 2 viruses
Or.. it can superinfect in someone with chronic hep B
This makes progression towards cirrhosis and flares much more aggressive
It seems to suppress hep B so viral load goes down, but it takes over causing cirrhosis etc
How do you Dx Hep D?
HBsAg must be present
HDV RNA is a marker of replication, used for monitoring treatment
Anti HDV IgM is present in acute infection then become IgG
Tx for Hep D?
Pegylated Interferon for at least 48weeks
TDF not recommended
What is the indication for treatment of hep D?
Persistent HDV replication
Clinical picture of Yellow Fever
15% of people develop severe disease which is jaundice, bleeding, hepatomegaly
Epistaxsis, coffee ground vomitus
Proteinuria
What are lab results of Yellow fever?
Albuminuria
Transaminase Elevation
When is the highest RPR seen in syphillis?
In secondary syphillis, can be subject to prozone phenomenon causing RPR negative
What is luese maligna?
Severe Rash seen in malignant syphilis
Stages and natural course of syphillis? Stages
Primary: Get exposed, about 10 days to 3 weeks develop chancre. Not everyone develops a chancre or is a very dismissable lesion.
Secondary: 3weeks to 3 months later see secondary syphillis which is Rash fever, neuro symptoms
Latent: This stage is asymptomatic. Can be early latent if <1yr
Tertiary: Gumma (Granulomatous response to treponema), bones, cardiac, nerve disease
It is unclear how many people go on to develop tertiary syphillis
Primary Stage of syphillis clinical manifestation?
Classical chancre, heaped up border with clean base, not necrotic or purulent
PAINLESS
RPR is positive in 70% of cases
Cannot be distinguished from herpes clinically
Direct inoculation can happen anywhere eg mouth or fingers
Very difficult to diagnose in females as is Painless so will typically be unaware lesion present
What is clinically
