Infection S6 (Done) Flashcards
Describe the basic features of the HIV virus
Retrovirus
Genus: lentivirus
Enveloped, spherical, 80-100nm diameter
Diploid ss+ RNA virus, non-segmented, linear
Compare HIV1 and HIV2
HIV1 is most common
HIV2 confined to W. Africa (mostly)
HIV1 is more virulent
How can HIV be transmitted?
Sexually
Blood and body fluids
Mother to child (Pregnancy and birth)
Describe HIV pathogenesis from infection to death
Viral DNA transcribed to ssDNA and integrated into host genome
Antigenic variation is rapid
Incubation period 2-3 weeks (up to 10 yrs) delaying seroconversion for weeks
Seroconversion = the development of HIV antibodies
Seroconversion can cause servoconversion illness, but is largely asymptomatic
Progressive loss of CD4+ T cells leads to immunodeficiency (AIDS)
Eventually exposes patient to opportunistic infection, kaposi sarcoma and malignancies
These invariably lead to death of the patient
Describe the classification of HIV
How does the existence of multiple types, groups and subtypes of HIV affect treatment?
Classification:
HIV can be split into types 1 and 2
Type one can be further grouped into M, N, O, P
M group has 9 subtypes, A, B, C, D, E, F, G, H, J, K
Treatment:
Treatments are broadly similar
Describe the infection of a cell with HIV and the subsequent generation of new viral particles
HIV virion fuses with host cell membrane via viral gp120/41 attachment and fusing with CD4/CCR5 complex
Release of diploid RNA with reverse transcriptase into host cytoplasm
Reverse transcription produces dsDNA
Integrase enzymes integrate viral dsDNA with host genome
Transcription occurs and viral RNA is produced that is translated into viral proteins
Viral proteins assemble around viral RNA
Immature virus pushes out of the cell taking some of the cell membrane (Budding)
Protein chains in the new virus are cut with protease enzymes and produce a working virus
Describe seroconversion illness
50-70% of patients have this acute syndrome lasting 2-6 wks after aquisition of HIV
25% of these are severe enough to seek medical attention
Symptoms:
Fever, Malaise
Arthralgia, headache
Sore throat and lymphadenopathy
Non-specific symptoms typical of acute viral infection
Early invasion of the nervous system may lead to meningitis, encephalitis, peripheral neuropathy or myelopathy
Describe the Seroconversion rash
Seen in about 25% of acute HIV patients
Non-specific erythrematous maculopapular rash (can involve palms/soles)
Usually resolves within 2-3 wks
How can HIV be identified via labratory diagnostic methods?
Virus can be cultured from circulating mono-nuclear cells
Genome detection by PCR and p24 antigen detected prior to seroconversion
ELISA used for antibody screening (post-seroconversion)
Confirmation of ELISA result w/western blotting
Describe a typical regimen of screening for HIV to make and confirm diagnoses.
For each screen, give what is identified by that screen
1st screen:
4th generation EIA (Enzyme immunoassay)
Can detect HIV antibody, IgMs and p24 antigen
Allows pre and post seroconversion detection
2nd screen (to confirm):
Second generation EIA
Can detect viral particles, purified HIV antigens or recombinant virus
3rd screen (further confirmation):
Nucleic acid testing (NAT)
Pooled samples tested via amplification of viral RNA via PCR
If positive, individual samples tested
Give some classes of antiretroviral drugs
Nucleoside reverse transcriptase inhibitor
Non-Nucleoside reverse transcriptase inhibitor
Protease inhibitors
Fusion inhibitors
Integrase inhibitors
Co-receptor/Entry inhibitors
All pretty self explanatory
Outline the principles of HIV treatment
Highly active antiretroviral treatment (HAART):
Use of a combination of antiretroviral drugs of different classes
Resistance often develops to these drugs and so drugs must be switched periodically
New resistances will occur, however sometimes these weaken old resistance, opening previously used lines of treatment
Give a basic description of the Hepatitis B virus
Genus: Orthohepadnavirus
Enveloped, pleiomorphic, 24-48nm diameter
Circular partially ds DNA
How many HB carriers are estimated worldwide?
What regions have high prevalence of HB?
400 million
Africa, Western Pacific, Asia
What are the possible ill effects of chronic HB infection?
Chronic Hepatitis
Cirrhosis
Heptacellular carcinoma
Bywhat mechanism does HBV replicate?
Reverse transcriptase
Outline HBV prophylaxis
Vaccination:
Wild type HB surface antigen (HBsAg) based
sAg mutants reduce vaccine effectiveness
If testing for HBsAg, mutant can give false negative
Hyperimmunoglobulin:
Post exposure prophylaxis
Newborns or needlestick injury
Give the lifetype risk of infection and distribution of HBV in high, intermediate and low risk groups
High:
Lifetime risk = >60%
Neonatal and early childhood infection common
Intermediate:
Lifetime risk = 20-60%
Infections occur in all ages
Low:
Lifetime risk = <20%
Most infections in adult risk groups
What are the routes of transmission for HBV?
Vertical - Mother to infant
Sexual
Percutaneous (blood, IV drugs, Sharp injury, tattoo)
What are the clinical features of acute HBV infection?
Incubation:
2-6 months
Symptoms:
Fever, Malaise, Jaundice
Acute case fatality:
0.5 - 1%
Give the rates of symptomatic infection in children and adults that aquire HBV
Children:
<10%
Adults:
30-50%
Compare rates of chronic infection in those infected with HBV between sex and age groups
Sex:
Male > Female
Age:
Infant - 90%
Child - 30%
Adult - <3%
What are the outcomes of chronic HBV infection?
Asymptomatic carrier:
Can later progress to chronic persistent hepatitis or liver cancer
Chronic persistent hepatitis:
Can lead to chronic active hepatitis and liver cancer
Chronic acitive hepatitis:
Can lead to liver cancer or cirrhosis
Compare the transmissibility of HIV and HBV via blood to blood event
HIV viraemic patient (HIV RNA+) = 1:300
HBV viraemic patient (HBeAg+) = 1:3
What immediate actions should be taken after an exposure event such as needlestick injury?
Wash the wound with soap and water (Hibiscrub and betadine not recommended)
Encourage bleeding
Report the incident to manager
Ask a colleague to approach patient about a blood sample, have a blood sample taken yourself
Make a risk assessment on the need for post-exposure prophylaxis (can consult on-call virologist/microbiologist)
How might you carry out a risk assessment for the need for post-exposure prophylaxis after a transmission event?
Seriousness of injury
Risk:
Blood to blood > Blood to mucous membrane > non-blood fluid to blood > fluid to mucous membrane
Were gloves worn? (Wiping effect on needle)
Patient status:
Is patient likely to have a blood borne virus?
Assess lifestyle, history, admission DDx, drug history
Outline HIV post exposure prophylaxis
Triple antiretroviral therapy
Combination depends on local background resistance prevalence
What is CRP?
An acute phase proteins, part of the acute phase reaction (increase or decrease in response to inflammation)
Produced by the liver
How is the liver involved in distant inflammation?
Microorganism cell wall products activate macrophages and monocytes
These cells release cytokines such as:
- Interleukin 1 (IL-1)*
- IL-6*
- -** **TNF*
Cytokines, especially IL-6 circulate in the blood and reach the liver
These cytokines stimulate the liver to produce proteins, the acute phase proteins
Give some other examples of acute phase proteins
Complement
Fibrinogen
Why is CRP useful clinically?
Up to 1000x increase when stimulated
Rapid production (within hours)
Easy to measure!
What is the function of CRP?
It is an opsonin (see wk 3)
Give some examples of events that may trigger the acute phase reaction and hence lead to an increase in CRP
Infection
Trauma
Surgery
Burns
Tissue infarction
Inflammation
Cancer
Give some other phenomena (ie. not CRP rise) that occur as a result of the acute phase reaction
Fever
Hormone secretion (E.g. Cortisol)
Blood changes (anaemia)
Metabolic changes
What is the erythrocyte sedimentation rate and why is it clinically important?
ESR:
The rate at which erythrocytes sediment during one hour
Use:
Increased fibrinogen causes RBCs to clump and settle faster
Therefore ESR can be use as a marker for increase fibrinogen and hence inflammation etc
