Understand the relevance of HIV, Hepatitis B and Hepatitis C in a global and UK context
HIV
- No change in numbers over the last decade
- Still many millions of people living with HIV
- TB & HIV go hand in hand globally
- Substantially fewer deaths due to HIV in the UK compared to globally
- If left untreated, it leads to AIDS and unusual infections such as oral candidasis, Kaposi’s sarcoma and pneumocystis pneumonia (PCP)
Hep B and C
- Greater numbers globally than those with HIV
- Untreated leads to end stage liver disease
- More untested individuals due to lack of screening programmes
Describe the principles of HIV structure and replication
Human Immunodeficiency virus:
Structure/details: (9)
- Retrovirus
- 2 Strands of single stranded RNA
- It infects cells with CD4 surface receptors (T-helper lymphocytes and monocytes/macrophages and dendritic cells)
- Has surface antigens (gp120 and gp41)
- 3 key enzymes (integrase, reverse transcriptase) protease)
- Viral Envelope (lipid)
- Capsid
- Reverse transcriptase
- Glycoprotein
Replication:
- Free virus in the blood binds to CD4 receptors (on T-helper lymphocytes and monocytes/macrophages and dendritic cells)
- Virus penetrates the cell and empties it’s contents into the cell
- ssRNA are converted into dsDNA by reverse transcriptase enzyme
- Viral DNA is integrated into the host’s DNA by integrate enzyme
- When the cell divides, the viral DNA is read and long chains of viral proteins are made and come together
- Immature virus pushes out of the cell, taking some of the cell membrane with it and the it breaks free of the cell
- Protein chains are cut by the protease enzyme into individual proteins that combine to make a working virus
4 stages of infection:
- Primary infection / seroconversion
- Latent infection
- Symptomatic infection
- Severe infection / AIDS
Describe the principles of HIV testing and treatment
Test anyone with: (7)
- Unusual symptoms (ie chronic weightloss or diahorrhea)
- Community with incidence rate of 2/1000
- Any STI/Hep B/Hep C
- Lymphoma
- Anal cancer
- Meningitis
- TB
- Serology (6)
- Full blood sample sent to lab
- 7-10 days to get results (slower than rapid test)
- Detects antibodies against HIV
- Detects HIV antigen itself
- May get false negative if performed too early - wait 4 weeks
- More accurate than rapid test - PCR test (5)
- Used for follow up and monitoring treatment response as opposed to initial HIV Testing
- Detects HIV nucleic acid
- Highly sensitive so detect very early infection (few days)
- Very expensive
- Slow results (so not used for initial HIV testing) - Rapid tests (7)
- Low cost
- Rapid test
- Detects antibodies against HIV
- Can be blood test (finger prick) or oral swab (saliva)
- Can be done at home as discrete postal test
- Very few false negatives
- May get a false positive result (need to confirm with serology)
Treatments
- ARV drugs - target enzymes in replication = start ASAP:
- Give 2 reverse transcriptase inhibitors and 1 other drug option e.g. protease inhibitor
- Post-exposure prophylaxis treatment
Apply the infection model to a patient with Hepatitis B and Hepatitis C
Hepatitis B
Pathogen - virus
Patient - jaundice, fatigue, abdominal pain, anorexia/nausea/vomiting and arthralgia (joint pain) or asymptomatic
Mechanism of infection - mainly vertical transmission(75%), sexual contact, IV drug use, close household contacts (low risk) where significant blood exposure, needle stick injuries (healthcare workers)
Process of infection - Hepatitis viruses replicate in hepatocytes leading to destruction of hepatocytes. Inflammation of the liver. Persistent HBsAg antigen after 6 months (Chronic Hep B). Incubation 6 weeks-6 months
Management - Chronic stage has no cure but anti-virals are given to suppress replication
Outcome - The vast majority of people infected in adulthood are able to fight off the virus and fully recover within 1 to 3 months. Most will then be immune to the infection for life. Babies and children with hepatitis B are more likely to develop a chronic infection.
Hepatitis C
Pathogen - Virus
Patient - 80% have no symptoms and the rest have vague: fatigue, decreased appetite, nausea, vomiting, abdominal pain, dark coloured urine, grey faeces, arthralgia and jaundice.
Mechanism of infection - IV drug users(90+%), sexual contact, vertical, needle stick injury
Process of infection - Hepatitis viruses replicate in hepatocytes leading to destruction of hepatocytes. Inflammation of the liver.
Management - 90% chance of cure with antiviral drug combo taken for 8-12 weeks - very expensive £10,000 - £60,000 per course.
Outcome - 80% become chronically infected and can develop chronic liver disease/cirrhosis leading to hepatocellular carcinoma, transplant or death
- 90% chance of cure with antiviral drug combo taken for 8-12 weeks
- Risk of re-infection as there is no vaccine currently.
Describe the concept of antimicrobial stewardship
- Coordinated interventions designed to improve and measure the appropriate use of antimicrobials by promoting the selection of the optimal
- antimicrobial drug regimen
- dose
- duration of therapy
- and route of administration.
- Antimicrobial stewards seek to achieve
- optimal clinical outcomes related to antimicrobial use
- minimize toxicity and other adverse events
- reduce the costs of healthcare for infections
- and limit the selection for antimicrobial resistant strains
Outline measures to ensure the appropriate use of antimicrobials
Assess:
- Necessity of antibiotics
- Whether they can be taken orally rather than IV
- Appropriateness to use specific rather than broad targeting antibiotics
- Need for authorisation from microbiology (some antimicrobials are restricted and you need a valid reason to prescribe it)
Apply the infection model to a patient with HIV and acquired immunodeficiency syndrome (AIDS)
HIV
Pathogen - Virus (human immunodeficiency virus)
Symptoms - Flu like illness 2-4 weeks after virus enters body ie fever, headache, muscle ache
Mechanism of infection/ way acquired - sexual contact/IV drug use/vertical transmission
Process of infection/how pathogen causes symptoms - replication in host cells
Management - antiretroviral drugs
Patient outcomes - chronic infections or death (if chronic infections left untreated)
AIDS
- Chronic condition caused by HIV that has leads to severe damage of immune system
- Risk factors - having HIV or other immune related illnesses like diabetes mellitus
- Non-transmittable as it is a collection of potential illnesses
- Same therapy for HIV alongside supportive treatments
Describe the principles of infection transmission and prevention with regard to Hepatitis
Transmission: (Hep B) (5)
- Vertical transmission (75% of cases WW)
- Sexual contact
- IV drug users
- Close household contacts
- Health care workers and needle stick injuries
Prevention: (Hep B)
- Mainly through vaccination (esp. of health care workers (NO CURE)
Transmission: (Hep C)
- IV drug users most at risk (>90% of cases)
- Sexual contact (<1%)
- Infants born to Hep C positive mothers (vertical transmission)
Prevention: (Hep C)
- NO VACCINE
- Just need to avoid high risk transmission situations
Describe the principles of Hepatitis structure, replication, testing and treatment
Structure:
Hepatitis B virus (HBV) is a double-stranded enveloped DNA virus.
Hepatitis C virus (HCV) is a single-stranded enveloped RNA virus that and icosahedral in shape
Replication:
Hepatitis = inflammation of the liver
Hepatitis virus works in a similar way to HIV in hijacking the hepatocytes specifically and integrating into the genome.
Testing: ( Hep C)
- More simple than Hep B testing!
- Only serological test is for the anti-hepatitis C antibody
- This antibody is not protective, can still get reinfected - only of diagnostic value
- Anti-hepatitis C antibody remains for life after clearance/cure, so do a viral PCR to look for Hepatitis C Virus RNA to confirm if the patient has a chronic infection.
Treatment: (Hep C)
- Can be cured!
- Directly acting antiviral drug combination for 8-12 weeks (>90% chance of cure) - but it’s very expensive!!
Testing: ( Hep B)
- Hepatitis B serology
This is the analysis of blood serum (cells or clotting factors) to see what immune response has occurred and look for the presence of extra substances. The serology of hepatitis B involves three antigens and three antibodies.
⇒ Surface antigen, after 6 weeks (HBsAg)
⇒ Highly infectious e-antigen (HBeAg)
⇒ Core antibody appears first (IgM)
⇒ e-antibody appears, less infectious now (HBeAb)
⇒ Surface antibody appears last, clears virus (HBsAb)
⇒ Core antibody persists for life (IgG)
Chronic Hep B infection = persistence of surface antigen after 6 months
- Another test that can be done is a HBV DNA PCR test to see how much viral DNA is in the body.
Treatment: (Hep B)
- NO CURE
- If caught, need to be on lifelong antivirals to suppress viral replication (but not required for everyone if they have a low viral load)
Describe the principles of infection transmission and prevention with regard to blood borne viruses in terms of needle stick injury
- If someone has received a needlestick injury, they must immediately bleed, wash and cover the wound and report to occupational health as soon as possible.
They will need to test blood, check vacc status, if needed give post exposure prophylaxis and retest bloods. - If healthcare worker gets needle stick injury from HIV/Hep B or C, antivirals should be started no later than 72 hours afterwards.
- The PEP treatment for HIV consists of 3 different antivirals (ARVs) for 28 days and then re-tests at 1 and 3 months.
- Post-exposure prophylaxis (PEP) is not very effective for hepatitis C
- The hepatitis B vaccine is very effective as post-exposure prophylaxis for a potential needlestick injury.
After this, they should be referred from counselling and advised to use condoms until they have received the all clear.
