Case 12: extra and HIV Flashcards
1
Q
Shingles vaccine
A
- Offered to all patients aged 70-79 years
- is live-attenuated and given sub-cutaneously
- Don’t give if immunocompromised
2
Q
Shingles progression
A
- Prodrome: acute neuralgia (tingling, burning pain with enlarged lymph nodes(typically 2-3 days)
- Infectious: rash (affects single dermatome in a band like distribution) rarely crosses the midline, pain where the rash is (7-10 days)
- Resolution: vesicles crust other and take a month to disappear
3
Q
Chicken pox pathophysiology
A
- spread via the respiratory route
- can be caught from someone with shingles
- infectivity = 4 days before rash, until 5 days after the rash first appeared*
- incubation period = 10-21 days
4
Q
Chicken pox clinical features
A
- Fever initially
- itchy, rash starting on head/trunk before spreading. Initially macular then papular then vesicular
- Generalised pruritic rash
- Macular -> Papular -> Vesicular -> Crusted
- systemic upset is usually mild
- Usually mild in healthy children, more severe if immunocompromised, neonates and adults
5
Q
Management of chicken pox
A
- Calamine lotion
- School exclusion:Advise that the most infectious period is 1–2 days before the rash appears, but infectivity continues until all the lesions are dry and have crusted over (usually about 5 days after the onset of the rash).
- Immunocompromised patients and newborns with peripartum exposure should receivevaricella zosterimmunoglobulin (VZIG). If chickenpox develops then IV aciclovir should be considered
6
Q
Infective endocarditis
A
An infection of the endocardial surface of the heart including one or more of the valves. Rare and life threatening
7
Q
IE pathophysiology
A
Turbulent blood flow causes damage to the smooth endothelium, causes accumulation of platelets, fibrin, leukocytes which can be infected by circulating microorganisms forming a vegetation.
8
Q
Risk factors for IE
A
- Age >60years, Male
- Intravenous drug use particularly increased risk of right sided IE
- Intravascular lines
- Chronic haemodialysis (usually have a fistula or a long-term haemodialysis catheter which can become infected)
- Immunosuppression
- Recentdental or surgical procedure
- Cardiac factors: history of prior IE, prosthetic heart valve, cardiac devices (pace maker) structural heart disease (valvular or congenital)
- Rheumatic heart disease with mitral valve affected
9
Q
Causes of IE
A
- Staphylococcusaureus (most common cause of IE, associated with IVDU)
- Viridians group streptococcus(more prevalent among some older populations and community-acquired IE, recent dental extraction)
- Enterococci (3rd highest cause, linked to health care contact and recurrent UTI’s)
- Streptococci bovis(high association with bowel cancer)
10
Q
Unusual causes of IE
A
- Coxiella burnetii(the causative agent of Q fever, associated with abattoirs / livestock)
- Bartonella spp (associated with alcoholism or homelessness)
- Brucella spp (travel to the Middle East or the Mediterranean or consumption of unpasteurized dairy products)
- Bartonella henselae (contact with cats )
- Aspergillus spp. (extensive health care contact in a patient with a prosthetic valve
11
Q
Clinical manifestations of IE
A
- Fever- with chills, anorexia and weight loss
- Non-specific: malaise, arthralgia, night sweats and abdominal pain
- Heart murmurs: usually in left IE
- Cutaneous manifestations: Petechiae and splinter haemorrhages
- Specific to IE: Janeway lesions (non-tender), Osler nodes (tender), Roth spots (haemorrhagic retinal lesions with a pale centre)
- Long standing disease: finger clubbing and Splenomegaly
12
Q
Pulmonary septic emboli
A
Is the most common presentation of isolated right-sided IE (10% of all cases of IE). Presents with a cough, dyspnoea, haemoptysis or pleuritic chest pain.
13
Q
Investigations or IE
A
- Blood cultures: 3 samples from different sites with a gap of 1-6hr. Must be taken before antibiotics. 2 sets within 1hr if septic and starting abx. Dont wait till temperature spike.
- Bloods: FBC, CRP, ESR, U&E, LFT
- Transthoracic echocardiogram (TTE): first line investigation
- Transoesophageal echocardiogram (TOE): Do if TTE is negative
- ECG
- CXR: to look for pulmonary septic emboli, congestive heart failure or ay abscess’s
- CT scan (thoracic, abdominal and pelvis): for metastatic infections
- Special investigations for prosthetic heart valves: 18F-FDG PET/CT, SPECT-CT
14
Q
Modified Duke criteria
A
- Used to diagnose infective endocarditis based on either Clinical or Pathological criteria
- Clinical criteria: Requires One major plus three minor criteria or five minor criteria
15
Q
DUKE’s major criteria
A
- Persistently positive blood cultures (Of organisms which cause IE) , cultures must be separated in time
- Imaging findings (echocardiogram) of endocardial involvement : vegetation, abscess, Prosthetic valve dehiscence, new regurgitation
16
Q
Duke’s pathological criteria
A
- Microorganisms demonstrated by culture or histology of a vegetation or emboli
- Vegetation or abscess confirmed by histology to be active endocarditis
- Both require surgical intervention: either culture of histology
17
Q
Duke’s minor criteria
A
- Predisposition (heart disease) or IVDU
- Fever >38
- Vascular phenomena (Janeway lesions)
- Immunological phenomena (Osler nodes, Roth spots)
- Microbiological phenomena
- PCR
- Echocardiographic findings
18
Q
Managing IE
A
- IV Antibiotics (i.e. amoxicillin and optional gentamicin): can delay based on blood culture results if stable
- HACEK organisms can be treated with Ceftriaxone
- Antibiotics are given for 4 weeks in native heart valves and 6 weeks in prosthetic
- Remove source of infection: i.e. intravascular catheter, intracardiac device, arteriovenous fistula. May need dental evaluation
- Colonoscopy: when group D streptococci is found on culture
- Valve surgery
19
Q
Different antibiotics for IE
A
- If stable wait for blood culture results
- Native valve: Amoxicillin with optional gentamicin
- Native valve with sepsis: Vancomycin and gentamycin
- Prosthetic valve: Vancomycin, Gentamycin and Rifampicin
- HACEK (gram negative): Ceftriaxone or Amoxicillin, Gentamicin for first 2 weeks, alternative is Ciprofloxacin
20
Q
When is valve surgery indicated
A
- IE-associated valvular regurgitation/dysfunction
- Associated complications i.e. septic emboli
- Heart failure
- Intracardiac abscess or large vegetations (>10mm)
- Infections not responding to antibiotics (fungal or antimicrobial resistant) 7 day cut off
21
Q
IE- Echo follow up
A
- If concerned about complications i.e. new murmur or embolic events
- Following antibiotic therapy as complete resolution of vegetation is uncommon so need to establish new baseline
- Remain under follow up for 1 year: monitor development of heart failure, end of treatment TTE, discuss recurrence
22
Q
IE: complications
A
- Cardiac: congestive heart failure, pericarditis
- Septic pulmonary emboli
- Neurological: embolic stroke, intracerebral haemorrhage
- Renal: renal infarction, abscess, glomerulonephritis
- Musculoskeletal: vertebral osteomyelitis, septic arthritis, psoas abscess
- Splenic infarct or abscess
- Systemic: rheumatoid factor may be raised
- Death: quarter die even with treatment. Without treatment all die.
- Left sided IE: emboli travel around the body except for the lung which is from the right
23
Q
IE: factors associated with worse prognosis
A
- Heart failure, renal failure, Brain haemorrhage, septic shock
- Larger vegetation size
- Microbiology (S.aureus, Fungi, Non-HACEK gram negative bacilli)
- Perivalvular abscess, severe valvular dysfunction
- Poor surgical candidate (early valve surgery confers a lower mortality risk)
24
Q
HIV
A
- A retrovirus which targets CD4+ T lymphocyte, Macrophages and dendritic cells
- Transmitted: sexual contact, IV drug use, and vertical
- HIV-1: more prevalent and aggressive
- HIV-2: less pathogenic and found in West Africa
25
HIV structure
- Contains single stranded RNA (two copies contained within the nuclear capsid)
- Nuclear capsid is made of viral p24 protein: target for serological tests (as well as HIV envelope protein)
- Cell membrane is made from a lipid derived from host T cell
- Contains enzymes: Protease, Integrase, Reverse Transcriptase
- Glycoprotein complex consisting of gp120 and three gp41 anchoring stems (anchor the complex to the lipid membrane)- allow HIV to attach to other cells (CD4 lymphocyte and Macrophages)
26
HIV: risk factors
- Unprotected sex
- Multiple sexual partners
- IV drug use
- Blood transfusion
- Mother to child transmission
- Occupational exposure
- High risk sexual behaviour: anal sex, prostitutes
- Sub-Saharan Africa
- Others STI’s
27
How HIV enters the cell
- HIV can infect CD4 T cells, macrophages and dendritic cells
- gp120 binds to CD4 and CXCR4 on T cells and CD4 and CCR5 on macrophages and releases their capsid into the host cell
- HIV viral envelope fuses with the target cell membrane and releases their viral contents into the cell
- mutations in CCR5 can give immunity to HIV
28
Mechanism of HIV integration
- After entering a cell reverse transcriptase creates dsDNA from the RNA (by reverse transcriptase enzyme) for integration into the host cell's genome by the viral integrase enzyme
- Drug resistance can develop in the reverse transcription step due to mutations
- Viral DNA can be dormant for many years
- When activated can reduce functionality and number of CD4 cells causing immunosuppression.
29
Mechanism of HIV replication
- viral DNA is transcribed back into RNA by host cell
- RNA is transported from the nucleus to the cytoplasm
- viral RNA is used to make viral proteins by the viral protease enzyme
- viral proteins form a new immature HIV which can infect other cells. Envelope is formed from lipid components of the host cell
- protease allows the virus to mature
30
HIV seroconversion
- Occurs 3-12 weeks post infection
- Increased symptoms associated with worse prognosis
- Features: sore throat, lymphadenopathy, malaise, myalgia, arthralgia, diarrhoea, diffuse maculopapular rash
- A glandular fever type picture
31
How the CD4 count changes
- Initially there is a transient decrease in CD4 during the seroconversion
- Afterwards the CD4 count recovers but not fully
- CD4 count is stable for 5 years then slowly declines
- Initial increase in HIV RNA and p24 antigen which then decline though not fully
32
Diagnosing HIV
- ELISA for HIV antibodies and p24 anitgens: Negative test within 45 days of exposure is unreliable. First line
- Point of care (POC) tests for HIV antibodies give results within minutes unreliable first 90 days. Get results quickly need to confirm with labs
- HIV RNA: for screening blood donors and in neonatal, indicates viral load
- At home testing kits: self sampling kits, point of care kits
33
CD4 level
- 500-1200 cells/mm is the normal range
- Under 200 cells/mm puts the patient at high risk of opportunistic infections
- Flow cytometry detect levels of CD4 lymphocytes
- Viral load is detected by PCR
34
HIV management
- Highly active anti-retroviral therapy (HAART): Two NRTI’s (i.e. Tenofovir plus Emtricitabine) and a PI or a NNRTI.
- Alternative combination of NRTI’s: ABC (abacavir) and 3TC (lamivudine)
- Summary: 2 NRTI’s + a 3rd drug from a different class
35
Outcomes of HIV treatment
- CD4 count and viral count can recover fully with medication meaning they can have a normal life expectancy
- Start medication from diagnosis
- CD4 count may remain low, if <200 need long term prophylaxis
- Viral load is how you monitor treatment progression
- Changes to treatment should only be made by a specialist
- Need combined therapies to prevent development of resistance (cant acquire enough mutations)
36
HIV: Entry inhibitors and examples of Integrase inhibitors
Entry inhibitors
- maraviroc, enfuvirtide
- prevent HIV-1 from entering and infecting immune cells
Integrase inhibitors examples: raltegravir, elvitegravir, dolutegravir
37
Nucleoside analogue reverse transcriptase inhibitors (NRTI)
- examples: zidovudine (AZT), abacavir, emtricitabine, didanosine, tenofovir
- general NRTI side-effects: peripheral neuropathy
- tenofovir: Adverse effects include renal impairment and ostesoporosis
- zidovudine: anaemia, myopathy, black nails
- MoA: mimics nucleotides that are used to form viral DNA
38
HIV: Non-nulceoside reverse transcriptase inhibitors (NNRTI)
- examples: nevirapine, efavirenz
- side-effects: P450 enzyme interaction (nevirapine induces), rashes
- MoA: bind directly to reverse transcriptase preventing it from adding new nucleotides to the growing DNA chains
39
HIV: Protease inhibitors (PI)
- examples: indinavir, nelfinavir, ritonavir
- side-effects: diabetes, buffalo hump, central obesity, P450 enzyme inhibition
- indinavir: renal stones, asymptomatic hyperbilirubinaemia
- MoA: prevents the breakup of new viral proteins so the building blocks for new viruses are not available
40
General side effects of anti-retroviral therapy
- D/V
- steatosis/ hepatitis
- mild rash
- lipodystrophy (fat reduction peripherally but gain centrally)
- diabetes and dyslipidaemia
41
HIV additional management
- Prophylactic co-trimoxazole: given if CD4 <200 to protect against PCP
- Yearly cervical smears
- Vaccinations against influenza, pneumococcal, HPV and hepatitis A and B. Avoid live vaccines
42
HIV: giving birth (viral load)
- <50: normal vaginal delivery
- >50: consider a pre-labour caesarean section
- >400: pre-labour caesarian is recommended
- >1000 or unknown: give IV zidovudine as an infusion during labour
43
HIV prophylaxis for baby: depending on mothers viral load and breast feeding
- Low-risk babies (mother’s viral load is under 50 copies per ml) are given zidovudine for 2-4 weeks
- High-risk babies are given zidovudine, lamivudine and nevirapine for four weeks
- Breast feeding: advised not but can if viral load undetectable
44
HIV prophylaxis
- PEP must be commenced within 72 hours of exposure
- PEP involves a combination of ART therapy. The current regime is emtricitabine/tenofovir (Truvada) and raltegravir for 28 days.
- Pre-exposure prophylaxis (PrEP) is also available to take before exposure. The usual choice is emtricitabine/tenofovir (Truvada).
45
AID's defining illness
- When CD4 count drops to a level allowing for opportunistic infections
- Examples: Kaposi sarcoma, PCP, CMV, Candidiasis (oesophageal or bronchial), lymphoma, tuberculosis
46
HIV: complications of CD4 >500
- GBS
- Chronic demyelinating neuropathy
- Idiopathic thrombocytopaenia
- Reifter’s syndrome
- Polymyositis
- Sjogrens syndrome
- Bell’s palsy
47
HIV: complications of CD4 350-500
- cutaneous manifestations e.g. folliculitis
- psoriasis/ eczema that is refractory to treatment
- shingles that is recurrent or multi-dermatomal
- bacterial pneumonia
- GBS or other demyelinating neuropathies
48
Complications of HIV: CD4 200-350
- Oral thrush: secondary to Candida albicans
- Hairy Leukoplakia: secondary to EBV
- diarrhoea illness due to parasitic infections such as cryptosporidiosis
- pulmonary TB
49
Complications of HIV: CD4 count 100-200
- Cryptosporidiosis
- Cerebral toxoplasmosis
- Progressive multifocal leukoencephalopathy: secondary to JC virus
- Pneumocystis jirovecii pneumonia
- Kaposi sarcoma secondary to HHV-8
- HIV dementia
50
Complications of HIV: CD4 count 50-100
- Aspergillosis: secondary to Aspergillus fumigatus
- Oesophageal candidiasis: secondary to Candida albicans
- Cryptococcal meningitis
- Primary CNS lymphoma: secondary to EBV
