Infection and immunology Flashcards
1
Q
Define varicella zoster
Where does it lie dormant
A
Primary infection is called varicella (chickenpox).
Reactivation of the dormant virus in the dorsal root ganglia, causes zoster (shingles).
Confusingly also known as herpes zoster in some texts.
2
Q
Explain the aetiology / risk factors of varicella zoster
Pathogenesis:
Where is the infection, where does virus replicate, where does it remain latent
A
VZV is an herpes ds-DNA virus. Highly contagious, transmission is by aerosol inhalation or direct contact with the vesicular secretions
Viral inhalation and infection of upper respiratory tract. Viral replication in regional lymph nodes, liver and spleen. By week 2– 3 infection spreads to skin producing rash then leading to clinical resolution. Virus remains latent in dorsal root ganglia (lifelong). Reactivation causes virus to travel down sensory axon to produce dermatomal shingles rash..
3
Q
Summarise the epidemiology of varicella zoster
A
Chickenpox peak incidence occurs at 4– 10 years. Shingles peak incidence occurs at > 50 years. About 90% of adults are VZV IgG positive (previously infected).
4
Q
Recognise the presenting symptoms of varicella zoster
A
Incubation period (=period between exposure to an infection and the appearance of the first symptoms) 14-21 days
Chickenpox: prodromal (=relating to or denoting the period between the appearance of initial symptoms and the full development of a rash or fever) malaise, mild pyrexia, sudden appearance of intensely itchy spreading rash affecting face and trunk more than extremities, the oropharynx, conjunctivae and genitourinary tract. As vesicles weep and crust over, new vesicles appear.
Shingles: May occur after a period of stress. Tingling/hyperaesthesia in a dermatomal distribution, followed by painful skin lesions. Recovery in 10– 14 days.
5
Q
Recognise the signs of varicella zoster on physical examination
A
Chicken pox: Maculopapular rash evolving into crops of vesicles with areas of weeping (exudate) and crusting (vesicles, macules, papules and crusts may all be present at one time), skin excoriation (from scratching), mild pyrexia.
Shingles: Vesicular macular papular rash, in a dermatomal distribution skin excoriation
6
Q
Identify appropriate investigations for varicella zoster and interpret the results
A
Both chickenpox and shingles are usually clinical diagnoses.
Vesicle fluid: Electron microscopy, direct immunofluorescence, cell culture, viral PCR (all rarely necessary).
Chickenpox: Consider HIV testing especially in adults with prior history of varicella infection.
7
Q
Generate a management plan for varicella zoster:
- Varicella? Children vs adults
- Shingles
- Prevention?
A
Chicken pox (primary infection):
- Children: symptomatic (calamine lotion (=anti-itch), analgesia, antihistamine if severe)
- If >13years old, immuno-suppressed, or have been on long term aspirin (if they’re under the age of 19, due to risk of Reye’s), they need antiviral agent- acyclovir
- Pain relief (aspirin and NSAIDs contraindicated, use paracetemol)
Shingles (reactivation):
-Start antiviral therapy within 72hrs to reduce risk of post-herpetic neuralgia.
IMMUNOCOMPETENT: valaciclovir OR famciclovir, are both better than aciclovir
IMMUNOCOMPROMISED: aciclovit
-Pain relief (NSAIDs are fine here) & calamine lotion
VZIG may be indicated in the immunosuppressed and in pregnant women exposed to varicella zoster. Chickenpox vaccine is licensed in the United Kingdom, but no guidelines available for appropriate use.
8
Q
Identify the possible complications of varicella zoster and its management
A
Chickenpox: Secondary infection, scarring, pneumonia, encephalitis, cerebellar syndrome, congenital varicella syndrome.
Shingles:
Postherpetic neuralgia,
zoster opthalmicus (rash involves opthalmic division of trigeminal nerve),
Ramsay Hunt ‘s syndrome (Ramsay Hunt syndrome (herpes zoster oticus) occurs when a shingles outbreak affects the facial nerve near one of your ears. In addition to the painful shingles rash, Ramsay Hunt syndrome can cause facial paralysis and hearing loss in the affected ear),
sacral zoster may lead to urinary retention,
motor zoster (muscle weakness of myotome at similar level as involved dermatome).
9
Q
Summarise the prognosis for patients with varicella zoster
A
Depends on the complications. Worse in pregnancy, the elderly and immunocompromised.
10
Q
When is chickenpox contagious from and until
A
Contagious from 48 h before the rash and until all the vesicles have crusted over (within 7– 10 days).
11
Q
Define osteomyelitis
A
Osteomyelitis is an inflammatory condition of bone caused by an infecting organism, most commonly Staphylococcus aureus.
Affects bone or bone marrow
It usually involves a single bone but may rarely affect multiple sites.
In actue osteomyelitis, dendritic cells and macrophages are trying to wipe out the infection (over a course of weeks). Usually this is successful, but sometimes it turns into chronic osteomyelitis lasting months to years.
Chronic osteomyelitis:
- Affected bone can become necrotic and separate from the healthy bone, known as a sequestrum.
- Healthy bone may then grow around the necrotic area, known as an involucrum
12
Q
Explain the aetiology / risk factors of osteomyelitis
A
Aetiology:
1. Haematogenous spread (most common)
Haematogenous osteomyelitis usually involves the metaphysis of long bones in children or the vertebral bodies in adults (vertebral osteomyelitis). In acute haematogenous osteomyelitis, the joint is usually spared, unless the metaphysis is intracapsular, as is found at the proximal radius, humerus, or femur.
- Direct inoculation of micro-organisms into bone (trauma, surgery)
- From contiguous focus of infection
The rising number of patients living longer with multiple comorbidities and the increasing incidence of bone and joint surgery have led to a higher proportion of contiguous focus infection, with haematogenous infections becoming less frequent, except in the immunocompromised host.
Despite these different causes all forms of acute osteomyelitis may evolve and become chronic, sharing a final common pathophysiology, with a compromised soft-tissue envelope surrounding dead, infected, and reactive new bone.
Risk factors: Penetrating injuries surgical contamination intravenous drug misuse diabetes mellitus periodontitis
13
Q
Summarise the epidemiology of osteomyelitis
A
The annual incidence was higher for men than for women and increased with age
incidence growing in older adults driven by secular increase in diabetes related cases.
14
Q
Recognise the presenting symptoms of osteomyelitis
A
Acute osteomyelitis:
- Non-specific pain at site of infection
- Fever
- Depending on location, may affect use of bone
Chronic:
- Prolonged fevers
- Weight loss (due to chronic inflammatory state)
15
Q
Recognise the signs of osteomyelitis on physical examination
A
Local inflammation, erythema or swelling
Low-grade fever
Reduced range of movement
Reduced sensation in diabetic foot ulcer
16
Q
Identify appropriate investigations for osteomyelitis and interpret the results
A
Bloods: WBC (usually raised in acute disease, normal in chronic), ESR (usually raised, can be used to monitor treatment), CRP (usually raised, may be more helpful than ESR as it normalises more rapidly after successful treatment)
Imaging: plain x-rays of affected area, bone scan or MRI, and bone biopsy
17
Q
Complication of osteomyelitis
A
Septic arthritis of an adjacent joint may be an early complication of acute osteomyelitis in children.
In both acute and chronic osteomyelitis the inflammation can involve the periosteum. An abscess can form between the bone and the periosteum, which can track up the bone
Infection can spread to:
- nearby joint
- overlying muscle
- skin
- blood vessels (leading to thrombophlebitis)
18
Q
Commonest organism causing osteomyelitis
A
Staphylococcus aureus most common, which is responsible for one third of all acute osteomyelitis and up to half of all vertebral osteomyelitis.
The next most common organisms implicated in acute osteomyelitis are streptococci, Enterobacteriaceae, and anaerobic bacteria.
Most infections in orthopaedics, including osteomyelitis, are caused by biofilm-forming bacteria
NOTE THAT SALMONELLA particularly affects individuals with sickle cell disease, so they are at risk for staph aureus and salmonella infections
Pastuerella multocida usually spreads form the skin to the bone from a scratch from a cat or dog
19
Q
What might an x-ray show in osteomyelitis
What about bone scan/MRI
What about bone biopsy
A
X-ray:
Thickening of the cortical bone and periosteum
Elevation of the periosteum (abscess)
Loss of normal architechture, especially tabecular architecture
Osteopenia (loss of bone mass), which becomes evident when >half bone matrix destroyed
Bone scan:
Confirm
Identify abscess
Bone biopsy:
Identify pathogen and confirm diagnosis
20
Q
What are vasculitides?
A
A heterogenous group of autoimmune disorders characterized by inflammation of blood vessels (vasculitis) and subsequent ischemia and damage to the organs supplied by these vessels.
21
Q
How can vascultides be classified and give some examples of each classification
A
Based on the size of the vessel affected, it can be classified into small-vessel, medium-vessel, or large-vessel vasculitis
There is overlap.
Large: GCA, Takayasu
Medium: Polyarteritis nodosa
Small:
Microscopic polyangiitis affects mall arteries, arterioles, capillaries and venules (but not veins)
Eosinophilic granulomatosis with polyangiitis (EGPA), also known as allergic granulomatosis or churg strauss, causes inflammation of small and medium-sized blood vessels (vasculitis)
Granulomatosis with polyangitis affects small arteries, arterioles, capillaries, venules and veins
22
Q
Vignette: woman >50, experiencing visual impairment, with a new-onet headache. What is the treatment
A
This is consistent with giant cell arteritis.
Mx: high dose glucocorticoids to prevent permanent vision loss. Aspirin to prevent ischaemic events
See MSK for all the boxes
23
Q
Vignette:
Asian female 35. Attended A&E with syncope and chest pain. Disparity of BP between the two arms. What is the management?
A
Takayasu arteritis
Asian females, typically < 40 years
Disparity in blood pressure between arms → “pulseless disease” (I can’t TAKA YA pulse)
Bruit over subclavian artery or abdominal aorta
Syncope and angina pectoris
Mx: glucocorticoids
24
Q
Takayasu arteritis:
Definition
Aetiology and risk factors
Differentiating from other vasculitides in the same classification?
A
Granulomatous inflammation of the aorta and its major branches, resulting in stenosis of involved blood vessels and subsequent vascular symptoms
25
Epidemiology of takayasu arteritis
Peak incidence: 15–45 years of age
Asian heritage
♀ > ♂ (3:1)
ASIAN WOMEN
YOUNGER THAN GCA (histologically the same)
26
Clinical features of takayasu arteritis
```
Symptoms:
Fever, malaise, arthralgia
Impaired vision
Movement-induced muscular pain in one or more limbs
Fainting and angina pectoris
```
```
Signs:
Reduced bilateral brachial AND radial pulse--> PULSELESS DISEASE
Raynauds phenomenon
Bilateral carotid bruits
HTN
```
Skin manifestations
Erythema nodosum
Urticaria
27
Investigations for takayasu
Treatment?
Raised ESR (but ESR is raised even more in giant cell)
GOLD STANDARD: angiography to look for vascular stenosis
Biopsy of affected vessel: granulomatous thickening of aortic arch; plasma cells and lymphocytes in media and adventitia; vascular fibrosis
Treat:
With corticosteroids. Surgical intervention (e.g. bypass) may be required if critical stenosis of aortic arch of branches occurs.
Antihypertensive treatment
28
Vignette: male with fever and malaise and abdominal , muscle and joint pain. Rash and ulcers and nodules.
Polyarteritis nodosa
29
Definition of polyarteritis nodosa
Granulomatous?
all and medium-sized vessels, which leads to tissue ischemia; most commonly involving skin, peripheral nerves, muscles, joints, gastrointestinal tract, and kidneys
It's not granulomatous, is NECROTISING
30
Epidemiology of polyarteritis nodosa
Assocation?
Important because more common in males than females which is unusual.
Peak incidence 45-65
Associated with hep B and hep C infection
31
Clinical features of polyarteritis nodosa
Are lungs affected?
Nonspecific symptoms: fever, abdominal, muscle, and joint pain
Renal involvement: hypertension, renal impairment (due to renal artery stenosis)
Coronary artery involvement; increased risk of myocardial infarction
Skin involvement: rash, ulcerations, nodules
Neurological involvement: polyneuropathy (mononeuritis multiplex), stroke
GI involvement: abdominal pain, melena, nausea, vomiting
*Usually spares the lungs*
Consider in young people who have had a stroke
32
Which investigations would you want to perform if you suspected polyarteritis nodosa, what would you expect to see
Hep B and C serology as often associated with these infections
A very raised ESR.
Anaemia, leukocytosis
ANCA-negative
Haematuria, proteinuria
Muscle biopsy: transmural inflammation of the arterial wall with leukocytic infiltration and fibrinoid necrosis
Angiography (if tissue cannot be biopsied) : umerous small aneurysms and stenosis of small and medium-sized vessels of the involved organs (pulmonary arteries not usually affected)
33
Differentiate investigations for Takayasu with that of polyarteritis nodosum
With takayasu angiography is gold standard to assess vascular stenosis
With PAN, muscle biopsy (in the tender muscle group) is gold standard, with angiography if that muscle if not easily accessible
34
Mnemonic for polyarteritis nodosum
In PAN, the Pulmonary Artery is Not involved, PANmural inflammation of the arterial wall is present, and PAN is often associated with hePANitis B!
Please note that PAN should be considered in young adults presenting with stroke or myocardial infarction! The diagnosis may be confirmed with a biopsy of involved tissue.
35
Granulomatosis with polyangitis (=Wegener granulomatosis) important features?
The C disease:
Curvy nose (saddle nose deformity), chronic sinusitis, cough, conjuncitivtis and corneal ulceration, cardiac arrhythmias, nonCaseating granulomas, cANCA, corticosteroids and cyclophosphamide as treatment
36
Somebody attends clinic having repeated sinus infections, as well as ear infections. Now she has a cough, dyspnea and is coughing up blood. There are red cell casts in the urine.
Granulomatosis with polyangiitis (Wegener)
37
Definition of granulomatosis with polyangiitis
Clinica features
Vasculitis affecting small vessels.
See above for the Cs.
Nasopharyngeal involvement: chronic sinusitis/rhinitis, saddle nose deformity
Chronic otitis media and mastoiditis
Treatment-resistant, pneumonia-like symptoms with cough, dyspnea, hemoptysis
Rapid progressive glomerulonephritis
(URT, LRT and renal feautures)
38
Investigations for granulomatosis with polyangiitis
PR3-ANCA/cANCA-associated
Biopsy shows granulomatous, necrotizing inflammation of vessels, kidneys, and the lungs.
Chest x-ray/CT: multiple bilateral cavitating nodular lesions
39
Definition of eosinophilic granulomatosis with polyangiitis (=churg-strauss syndrome)
a multisystem disease characterized by necrotizing granulomatous vasculitis with eosinophilia, which most commonly involves the lungs and the skin but can also affect the renal, cardiovascular, gastrointestinal, central, and peripheral nervous systems.
40
Potential trigger for eosinophilic granulomatosis with polyangiitis (=churg-strauss syndrome)
Montelukast
41
Clinical features of eosinophilic granulomatosis with polyangiitis (=churg-strauss syndrome)
Chief complaint is severe allergic asthma attacks
Allergic rhinitis/sinusitis
Skin nodules, palpable purpura
Pericarditis
Gastrointestinal involvement: bleeding, ischemia, perforation
Pauci-immune glomerulonephritis
CNS: impaired mental status, mononeuritis multiplex (loss of motor and sensory function)
42
Most helpful diagnostic tool?
Most helpful is:
Biopsy (confirmatory test): tissue eosinophilia and necrotizing granuloma. Biopsy anywhere affected.
Peripheral blood eosinophilia
↑ IgE level
Cirulating MPO-ANCA, pANCA
43
Overall statement for eosinophilic granulomatosis with polyangiitis (churg strauss)
Treatment
Churg-Strauss syndrome = pANCA and polyneuropathy (foot or wrist drop), allergic rhinitis/sinusitis/asthma, vasculitis, eosinophilia, and skin nodules
Treatment same as Wegener: Glucocorticoids, cyclophosphamide
44
Definition of microscopic polyangiitis
necrotizing vasculitis of small vessels, typically with renal, skin, and pulmonary involvement; however, multiple organ systems may be affected
45
Clinical features of microscopic polyangiitis. How can it be differentiated from other small vessel vasculitides?
Clinical features:
Renal: pauci-immune glomerulonephritis with hypertension (--> poor prog)
Lungs: pulmonary vasculitis with hemoptysis
Skin: palpable purpura, nodules, necrosis
46
Diagnostic features of microscopic polyangiitis
Biopsy of involved organ: fibrinoid necrosis with infiltration of neutrophils; no granulomas
Laboratory findings: MPO-ANCA/pANCA (∼ 70% of cases)
Similar to granulomatosis with polyangiitis but spares the nasopharynx!
47
Define cellulitis & erysipelas
Cellulitis is an acute spreading infection of the skin with visually indistinct borders that principally involves the dermis and subcutaneous tissue.
Erysipelas is a distinct form of superficial cellulitis with notable lymphatic involvement and is raised, sharply demarcating it from uninvolved skin. Non purulent
Cellulitis does not have sharp, well-defined borders, unlike an erysipelas infection, which does.
48
Explain the aetiology / risk factors of cellulitis & erysipelas
2 most common causative organisms for cellulitis
What is the most likely cause of cellulitis if the infection is non-purulent
What is the most common organism for erysipelas
Common risk factors of cellulitis include
2 common organisms for cellulitis: Staphylococcus aureus or beta-haemolytic streptococci (e.g. GAS which is strep pyogenes).
Consider MRSA(!!)
However, a number of others also can cause it.
Non-purulent cellulitis is most commonly due to beta-haemolytic streptococci (Meeran told us that!). Cellulitis in association with a purulent focus, or recent furunculosis, should prompt consideration of Staphylococcus aureus, including MRSA, as a possible aetiology.
Erysipelas is almost always caused by group A streptococcus (i.e. non purulent, but demarcated!)
In many instances, tinea pedis may cause a disruption in the cutaneous barrier and allow entry to offending bacterial organisms (e.g. in the toes like the homeless patient- tinea pedis interdigitalis)
Risk factors:
- Recent surgery, trauma, or animal bite (cat, dog, insect).
- Prior episodes of cellulitis, pre-existing lymphoedema or venous insufficiency, and tinea pedis interditialis can all predispose to this condition
- Poor hygeine
- Poor vascularisation of tissue (e.g diabetes mellitus)
49
Recognise the presenting symptoms of cellulitis & erysipelas
Signs and symptoms include an area of redness which increases in size over a couple of days.
A swollen, red, tender, inflamed area of skin with poorly-defined borders is characteristic of cellulitis
Raised erythema with clear demarcations is a hallmark of erysipelas, a superficial form of cellulitis.
50
Recognise the signs of cellulitis & erysipelas on physical examination
Specifically erysipelas?
If it's with abscess
If periorbital vs if orbital cellulitis
Macular erythema with indistinct borders, warmth, tenderness, and oedema.
Bullous changes can occur in some cases.
Identify any tinea pedis/disruption of cutaneous barrier
Erysipelas: Raised intense erythema and oedema as well as borders that are pointedly demarcated from uninvolved skin
Abscess: test for fluid thrill or fluctuation. Aspirate if pus suspected
Periorbital: swollen eyelids and conjunctival infection
Orbital cellulitis: proptosis, impaired acuity and eye movement. Test for RAPD, visual acuity and colour vision (to monitor optic nerve function)
51
Identify appropriate investigations for cellulitis & erysipelas and interpret the results
If query osteomyelitis?
If with abscess?
If NF suspected?
If orbital cellulitis suspected?
1st investigations:
FBC- raised WCC (non-specific, but normal results make it less likely)
Purulent focus culture- may help to identify the presence of resistant pathogens such as MRSA and guide antibiotic selection.
To consider:
Interdigital space culture- lower extremity cellulitis with ipsilateral tinea pedis interdigitalis should do this investigaiton. Can be of use in confirming the organism
Skin biopsy- In cases where the diagnosis is in doubt, skin biopsy is recommended. In addition, in immunocompromised patients who are unresponsive to initial therapy, it can help to identify an unusual pathogen.
Blood culture- usually poor yield in cellulitis so routine use not recommended. Only if constitutional symptoms that might indicate bacteraemia OR if immunocompromised.
Plain radiographs not generally useful unless subjacent osteomyelitis
If an abscess is suspected, an ultrasound may be useful for confirmation
MRI may be helpful if necrotising fasciitis (NF) is suspected. It should not delay surgical consultation if NF is a consideration
CT/MRI if orbital cellulitis suspected, to assess the posterior spread of infection
52
Generate a management plan for cellulitis & erysipelas
Which antibiotic for each causative organism?
What if there is no abscess
```
Medical:
Oral penicillins (e.g. fluclox, benzylpenicillin, coamox) or tetracyclins effective in most community acquired cases. First generation cephalosporins also mentioned.
```
Surgical:
Orbital decompression may be required in orbital cellulitis. This is an emergency
Abscess:
Can be aspirated, incised and drained, or excised completely.
Treatment of erysipelas should follow the same principles as that for cellulitis
53
Identify the possible complications of cellulitis & erysipelas and its management
Sloughing of overlying skin. Localised tissue damage.
Orbital cellulitis: permanent vision loss, spread to brain, abscess formation, meningitis, cavernous sinus thrombosis
54
Summarise the prognosis for patients with cellulitis & erysipelas
Good with treatment
55
Which type of cellulitis is an emergency.
What is the most common causative organism
Investigations?
What is the management
In cases of orbital and preseptal (periorbital) cellulitis, differentiating between the two is important, as orbital cellulitis is an emergency and may require surgical intervention in addition to antimicrobial therapy.
Haemophilus influenzae is most common cause. Infection often arises in adjacent sinuses.
Proptosis and pain or limitation with eye movement suggest orbital disease.
A computed tomography scan is useful in discriminating between orbital and preseptal (periorbital) cellulitis and should be ordered if these diagnoses are being considered.
56
# Define infectious mononucleosis
What is the cause, and what type of pathogen is it
Clinical syndrome caused by primary EBV infection. Also known as glandular fever.
EBV is a gamma herpes dsDNA virus. EBV infects oropharyngeal epithelial cells, leading to B cell infection with incorporation of the viral DNA into host DNA
Humoral and cellular immune response and production of IL2 and IFN-g.
The atypical lympocytes (known as Downey cells) are mostly CD8+ T cells.
Lytic phase controlled by immune response, but EBV remains latent in lymphocytes
57
Explain the aetiology / risk factors of infectious mononucleosis
Transmission
Present in pharyngeal secretions of infected individuals and is transmitted by close contact, e.g. kissing or sharing eating utensils.
58
Summarise the epidemiology of infectious mononucleosis
1– 6 years (usually asymptomatic!!) and 14– 20 years; > 90% of adult population are EBV immunoglobulin (Ig) G positive.
59
Recognise the presenting symptoms of infectious mononucleosis
Incubation period?
4-8 weeks incubation
Abrupt onset: sore throat, fever, fatigue, headache, malaise, anorexia, sweating abdo pain
60
Recognise the signs of infectious mononucleosis on physical examination
Pyrexia
Oedema and erythema of pharynx, fauces and soft palate, with white/creamy exudate on the tonsils which becomes confluent within 1– 2 days, palatal petechiae.
Cervical/generalized lymphadenopathy, splenomegaly (50– 60%), hepatomegaly (10– 20%). Jaundice (5– 10%)
61
Identify appropriate investigations for infectious mononucleosis and interpret the results
What are heterophile antibodies
Blood: FBC (leukocytosis), LFT (raised aminotransferases)
Blood film: lymphocytosis (>20% atypical lymphocytes, most of which are CD8 +ve T cells)
Paul-Bonnell/Monospot test: detects heterophile antibodies. These are antibodies produced in response to EBV but are not actually against EBV antigents. NOTE: 15% are heterophile Ab negative, especially if patient <14yo!
Throat swaps to exclude streptococcal tonsilitis
IgM/IgG yo EBV viral capsid antigen (VCA): usually present at onset of illness. Only in patients with compatible syndrome AND negative monospot test
IgG against EBNA (epstein barr nuclear antigen: Appears 6-12 weeks after symtpom onset. Presence of IgG EBNA, OR absence of IgG and IgM VCA, excludes acute primary EBV infection, and should prompt consideraton of CMV, HIV and toxoplasmosis
62
Generate a management plan for infectious mononucleosis
What advice
Bed rest, paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for fever, throat discomfort and malaise.
Corticosteroids may be indicated for severe cases (e.g. haemolytic anaemia, severe tonsilar swelling, obstructive pharyngitis).
Advise against contact sports for 2 weeks, as increased risk of splenic rupture
63
Identify the possible complications of infectious mononucleosis and its management
Despite humoral and T cell immune responses, which control the initial lytic infection, EBV remains latent in lymphocytes. Reactivation may occur following stress or immunosuppression
Resp: Airway obstruction by oedematous pharynx, secondary bacterial throat infection or pneumonitis
Haematological: haemolytic or aplastic anaemia, thrombocytopaenia
GI/renal: splenic rupture, fulminant hepatitis, pancreatitis, mesenteric adenitis, renal failure
CNS: GBS, encephalitis, viral meningitis, brachial plexitis
EBV ass. malignancy: Burkitt's lymphoma (SS Africa), nasopharyngeal carcinoma (China), post-transplant lymphoma, hodgkin's lymphoma
64
Summarise the prognosis for patients with infectious mononucleosis
Most make an uncomplicated recovery in 3– 21 days. Immunodeficiency and death can occur very rarely.
65
Giving someone with glandular fever certain Abx will result in a skin manifestation.
Which Abx and which skin manifestation
Widespread maculopapular rash in glandular fever patients who have received ampicillin/amoxicillin.
Nearly 100% of patients with infectious mono will develop this!
Note that the Abx aren't given for the infection! Because its a gamma herpes ds-DNA so abx won't work
66
Which of these is NOT an indication for CS use in patients with infectious mononucleosis?
haemolytic anaemia,
severe tonsilar swelling,
confluent white/creamy exudate on tonsils,
obstructive pharyngitis,
confluent white/creamy exudate on tonsils
The other 3 are indications for CS use
67
What can cause false positives to the monospot test?
pregnancy, autoimmune disease, lymphoma/leukaemia
68
Give examples of live attenuated viruses.
What is an absolute contraindication for these
The live attenuated vaccines are - MMR, Varicella + Zoster, Sabin polio (not salk is killed), Influenza, Rotavirus and Yellow Fever.
Live vaccines are absolutely contraindicated in immunosuppressed individuals such as those who are taking two immunosuppressant drugs to prevent graft rejection. The intramuscular vaccine is preferred for patients in this situation
Although the intranasal influenza vaccine is a live virus, the intramuscular influenza vaccine is an inactivated (killed) vaccine that cannot cause the flu. So this would be preferred in immunosuppressed people
69
Which conditions are the following antibodies associated with:
Anti-Saccaromyces cerevisiae antibody
Antimitochondrial antibody
Antismooth muscle antibody
Cytoplasmic antineutrophil cytoplasmic antibody
Perinuclear antineutrophil cytoplasmicantibody
Anti-Saccharomyces cerevisiae antibodies (ASCA) can often be seen in Crohn disease patients.
Antimitochondrial antibody (AMA) is correlated with primary biliary cirrhosis (PBC). PBC involves the destruction of the intrahepatic bile ducts and is not usually characterized by radiological abnormalities
Antismooth muscle antibodies (ASMA) are found in 20-50% of primary sclerosing cholangitis cases. They are highly specific in the diagnosis of autoimmune hepatitis.
C-ANCA is associated with granulomatosis with polyangiitis (GPA), previously known as Wegener disease. GPA is generally characterized by symptoms involving the ears, nose, and throat (sinusitis, otitis media), lungs (hoarseness, cough, dyspnea), or kidneys (hematuria, proteinuria).
In 80% of cases of PSC (and UC), there is an increase in perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), although it is not specific for PSC (it is also found in microscopic polyangiitis and Churg-Strauss syndrome among others).
70
Treatment of neisseria gonorrhoea infection
Treatment is with a third generation cephalosporin, such as ceftriaxone administered as a single intramuscular (IM) dose.
Current recommendations include coverage for presumed co-infection of Chlamydia trachomatis with azithromycin or doxycycline.
71
Clinical triad for chlamydia?
What is interesting about chlamydia's cell wall
Reactive arthritis, conjunctivits and urethritis.
C. trachomatis has a cell wall that lacks muramic acid and unusually, also lacks peptidoglycan.
72
What is interesting about gonorrhoeae cell wall
Neisseria gonorrhoeae has an unusual cell wall for a gram negative organism in that it lacks lipopolysaccharide and instead has lipooligosaccharide.
73
What is interesting about the structure of haemophilus influenza
Haemophilus influenza has a polyribosylribitol phosphate component in its capsule, and the vaccine against this organism has this polysaccharide conjugated to a protein to enhance immunogenicity.
74
Positive culture on chocolate agar?
Chocolate agar is a medium enriched with lysed blood cells (giving it its color), which provides necessary nutrients for the fastidious Neisseria gonorrhea.
75
How do you distinguish streptococcus pyogenes from streptococcus agalactiae
GBS is beta-hemolytic and bacitracin-resistant.
Group A Streptococcus (strep pyogenes), which is gram-positive, beta-hemolytic, and bacitracin-sensitive
The infections they cause are also different.
Streptococcal pharyngitis is the most common form of pharyngitis and caused by group A Streptococcus (GAS)
Group B Streptococcus (GBS), or Streptococcus agalactiae, can cause meningitis, pneumonia, and sepsis in neonates or young infants
76
What does alpha, beta and gamma haemolysis look like on plate
Alpha-hemolysis manifests as a green clearing due to incomplete hemolysis yielding biliverdin.
Beta-hemolytic, meaning that growth on sheep blood agar plates will show a golden clearning around each colony due to complete breakdown of heme.
Gamma-hemolysis refers to the absence of hemolysis.
77
What can be used to diagnose candidate albicans
A potassium hydroxide preparation of the scrapings can be used to diagnose candidiasis.
78
What disease does group A beta haemolytic streptococcus cause
Aka strep pyogenes.
Pharyngitis (infection of the throat).
Can cause scarlett fever, rheumatic fever, acute glomerulonephritis, sydenham chorea
79
What is the cause of glomerulonephriits resulting from pharyngeal/skin infections due to group A beta haemolytic streptococcus?
How does it present
Poststreptococcal glomerulonephritis is an immune-complex disorder whose antigen-antibody interaction is not yet well-defined.
Patients would usually present with dark urine and periorbital edema.
Edema is a result of a defect in renal excretion of salt and water. The severity of edema is often disproportionate to the degree of renal impairment.
80
Haemolytic uraemic syndrome is usually a complication of which infections
Hemolytic-uremic syndrome is a complication of a variety of enteric bacteria, including E. coli, S. dysenteriae, S. typhi, and C. jejuni. It can also be caused by some viruses and some fungi.
81
Subacute sclerosing panencephalitis is associated with which infection
Subacute sclerosing panencephalitis is a deadly encephalitis caused by persistent rubeola (measles) infection. It primarily affects children and young adults, and there is no cure currently.
82
AIDs definiting illnesses
include candidiasis
(of the oesophagus, trachea, bronchi or lungs), cervical cancer, Burkitt’s lymphoma,
cytomegalovirus retinitis, mycobacterium avium complex, Pneumocystis jiroveci
pneumonia and toxoplasmosis.
83
HSV1 is a dsDNA virus.
Primary infection can cause which manifestations
Primary infection is
mostly asymptomatic, but may cause pharyngitis, gingivostomatitis and herpetic
whitlow (digital blisters/pustules).
84
What happens following primary infection with HSV1
Following primary infection, HSV1 becomes
dormant, classically in the trigeminal ganglia.
Reactivation may occur due to physical
or emotional stress or immunosuppression, and presents as herpes labialis (cold
sores).
85
What does infection with HSV2 cause
HSV2 is almost exclusively sexually transmitted and it causes genital herpes
(presenting with genital or anal blisters, often with dysuria, fever and malaise).
86
# Define viral hepatitis A & E
Type of virus
Hep A is only Acute hepatitis (hep A=Acute!)
HAV is a non-enveloped RNA picornavirus,
Hep E is usually acute, but can become chronic in immunosuppressed people only.
HEV is a non-enveloped RNA calicivirus
87
Explain the aetiology / risk factors of viral hepatitis A & E
Route of transmission
What causes the damage
BOTH transmit via the faecal-oral route. HEV also can pass from mother to child during birth
DAMAGE: liver hepatocyte necrosis and liver inflammation caused by the immune response. CD8+ T cells and NK cells target infected cells.
88
Summarise the epidemiology of viral hepatitis A & E
HAV endemic in developing world, infection often subclinical. Better sanitation in developed world means that seroprevalence is lower.
HEV endemic in Asia, African and Central America
Contaminated food and water - often affects travellers
89
Recognise the presenting symptoms of viral hepatitis A & E
Incubation period for HAV and HEV is 3-6 weeks
Prodromal: malaise, anorexia (DISTASTE FOR CIGARETTES IN SMOKERS), fever, nausea, vomiting
Hepatitis: prodrome followed by dark urine, pale stools and jaundice lasting ~3 weeks. May last up to several weeks in HAV because of cholestatic hepatitis
90
Recognise the signs of viral hepatitis on physical examination A & E
Pyrexia, jaundice, tender hepatomegaly, spleen may be palpable (20%).
Absence of stigmata of chronic liver disease, although a few spider naevi may appear, transiently.
91
Identify appropriate investigations for viral hepatitis A & E and interpret the results
Blood: LFT (greatly increased AST and ALT. Increased bilirubin (conguated) and alkaline phosphatase), increased ESR.
In sever cases, albumin may reduce and platelets increase.
Serology for HAV:
Anti-HAV IgM antibodies are elevated for 6 weeks (disappears after 3-5 months)
Anti-HAV IgG antibodies tend to rise a couple of weeks after the IgM and usually persist for life
Serology for HEV:
- anti-HEV IgM elevated for around 2 months.
- anti-HEV IgG rises at around the same time.
- anti-HEV IgG persist only for a few years and IgM fall within months
- HEV RNA in stools is checked. In chronic hep E, HEV RNA persists in the stools and serum for >6 months
92
Generate a management plan for viral hepatitis A & E
What can be given for pruritis
How can it be prevented
Are they notifiable diseases
TREATMENT for both: Giving fluids in the case of dehydration. Anti-emetics, antipyretics. Colestyramine for severe pruritis.
Hep A:
- Supportive treatment if confirmed hep A. No antivirals. Avoid paracetemol/alcohol.
- If worsening jaundice and encephalopathy they might need liver transplant (<1%)
If exposed to hep A AND unvaccinated:
- Post-exposure prophylaxis with intramuscular immune globulin (preferred in over 40s, immunocompromised, chronic liver disease, people allergic to vaccine, people younger than 12)
- Or hep A vaccine
HEV specific:
- Hep E may require a liver transplant if it causes acute liver failure (i.e. IN PREGNANCY!!!!!)
- Chronic hep E in immunosuppressed patients may need you to reduce the dose of immuosuppressants and give ribavirin for 12 weeks
PREVENTION (vaccine for hep A only):
Vaccination with attenuated virus for children and adults before they go to a high risk country.
2 doses of the vaccine given 6 months apart
93
Identify the possible complications of viral hepatitis A & E and its management
Fulminant hepatic failure in tiny, tiny percentage of HAV cases (0.1%)
Cholestatic hepatitis with prolonged jaundice and pruritus may develop after HAV infection.
-------------------
Fulminant hepatic failure in 1-2% of HEV cases BUT UP TO 20% IN PREGNANT WOMEN
-------------------
Post-hepatitis syndrome: Continued malaise for weeks to months.
94
Summarise the prognosis for patients with viral hepatitis A & E
Recovery is usual within 3–6 weeks. Occasionally, a relapse during recovery. There are no chronic sequelae. Fulminant hepatic failure carries an 80% mortality.
95
Schirmers test assesses for what condition
Schirmer’s test assesses tear production in patients with Sjögren’s syndrome.
96
What is herpes simplex keratitis
Herpes simplex keratitis is an infection of the cornea which causes a branched lesion
on the cornea known as a ‘dendritic ulcer’.
It usually presents in adults due to
reactivation of HSV, which has been lying dormant in the trigeminal nerve.
97
What is acute vs chronic viral hepatitis
ACUTE lasts <6 months
The patient is symptomatic
CHRONIC lasts >6 months and the individual can sometimes be asymptomatic OR it can cause fever, fatigue, loss of appetite and extrahepatic symptoms.
On the physical examination, with acute hepatitis, there’s typically hepatomegaly, but with chronic hepatitis, the liver may feel normal on palpation, and if there’s cirrhosis, the lower margin of the liver can feel irregular.
98
What if a blood sample is anti-HAV IgG antibodies postiive and anti-HAV IgM negative
The person is either vaccinated or has had prior infection
99
CRITICAL QUESTION:
In viral hepatitis, what is the cause of jaundice, pale stools and dark urine
The jaundice is NOT caused by decreased conjugation of bilirubin because of enzymes (like in Gilberts) or reduced hepatocyte uptake (like in portosystemic shunts).
It is caused by a failure of the hepatocytes to excrete the bilirubin that it has successfully conjugated. The active exporter of bilirubin is sensitive to damage).
Thus the bilirubin gets stuck in the hepatocytes and doesn't make it out into the bowel.
This makes the stools pale (due to lack of stercobilin), fould smelling and floating (steatorrhoea, due to lack of bile salts which normally solubilise fats in food)
And urine may become dark due to conjugated bilirubin, which is water soluble, being excreted by the kidneys
100
Define viral hepatitis B
Hepatitis caused by infection with hepatitis B virus (HBV), which may follow an acute or chronic course.
Chronci is defined as viraemia and hepatic inflammation continuing > 6 months
101
Explain the aetiology / risk factors of viral hepatitis B
Transmission?
Histology?
Risk factors?
HBV is an enveloped, partially double- stranded DNA virus.
Transmission is by sexual contact, blood and vertical transmission
Antibody- and cell- mediated immune responses to viral replication lead to liver inflammation and hepatocyte necrosis.
Histology can be variable, from mild to severe inflammation and changes of cirrhosis
RISK FACTORS:
- IV drug abuse
- Unscreened blood and blood products
- Infants of HbeAg-positive mothers
- Sexual contact with HBV carriers
102
Summarise the epidemiology of viral hepatitis B
Common
Common in Southeast Asia, Africa and Mediterranean countries.
103
Recognise the presenting symptoms of viral hepatitis B
What % of adults, children, and infants (infected perinatally) have chronic infection
How do you know if they are chronically infected
Incubation 1-6 months (compared with 3-6 weeks for hep A/E)
Nearly all children, and 50% of adults (especially those with HIV) have an ASYMPTOMATIC acute infection
Those who are symptomatic can have similar symptoms to hep A
1-2 week prodrome malaise headache, anorexia, nausea, vomiting, diarrhoea and RUQ pain and jaundice
OR
May experience SERUM SICKNESS TYPE ILLNESS (fever, arthralgia, polyarthritis, urticaria, maculopapular rash
Recovery usually within 4-8 weeks. One percent may develop fulminant liver failure.
Most adults then clear the infection, but 5% progress to chronic. In contrast 20-50% of young children develop chronic. And 90% of infants infected perinatally.
Chronic hepatitis is indicated by persistently elevated HBs antigen levels, as well as high HBV DNA and transaminase levels in cases of persistent liver inflammion, for more than 6 months
104
Recognise the signs of viral hepatitis B on physical examination
Acute: Jaundice, pyrexia, hepatomegaly, splenomegaly, cervical lymphadenopathy in 10-20%.
Urticaria/maculopapular rash
Chronic: may have no findings, or signs of chronic liver disease or decompensation
ALSO extraheaptic manifestations in CHRONIC infection are:
- Polyarteritis nodosa
- Membranous glomerulonephritis
105
Identify appropriate investigations for viral hepatitis B and interpret the results
WHICH ONE IS MEASURED TO TEST FOR SUCCESSFUL VACCINATION?
GENERATION OF WHICH ANTIBODY SHOWS THAT THE INFECTION HAS BEEN CLEARED.
HEP B VIRAL SEROLOGY.
1) Hepatitis B surface antigen (HBsAg) and anti-HBs antibody.
The anti-HBs antibody is not produced at a high enough level for detection until AFTER the infection has been cleared (i.e in chronic hep B, anti-HBs antibody will be negative)
So if there's infection, HBsAg is positive, but anti-HBsAg will be negative.
If anti-HBs is positive, and HBsAg is negative, it means that the infection is cleared OR the person is vaccinated. Note that vaccination of hep B is with surface antigen.
If they are both negative, either you've never been exposed before OR you've cleared the infection (so HBsAGg is gone), but the level of antibody hasn't yet risen enough for detection.
2) Hepatitis B core antigen (HBcAg) and anti-HBc antibody
HBcAg rises in the infection
There's IgM-anti-HBc and IgG-anti-HBc antibodies.
Neither rise with vaccine.
In acute HBV, IgM-anti-HBc and IgG-anti-HBc become positive.
Overtime, regardless of whether the infection clears, IgM-anti-HBc falls, and IgG-anti-HBc remains positive. So this just tells you about passage of time not whether the infection is cleared
3) HBeAG (hepatitis B e antigen)
If it's positive then the virus is actively replicating.
If it's negative, the virus may not be actively replicating OR because there's no virus at all.
4) HBV DNA PCR
If it's high level, then the virus is actively replicating and highly infection
If it's at a low level, then the virus is around but not actively replicating
None means there's no virus
------------------------
LFTs: Highly raised AST and ALT. Raised bilirubin and alk phos
Clotting: increased PT in severe disease
Liver biopsy: percutaneous, or transjugular if clotting is derange or ascites is present
106
Generate a management plan for viral hepatitis
Prevention?
Vaccination?
Acute?
Chronic? --> What are the indications for antivirals?
Prevention: blood screening, safe sex, instrument sterilisation
Passive immunisation: Hepatitis B immunoglobulin is given following acute exposure and to neonates born to HbeAg-positive mothers (in addition to active immunisation)
Active immunisation: Recombinant HbsAg vaccine for at risk individuals and neonates born to HBV positive mothers. This immunisation against HBV also protects against HDV
Acute HBV hep:
- 95% of immunocompetent people with acute infection will generate anti-HBs antibody without needing any treatment.
- Symtpomatic treatment with bed rest, antiemetics, antipyrretics and cholestyramine for pruritis. Notification to consultant in communicable disease control.
- If they have a severe protracted course, they might need entecavir/tenofovir. Continue treatment until presence of anti-HBs antibody is confirmed, or indefinitely in patients who undergo transplantation
- If they have fulminant liver failure, transplantation may be needed
Chronic HBV hepatitis:
- Indications for treatment with antivirals:
1) HbeAg-positive or HbeAg-negative chronic hepatitis (depending on ALT and HBV DNA levels)
2) Compensated cirrhosis and HBV DNA >2000IU/mL, entecavir/tenofovir given infedinitely.
3) Decompensated cirrhosis and detectable HBV DNA by PCR- entecavir/tenofovir started regardless
Give subcutaneous injection of interferon alpha (standard or pegylated, which has a longer half life), or nucleos/tide analogues (adefovir, entecavir, tenofovir).
Interferon alpha is a cytokine which augments natural antiviral mechanisms
107
Identify the possible complications of viral hepatitis and its management
Side effects of interferon alpha?
Fulminant hepatic failure
Chronic HBV infection (10% in adults, MUCH higher in neonates)
Cirrhosis and hepatocellular carcinoma
Extrahepatic immune complex disorders like glomerulonephritis, polyarteritis nodosa
Superinfection with HDV may lead to acute liver failure or more rapidly progressive disease
-------------------------
Side effects of interferon alpha: flu like symptoms, fever, chills, myalgia, headaches, bone marrow suppression and depression, necessitating discontinuation in 5-10% of patients
108
Summarise the prognosis for patients with viral hepatitis
In adults;
10% become chronic, of these, 20-30% develop cirrhosis.
109
What can be measured every 6 months to assess if there is hepatocellular carcinoma in Hep B
Alpha fetoprotein levels
110
# Define viral hepatitis D
Type of virus
| Transmission?
A defective virus.
It is a single stranded RNA virus coated with hepatits B surface antigen (HBsAg).
It is also transmitted by the blood/bodily fluid route.
Only 2 circumstances that it can be transmitted to give acute hepatitis D:
1. Co-infection of HBV and HDV (i.e. the person is infected with both at the same time)
2. Superinfection of a HBV patient with HDV (i.e. a carrier of HBV is subsequently infected with HDV)
Often, the virus is not cleared and it becomes a chronic infection
Antibody- and cell- mediated immune responses to viral replication lead to liver inflammation and hepatocyte necrosis.
111
Explain the aetiology / risk factors of viral hepatitis D
Infection with HBV is necessary for infection.
Can be transmitted through blood and bodily fluid
112
Summarise the epidemiology of viral hepatitis D
Found worldwide
113
Recognise the signs and symptoms of viral hepatitis on physical examination D
As for hep B
114
Identify appropriate investigations for viral hepatitis and interpret the results D
First you must demonstrate confirmation of hepatitis B infection.
In acute hepatitis D:
- HDV IgM is positive
- HDV IgG are negative
- Serum HDV RNA is positive
- HDAg may be positive or negative (it disappears very quickly following infection)
In chronic hepatitis D:
- HDV IgM is negative
- HDV IgG are positive
- Serum HDV RNA is positive
- HDAg is negative (it disappears very quickly following infection)
115
Generate a management plan for viral hepatitis D
Initiated IF:
- Elevated HDV RNA AND
- Elevated AST & ALT
Pegylated INF alpha-2a or 2b is given once a week for 2 months
Prevention is established through hep B vaccination
116
Identify the possible complications of viral hepatitis and its management D
As for hep B
117
Summarise the prognosis for patients with viral hepatitis D
As for hep B
118
# Define viral hepatitis C
Type of virus
Can cause acute AND chronic hepatitis. But chronic in 80% of cases
Caused by contact with blood and bodily fluid and vertical transmission
Type:
HCV is a small, enveloped, single-stranded RNA virus of the flavivirus family.
As it is an RNA virus, fidelity of replication is poor and mutation rates are high, resulting in different HCV genotypes, and even in a single patient, many viral quasi-species may be present.
Risk groups:
- Recipients of blood and blood products prior to blood screening
- IV drug users, non-sterile acupuncture and tattooing,
- Those on haemodialysis and health care workers.
- Sexual and vertical transmission is uncommon (1–5%, risk in those co-infected with HIV).
119
Explain the aetiology / risk factors of viral hepatitis C
What are the extra-hepatic manifestations
EXTRAHEPATIC:
- Cryoglobinaemia (increased blood viscosity)
- Membranoproliferative glomerulonephritis
- Porphyria cutanea tarda
120
Summarise the epidemiology of viral hepatitis C
.
121
Recognise the presenting symptoms of viral hepatitis C
90% of acute infections are asymptomatic with <10% becoming jaundiced with a mild flu-like illness
May be diagnosed with incidental abnormal LFT or in older individuals with complications of cirrhosis
122
Recognise the signs of viral hepatitis C on physical examination
May be no signs, or may be signs of chronic liver disease in long standing infection.
Less common extra-hepatic manifestation:
Cryoglobinaemia (increased blood viscosity) --> headaches and confusion
Erosions and blisters on the skin (Porphyria cutanea tarda) (these are also caused by cryoglobinaemia causing a small vessel vasculitidis)
Renal dysfunction (glomerulonephritis)
123
Identify appropriate investigations for viral hepatitis C and interpret the results
Hep C serology:
Check anti HCV IgG
If it's positive, look at the HCV RNA. If it's positive then there's a hep C infection. If it's negative then the infection has cleared
If HCV RNA remains positive for >6 months then it's a chronic HCV infection, otherwise it's chronic
APRI score (AST to platelet ratio index) --> to predict the degree of fibrosis.
[(Individual's AST/Normal AST)/platelet count].
Below 0.5=minimal fibrosis
0. 5-1.5= in-between
1. 5+=significant fibrosis
On liver biopsy: LYMPHOID FOLLICLES IN THE PORTAL TRACTS. Fatty change and cirrhosis
124
Generate a management plan for viral hepatitis C
Prevention
Prevention:
-Screening of blood, blood products and organ donors, needle exchange schemes for IV drug users, instrument sterilisation. NO VACCINE AT PRESENT.
Medical
ACUTE: No specific management, mainly suipportive (e.g. antipyretics, antiemetics, cholestyramine). Specific antiviral treatment can be delayed for 3–6 months.
With cirrhosis:
For individuals with cirrhosis, there's high risk of developing hepatocellular carcinoma. So USS every 6 months, and alphafetoprotein levels checked for tumours.
```
-Compensated cirrhosis:
Sofosbuvir + velpatasvir/daclatasvir for 12 weeks
OR
Glecaprevir + pibrentasvir for 12 weeks
OR
Sofosbuvir + daclatasvir for 24 weeks
```
```
-Decompensated cirrhosis:
Sofosbuvir + velpatasvir for 24 weeks
OR
Sofosbuvir + daclatasvir for 12 weeks
In some cases, liver transplantation
```
Without cirrhosis:
Sofosbuvir + velpatasvir for 12 weeks
OR
Glecaprevir + pibrentasvir for 8 weeks
Rapid medicine:
Pegylated interferon-a and ribavarin (guanosine nucleotide analogue) is the treatment strategy of choice.
HCV genotype 1 or 4: 24-48 weeks
HCV genotype 2 or 3: 12-24 weeks.
Monitoring of HCV viral load is recommended after 12 weeks of treatment to determine efficacy of treatment. Regular ultrasound of liver may be necessary if the patient has cirrhosis.
125
Identify the possible complications of viral hepatitis C and its management
Fulminant hepatic failure in the acute phase,
chronic HCV carriage,
cirrhosis and hepatocellular carcinoma
less commonly porphyria cutanea tarda, cyroglobinaemia and glomerulonephritis
126
Summarise the prognosis for patients with viral hepatitis C
Approx 80% of exposed progress to chronic HCV,
of these, 20-30% develop cirrhosis over 10-20 years
127
What is Ramsay Hunt syndrome
How does it present
Ramsay Hunt
syndrome is a type of shingles caused by reactivation of varicella zoster in the
geniculate ganglion of the facial nerve.
It presents with facial nerve palsy, altered
taste, dry eyes/mouth and a vesicular rash in the ear canal.
128
How can a diagnosis of malaria be investigated
Malaria is diagnosed following the microscopic analysis of blood films. There are two main types of blood films, thin and thick.
Thin films preserve the appearance of the parasites allowing species
identification.
Thick films screen a larger volume of blood allowing higher sensitivity
when picking up low level infections.
129
What is onycholysis and what are the causes
Onycholysis is a common nail condition characterised by painless separation of the
fingernail or toenail from the nailbed.
DR PITHS:
Drugs (tetracyclines, oral contraceptive, diabetes drugs)
Reactive arthritis
```
Psoriasis
Infection (ESPECIALLY FUNGAL)
Trauma
Hyper- and hypothryoidism
Sarcoidosis, scleroderma
```
130
Define necrotising fasciitis
necrotizing fasciitis is an infection of the deep soft tissues that results in the destruction of the muscle fascia and overlying subcutaneous fat.
131
Explain the aetiology / risk factors of necrotising fasciitis
Most commonly a synergistic polymicrobial infection spreading along fascial planes. Often caused by group A b haemolytic Strep pyogenes, or gram negative and anaerobic synergistic infection e.g. enterococci and bacteroids
RF: diabetes, PVD, leg ulcers, malignancy, immunosuppression and steroid use.
OCCASIONALLY occurs without obvious predisposition or in relation to puncture wounds, ulcers or surgical wounds
Commonly involves extremeties, especially those with diabetes and PVD.
132
Summarise the epidemiology of necrotising fasciitis
Gangrenen relatively common
Gas gangrene and nec fasciitis are uncommon
133
Recognise the presenting symptoms of necrotising fasciitis
It can evolve over hours, leading to systemic toxicity, limb loss, and death.
Pain often severe and out of proportion to the apparent physical signs.
Initially, the tissue may be red, but then can quickly cause severe pain, fever, and crepitus, with the overlying skin developing into patches of red-purple.
Over the course of a few days the skin can breakdown and bullae can form - over time developing areas of gangrene.
134
Recognise the signs of necrotising fasciitis on physical examination
Area of erythema and oedema, areas of haemorrhagic blisters may be present with crepitus on palpation
Associatied signs or systemic inflammatory response and sepsis:
- Pyrexia
- Tachycardia
- Tachypnoea and
- Hypotension
135
Identify appropriate investigations for necrotising fasciitis and interpret the results
Management?
USS can be used when necrotising fasciitis is suspected
In necrotizing fasciitis, a CT scan is often done as well, although diagnosis is always made through exploratory surgery.
Agrressive debridement of all infected tissues to limit spread and systemic sepsis
136
Triad of symptoms seen with granulomatosis with polyangiitis
triad of upper and lower respiratory
tract involvement (nosebleeds and haemoptysis) and glomerulonephritis (haematuria
and proteinuria).
saddle nose is another clinical feature too
Associated with cANCA
137
How would you distinguish Goodplastures from granulomatosis with polyangiitis
Nose bleeds aren't a feature of Goodpastures
138
What antibodies is autoimmune hepatitis associated with
anti-LKM and anti-smooth muscle antibodies (ASMA)
139
How is systemic inflammatory response syndrome
Heart rate >90bpm
Resp rate >20/min or PaCo2<4.3 kPa
Temp >38 or <36
WCC <4 x 10^9 or >12*10^9
140
What is the difference between SIRS and sepsis
Sepsis is a spectrum with varying degrees of severity. Septicaemia refers to the
presence of an organism within the blood. Sepsis is, in simple terms, the
combination of septicaemia and SIRS.
141
What is a marker of severe sepsis
Severe sepsis occurs when septic patients
| begins to show evidence of organ hypoperfusion (e.g. elevated serum lactate).
142
T/F conjunctivitis usually becomes bilateral
Initially, the disease may only affect one eye but it will usually
become bilateral.
143
What other treatment must be given with antibiotics for TB and why
Pyridoxine (vitamin B6) MUST be given alongside TB treatment because isoniazid (one of the 4 Abx used to treat TB) causes vit b6 deficiency, which causes peripheral neuropathy
144
What are the complications of herpes zoster opthalmicus
Shingles affecting opthalmic branch of the trigeminal nerve
Usually, conjuncitivitis occurs, sometimes with a mild keratitis.
Corneal ulcers, uveitis or involvement of retina or optic nerve can occur.
Extraocular palsies are rare
145
When are you worried about herpes zoster infection
If the tip of the nose is affected by the rash, then the nasociliary nerve is involved, and thus the eyeball is more likely also to be involved (Hutchinson’s sign, said to be an exam favourite item in postgraduate exams).
146
Best prophylactic Abx in the following circumstance:
- Those in close quarters with someone who has and bacterial meningitis
- Chaning long term urinary catheter
- Malaria
- Bite wound
Rifampicin is the appropriate drug to use for bacterial men
Gentamicin is used as prophylaxis for changing a long-term urinary catheter.
Doxycycline may be used for malaria prophylaxis.
Co-Amoxiclav may be used for prophylaxis of a bite wound.
147
What are the indications for giving prophylactic Abx for PCP?
All patients with a CD4 count < 200 cells/mm3 or a CD4 percentage < 14% on two separate occasions should be offered PCP prophylaxis in the form of daily oral co-trimoxazole treatment first line, as they are at significant risk of opportunistic infection.
The same applies to patients with a previous PCP diagnosis until their CD4 is > 200 and their viral load has been undetectable for 6 months.
148
What are the 4 phases of chronic carriage
Which types progress fastest to cirrhosis and cancer
Over 90% of infants born to HBV eAg positive mothers will become chronic carriers unless immunised. There are 4 phases of chronic carriage:
1) Immune tolerant- HBV eAg positive, normal aminotransferase levels, little or no necroinflammation on liver biopsy
2) Immune active- HBV eAg positive, raised aminotransferases, progressive necroinflammation and fibrosis on liver biopy
3) Inactive HBV carrier- HBV sAg positive, eAg negative, low levels of HBV DNA and normal aminotransferases
4) eAg negative chronic active hepatitis- Precore, core promotormutations, eAg negative, detectable HBV DNA, progressive inflammation and fibrosis
Types 2 and 4 may progress to cirrhosis and liver cancer, with type 4 generally progressing fastest
149
In what percentage of HBV pregnancies does vertical transmission occur
Vertical transmission of HBV occurs in 90% of pregnancies where the mother is HBV eAg positive and reduces to 10% when the mother is HBV sAg positive and eAg negative
HBV may exacerbate after the end of pregnancy.
150
What % of infected HBV infants become chronic carriers
90%
151
What is affected with HBV:
misscarriage & delivery, or breast feeding?
There is an increased risk of miscarriage and preterm labour in mothers with acute HBV infection
Breast feeding is fine to do
152
What happens to baby born to onfectious HBV mother
nfants born to infectious mothers are vaccinated from birth, usually in combination with Hepatitis B specific immunoglobulin. This reduces vertical transmission by 90%
153
When is the infectious period of HBV in acute disease
In acute disease, the infectious period of HBV is from 2 weeks before the onset of jaundice until the patient becomes HBV sAg negative.
154
Somebody comes to the GP telling you they have had sex 2 weeks ago with someone they now found was HBV positive.
What can be done
Specific hepatitis B immunoglobulin (HBIG) can be given to a non-immune contact after a single unprotected sexual exposure or parenteral exposure/needlestick injury if the donor is known to be infectious. This works best WITHIN 48 hours and is of no use after 7 days.
So this can't be done here
BUT
Vaccination theoretically will provide some protection from disease when started up to 6 weeks after exposure.
155
How do you test for effectiveness of HBV vacccine?
this is demonstrated on serology with HBV antiHBs titres of over 10 i.u./l.
156
Which hepatitis carries a poor response to therapy, and causes rapid progression of another hepatitis, and makes another hepatitis very severe
Hep D, which requires the hepatitis B virus outer coat. It is thus only found in patients with HBV.
It is associated with a high rate of fulminant hepatitis and progression of chronic hepatitis to cirrhosis. It should be suspected if acute hepatitis is severe, if chronic HBV carriers get a further attack of Acute hepatitis or if the liver disease in chronic HBV is rapidly progressive
157
What stain is used for malaria
Giemsa
158
What stains are the following for:
India Ink
Sudan black
India ink- cryptococcus spp
Sudan black - AML
159
What is Behcet's disease
Inflammaotry multisystem disease featuring triad of orogenital ulceration and uveitis.
160
What is the HLA assocation of Behctes
HLA-B51
161
What is the investigation for Behcets
Pathergy test (needleprick inflamed and sterile pustile develop with 24-48htrs.
Complement levels, family history
162
Seoptic arthritis requires which level of white cells in the joint aspirate
a diagnosis of
septic arthritis
requires WBCs >50,000 cells/µL
163
What are the causes of septic arthritis
Sexually active?
Children?
Elderly/IVDU?
Generally, the most common causative organisms
are S. aureus, streptococci and Neisseria gonorrhoeae
```
Unprotected sex
is a risk factor for
septic arthritis
most characteristically by
Neisseria gonorrhea
infection.
```
H. influenzae is a common cause in children. E. coli can cause septic arthritis
in the elderly and IV drug users. TB is a rare cause of septic arthritis.
164
Self mutilation by nail biting and gout
Lesch nyan syndrome- X linked disorder.
165
What is malaria
Parasitic infection- protozoa Plasmodium.
Most serious is plasmodium falciparum.
166
Aetiology and risk factor for malaria
Transmitted by bite of female Anopheles mosquito
They protozoa infect RBCs and grow intracellularly
1. Sporozoites injected into blood by mosquito
2. Exoerythrocytic schizogeny in hepatocytes
3. Merozoites are produced from this, which reinvade the blood and, inside RBCs, go from trophozoite to multinucleated schizonts (erythrocytic schizogeny)
4. RBCs rupture and release merozoites
5. Gametocytes taken up by anopheles mosquitoes and fevelop into sporozoites again ijn their gut and migrate to salivary gland.
Innate immunity: Sickle cell trait, G6PD deficiency, pyruvate kinase deficiency, thalassaemias)
167
Epidemiology of malaria
...
168
History for malaria
Peaks?
Cerebral malaria
Suspect in any fevereish traveller. Incubation UP TO 1 YEAR, but USUALLY 1-2 WEEKS.
Cyclical symptoms of high fever, flulike symptoms, severe sweating and shivering cold/rigors.
Peak temps coincide with rupture of intra-erythroctic schizonts:
- Every 48h for P falciparum/vivax/ovale
- Every 72hr for P malariae
P Falciparum is dangerous in pregnancy
Cerebral malaria: headache, disorientation, coma
169
Signs of malaria
Pyrexia/rigors, anaemia, hepatosplenomegaly
170
Investigations for malaria
Thick/thin blood film using Field's or Giemsa's stain.
Measure daily for detection and quantitative count of level of intracellular ring forms. Has to be negative for 3 days to exclude malaria. >2% in P. falciparum malaria is severe.
Thick-->detect presence of parasite
Thin--> detect species of malaria.
Trophozoites are most often identified, inside RBCs
171
What is a fixed drug eruption and what are the usual causes
```
Fixed drug eruption is a relatively common reaction that occurs with drug reexposure. It is characterized by
erythematous
,
edematous
plaques with a grayish center or frank bullae, recurring at the same sites. Lips, tongue, genitalia, and face are commonly affected.
Sulfonamides
and
anticoagulants
are common cultprits.
```
172
What can causes steven johnson syndrome, and what type of reaction is that
Type IV
allopurinol
,
aromatic
```
anticonvulsants
,
sulfonamides
,
lamotrigine
, and oxicam
non-steroidal anti-inflammatory drugs
(
NSAIDs
) and penicillin
```
173
What is the diagnostic test for behcets disease
Pathergy test (needle prick becomes inflamed and a sterile pustule develops within 24–48h). Complement levels, family history.
174
HLA association of behcets
HLA-B51,
cardiolipid antibodies (anti-phospholipid) can be present
175
Prevalence of behcets- males or female more common?
Male>>female
176
Infectious trigger for bechets?
Parvovirus, HSV
177
Hx of behcets
```
Oral aphthosis
Genital aphtosis
Occular lesions (conjunctivitis!)
Skin lesions
Neurological manifestations
Vascular manifestations
```
178
Sepsis 6
3 OUT:
- Blood cultures
- Serum lactate and Hb
- Urine output
3 IN:
- IV Abx
- IV fluids
- High flow o2
179
What is the most common cause of candidiasis
Candida albicans
180
What is candidiasis
Candidiasis is a fungal infection caused by a yeast (a type of fungus) called Candida.
181
What type of infections can C albicans cause in immunocompetent people
Immunocompetent:
Thrush (affecting oral cavity)
Vaginal yeast infections (if there is an underlying pH imbalance)
Infection of of the intertriginous areas of skin (axillae or gluteal folds)
182
What type of infections can C albicans cause in immunocomprimised people
Which area is most comomonly infected
More widespread and systemic infections may occur in immunocompromised individuals (e.g., neonates, diabetics, and HIV patients), with the esophagus most commonly affected (candida esophagitis)
183
T/F candida albicans forms hyphae
Where can is usually be found in the body
T
C. albicans is a type of oval, budding yeast (see general mycology)
Forms hyphae and long pseudohyphae
Ubiquitous on healthy skin, as well as in the oropharyngeal cavity, gastrointestinal tract, genitourinary tract, and vagina
184
Risk factor for candidasis infection
Immunosuppression:
HIV, DM, certain patient groups (ICU, transplant, surgical patients, neonates)
Medicines:
Medications: antibiotics, steroids, cytostatic agents, immunosuppressive therapy
Increased Estrogen levels during pregnancy
Smoking cigarettes
185
Pathophysiology of local candidasis infection
imbalance in local flora (e.g., triggered by antibiotic use) --> local overgrowth of C. albicans ---> local mucocutaneous infection (e.g., oropharyngeal infection, vaginitis)
186
Pathophysiology of systemic candidiasis infection
local mucocutaneous infection --> breach of skin/mucosal barrier or translocation (IV catheterisation, ascending infection in pyelonephritis, or resorption via GIT) --> direct invasion of bloodstream (candidemia) --> spread to visceral tissues --> disseminated organ infection (e.g., pyelonephritis, endocarditis)
187
Diagnosis of candidasis infection
A suspected diagnosis based on clinical appearance requires confirmation with additional tests.
KOH test on a wet mount preparation of scrapings or smears: can see budding yeasts, hyphae
Blood or tissue culture (BEST CONFIRMATORY TEST).
Endoscopy:
- In immunocompetent individuals with odynophagia
- When candida infection not responsive to oral fluconazole therapy
Findings: white mucosal plaque-like lesions
188
You find a HIV infected patient who you suspect candidasis. You perform a blood culture and you find the pathogen forms germ tubes at 37 degrees. What is the likely pathogen
Candida spp. form yeast cells and pseudohyphae at 20–25°C
Candida albicans forms germ tubes at 37°C
So in this cases candida albicans
189
Treatment for local mucocutaneous candidiasis:
- Vaginal yeast infection
- Eosophageal candidiasis
-Vaginal yeast infection: either topical antifungal agent (clotrimazole cream) 3-14 days or singe dose fluconazole
-Eosophageal candidiasis.
First line: oral or IV fluconazole for 14-21 days
190
Biopsy of skin lesion in drug induced lupus would show what
Hydropic degeneration of the
basal layer
of the epidermis is characteristic of lesions in drug-induced
lupus
(produces discoid rash in sun exposed areas e.g. face)
191
Define gastroenteritis
Acute inflammation of the lining of the GI tract, manifested by nausea, vomiting, diarrhoea and abdominal discomfort.
192
Broad causes of gastroenteritis
Bacterial
Viral
Toxins
Protozoa
193
Bacterial causes of gastroenteritis
Campylobacter jejuni, Escherichia coli (particularly 0157), Salmonella, Shigella, Vibrio cholerae, Listeria, Yersinia enterocolitica
194
Protozoal causes of gastroenteritis
Entamoeba histolytica, Cryptosporidium parvum, Giardia lamblia
195
Which toxins can cause gastroenteritis
Improperly cooked meat (S. aureus, C. perfringens), old rice (B. cereus, S. aureus), eggs and poultry (Salmonella), milk and cheeses (Listeria, Campylobacter), canned food (botulism).
196
Example of non-inflammatory mechanism of gastroenteritis
V cholera, EHEC produce enterotoxins that cause enterotoxins to secrete water and electrolytes
197
Example of inflammatory mechanism of gastroenteritis
e.g. Shigella, enteroinvasive E. coli release cytotoxins and invade and damagethe epithelium, with greater invasion and bacteraemiain the case of Salmonella typhi.
198
Hx of gastroenteritis
Sudden onset nausea, vomiting, anorexia
Diarrhoea (bloody or watery), abdominal pain or discomfort, fever and malaise. Enquire about recent travel, antibiotic use and recent food intake (how cooked, source and whether anyone else ill).
199
gastroenteritis and paralysis?
Botulinum causes paralysis
200
Examination of gastroenteritis
Diffuse abdominal tenderness, abdominal distension and bowel sounds are often increased.
If severe, pyrexia, dehydration, hypotension, peripheral shutdown.
201
Investigations of gastroenteritis
The diagnosis of gastroenteritis is usually made on the basis of clinical symptoms and signs. Stool cultures are usually not necessary for most adults who present with acute, watery diarrhoea.
The person is systemically unwell.
There is blood or pus in the stool.
The person is immunocompromised.
There is a history of recent hospitalization and/or antibiotic treatment.
Diarrhoea occurs after foreign travel to anywhere other than Western Europe, North America, Australia, or New Zealand.
Diarrhoea is persistent and giardiasis is suspected.
There is uncertainty about the diagnosis of gastroenteritis.
202
Management of gastroenteritis
Assess for shock and dehydration.
You might need to admit (s vomiting and unable to retain oral fluids.
Has features of shock or severe dehydration)
Give rehydration advice. Consider oral rehydration salt in those older than 60, frail etc. IV rehydration may be necessary in those with severe vomiting.
Empirical antibiotics are not generally helpful for acute gastroenteritis managed in primary care. Most infections are self-limiting. Antibiotic treatment is only warranted if severe or the infective agent has been identified
203
Somebody has gastroenteritis, which has been found to be caused by entamoeba histolytica. How would you treat.
Antibiotic treatment is usually recommended for all people with amoebiasis.
The antibiotic of choice is metronidazole, followed by a 10-day course of diloxanide
204
Somebody has gastroenteritis, which has been found to be caused by campylobacter. How would you treat.
Abx not necessary for mild treatment.
Consider for severe symptoms (bloody diarrhoea, immunocompromised, more than 8 stools per day, symptoms longer than 1 week)
IF indicated as described above, prescribe erythromycin 250mg to 500mg for 5-7 days.
205
Somebody has gastroenteritis, which has been found to be caused by Escherichia coli 0157 (VTEC). How would you treat.
Management is entirely supportive; there is no specific treatment for gastroenteritis due to Vero cytotoxin-producing Escherichia coli 0157 (VTEC).
Do not prescribe antibiotics.
Avoid antimotility drugs, such as loperamide or diphenoxylate, and opioids.
Advise against the use of nonsteroidal anti-inflammatory drugs, such as ibuprofen.
206
Somebody has gastroenteritis, which has been found to be caused by Salmonella. How would you treat.
Antibiotic treatment is not recommended for healthy people with gastroenteritis due to Salmonella infection.
If they are over 50, immunocompromised and have cardiac valve disease, give ciprofloxacin twice a day for 1 day only.
207
Complications of gastroenteritis
Dehydration,electrolyte imbalance, pre-renal failure.
Secondary lactose intolerance (particularly in infants).
Sepsis and shock (particularly Salmonella and Shigella).
Haemolytic uraemic syndrome is associated with toxins from E. coli 0157.
Guillian–Barre syndrome may occur weeks after recovery from Campylobacter gastroenteritis
208
Side effects of ribavarina and interferon
Ribavirin toxicity can cause hemolytic anemia, and interferon alpha-2a can cause bone marrow depression. This can lead to decreased oxygen-carrying capacity of the blood resulting in fatigue and shortness of breath.
209
HEPATITIS SEROLOGY
https://www.healthunit.com/interpretation-hepatitis-serology#hepa
210
Which drug can cause progressive multifocal leukoencephalopathy and what virus is it as a result of
Progressive multifocal leukoencephalopathy
only occurs in majorly immunocompromised individuals, such as those receiving
natalizumab
for
Crohn disease
. It is caused by the John Cunningham (JC) virus and typically presents with hyperintensive lesions on T2 MRI, as well as signs of progressive
neurological
damage.
211
What is the risk of hep B, hep C and HIV infection following needlestick injury from an infected patient
The risk of transmission of both hepatitis B and C is greater than HIV from a needle stick injury (roughly 1 in 3 for HBV, 1 in 30 for HCV and 1 in 300 for HIV).
212
Causes of infection with HIV
Sexual intercourse:
-Heterosexual most common worldwide, but increase risk in homosexuals in the west
2. Bloods (and other bodily fluid). Mother to child, needles, blood products, organ
213
How does HIV cause damage
HIV enters the CD4 lymphocytes following binding of its envelope glycoprotein (gp120) to CD4 and a chemokine receptor.
Reverse transcriptase (in viral core) reads RNA to manufacture DNA, which is incorporated into the host genome.
Dissemination of virions leads to cell death and eventually to T-cell depletion.
214
Outline the stages of HIV infection
1. Serovonversion (4-8 weeks post infection).
self-limiting – fever, night sweats, generalized lymphadenopathy, sore throat, oral ulcers, rash, myalgia, headache, encephalitis, diarrhoea.
2. Early/asymptomatic. 18 months-15years+.
apparently well–some patients may have persistent lymphadenopathy (>1cm nodes, at 2+ extrainguinal sites for >3 months). Progressive minor symptoms, e.g. r1ash, oral thrush, weight loss, malaise.
3. AIDS.
Syndrome of secondary diseases reflecting severe immunodeficiency or direct effect of HIV infection (CD4 cell count <200/mm3).
215
Outline direct effects of HIV infection
Neuro: polyneuropathy, myelopathy, dementia
Lung: Lymphocytic interstitial pneumonitis
Heart: Cardiomyopathy, myocarditis.
Haemotological: Anaemia, thrombocytopenia.
GI: Anorexia, HIV enteropathy, severe wasting
Eyes: cotton wool spots
216
Infection of tongue secondary to HIV infection?
Epstein–Barrvirus(EBV)(oral hairy leukoplakia on the side of the tongue)
217
What are the fungal infections that HIV positive people can have
Pneumocystis pneumonia (PCP), Cryptococcus (meningitis), Candida (oral, airway, genital, oesophageal), invasive aspergillosis
218
What are the protozoal infections that HIV positive people can have
Toxoplasmosis, cryptosporidia and microsporidia (diarrhoea).
219
What are the features of toxoplasmosis infection
cerebral abscess, chorioretinitis, encephalitis
220
Investigations if you suspect HIV
1. HIV ELISA. False negatives can occur during window period immediately after infections before antibodies have been made.
A positive result should be confirmed with a Western blot or second ELISA.
The window period can be reduced to 2 to 4 weeks by using fourth-generation tests and those that include IgM antibodies to HIV and/or HIV antigen (p24) assays
Serum p24 antigen/serum HIV DNA PCR.
TO INDICATE IMMUNE STATUS AND ASSIST IN STAGING:
CD4 count
TO MONITOR THERAPY RESPONSE:
Serum viral load (HIV RNA)
221
What investigation for PCP infection
CXR bilateral perihilar/ground glass shadowing, bronchoalveolar lavage
222
What investigation for cryptococcal meningitis
Brain CT or MRI, lumbar puncture – cerebrospinal fluid (CSF) microscopy (India ink staining), culture, ELISA for antigen
223
What investigation for CMV
Colonoscopy and biopsy (cytomegalic cells with inclusions)
224
What investigation for toxoplasmosis
Brain CT or MRI shows ring-enhancing lesions
225
What investigation for cryptosporidia/microsporydia
Stool microscopy (causes diarrhoea)
