Infectious Diseases Flashcards
Definition of pneumonia
Infection of lung tissue causing inflammation and sputum filling the airways and alveoli.
What are the types of pneumonia
- Community Acquired Pneumonia (CAP)
- Hospital Acquired Pneumonia (HAP)
- Aspiration pneumonia
- Atypical pneumonia
Symptoms of pneumonia
- SOB
- cough with purulent sputum
- fever
- haemoptysis
- pleuritic chest pain
- delirum
- sepsis
Signs of pneumonia
Characteristic chest signs
* bronchial breath sounds = harsh breath sounds due to consolidation
* focal coarse crackles = air passing through sputum
* dullness to percussion - lung collapse &/or consolidation
Sepsis secondary to pneumonia
* tachypnoea
* tachycardia
* hypoxia
* hypotension
How is the severity of pneumonia assessed?
CURB-65 (CRB-65 out of hospital)
* Confusion: abbreviated mental test ≤8 or disorientated
* Urea >7
* RR ≥ 30
* BP: SBP <90 or DBP ≤60
* Age ≥65
0-1 = mild, consider treatment at home
≥2 = moderate, consider hospitalisation
≥3 = severe, consider intensive care assessment
Common bacterial causes of pneumonia
- streptococcus pneumoniae (50%)
- haemophilus influenzae (20%)
Other bacterial causes and associations of pneumonia
- moraxella catarrhalis in the immunocompromised or chronic pulmonary disease
- pseudomonas aeruginosa in patients with cystic fibrosis or bronchiectasis
- staphylococcus aureus in patients with cystic fibrosis
Causes of atypical pneumonia
Mycoplasma pneumoniae
* can cause rash = erythema multiforme (pink ring, pale centre)
* can cause neurological symptoms
Chlamydophila pneumoniae = mild to moderate chronic pneumonia and wheeze
Coxiella burnetii = typically contracted from contact with infected birds
Legionella pneumophila
* caused by infected water supplies or air conditioning units
* Can cause SIADH = hyponatraemia
Investigations for pneumonia
- Basic Obs
- CXR
- Bloods: FBC, U+E, LFT, CRP, blood culture
- Sputum culture
- O2 sats, ABG if <92% or severely unwell
Abx for CAP
- Mild-moderate: amoxicillin PO. Clarithromycin or doxycycline if allergic.
- Severe: co-amoxiclav, cefuroxime, or cefotaxime IV (or levofloxacin if allergic), plus clarithromycin IV
- If hospitalised, start within 4 hrs. Monitor response to treatment with CRP
Abx for HAP
- Piperacilin/tazobactam, 3rd generation cephalosporin, meropenem, or levofloxacin IV.
- Co-amoxiclav is a PO alternative or stepdown
- Add vancomycin or teicoplanin or linezolid if MRSA suspected
Abx for aspiration pneumonia
clindamycin, levofloxacin, or piperacilin/tazobactam
Duration of abx in pneumonia
- 5 days total usually sufficient
- longer if remains febrile or unstable, or for certain pathogens e.g. pseudomonas
- If starting IV, review after 48 hrs for possible PO stepdown
Supportive care in pneumonia
- oxygen
- fluids
- paracetamol
Prognosis of pneumonia
- fever should resolve within 1 week
- cough and SOB may take up to 6 weeks to resolve
- fatigue may persist up to 3 months
Complications of pneumonia
- Respiratoy failure
- sepsis and septic shock
- uncomplicated parapneumonic pleural effusion, empyema, or lung abscess
- Death: 1% in community, 10% if admitted
Pathophysiology of infective endocarditis
- infection of the endocardium, usually a (prosthetic or native) valve (mitral or aortic), usually following transient bacteraemia and turbulent flow past valve
- leads to formation of vegetation on valves containing bacteria, fibrin and platelets
Causes of infective endocarditis
- bacterial: strep viridans, staph aureus
- fungal: candida, aspergillus
- non-infective: cancer, SLE
Key features of infective endocarditis
Murmer (85%) + fever
Septic signs and symptoms of infective endocarditis
- fevers, rigors and night sweats
- malaise
- weight loss
- splenomegaly
- clubbing
Signs of subacute infective endocarditis
Usually due to immune-complex depositions and vasculitis
- Petechiae and splinter haemorrhages
- Janeway lesions: painless plantar/palmar lesions
- Osler’s nodes: painful infarcts in distal phalanges
- Roth spots: retinal haemorrhages with pale centre
- Glomerulonephritis
Risk Factors for infective endocarditis
Increased turbulent flow
* valve disease
* prosthetic valves
* structural disease: unrepaired PDA, VSD
* rheumatic heart disease
Increased pathogen entry and bacteraemia
* IV drug use
* haemodialysis
* dermatitis
Chronic disease
* Diabetes
* Kidney disease
Investigations in infective endocarditis
Blood cultures
* 3 sets from different sites before starting abx
* within 6 hours if subacute, within 1.5 hrs if acute
* 90% sensitive
Bloods
* FBC: normocytic anaemia
* ↑ neutrophils
* ↑ ESR/CRP
* Rheumatoid factor may be +ve (due to IE itself or RA)
Heart investigations
* Echo: transthoracic, then transoesophageal if -ve
* CXR: cardiomegaly
* ECG: ↑PR interval. Monitor to decide whether surgery required
Urinalysis: microhaematuria
Duke Criteria in Infective Endocarditis
Diagnosis requires any 1 of:
* 2 major
* 1 major plus 3 minor
* 5 minor
Major Criteria
* +ve blood culture x2 or persistent
* +ve echo: vegetation, abscess, new regurgitation, or prosthetic valve dehiscence
Minor criteria
* RF +ve
* fever
* vascular immune-complex signs
* +ve blood culture (x1)
* +ve echo for other abnormality
Acute Management of Infective Endocarditis
Abx as soon as blood cultures taken:
* 4-6 weeks, including at least 2 weeks IV initially
* Empiric therapy and for streptococci: benzylpenicillin (or amoxicillin) + gentamicin
* staph. aureus: flucloxacillin if native valve, add rifampicin and gentamicin if prosthetic valve
Surgery:
* Debridement, repair or replacement required in 20%
* Indications: refractory HF, persistant sepsis or emboli, or fungal IE
Bacterial causes of meningitis
- <3 months old = Group B strep
- 3 months - 45 yrs = neisseria meningitidis
- > 45yrs = strep. pneumoniae
- other causes = staph. aureus, e. coli, h. influenzae
- Listeria monocytogenes: may occur in pregnancy, neonates, the alcohol misusers
Viral causes of meningitis
- enteroviruses; coxsackie, echovirus
- herpes simplex, HSV2 more than HSV1
- Mumps
- Measles
Fungal causes of meningitis
- Cryptococcus neoformans
- it has an insidious onset
Non-infectious causes of meningitis
- cancer: carcinomatous meningtitis
- drugs: co-amoxiclav, NSAIDs, IVIg, azathioprine
- Inflammatory and autoimmune sarcoidosis, SLE, Behcet’s
Epidemiology of meningitis
- 40% of cases of bacterial meningitis are in children aged <15 years
- Commonest in first few months of life, affecting 1/2000 per year, then incidence drops to around 1/100,000 per year for the rest of life
Symptoms of meningitis
- Classic triad: fever, stiff neck, headache/altered mental status
- vomitting
- photophobia
- mottled skin
- confusion
- seizures
- rigors
- cold hands and feet
Signs of meningitis
- Kernig’s sign: with hip and knee flexed, pain limits passive extension of the knee
- Brudzinskis sign: neck flexion leads to involuntary hip and knee flexion
- Both are around 10% sensitive and 90% specific for meningitis
- Cerebral oedema = loss of consciousness, papilloedema, and focal CNS signs
Meningococcaemia
* petechiae and purpura: look carefully all over including backs of legs etc
* septic shock: hypotension, ↓ capillary refill
* DIC
Risk Factors for meningitis
- immunosuppression, including complement deficiencies and asplenia
- Skull fracture or anatomical defects
- crowding: university halls, military barracks, Hajj
Investigations for meningitis
Bloods
* ↑WBC, ↑CRP
* U&Es and LFTs
* Blood culture +/- N. meningitidis PCR
* Coag: DIC
Lumbar puncture:
* CT and opthalmoscopy 1st if ↑ICP suspected
* Bacterial CSF: ↑polymorphs, ↑proteins, ↓glucose, bacteria on culture, gram stain. Listeria can be mixed polymorphs and lymphocytes
* TB CSF: ↑lymphocytes, ↑protein, ↓glucose, ZN stain +ve
* Viral CSF: ↑lymphocytes, viral PCR +ve
Other investigations
* Throat swab for N. meningitidis
* CXR: pneumococcal pneumonia, TB
Acute Management of meningitis
- resuscitate, including oxygen and fluids
- broad spectrum IV abx stat, e.g. cefotaxime. Add amoxicillin if age>50 or <3 months. Benzylpenicillin IM if pre-hospital
- dexamethasone IV if >3months old: ↓neurological complications, but doesn’t affect mortality
Public health measures for meningitis
- notify public health about any case of meningitis or meningococcaemia
- isolate patient
- prophylactic abx: single dose of ciprofloxacin or 2 days of rifampicin. Give to all close contacts from the last 7 days, regardless of vaccination status
Complications of meningitis
- short term: ↑ICP, shock, DIC, subdural effusions, SIADH, seizures, venous sinus thrombus
- long term: cranial nerve palsies, deafness, limb amputation, memory or cognitive problems
Prognosis of meningitis
- 5% mortality rate in meningococcal
- 25% mortality rate in pneumococcal
- 35% mortality rate for listeria
What is encephalitis
Inflammation of the brain
Viral Causes of encephalitis
Most common
* Herpes simplex (HSV1>HSV2)
* VZV
* EBV
Others
* CMV
* HIV seroconversion
* measles
* mumps
* arboviruses (west Nile, Japanese, tick borne, St Louis)
* rabies
Other causes of encephalitis
- Autoimmune
- Idiopathic
- bacterial meningitis –> meningoencephalitis
- TB
- protozoa: malaria
- fungal: Aspergillus,Cryptococcus
Epidemiology of encephalitis
- annual incidence: 1/20,000
- Most common under 1 year old or over 65
Signs and Symptoms of Encephalitis
- Initially non-specific: fever, headache, nausea, vomiting, malaise
- Neuro symptoms: seizures, odd behaviour or confusion, ↓level of consciousness, focal signs
History for Encephalitis
include travel and bite exposure
Investigations for encephalitis
Bloods
* blood culture
* serum viral PCR
* If suspected: toxoplasma IgM, malaria film
Image with MRI or contrast-enhanced CT
* Temporal lobe inflammation: usually HSV or autoimmune
* meningeal irritation: meningoencephalitis
Special tests
* LP: ↑protein (most causes), ↑lymphocytes (viral, autoimmune), ↑PMNs (bacterial), ↓glucose (bacterial). Identify pathogen with viral PCR and gram stain
* EEG: optional
Management of Encephalitis
- Aciclovir IV stat to cover HSV. Continued for 14-21 days if HSV confirmed
- Consider ganciclovir for CMV if immunocompromised
- anticonvulsants for seizures
- autoimmune encephalitis: immunosuppressants (steroids, IVIg, plasma exchange) and treat for any underlying cancer
- If infectious notify public health authorities
Complications of encephalitis
- Short term: seizures, ↑ICP, SIADH, diabetes insipidus
- Long term: neurological complications, including motor and cognitive problems
Prognosis of encephalitis
- 10% mortality overall
- For HSV, treatment reduces mortality from >50% to 20%
Pathogens that cause gastroenteritis
- Viral: norovirus, rotavirus, astrovirus, adenovirus
- Bacteria: campylobacter jejuni, salmonella (usually S. enteriditis), shigella, E. coli, vibrio cholera, clostridium difficile
- protozoa: giardia, cryptosporodium, cyclospora, entamoeba
Transmission of gastroenteritis
- most are faecal-oral, and can be person to person, water-borne or foodborne
- some are zoonotic
- campylobacter, shigella and giardia can be sexually transmitted, especially in MSM
Signs and symptoms of gastroenteritis
- acute diarrhoea and/or vomitting
- anorexia
- malaise
- fever
- weight loss
Investigations in gastroenteritis
- most cases require minimal if any
- stool culture and microscopy if there is bloody stool, the patient is immunocompromised, there is recent travel to the developing world, or symptoms are prolonged (>7 days)
- Basic bloods if unwell: FBC (↑WBC), U&E (dehydration), CRP, LFT
Management of gastroenteritis
most cases do not require admission and can be managed at home with regular oral fluid intake
Inpatient management
* fluids (PO or IV)
* anti-emetics or anti-diarrhoeals if severe (do not give in dysentry)
* abx if systemically unwell or immunocompromised. Ciprofloxacin (campylobacter, salmonella, shigella) or tetracycline (V. cholera)
Infection control
* isolate patients with D+V
* any food poisoning or suspected food poisoning is a notifiable disease
Complications of gastroenteritis
- lactose intolerance
- Guillian-Barre syndrome
- Reactive arthritis
- Haemolytic uraemic syndrome after E. coli
Pathophysiology of C. diff infection
- gram +ve anaerobic bacillus
- transmitted by spores from people or the environment
- often follows abx course, especially clindamycin, cephalosporins or quinolones, which eliminate gut commensals (usually post 4-9 days, but can be up to 8 wks)
Presentation of C. diff infection
- Profuse watery diarrhoea. Bloody stool can occur but is rare
- abdominal pain and tenderness
- fever
Investigations in C. diff infection
- ↑WBC, sometimes very elevated. ≥15 = severe c. diff
- U&E. AKI = severe c. diff
- Stool PCR ± toxin immunoassay to confirm
Management in c. diff infection
- Stop any abx which may be causing it
- none-severe and sever: vancomycin PO = 1st line, fidaxomicin PO if vancomycin ineffective
- Life-threatening (shock, ileus, or megacolon): vancomycin PO/PR ± metronidazole IV. May need colectomy if there is toxic megacolon
- Consider faecal microbiota transplantation for recurrent disease
Complications of C. diff infection
- pseudomembranous colitis
- toxic megacolon
What is bacteriuria
bacteria in urine. may or may not be symptomatic
What is a UTI
significant bacteriruria (≥100,000 colony forming units/mL in MSU) + symptoms
What is a complicated UTI
UTI in the presence of certain risk factors, including renal or urinary tract abnormality, voiding difficulty, ↓ kidney function, indwelling catheter, immunosuppression, or virulent organism
Pathogens that cause UTIs
- E. coli (90%)
- Staph. saprophytics: occurs in sexually active women
- proteus mirabilis: suggests kidney stones
- enterococcus facealis: causes prostatis
- Klebsiella: usually in catheterised patients
- Staph. aureus: from haematogenous spread
- STIs: chlamydia, gonorrhoea
Epidemiology
- annual incidence: 1/10 women, 1/100 men
- Lifetime risk: 1/2 women, 1/20 men
- Risk increases with age
- Although less common in men, they account for 40% of UTI hospitalisations
Symptoms of UTIs
- cystitis (lower UTI): frequency, urgency, dysuria, nocturia, haematuria, suprapubic ache
- acute pyelonephritis (upper UTI): fever ± rigors, loin pain, systemically unwell (e.g. vomiting)
Signs of UTIs
- fever
- suprapubic or loin tenderness
- cloudy or smelly urine
- swollen, boggy, tender prostate (prostatitis)
- Discharge (STI urethritis)
Risk Factors for UTIs
- demographic: female, age
- pregnancy
- pathogen exposure: sexually active, catheter
- stagnant flow: obstruction (prostate, stones), retention, extended holding
- infection prone states: diabetes, immunosuppression
Other differential diagnoses alongside UTI signs/symptoms
- overactive bladder
- STIs
- non-infectious inflammation: atrophic vaginitis, interstitial cystitis
- vaginitis
- stones
- bladder or renal cancer
Investigations for UTIs
Urine dipstick:
* nitrites or leukocytes esterase +ve
* if +ve: start treatment and send MSU for M,C&S
* If -ve: send MSU anyway if strong clinical suspicion, male, child, pregnant or immunosuppressed
MSU MC+S
* Microscopy shows leukocytes ± bacteria
* If <100,000 CFU/mL but pyuria (>20 WBC/mm3) = sterile pyuria (prev. treated UTI, prostatitis, STI, TB, appendicitis, bladder tumour, stones, PKD)
* if many different organisms, suspect contaminated (not mid-stream) and repeat MSU
Further investigations if indicated
* pyelonephritis: FBC, U+E, CRP, blood cultures
* Blood glucose to rule out diabetes
* Imaging: kidney US (obstruction/hydronephrosis), post-void bladder US, CT KUB (stones)
General Approach to manage UTIs
- Abx if symptomatic
- paracetamol +/or NSAIDs for symptom relief
- remove catheter if present
Treatment of lower single UTI in women
- nitrofurantoin (if eGFR≥45) or trimethoprim PO for 3 days
- pregnancy: treat even if asymptomatic. Nitrofurantoin 1st line (unless at term), amoxicillin or cefalexin 2nd line, all PO for 7 days
- any other complicated UTI: trimethoprim or nitrofurantoin PO for 7 days
Preventing recurrent UTI in women
- behavioural and lifestyle: increase daily water intake, pre/post coital washing, avoid spermicides and diaphragm
- consider vaginal oestrogen if post-menopausal
- prophylactic abx if very disruptive: nitrofurantoin if eGFR≥45 or trimethoprim PO taken post-coitus if sex-related, otherwise daily
Urology referral and imaging indications for UTI
- failure of other measures
- has risk factors for urinary tract abnormality: obstructive symptoms, history of stones, urinary tract surgery, gynae cancer
- immunosuppressed
- recurrent UTI with haematuria: urgent referral for suspected cancer
Treatment of lower UTI in men
- nitrofurantoin (if eGFR≥45) or trimethoprim PO 7 days for cystitis
- ciprofloxacin PO for 2-4 wks if there if prostatis, IV if severely unwell
Treatment for upper UTI
- most upper UTIs are uncomplicated and can be managed with PO abx (cefalexin or ciprofloxacin for 7-10 days)
- if there is no response within 24hrs, signs of sepsis or in complicated UTI = hospitalisation and consider IV abx, e.g. 2nd-3rd generation cephalosporin or ciprofloxacin
Complications of UTIs
- infectious spread: pyelonephritis, perinephric or intrarenal abscess, prostatis, sepsis
- Kidney: AKI, hydronephrosis
- recurrence: 1 in 3 women, usually reinfection (new pathogen)
Prognosis of UTIs
symptoms resolve in 3-4 days with an effective abx, vs 5-7 days without treatment (or with a resistant organism)
What is cellulitis
Inflammation of dermis and subcutaneous tissue. Most commonly group A strep, then staph aureus
Signs and symptoms of cellulitis
Skin:
* inflammation: painful, red, hot, swollen
* poorly demarcated
* precipitating lesion: trauma, ulcer, bite, skin damage from chronic condition
* may have associated skin abscess
non-dermal features:
* lymphadenopathy
* systemic symptoms: fever
Common sites for cellulitis
- lower legs (NOTE: bilteral lower leg cellulitis is rare, consider venous eczema)
- canula site
Risk factors for cellulitis
- previous cellulitis
- chronic disease: diabetes, chronic kidney disease or liver disease, cancer
- immunodeficiency
- venous insufficiency
- age
- skin disease, e.g. tinea pedis
Investigations for cellulitis
Affected area:
* look for portal of entry and ask about trauma
* draw around edge of area to monitor progress
* swab for culture only needed for severe/resistant infections, or unusual exposures (penetrating injury, water-born, acqiured abroad)
Bloods if systemic symptoms:
* ↑WBC and ↑CRP
* Blood cultures
Investigate associated conditions
* foot Xray for osteomyelitis
* D-dimer, ultrasound and Well’s score if suspected DVT
Management of cellulitis
Abx
* flucloxacillin PO for 5-7 days 1st line for most
* if penicillin allergyc, doxycycline or clarithromycin PO
* if near eyes or nose, or for human/animal bite wounds, co-amoxiclav PO
* if severe, cefuroxime, ceftriaxone, flucloxacilling, co-amoxiclav, or clindamycin IV
* if MRSA, vancomycin, tecioplanin or linezolid IV
Analgesia
* simple analgesia PO
* leg elevation can ease pain
If at cannula site
* remove cannula, resite, and culture needle tip
Complications of cellulitis
- thrombophlebitis
- sepsis
- toxic shock syndrome
- lymphangitis and secondary lymphoedema
- cavernous sinus thrombosis if facial
pathophysiology of necrotizing fasciitis
- Bacteria enters through a break in the skin following surgery, trauma, IV injection, or insect bite
- Infection spreads rapidly across fascial layer, leading to tissue death of fascia and subcutaneous tissue
Types of necrotizing fasciitis and common causes
- Polymicrobial (type 1)
- Monomicrobial (type 2) = Group A strep, with tissue destruction driven by exotoxins A, B & C
Risk factors for necrotizing fasciitis
- IV drug use
- diabetes
- obesity
Signs and symptoms of necrotizing fasciitis
- Rapidly expanding, inflammed area of skin. May progress to bullae and dusky, purplish discolouration
- severe pain out of proportion to skin signs
- skin crepitus: crackly on palpation
- sepsis and systemic symptoms
Investigations in necrotizing fasciitis
- Bloods: ↑WBC, ↑CK, ↑lactate
- XR, CT, or MRI may help aid diagnosis, showing gas in soft tissue
Management of necrotising fasciitis
- urgent surgical debridement
- IV abx: carbapenem + clindamycin ± MRSA coverage (e.g. vancomycin)
What is septic arthritis
bacterial infection of a joint that can rapidly destroy it
common pathogens that cause septic arthritis
- staph. aureus
- N. gonorrhoea
- gram -ve bacilli
Signs and symptoms of septic arthritis
- acute monoarthritis: hot, red, swollen, painful joint. May be immobile
- Most commonly affects knee
- Fever, systemically unwell
Risk factors for septic arthritis
- RA
- diabetes
- immunosuppression
- kidney failure
- joint replacement
Investigations for septic arthritis
Bloods and microbiology
* FBC and CRP
* Joint aspiration: gram stain and culture
* blood culture
Imaging
* XR should be done but is often normal
* CT and MRI is more sensitive but only used if there is diagnostic uncertainty
Management of septic arthritis
- Abx for 4-6 weeks , initially IV for 2 weeks. Flucloxacillin for staph. aureus, vancomycin for MRSA, or cefataxime for N. gonorrhoea or gram -ve bacilli. Start after joint aspiration
- drainage of joint if severe. This may involve serial aspirations if the joint is easily accessible (knee, elbow), or open washout in theatre if less accessible (e.g. hip)
- splinting
Pathophysiology of osteomyelitis
- Infection can come from direct/contiguous spread (cellulitis, abscess, trauma, surgery prosthesis), or haematogenous spread, which is commoner in kids, patients with urinary catheters, or TB
- Once infected, leukocytes enter bone, releasing enzymes which cause bone lysis and leave necrotic areas known as sequestra. New bone often forms around this
- Chronic osteomyelitis if >6 months of infection
Pathogens that cause osteomyelitis
- Staph. aureus = most common
- Less common = strep. pyogenes (kids), H. influenzae (kids), gram -ve bacilll (elderly)i, pseudomonas aerguinosa (IV drug users)
General features of osteomyelitis
- Local inflammation
- pain
- slight effusion of neighbouring joints
- systemic symtoms
- can be asymptomatic in diabtes due to neuropathy
Signs and symptoms of vertebral osteomyelitis
- localised spine inflammation
- Chronic back pain, which may be worse at rest and at night
- there is often associated discitis
Risk factors for osteomyelitis
Portal for pathogen entry
* Trauma: open fracture or orthopaedic surgery
* surgical prostheses
* IVDU
Diseases
* TB
* diabetes
* peripheral vascular disease
* immunosuppression
* alcoholism
* sickle cell disease
Investigations for osteomyelitis
Blood and microbiology
* ↑WBC/ESR/CRP
* bone culture is gold standard
* also culture blood, pus, and local joint effusion
* look for cause e.g. urine
Imaging
* X-ray: dark area in bone, soft tissue swelling. Signs may be minimal in acute infection
* MRI provides clearer picture if diagnosis is uncertain
Management of osteomyelitis
- abx for 6 weeka, IV then PO, Flucloxacillin ± fusidic acid or rifampicin in first 2 weeks
- Debridement to drain pus and remove sequestra if severe
- chronic osteomyelitis may require 12 weeks of abx and extensive surgery
Complications of osteomyelitis
- septic arthritis
- fracture
- deformity
Epidemiology of malaria cases imported to the UK
- 1500 cases annually, many from those visiting family members in country of origin
Species
* Plasmodium falciparum: 80%, usually Africa
* Plasmodium vivax: 10%, usually South Asia
* Plasmodium ovale & Plasmodium malariae: 10%
General signs and symptoms of malaria
- Fever: all tertian (48-hourly) except quartan (72-hourly) in P. malariae. These classic patterns aren’t always seen
- rigors
- headache
- diarrhoea and vomitting
- hepatosplenomegaly
Signs and symptoms of falciparum malariae
- Flu-like prodrome: myalgia, malaise, headache, anorexia
- irregular fever initially
- Jaundice
Signs and symptoms of complicated falciparum malaria
- Mortality approaches 100% if sever and untreated
- cerebral malaria: altered mental status, seizures, coma, decerebrate posturing, ↑plantars, teeth-grinding
- AKI
- Bleeding: haemoglobinuria (blackwater fever), DIC, retinal haemorrhages
- Metabolic: hypoglycaemia, metabolic acidosis
- ARDS and pulmonary oedema
- splenic rupture
- shock
Investigations to diagnose malaria
Blood films
* serial testing: up to 3 times if 1st -ve
* Thick film - quick yes or no malaria - and thin film - which subtype
* Also shows parasitaemia (%RBCs afected) and stage, with imminent decline in patient condition due if there are ↑shizofonts. Dangerous if parasitaemia >2%, life threatening if >5%
* Simple but less sensitive antigen detection kits are available too
Investigations to do in malaria patients
Bloods:
* FBC: anaemia, low platelets (due to increased spenic activity during haemolysis = increased clearance)
* Coag: DIC
* Hypoglycaemia
* ABG: metabolic acidosis
* U+E: AKI
Other tests:
* urinalysis: blood
* blood cultures to rule out bacterial sepsis
Prophylaxis for malaria
- Start 1 week before to check for side effects, and continue until 4 weeks after
Areas without chloroquinine resistance
* chloroquinine (daily) + proguanil (weekly)
Areas with chloroquinine resistance (any 1 of)
* atovaquone/proguanil. Few side effects and is taken from 1 day before
* doxycycline
* mefloquine (Larium): once weekly
Also
* long sleeves dusk till dawn
* mosquito nets
* DEET repellent
Treatment for malaria
- P. vivax, P.ovale & P. malariae: chloroquinine + primaquine
- Uncomplicated P. falciparum: 1st line artemether/lumefantrine (Riamet). 2nd line: quinine/doxycycline, or atovaquone/proguanil
- Complicated P. falciparum (cerebral, renal, or shock): artesunate IV (preferably), or quinine IV + doxycycline IV/PO. Careful monitoring of fluid, lactate, U+E. Transfuse if anaemic
Complications of malaria
- P. vivax & P. ovale can remain dormant in the liver as hypnozoites and relapse years later. Cause tropical splenomegaly syndrome if recurrent
- P. malariae can lielow in blood for years, with or without symptoms
Side effects of chloroquine
- Headache
- psychosis
- retinopathy
- Contraindication: epilepsy
Side effects of primaquine
- epigastric pain
- triggers haemolysis in G6PD deficiency (check 1st and give atovaquone/proguanil if +ve)
Side effects of atovaquone/proguanil
- abdo pain
- nausea
- dizziness
Side effects of mefoquine
- nauea
- dizziness
- insomnia
- vivid dreams
- psychosis
- Contraindication: epislepsy, psychosis
Side effects of doxycycline
- photosensitivity
- diarrhoea
- oesophagitis
What pathogen causes TB
Infection by one of the Mycobacterium tuberculosis complex: M. tuberculosis, M. bovis, or M. africanum
How is TB spread
Respiratory transmission
Histological finding in TB
Caseating granuloma that can spread to local lymph nodes
Systemic features of TB
- fatigue
- malaise
- fever
- night sweats
- weight loss
- anorexia
- immunosuppression
Signs and symptoms of pulmonary TB
- Chronic productive cough ± haemoptysis, clubbing
- can progress to pneumonia, pleural effusion, lobar collapse, and bronchiectasis
- accounts for 60% of TB causes in UK
Signs and symptoms of genitourinary TB
- frequency, dysuria, loin/back pain, haematuria
- can progress to renal TB, salpingitis, epididymitis, and cystitis
- 2nd most common TB presentation in UK
Other types of TB (apart from pulmonary and genitourinary)
- Skeletal TB: most commonly affects spine (Pott’s disease). Can lead to vertebral collapse
- Skin TB (aka lupus vulgaris): rough nodules, often on the face or shin which are +ve for AFB, scrofula (cold cervical lymphadenopathy), erythema nodosum, erythema multiforme
- Peritoneal TB: abdomincal pain, diarrhoea, vomiting, ascites
- TB meningitis: neurological signs are usually preceded by weeks of systemic symptoms
- TB pericarditis: acute or constrictive pericarditis
Signs and symptoms for miliary TB
- affects multiple organs so symptoms are varied
- there are often retinal signs
Risk factors for TB
- contact with infected individuals
- South Asian or African
- Homeless
- Immunosuppressed, including HIV and extremes of age
What is the first line investigation in TB
CXR, get it even in extrapulmonary TB
CXR findings in primary TB infection
- Distinct Ghon fous in the middle zone, or an area of patchy consolidation. Sometimes the parenchymal focus is too small to detect
- Extra-parenchymal findings: ipsilateral hilar lymphadenopathy (especially in kids), effusion (especially in adults)
- these signs may resolve following successful immune response, leaving just calcified nodies in 1/3
CXR findings in secondary TB infection
- cavitating lesion (air-filled) in the apices, especially in the right
- other signs including patchy consolidation and linear or nodular opacities
CXR findings in miliary TB
- Diffuse 1-10mm shadows throughout lung fields
- The term miliary is used to describe a CXR where there are more nodules than can be easily counted
Microbiological Investigation in TB
Getting samples:
* pulmonary: 3 sputum samples (including 1 early morning), idaelly spontaneous. Otherwise induce with nebulised saline or do bronchoalveolar lavage.
* extra-pulmonary: aspirate or biopsy lymph nodes, ascites, organs, pus, urine, or CSF
Investigations
* MC+S: AFB smear and microscopy usually involves Ziehl-Neelson staining which is around 65% sensitive. Culture in a Lowenstein-Jenson medium typcially takes 4-8 weeks and is around 80% sensitive
* NAAT allow diagnosis a week earlier than culture, with a similar sensitivity
* PCR for rifampicin resistance
* Histology of biopsies for caseating granuloma
Immunological testing in TB
Methods
* Mantoux (aka PPD): a tuberculin skin test. A delayed hypersensitivity response to tuberculin develops from 2-10 weeks after primary infection. Also +ve post BCG vaccination
* Interferon gamma release assays (IGRA): measures T cell response to TB antigens.
Uses and limitations
* Bother are around 80% sensitive
* cannot distinguish between latent and active TB
* more useful for screening contacts than diagnosis. Mantoux usually first, then confirmed with IGRA, or use IGRA first in those with previous BCG
Other investigations for TB (apart from CXR, Microbiological & Immunological testing)
- HIV screening
- Basic bloods - FBC, LFT, U+E - may show systemic and extrapulmonary disease, and are required for baseline values before starting treatment
- imaging for suspected extrapulmonary TB: CT/MRI (CNS, abdo, bone), US (pericardial, lymph nodes, GU), XR (bone)
Infection control in active TB
- Notify public health authorities
- screen close contacts
- for pulmonary TB, isolate patient in a single room, ideally negative pressure, for first 2 weeks of treatemnt. Have them wear msak if they leave the room.
- Masks and gowns for healthcare workers are only needed for aerosol-generating procedures like sputum induction of bronchoscopy, or for multiple drug resistant TB
Drug treatment in active TB
- Treat before confirmation by culture if clinical suspicion is high. Consider continuing treatment even if culture is negative but clincal signs are strong
- 6 months treatment with RIPE (rifampicin, isoniazid, pyranizamide & ethambutol) = 4 for 2 months, 2 for 4 months
- Add further 6 months of dual therapy for meningeal TB
- Add steroids for meningeal and pericardial disease
- consider directly observed therapy (DOT) to increase adherance
management in latent TB
Offer treatment to those with latent TB plus any 1 of:
* close contacts with active TB
* At high risk of progression to active TB: immunosuppressed, aged <5yrs, alcoholic, IVDU, diabetes or CKD
* immigrants from high incidence countries
* healthcare workers
Drug options
* 3 months isoniazid + rifampicin
* 6 months isoniazid monotherapy if need to avoid rifampicin e.g. on antiretrovirals
Prevention of TB
Mantoux/IGRA screening for:
* Healthcare workers who are unvaccinated or from high incidence countries
* close contacts (household partner) of people with active TB
* Immigrants from high incidence countries
Actions
* If -ve, give BCG
* If +ve, asses for active TB and treat latent/active TB as needed
* in older immigrants, benefits of BCG (if age >35) and latent TB treatment (if age >65) may be smaller so are not routinely indicated
BCG vaccine
* redues infection risk by 25% and active TB risk by 70% (in children)
* in addition to those identified through screening, give to children at risk
* also offer to those at high risk through occupational exposure
Side effects of rifampicin
- hepatitis (so stop if increase bilirubin)
- orange urine/tears
- P450 inducer (inactivates warfarin and contraceptive pill)
- flu-like symptoms
Side effects of isoniazid
- hepatitis
- agranulocytosis
- P450 inhibitor
- peripheral neuropathy can result from pyridoxine depletion, so give supplements to all
Side effects of pyrazinamide
- hepatitis
- arthralgia
Side effects of ethambutol
- optic neuritis
- colour vision goes first, so check it using Ishihara charts before starting
What type of virus is HIV
A single stranded, RNA retrovirus
How is HIV transmitted
- sex (including oral)
- IV drug use
- blood transfusions
- vertically
How does HIV enter cells
- attaches to CD4 T cells and macrophages
- Then integrates into DNA
- moves to lymph nodes
Time of course of HIV infection
- 1-6 weeks post-infection, seroconversion illness occurs, similar to infectious mononucleosis
- Then latent as the immune system mounts partial response but CD4 count drops progressively. During this time 30% develop persistent (> 3mnths) generalised lymphadenopathy
- after around 10 years, infections and cancers begin to develop
Stages of HIV
Normal CD4 count is about 800 cells/mm3
* Stage 1 ≥ 500
* Stage 2 < 500
* Stage 3 < 200
Signs and symptoms of seroconversion illness
- lymphadenopathy
- pharyngitis
- systemic: fever, malaise
- pain: myalgia, headache
- maculopapular rash
- lasts 1-2 weeks
Respiratory presentation of HIV
- Pneumocystis jiroveci. Fungal infection that causes dry cough, sweats, SOB and desaturation on exertion, but no chest signs
- Other fungal infections: aspergillus, cryptococcus, histoplasma
- TB: pulmonary TB or atypical and disseminated forms such as miliary TB and TB meningitis
- Strep and staph pneumonia
- CMV
Neurological presentation of HIV
- Toxoplasma encephalitis: protozoal infection. Focal neurological signs
- Cryptococcal meningitis: fungal infection. Causes insidous, chronic meningitis, usually without stiff neck
- Primary cerebral lymphoma
- progressive multifocal leukoencephalopathy: JC virus infection
- HIV dementia: neurological decline in multiple domains, in the absence of other infection
- HIV peripheral neuropathy
Skin presentation of HIV
- Kaposi’s sarcoma: due to human herpes virus 8. Purple papules on the face, mouth, back, lower limbs, or genitalia. Can also affect GI and respiratory tract
- Multi-dermatomal zoster (shingles)
- Recalcitrant psoriasis
HIV presentation in the mouth
- oral and oesophageal candidiasis
- oral hair luekoplakia: non-malignany white growths on the lateral tongue due to EBV
- HSV and aphthous mouth ulcers
GI presentation of HIV
- Cryptosporidiosis: protozoa. Chronic diarrhoea
- CMV colitis
- HIV wasting syndrome: unexplained weight loss >10%
- Mycobacterium avium complex (MAC): GI, lung or disseminated
- Fungal: cryptococcus, histoplasma
- Other bacteria: salmonella, shigella
- Hepatitis B and C
Cancers in relation to HIV
B-cell lymphoma: EBV related
Cervical and anal cancers: HPV related
Lung cancer
Head and neck cancers
HIV presentation in the eye
CMV retinitis. Mozarella pizza sign on fundoscopy
Infections by CD4 level in HIV
- 200 - 500:
- 100 - 200:
- 50 - 100:
- <50:
- 200 - 500: TB, candida, VZV, Kaposi’s, other pneumonias
- 100 - 200: PCP, histoplasmosis, PML
- 50 - 100: atypical TB, CMV, retinitis/colitis, toxoplasmosis, cryptosporidiosis, cryptococcal meningitis
- <50: MAC
Investigations to make a HIV diagnosis
- Serum HIV combined antibody + p24 antigen test screen, then confirm with Western Blot. 50% detectable within 1 month of infection, and nearly all by 6 months
- If +ve, screen for: TB, hepatitis A-C, syphilis, Toxoplasma, CMV
- Genotype testing to guide drug treatment
- Pregnancy test for women
- Baseline bloods: FBC, U&E, LFT, lipids, glucose
Tests for specific presentations in HIV
- PCP:
- Toxoplasma:
- Cryptococcal meningitis:
- PCP: CXR shows bilateral interstitial infiltrates
- Toxoplasma: contrast-enhancing lesions on CT/MRI brain
- Cryptococcal meningitis: cryptococcal antigen in CSF and serum
Monitoring in HIV
- 3 to 6 months: CD4 count, HIV quantitative RNA PCR (viral load), FBC
- Annual: U&E and LFTs, lipids, glucose
Lifestyle and preventative management of HIV
- counseling to prevent high-risk sexual behaviour. Lifelong condom use traditionally recommended, but good evidence that those with undetectable viral load cannot transmit even during condomless sex.
- Assistance with partner notification and contact tracing
- Vaccines: heptatitis A and B, annual flu, pneumococcal vaccine, HPV. Avoid live ones if CD4<200
Combination antiretroviral therapy for HIV
- Triple therapy: {2 x NRTI} + {NNRTI or protease inhibitor or integrase inhibitor}
- Research suggests clear benefits of starting treatment as soon as diagnosis is made
Common side effects of antiretroviral therapy
GI
* Diarrhoea and vomiting
* Hepatitis, especially nevirapine
Skin
* Mild rash
* In rare cases, hypersensitivity or SJS/TEN
Metabolic
* Lipodystrophy: fat reduction peripherally (head and limbs) but gain centrally. Seen with protease inhibitors, but possible with all
Common drug interactions with ART
- AEDs: phenytoin and carbamezapine should be avoided
- Sildenafil: use lower dose
- Lorazepam should be avoided
Definition of Pyrexia of Unknown Origin (PUO)
- Temperature >38 degrees for > 3 weeks, which is still undiagnosed after 1 week of hospital investigation
- Sub-types of fever of unknown origing: neutropenic, HIV, nosocomial
Causes of PUO
- Infection: abscess (chest/abdo/pelvic), infective endocarditis, TB, osteomyelitis, UTI, biliary infection, non-bacterial
- Connective tissue disease: polymyalgia rheumatica, temporal arteritis, adult-onset Still’s disease, SLE, RA, PAN
- Cancer: lymphoma, leukaemia, renal cell cancer
- Others: drugs, IBD, PE, sarcoidosis, amyloidosis, thyrotoxicosis, Addison’s
Important infections to rule out for fever in a returning traveller
- malaria
- typhoid and paratyphoid fever
- influenza, HIV, viral hepatitis
Fever in a returning traveller: DDx if short incubation (<10 days)
- influenza
- Arboral: yellow fever, dengue
- Rickettsial infection
- relapsing fever
- leptospirosis
Fever in a returning traveller: DDx if intermediate incubation (10-21 days)
- malaria
- enteric fever: typhoid and paratyphoid
- viral haemorrhagic fever
- leptospirosis
Fever in a returning traveller: DDx if long incubation (>3 weeks)
- malaria
- acute shistosomiasis
- Viral: hepatitis A-E, HIV seroconversion
- Protozoal: african trypansomiasis, amoebic liver abscess
- TB
- rabies
Fever in a returning traveller: DDx if Carribean and Latin America
- arboviruses: dengue, Zika, yellow fever
- malaria in certain areas
- bacterial: bartonellosis
- Fungal: histoplasmosis
Fever in a returning traveller: DDx if South Asia
- arboviruses: dengue
- bacterial: enteric fever
- malaria
Fever in a returning traveller: DDx if Sub-saharan Africa
- Malaria
- bacterial: Ricketsial infection, enteric fever
- arboviruses: dengue, yellow fever
- helminths: acute shistosomiasis
- viral haemorrhagic fever: Ebola, Marburg, Lassa
What are the 5 moments of hand hygiene
BARFS
* Before patient contact
* Before Asceptic technique
* Right after patient contact
* After body Fluid contact
* After patient Surroundings contact
What are some notifiable diseases
- CNS: meningitis, encephalitis
- Respiratory: TB, Legionnaires, whooping cough, anthrax, SARS
- GI: food poisoning, haemolytic uraemic syndrome, infectious bloody diarrhoea, cholera, diptheria, enteric fever (typhoid, paratyphoid)
- Skin: leprosy, plague, small pox
- Neurological: rabies, botulism, tetanus
- malaria
- measles, mumps, rubella
- Infectious group A strep infections
- yellow fever
- viral haemorrhagic fever
Examples of gram +ve cocci
- staphylococcus
- streptococcus
- enterococcus
Examples of gram +ve bacilli
- clostridium (anaerobe)
- listeria monocytogenes
Examples of gram -ve cocci
- neisseria
- moraxella
examples of gram -ve bacilli
- E. coli
- Shigella
- Salmonella
- Campylobacter jejuni
- helicobacter pylori
- haemophilus influenzae
Mechanism of Action of penicillins
- inhibits synthesis of peptidoglycan layer of bacterial cell wall
- Some bacteria produce beta-lactamase and require the use of beta-lactamase resitant (BLR) penicillins
Side effects of penicillins
- Rash
- diarrhoea (esp. co-amoxiclav)
- hypersensitivity: anaphylaxis, serum sickness
- encephalopathy
- renal: AIN, crystalluria (amoxicillin)
- liver: cholestasis (flucloxacillin)
Contraindications of penicillins
- hypersensitivity
- reduce dose in renal impairment
Examples of penicillins
- amoxicillin
- co-amoxiclav
- flucloxacillin
Mechanism of Action of cephalosporins
beta lactam = inhibits synthesis of peptidoglycan layer of bacterial cell wall
Contraindications of cephalosporins
- hypersensitivity
- potentiates warfarin
- don’t cover anaerobes
- autoimmune haemolytic anaemia
Examples of cephalosporins
- cefalexin
- cefuroxime
- ceftriaxone
- cefepime
Mechanism of action of carbapenems
beta lactam = inhibits synthesis of peptidoglycan layer of bacterial cell wall - with beta-lactamase resistance
Side effects of carbapenems
- neuro: headache, dizziness, seizure
- GI: diarrhoea and vomiting
- haematological: anaemia, eoisinophilia, decreased WBCs
Contraindications of carbapenems
- pregnancy
- breast feeding
Examples of carbapenems
- imipenem
- meropenem
Mechanism of action of aminoglycosides
inhibits protein synthesis at the bacterial 30S ribosome site
Contraindications and interactions of aminoglycosides
- pregnancy
- furosemide
- myasthenia gravis: exacerbates weakness
side effects of aminoglycosides
- ototoxicity
- nephrotoxicity
examples of aminoglycosides
- gentamicin
- streptomycin
Mechanism of action of tetracyclines
inhibits protein synthesis at the bacterial 30S ribosome site
Side effects of tetracyclines
- photosensitivity
- diarrhoes and vomiting
Contrainidications of tetracyclines
- pregnancy
- breast feeding
- children <12 yrs
- kidney failure
Examples of tetracyclines
- doxycycline
- tetracycline
- tigecycline
Mechanism of action of macrolides
inhibits protein synthesis at the bacterial 50S ribosome
Side effects of macrolides
- GI: nausea, vomiting, and diarrhoea
- hepatotoxicity
- rash
contraindications for macrolides
potentiates
* warfarin
* statins
* theophylline
* ergotamine
* carbamezapine
Examples of macrolides
- azithromycin
- erythromycin
- clarithromycin
Mechanism of action of quinolones
inhibits bacterial DNA synthesis via topoisomerase II or DNA gyrase inhibition
contraindications of quinolones
pregnancy
Side effects of quinolones
- GI: diarrhoea and vomiting, C. diff
- Neuro: headache, dizziness, seizure risk in those with epilepsy, peripheral neuropathy
- MSK: tendon rupture, arthralgia
- CV: increased QT, aortic dissection and rupture
- rash
- raised LFTs
Examples of quinolones
- ciprofloxacin
- levofloxacin
- moxifloxacin
Mechanism of action of glycopeptides
inhibits synthesis of peptidoglycan layer of bacterial cell wall
examples of glycopeptides
- vancomycin
- teicoplanin