Infections — Disease Index & Clinical Criteria

Written by Betra Youhanna, a medical student and not a doctor — check every detail against your own teaching.

Deck-derived finals-triage sheet · 76 disease entries + 17 criteria across 13 lectures · ICC-3

C/P — Clinical Presentation

Inves — Investigations

Mng — Management

Special — Pathognomonic / disease-unique

Immunisation & Vaccines

6 entries

Vaccine Classification & Principles

Definitions

Immunisation — umbrella term = manipulating the immune response to fight infection (covers vaccines + immunoglobulins)
Vaccination — administering vaccines only
Active immunity — natural infection or vaccines · Passive immunity — natural maternal antibody or immunoglobulin (normal/specific)

Classification

Live — natural (vaccinia/smallpox) or attenuated
Killed / inactivated — whole · subcellular/subunit (acellular) · subunit + conjugate · toxoid

Goals — Herd Immunity

Primary aim — prevent infection in the individual
Secondary aim — break transmission + protect unvaccinated members of the population

Key Points

Herd immunity indirectly protects those who cannot be vaccinated (immunocompromised, allergic)
Polysaccharide must be conjugated to protein for children <2 y — they do not respond to polysaccharide alone

Live Attenuated Vaccines

Nature

Diminished virulence but retained antigens
Natural live example — vaccinia (smallpox)

Examples

BCG · MMR · OPV (Sabin) = the live polio vaccine · Varicella · Yellow fever

Advantages

Fewer doses required
Long-lasting local + systemic immunity

Cautions

May revert to wild-type (e.g. polio); less stable
Contraindicated in immunosuppression + pregnancy (can cause natural illness)

Killed / Inactivated Vaccines

Nature

No reversion to wild type · safe in immunocompromised · stable
Disadvantages — more expensive, multiple doses + boosters, uncertain protection length, common local reactions, may be poorly immunogenic

Subtypes & Examples

Whole — IPV (Salk), Rabies, Hepatitis A
Subunit — Hep B (recombinant), Influenza, 23-valent pneumococcal polysaccharide, B. pertussis
Conjugate (polysaccharide + immunogenic protein) — 7-valent pneumococcal, Hib, MenC
Toxoid (inactivated toxin — formaldehyde or genetic mutation) — tetanus

Conjugate Rationale

Conjugation makes polysaccharide immunogenic in children <2 y (who do not respond to plain polysaccharide)

Key Points

Local reactions more common than live (killed > live)
IPV Salk = killed polio; OPV Sabin = live polio (contrast pair)

Passive Immunisation & Immunoglobulins

Nature

Short-term protection only, but immediate
Can be used alone or with an active vaccine

Types of Ig

Normal immunoglobulin — Measles, Hepatitis A
Specific immunoglobulin — Hepatitis B, Varicella-zoster, Tetanus, Rabies

Combined Active + Passive

Post-exposure prophylaxis — Hep B Ig + Hep B vaccine for newborns of HBV+ mothers and after HBV+ needlestick injury

Key Points

VZIG for seronegative pregnant women / neonates / immunocompromised exposed to varicella (chickenpox) or zoster (shingles)

Vaccine Adverse Effects & Contraindications

Side Effects

Fever · local reactions · convulsions · disease-like reactions (rash / meningitis / encephalitis) · blood clotting disorders · anaphylaxis (rare)
Local reactions more common with killed > live

Contraindications (relative)

Not absolute — precautions needing clinical judgment: live vaccine + immunocompromised; live vaccine + pregnancy; antibiotic / egg allergy (review each vaccine); previous vaccine reaction; FHx adverse reaction; undiagnosed/unstable neurological conditions

Reference

Check the "Green Book" (free online) for other contraindications

Myth-Busting

Multiple vaccines do not overload an infant's immune system
No causal MMR–autism link (Kaye et al, BMJ 2001 — divergent trends, no correlation)

physiology · background · low-yield

Background

Rebuttal to immune-overload fear — everyday mishaps (scraped knees, sore throats) place a greater demand on the immune system than the inert antigens in vaccines
Routine vaccination timing is deliberate — vaccines are timed to protect babies when they need it most

Special-Case & Individual Vaccines

BCG

Live attenuated; negative skin test first (unless <3 months)
Targets — contacts of active respiratory TB, people from high-TB areas, health-service staff

Influenza / Hepatitis B

Influenza — every autumn/winter; DM, immunosuppression, chronic resp/cardiac/renal/liver disease, >65 y, HCW & carers
Hepatitis B — IVDU, close family of a case, infants of HBV+ mothers, haemophilia/renal failure, travel, HCW; ~3 doses + booster at 5 y

Varicella / Pneumococcal

Varicella — live-attenuated (Japan 1974), universal in US, immunity ≥20 y; seronegative HCW + close contacts of immunocompromised
23-valent pneumococcal polysaccharide — no response <2 y; asplenia, diabetics, chronic CVS/resp/renal disease, >65 y

Asplenia / Hyposplenism

Lifelong risk from encapsulated organisms — S. pneumoniae, H. influenzae, N. meningitidis
Give meningococcal + Hib + pneumococcal vaccines; revaccination may be needed

physiology · background · low-yield

Background

Varicella vaccine — potential unknown long-term concern: ? more shingles (herpes zoster)

Epidemiology/Risk

Varicella vaccine adverse reactions in 4–7% — mild only (fever, rash, local reaction)

Fever

1 entry

Fever of Unknown Origin (FUO)

Definition

Fever — exceeds normal daily variation + raised hypothalamic set point (>37.2 °C before noon, >37.7 °C after noon)
Classic FUO — >38.3 °C (101 °F) on several occasions, >3 weeks' duration, no diagnosis despite 1 week inpatient investigation OR 3 outpatient visits
4 categories — Classic · Nosocomial (hospital-acquired) · Neutropenic/immunocompromised · HIV-related (cutoffs → Criteria tab)

Inves — stepwise, least-invasive first

Step 1 — comprehensive history + examination hunting for PDCs (potential diagnosis clues); begin least invasive to avoid harm/cost
Minimum workup — FBC, CMP/electrolytes, ESR, CRP, ferritin, LFTs, TSH, LDH, CK, urinalysis + urine culture, blood cultures ×3, ANA, RF, HIV-1/2 serology, hepatitis A/B/E, EBV, CMV, TB skin test or IGRA
Imaging — CXR/CT chest, CT abdo/pelvis, abdo-pelvic USS, lower-limb venous duplex, echocardiography (TTE/TEE)
Second-tier — MRI, 18FDG-PET/CT, targeted biopsy (lymph node, liver, temporal artery, bone marrow)
Additional second-tier labs — cryoglobulins, ANCA, complement studies, peripheral blood smear, serum protein electrophoresis (SPEP)

Mng

Treat the identified cause; proceed stepwise (avoid premature invasive workup)
Empiric NSAIDs or immunosuppressants (corticosteroids) only after discussing risks/benefits with the patient

Special

Commonest cause category in the developed world = noninfectious inflammatory disorders (not infection or malignancy)
Causes — infection (IE, osteomyelitis, occult abscess, TB, brucellosis), neoplasm (lymphoma, leukaemia), autoimmune (SLE, RA, GCA, sarcoid, PAN), other (drug fever, factitious, recurrent PE)
Infectious causes also span viral (HIV, EBV, CMV, viral hepatitis, enterovirus) and fungal / protozoal (e.g. malaria) / other parasitic infections

physiology · background · low-yield

Microbiology

Bacterial causes — organ-specific also include sinusitis, cholangitis, UTI, meningitis; non-organ-specific include Q-fever, Salmonella, Yersinia, tularaemia, septic phlebitis, rheumatic fever, Lyme disease, Whipple's disease

Other

Neoplastic causes also include solid tumours; 'other' causes also include trauma, non-infectious hepatitis

Background

PUO (pyrexia of unknown origin) — alternative abbreviation for FUO
Fever in FUO does not have to be persistent

Epidemiology/Risk

Most persistent fevers are diagnosed within one week of hospital evaluation
Infectious causes evolving globally due to increased global travel and use of immunomodulating drugs

Gram-Positive Bacterial Infections

12 entries

Staphylococcus aureus

C/P

Gram-positive cocci in clusters; skin + nasal commensal (~80% adults)
Pyogenic — folliculitis, carbuncles, abscesses, pneumonia
Bloodstream — osteomyelitis, endocarditis, meningitis
Toxin-mediated — food poisoning, toxic shock syndrome, scalded skin syndrome
Device-related — IV line, pacemaker

Inves

Coagulase-positive — divides the genus; highly virulent
Samples — pus, tissue, blood, vomitus; Gram stain = GPC in clusters
Blood agar 18–24 h; catalase +, coagulase +, DNase +; PCR

Mng

MSSA — flucloxacillin / nafcillin / cefazolin (cephalexin or dicloxacillin for simple skin); clindamycin alternate
MRSA — vancomycin (severe/complex); clindamycin, co-trimoxazole, linezolid, or daptomycin
Duration by syndrome — skin 5–7 d · complex SSTI 2–4 wk · bacteraemia 2–4 wk · osteomyelitis 4–6 wk · pneumonia 10–14 d
Decolonisation / prevention — topical nasal mupirocin reduces nasal colonisation (not reliably successful at preventing surgical infection; unclear MRSA benefit); contact precautions (private room, gloves, gown, handwashing)
Daptomycin is inactivated by lung surfactant → cannot be used for pneumonia; linezolid is favoured for MRSA pneumonia

Special

SSSS — toxin-secreting strain, cleavage at stratum corneum; children <5 y; large flaccid blisters that shear (Nikolsky sign +); Rx flucloxacillin
TSS — TSST-1 superantigen → cytokine release; historically tampon/vaginal colonisation; abrupt fever, shock, diffuse macular rash, desquamation of palms + soles; ~5% mortality; supportive + eradicate organism

physiology · background · low-yield

Other

Decolonisation approach deserving further study — combining topical mupirocin with antibacterial baths (e.g. chlorhexidine) or systemic agents

Coagulase-Negative Staphylococci

C/P

Much less virulent than S. aureus; skin commensal
True infection = prosthetic devices (valves, joints, pacemakers) — biofilm formers

Inves

Coagulase-negative (S. epidermidis, S. haemolyticus)
Common contaminant in blood cultures, LP, joint tap — clinical judgment needed

Mng

High flucloxacillin resistance → glycopeptides (vancomycin) ± oral adjuncts
Often requires hardware removal

Special

Biofilm on foreign material is the defining niche

Streptococcus pyogenes (Group A Strep)

C/P

β-haemolytic Group A; highly virulent + transmissible (isolate inpatients)
Pharyngitis, skin/soft-tissue infection
Post-strep sequelae — rheumatic fever, glomerulonephritis

Inves

Throat swab culture; Lancefield grouping (Group A)

Mng

Penicillin V 10 days (or amoxicillin 10 d; benzathine penicillin G single IM dose)
Pen-allergic — cephalexin/cefadroxil (avoid if immediate hypersensitivity), clindamycin, azithromycin 5 d, clarithromycin

Special

Rheumatic fever — cross-reaction of bacterial M-protein with host tissues (rash, migratory arthritis, carditis)
Post-strep GN — subepithelial "humps", fibrinoid necrosis → nephritic syndrome (Type III hypersensitivity)

Scarlet Fever

C/P

Erythrogenic toxin in a host lacking neutralising antitoxin; mainly children
2–4 days after strep pharyngitis; fever, rigors, headache, vomiting, regional lymphadenopathy
Rash blanches on pressure, appears day 2, lasts ~5 d, then desquamation; spares face/palms/soles; circumoral pallor

Inves

Typical clinical features + throat swab culture

Mng

Penicillin (drug of choice) — reduces the 10–21 day infectivity window

Special

Strawberry tongue (white coating + prominent bright-red papillae) → raspberry tongue (coating shed, raw red)
Complications — peritonsillar / retropharyngeal abscess, otitis media

Streptococcus pneumoniae (Pneumococcus)

C/P

α-haemolytic, highly virulent, encapsulated diplococcus
Commonest — bacterial pneumonia, otitis media; also meningitis + primary bacteraemia
In asplenic patients — often no obvious focus, mortality up to 50%

Inves

Gram stain — Gram-positive encapsulated diplococci; blood cultures

Mng

Ceftriaxone — immediate/empiric (esp. asplenic bacteraemia)
Asplenic prevention — PCV13 then PPSV23, MenACWY, Hib, influenza; PO penicillin prophylaxis if <2 y or previous sepsis

Special

Encapsulated → overwhelming post-splenectomy infection risk

Viridans / Other Streptococci & Enterococci

C/P

Viridans (green, α-haemolytic) — mucosal commensals, low virulence → endocarditis if mucosal damage
S. milleri group → visceral abscesses (liver / brain)
Group B (S. agalactiae) — female genital commensal, neonatal pathogen
Enterococci — gut commensal; polymicrobial abdomino-pelvic sepsis, endocarditis + UTI

Inves

Blood-agar haemolysis pattern; Lancefield grouping

Mng

Enterococci — amoxicillin first-line; glycopeptides (teicoplanin/vancomycin) second-line
Enterococci intrinsically resistant to cephalosporins + carbapenems

Special

Group D strep bacteraemia → colonic malignancy + endocarditis association
S. milleri = the abscess-former

physiology · background · low-yield

Microbiology

Groups C & G — cause infections similar to Group A but may be commensal

Listeria monocytogenes

C/P

Aerobic Gram-positive rod; bacteraemia, meningitis, miscarriage
At-risk — immunocompromised, pregnant, >55 y, neonates

Inves

Blood-culture Gram stain — Gram-positive rods
May produce lymphocytic CSF in meningitis

Mng

Amoxicillin / ampicillin (penicillin-sensitive); co-trimoxazole if penicillin anaphylaxis

Special

Resistant to cephalosporins — why amoxicillin is added to empiric meningitis cover in >55 y / immunocompromised
Food sources — soft cheese, pâté, uncooked/processed meat, coleslaw

physiology · background · low-yield

Epidemiology/Risk

Environmental reservoirs — dust, animal feed, water/sewage, numerous animal species and asymptomatic human carriers

Corynebacterium & Bacillus

C/P

C. diphtheriae — highly contagious oropharyngeal respiratory illness; complication = neuropathy
B. anthracis — anthrax (zoonosis); cutaneous + pulmonary forms
B. cereus — food poisoning: toxaemia → vomiting; enterotoxin → diarrhoea

Inves

Clinical + culture

Mng

Diphtheria — antitoxin + erythromycin; public health (childhood immunisation, contact tracing, prophylaxis)

Special

Lactobacillus = protective vaginal commensal (guards against bacterial vaginosis)

Clostridium botulinum (Botulism)

C/P

Descending flaccid paralysis + autonomic dysfunction
Sources — foodborne (home canning), wound (IVDU), infant (gut colonisation from honey)

Inves

Largely clinical

Mng

Supportive (ventilation) + antitoxin; benzylpenicillin + debridement for wound botulism

Special

Toxin cleaves SNARE proteins (synaptobrevin, syntaxin, SNAP-25) → blocks acetylcholine release

physiology · background · low-yield

Mechanism

Toxin structure — heavy chain binds the neuron receptor + light chain enters the cell and cleaves SNARE proteins

Clostridium tetani (Tetanus)

C/P

Wound contamination; incubation 24 h – 3 wk (severity ∝ wound proximity/size)
Generalised spastic paralysis, muscle spasms, trismus (lockjaw), risus sardonicus, rigidity of abdominal/paraspinal muscles
Sympathetic hyperactivity — tachycardia, hypertension, dysrhythmias, sudden death
Entry routes — contaminated cuts / burns / animal bites, IV drug use / body piercings / surgery; neonatal tetanus via umbilical stump contamination (childbirth or abortion)

Inves

Diagnosis is clinical

Mng

Wound cleaning + debridement, muscle relaxants, human tetanus immunoglobulin, benzylpenicillin, active immunisation

Special

Toxin = tetanospasmin
Prophylaxis = toxoid vaccine + human tetanus immunoglobulin
Local tetanus — rigidity + muscle spasm confined to the site of inoculation (vs the generalised form)

physiology · background · low-yield

Other

Recurrent tetanic muscle spasms may cause fractures

C. perfringens & C. difficile

C/P

C. perfringens — food poisoning (enterotoxin → diarrhoea, mass-produced food); gas gangrene after penetrating injury
C. difficile — pseudomembranous colitis, antibiotic-associated; complications = toxic megacolon + perforation

Inves

C. difficile — toxin detection

Mng

C. difficile — stop the offending antibiotic if possible; oral metronidazole or oral vancomycin

Special

Oral vancomycin stays in the gut (does not absorb) — ideal for C. diff colitis

Nocardia & Actinomyces

C/P

Nocardia — immunocompromised patients; pneumonia + brain abscess
Actinomyces — anaerobe, mucosal commensal; triggered by IUCD or dental work

Inves

Nocardia — weakly acid-fast (stains with Ziehl-Neelsen); grows 3–14 d
Actinomyces — slow to grow

Mng

Nocardia — co-trimoxazole
Actinomyces — penicillin + local excision

Special

Both are branched Gram-positive rods; Nocardia is partially/weakly acid-fast

CNS Infections

8 entries

Bacterial (Pyogenic) Meningitis

C/P

Fever, headache, neck stiffness ± altered conscious level; PMN in CSF
Cranial nerve involvement (deafness, imbalance); focal/generalised seizures frequent; Kernig + Brudzinski signs
Organisms by age — children <10 + young adults: N. meningitidis, S. pneumoniae · newborns: Group B Strep, E. coli, Listeria · older adults: S. pneumoniae or Listeria
Crowded / close-contact settings raise meningococcal risk — university halls, boarding schools, military barracks, prisons, Hajj pilgrimage; Hajj entry requires proof of MenACWY vaccination

Inves

LP — after CT if focal signs / reduced GCS / immunocompromised; check papilloedema before (raised ICP contraindicates); opening pressure + protein/glucose/cell count/Gram + culture
Bacterial CSF — turbid, low glucose, high protein, ≥1000 WBC (PMN predominant), raised opening pressure, raised LDH (vs viral)
Blood cultures ×2, CBC, CRP; PCR

Mng

IV ceftriaxone 2 g BD (or cefotaxime 2 g 6-hrly) empirical; add amoxicillin/ampicillin 2 g 4-hrly if >60 y or immunocompromised (Listeria cover)
Add vancomycin or rifampicin 600 mg BD if penicillin resistance suspected (recent travel); chloramphenicol 25 mg/kg 6-hrly if penicillin/cephalosporin anaphylaxis
Switch to benzylpenicillin if meningococcus confirmed & sensitive; urgently notify public health
Close-contact prophylaxis — single-dose ciprofloxacin OR rifampicin 600 mg BD ×2 days
Corticosteroids / osmotic diuretics if impending herniation. Duration — meningococcus 5 d · pneumococcus 10–14 d · H. influenzae 10 d · Enterobacteriaceae 21 d
Gram-negative bacilli / Enterobacteriaceae — continue cephalosporin + seek specialist advice; consider IV meropenem 2 g tds if resistance suspected (treat 21 days)

Special

Non-neuro complications — endocarditis, thrombocytopenia, acute adrenal failure
Prevention vaccines — MenC, MenACWY135, pneumococcal, Hib (MenB in trials)

physiology · background · low-yield

Microbiology

Adults — also Gram-negative rods (in addition to S. pneumoniae)

Exam technique

Brudzinski's sign — neck flexion causes reflex hip + knee flexion; Kernig's sign — hamstring stiffness prevents straightening the leg with hip flexed to 90°

Other

Add co-trimoxazole 10-20 mg/kg (four divided doses) if >60 y or immunocompromised AND penicillin anaphylaxis (also alternative for Listeria)

Tuberculous Meningitis & CNS TB

C/P

TBM — droplet inhalation → Rich focus → ruptures into subarachnoid space → thick basal exudate → cranial nerve palsies + obstructive hydrocephalus
TB encephalopathy — infants/children only; convulsions/stupor/coma without meningism or focal deficit
Tuberculoma — space-occupying mass → focal deficits + systemic symptoms

Inves

CSF — lymphocytic, low glucose, high protein; acid-fast / Ziehl-Neelsen stain
Tuberculoma on MRI — well-circumscribed, fibrous-encapsulated (cerebellum, basal ganglia, cortex); often bilateral → little midline shift

Mng

Anti-tuberculous therapy (RIPE) — see Antimicrobial Agents

Special

Rich focus — subpial/subependymal caseous focus; its rupture seeds the basal cisterns
CNS TB classes — TBM, TB encephalopathy, TB vasculopathy, tuberculoma, TB brain abscess (spinal: Pott's spine/paraplegia)
TB brain abscess — encapsulated collection of pus with viable tubercle bacilli, without a tubercular granuloma; MRI = thick-walled ring-enhancing cystic lesion with mass effect (mimics pyogenic abscess)

physiology · background · low-yield

Other

TB encephalopathy CSF — largely normal or only slight rise in protein/cells (deceptively bland)
Spinal CNS TB also includes non-osseous spinal tuberculoma and spinal meningitis (beyond Pott's spine/paraplegia)

Brain Abscess

C/P

Triad — generalised infection (irregular pyrexia, malaise, nausea) + raised ICP (headache worse on exertion, paroxysmal → severe, papilloedema, projectile vomiting) + focal signs (depend on position)
Sources — contiguous (otogenic, sinus, trauma) or haematogenous (IE, empyema/pneumonia)
Causative organisms — streptococci and staphylococci (empyema is polymicrobial)

Inves

MRI brain with contrast, CT brain, MRV (if venous thrombosis suspected) — ring-enhancing lesion
LP is contraindicated (mass effect / raised ICP)

Mng

Empirical 3rd-gen cephalosporin (aerobes) + metronidazole (anaerobes)
Surgery — excision or stereotactic aspiration; corticosteroids/hyperosmolar agents for cerebral oedema

Special

Hollow cavity of liquefactive necrosis walled by reactive glia + neutrophils
Subdural empyema — accumulation of pus in the subdural space; polymicrobial (staphylococci + anaerobic gram-negatives)

Viral (HSV) Encephalitis

C/P

Prodrome (fever, malaise, myalgia) → leptomeningeal irritation (headache, fever, neck stiffness)
Disturbed conscious level, generalised/focal fits, behavioural change/agitation
HSV targets inferior + medial temporal lobes → haemorrhagic meningoencephalitis

Inves

PCR on CSF = gold standard
CSF — aseptic pattern (elevated protein, otherwise normal); EEG — temporal epileptiform discharges

Mng

IV acyclovir 10 mg/kg tds for 14–21 days; control fever + antiepileptics

Special

Temporal-lobe haemorrhagic necrosis; mortality 70% if untreated
Eosinophilic intranuclear inclusions — "eosinophilic masses of packed viral particles"
Other causes — VZV/chickenpox, measles (→ subacute sclerosing panencephalitis, SSPE), enterovirus, arboviruses

physiology · background · low-yield

Other

Complications — respiratory tract, urinary tract, and nosocomial infections

Cryptococcal & Fungal CNS Infection

C/P

Cryptococcal — subacute lymphocytic meningitis in immunocompromised (HIV CD4 <100); headache, fever
Fungal CNS (Candida / Aspergillus / Cryptococcus) — chronic meningitis ± encephalitis, venous sinus thrombosis, brain granuloma/abscess; weeks-to-month onset
Rhinocerebral mucormycosis — highly aggressive in immunocompromised (transplant) / poorly-controlled diabetics; spreads from the sinuses → orbit (ophthalmoplegia) → brain with intracranial extension
Fungal CNS also causes infarction and mycotic aneurysms (in addition to venous sinus thrombosis and granuloma/abscess)

Inves

CSF — lymphocytic, low glucose, raised protein, raised opening pressure
India ink — encapsulated yeast (clear halo); cryptococcal antigen + CSF culture

Mng

Amphotericin B + 5-flucytosine; start ART after 2 weeks of antifungal therapy
Amphotericin B for other fungal CNS infection

Special

"Soap bubble" lesions — dilated Virchow-Robin spaces filled with mucoid material
Thick polysaccharide (mucin) capsule → paucity of inflammatory response

physiology · background · low-yield

Epidemiology/Risk

Cryptococcus environmental source — soil containing bird droppings

Rabies

C/P

Inoculation of saliva through broken skin (dog bite; 80% give a bite history); incubation 3 wk – months/years
Prodrome — flu-like + tingling at bite site; then hallucinations, agitation, delirium, fits
Hydrophobia — spasm of pharyngeal + laryngeal muscles at the sound of water

Inves

Clinical + bite history
Fluorescent antibody technique on saliva/skin/urine/CSF; PCR on CSF

Mng

Wound cleaned with detergent + water; passive (human rabies Ig) + active (human diploid cell vaccine) immunity; anticonvulsants + muscle relaxants
Give post-exposure prophylaxis immediately after the bite

Special

Hydrophobia is the hallmark; may cause paralysis in the bitten extremity

Progressive Multifocal Leukoencephalopathy (PML)

C/P

JC virus reactivation when immunocompromised (HIV, CLL, natalizumab therapy)
Insidious onset but rapid course — progressive behavioural changes, seizures, focal deficit; death within a couple of months

Inves

MRI — multifocal subcortical white-matter lesions

Mng

No specific treatment (restore immunity where possible)

Special

Targets oligodendrocytes → patchy demyelination scattered through the CNS

HIV Neurological Complications

C/P

HIV (RNA virus) can affect any part of the neuroaxis
3 mechanisms — direct (HAND — HIV-associated neurodegenerative disorder), immunocompromise-related opportunistic infection, peripheral nervous system affection

Inves

Depends on mechanism (imaging, CSF for opportunistic pathogens)

Mng

ART + treat the specific opportunistic infection

Special

Cross-refers to PML, cerebral toxoplasmosis, cryptococcal meningitis, CMV encephalitis

Allergy & Cutaneous Drug Reactions

6 entries

Urticaria

C/P

Superficial dermal swellings — pruritic, pink or pale-centred; individual wheals come and go within 24 h
Acute initially; chronic if ≥6 weeks
Distribution — wheals only 50% · wheals + angioedema 40% · angioedema only 10%
Causes of acute urticaria — idiopathic 50%, URTI 40%, drugs 9%, foods 1%; drug triggers = NSAIDs, aspirin, ACE inhibitors, opiates, antibiotics, radiocontrast media

Inves

CBC (eosinophilia), serum IgE / RAST, skin prick test, challenge test

Mng

Allergen avoidance, antihistamines, corticosteroids
Leukotriene receptor antagonist (montelukast); omalizumab (SC anti-IgE); desensitisation

Special

Mast-cell dependent — allergic (Type I / IgE) or autoimmune; non-immunologic trigger = opiates

physiology · background · low-yield

Mechanism

Wheals arise from transient skin/mucosal swellings due to plasma leakage

Exam technique

Allergy history — establish time-lag exposure→onset, previous allergic symptoms, drug intake, home allergens (e.g. house dust mites), family history, occupation; reaction usually within minutes, occasionally delayed

Angioedema (Hereditary & Acquired)

C/P

Deep swellings of skin/mucosa, often painful, no colour change; life-threatening via laryngeal oedema
Hereditary — C1 esterase inhibitor deficiency; recurrent angioedema without urticaria/pruritus; high kinin, low complement, +FHx, GI involvement (abdominal pain/diarrhoea)
Acquired — ACE inhibitors, malignancy, autoimmune disease

Inves

C1 esterase inhibitor level + complement studies

Mng

Anti-kinin directed; stop ACE inhibitor
Kinin-dependent → antihistamines + adrenaline are ineffective

Special

ACEi mechanism — inhibits bradykinin degradation (kininase) → elevated bradykinin → vascular permeability (mast-cell independent)

physiology · background · low-yield

Background

HAE swelling sites — legs, hands, face, upper respiratory tract, GI tract

Anaphylaxis

C/P

Rapid onset; requires priming + re-exposure; systemically absorbed allergen (ingested/parenteral)
Initial tingling/itching/warmth → generalised flush, hypotension, bronchospasm, facial/laryngeal oedema
N/V/D; arrhythmias/MI can follow; death within minutes

Inves

Clinical diagnosis — do not delay treatment for tests

Mng

ABCDE — lie flat, feet raised; clear airway; O₂; venous access
Adrenaline SC 0.5 mg (first-line) + IV hydrocortisone; admit ICU
Long-term — prevention, EpiPen (self-administered epinephrine pen), desensitisation

Special

Combines angioedema (deep swelling) + urticaria (rash) + systemic compromise

Erythema Multiforme

C/P

Target lesions favouring acrofacial / extremity sites
EM minor — no mucosal/systemic involvement · EM major — extremities+face, severe mucosal, systemic (fever/arthralgia)

Inves

Clinical

Mng

Treat precipitant + supportive care

Special

Most common precipitant = preceding HSV infection (also Mycoplasma pneumoniae); drugs rare
Does NOT progress to TEN

Stevens-Johnson Syndrome / TEN

C/P

Severe mucocutaneous — high fever (39 °C), tachycardia, hypotension (90/60), severe mucosal erosions (crusted lips/eyes, inability to swallow), progressive skin peeling
Triggers — drugs: NSAIDs, antibiotics, antiepileptics (e.g. carbamazepine)
SJS <10% BSA · overlap 10–30% · TEN >30% detachment
Systemic toxicity in SJS — fever, lymphadenopathy, hepatitis, cytopenia; severe mucosal involvement can cause malnutrition

Inves

History + clinical; skin biopsy (clinicopathological correlation); CBC, U&E, LFTs

Mng

Stop the offending drug; admit (ITU for TEN); fluid replacement + urinary catheter; wound + eye + mouth care
IVIg (first-line), cyclosporine, prednisolone, biological agent (etanercept); exclude infection
Burn-unit supportive care — oil-based emollient, warmth, IV fluid if necessary

Special

Type IV hypersensitivity; TEN > SJS severity — dermatological emergency

Exanthematous (Morbilliform) Drug Eruption

C/P

Most common cutaneous drug reaction
Erythema, macules + papules; confluence on the trunk; prominent pruritus; no mucosal/systemic toxicity

Inves

Clinical

Mng

Topical steroids, antihistamines, supportive; clears within 2 weeks of stopping the drug

Special

Self-limiting — the benign end of the cutaneous drug-eruption spectrum

Herpesviruses

5 entries

Herpes Simplex Virus (HSV 1 & 2)

C/P

HSV-1 orolabial (herpetic gingivostomatitis in children, cold sores) · HSV-2 genital
Painful grouped vesicles on erythematous base; prodrome tingling/pain/itching 6–12 h before lesions
Complications — herpetic whitlow (fingers), gladiatorum (contact sports), eczema herpeticum (atopic dermatitis), keratoconjunctivitis, neonatal herpes (HSV-2), HSV encephalitis
Primary genital herpes — severe systemic illness ~3 wk (fever, dysuria, herpetic proctitis, inguinal lymphadenopathy, complications common); recurrent is milder + shorter (8–10 d)
Erythema multiforme — target lesions (an HSV-triggered eruption)
Neonatal herpes (HSV-2, mother's 3rd-trimester primary infection) — 3 forms: localised skin/eye/mouth (40%), CNS/encephalitis (35%), disseminated hepatitis/pneumonia (25%, fatal); may present up to 6 wk post-delivery
Ocular HSV — keratitis, retinal necrosis and chorioretinitis can lead to blindness (beyond keratoconjunctivitis)

Inves

Clinical (main); PCR = gold standard for CNS; viral culture within 48 h; immunofluorescence distinguishes type 1 vs 2
Tzanck smear — multinucleated giant cells + eosinophilic intranuclear inclusions (rapid)
Dendritic corneal ulcer highlighted by Rose Bengal stain

Mng

Acyclovir oral/topical/IV per severity; valaciclovir + famciclovir = prodrugs with greater oral bioavailability; effective within 72 h of lesion
Neonatal — IV acyclovir 20 mg/kg tds ×3 wk; encephalitis — IV acyclovir 10 mg/kg tds 2–3 wk
Neonatal prevention — screen pregnant women, elective Caesarean section, prophylactic acyclovir in 3rd trimester until delivery

Special

Latency in sensory ganglia — HSV-1 trigeminal, HSV-2 sacral (retrograde axonal transport)
Reactivation triggers — stress, fever, UV light, tissue damage, immunosuppression

physiology · background · low-yield

Epidemiology/Risk

HSV-1 ~50% seropositive by age 30; HSV-2 seroprevalence rises with age (~5% → 15%) and partner number; genital ulcers increase HIV-acquisition risk

Other

Immunocompromised — erosive mucocutaneous lesions are HSV until proven otherwise; progressive spread to respiratory tract, oesophagus, GI tract; treat empirically on suspicion

Epidemiology/Risk

HSV encephalitis incidence ~1 per million per year

Varicella / Chickenpox

C/P

Usually children; incubation 10–20 d; fever prodrome
Pruritic macule → papule → vesicle → pustule → crust; generalised polymorphic, mainly trunk + head; heals 1–3 wk, may scar
Severe in adults (esp. pregnant) + immunocompromised
Highly communicable — airborne/droplet/direct contact; infectious from 48 h before rash (respiratory secretions) + vesicle fluid

Inves

Clinical; DFA, PCR (vesicle fluid), Tzanck smear (multinucleated giant cells)

Mng

Symptomatic — trim nails, calamine, oral antihistamine, acetaminophen; avoid NSAIDs
Antivirals — immunocompromised: IV acyclovir 10 mg/kg tds; pregnant/adults within 3 d of rash: oral acyclovir 800 mg 5×/day or IV

Special

Complications — secondary bacterial infection, pneumonitis, haemorrhagic chickenpox (immunocompromised), encephalitis/cerebellar ataxia, congenital varicella syndrome
VZIG for high-risk exposed contacts

physiology · background · low-yield

Other

Neurological complications also include transverse myelitis (alongside encephalitis / cerebellar ataxia)

Herpes Zoster (Shingles)

C/P

Reactivation of latent VZV from sensory ganglia; elderly + immunocompromised
Pain precedes lesions; painful grouped herpetiform vesicles on erythematous base; unilateral dermatomal; head + trunk
Phases — pre-eruptive (1–10 d) → acute eruptive → chronic (PHN)

Inves

Clinical; DFA, PCR, Tzanck smear

Mng

Rest + analgesics; oral acyclovir 800 mg 5×/day ×7 d (within 72 h); calamine; anticonvulsants (gabapentin/pregabalin)
Immunocompromised — IV acyclovir 10 mg/kg tds; ophthalmic — within 7 d, oral ACV or valaciclovir

Special

PHN — pain ≥1 month post-infection; TCAs (nortriptyline/amitriptyline), capsaicin/lidocaine, gabapentin
Forms — Ramsay Hunt syndrome (zoster oticus), zoster ophthalmicus, disseminated zoster (>10–12 extra-dermatomal vesicles), zoster sine herpete
Prevention — Varivax (children), Shingrix (older adults — more complications)
CNS involvement (immunocompromised) — anterior-horn motor weakness, cranial-nerve palsies, diaphragmatic paralysis, Guillain-Barré, transverse myelitis; meningoencephalitis life-threatening; CSF pleocytosis without raised protein

physiology · background · low-yield

Other

Disseminated zoster mortality 5–15% (encephalitis, hepatitis, pneumonitis); >10–12 extra-dermatomal vesicles 7–14 d after onset = sign of suppressed immunity
PHN — sustained-release oxycodone 10–20 mg bd as an additional analgesic option

Cytomegalovirus (CMV)

C/P

Immunocompetent — asymptomatic or mononucleosis (fever, rash, leucocytosis) without pharyngeal exudate or heterophile antibodies (vs EBV)
Immunocompromised (CD4 <50) — retinitis, pneumonitis, colitis (GI bleeding), hepatitis, encephalitis
Congenital — commonest cause of congenital infection; sensorineural hearing loss (TORCH)
Immunocompromised end-organ disease also includes oesophagitis, poly-radiculopathy, transverse myelitis, sub-acute encephalitis, pancytopenia; CMV hepatitis → fulminant liver failure
Congenital CMV — growth retardation / low birth weight, congenital malformations, fetal loss (stillbirth)

Inves

Histology — CMV inclusion bodies (basophilic intranuclear "owl's eye" with clear halo); IHC; quantitative PCR

Mng

IV ganciclovir (gold standard), oral valganciclovir; foscarnet or cidofovir if ganciclovir-resistant
Intravitreal ganciclovir for retinitis; prevention — seronegative donor, safe blood products
Prophylactic antivirals for all at-risk (seropositive) patients; CMV immunoglobulin has limited role; vaccine under development

Special

"Owl's eye" intranuclear inclusions; "pizza-pie" retinitis on fundoscopy
Cytomegalic cells 2–4× larger than normal; latency in monocytes/myeloid progenitors

physiology · background · low-yield

Epidemiology/Risk

Transmission — blood products / organ transplant, breastfeeding, close-contact shedding, perinatal, sexual

Background

CMV infection = virus present in body fluid/tissue; CMV disease = infection + symptoms and/or end-organ involvement

Other

A negative PCR does not exclude CMV in the immunocompromised; drug-resistance testing (e.g. ganciclovir resistance) available

Epstein-Barr Virus (EBV) / Infectious Mononucleosis

C/P

Transmission via saliva (kissing disease); incubation 30–50 d
Infectious mononucleosis triad — tonsillitis + exudate, fever, lymphadenopathy; fatigue, malaise, splenomegaly
Complications — splenic rupture, airway obstruction (tonsillar oedema), acute acalculous cholecystitis

Inves

CBC — lymphocytosis with atypical lymphocytes; LFTs may be abnormal
Heterophile antibody test (Monospot) — IgM; VCA IgM (acute) / IgG (chronic)

Mng

Symptomatic (analgesics/antipyretics); corticosteroids if airway compromise or autoimmune complications; antivirals reduce oral shedding
Splenic rupture — conservative (analgesia, splenic artery embolisation) or splenectomy (needs post-op immunisation + antibiotics); airway obstruction — steroids, tracheotomy/intubation

Special

Oncogenic — nasopharyngeal carcinoma (S Asia), endemic Burkitt's lymphoma (tropical Africa), Hodgkin's, PTLD/NHL (AIDS/transplant), X-linked lymphoproliferative (Duncan)
Avoid contact sports (splenic rupture risk)
Other complications — myocarditis, encephalitis, haemophagocytic lymphohistiocytosis, pancreatitis, autoimmune haemolytic anaemia
DDx of glandular fever — CMV, HIV, HHV-6, Toxoplasma

physiology · background · low-yield

Background

Discovered 1964; 2 types (A/B); immortalises/transforms B cells; no approved vaccine to date

Other

Post-acute — organomegaly persists 1–3 months; chronic fatigue syndrome may develop

HIV & Opportunistic Infections

9 entries

HIV Infection & Antiretroviral Therapy

C/P

RNA retrovirus; transmission — sexual, blood transfusion, infected needles
Acute HIV — fever, myalgia/arthralgia, fatigue, headache ± lymphadenopathy + pharyngitis
Opportunistic-infection risk stratified by CD4 count (→ Criteria tab)

Inves

HIV-1/2 serology; CD4 count (predisposition to OI when <50/µL)

Mng

HAART / ART — 4 classes: entry inhibitors (CD4/CCR5/CXCR4), reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors
Retroviral cycle target — endocytosis → uncoating → reverse transcription → integration → transcription → assembly → budding

Special

CD4 <50 → tissue-invasive OI (CMV, MAC); AIDS-defining illnesses (PCP, toxo, Kaposi, etc.)

physiology · background · low-yield

Background

Organ-based opportunistic-infection map — pulmonary (mycobacterial, CMV, Pneumocystis) · GI (MAC, CMV, Cryptosporidium) · CNS (Cryptococcus, HSV, CMV, Toxoplasma) · malignancy (Kaposi sarcoma, non-Hodgkin lymphoma)

Epidemiology/Risk

Diarrhoea is perhaps the most common complaint in AIDS — nearly 100% of AIDS patients in developing countries report it (opportunistic causes: MAC, CMV, Cryptosporidium)

Pneumocystis jirovecii Pneumonia (PCP)

C/P

Opportunistic yeast-like fungus; HIV (CD4 <200), BMT, haematological malignancy, steroids
Progressive exertional dyspnoea (95%) + non-productive dry cough (95%), fever, chest discomfort, weight loss; haemoptysis rare

Inves

HRCT — diffuse ground-glass opacity, perihilar; CXR — bilateral ground-glass pneumonitis
Induced sputum (HIV) or BAL; silver stain (Gomori methenamine — cup/boat-shaped cysts 4–6 µm, brownish-black), fluorescent antibody, PCR, Beta-D glucan

Mng

Co-trimoxazole (trimethoprim-sulfamethoxazole) — drug of choice; ART
Does NOT respond to antifungal therapy despite being a fungus

Special

Alveoli filled with pink foamy amorphous exudate → the dry, non-productive cough

physiology · background · low-yield

Microbiology

Alternative histological forms — solitary necrotizing granulomas or miliary disease, which lack the classic intra-alveolar foamy exudate; usual reaction is mild (fibrin exudate + hyaline membranes). Chills also a listed symptom.

Epidemiology/Risk

Transmission is airborne / person-to-person

Cerebral Toxoplasmosis

C/P

Leading cause of focal CNS disease in AIDS; late phase; CD4 <100–200 (greatest risk <50)
Confusion/drowsiness, seizures, focal weakness, language disturbance, headache/fever; chorioretinitis
Reactivation of Toxoplasma gondii
If untreated → progresses into coma

Inves

Serology — rising anti-Toxoplasma IgG (reactivation); IgM if newly acquired
MRI (superior) — multiple ring-enhancing lesions (characteristic but not diagnostic)
Brain biopsy if single lesion + negative serology OR no response to 14 d empiric therapy
Ring-enhancing lesion DDx (identical MRI appearance) — primary CNS large B-cell lymphoma, CNS tuberculosis, CNS fungal infection

Mng

Sulphadiazine + pyrimethamine + folinic acid (therapeutic trial often precedes biopsy)

Special

True cyst wall containing bradyzoites; usually multiple lesions (vs solitary lymphoma)

physiology · background · low-yield

Mechanism

Mechanisms beyond reactivation — haematogenous spread of previously acquired infection; occasionally primary infection

Epidemiology/Risk

Reactivation risk criteria — CD4 <100/mm³ + Toxoplasma-seropositive + not on effective prophylaxis/HAART

Microbiology

Biopsy histology — lymphocytic meningitis, astroglial/microglial nodules (reparative), lymphocytic vasculitis, diffuse encephalitis

Primary CNS Lymphoma

C/P

2nd most common mass lesion in AIDS (after toxoplasmosis); diffuse large B-cell; late HIV
EBV-associated in almost all cases; focal signs + altered mental status

Inves

CSF EBV (vs serum anti-Toxoplasma antibodies); MRI — usually solitary (vs multiple in toxo)
Stereotactic brain biopsy for definitive diagnosis — vasocentric infiltrates of large lymphocytes

Mng

Radiotherapy (2–5 mo survival, benefits >75%) + chemotherapy (16–28 mo); improved with HAART; ~1 mo untreated

Special

Solitary lesion + CSF EBV distinguishes it from (multiple, serum-antibody) toxoplasmosis

physiology · background · low-yield

Other

vs Toxoplasmosis — headache is a constant finding in toxo (inflammation) but site-dependent in lymphoma; lymphoma infiltrates may show areas of necrosis

Kaposi Sarcoma

C/P

Low-grade angioproliferative vascular tumour; HHV-8 / KSHV; AIDS-defining
Variants — classic (elderly men, lower limb) · endemic African · iatrogenic (transplant) · AIDS-associated (most aggressive, disseminated)
Violaceous patch → plaque → nodule; skin, lung, GI tract

Inves

Biopsy — dermal spindle-cell fascicles + blood-filled slit-like spaces; IHC for HHV-8 (nuclear staining)

Mng

ART (primary); intralesional vinblastine; IV doxorubicin

Special

HHV-8-driven; spindle cells; multiple clinical stages may coexist

physiology · background · low-yield

Epidemiology/Risk

Classic/sporadic variant — Mediterranean, Eastern Europe & central equatorial Africa; indolent course; may associate with a secondary malignancy

Mechanism

Pathogenesis — HHV-8-infected endothelial cells undergo altered lymphatic differentiation + cytokine-driven angiogenesis; cell of origin = pluripotent mesenchymal progenitor cell

Mycobacterium avium Complex (MAC)

C/P

Non-tuberculous mycobacteria (M. avium + M. intracellulare); environmental
Severe immunodeficiency (CD4 <50); fever, lethargy, diarrhoea

Inves

Endoscopic biopsy, blood cultures, bone-marrow cultures
Diffuse yellowish-white nodules 5–10 mm (duodenum); foamy histiocytes (H&E) packed with acid-fast organisms

Mng

Macrolide-based antimycobacterial therapy + immune reconstitution (ART)

Special

Foamy histiocytes stuffed with acid-fast bacilli — no robust granuloma in the immunocompromised host

Cryptosporidium parvum

C/P

Protozoal parasite; self-limited in immunocompetent, fulminant in immunocompromised
Severe explosive watery diarrhoea in AIDS; distal ileum + proximal colon

Inves

Oocysts in stool with modified acid-fast stain
Biopsy — 2–5 µm round basophilic "blue beads" at apex of enterocytes (intracellular but extra-cytoplasmic)

Mng

Immune reconstitution (ART) — prognosis tied to immune recovery

Special

"Blue beads" on the enterocyte luminal border (contrast: H. pylori sits outside the cell)

physiology · background · low-yield

Epidemiology/Risk

CD4-dependent course — CD4 <50 → fulminant diarrhoea; CD4 >150–180 → self-limited

Microbiology

Associated epithelial changes — cryptitis and epithelial apoptosis

Invasive Pulmonary Aspergillosis

C/P

Neutropenic host (ANC <0.5 ×10⁹/L, esp. prolonged) — e.g. ALL post-chemotherapy
Fever persisting despite broad-spectrum antibiotics

Inves

CT — halo sign (consolidation + surrounding ground-glass) + crescent sign
BAL histology + culture; galactomannan (BAL/serum), Beta-D glucan; species — A. fumigatus, flavus, niger, terreus

Mng

Antifungals — amphotericin, azoles, or echinocandins

Special

Halo + crescent signs; risk directly proportional to the duration of neutropenia

Molluscum Contagiosum

C/P

Poxvirus; direct contact / fomites / sexual / autoinoculation
Multiple firm pruritic pink umbilicated nodules ≤4 mm; skin/trunk/face/anogenital
Large + widespread on the face in immunocompromised

Inves

Clinical; histology — eosinophilic cytoplasmic inclusions (molluscum bodies) displacing nuclei peripherally

Mng

Self-limiting in immunocompetent; supportive / lesion-directed therapy

Special

Central umbilication + molluscum bodies are the signature

physiology · background · low-yield

Microbiology

Architecture — lobulated endophytic hyperplasia forming a circumscribed intradermal pseudotumor

Immunocompromised & Transplant Host

5 entries

Opportunistic Infection — Principles & Sources

Definition

Infections that are more frequent or more severe because of immunosuppression
Organisms — low-pathogenicity (CoNS, Pseudomonas, Candida, PCP, CMV) OR conventional pathogens causing atypical/disseminated disease
Atypical examples — miliary TB (renal transplant), measles (leukaemic child), disseminated HSV (BMT), CNS toxoplasmosis (AIDS)

Sites

Mouth/throat, skin, gut, lungs, kidneys/bladder (catheter), drip/central-line site

Mng

Pathogen-directed therapy + restore immunity where possible

Special

Endogenous (gut flora, Candida, HSV reactivation) vs exogenous (MRSA, resistant GNB, Aspergillus, Pseudomonas, Listeria, transplant CMV)
Immune-defect → pathogen: humoral/antibody defect (myeloma, CLL, AIDS) → encapsulated bacteria (S. pneumoniae, H. influenzae), Mycoplasma, Campylobacter, Giardia, enterovirus; T-cell defect (HIV, lymphoma, steroids) → intracellular pathogens (viruses, TB, protozoa) + fungi
Complement deficiency → S. pneumoniae, Neisseria; asplenia (splenectomy, trauma, sickle cell) → encapsulated organisms (S. pneumoniae, H. influenzae, N. meningitidis) + Plasmodium

physiology · background · low-yield

Microbiology

Additional exogenous sources — environmental mycobacteria; hands/environment/air/water/food

Background

Clinical approach — define the clinical syndrome, timeline, exposure risk; characterise the immunodeficiency (type, how profound, duration); consider both typical and unusual pathogens (sometimes >1 present)
Patient prevention advice — neutropenic diet (no raw meat/eggs, wash fruit/veg), avoid cat litter/animal waste + gloves for gardening (mould/zoonoses), electric shaver + soft toothbrush to avoid trauma

Primary Immunodeficiency Disorders

Overview

>400 inborn errors of immunity (>200 single-gene mutations); predispose to autoimmunity + malignancy
Distribution — antibody (65%, most common) · combined cellular+antibody (15%) · phagocytic (10%) · cellular (5%) · complement (5%)

Inves

Immunoglobulin subclass levels; genetic testing

Mng

Immunoglobulin replacement / definitive therapy per subtype

Special

Combined — SCID, Wiskott-Aldrich (small platelets, thrombocytopenia, eczema, bloody diarrhoea), DiGeorge (thymic), Hyper-IgE
Antibody — X-linked agammaglobulinemia (BTK mutation), CVID; Phagocyte — chronic granulomatous disease (oxidative burst), Kostmann (HAX1); Autoinflammatory — familial Mediterranean fever
Leucocyte adhesion defect — phagocyte adhesion failure; presents with leucocytosis + periodontitis

physiology · background · low-yield

Microbiology

Further subtypes — antibody: CD40L deficiency (hyper-IgM); immune dysregulation: familial haemophagocytic lymphohistiocytosis; innate: TLR mutations; complement phenocopy: interleukin autoantibodies; syndromic combined: DNA-repair defects

Background

CVID — characterised by ≥2 reduced antibody subclasses

Secondary Immunodeficiency

Causes

Infection (HIV, measles, mumps, rubella), malignancy (Hodgkin, CLL, myeloma, solid tumours)
Immunosuppressive drugs, malnutrition, age extremes, splenectomy/trauma, autoimmune (SLE, RA)
Metabolic (diabetes, renal/hepatic insufficiency), burns, major surgery, alcohol, pregnancy

Inves

Directed at the underlying cause

Mng

Treat/remove the cause + targeted prophylaxis

Special

Immunosuppressive therapy is the commonest iatrogenic cause (chemotherapy, transplant conditioning, GVHD, rejection)

physiology · background · low-yield

Epidemiology/Risk

Further causes — radiation, toxic chemicals, IV drug abuse, allogeneic blood transfusion; infective (bacterial, mycobacterial, parasitic)

Neutropenia & Febrile Neutropenia

C/P

ANC <500/µL = increased serious-infection risk; <100/µL = severe (duration + severity correlate with infection)
Low-grade fever, sore mouth, odynophagia, gingival pain, skin abscesses, recurrent sinusitis/otitis, pneumonia
Febrile neutropenia — >38.3 °C single reading OR >38 °C sustained >1 h

Inves

ANC = WBC × (% neutrophils + % bands); blood cultures
Weekly CMV PCR + galactomannan in BMT patients

Mng

Start antibiotics immediately; empiric monotherapy — cefepime, meropenem, imipenem-cilastatin, or piperacillin-tazobactam
Add aminoglycoside (gentamicin) if unstable/septic; add vancomycin if MRSA or Corynebacterium suspected
Prophylaxis high-risk (<100 for >7 d) — oral fluoroquinolone + antifungal (triazole or echinocandin)

Special

Gram-negatives most concerning; S. epidermidis the notable GP organism (indwelling central line); fungal (Candida, Aspergillus) with persistent/recurrent fever

physiology · background · low-yield

Microbiology

Viral causes (preventable with prophylaxis) — reactivation of HSV-1/2, VZV, EBV, CMV; community respiratory viruses (adenovirus, rhinovirus, coronavirus, metapneumovirus)
Common source flora — gut: Enterobacteriaceae, Enterococcus, oral streptococci, Candida, Pseudomonas; skin: coagulase-negative staph, diphtheroids; anaerobic/polymicrobial rare; consider TB if risk factors

Background

Stop all suspected offending drugs until the aetiology is established (drug-induced neutropenia)

Infections in Organ Transplantation

Sources & Timeline

Sources — donor-derived, nosocomial/technical, reactivation of latent infection, community-acquired, recipient-derived
<1 month — nosocomial/technical: MRSA, VRE, catheter/wound/aspiration, C. difficile, anastomotic leaks; donor-derived (HSV, West Nile, rabies)
1–6 months — opportunistic: PCP, herpesviruses (HSV/VZV/CMV/EBV), BK virus nephropathy, Listeria/Nocardia/Toxoplasma, TB, cryptococcus
>6 months — community-acquired (CAP, UTI), fungal (Aspergillus, Mucor, Nocardia), late viral (CMV colitis/retinitis, hepatitis, HSV encephalitis, PML), malignancy (skin cancer, PTLD)

Inves

Pathogen-directed; preemptive weekly CMV PCR + galactomannan in high-risk patients

Mng

Prophylaxis — cotrimoxazole (renal transplant at 3 months); BMT — cotrimoxazole + itraconazole + aciclovir

Special

Latent-infection reactivation (CMV, HSV, TB) is the defining transplant risk; CMV donor/recipient serostatus mismatch drives morbidity

physiology · background · low-yield

Microbiology

Additional <1 month — non-albicans Candida; donor-derived LCMV, HIV, Trypanosoma cruzi (Chagas); recipient colonisers Aspergillus/Pseudomonas
Additional 1–6 month — Strongyloides, Leishmania, HBV/HCV, adenovirus/influenza; >6 month — Rhodococcus, atypical moulds

Antimicrobial Agents

8 entries

Beta-lactams

Spectrum

Inhibit bacterial cell-wall synthesis. Narrow — penicillin, amoxicillin, flucloxacillin · Broad — co-amoxiclav, piperacillin-tazobactam · Cephalosporins — cefuroxime, cefotaxime, ceftriaxone · Carbapenem — meropenem
Good GP + GN (broader agents); resistant-GN best = pip-taz, meropenem; anaerobes (broad agents); no mycobacteria

Clinical Use

Most commonly used class — respiratory/IE, skin/soft tissue/bone/joint, UT/GU, meningitis (cross BBB when inflamed); often in combinations

PK / Specific Drugs

Oral + IV; good tissue penetration; renally excreted
Flucloxacillin — penicillinase-resistant, anti-staph (impetigo, cellulitis, septic arthritis, osteomyelitis)
Co-amoxiclav = amoxicillin + clavulanic acid (β-lactamase inhibitor) — covers S. aureus, E. coli, H. influenzae
Flucloxacillin also covers staph pneumonia and infective endocarditis (and folliculitis) beyond skin/joint infection

Toxicity & Resistance

Rash/hypersensitivity 1–10%, anaphylaxis 0.05%; antibiotic-associated colitis (cephalosporins/broad-spectrum)
Absolute CI = anaphylaxis/serious hypersensitivity; safe in pregnancy

Glycopeptides (Vancomycin, Teicoplanin)

Spectrum

Inhibit cell-wall synthesis (earlier stage than β-lactams); Gram-positive only (aerobic + anaerobic), no GN

Clinical Use

GP infection when resistance or penicillin anaphylaxis a problem — MRSA, enterococci
Oral vancomycin for C. difficile colitis

PK / Dosing

IV usually (teicoplanin can be IM); oral vanco stays in the gut; long half-life (once/twice daily); renal excretion
Renal impairment is not an absolute contraindication — prescribe less frequently + monitor levels more closely

Toxicity & Resistance

Nephrotoxicity + ototoxicity — monitor levels (vanco > teico)
"Red person syndrome" if vancomycin infused too fast — give at 1 mg/min

Macrolides

Spectrum

Erythromycin, clarithromycin, azithromycin. Inhibit protein synthesis (peptide chain dissociates during translocation)
Good GP (staph resistance a problem); poor GN except respiratory (H. influenzae, Legionella, M. cat); good intracellular (chlamydia); clarithromycin = mycobacteria

Clinical Use

Alternative to β-lactams (respiratory/skin); atypical pneumonia; Campylobacter/enteric; azithromycin for chlamydia + enteric fever

PK / Dosing

Oral + IV; good tissue penetration; azithromycin = long half-life (intracellular); renal excretion

Toxicity & Resistance

GI disturbance (erythromycin worst); azithromycin CI in hepatic impairment

physiology · background · low-yield

Exam technique

Shared class suffix mnemonic — "-THROMYCINS"

Aminoglycosides

Spectrum

Gentamicin, amikacin, streptomycin. Inhibit protein synthesis (30S — codon misreading)
Lack activity vs streptococci (use synergistically with penicillins); good GN + Pseudomonas; no anaerobes; poor intracellular; streptomycin = mycobacteria

Clinical Use

Not monotherapy (except ear/eye drops); empirically with a β-lactam; septicaemia (urinary/biliary/respiratory/GI); IE with β-lactam

PK / Dosing

Poorly absorbed orally → given by injection; renal excretion
Gentamicin 7 mg/kg; send a 6–14 h post-dose level (Hartford nomogram)

Toxicity & Resistance

Ototoxicity + nephrotoxicity — monitor levels; care when co-administered with diuretics

Quinolones

Spectrum

Ciprofloxacin, moxifloxacin, levofloxacin. Inhibit DNA gyrase (nucleic-acid synthesis)
Poor GP (moxi/levo good for S. pneumoniae); good GN + Pseudomonas (moxifloxacin has NO pseudomonas activity); limited anaerobes; intracellular (enteric fever, Legionella); moxi = mycobacteria

Clinical Use

When GN a problem + patient penicillin-allergic; UTI, GI infection; moxifloxacin for LRTI + mycobacterial

PK / Dosing

Oral + IV

Toxicity & Resistance

Lowers seizure threshold; tendon damage; not licensed in children (effects on immature joints) — relative

physiology · background · low-yield

Mechanism

DNA gyrase inhibition blocks relaxation of positively supercoiled DNA

Anti-tuberculous Drugs

First-line Agents

Rifampicin · Isoniazid · Pyrazinamide · Ethambutol (RIPE)

Clinical Use

Pulmonary + extra-pulmonary TB (including TB meningitis)

Regimen

Used in combination to prevent resistance

Note

Rifampicin also used for meningococcal prophylaxis (600 mg BD ×2 days)

Antifungal Agents

Targets & Classes

Yeasts + filamentous fungi; local to invasive infection. Three classes — azoles, polyenes, echinocandins

Clinical Use

Chosen by fungal species + severity (e.g. amphotericin B for CNS/invasive disease)

Mechanisms

Azoles (fluconazole, itraconazole) — inhibit ergosterol synthesis/binding in the cell membrane
Polyenes (amphotericin) — bind ergosterol → form pores → leakage + cell death
Echinocandins (caspofungin)

Note

Amphotericin B is the workhorse for fungal CNS infection (± 5-flucytosine for cryptococcus)

Antimicrobial Prophylaxis & Stewardship

Prophylaxis Indications

Secondary N. meningitidis / H. influenzae meningitis cases; pneumococcal (asplenia/hyposplenism); TB close contacts; surgical patients; rheumatic-fever recurrence

Stewardship Principle

"Start Smart then Focus" — do NOT start antibiotics without clinical evidence of bacterial infection

Start Smart

Drug-allergy history; prompt effective treatment (within 1 h for severe sepsis); comply with local guidance; document indication/dose/route + review/stop date; obtain cultures before therapy where possible

Then Focus & Resistance

Review at 48–72 h → STOP · IV-to-oral switch · change · continue · OPAT
Resistance — natural vs acquired; mechanisms (reduced permeability, efflux, degradation, target modification/protection); genetic — chromosomal mutation (vertical); conjugation/transduction/transformation (horizontal)

physiology · background · low-yield

Microbiology

Horizontal resistance transfer — conjugation (plasmid-mediated), transduction (phage DNA), transformation (donor DNA); vertical = chromosomal mutation

Background

Side effects common to most antimicrobials — nausea, diarrhoea, rash; common contraindications — liver failure, renal failure, children, pregnancy

Tropical & Imported Infections

5 entries

Enteric Fever (Typhoid)

C/P

Salmonella (typhi/paratyphi); return from endemic area (e.g. India)
Unremitting stepwise fever, headache, abdominal pain + constipation
Relative bradycardia (Faget sign); rose spots on abdomen; hepatomegaly

Inves

Blood cultures ×3 — grow a Gram-negative organism (Salmonella)

Mng

Ceftriaxone 2 g IV OD (after sending cultures) then oral azithromycin for 7 days

Special

Faget sign (relative bradycardia) + rose spots (blanchable erythematous papules) = the classic pairing

Tick Typhus (Rickettsia)

C/P

Return from African game park / South Africa; fever + lethargy
Eschar (bite with a scab), local lymphadenopathy, sparse papular rash

Inves

Rickettsial serology

Mng

Doxycycline for 7 days

Special

The eschar at the tick-bite site is the diagnostic clue
The eschar is classically termed the tache noire; classic triad = fever + sparse maculopapular rash + eschar

physiology · background · low-yield

Epidemiology/Risk

a.k.a. African tick bite fever — very common in South Africa and the Mediterranean

Amoebic Liver Abscess

C/P

Return from endemic area (e.g. India); fever, sweats, RUQ pain but no diarrhoea
Tender hepatomegaly + dull right lung base (raised hemidiaphragm)
Causative organism Entamoeba histolytica; can cause a right-sided pleural effusion / raised hemidiaphragm

Inves

Neutrophilia, raised ALP; USS — abscess in right liver lobe
Amoebic serology positive in 95–100%

Mng

Metronidazole (or tinidazole) PLUS diloxanide furoate (luminal agent)

Special

Amoebic serology is highly sensitive; abscess classically in the right lobe

Schistosomiasis

C/P

Freshwater exposure in Africa; tiredness, urinary frequency, haematuria
Brief itchy, slightly oedematous rash while away = Katayama fever (acute schistosomiasis)

Inves

Eosinophilia
Terminal urine for S. haematobium eggs; serology; stool O,C,P; rectal snips

Mng

Antiparasitic therapy after confirming ova (see local guidance)

Special

Katayama fever (urticarial rash) + terminal haematuria point to S. haematobium

physiology · background · low-yield

Other

Physical examination is often unremarkable

Malaria

C/P

Plasmodium protozoa via female Anopheles mosquito; P. falciparum = worst prognosis
Paroxysms of high fever, rigors, profuse sweating; headache, myalgia, back pain, splenomegaly
Severe (falciparum) — cerebral malaria (coma, convulsions), severe anaemia, DIC, blackwater fever (haemoglobinuria), hypoglycaemia, lactic acidosis, renal failure (ATN), algid malaria (circulatory collapse), pulmonary oedema/ARDS
Markers of severity — hyperpyrexia, hyperparasitaemia, jaundice, prostration (extreme weakness), impaired but rousable consciousness
Cerebral malaria — unrousable coma, convulsions, gaze abnormalities, neck stiffness & rigidity (must exclude other causes)

Inves

Thick + thin blood films ×3 (thick for low parasitaemia)
Rapid dipstick — HRP2 (Pf) + pLDH antigens; parasitaemia % guides severity

Mng

Non-falciparum — chloroquine 600 mg then 300 mg; primaquine 15 mg ×14 d for P. vivax/ovale (clears hypnozoites — check G6PD first)
Falciparum — quinine sulfate + doxycycline/clindamycin/pyrimethamine-sulfadoxine, OR artemether-lumefantrine / atovaquone-proguanil / mefloquine
Severe — IV quinine 10 mg/kg every 8 h (SE — cinchonism, deafness, arrhythmias) + supportive care
Uncomplicated (not vomiting, parasitaemia <2%, ambulant) — oral malarone 4 tabs/day ×3 d, or oral quinine 600 mg TDS until film negative then doxycycline 100 mg ×7 d; severe = vomiting / parasitaemia >2% / severity markers

Special

P. falciparum cytoadherence ("knobs") → sequestration → severe multi-organ disease
Hypnozoites (P. vivax/ovale) → relapse; recrudescence (falciparum) from partial treatment; fever periodicity by species (→ Criteria tab)

physiology · background · low-yield

Mechanism

Life cycle — Anopheles injects sporozoites → mature to merozoites in hepatocytes (1–2 wk); erythrocytic cycle merozoite→trophozoite→schizont→ruptured schizont (2–3 d) releases TNF + inflammatory cytokines driving fever paroxysms
Haemolytic anaemia from destruction of parasitised and non-parasitised RBCs + dyserythropoiesis; blackwater fever = intravascular haemolysis usually triggered by oxidant drugs

Other

DDx — meningitis, typhoid, septicaemia, influenza, dengue, hepatitis, leptospirosis, relapsing fever, viral encephalitis, trypanosomiasis

Epidemiology/Risk

Severe malaria usually in non-immune individuals and children in endemic areas

Background

Prevention — cover exposed skin, insecticide-treated bed nets, insect repellents; a single infection confers no lasting immunity (reinfection common in endemic areas)
Supportive therapy — paracetamol / tepid sponging, anti-emetics, IV fluid rehydration, vital-sign monitoring, ICU if needed

Microbiology

Rapid dipstick uses monoclonal Abs vs Pf HRP2 & pLDH antigens (~90% sensitivity/specificity for falciparum); a negative film does not exclude disease (sequestration)

Arboviruses & Viral Haemorrhagic Fevers

11 entries

VHF & Arbovirus — Overview

C/P

Arbovirus = arthropod-borne zoonotic viruses (>385); vectors — Culex, Aedes, Anopheles + ticks; generally mild, short incubation (<10 d)
Pyrexia, conjunctival suffusion, rash, retro-orbital pain, myalgia, arthralgia; biphasic illness
VHF — mild/no symptoms in 80%, severe multi-system in 20%; humans not the natural reservoir; endemic — Lassa, Marburg, Ebola, Congo-Crimean (yellow fever + dengue less severe)
Severe VHF — oedema of head and neck, encephalopathy, coagulopathy
VHF incubation 2–21 days, insidious onset; infectious once clinically symptomatic

Inves

Virus (culture/PCR), antigen (ELISA), antibody; leukopenia, thrombocytopenia, prolonged APTT

Mng

Supportive; isolation + full barrier protection (side room, gown/gloves/mask/eyes, space suit)

Special

Haemorrhage — increased vascular permeability, capillary fragility, consumptive coagulopathy (endothelial + platelet dysfunction)
Not airborne but may be transmitted by aerosols

physiology · background · low-yield

Mechanism

Severe arbovirus encephalitis results from cerebral invasion by the virus
VHF spread via infected body fluids — blood, saliva, vomitus, stools, genital secretions, possibly sweat; cross-infection via needles

Background

Average duration of fever in VHF ≈ 16 days

Yellow Fever

C/P

Flaviviridae ssRNA; Aedes aegypti (urban), sylvatic cycle (monkeys); incubation 3–6 d; mortality up to 40%
Phases — acute (fever 39–40 °C, flushed face, conjunctival suffusion, retrobulbar pain, myalgia; Faget's sign from day 2) → remission → toxic (jaundice, hepatomegaly, ecchymosis, bleeding gums, haematemesis/melena)
Toxic-phase multi-organ failure — myocardial fibre damage → arrhythmia; renal tubular damage → renal failure
Terminal phase — delirium → stupor → coma

Inves

Virus isolation (first 3 days), PCR; impaired LFTs, thrombocytopenia, coagulation defects, leukopenia with relative neutropenia
Councilman bodies in liver

Mng

Supportive (rest, fluids, bed rest under mosquito nets); acetaminophen; avoid NSAIDs / aspirin / ibuprofen (bleeding)
Live attenuated 17D vaccine (single SC); valid 10 y (protection likely lifelong); CI <9 months, immunosuppressed, severe egg/ingredient allergy

Special

Faget's sign (fever + relative bradycardia) · Councilman bodies (liver) · haematemesis + melena in the toxic phase
"Coffee-ground" vomit from gastric-mucosa erosion in the toxic phase

physiology · background · low-yield

Epidemiology/Risk

Three transmission cycles — sylvatic (monkeys; Ae. africanus in Africa, Haemagogus/Sabethes in S. America), urban (Ae. aegypti), intermediate (Africa only; semi-domestic Ae. furcifer/simpsoni)

Microbiology

Serodiagnosis limited by cross-reactivity with other flaviviruses in endemic areas

Other

Transaminases rise 48–72 h after initial symptoms
Vaccine in pregnancy — at the discretion of the provider

Mechanism

Terminal coma from cerebral oedema, microscopic perivascular haemorrhage, uraemia, haemorrhagic shock

Dengue Fever

C/P

Flavivirus, 4 serotypes; Aedes aegypti (+ albopictus); incubation 5–6 d; "break-bone fever"
Abrupt fever, headache, retro-orbital pain (worse on eye movement), severe backache/bony pain; facial flushing, conjunctival suffusion, lymphadenopathy, petechiae/rash; saddleback (biphasic) fever
DHF/DSS — after 2nd infection with a different serotype → capillary leak, thrombocytopenia, hypotension, shock/haemorrhage; mortality up to 44%

Inves

Serology / PCR; leucopenia + thrombocytopenia; DHF — depressed complement + DIC
Course — febrile (d1–3) → critical (d4–6: platelet nadir, haematocrit peak) → recovery (d7–10, fluid overload risk)
Classic dengue — clotting normal despite thrombocytopenia

Mng

Supportive with analgesics + adequate fluid replacement; corticosteroids of no benefit; no effective vaccine yet

Special

Sequential infection with a different serotype predisposes to DHF; saddleback fever curve

physiology · background · low-yield

Epidemiology/Risk

Most common arthropod-borne viral infection in humans
Mosquito nets not very effective — Aedes bites in the daytime

Exam technique

No neck stiffness or photophobia (helps exclude meningitis)

Background

Convalescence phase — severe fatigue, feeling of being unwell and depression lasting several weeks

Congo-Crimean Haemorrhagic Fever

C/P

Bunyaviridae; mainly Asia + Africa; hosts = cattle + hares; tick vector; incubation 3–6 d
Influenza-like illness with fever + haemorrhagic manifestations; mortality 10–50%

Inves

PCR / serology (barrier-nursed VHF workup)

Mng

Supportive + strict isolation

Special

Tick-borne bunyavirus — the one VHF with a tick (not mosquito) vector

Rift Valley Fever

C/P

Livestock disease (sheep, goats, camels, cattle); southern + Eastern Africa; vectors Culex pipiens + Aedes caballus; also bite of infected animal / raw animal products
Incubation 3–6 d, biphasic; mild (fever, weakness, back pain, dizziness); severe — retinopathy, meningoencephalitis, haemorrhage, hepatic necrosis; mortality ~50% in severe forms

Inves

Serology / PCR

Mng

Supportive; animal vaccination (cattle); avoid raw animal tissues/fluids, cook meat/milk

Special

No documented person-to-person transmission; prevention centres on vaccinating livestock

Lassa Fever

C/P

Arenavirus; rat reservoir; via food contaminated by rat urine/saliva; person-to-person via body fluids
Only 10–30% symptomatic; incubation 7–18 d, insidious; fever, myalgia, severe backache, sore throat/pharyngitis/lymphadenopathy (>50%), maculopapular rash
Severe — epistaxis, GI bleeding, irreversible hypovolaemic shock; mortality 15–20% (hospitalised)

Inves

Serial serology + RT-PCR (throat swab, serum, urine)

Mng

Supportive + strict isolation

Special

Rat-borne arenavirus; death from irreversible hypovolaemic shock

West Nile Virus

C/P

Culex mosquitoes; wild birds = reservoir; humans/horses = accidental hosts
~1 in 5 develop fever, body aches, arthralgia, vomiting, rash, eye pain
Severe neuroinvasive disease — encephalitis, neck stiffness, disorientation, muscle weakness, paralysis

Inves

Serology / PCR

Mng

Supportive; prevent mosquito bites (long sleeves/trousers)

Special

The arbovirus with a Culex (not Aedes) vector + prominent neuroinvasive disease

Chikungunya

C/P

Aedes aegypti + albopictus; fever, headache, maculopapular rash, myalgia, migratory polyarthritis, encephalitis
>20% still have recurrent joint pains after 1 year; mortality ~0.1%; elderly/very young most vulnerable

Inves

Serology / PCR

Mng

NSAIDs for joint pain; virus-like-particle vaccine in clinical trial

Special

Intense, long-lasting migratory polyarthritis is the signature

physiology · background · low-yield

Mechanism

Neurological complications arise from a viral strain with mutations conferring higher neurovirulence

Ebola Virus Disease

C/P

Natural host = fruit bats; human-to-human spread; 5 species; fatality 25–90% (avg ~50%)
Acute — severe headache, myalgia, vomiting, high fever, prostration, sore throat; day 5 maculopapular facial rash + profuse GI symptoms; day 7–16 internal + external bleeding
Exam signs — hepatosplenomegaly, facial oedema, red eyes, rash

Inves

PCR / antigen (ELISA) — great care handling specimens

Mng

Supportive; ribavirin in the first week; strict isolation (flexible-film isolator)

Special

Fruit-bat reservoir; haemorrhagic phase day 7–16
Prominent/characteristic chest pain, dry cough and hiccups

Zika Virus

C/P

Flavivirus (closely related to dengue); Aedes mosquitoes; usually unremarkable / self-limiting
Fever, myalgia, eye pain, prostration, maculopapular rash
Microcephaly in infants (congenital, Zika RNA in brain tissue); Guillain-Barré with epidemics

Inves

Serology — complicated by cross-reactivity with dengue

Mng

Supportive

Special

Congenital microcephaly + Guillain-Barré association define its significance

Hantavirus

C/P

Enzootic viruses of wild rodents; spread by aerosolised excreta (NOT by insect vectors)
Korean haemorrhagic fever (HFRS); mortality 5–10%; phases — fever → shock + haemorrhage → oliguric
Also acute respiratory distress after inhaling aerosolised rodent faeces

Inves

ELISA for specific antibodies

Mng

Supportive; avoid aerosolising rodent droppings, wear a mask when cleaning infested areas

Special

No insect vector — transmission is by inhaled rodent-excreta aerosols

Definitions & Diagnostic Criteria

3 entries

Fever & FUO — Definitions & Categories

Definition of Fever

Exceeds normal daily variation + raised hypothalamic set point
>37.2 °C before noon · >37.7 °C after noon

Classic FUO

>38.3 °C (101 °F) on several occasions · >3 weeks' duration · no diagnosis despite 1 week inpatient investigation OR 3 outpatient visits

Four Categories

Category	Temperature	Setting / minimum workup
Classic	>38.3 °C several occasions	>3 wk; 3 outpatient visits OR 3 days inpatient OR 1 wk invasive ambulatory workup
Nosocomial	>38.3 °C several occasions	Hospitalised, not incubating on admission; 3 days investigation incl. 2 days culture incubation
Neutropenic	>38.3 °C several occasions	Neutrophils <500/µL (or falling); ≥2 days culture incubation
HIV-associated	>38.3 °C several occasions	>4 wk outpatient OR >3 days inpatient; 3 days workup incl. 2 days cultures

Causes (developed world)

Noninfectious inflammatory disorders dominate — then infection, neoplasm (lymphoma, leukaemia), other (drug fever, factitious, recurrent PE)

CSF Findings in Meningitis

Parameter	Normal	Bacterial	Viral	Fungal	Tubercular
Opening pressure	<20 cm	Elevated	Usually normal	Variable	Variable
WBC / mm³	<5	≥1000	<100	Variable	Variable
Predominant cell	—	PMN	Lymphocytes	Lymphocytes	Lymphocytes
Protein	<0.5 g/L	Mild–marked ↑ (>1)	Normal–elevated	Elevated	Elevated
CSF : serum glucose	<66%	Low	Usually normal	Low	Low

LDH is raised in bacterial meningitis but not viral — a useful discriminator. Colour: bacterial turbid, viral clear.

Neutropenia & Febrile Neutropenia — Definitions

Neutropenia Thresholds

ANC <500/µL — increased risk of serious infection
ANC <100/µL — severe neutropenia
Duration + severity correlate with infection incidence/severity
ANC = WBC × (% neutrophils + % bands)

Febrile Neutropenia

>38.3 °C (101 °F) single reading OR >38 °C (100.5 °F) sustained >1 hour
High-risk (ASCO/IDSA) — <100 neutrophils/µL for >7 days

Empiric Therapy

Start antibiotics immediately — monotherapy: cefepime, meropenem, imipenem-cilastatin, or piperacillin-tazobactam
Add aminoglycoside if unstable/septic; add vancomycin if MRSA or Corynebacterium suspected

Severity & Risk Classifications

4 entries

HIV — CD4 Count & Opportunistic-Infection Risk

CD4 (cells/µL)	Typical infections / conditions
>500	No increased risk
200–500	S. pneumoniae / TB · oral candida · Kaposi sarcoma · VZV / HSV · molluscum
100–200	PCP (Pneumocystis) · JCV (PML) · histoplasmosis · coccidioidomycosis
50–100	Toxoplasmosis · cryptosporidiosis · cryptococcus · CMV
<50	Mycobacterium avium complex (MAC); tissue-invasive CMV

Toxoplasma reactivation risk rises <100; CMV retinitis typically CD4 ≈10. General OI predisposition once CD4 <50/µL.

WHO Severe Malaria — Markers of Severity

Organ-Specific Complications (P. falciparum)

Cerebral malaria — unrousable coma, convulsions, gaze abnormalities, neck stiffness/rigidity
Severe anaemia — destruction of parasitised + non-parasitised RBCs + dyserythropoiesis
DIC / haemorrhage / thrombocytopenia; GI bleeding
Blackwater fever — haemoglobinuria from intravascular haemolysis (often oxidant-drug triggered)
Hypoglycaemia — glycogen depletion + parasite glucose use
Lactic acidosis — tissue ischaemia → anaerobic glycolysis
Renal failure — rising creatinine + oliguria (acute tubular necrosis)
Algid malaria — circulatory collapse (± complicating sepsis)
Pulmonary oedema / ARDS — high mortality (± fluid overload)

Other Markers

Hyperpyrexia · hyperparasitaemia · jaundice · prostration · impaired but rousable consciousness

Dengue — Clinical Course & Severity

Course of Illness

Phase	Days	Clinical / Lab
Febrile	1–3	Dehydration; platelet count drops; viraemia
Critical	4–6	Shock / bleeding, organ impairment; platelet nadir, haematocrit peak; IgM/IgG begin to rise
Recovery	7–10	Reabsorption / fluid-overload risk; platelet rises, haematocrit normalises; IgM/IgG high

Dengue Haemorrhagic Fever / Shock Syndrome

Requires ≥2 sequential infections with different serotypes
Capillary leak syndrome · thrombocytopenia · hypotension · shock + haemorrhage; mortality up to 44%

Cutaneous Eruptions — EM / SJS / TEN Spectrum

Type	Lesion / BSA	Distribution	Mucosal	Systemic	→ TEN?	Precipitants
EM minor	Typical target	Extremities	Absent/mild	Absent	No	HSV
EM major	Typical target	Extremities, face	Severe	Fever/arthralgia	No	HSV, Mycoplasma
SJS	Atypical targets, <10% BSA	Trunk, face (+)	Severe	Usually present	Possible	Drugs
SJS/TEN overlap	10–30% detachment	Trunk, face, neck (++)	Severe	Always	Likely	Drugs
TEN	>30% detachment	Distal limbs, trunk, face, neck (+++)	Severe (resp + GI)	Always (+ nephritis)	—	Drugs

Drugs most incriminated in SJS/TEN — NSAIDs, antibiotics, antiepileptics. EM does not progress to TEN. SJS/TEN = Type IV hypersensitivity.

Microbiology & Classifications

6 entries

Immunodeficiency Categories & Associated Pathogens

Defect	Causes	Associated pathogens
Humoral (B cells, antibodies)	Myeloma, CLL, AIDS	S. pneumoniae, H. influenzae, Mycoplasma, Campylobacter, Giardia, Enterovirus
T cell	Primary immunodeficiency (inherited); HIV, lymphoma, steroids	Intracellular (virus, TB, protozoa); fungal
Neutropenia	Chemotherapy, BMT	Gram-negatives, Candida, Aspergillus, gut/skin flora
Complement	Inherited/acquired	S. pneumoniae, Neisseria
Asplenia	Splenectomy, trauma, sickle cell	S. pneumoniae, H. influenzae, N. meningitidis, Plasmodium

Herpesvirus Family Classification

Subfamily	Virus (HHV)	Major diseases
Alpha	HSV-1 (HHV1)	Cold sores, encephalitis, erythema multiforme
	HSV-2 (HHV2)	Genital infection, erythema multiforme
	VZV (HHV3)	Chickenpox, zoster
Beta	CMV (HHV5)	Hearing loss, retinitis
	HHV6B	Exanthem subitum, febrile fits
	HHV7	Exanthem subitum, febrile fits
Gamma	EBV (HHV4)	Glandular fever, Burkitt's lymphoma
Gamma	KSHV (HHV8)	Kaposi's sarcoma

Antimicrobial Mechanisms of Action

Target	Drug classes
Cell-wall synthesis	Penicillins, cephalosporins, monobactams, carbapenems, glycopeptides, cycloserine, bacitracin
Cell membrane	Polymyxins
Folic-acid metabolism	Trimethoprim, sulphonamides (block DHFA / THFA)
DNA gyrase	Quinolones
DNA-directed RNA polymerase	Rifampicin
Protein synthesis — 50S	Macrolides, chloramphenicol, lincosamides
Protein synthesis — 30S	Tetracyclines, aminoglycosides, spectinomycin
Protein synthesis — tRNA	Mupirocin

Malaria — Species Comparison

Species	Fever cycle	Clinical name	Key feature
P. falciparum	Variable (48 or 24 h)	Malignant tertian	Worst prognosis; cytoadherence; recrudescence from partial Rx
P. vivax	48 h	Tertian	Relapse from hypnozoites → primaquine (check G6PD)
P. ovale	48 h	Tertian	Relapse from hypnozoites → primaquine
P. malariae	72 h	Quartan	Longest cycle
P. knowlesi	24 h	—	Shortest cycle

Relapse (vivax/ovale — dormant hypnozoites) vs recrudescence (falciparum — incomplete treatment) vs reinfection.

Vaccine Classification

Type	Examples
Live — natural	Vaccinia (smallpox)
Live — attenuated	BCG, MMR, OPV (Sabin), varicella, yellow fever
Killed — whole	IPV (Salk), rabies, hepatitis A
Killed — subunit	Hep B (recombinant), influenza, 23-valent pneumococcal polysaccharide, B. pertussis
Killed — conjugate	7-valent pneumococcal, Hib, MenC (protein-conjugated → works <2 y)
Toxoid	Tetanus (inactivated toxin — formaldehyde / genetic mutation)

Live CI in immunosuppression + pregnancy; killed safe in immunocompromised but need boosters + cause more local reactions.

Other Antimicrobials (lecturer self-study list)

The Antimicrobials lecture flags these as "others you need to know something about" — go through the same scheme (spectrum · clinical use · PK · side effects) in less detail for each.

Agent	Class / target	Key use in this module
Trimethoprim	Folate synthesis inhibitor	UTI; as co-trimoxazole for PCP + toxoplasmosis prophylaxis/treatment
Chloramphenicol	50S protein synthesis	Reserved — bacterial meningitis in penicillin/cephalosporin anaphylaxis
Metronidazole	Anaerobes + protozoa	Brain abscess (anaerobes), C. difficile colitis, amoebic liver abscess
Clindamycin	50S; Gram-positive + anaerobes	S. aureus / Group A Strep, malaria adjunct
Doxycycline	Tetracycline (30S)	Tick typhus, malaria (treatment + prophylaxis), atypicals
Rifampicin	DNA-directed RNA polymerase	Anti-TB; meningococcal + Hib contact prophylaxis
Fusidic acid	Protein synthesis	Anti-staphylococcal (skin/bone) — combine to limit resistance
Linezolid	Oxazolidinone	MRSA / resistant Gram-positives
Nitrofurantoin	—	Lower urinary tract infection

Schedules & Protocols

4 entries

Egyptian Childhood Vaccination Schedule

Vaccine	Schedule
BCG	Birth
OPV	Birth, 2, 4, 6, 9, 18 months
DTwP	2, 4, 6, 18 months
DTwP-Hep / Hep B	2, 4, 6 months
MMR	12, 18 months
MenAC	3, 6, 12, 15 years

UK Childhood Vaccination Schedule

Age	Vaccines
2 months	DTaP/IPV/Hib (5-in-1) + Pneumococcal
3 months	DTaP/IPV/Hib + MenC
4 months	DTaP/IPV/Hib + MenC + Pneumococcal
12 months	MenC + Hib
13 months	Pneumococcal + MMR (1st)
3–5 years	DTaP/IPV + Hib and MMR (2nd)
13–18 years	Td + IPV (low-dose "little d")

5-in-1 = diphtheria toxoid + tetanus toxoid + acellular pertussis + IPV + Hib conjugate. HPV — all boys + girls from 12–13 (2 doses; 3 doses if started >15 y).

Stewardship — Start Smart Then Focus

Start Smart

Do NOT start antibiotics without clinical evidence of bacterial infection
Take a thorough drug-allergy history
Initiate prompt effective treatment — within 1 hour for severe sepsis
Comply with local antimicrobial guidance
Document clinical indication, dose + route, and a review/stop date
Obtain cultures before commencing therapy where possible

Then Focus (review at 48–72 h)

Check microbiology → decision: STOP · IV-to-oral switch · change antibiotic · continue · OPAT (Outpatient Parenteral Antibiotic Therapy)
Document the decision, next review date + stop date

Hartford Nomogram — Aminoglycoside Dosing

Dosing & Monitoring

Single daily dose 5–7 mg/kg (7 mg/kg at RFH)
Take one level 6–14 h after the dose
Plot concentration (y-axis, mg/L) vs time from infusion start to sample (x-axis, hours)
Zone read-off gives the dosing interval — Q24h · Q36h · Q48h

Antimicrobial Classes — Spectrum, Clinical Use & Side Effects

Companion to Antimicrobial Mechanisms of Action (targets) — this is the clinical dimension the lecture drills: for each group think spectrum · clinical use · side effects. Before starting any agent: no antimicrobials for viral infection; weigh allergy, renal/liver impairment, severity, immunocompromise, pregnancy/breastfeeding/OCP; take cultures first; consult local policy; set dose, route & duration.

Class (examples)	Spectrum	Clinical use	Key side effects / notes
Beta-lactams — narrow: penicillin, amoxicillin, flucloxacillin; broad: co-amoxiclav, piperacillin-tazobactam, cefuroxime/cefotaxime/ceftriaxone, meropenem	Gram+ good (resistance an issue); Gram− & anaerobe good for broader-spectrum agents; broadest (pip-taz, meropenem) cover resistant Gram−; no mycobacteria	Commonest & most important group; respiratory/IE, skin-soft-tissue-bone-joint, UT/GU, meningitis (cross BBB when meninges inflamed); often in combinations	Rash/hypersensitivity (1–10%), anaphylaxis (~0.05%); antibiotic-associated diarrhoea/colitis (esp. cephalosporins & broad-spectrum); safe in pregnancy
Glycopeptides — vancomycin, teicoplanin	Gram+ only (incl. MRSA, enterococci); none for Gram−, anaerobes, mycobacteria, atypicals	MRSA & enterococcal infection (skin/joint/pneumonia/IE); when resistance or penicillin anaphylaxis is a problem; *oral vancomycin for C. difficile* colitis** (stays in gut)	Nephrotoxic & ototoxic in toxic amounts — monitor levels (vanco > teico); red person (red man) syndrome if infused too fast → give slowly
Macrolides (“-thromycins”) — erythromycin, clarithromycin, azithromycin	Gram+ good (staph resistance a problem); atypicals good (Chlamydia, Legionella, Mycoplasma); respiratory Gram− (H. influenzae, M. cat); some mycobacteria (clarithromycin); azithromycin for enteric fever	Alternative to beta-lactams for respiratory & skin/soft-tissue infection (penicillin allergy); atypical pneumonia; azithromycin for Chlamydia	GI upset (marked with erythromycin, less with others); hepatic impairment a contraindication with azithromycin
Aminoglycosides — gentamicin, amikacin, streptomycin	Gram− & Pseudomonas good; lack intrinsic anti-streptococcal activity but synergise with penicillins; poor for anaerobes & intracellular pathogens; streptomycin has some anti-mycobacterial activity	Empirical sepsis with a beta-lactam when Gram− source likely (urinary/biliary/respiratory/GI); synergy in IE; not used as monotherapy (except ear/eye drops)	Nephrotoxic & ototoxic at high levels — monitor (Hartford nomogram); caution with diuretics; parenteral only (poorly absorbed orally)
Quinolones — ciprofloxacin, levofloxacin, moxifloxacin	Gram+ poor (but moxi/levo good for S. pneumoniae); Gram− good (moxi has no anti-Pseudomonas activity); intracellular good (enteric fever, Legionella); moxi most anti-mycobacterial	Empirical when Gram− likely & patient penicillin-allergic; UTI, GI, respiratory (if pneumococci not involved); moxifloxacin for LRTI incl. mycobacterial	Lowers seizure threshold; tendon damage; relative CI in children (joint effects in immature animals)

Beta-lactam sub-agents worth naming

Flucloxacillin — penicillinase-resistant; for Staphylococcus aureus (impetigo, cellulitis, folliculitis, septic arthritis, osteomyelitis, pneumonia, IE)
Co-amoxiclav (Augmentin) — amoxicillin + clavulanic acid (a beta-lactamase inhibitor covering the enzymes of S. aureus, E. coli, H. influenzae); used when broad cover needed (e.g. GAS + S. aureus together)

TB — first-line (RIPE, used in combination)

Rifampicin · Isoniazid · Pyrazinamide · Ethambutol

Antifungals — three main classes

Azoles (fluconazole, itraconazole) — inhibit ergosterol synthesis in the fungal cell membrane
Polyenes (amphotericin) — bind ergosterol → membrane pores → leakage and cell death
Echinocandins (caspofungin) — inhibit fungal cell-wall glucan synthesis

Prophylaxis — 5 common indications

Prevent secondary cases of N. meningitidis / H. influenzae meningitis (contacts)
Prevent pneumococcal infection in asplenia / hyposplenism
Prevent TB in close contacts
Surgical prophylaxis
Prevent recurrence of rheumatic fever