Infections in the Immunocompromised Host

Strictly sourced from ICC3-026 Infections in the Immunocompromised Host 2024-2025

Part A — Foundations

🧬

Core Definitions

Opportunistic = normal organism + broken host. Severity follows depth & duration of deficiency.
Opportunistic InfectionInfections more frequent OR more severe because of immunosuppression
Neutropenia<100 neutrophils/µL for >7 days = profound protracted neutropenia (ASCO/IDSA threshold for prophylaxis)
Primary immunodef.Over 400 inborn errors of immunity; caused by >200 known single gene mutations
ANC calculationWBC × (% neutrophils + % bands)
ANC <500 = Neutropenia risk threshold  |  ANC <100 = Severe neutropenia
🦠

Types of Opportunistic Organisms

Two categories: low-virulence organisms vs conventional pathogens behaving atypically.
Low Pathogenicity
Atypical Conventional
  • Coagulase negative staphylococcus
  • Pseudomonas aeruginosa
  • Candida albicans
  • Pneumocystis jirovecii (PCP)
  • Cytomegalovirus (CMV)
  • Miliary tuberculosis in renal transplant recipient
  • Measles in a leukaemic child
  • Disseminated HSV in a BMT recipient
  • CNS toxoplasmosis in an AIDS patient
🔄

Sources & Transmission Routes

Know whether the source is inside (endogenous) or outside (exogenous) the patient.
Endogenous
Exogenous
Routes
  • Gut flora
  • Candida albicans
  • Reactivation of HSV
  • MRSA, Resistant Gram-negatives
  • Aspergillus, Environmental mycobacteria
  • Pseudomonas, Listeria
  • Primary CMV from transplanted organ
Hands/Environment Air Water Food Organ transplant

Herpes viruses: direct contact (skin/mucous membranes). Humans are the only reservoir.

📍

Common Infection Sites

Infection can occur anywhere — but these 6 sites dominate.
Mouth & throat Skin Gut Lungs Kidneys/Bladder (esp. with catheter) Drip / Central line site

Part B — Disease Reference

Kaposi Sarcoma

🩸

Clinical Presentation

SBA: 35F, HIV+ve CD4 ~20, fever + skin lesions → AIDS-defining diagnosis.
HIV CD4 ~20AIDS defining
  • Angioproliferative disorder: Skin, Lung, GI tract
  • "Classic" form (pre-HIV era): affects old men
🔬

Investigations

Tissue diagnosis is required.
BiopsyConfirms diagnosis
💊

Management

Immune reconstitution first; local chemo if needed.
  • 1
    Primary: ART (anti-retroviral therapy)
  • 2
    Consider intralesional Vinblastine OR IV Doxorubicin

Pneumocystis Jirovecii Pneumonia (PCP)

🫁

Clinical Presentation

SBA: HIV male CD4 150, SOB + dry cough + bilateral ground glass on CXR.
HIV CD4 <200BMTHaem malignancySteroids / Wegener's
  • Fever, dry cough, respiratory failure
  • Transmission: airborne, person-to-person
  • Organism: Fungi
🩻

Investigations

Imaging suggests; stains and molecular confirm.
CXR"Ground glass", bilateral pneumonitis
SamplingInduced sputum (in HIV) or BAL
DiagnosticsFluorescent antibody, silver stains, PCR, B-D Glucan
H&E stainCollections of foamy histiocytes, well-formed necrotizing granuloma
Acid-fast stainNumerous organisms within histiocytes
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Management

Treat the infection; restore immunity; prevent recurrence.
  • 1
    Acute: Cotrimoxazole (oral trimethoprim-sulphamethoxazole)
  • 2
    Start ART (if HIV+ve)
Prophylaxis: Cotrimoxazole if: HIV CD4<200 | Renal Tx (3 months) | BMT

Cytomegalovirus (CMV)

👁️

Clinical Presentation

SBA: 40M HIV+ve CD4 10, fever + blurring of vision → CMV Retinitis. Fundoscopy = "pizza pie appearance".
CD4 ~10 for retinitisDNA Herpes VirusBody fluid transmission
Presentation
End-Organ
  • Often asymptomatic reactivation
  • Symptomatic: Fever, rash, leucocytosis
  • Seroprevalence: 40-60% IgG (Western); >90% IgG (African)
  • Latency in monocytes and BM progenitor cells
  • Primary acquisition possible from transplanted organ
  • Retinitis ("pizza pie appearance")
  • Hepatitis (fulminant liver failure)
  • Oesophagitis, Colitis, Pneumonitis
  • CNS: Poly-radiculopathy, transverse myelitis, sub-acute encephalitis
  • Rarely: PUO, pericarditis, myocarditis, Guillain-Barré, cytopenias
🔬

Investigations

Confirm viral replication; negative PCR does NOT exclude infection.
Quantitative PCRCMV DNA detection. Negative PCR does not exclude CMV
SerologyIgG / IgM testing
FundoscopyPizza pie appearance in retinitis
HistopathologyCytomegalic cells with intranuclear "owl's eye" inclusion bodies
PharyngealExudate absent + heterophile antibodies absent (unlike EBV)
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Management

Treat with antivirals; test for resistance; use preemptive PCR monitoring in BMT.
  • 1
    Oral Valganciclovir OR IV Ganciclovir (test for drug resistance)
  • 2
    Alternatives: Foscarnet OR Cidofovir
  • 3
    Retinitis: add intravitreal Ganciclovir
Prophylaxis: Antiviral therapy for all seropositive patients at risk.
Preemptive (BMT): Weekly CMV PCR | Weekly galactomannan → treat if positive

Cryptosporidium parvum Colitis

💧

Clinical Presentation

SBA: HIV patient with repeated attacks of diarrhoea. CD4 <50 = fulminant; CD4 >150-180 = self-limited.
CD4 <50 = fulminantCD4 >150-180 = self-limited
  • Severe explosive watery diarrhoea in immunocompromised
  • Most prevalent in distal ileum and proximal colon
  • History: duration, frequency, severity, fever, abdominal pain, tenesmus, weight loss
🔬

Investigations

Clinical history is primary diagnostic tool as stated in lecture.
Clinical historyDuration, frequency, severity, consistency, fever, abdominal pain, tenesmus, weight loss
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Management

Prognosis depends entirely on immune reconstitution.
  • 1
    Reconstitute the immune system — therapy success determines prognosis

Mycobacterium Avium Intracellulare (MAC)

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Clinical Presentation

SBA: HIV patient with repeated attacks of diarrhoea, severe immunodeficiency. Found in soil, water, birds, animals.
Severe immunodeficiencyEnvironmental reservoir
  • Systemic: Fever and lethargy
  • GI: Small bowel infection
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Investigations

Endoscopic biopsy is key.
CulturesEndoscopic biopsy / blood / bone marrow cultures → finds organism
H&E stainCollections of foamy histiocytes
Acid-fast stainNumerous organisms within histiocytes
💊

Management

Immune reconstitution is primary treatment.
  • 1
    Reconstitute the immune system

HIV-Associated CNS Lymphoma

🧠

Clinical Presentation

Similar to toxoplasmosis BUT no constant headache — due to absence of inflammation.
  • Presentation similar to toxoplasmosis
  • Headache NOT a constant finding (lack of inflammation differentiates from toxo)
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Investigations

Clinical differentiation from toxoplasmosis.
Clinical assessmentDifferentiates from toxoplasmosis (no constant headache)
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Management

Radiotherapy is primary treatment.
  • 1
    Radiotherapy — benefits >75% of patients
  • 2
    Chemotherapy

Progressive Multifocal Leukoencephalopathy (PML)

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Clinical Presentation

JC virus destroys oligodendrocytes → patchy demyelination scattered through CNS.
HIVCLLNatalizumab
  • Oligodendrocytes loaded with JC virus → destruction + myelin breakdown
  • Patchy demyelination scattered through the CNS
🩻

Investigations

Imaging demonstrates demyelination.
Pathology/ImagingDemonstrates demyelination
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Management

  • 1
    Immune system reconstitution

Listeria Monocytogenes

🦠

Clinical Presentation

SBA: 30yo renal transplant recipient 3 months post-Tx, fever → blood culture = Gram+ve rods.
Aerobic Gram+ve rodImmunosuppressedPregnantAge extremes (>55, neonates)
  • Disease: Meningitis, bacteraemia, miscarriage, congenital infection
  • Reservoir: Dust, food (soft cheeses, pâté, coleslaw, uncooked meat), water, sewage, animals
🔬

Investigations

Isolate from sterile sites.
Gram stainAerobic Gram-positive rod
Blood culturePositive for Listeria
CSF analysisMay produce lymphocytic CSF
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Management

  • 1
    Amoxycillin OR Penicillin

Streptococcus pneumoniae Bacteraemia (Asplenia)

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Clinical Presentation

SBA: 23M splenectomy post-RTA, 6 months later fever with no obvious focus → immediate Ceftriaxone.
Gram+ve diplococcus, capsulatedAsplenia
  • Causes of asplenia: Splenectomy, Trauma, Sickle cell
  • Common focus: Pneumonia, otitis, sinusitis, meningitis, primary bacteraemia
  • Mortality up to 50% in asplenic patients; often NO obvious focus
Mortality up to 50% in asplenic patients — DO NOT DELAY antibiotics
🔬

Investigations

Do not delay treatment for cultures.
Gram stainGram-positive diplococcus; capsulated
Blood/CSF culture or PCRPositive for S. pneumoniae
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Management

  • 1
    Empiric immediate Ceftriaxone
  • 2
    If sensitive: IV Benzylpenicillin; if resistant: Vancomycin + Rifampicin
Prevention in asplenia:
Vaccines: PCV13 followed by PPSV23 + Meningo + HIB + Influenza
Prophylaxis: PO Penicillin for <2yrs and previous sepsis

Bacterial Meningitis

🧠

Clinical Presentation

SBA: 20yo university student flu-like illness + headache → found cold and unresponsive next morning.
Young adults: N. meningitidisOlder: S. pneumoniae / ListeriaInfants: E. coli / Grp B strep
  • Neurological: Focal or generalized seizures (frequent)
  • Cranial nerves: Deafness, imbalance
  • Non-neurological: Endocarditis, thrombocytopenia, acute adrenal failure
🔬

Investigations

Gram stain narrows organism; culture/PCR guides specific therapy.
Gram stainGram+ve diplococci (S. pneumo) | Gram-ve diplococci (N. mening) | Gram+ve bacilli (Listeria) | Gram-ve bacilli (Enterobacteriaceae)
Blood/CSF culture or PCRGuides specific therapy
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Management

  • 1
    Ceftriaxone 2g bd IV OR Cefotaxime 2g 6-hourly IV
  • 2
    Add Amoxicillin/Ampicillin if aged >60 OR immunocompromised (covers Listeria)
  • 3
    Treat complications: dehydration, anticonvulsants, osmotic diuretics or corticosteroids
Prophylaxis (N. meningitidis contacts): Single dose Ciprofloxacin OR Rifampicin 600mg bd for 2 days
Vaccines: N. meningitidis C, ACYW135 | S. pneumoniae | H. influenzae type B

Corynebacterium diphtheriae

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Clinical Presentation

Highly contagious upper respiratory tract illness with life-threatening complications.
Gram+ve rod
  • Upper respiratory tract illness
  • Complications: Myocarditis and Neuropathy
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Investigations

Gram stainGram-positive rods
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Management

  • 1
    Antitoxin + Erythromycin
  • 2
    Contact tracing and prophylaxis
Vaccines: Childhood immunization

Bacillus anthracis

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Clinical Presentation

Gram+ve rodZoonosis
  • Cutaneous anthrax OR Pulmonary anthrax
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Investigations

Gram stainGram-positive rods
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Management

Not explicitly specified in lecture slides.

Clostridium botulinum

⬇️

Clinical Presentation

Descending flaccid paralysis + autonomic dysfunction. Three exposure routes.
Foodborne (home canning)Wound (IVDUs)Infant (honey)
  • Descending flaccid paralysis
  • Autonomic dysfunction
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Investigations

DiagnosisClinical presentation
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Management

  • 1
    Supportive care
  • 2
    Antitoxin
  • 3
    Wound only: Benzylpenicillin + Debridement

Clostridium tetani

⬆️

Clinical Presentation

Tetanospasmin toxin → generalized SPASTIC paralysis (opposite of botulism which is flaccid).
Wound contamination
  • Lockjaw (trismus), fractures from recurrent spasms
  • Generalized spastic paralysis and muscle spasms
  • Sympathetic hyperactivity: tachycardia, hypertension, dysarrhythmias, sudden death
🔬

Investigations

DiagnosisClinical — spasm history + wound history
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Management

  • 1
    Supportive (ventilation), muscle relaxants
  • 2
    Wound debridement
  • 3
    Human tetanus immunoglobulin (passive)
  • 4
    Benzylpenicillin
Vaccines: Toxoid vaccine (active immunity)

Lassa Fever

🐀

Clinical Presentation

Arenavirus. Rat reservoir. IP 7-18 days, insidious onset.
Rat reservoirArenavirus family
  • Incubation: 7–18 days, insidious onset
  • Fever, myalgia, severe backache, malaise, headache
  • Transient maculopapular rash, sore throat, pharyngitis, lymphadenopathy >50%
  • Severe: Epistaxis, GI bleeding, irreversible hypovolaemic shock
🔬

Investigations

Serial serologyEvaluates antibodies
RT-PCR (throat swab)Genome detection
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Management

  • 1
    Supportive treatment for shock

Rabies

🐕

Clinical Presentation

SBA: 36M from Mexico, jaw pain 3 days, animal bite history. IP = 3 weeks to years.
80% animal bite history
  • Incubation: 3 weeks to years
  • Initial: flu-like + tingling at bite site
  • Cerebral: Hallucinations, nightmares, agitation, delirium, seizures, hydrophobia
  • Neuromuscular: Paralysis in bitten extremity
🔬

Investigations

Fluorescent antibodyConfirms virus antigen from saliva, skin, urine, CSF
SerologyAntibodies in serum and CSF
PCR of CSFDetects viral genome
💊

Management

  • 1
    Clean wound with detergent and water
  • 2
    Anticonvulsants and muscle relaxants
  • 3
    Passive: Human rabies immunoglobulins
  • 4
    Active: Human diploid cell vaccine

Viral Encephalitis (HSV)

🧠

Clinical Presentation

HSV-1HSV-2
  • Pathology: Extensive necrosis, macrophage reaction, neovascularization
  • End-stage: Brain atrophy and gliosis
🩻

Investigations

ImagingDetects degrees of brain destruction, inflammatory and reactive changes
HistopathologyPerivascular mononuclear cells and brain necrosis
MicroscopyViral intranuclear inclusions (eosinophilic masses of packed viral particles)
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Management

  • 1
    Treatment required to prevent brain atrophy and gliosis

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis

⚠️

SJS vs TEN — Head to Head

Rare, potentially fatal adverse cutaneous drug reactions — differ only by extent of BSA involvement.
Most common culprit drugs: NSAIDs, Antibiotics, Antiepileptics
FeatureSJSSJS-TEN OverlapTEN
BSA detachment<10%10–30%>30%
Rash typeDusky-red macules, macular atypical targets, epidermal detachment—Similar to SJS, higher confluence (+++)
LocationTrunk, Face—Trunk, Face, Neck
MucosalMucocutaneous tenderness, erythema—Severe respiratory + GIT mucosa involvement
SystemicFever, LN, Hepatitis, Cytopenia—More severe
Management (BOTH): 1. Immediate discontinuation of culprit drug  2. High-dose IVIG  3. Supportive care

Part C — Quick Reference & Prevention

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Immunodeficiency Classification Table

Know the deficiency → predict the organism. This is the exam question framework.
TypeAffected CellsAcquired CausesOrganisms at Risk
HumoralB cells, plasma cells, antibodiesMyeloma, CLL, AIDSS. pneumoniae, H. influenzae, Mycoplasma, Campylobacter, Giardia, Enterovirus
T cellsT cellsHIV, BMT, Lymphoma, SteroidsIntracellular pathogens — virus, TB, protozoa
NeutropeniaNeutrophil granulocytesChemoRx, BMTBacterial infections, Fungal infections
ComplementComplement—S. pneumoniae, Neisseria
AspleniaSpleenSplenectomy, Trauma, Sickle cellS. pneumoniae, H. influenzae, N. meningitidis, Plasmodium
Inherited cause for ALL rows = Primary Immunodeficiency Syndromes
📊

HIV Risk by CD4 Count

CD4 CountOrganisms / Risk
>500No increased risk
200–500S. pneumoniae, Tuberculosis, Oral candida, Kaposi Sarcoma, VZV, HSV, Molluscum
100–200PCP, JCV (PML), Histoplasmosis, Coccidioidomycosis
50–100Toxoplasmosis, Cryptosporidiosis
<50Cryptococcus, CMV, Mycobacterium Avium Intracellulare (MAC)
CD4 <50 → Cryptococcus, CMV retinitis, MAC  |  CD4 <200 → PCP prophylaxis threshold
⏳

Solid-Organ Transplant Infection Timeline

Time Post-TxInfections
<1 Month
Nosocomial/Technical		 MRSA, VRE, Candida (non-albicans), Aspiration, Catheter/Wound infection, Anastomotic leaks, C. difficile
Donor-derived (uncommon): HSV, LCMV, Rabies, West Nile, HIV, T. cruzi
Colonization: Aspergillus, Pseudomonas
1–6 Months With prophylaxis: Polyomavirus BK, C. diff, HCV, Adenovirus, Influenza, Cryptococcus, TB
Without prophylaxis: PCP, Herpesviruses (HSV/VZV/CMV/EBV), HBV, Listeria, Nocardia, Toxoplasma, Strongyloides, Leishmania, T. cruzi
>6 Months
Community/Late		 CAP, UTI, Aspergillus, Atypical molds, Mucor, Nocardia, Rhodococcus
Late viral: CMV (colitis/retinitis), HBV/HCV, HSV encephalitis, JC (PML)
Skin cancer, lymphoma (PTLD)
🦠

S. aureus Clinical Spectrum

Pyogenic DiseasesToxin-Mediated DiseasesOther
Localized skin (folliculitis, carbuncles, abscesses), Pneumonia, Bloodstream → Osteomyelitis / Endocarditis / Meningitis Food poisoning, Toxic shock syndrome, Staphylococcal scalded skin syndrome Prosthetic device-related (IVC-associated, pacemaker infections)
⚡

Varicella vs Zoster

FeatureVaricella (Chickenpox)Zoster (Shingles)
Reactivation of latent virus from sensory gangliaNoYes
Susceptible ifSeronegative for VZV IgGSeropositive for VZV IgG
Acquired by contact with varicella or zosterYesNo
Infectious virus present inRespiratory secretions (48h before rash) + Vesicle fluidVesicle fluid only
InfectiousnessHighly communicableLow rate of transmission
Route of transmissionDirect contact, droplet or airborne spreadDirect contact, droplet or airborne
🧠

Common CNS Infections

TypeClinical SyndromeCommon Causative Organisms
BacterialAcute pyogenic meningitisE. coli / Grp B strep (infants) | N. meningitidis (young adults) | S. pneumoniae / Listeria (older adults)
BacterialChronic meningitisMycobacterium tuberculosis
LocalizedAbscessStreptococci and staphylococci
LocalizedEmpyemaPolymicrobial (staphylococci, anaerobic Gram-negative)
ViralAcute aseptic meningitisEnteroviruses, Measles (SSPE), Influenza, LCMV
ViralEncephalitic syndromesHSV-1/2, CMV, HIV, JC polyomavirus (PML)
✅

Complete Prophylaxis Guide

Learn indication first → drug second. Every named indication in the lecture is here.
Antibacterial
Antifungal
Antiviral
Vaccines
Post-Exposure
  • 1
    Profound protracted neutropenia (<100/µL >7 days): Oral Fluoroquinolone
  • 2
    N. meningitidis contacts: Single dose Ciprofloxacin OR Rifampicin 600mg bd × 2 days
  • 3
    Asplenic patients <2yrs or previous sepsis: PO Penicillin
  • 1
    Profound neutropenia (high risk): Oral Triazole OR parenteral Echinocandin
  • 2
    BMT patients: Itraconazole
  • 3
    Preemptive (BMT): Weekly galactomannan monitoring
  • 1
    HIV CD4 <200: Cotrimoxazole
  • 2
    Renal Tx (3 months): Cotrimoxazole
  • 3
    BMT: Cotrimoxazole + Aciclovir
  • 4
    Seropositive patients at risk (CMV): Antiviral therapy
  • 5
    Preemptive (BMT): Weekly CMV PCR → treat if positive
  • 1
    Asplenic: PCV13 → PPSV23 + Meningo + HIB + Influenza
  • 2
    Hyposplenic: HIB, Pneumo, Meningo, Influenza
  • 3
    Meningitis: N. meningitidis C, ACYW135 | S. pneumoniae | H. influenzae type B
  • 4
    Tetanus: Toxoid vaccine
  • 5
    Rabies: Human diploid cell vaccine (active)
  • 6
    Diphtheria: Childhood immunization
  • 1
    VZV exposure (seronegative pregnant, neonates, immunocompromised): Passive immunization
  • 2
    HBV +ve mother newborn / HBV needlestick: Hep B Ig + Hep B vaccine
  • 3
    Rabies exposure: Human rabies immunoglobulins (passive) + Human diploid cell vaccine (active)
  • 4
    Tetanus wound: Human tetanus immunoglobulin
📋

Conclusion — Clinical Framework

When faced with a patient with a history suggestive of infection: Take a good history.
History Framework
SJS/TEN Summary
  • 1
    The clinical syndrome
  • 2
    The timeline
  • 3
    The exposure risk
  • 4
    The host: What is the immunodeficiency? How profound and for how long?
  • 5
    What type of organism are they at risk of? "Typical"? "Unusual" (Bacterial? Viral? Fungal? Mycobacterial? Parasitic?)? Sometimes >1 pathogen.
  • 6
    Prevention of infection
SJS and TEN are rare, potentially fatal adverse cutaneous drug reactions.
Characterized by: mucocutaneous tenderness + erythema + extensive exfoliation.

SJS = <10% BSA  |  SJS-TEN overlap = 10-30% BSA  |  TEN = >30% BSA

Most frequently incriminated drugs: NSAIDs, Antibiotics, Antiepileptics

Management: Immediate discontinuation of culprit drug + High-dose IVIG + Supportive care