Clinical Reference · Phase 3

Infections Notes

ICC3-026 · 2024–2025 Immunocompromised Host Strictly Lecture-Sourced

Diseases Covered

Deficiency Types

400+

Primary Immunodeficiencies

ANC<500

Neutropenia Threshold

🧬

Core Definitions

Opportunistic = normal organism + broken host. Severity ∝ depth & duration of deficiency.

Opportunistic InfxMore frequent OR more severe due to immunosuppression

Neutropenia<100 cells/µL for >7 days = profound protracted (ASCO/IDSA threshold)

Primary ImmunodefOver 400 inborn errors; >200 known single gene mutations

ANC formulaWBC × (% neutrophils + % bands)

ANC <500 → Neutropenia risk | ANC <100 → Severe neutropenia

🦠

Opportunistic Organism Types

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 TB in renal transplant recipient
Measles in a leukaemic child
Disseminated HSV in a BMT recipient
CNS toxoplasmosis in an AIDS patient

🔄

Sources & Transmission

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 in the immunocompromised.

Mouth & throat Skin Gut Lungs Kidneys / Bladder Central line site

Catheter use significantly increases urinary tract risk.

🩸 Kaposi Sarcoma

🩸

Clinical Presentation

SBA: 35F, HIV+ CD4 ~20, fever + skin lesions → AIDS-defining diagnosis.

CD4 ~20AIDS-defining

Angioproliferative disorder — affects Skin, Lung, GI tract
"Classic" pre-HIV form: elderly men, indolent

🔬

Investigations

Tissue diagnosis is mandatory.

BiopsyConfirms diagnosis — required

💊

Management

1
Primary: ART — immune reconstitution first
2
Intralesional Vinblastine OR IV Doxorubicin

🫁 PCP — Pneumocystis jirovecii Pneumonia

🫁

Clinical Presentation

SBA: HIV male CD4 150 → SOB + dry cough + bilateral ground glass on CXR.

CD4 <200BMTHaem malignancySteroids / Wegener's

Fever, dry cough, progressive respiratory failure
Transmission: airborne, person-to-person
Organism class: Fungi

🩻

Investigations

Imaging suggests; stains and molecular confirm.

CXR"Ground glass" — bilateral pneumonitis

SamplingInduced sputum (HIV) or BAL

DiagnosticsFluorescent antibody, silver stains, PCR, β-D-Glucan

H&E stainFoamy histiocytes, necrotizing granuloma

Acid-fast stainNumerous organisms within histiocytes

💊

Management

1
Acute: Cotrimoxazole (oral TMP-SMX)
2
Start ART if HIV positive

Prophylaxis: Cotrimoxazole — HIV CD4<200 | Renal Tx ×3 months | BMT

👁️ Cytomegalovirus (CMV)

👁️

Clinical Presentation

SBA: 40M HIV+ CD4 10, fever + blurring of vision → CMV Retinitis. Fundoscopy = "pizza pie".

CD4 ~10 for retinitisDNA Herpes VirusBody fluid transmission

Presentation

End-Organ Disease

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
Rare: PUO, pericarditis, myocarditis, Guillain-Barré, cytopenias

🔬

Investigations

Negative PCR does NOT exclude CMV infection.

Quantitative PCRCMV DNA detection — –ve PCR does not exclude CMV

SerologyIgG / IgM testing

Fundoscopy"Pizza pie appearance" in retinitis

HistopathologyCytomegalic cells with "owl's eye" intranuclear inclusions

PharyngealNo exudate; no heterophile antibodies (unlike EBV)

💊

Management

1
Oral Valganciclovir OR IV Ganciclovir (test for resistance)
2
Alternatives: Foscarnet OR Cidofovir
3
Retinitis: add intravitreal Ganciclovir

Prophylaxis: Antiviral for all seropositive patients at risk.

Preemptive (BMT): Weekly CMV PCR + weekly galactomannan → treat if positive

💧 Cryptosporidium parvum Colitis

💧

Clinical Presentation

SBA: HIV patient, repeated watery diarrhoea. CD4 determines severity and prognosis.

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, pain, tenesmus, weight loss

🔬

Investigations

Clinical HxDuration, frequency, severity, consistency, fever, abdominal pain, tenesmus, weight loss — primary diagnostic tool

💊

Management

1
Reconstitute the immune system — therapy success determines prognosis

🦠 MAC — Mycobacterium Avium Complex

🦠

Clinical Presentation

HIV patient, severe immunodeficiency. Reservoir: soil, water, birds, animals.

Severe immunodeficiencyEnvironmental reservoir

Systemic: Fever and lethargy
GI: Small bowel infection → diarrhoea, malabsorption

🔬

Investigations

CulturesEndoscopic biopsy / blood / bone marrow cultures

H&E stainCollections of foamy histiocytes

Acid-fast stainNumerous organisms within histiocytes

💊

Management

1
Reconstitute the immune system

🧠 HIV-Associated CNS Lymphoma

🧠

Clinical Presentation

Similar to toxoplasmosis BUT headache is NOT a constant feature — due to absent inflammation.

Presentation mimics toxoplasmosis
Headache NOT constant — distinguishes from toxo (which has consistent headache)

🔬

Investigations

ClinicalAbsent constant headache differentiates from toxoplasmosis

💊

Management

1
Radiotherapy — benefits >75% of patients
2
Chemotherapy

🧠 PML — Progressive Multifocal Leukoencephalopathy

🧠

Clinical Presentation

JC virus destroys oligodendrocytes → patchy demyelination scattered through the CNS.

HIVCLLNatalizumab

Oligodendrocytes loaded with JC virus → destruction + myelin breakdown
Patchy demyelination scattered through the CNS

🩻

Investigations

Imaging / PathDemonstrates patchy demyelination throughout CNS

💊

Management

1
Immune system reconstitution

🦠 Listeria monocytogenes

🦠

Clinical Presentation

SBA: 30yo renal Tx, 3 months post-op, 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

Gram stainAerobic Gram-positive rod

Blood culturePositive for Listeria

CSF analysisMay produce lymphocytic CSF

💊

Management

1
Amoxycillin OR Penicillin

🦠 S. pneumoniae Bacteraemia (Asplenia)

🦠

Clinical Presentation

SBA: 23M post-splenectomy (RTA), 6 months later fever + no obvious focus → immediate Ceftriaxone.

Gram+ve diplococcus, capsulatedAsplenia

Causes of asplenia: Splenectomy, Trauma, Sickle cell disease
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 antibiotics while waiting for cultures.

Gram stainGram-positive diplococcus; capsulated

Culture / PCRBlood and CSF

💊

Management

1
Empiric immediate Ceftriaxone
2
Sensitive: IV Benzylpenicillin | Resistant: Vancomycin + Rifampicin

Asplenia prevention:
Vaccines: PCV13 → PPSV23 + Meningo + HIB + Influenza
Prophylaxis: PO Penicillin — <2yrs old and previous sepsis

🧠 Bacterial Meningitis

🧠

Clinical Presentation

SBA: 20yo student, flu-like + headache → found cold and unresponsive next morning.

Young: N. meningitidisOlder: S. pneumo / ListeriaInfants: E. coli / GrpB strep

Neurological: Focal or generalized seizures
Cranial nerves: Deafness, imbalance
Non-neuro: Endocarditis, thrombocytopenia, acute adrenal failure

🔬

Investigations

Gram stain narrows organism; culture / PCR guides therapy.

Gram stainGram+ve diplococci (S. pneumo) | Gram−ve diplococci (N. mening) | Gram+ve bacilli (Listeria) | Gram−ve bacilli (Enterobact.)

Blood / CSFCulture or PCR — guides specific therapy

💊

Management

1
Ceftriaxone 2g bd IV OR Cefotaxime 2g 6-hourly IV
2
Add Amoxicillin if age >60 OR immunocompromised — covers Listeria
3
Treat complications: dehydration, anticonvulsants, osmotic diuretics / corticosteroids

Prophylaxis (N. meningitidis contacts): Single dose Ciprofloxacin OR Rifampicin 600mg bd × 2 days

Vaccines: N. meningitidis C, ACYW135 | S. pneumoniae | H. influenzae type B

🦠 Toxin-Mediated Bacterial Infections

🦠

Corynebacterium diphtheriae

Gram+ve rodHighly contagious URT illness

Complications: Myocarditis and Neuropathy

Gram stainGram-positive rods

1
Antitoxin + Erythromycin
2
Contact tracing and prophylaxis

Vaccines: Childhood immunization

⚠️

Bacillus anthracis

Gram+ve rodZoonosis

Cutaneous anthrax
Pulmonary anthrax (inhalation)

Gram stainGram-positive rods

Management not explicitly specified in lecture slides.

⬇️

Clostridium botulinum

Descending FLACCID paralysis + autonomic dysfunction. Three routes.

Foodborne (home canning)Wound (IVDUs)Infant (honey)

Descending flaccid paralysis
Autonomic dysfunction

DiagnosisClinical presentation

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

⬆️

Clostridium tetani

Tetanospasmin → generalized SPASTIC paralysis — opposite of botulism (flaccid).

Wound contamination

Lockjaw (trismus), fractures from recurrent spasms
Sympathetic hyperactivity: tachycardia, hypertension, dysarrhythmias, sudden death

DiagnosisClinical — spasm + wound history

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. Incubation 7–18 days, insidious onset.

Rat reservoirArenavirus

Incubation: 7–18 days, insidious onset
Fever, myalgia, severe backache, malaise, headache
Maculopapular rash, sore throat, pharyngitis, lymphadenopathy (>50%)
Severe: Epistaxis, GI bleeding, irreversible hypovolaemic shock

🔬

Investigations

Serial serologyEvaluates antibody response

RT-PCR (throat swab)Genome detection

💊

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 AbVirus antigen from saliva, skin, urine, CSF

SerologyAntibodies in serum and CSF

PCR of CSFDetects viral genome

💊

Management

1
Clean wound with detergent and water immediately
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 brain destruction, inflammatory and reactive changes

HistopathologyPerivascular mononuclear cells and brain necrosis

MicroscopyViral intranuclear inclusions (eosinophilic packed viral particles)

💊

Management

1
Treatment required to prevent brain atrophy and gliosis

⚠️ Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis

⚠️

SJS vs TEN — Complete Comparison

Rare, potentially fatal adverse cutaneous drug reactions — differ only by extent of BSA involvement.

Most common culprit drugs: NSAIDs · Antibiotics · Antiepileptics

Feature	SJS	SJS–TEN Overlap	TEN
BSA detachment	<10%	10–30%	>30%
Rash type	Dusky-red macules, macular atypical targets, epidermal detachment	—	Similar, higher confluence
Location	Trunk, Face	—	Trunk, Face, Neck
Mucosal	Mucocutaneous tenderness, erythema	—	Severe respiratory + GIT mucosa
Systemic	Fever, LN, Hepatitis, Cytopenia	—	More severe throughout

Management (BOTH): 1. Immediate discontinuation of culprit drug 2. High-dose IVIG 3. Supportive care

📊 Immunodeficiency Classification

📊

Deficiency → Predicted Organism

Know the deficiency → predict the organism. This is the exam question framework.

Type	Affected Cells	Acquired Causes	Organisms at Risk
Humoral	B cells, plasma cells, antibodies	Myeloma, CLL, AIDS	S. pneumoniae, H. influenzae, Mycoplasma, Campylobacter, Giardia, Enterovirus
T cells	T lymphocytes	HIV, BMT, Lymphoma, Steroids	Intracellular pathogens — viruses, TB, protozoa
Neutropenia	Neutrophil granulocytes	Chemotherapy, BMT	Bacterial infections, Fungal infections
Complement	Complement system	—	S. pneumoniae, Neisseria spp.
Asplenia	Spleen	Splenectomy, Trauma, Sickle cell	S. pneumoniae, H. influenzae, N. meningitidis, Plasmodium

Inherited cause for ALL rows = Primary Immunodeficiency Syndromes (>400 described)

📊 HIV Risk by CD4 Count

📊

HIV CD4 Count → Infection Risk

CD4 Count (cells/µL)	Organisms / Conditions at Risk
>500	No increased risk
200–500	S. pneumoniae, Tuberculosis, Oral candida, Kaposi Sarcoma, VZV, HSV, Molluscum
100–200	PCP, JCV (PML), Histoplasmosis, Coccidioidomycosis
50–100	Toxoplasmosis, Cryptosporidiosis
<50	Cryptococcus · CMV · Mycobacterium Avium Complex (MAC)

CD4 <50 → Cryptococcus, CMV retinitis, MAC | CD4 <200 → PCP prophylaxis threshold

⏳ Solid-Organ Transplant Infection Timeline

⏳

Transplant Infection Timeline

Time Post-Transplant	Infections
<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) Late malignancy: Skin cancer, lymphoma (PTLD)

🦠 Classification Tables

🦠

S. aureus Clinical Spectrum

Pyogenic	Toxin-Mediated	Device-Related
Skin (folliculitis, carbuncles, abscesses), Pneumonia, Bloodstream → Osteomyelitis / Endocarditis / Meningitis	Food poisoning, Toxic shock syndrome, Scalded skin syndrome	IVC-associated, pacemaker infections

⚡

Varicella vs Zoster

Feature	Varicella	Zoster
Reactivation	No	Yes
Susceptible if	VZV IgG seronegative	VZV IgG seropositive
Infectious virus in	Respiratory secretions (48h pre-rash) + vesicle fluid	Vesicle fluid only
Infectiousness	Highly communicable	Low transmission rate

🧠

Common CNS Infections by Syndrome

Type	Clinical Syndrome	Common Causative Organisms
Bacterial	Acute pyogenic meningitis	E. coli / Grp B strep (infants) \| N. meningitidis (young adults) \| S. pneumoniae / Listeria (older adults)
Bacterial	Chronic meningitis	Mycobacterium tuberculosis
Localized	Abscess	Streptococci and staphylococci
Localized	Empyema	Polymicrobial (staphylococci, anaerobic Gram-negative)
Viral	Acute aseptic meningitis	Enteroviruses, Measles (SSPE), Influenza, LCMV
Viral	Encephalitic syndromes	HSV-1/2, CMV, HIV, JC polyomavirus (PML)

✅ Complete Prophylaxis Guide

✅

Prophylaxis by Drug Class

Learn indication first → drug second. Every named indication in the lecture is captured 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 → treat if positive

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 + Meningococcal + HIB + Influenza
2
Hyposplenic: HIB, Pneumococcal, Meningococcal, Influenza
3
Meningitis: N. meningitidis C, ACYW135 | S. pneumoniae | H. influenzae type B
4
Tetanus: Toxoid vaccine (active immunity)
5
Rabies: Human diploid cell vaccine (active)
6
Diphtheria: Childhood immunization schedule

1
VZV exposure (seronegative pregnant / neonates / immunocompromised): Passive immunization
2
HBV+ 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 (passive)

📋 Clinical Decision Framework

📋

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