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MI9.1-3 | Zoonotic & Opportunistic Infections — SDL Guide (Part 2)

Opportunistic Infections (OI) in Immunocompromised Hosts (MI9.2)

Infographic showing risk factors for opportunistic infections, CD4-based OI thresholds in HIV, and the transmission, reactivation, diagnosis, and treatment of toxoplasma encephalitis. — **Panel A:** Immunocompromised host; HIV/AIDS; prolonged corticosteroid therapy; neutropenia post-chemotherapy; organ/stem cell transplant; haematological malignancy; uncontrolled diabetes; weakened immune shield; reduced CD4 T cells; reduced neutrophils. **Panel B:** CD4 count threshold ladder; CD4 <500: Oral candidiasis, Herpes zoster, Bacterial pneumonias; CD4 <200: PCP Pneumocystis jirovecii, Toxoplasma encephalitis, Histoplasmosis; CD4 <100: Cryptococcal meningitis, CMV retinitis; CD4 <50: MAC, CMV colitis, EBV-driven CNS lymphoma. **Panel C:** Toxoplasma gondii; cat definitive host; oocysts in cat faeces; undercooked meat with bradyzoites; latent tissue cyst; HIV reactivation; ring-enhancing basal ganglia lesions; seizures; focal deficits; serum IgG; brain MRI; CSF PCR; TMP-SMX response trial; sulfadiazine; pyrimethamine; folinic acid; secondary prophylaxis until CD4 >200.

Predisposing conditions: HIV/AIDS, prolonged corticosteroid therapy, neutropenia (post-chemotherapy), organ/stem cell transplant, haematological malignancies, uncontrolled diabetes.

OIs classified by CD4 count threshold (HIV patients):

CD4 Count	OI
<500	Oral candidiasis, Herpes zoster, Bacterial pneumonias
<200	PCP (Pneumocystis jirovecii), Toxoplasma encephalitis, Histoplasmosis
<100	Cryptococcal meningitis (C. neoformans), CMV retinitis
<50	MAC (M. avium complex), CMV colitis, CNS lymphoma (EBV-driven)

Key OIs:

Toxoplasma encephalitis (Toxoplasma gondii):
- Obligate intracellular parasite; definitive host: cats; transmission via undercooked meat (bradyzoites) or oocysts (cat faeces)
- HIV patients: reactivation of latent tissue cysts → ring-enhancing lesions on MRI (basal ganglia) → seizures, focal deficits
- Diagnosis: Serum IgG (past infection = latent cyst); brain MRI + empirical TMP-SMX response trial; PCR of CSF
- Treatment: Sulfadiazine + pyrimethamine + folinic acid; lifelong secondary prophylaxis until CD4 >200

Cryptococcal Meningitis (Cryptococcus neoformans):
- Encapsulated yeast; pigeon droppings; India ink (cryptococcal capsule appears as halo around dark yeast)
- Subacute meningitis in HIV (CD4 <100); elevated opening pressure; CSF: mild pleocytosis
- Diagnosis: India ink of CSF; Cryptococcal Antigen (CrAg) lateral flow assay (serum/CSF — rapid, highly sensitive); culture on Sabouraud's/Niger seed agar (melanin production — black colonies)
- Treatment: Liposomal amphotericin B + flucytosine (induction) → fluconazole (consolidation and maintenance)

Educational diagram showing India ink microscopy of Cryptococcus neoformans in CSF with clear capsular halos, diagnostic CrAg testing, pathogenesis, and distinction from Candida. — **Panel A:** India ink CSF preparation; dark background; Cryptococcus neoformans; dark-staining yeast cell; clear capsular halo; narrow-based budding yeast; magnified inset of capsule and yeast body.. **Panel B:** Diagnostic workflow; HIV patient with headache and neck stiffness; CSF sample; India ink microscopy; Cryptococcal antigen lateral flow assay; most sensitive rapid test.. **Panel C:** Risk and spread; immunocompromised host; inhalation from environment; pulmonary entry; hematogenous dissemination; CNS involvement; cryptococcal meningitis.. **Panel D:** Differential morphology; Cryptococcus neoformans with clear capsule on India ink; Candida species on KOH mount with budding yeast and pseudohyphae..

Candida infections in immunocompromised:
- Oral thrush (CD4 <500) → oesophageal candidiasis (AIDS-defining, CD4 <200)
- Candidaemia in neutropenic patients and ICU (central line, broad-spectrum antibiotics)
- Diagnosis: KOH mount (pseudohyphae + budding yeast); blood culture in BACTEC; MALDI-TOF for species identification
- Treatment: Fluconazole (non-severe); echinocandins (caspofungin) for invasive/fluconazole-resistant

CMV retinitis: CD4 <50; painless progressive visual loss; 'pizza pie' retina on fundoscopy; PCR of vitreous; Ganciclovir IV + oral valganciclovir maintenance

SELF-CHECK

A 40-year-old HIV-positive patient presents with 3 weeks of severe headache, neck stiffness and photophobia. CSF analysis shows: lymphocytic pleocytosis, low glucose, elevated protein. India ink stain shows organisms with clear halos. The MOST sensitive rapid diagnostic test available is:

A. Serum VDRL

B. Cryptococcal Antigen (CrAg) lateral flow assay

C. Serum ASO titre

D. Widal test

Reveal Answer

Answer: B. Cryptococcal Antigen (CrAg) lateral flow assay

India ink showing organisms with capsular halos in CSF of an HIV patient confirms Cryptococcal meningitis. The CrAg lateral flow assay (serum or CSF) has >99% sensitivity and >95% specificity — it is the recommended rapid test by WHO and NACO for diagnosis and targeted screening (CrAg screening when CD4 <100).

Choosing the Right Investigation (MI9.3)

A four-panel infographic explains how epidemiological clues and syndrome patterns guide investigation tiers and interpretation in suspected zoonotic, opportunistic, and emerging infections. — **Panel A:** Investigation selection framework showing Epidemiological clue, Syndrome recognition, Investigation tier, animal contact, occupation, geography, immune status, and season.. **Panel B:** Syndrome recognition cards showing Leptospirosis, Plague, Rabies, and Cryptococcus with key clinical clue combinations.. **Panel C:** Investigation tier timeline showing Rapid bedside tests, Microscopy, Molecular PCR, Serology, and Culture with representative examples.. **Panel D:** Interpretation principles showing window period, paired sera with 4-fold titre rise, culture as definitive but slow and biohazardous, and PCR sensitivity in early disease..

Framework for investigation selection in suspected zoonosis/OI:

Step 1 — Epidemiological clue (animal contact, occupation, geography, immune status, season)
Step 2 — Syndrome recognition (fever + jaundice + AKI → leptospirosis; fever + lymph node + bubo → plague; altered sensorium + hydrophobia → rabies; subacute meningitis + HIV → cryptococcus)
Step 3 — Investigation tier:
- Rapid bedside test (minutes): RDTs — RK39 for Kala-azar, CrAg LFA for Cryptococcus, Leptocheck for Leptospirosis, HRIG eligibility score for rabies exposure
- Microscopy (hours): Dark-field for Leptospira, India ink for Cryptococcus, Seller's stain for Negri bodies (Rabies), Giemsa for intracellular pathogens
- Serology (hours–days): MAT for Leptospirosis, SAT/2-ME for Brucella, Widal for typhoid (not a zoonosis per se), IgM ELISA
- Culture (days–weeks): Blood/bubo/bone marrow culture (BSL considerations for Brucella/Plague)
- Molecular (hours): PCR/RT-PCR for rabies, Nipah, KFD, Leptospira

Interpretation principles:
- A negative RDT does not rule out infection in early disease (window period)
- Paired sera (acute + convalescent, 2–4 weeks apart) with 4-fold rise in titre = gold standard serology
- Culture positivity = definitive diagnosis but slow and biohazardous for BSL-3 organisms
- PCR is most sensitive in the early/acute phase before antibody development

⚠ DRAFT — coordinates pending review

Interactive practice: Label the Diagram

Interactive practice: True / False

Interactive practice: Put in Order

Interactive practice: Multiple Choice