A 28-year-old woman from Mumbai with known HIV infection (on ART for 2 years) presents with a 2-month history of progressive headache, neck stiffness, and low-grade fever. She reports good adherence to antiretroviral therapy. CD4 count is 320 cells/μL. Lumbar puncture shows: CSF protein 180 mg/dL, glucose 40 mg/dL (serum glucose 100 mg/dL), WBC 45 cells/μL (80% lymphocytes), India ink stain negative, Gram stain negative. What is the most likely diagnosis?

Explanation

## Differential Diagnosis of Meningitis in HIV **Key Point:** The CSF profile (very high protein, markedly low glucose with low CSF:serum glucose ratio, lymphocytic pleocytosis, negative India ink) in an HIV patient with CD4 320 is most consistent with **tuberculous meningitis (TBM)**, not cryptococcal meningitis. ### CSF Analysis: The Critical Clue | Parameter | TBM | Cryptococcal | Viral | Toxoplasma | |-----------|-----|-------------|-------|------------| | **Protein** | Very high (100–500) | Moderately high (50–200) | Mildly elevated (20–100) | Normal to mildly elevated | | **Glucose** | Very low (<45) | Moderately low (20–40) | Normal to mildly low | Normal | | **CSF:Serum glucose ratio** | <0.4 (often <0.3) | 0.3–0.5 | >0.4 | Normal | | **Cell count** | 100–500 (lymphocytic) | 20–150 (lymphocytic) | 50–500 (lymphocytic) | Normal to mildly elevated | | **India ink stain** | Negative | **Positive (50–80%)** | Negative | Negative | | **Gram stain** | Negative | Negative | Negative | Negative | **High-Yield:** **Markedly low CSF glucose + very high protein + negative India ink = TBM, not cryptococcal meningitis.** ### Why NOT Cryptococcal Meningitis? Although cryptococcal meningitis is common in HIV (CD4 <100), this patient's CSF glucose is **disproportionately low** (40 mg/dL with serum 100 = ratio 0.4). Cryptococcal meningitis typically has: - CSF glucose 20–40 mg/dL but CSF:serum ratio often 0.3–0.5 - **India ink stain positive in 50–80%** of cases (negative here) - Antigen testing (serum/CSF cryptococcal antigen) would be positive **Clinical Pearl:** A negative India ink does NOT exclude cryptococcal meningitis, but combined with the **very high protein (180)** and **markedly low glucose ratio**, TBM is more likely. ### Diagnostic Confirmation for TBM 1. **GeneXpert MTB/RIF** on CSF (WHO-recommended; sensitivity ~80%) 2. **AFB smear microscopy** (low sensitivity ~10%) 3. **TB culture** (gold standard but slow; 2–8 weeks) 4. **Clinical score** (Lancet criteria) — high score supports diagnosis 5. **Imaging:** MRI shows basilar enhancement, hydrocephalus, spinal involvement ### Management of TBM in HIV 1. **Anti-TB drugs:** HRZE (isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months, then HR for 7 months 2. **Adjunctive corticosteroids:** Dexamethasone 0.3 mg/kg/day × 8 weeks (reduces mortality and disability) 3. **ART timing:** Defer if CD4 <50; start at 2 weeks if CD4 50–200; start immediately if CD4 >200 4. **Drug interactions:** Rifampicin induces protease inhibitors and NNRTIs — adjust ART regimen **Warning:** Do NOT delay anti-TB therapy while awaiting culture confirmation; clinical diagnosis + GeneXpert positivity is sufficient to start treatment. [cite:Harrison 21e Ch 197]