Tuberculous Meningitis
The most likely diagnosis is B. Tuberculous meningitis, based on the combination of subacute presentation (3 weeks of symptoms), IV drug use as a risk factor, and the characteristic CSF profile showing lymphocytic predominance, markedly elevated protein (3 g/L), and critically low CSF/plasma glucose ratio (<0.4). 1
Key Diagnostic Features Supporting TB Meningitis
The CSF/plasma glucose ratio of <0.4 is the most critical diagnostic finding here. The CDC states that in TB meningitis, the CSF/plasma glucose ratio is typically <0.5, which is very low compared to viral meningitis where the ratio remains >0.36 1. Your patient's ratio is even lower at <0.4, making TB meningitis highly likely 1.
CSF Profile Analysis
The CSF findings strongly favor TB meningitis over other etiologies:
- Lymphocytic predominance: Characteristic of TB meningitis, though neutrophils may predominate early in the disease course 1, 2
- Markedly elevated protein (3 g/L): TB meningitis typically shows protein >1 g/L, and values this high (3 g/L) are classic for TB 1, 3
- Hypoglycorrhachia with low CSF/plasma ratio: A CSF glucose <2.2 mmol/L has 68% sensitivity and 96% specificity for TB meningitis 1
Clinical Presentation
The 3-week history of fever and headache represents the subacute presentation typical of TB meningitis 2, 3. Research shows that clinical history >5 days is independently predictive of TB meningitis with 93% sensitivity when combined with other parameters 3.
Why Not the Other Options?
Bacterial Meningitis (Option C) - Ruled Out
Acute bacterial meningitis would show neutrophil predominance (80-95%), not lymphocytic predominance 1. Additionally, bacterial meningitis presents acutely (hours to days), not over 3 weeks 4, 3. The CSF protein of 3 g/L and subacute course effectively exclude typical bacterial meningitis 3.
Viral Meningitis (Option A) - Ruled Out
Viral meningitis typically presents with normal or only slightly low CSF glucose, and the CSF/plasma glucose ratio remains >0.36 1, 5. Your patient's ratio of <0.4 and the markedly elevated protein (3 g/L) are inconsistent with viral etiology 1.
Fungal Meningitis (Option D) - Less Likely
While fungal meningitis can produce a similar CSF profile with lymphocytic predominance and low glucose 6, it is less common than TB meningitis in IV drug users 6. The retrospective analysis shows that among HIV-infected patients, fungal meningitis accounts for 38% of hypoglycorrhachia cases, but TB remains a critical consideration 6. Without specific risk factors for fungal infection (such as confirmed HIV/AIDS or severe immunosuppression), TB meningitis is more likely given the classic presentation 2, 3.
Critical Clinical Context: IV Drug Use
IV drug users have increased risk for TB meningitis due to:
- Higher rates of HIV infection (which should be tested) 4
- Social determinants including homelessness and incarceration 2
- Malnutrition and immunosuppression 2
All patients with meningitis should have an HIV test, as HIV-positive patients have higher incidence and mortality from both TB and bacterial meningitis 4.
Diagnostic Algorithm Applied
Using the validated diagnostic rule from research, your patient meets multiple criteria for TB meningitis 3:
- ✓ Clinical history >5 days (3 weeks)
- ✓ Headache present
- ✓ CSF white cell count <1000/mm³ (implied by lymphocytic predominance)
- ✓ Lymphocyte proportion >30%
- ✓ Protein content >100 mg/dL (3 g/L = 3000 mg/dL)
Application of 3 or more of these parameters reveals 93% sensitivity and 77% specificity for TB meningitis 3.
Immediate Management Implications
Treatment for TB meningitis should be initiated immediately, as clinical suspicion is strongly supported by the CSF studies 2. Empiric treatment should include at least four first-line drugs: isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol 2. Adjunctive corticosteroids have been shown to improve mortality in TB meningitis 2.