NM, a 35-year-old female, presented to the Mulago Hospital with a 14-day history of gradual onset of headache and a 6-month history of nuchal pain, photophobia, recurrent high-grade fevers, malaise, and no past history of treatment for opportunistic infections. The 6-month history of poor health concerned NM's relatives and prompted them to do an HIV test without NM's consent or awareness 3 weeks prior to admission, the results of which were positive. On admission, she was delirious, her GCS was 15/15, her Karnofsky score was 60%, Kernig's sign was positive, and her neck was stiff. Papilledema could not be assessed because the patient was delirious and resistant. The physical exam revealed generalized hyperreflexia (3+) with normal power, tone, and sensation in all 4 limbs, and bilaterally down-going toes. The remainder of the physical exam was unrevealing. Based on the findings, the working diagnosis was acute bacterial meningitis (ABM). An LP was done within 24 hours of admission and the patient was started on empirical IV ceftriaxone (2g QD). On the second day of admission, the patient deteriorated clinically with the development of aphasia and a GCS of 9/15. She continued being managed for ABM until the third day of admission when LP results were obtained. The results showed a white blood cell count of 250 cells/ml3 (predominantly lymphocytes), protein of 120 mg/dL, India ink and Gram-stain were negative, and the ZN stain was significant for 1+ acid fast bacilli (AFB), 2+ WBC, with cultures to follow. The diagnosis changed to tuberculous meningitis (TBM) and she was started on a 2-month induction treatment for tuberculosis consisting of a 4-drug regimen (Isoniazid, Ethambutol, Rifampicin, Pyrazinamide [HERZ]) and IV dexamethasone (8mg q8h), and the ceftriaxone was stopped. On the fifth day of admission, the patient deteriorated further and developed respiratory distress. High flow 02 was added to the patient's treatment, but the patient rapidly deteriorated and died the same day. The likely cause of death was uncal-tonsilar herniation due to raised intracranial pressure.
The difficulty in interpreting CSF results is not unique to this case. CSF results can be very similar in partially treated bacterial meningitis and early TBM and making a clear diagnosis is often extremely challenging. Delays in diagnosis and treatment are major contributing factors to the high mortality and, as a result, approximately 30% of patients with TBM die despite anti-tuberculosis chemotherapy. Even though anti-TB treatment in Uganda is free, the free drugs at the Mulago Hospital are dispensed only two times per week, meaning that patients presenting on non-dispensing days must purchase their own medication. Since NM did not present on a dispensing day, she had to buy the initial 3 doses of treatment. In Uganda, most drugs are not supplied by the hospital and it is upon the patient to purchase their own drugs, making hospital stay affordable only to those with money.