NR, a 32-year-old female, was brought into the Mulago Hospital by her neighbours who found her "unconscious" in her house. They reported that she complained of feeling "unwell" for the past 3 days. On admission, she was found to be semicomatose with a fever of 38.4 C, stertorous respiration, healed scars suggestive of maculo-papular rash (unknown serostatus), GCS was 11/15, neck was stiff, Kerning's sign indeterminable, generalized brisk reflexes, normal muscle bulk, and no papilledema. Her cardiorespiratory exam was normal. Upon arrival to the casualty department, she was managed for cerebral malaria (600 mg IV quinine in a 500ml 5% dextrose solution). She was then transferred to the emergency room, where the working diagnosis was bacterial meningitis. IV quinine was stopped and IV ceftriaxone (2g QD) was started. An LP was done within 24 hrs of admission. Results were obtained on the second day of admission and showed 800 cells/cm3 (predominately lymphocytes), protein 80 mg/dL, negative India ink, Gram stain, and ZN stain, and no bacterial growth on overnight culture. Based on these findings, the working diagnosis changed to tuberculous meningitis. Oral anti-TB drugs were started (two months intensive phase of 800mg Ethambutol, 450 mg Rifampicin, 1.2 g Pyrazinamide, 300 mg Isoniazid QD) and ceftriaxone was stopped. Patient improved over the subsequent 7 days with a GCS of 15/15. However, despite improvement, the patient complained of continued mild headache and had a spiking fever and therefore remained under hospital care. On the 15th day after admission, she started deteriorating; she had a worsening headache, fluctuating mental status, papilledema, and no focal neurological signs. An LP was repeated despite increased intracranial pressure (in the setting of Cryptococcal meningitis, lumbar punctures are not contraindicated and therapeutic LPs are often done despite increased intracranial pressure - see discussion). The analysis revealed turbid CSF, 250 cells/cm3 (predominately lymphocytes), protein 120 mg/dL, Gram stain 2+ encapsulated yeast cells, 1+ gram negative rods, 2+ leukocytes, India ink 2+ for encapsulated yeast cells, negative ZN stain, culture isolated 2+ Cryptococcus neoformans. The diagnosis changed to mixed Cryptococcal meningitis (CM) and gram-negative bacterial meningitis. Treatment was modified to IV Amphoteracin B (50 mg QD) for 14 days, IV ceftriaxone (2g QD) for 10 days. After the 4th day of treatment, the patient dramatically improved and was discharged after the completion of Amphoteracin B treatment, 36 days after admission.
The case demonstrates many findings common in Uganda. Firstly, it illustrates an example of the most common pathology in patients presenting with fever, plasmodium falciparum infection (malaria). The case also shows the diagnostic challenges associated with the initial improvement response observed with anti-TB treatment which is then followed by deterioration as is demonstrated by the altered LP results. Similar improvement of symptoms after anti-tuberculosis treatment has been reported, with the reason for improvement is not understood. Additionally, the case is an example of clinical diagnosis of HIV using the criteria of a major opportunistic infection (CM). The patient received voluntary counseling and was referred to the infectious disease clinic after discharge. It is important to note that if the patient had been in the standard of care arm of the study, as opposed to the algorithmic arm, a repeated LP would not have been performed because the patient initially improved with anti-TB drugs. In the algorithm arm, patient deterioration calls for a repeated LP.