A 12-year-old girl presented to hospital A with a complaint of headache for one month. The headache was of sudden onset, and it gradually increased in severity over the period of time. Headache was associated with multiple episodes of vomiting. Fever was off and on. There was no history of any skin rashes, seizure, or loss of consciousness. Neither there was history of contact with a tuberculosis patient nor had she past history of any significant illnesses.
She looked ill. General examination showed heart rate 64/min, respiratory rate 30/min, temperature 37.1 C (98.7 F), and blood pressure 90/60 mm Hg. On chest examination, bilateral vesicular sounds with no added sounds were noted. Cardiovascular examination revealed normal first and second heart sounds with a pansystolic murmur. Abdomen was soft and nontender. Hepatomegaly (2 cm) was detected. No splenomegaly was detected. Glasgow comma score was 14/15. Pupils were bilateral reactive 4 mm, and the fundus showed signs of early papilledema. Examination of musculoskeletal system revealed muscle bulk was slightly decreased, tone was flaccid, and power was 4/5 in all limbs. Sensory perception was intact, tendon reflexes were grade II, and the plantar was down-going. Kernig's and Brudzinski's signs were positive. The patient was admitted with a working diagnosis of meningitis.
Investigation showed hemoglobin 13.2 g/dL (11.5-14.0 g/dL), white blood cell (WBC) count 13,000/mm3 (5,000-12,000/mm3) (neutrophil 85% (40-70%), lymphocyte 10% (28-48%), monocyte 5% (2.0-10.0%), and eosinophil 0% (2.0-6.0%)), platelets 211,000/mm3 (150,000-400,000/mm3), and erythrocyte sedimentation rate 31 mm in first hour (<20 mm). Red cell indices, liver function tests, and clotting profiles were within a normal range. Random blood sugar was 105 mg/dL (70-200 mg/dL), blood urea nitrogen was 30 mg/dL (6-20 mg/dL), and serum creatinine was 0.46 mg/dL (0.6-1.1 mg/dL). Tests for human immunodeficiency virus I and II, hepatitis B surface antigen, and hepatitis C virus were negative. Ultrasound abdomen showed mild hepatomegaly, chest X-ray showed bilateral consolidation, and MRI brain showed enhancement and mild thickening of leptomeninges without basal exudates and without hydrocephalous, features suggestive of meningoencephalitis. Echocardiograph showed perimembranous ventricular septal defect (VSD) with a size of 12 mm and was partially closed by the septal leaflet of tricuspid valve and with mild tricuspid regurgitation with normal pulmonary artery pressure.
Lumbar puncture was done. The opening pressure was 27 cm of H2O (7 to 20 cm of H2O). Results of routine and biochemistry investigation of CSF were RBC 3 cells (0 cells), WBC 204 cells (<5 cells) (neutrophil 5% (30-40%) and lymphocyte 95% (60-70%)), sugar 46 mg/dL (50-80 mg/dL), protein 24 mg/dL (15-45 mg/dL), and adenosine deaminase 2.1 U/L (<3.0 U/L). Gram stain, staining for acid-fast bacilli (AFB), India ink preparation, and culture were negative. CrAg test was not available in the hospital. Blood culture and urine culture results were negative. With these investigation findings, the patient was diagnosed with meningoencephalitis with VSD, and antimicrobial treatment was started.
The patient was treated with injection (inj) ceftriaxone 1.5 g intravenous (iv) 12 hourly and inj vancomycin 100 mg iv 6 hourly for 7 days. During hospitalization, she had one episode of seizure, which was treated by antiepileptics. She could not maintain oxygen saturation (SpO2) with room air, and supplemental oxygen was provided. After 7 days of the antimicrobial treatments, her general condition did not improve. She was then brought to hospital B.
At the time of admission to hospital B, she was at semiconscious state. She was admitted to the pediatric intensive care unit. Further laboratory investigations: leptospira immunoglobulin M, brucella immunoglobulin M, malaria antigens, and Mantoux tuberculin skin tests were done, and all came out negative. Blood culture and urine culture were negative. Sputum AFB and culture were negative. GeneXpert was not available. It was important to rule out tubercular meningitis. There was no history of contact with active tubercular patients, CSF color was clear, CSF AFB staining was negative, and CSF ADA was not raised. Therefore, we did not consider tubercular meningitis as the first differential diagnosis. CSF India ink preparation showed Cryptococcus spp. (5 to 10 muM in size) with surrounding with a capsule (Figure 1). CSF culture, Sabouraud dextrose agar media, after 48 hours showed whitish mucoid colonies (Figure 2). CrAg test in CSF by enzyme immunoassay was positive. CM was diagnosed and treated with inj lysosomal amphotericin B 100 mg in 750 ml 5% dextrose iv over 2 hours once a day and inj flucytosine 625 mg in 50 ml iv 6 hourly.
The general condition of the patient did not improve despite the treatment for CM. She had one episode of seizure, which was treated with antiepileptics. She developed severe respiratory distress; she was intubated and kept on mechanical ventilation. On 9th day of admission, she died.