A 50 years old Aryan female from Lalitpur district, Nepal, presented to Patan Hospital Emergency Department in December 2018 with complaints of abdominal pain that had persisted for two days. She had multiple episodes of vomiting. In terms of the patient's history, she had been treated with amlodipine and atenolol for hypertension and undergone a total abdominal hysterectomy 5 years prior for fibroids. She was a farmer living in suburban area of Lalitpur and involved in growing of vegetables and rearing of cows and poultry. On assessment, her blood pressure was 170/100 mmHg and her pulse rate was 88 beats per minute. Temperature was 98 degree Fahrenheit. Abdominal examination showed tenderness in the right upper quadrant.
Below are the laboratory parameters with normal range in parentheses:
Complete blood count : white cell count 8.4 (4-10) X 10^9/L ; neutrophils 60 % ; lymphocytes 37 % ; monocyte 1 % ; eosinophil 2 % ; red blood cells 4.8 (4.2-5.4) x 10^12/L; hemoglobin 12.5 ( 12-15) g/dL ; platelets 145 ( 150-400) X 10^9/L
Biochemistry: random blood sugar 124 (79-160) mg/dL; urea 28 (17-45) mg/dL; creatinine 0.7 (0.8-1.3) mg/dL; sodium 135 (135-145) mmol/L; potassium 3.8 (3.5 - 5) mmol/L; calcium 8.5 (8.4-10.2) mg/dL; albumin 3.4 (3.5-4) gm/dL; magnesium 1.8 (1.6-2.3 mg/dL); amylase 45 (30-125) U/L; lipase 56 (10-150) U/L.
Hepatic panel: bilirubin total 2 (0.1-1.2) mg/dL and direct 0.5 (0-0.4) mg/dL; alanine transaminase 53 (5-30) units/L; aspartate transaminase 47 (5-30) units/L; alkaline phosphatase 76 (50-100) IU/L
Ultrasound of the abdomen revealed a gallstone with a thickened gall bladder wall. She was admitted to the surgical ward with a provisional diagnosis of biliary colic, and managed conservatively with intravenous fluids, anti-emetics and analgesics. Her pain subsided. and her blood pressure also fell down to normal range with analgesia. But she developed a headache from 2 nd day and fever of 101 degrees Fahrenheit on the 4 th day. Injection ceftriaxone 1 gram twice daily was started empirically. The next day, she developed altered sensorium. Neurological examination revealed disorientation to time, place and person with neck stiffness but no papilledema or any focal neurological deficit. Plantar reflex was normal bilaterally.
Plain computed tomography (CT) of the head was normal. Cerebrospinal fluid (CSF) analysis revealed the following (with normal range in parentheses): Red blood cells= 6 (0-10)/mm^3; white blood cells = absent (0-5/mm^3); protein= 45 (20-45) mg/dL; sugar= 71 (45-80) mg/dL; lactate= 2 (1.1-2.8) mmol/L; adenosine deaminase (ADA) = 6.2 U/L; GeneXpert was negative for Mycobacterium Tuberculosis; CSF India ink staining was negative; Bacterial culture showed no growth over 48 hours. However, CSF cryptococcal antigen was positive by latex agglutination (Latex-Cryptococcus Antigen Detection System; IMMY). Serological test for HIV were negative.
With the diagnosis of cryptococcal meningitis, she was transferred to the intensive care unit (ICU) and liposomal amphotericin B (4 mg/kg/day) and Fluconazole (800 mg daily) were prescribed while ceftriaxone was continued. Unfortunately her family members could not afford the expensive liposomal amphotericin B. The government of Nepal provides liposomal amphotericin B (single dose of 10 mg/kg) free of cost to patients with visceral leishmaniasis (VL) . We wrote an application letter to the relevant authority to request liposomal amphotericin B for the patient. We asked for a total of 56 vials of the medicine (each vial contained 50 mg of liposomal amphotericin B) that would be sufficient for a two-week course. The relevant government authority refused to provide liposomal amphotericin B to our patient stating that the drug is to be dispensed to patients with VL only, as per the government policy. She was then started on fluconazole alone, but her status deteriorated. In addition, she also developed right sided hemiparesis 3 days following the diagnosis. Magnetic resonance imaging (MRI) of the brain was performed that revealed an acute infarct involving the left parietal lobe and basal ganglia, with multiple acute lacunar infarcts in the bilateral frontal and parietal lobes and bilateral cerebellum. She was in sinus rhythm. Echocardiography was normal. Aspirin 75 mg and atorvastatin 40 mg daily were administered as a result.
In a few days, her family members provided the liposomal amphotericin B. They revealed that they had connections with influential politicians who helped them acquire the medicine from the same government center who had previously refused them. She then received the two-week course of liposomal amphotericin B along with fluconazole. The patient improved gradually. She had hypokalemia during treatment with Amphotericin B which was managed with a potassium chloride infusion at 5 mEq/hour. She started showing improvement in her higher mental functions after the 5th day of amphotericin B administration.
After completion of 2 weeks of Amphotericin B, her higher mental function had returned to normal, and she could walk on her own with some residual weakness in her right upper limbs. She was then discharged from hospital and daily fluconazole 800 mg was continued for 8 more weeks.
On first follow up 1 week following discharge she was doing well. She was last seen in February 2019 after completing 8 weeks of fluconazole 800 mg daily. She was asymptomatic and was prescribed a daily tablet of fluconazole 400 mg for 1 year.