Co-infection due to Mycobacterium tuberculosis, Cryptococcus and Naegleria fowleri has not been reported till now in literature, to the best of our knowledge. Here we report a curious case of co-infection of the central nervous system due to these three pathogens in an apparently immune-competent, HIV negative boy. The 15 year old boy was a diagnosed case of tubercular meningitis and was on anti-tubercular and anti-epileptic treatment. However, two months later he presented again in the emergency department with sudden loss of consciousness. His CSF showed presence of capsulated budding yeast cells (suggestive of Cryptococcus) and flagellated parasites (resembling the flagellated stage of Naegleria fowleri). CSF was also positive for Cryptococcal antigens by Latex Agglutination test. The boy was HIV negative and apparently immuno-competent. He was subsequently put on amphotericin B therapy for six weeks. Repeat microscopy, done towards the end of amphotericin B course, showed clearing of CSF. However, the patient's condition improved only slightly, owing to neurological damage caused by the pathogens as suggested by brain CT and MRI scans. Thus infection caused by the members of three different kingdoms in an apparently immunocompetent boy highlights the importance of thinking beyond the ordinary causative pathogens, and actively searching for rarer etiologies to ensure timely intervention; especially in nonresponsive cases.

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