Answer: Primary Amoebic Meningoencephalitis (PAM) due to Naegleria fowleri. Naegleria fowleri trophozoites can be seen in both the CSF and the brain tissue. Note how the trophozoites originate from the leptomeninges and invade into surrounding brain tissue.
The trophozoites have a relatively small nucleus and large central karyosome, which allows them to be differentiated from human cells such as macrophages.
Similarly, the chromatin pattern with large karyosome differentiates the trophozoites of the free-living amoebae from those of Entamoeba histolytica (a rare cause of amebic CNS infection).
Although Naegleria fowleri has cyst, trophozoite, and flagellated forms in nature, it exists only in the trophozoite stage in humans, unlike the other free-living amebae (Balamuthia mandrillaris and Acanthamoeba spp.) which also have cyst forms in humans.
In this case, the characteristic trophozoites, lack of cyst forms, location in the meninges, and classic clinical history all support the diagnosis of PAM.