26.4 Fungal and parasitic diseases of the nervous system  (Page 2/15)

Amoebic meningitis

Primary amoebic meningoencephalitis (PAM) is caused by Naegleria fowleri . This amoeboflagellate is commonly found free-living in soils and water. It can exist in one of three forms—the infective amoebic trophozoite form, a motile flagellate form, and a resting cyst form. PAM is a rare disease that has been associated with young and otherwise healthy individuals. Individuals are typically infected by the amoeba while swimming in warm bodies of freshwater such as rivers, lakes, and hot springs. The pathogenic trophozoite infects the brain by initially entering through nasal passages to the sinuses; it then moves down olfactory nerve fibers to penetrate the submucosal nervous plexus, invades the cribriform plate, and reaches the subarachnoid space. The subarachnoid space is highly vascularized and is a route of dissemination of trophozoites to other areas of the CNS, including the brain ( [link] ). Inflammation and destruction of gray matter leads to severe headaches and fever. Within days, confusion and convulsions occur and quickly progress to seizures, coma, and death. The progression can be very rapid, and the disease is often not diagnosed until autopsy.

N. fowleri infections can be confirmed by direct observation of CSF; the amoebae can often be seen moving while viewing a fresh CSF wet mount through a microscope. Flagellated forms can occasionally also be found in CSF. The amoebae can be stained with several stains for identification, including Giemsa-Wright or a modified trichrome stain. Detection of antigens with indirect immunofluorescence, or genetic analysis with PCR, can be used to confirm an initial diagnosis. N. fowleri infections are nearly always fatal; only 3 of 138 patients with PAM in the United States have survived. US Centers for Disease Control and Prevention, “ Naegleria fowleri —Primary Amoebic Meningoencephalitis (PAM)—Amebic Encephalitis,” 2016. Accessed June 30, 2016. http://www.cdc.gov/parasites/naegleria/treatment.html. A new experimental drug called miltefosine shows some promise for treating these infections. This drug is a phosphotidylcholine derivative that is thought to inhibit membrane function in N. fowleri , triggering apoptosis and disturbance of lipid-dependent cell signaling pathways. Dorlo, Thomas PC, Manica Balasegaram, Jos H. Beijnen, and Peter J. de Vries, “Miltefosine: A Review of Its Pharmacology and Therapeutic Efficacy in the Treatment of Leishmaniasis,” Journal of Antimicrobial Chemotherapy 67, no. 11 (2012): 2576-97. When administered early in infection and coupled with therapeutic hypothermia (lowering the body’s core temperature to reduce the cerebral edema associated with infection), this drug has been successfully used to treat primary amoebic encephalitis.