Treatment with the usual antiprotozoal agents is largely ineffective. Because of the in vitro sensitivity of Naegleria to amphotericin B, this drug has been used by the same schedule as for cryptococcal meningitis. Other suggested regimens have been various combinations of trimethoprim-sulfamethoxazole, rifampin, and antifungal agents Miltefosine, a new drug, is being studied independently and in combination with other drugs for treatment of naegleria and acanthamoeba.
A number of other protozoal diseases are of great importance in tropical regions. The main one of concern here is cerebral malaria, which complicates approximately 2 percent of cases of falciparum malaria. It has been estimated that there are approximately 200 million cases per year worldwide and about half million deaths from malaria. This is a rapidly fatal disease characterized by headache, seizures, and coma, with diffuse cerebral edema and only very rarely by focal features such as hemiplegia, aphasia, hemianopia, or cerebellar ataxia. Bruxism and hiccoughs have been commented on as common features in case reports. Cerebral capillaries and venules are packed with parasitized erythrocytes and the brain is dotted with small foci of necrosis surrounded by glia (Dürck nodes). A retinopathy consisting of macular whitening, orange or white discoloration of retinal vessels, and intraretinal blot-type hemorrhages, has been suggested as a dependable sign of severe malaria as summarized by Beare and colleagues.
These findings have been the basis of several hypotheses (one of which attributes the cerebral symptoms to mechanical obstruction of the vessels), but none is entirely satisfactory. Also, it seems unlikely that a disorder of immune mechanisms is directly involved in the pathogenesis (see the reviews by Newton et al and by Turner for a discussion of current hypotheses). In a study by Seydel and colleagues, the presence on MRI of cerebral swelling was associated with fatal outcome. They found a variety of signal changes in the cerebra, none consistent among patients, but including varying degrees of cerebral edema and diffusion restriction.
Usually, the neurologic symptoms appear in the second or third week of the infection, but they may be the initial manifestation. Children in hyperendemic regions are the ones most susceptible to cerebral malaria. Among adults in nonenedmic areas, only pregnant women and nonimmune individuals who discontinue prophylactic medication are liable to CNS involvement (Toro and Roman). Useful laboratory findings are anemia and parasitized red blood cells. The CSF may be under increased pressure and sometimes contains a few white blood cells, and the glucose content is normal. With Plasmodium vivax infections, there may be drowsiness, confusion, and seizures without invasion of the brain by the parasite.
Treatment Quinine and artesunate, and related drugs are curative if the cerebral symptoms are not pronounced, but once coma and convulsions supervene, 20 to 30 percent of patients do not survive. Mefloquine, artemether with lumefantrine, and atovaquone are increasingly being used. It had been stated that the administration of large doses of dexamethasone, given as soon as cerebral symptoms appear, may be lifesaving, but most studies demonstrate that corticosteroids are ineffective. Blood or exchange transfusions may confer a modest benefit on survival in severe cases.