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There is very little information on the antibody response to N. fowleri infections, probably because most of the patients die too soon to produce detectable levels. However, in one patient who survived, a specific antibody titer of 4096 to N. fowleri was demonstrated by an immunofluorescence test in serum samples obtained at 7,10 and 42 days of hospitalization (Seidel et al., 1982). Serum antibodies to N. fowleri persisted after 4 years (Visvesvara and Stehr-Green, 1990). Antibodies to Naegleria species and N. fowleri have also been reported in apparently healthy persons (John, 1982; Marciano-Cabral, 1988; Martinez and Visvesvara, 1997). Free-living amebas, especially Acanthamoeba, have been isolated from human throats, suggesting that the amebas may exist transiently and cause no harm to healthy persons. Antibodies to Acanthamoeba have also been detected in patients suffering from upper respiratory tract illnesses in the UK; 20% of 128 patients hospitalized for respiratory problems had complement-fixing (CF) antibody to Acanthamoeba spp. (Martinez, 1980; Visvesvara and Stehr-Green,
1990), indicating that many unrecognized infections caused by Acanthamoeba may exist in nature. It is interesting to note that Kenney (John, 1993;
PRINCIPLES AND PRACTICE OF CLINICAL PARASITOLOGY
Martinez and Visvesvara, 1997; Visvesvara and Stehr-Green, 1990) also demonstrated CF antibody to A. culbertsoni in two of 1000 serum samples collected randomly. Notably, one of the serum samples was from a patient with an old brain infarct. The initial serum sample had a CF titer of 8 and rose to 16 and 64 in subsequent samples taken after 1 and 2 months, respectively. The patient subsequently died of cerebral hemorrhage and amebas were demonstrated in the brain sections, but unfortunately the species of the ameba was not identified. In another study, Cleland et al. (cited in Martinez and Visvesvara, 1997; Visvesvara and Stehr-Green, 1990) detected an increase in titer from 256 to 1024 against A. rhysodes in serum samples collected 16 months apart from a Nigerian patient from whose CSF A. rhysodes was repeatedly isolated. Immunofluorescent and precipitin antibody to Acanthamoeba has also been demonstrated in patients with Acanthamoeba keratitis. Antibodies to Acanthamoeba species have also been detected in apparently healthy persons (John, 1993; Martinez and Visvesvara, 1997; Visvesvara and Stehr-Green, 1990).
The significance of antibodies to Naegleria and Acanthamoeba in apparently healthy people is not clear. One reason for this is probably the ubiquity and the universal distribution of these amebas in nature, resulting in the exposure of most humans to the various amebic antigens, resulting in the development of antibodies.
Ferrante (1991) has suggested that human serum containing IgG and IgM antibodies is the first-line of defense against Acanthamoeba infection in humans. Immunoglobulins and complement promote recognition of the amebas by neutrophils, macrophages and probably lymphocytes. These cells destroy amebas in the normal immunocompetent host. However, in the immunosuppressed individual, due to the lack of T lymphocytes and impairment of cell-mediated immunity, free-living amebas continue to proliferate and produce structural damage to the CNS and other tissues (Martinez, 1982).
During the last few years there have been significant advances regarding molecular biology
techniques for the diagnosis of infectious diseases. Southern blots, isoenzyme profiles and chromatographic analysis have been used to type and differentiate strains of free-living amebas. Mitochondrial DNA fingerprinting by restriction fragment length polymorphism of Acanthamoeba spp. has been used to compare and classify clinical and environmental isolates. Genus- and subgenus-specific oligonucleotide probes for Acanthamoeba spp. have also been developed. Immunoperoxidase and immunofluorescence methods using monoclonal antibodies directed against specific strains of free-living amebas have the advantage of specificity for a single antigen and therefore can be used for precise identification and differentiation of isolates.
Naegleria fowleri is widely distributed throughout the world and has been isolated from freshwater, thermal discharges of power plants, heated swimming pools, hydrotherapy and remedial pools, aquaria, sewage, and even from the nasal passages and throats of healthy individuals. The typical cases of PAM occur in the hot summer months, when large numbers of people engage in aquatic activities in freshwater bodies, such as lakes, ponds and swimming pools that may harbor these amebas (John, 1982; Marciano-Cabral, 1988; Martinez and Visvesvara, 1997; Visvesvara and Stehr-Green, 1990).
Acanthamoeba spp. have been isolated from soil, bottled mineral water, the cooling towers of electric and nuclear power plants, physiotherapy pools, jacuzzis, heating, ventilating and air-conditioning units, dialysis machines, dust in the air, bacterial, fungal and mammalian cell cultures, contact lens materials, the nose and throat of patients with respiratory complaints, and healthy individuals. Acanthamoeba spp. have been known to harbor Legionella sp. and Mycobacteria (John, 1993; Martinez and Visvesvara, 1997; Visvesvara and Stehr-Green, 1990).