2004). In those cases, there was very early diagnosis and administration of intravenous and intrathecal or intraventricular amphotericin B. with intensive supportive care (2004). One survivor received miconazole intravenously and intrathecally and rifampicin orally (2004). Other treatment options include the drugs rifampicin and micoazole.
Khan (2008) notes that the mortality rate for PAM is 95%. Again, one of the major obstacles to effective treatment is the rapid progression of the disease. Another obstacle is the paucity of drugs that have the ability to cross the blood-brain barrier (Schuster & Visvesvara 2004; Khan 2008). Nevertheless, there have been documented recoveries from PAM (Seidel 1982; Wang 1993; Khan 2008). Early recognition and treatment of the disease appear to be the chief elements in successful outcomes (2008). At the time of Khan's (2008) writing, the drug of choice for treatment of human cases was amphotericin B. In conjunction with rifampin as well as other antifungal agents. The patients who have effectively recovered from PAM have been treated with amphotericin B. either alone or with the aforementioned combinations. Treatment with amphotericin B. And fluconazole intravenously followed by oral administration of rifampicin led to the successful treatment of a 10-year-old child who developed PAM (Vargas-Zepeda 2005; Khan 2008). Optimal therapy for PAM, however, has not yet been developed since not all patients treated with amphotericin B. survive. Poungvarin and Jariya (1991; Khan 2008) posited that a triple combination of low dose amphotericin B. administered intravenously for 14 days with oral rifampacin and oral ketoconazole for 1 month would result in a more favorable outcome than when a high dose of amphotericin B. was administered intrathecally.
Because of the limited amount of drugs available for treatment of human cases of PAM, a number of studies to assess the efficacy of therapeutic agents has been conducted in vitro and in vivo. For in vivo studies the mouse model of PAM has been used most extensively (Khan 2008). However, use of this animal model has translational limitations to the human (2008).
For example, due to a faster rate of metabolism in the mouse, one may not obtain a true indication of whether the drugs that are effective in the mouse will also be effective in the human. Thong et al. (1979( treated PAM in Balb/c mice with a combination of amphotericin B. And rifamycin. Rifamycin alone was found to be ineffective. However, a synergistic effect was observed when rifamycin was used in combination with amphotericin B. resulting in increased survival in mice (Khan 2008).
A number of animals have been used to study PAM including mice, guinea pigs, sheep, and rabbits. The mouse model has been used most extensively since it resembles the disease in humans and the immune system of the mouse is well characterized (Khan 2008). The nasal passages involving attachment to the olfactory epithelium can be used as the portal of entry by Naegleria fowleri to mimic natural exposure in humans (2008). Also, migration via the olfactory nerves across the cribriform plate to the brain is similar in mice and humans (Martinez 1973; Khan 2008). Lastly, mice infected intranasally develop a fatal disease resembling PAM in humans (2008). To produce PAM in the mouse, usually a trophozoite suspension (10:1 containing 104 to 105 amoebae) in water or medium, can be instilled into the nasal passages using Eppendorf pipette (2008). Mice display symptoms that include "ruffled fur, arched posture, loss of appetite, and a loss of equilibrium, within 4 to 5 days and up to 21 days post inoculation depending on the inoculum size and the virulence of the strain of amoebae" (2008). Naegleria fowleri strains that are low in virulence can cause "sub-acute or chronic encephalitis while highly virulent strains can cause death within 4 days post intranasal instillation" (Dempe et al. 1982; Whiteman & Marciano-Cabral 1989; Khan 2008).
Infection of Naegleria fowleri can be avoided if one pays attention to where past outbreaks where the infection has been acquired has occurred. Owners of swimming pools should maintain residual chlorine level of 1-2 parts per million and community pools should always be inspected. If there is any suspicion that a community pool isn't adequately maintained, then one should not swim in it. Blowing the nose forcefully after swimming is also a good idea. There are many local government agencies that are now organizing education campaigns as a form of prevention because of the lack of treatment for Naegleria fowleri. It should also be mentioned that people who are infected with Naegleria fowleri are not contagious.
The immune response to Naegleria fowleri has been studied in animals as well as in humans. Surveys for antibodies to Naegleria fowleri in human sera have been conducted on people from Australia, New Zealand, the United States, and the Czech Republic (Khan 2008). Antibodies have been identified using "indirect immunofluorescence assays, agglutination assays, Western immunoblot analysis, ELISA and radial immunodiffusion" (2008). Antibodies have been found to be present in apparently healthy individuals (Marciano-Cabral 1987; Reilly 1983; Khan 2008), individuals with acute respiratory disease (Power 1994; Khan 2008), hospitalized patients (Dubray 1987; Khan 2008), and patients with PAM (Cursons 1977; Seidel 1982; Khan 2008). Although titers for these anti-Naegleria fowleri antibodies have been different depending on the study, they illustrate that nearly all human sera tested are positive, indicating that exposure to Naegleria fowleri is common as well as widespread (2008).
While infection with Naegleria fowleri results in the elicitation of antibodies, at the time of Khan's (2008) publication, a correlation of susceptibility to PAM and the humoral immune status of the host had not been found. The lack of any kind of correlation may be due to the rapid progression of PAM that may not give adequate time for the host to mount all immune response of sufficient titer to exert a protective effect (2008).