Naegleria fowleri after 50 years: is it a neglected pathogen?

Abstract

It has been 50 years since the first case of primary amoebic meningoencephalitis (PAM), an acute and rapidly fatal disease of the central nervous system (CNS), was reported in Australia. It is now known that the aetiological agent of PAM is Naegleria fowleri, an amoeba that is commonly known as 'the brain-eating amoeba'. N. fowleri infects humans of different ages who are in contact with water contaminated with this micro-organism. N. fowleri is distributed worldwide and is found growing in bodies of freshwater in tropical and subtropical environments. The number of PAM cases has recently increased, and the rate of recovery from PAM has been estimated at only 5 %. Amphotericin B has been used to treat patients with PAM. However, it is important to note that there is no specific treatment for PAM. Moreover, this amoeba is considered a neglected microorganism. Researchers have exerted great effort to design effective drugs to treat PAM and to understand the pathogenesis of PAM over the past 50 years, such as its pathology, molecular and cellular biology, diagnosis and prevention, and its biological implications, including its pathogenic genotypes, its distribution and its ecology. Given the rapid progression of PAM and its high mortality rate, it is important that investigations continue and that researchers collaborate to gain better understanding of the pathogenesis of this disease and, consequently, to improve the diagnosis and treatment of this devastating infection of the CNS.

A case of Naegleria fowleri related primary amoebic meningoencephalitis in China diagnosed by next-generation sequencing

“…AmB, which is a common drug in clinic and is primarily used as an antifungal medication, has an amoebicidal effect and has been used to treat PAM since 1970. However, the recovery rate with AmB is only 5% (15 recoveries/300 cases worldwide), and this drug can be toxic to humans [ 3 ]. Miltefosine, a drug developed against breast cancer and Leishmania infections, possesses activity against free-living amoeba species in vitro [ 8 , 9 ], and is now recommended for the treatment of PAM by the Centers for Disease Control and Prevention in the USA [ 10 ], while is not currently available in China.…”

“…In addition, miltefosine should be administered in combination with AmB and other drugs, such as rifampin and fluconazole, as soon as possible after diagnosing PAM. In addition to drug treatment, physical procedures like CSF drainage, hyperosmolar therapy, moderate hyperventilation and hypothermia have been employed in the treatment of PAM [ 3 , 16 ].…”

“…N. fowleri usually infects people through the nose cavity when in contact with contaminated water. N. fowleri is commonly known as a “brain-eating amoeba” because of its induction of severe encephalitis in the brain upon infection, with a fatality rate of over 95% [ 3 ]. There are over 40 species of Naegleria , but only N. fowleri infections results in PAM [ 1 ].…”

“…PAM has a rapid, acute disease progression, with an incubation period varying from 2 to 15 days, and death typically occurring 3–7 days after the onset of symptoms [ 1 ]. N. fowleri has been reported worldwide including America, Australia, Thailand, Hong Kong and Taiwan [ 4 ], and about 300 cases in total have been reported in 50 years since the first case was reported in 1965 [ 3 ]. Prompt diagnosis is important in order to start treatment as soon as possible.…”

Inhibition of fatty acid oxidation as a new target to treat Primary Amoebic Meningoencephalitis by repurposing two well-known drugs

“…A wide range of antifungals and antibiotics have been used to treat PAM with varying degrees of effectivity. Most evidence is available for Amphotericin B (AMB) and Miltefosine (MIL), but because of the high mortality rate, more effective drugs are urgently needed (10).…”