Naegleria fowleri (brain-eating amoeba)
Naegleria fowleri, commonly referred to as the brain-eating amoeba, is a free-living amoeba that primarily causes a rare but severe brain infection known as primary amoebic meningoencephalitis (PAM). This organism thrives in warm freshwater environments, such as lakes and hot springs, as well as in soil. Infection typically occurs when water containing the amoeba enters the body through the nose, often during water-related activities like swimming. Once inside, N. fowleri can migrate to the central nervous system, leading to serious neurological damage and a high mortality rate; 95% to 99% of PAM cases result in death.
Symptoms of PAM can develop rapidly, usually within two to eight days, and may include severe headache, fever, nausea, and sensitivity to light, among others. Despite the rarity of infections—143 cases reported in the U.S. from 1962 to 2016—medical professionals face challenges in treating PAM, as effective treatments are limited and largely based on in vitro studies and case reports. The antifungal drug amphotericin B is commonly used, along with other medications, though survival rates remain low, with very few patients having survived the infection. Given its seriousness and the high fatality rate associated with N. fowleri infections, understanding and awareness of this organism are crucial for public health.
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Naegleria fowleri (brain-eating amoeba)
Naegleria fowleri, also known as the brain-eating amoeba, is the primary cause of the infectious disease called primary amoebic meningoencephalitis (PAM). N. fowleri is a free-living amoeba that belongs to phylum Percolozoa and is known to thrive in different kinds of environments such as soil and freshwater. N. fowleri infections rarely occur; however, 95 percent to 99 percent of PAM cases are severe and even fatal. PAM cases have been reported in Europe, Asia, Australia, and the United States. According to the US Centers for Disease Control and Prevention, there were 143 reported PAM cases in the United States between 1962 and 2016, of which only four are known to have survived. Based on the severity of outcome of PAM cases, there is an urgent need to identify factors that contribute to the high mortality rate that has been associated with N. fowleri infections, despite significant technological improvements in the medical field.
Background
Naegleria fowleri has attracted extensive media attention in the twenty-first century because of its associated high mortality rate. N. fowleri is a free-living amoeba that thrives in various environments (amphizoic), including water, soil, or within a specific host, which can include the human central nervous system. Infections due to N. fowleri have been reported in children as well as adults who have engaged in recreational water activities such as swimming or diving. This amoeba enters the human body through the nose, particularly while swimming. N. fowleri that attaches to the epithelial cells that line the nasal cavity, which is then followed by its migration to nerves situated in the nasal area, ultimately reaching the central nervous system (spinal cord and brain). The entry of this amoeba into the nerve cells lining the nasal cavity induces the immune system of the human body to activate macrophages and neutrophils to combat the infection.
N. fowleri may enter the human body during its trophozoite developmental stage. At this stage, N. fowleri possesses food cups on its surface that allows capture of food resources, which include bacteria, other fungi, and even human tissues. In additional, N. fowleri trophozoites produce cytolytic (cell destructive) molecules such as hydrolases, neuraminidases, as well as phospholipases that destroy the membrane structure of nerve cells. The combination of using food cups for gathering nutrients and the release of cytolytic molecules makes N. fowleri an effective nerve-destroying amoeba that induces severe nerve damage and eventually, destruction of the central nervous system, thereby resulting in death. PAM infections are therefore considered as a public health problem because they can easily be acquired from the environment and are associated with a high mortality rate.
The clinical symptoms of PAM often develop within two to eight days after infection. The most common signs of N. fowleri infection include sudden headache, high fever, neck rigidity that involves involuntary raising of knees and thighs when the neck is raised (Brudzinski sign), pain when straightening the knee as the leg is raised at a 90 degree angle to the hip (Kernig sign), nausea, vomiting, restlessness, irritability, rhinitis, extreme sensitivity to light (photophobia), seizures, and even coma, among others.
N. fowleri Today
Because of the extremely low number of N. fowleri infections that occur in humans, no clinical trials assessing the efficacy of a specific treatment regimen relative to other medications have been conducted as of 2016. The majority of the information regarding the medication efficacy of drugs used for the treatment of PAM is based on laboratory (in vitro) investigations or case reports. The currently accepted treatment for PAM is amphotericin B, which is an antifungal drug that is often used for systemic fungal infections. This drug has been extensively examined in vitro and has also be described in a number of case reports. There are also other antifungal drugs that have been administered to patients diagnosed with PAM, which include miconazole, fluconazole, miltefosine, azithromycin, as well as rifampin. In vitro studies have also assessed the efficacy of antifungal agents, hygromycin, zeocin, clarithromycin, and several others.
As of November 2015, seven patients have been reported to survive PAM around the world, with three survivors in the United States and one in Mexico (as of 2016, there were four survivors in the United States). The first report of a patient surviving an N. fowleri infection in North America was in 1978 in California. The survivor was a nine-year-old girl who went swimming for two days in Deep Creek Hot Springs, which is situated in the San Bernardino National Forest. Upon presentation of clinical symptoms, the patient was administered the amphotericin B, which is an antifungal drug that is generally used for the treatment of systemic fungal infections. In addition, other antifungal drugs, namely, miconazole, were also administered to the patient. Both amphotericin B and miconazole were given via an intravenous line as well as intrathecally.
In 2013 there were two survivors of PAM reported in the United States. One survivor was a twelve-year-old girl who contracted the infection after visiting a water park in the vicinity of Little Rock, Arkansas. In addition to treatment with antifungal drugs, her medical team used induced hypothermia to reduce brain swelling. The other survivor, an eight-year-old boy, developed brain damage as a result of the infection. He received antifungal drugs but induced therapeutic hypothermia was not used as a treatment.
In August 2016, Sebastian DeLeon became the fourth person to survive PAM in the United States. DeLeon, who was sixteen years old at the time, became symptomatic while on vacation with his family in Orlando, Florida. DeLeon was successfully treated at the city’s Florida Hospital for Children, where Dr. Humberto Liriano and a team of pediatric infectious disease specialists worked with the Centers for Disease Control to save DeLeon’s life. DeLeon was placed on a breathing tube and in a drug-induced coma, and given miltesfosine and other antimicrobials. The Florida Department of Health reported that DeLeon contracted the infection while swimming on private property in Broward County.
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