Medicinal professionals are employing novel methodologies and pharmaceuticals in an endeavor to eradicate severe brain ailments.
New medications might aid patients battling life-threatening infections caused by “brain-eating” amoebas. (Image credit: Marilyn Perkins for Live Science)Subscribe to our newsletter
Over a decade ago, on a warm Saturday in San Antonio, an 8-year-old boy was taken to the hospital following days of fever, headache, nausea, and aversion to light. His mother, residing near the Texas-Mexico border, had sought medical attention for him at various clinics in Mexico, but his health deteriorated. By then, the child had lost consciousness and was not responding to sound, light, or any other external stimuli.
The medical team placed the child on a ventilator and initiated a rapid investigation to determine the cause of his illness. Their discovery, found swimming in the boy’s cerebrospinal fluid, was an organism that offered little hope: Naegleria fowleri, more commonly referred to as a “brain-eating amoeba.”
However, Conrad had recently learned about an emerging treatment option, miltefosine, which had received approval as an experimental therapy for N. fowleri infections. He incorporated it into the boy’s treatment plan, which already included other antimicrobial and anti-inflammatory agents.
“We employed a ‘kitchen sink’ approach,” Conrad shared with Live Science. “It’s a formidable disease, so we utilized every conceivable intervention.”
The child’s outlook was bleak. He had been ill for five days prior to arriving in San Antonio, and the majority of individuals infected with N. fowleri perish approximately five days after symptom onset. According to the Centers for Disease Control and Prevention (CDC), there were 157 confirmed human cases of N. fowleri infection in the United States between 1962 and 2022. Only four individuals survived.
Globally, the statistics are comparable. Contracting an infection from this amoeba is uncommon, and surviving is exceedingly rare. Nevertheless, the few recent survivors may owe their recovery to miltefosine, the most recently endorsed new medication for primary amebic meningoencephalitis (PAM), the illness caused by the amoeba. Additional medications might also be on the horizon. The critical question remains whether these treatments can be administered before irreversible damage occurs.
‘A bull in a china shop’
N. fowleri flourishes in warm freshwater environments, typically around 80 degrees Fahrenheit (26.6 degrees Celsius) or higher, though it can persist in cooler temperatures as well, according to the CDC. It infects humans inadvertently when water is propelled into the nasal passages, driving the amoeba through a delicate bone structure called the cribriform plate to the olfactory nerve, which serves as a direct pathway to the brain.
A microscopic view of N. fowleri. (Image credit: BSIP SA via Alamy Stock Photo)
Individuals with weakened immune systems face a heightened risk, noted Dr. Juan Fernando Ortiz, a neurology resident at Corewell Health in Grand Rapids, Michigan, who authored a research paper on treating these infections. Boys under the age of 14 constitute a disproportionately large number of cases, according to the CDC, possibly because they are more prone than other demographics to activities that propel water into the nose, such as jumping and diving. While most instances are linked to natural bodies of water, there have been infrequent associations with treated water, such as in splash pads. In a few rare occurrences, infections have resulted from using tap water in neti pots for sinus rinsing.
The case of the child being treated by Conrad and his colleagues in August 2013 followed a tragically common pattern of infection. He had spent the summer with his mother at an unofficial campsite along the banks of the Rio Grande, which lacked running water. Residents bathed in the river, and the child enjoyed playing in the shallow areas.
It is highly probable that this is where he encountered the amoeba, which Conrad and his team were now tasked with eradicating—before it could inflict further devastation beyond the child’s capacity to survive.
The most prudent course of action for individuals concerned about their potential exposure is to presume that Naegleria fowleri amoebae are present in all freshwater environments.
Dr. Julia Haston, medical epidemiologist with the CDC’s Waterborne Disease Prevention Branch.
PAM causes fatality through extensive destruction of brain tissue. The amoeba itself contributes to some of this destruction directly, earning it the “brain-eating” designation. However, a significant portion of the brain damage stems from the body’s vigorous immune response to an invader within the central nervous system, as explained by Conrad. Organisms that evolve to inhabit a host body typically possess mechanisms to dampen their host’s immune reactions, thereby preserving their food source. Conversely, N. fowleri, having no inherent need for a host, lacks such adaptations. “It behaves like a bull in a china shop,” Conrad remarked.
Fortunately, the number of N. fowleri infections in the U.S. each year ranges between zero and six, and there is no indication that these infections are becoming more prevalent, stated Dr. Julia Haston, a medical epidemiologist with the CDC’s Waterborne Disease Prevention Branch. Although the majority of cases occur in Texas, Florida, and other southern states, there has been a higher-than-usual incidence in the northern U.S. in recent years, potentially due to climate change warming waterways to temperatures favorable for the amoebas, Haston suggested. A 2021 study also documented an increase in cases in the Midwest, extending as far north as Minnesota.
“The safest approach for individuals contemplating their risk… is to simply assume that Naegleria fowleri amoebae are present in all freshwater bodies,” Haston advised. “This includes lakes, rivers, and any naturally occurring freshwater source.”
N. fowleri infections are frequently contracted by young boys while engaging in activities in freshwater bodies. (Image credit: EvgeniiAnd via Getty Images)A Hail Mary works
To combat the amoeba attacking the San Antonio patient’s brain, Conrad and his team utilized a then-emerging therapy, miltefosine. This drug, an antimicrobial initially employed to treat leishmaniasis, an illness caused by a tropical parasite, had demonstrated encouraging results against N. fowleri in studies, leading the CDC to distribute it for PAM cases. Miltefosine has the ability to cross the blood-brain barrier and is generally well-tolerated by patients, according to Ortiz. This is significant, as numerous antiparasitic medications also harm human cells, he added.
The medical professionals procured the medication from the CDC. (Currently, it is commercially available under the brand name Impavido.) It was delivered 14 hours after the child’s admission.
The child survived.
However, he bore lasting effects. Upon discharge from the hospital, the boy could breathe independently but had limited other capabilities. Following months of rehabilitation, he regained some functions, but his family continued to assist him with fundamental daily self-care tasks, Conrad reported.
That same summer, however, a 13-year-old girl in Arkansas contracted the amoeba while swimming in a man-made pond. She received prompt treatment, including miltefosine, and recovered. After six months of rehabilitation, she experienced no lingering neurological deficits from this near-fatal encounter, according to a 2015 case report detailing her treatment.
She and the boy from Texas were the first survivors of PAM in the U.S. since 1978. In 2016, a 16-year-old boy in Florida contracted PAM and was treated with miltefosine; he also made a full recovery.
Nevertheless, not all PAM patients who have been administered miltefosine have survived. Even with the advent of the new drug, PAM retains a fatality rate exceeding 97%, according to the CDC.
Each summer, a small number of new PAM cases emerge across the nation, and medical professionals are continuously striving to enhance treatment protocols. They are increasingly investigating strategies such as lowering patients’ body temperature to approximately 95 F (35 C), a method that some studies suggest may improve outcomes in cases of brain trauma, according to Conrad.
A microscopic depiction of amoebic meningoencephalitis caused by N. fowleri. (Image credit: Smith Collection/Gado via Getty Images)
Potentially new pharmaceuticals may also emerge. Miltefosine can induce toxic side effects affecting the kidneys and liver and is not accessible in developing nations, stated Jacob Lorenzo-Morales, a senior lecturer in parasitology and the director of the University of La Laguna Institute of Tropical Diseases and Public Health of the Canary Islands.
Consequently, Lorenzo-Morales and his team are exploring alternative options. One of the most promising is nitroxoline, an antibiotic utilized in Europe for treating urinary tract infections. In August 2023, Lorenzo-Morales and his associates reported in the journal Antibiotics that in laboratory cultures, low concentrations of nitroxoline triggered cell death in N. fowleri without causing adverse effects on host cells. This medication has also been successfully employed to treat a patient infected with a different brain-eating amoeba, Balamuthia mandrillaris.
Currently, they are conducting animal trials and anticipate presenting favorable outcomes at the upcoming international Free-Living Amoebae Meeting, a biennial gathering for amoeba researchers. Nitroxoline is already widely available globally, Lorenzo-Morales noted, and because it has prior approval for human use, extensive clinical trials will not be necessary; physicians can begin administering the medication off-label.
New alternatives
Furthermore, efforts are underway to discover novel medications effective against PAM. Some researchers are investigating the development of mRNA vaccines against N. fowleri infection, with a 2024 study published in the journal Scientific Reports utilizing modeling of the amoeba’s surface characteristics to propose potential vaccine designs. (The authors of this study did not reply to inquiries from Live Science.)
If the disease progresses too far, the choice of medication becomes irrelevant; the patient will typically not recover.
Julia Walochnik, professor of tropical medicine at the Medical University of Vienna
Lorenzo-Morales and his collaborators are also examining the effects of a pigment known as elatol, derived from red algae. “We have identified certain key compounds from red algae that exhibit significant activity against various free-living amoebas, including Naegleria, at concentrations even lower than those used in current treatments,” he stated.
However, the researchers are presently conducting these tests in laboratory settings. Transitioning to human trials necessitates financial backing from pharmaceutical companies. This can be challenging, Lorenzo-Morales explained, as companies may perceive limited profit potential from a “rare” condition like PAM. Nevertheless, he suggested that PAM remains frequently undiagnosed, potentially indicating a larger market than pharmaceutical executives might assume.
A race against time
Perhaps the most immediate prospect for current patients lies in achieving earlier disease recognition. The window for saving individuals with PAM is narrow, commented Julia Walochnik, a professor of tropical medicine at the Medical University of Vienna who specializes in amoebic diseases. “If the diagnosis comes too late, the specific drug administered becomes inconsequential; the patient will generally not survive,” she informed Live Science.
The delayed initiation of treatment might account for the severe brain damage sustained by Conrad’s 8-year-old patient, whereas the other young individual treated around the same period experienced a more complete recovery.
The diagnostic test for the amoeba is straightforward: a sample of the fluid surrounding the brain and spinal cord is analyzed for motile single-celled organisms. However, physicians might not consider ordering this test promptly, as PAM symptoms can mimic those of more common viral and bacterial meningitis. Families of children who have perished from the disease are increasingly engaged in raising public awareness, which could hopefully lead to faster diagnosis and treatment. For instance, the Jordan Smelski Foundation for Amoeba Awareness, established by the parents of an 11-year-old boy who died of PAM in 2014, organizes educational initiatives for healthcare professionals and the general public.
Increased awareness is proving beneficial, according to Lorenzo-Morales. “In every clinical case we’ve been involved with over the past four to five years, the diagnosis has been swift,” he stated. “This was not the case previously.”
Editor’s Note: This article was originally published on July 26, 2024.
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