Granulomatous amoebic encephalitis | |
---|---|
T2-weighted MRI showing a necrotic brain abscess as a result of GAE caused by an infection of Acanthamoeba . | |
Specialty | Infectious diseases |
Symptoms | Fever, headaches, personality changes [1] |
Complications | seizures, coma, risk of death |
Causes | Acanthamoeba spp., Balamuthia mandrillaris , and Sappinia pedata |
Treatment | Nitroxoline, miltefosine |
Granulomatous amoebic encephalitis (GAE) [2] is a rare, often fatal, subacute-to-chronic central nervous system disease caused by certain species of free-living amoebae [3] of the genera Acanthamoeba , Balamuthia and Sappinia . [4] [5] The term is most commonly used with Acanthamoeba. In more modern references, the term "balamuthia amoebic encephalitis" (BAE) is commonly used when Balamuthia mandrillaris is the cause. [6] [7] [8] [9] Similarly, Sappinia amoebic encephalitis (SAE) is the name for amoebic encephalitis caused by species of Sappinia . [10]
GAE starts slowly, with symptoms like headache, nausea, dizziness, irritability and a low-grade fever. The CNS symptoms depend on the part of the brain that is infected. Changes in behavior are an important sign. Other CNS signs may include seizures, focal neurologic signs, diplopia (double vision), cranial nerve palsies, ataxia, confusion, and personality changes. [1]
Some of the symptoms may mimic glioma (especially brainstem glioma), or other brain diseases, which may hamper timely diagnosis. The symptoms are caused by inflammatory necrosis of brain tissue brought on by compounds released from the organisms. [11]
The condition can be difficult for doctors to diagnose, because it is a rare disease. [12] A brain biopsy will reveal the presence of infection by pathogenic amoebas. In GAE, these present as general inflammation and sparse granules. On microscopic examination, infiltrates of amoebic cysts and/or trophozoites will be visible. [13]
The causative organism for SAE was originally identified as Sappinia diploidea , [14] [15] but is now considered to be Sappinia pedata . [16]
Antifungal drugs including ketoconazole, miconazole, 5-flucytosine and pentamidine have been shown to be effective against Acanthamoebain vitro. [17]
Like with Acanthamoeba, infection of the brain with this organism rapidly turns fatal in most cases. [18] However some survivors have been reported:
Two patients survived after being successfully treated with a therapy consisting of flucytosine, pentamidine, fluconazole, sulfadiazine, and azithromycin. Thioridazine or trifluoperazine was also given. Successful treatment in these cases was credited to "awareness of Balamuthia as the causative agent of encephalitis and early initiation of antimicrobial therapy." [19]
In one case, cloxacillin, ceftriaxone, and amphotericin B were tried, but this treatment protocol did not prove effective. [20]
In 2018 a metagenomic sequencing analysis identified Nitroxoline as amoebicidal agent against the Balamuthia mandrillaris. [21]
In 2021 a patient recovered after treatment with nitroxoline. [22] [23] The man had been given a recommended drug therapy (pentamidine, sulfadiazine, azithromycin/clarithromycin, fluconazole, flucytosine, and miltefosine) but progressed negatively. Therefore with the permission of the FDA the regime was complemented with the unapproved drug. Nitroxoline had previously been identified via a clinical metagenomic next-generation sequencing analysis to be a compound that could be repurposed as an amoebicidal agent against Balamuthia mandrillaris. [21] The brain abscess shrank only one week later and the man later recovered.
It has been treated with azithromycin, pentamidine, itraconazole, and flucytosine. [15]
Even with treatment, CNS infection with Acanthamoeba is often fatal, and there are very few recorded survivors, almost all of whom had permanent neurocognitive deficits. [17] The prognosis is largely influenced by the time of diagnosis, how virulent and sensitive the Acanthamoeba strain is, and, most crucially, the immune status of the affected person. Due to it commonly being an opportunistic infection, the prognosis is generally poor, with a mortality rate approaching 90%. [1]
Sappinia pedata can cause GAE, however only one case of GAE due to S. pedata infection has ever been reported, and the patient survived without any long-term consequences. [24]
Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, trouble speaking, memory problems, and problems with hearing.
Acanthamoeba is a genus of amoebae that are commonly recovered from soil, fresh water, and other habitats. The genus Acanthamoeba has two stages in its life cycle, the metabolically active trophozoite stage and a dormant, stress-resistant cyst stage. In nature, Acanthamoeba species are generally free-living bacterivores. However, they are also opportunistic pathogens able to cause serious and sometimes fatal infections in humans and other animals.
Free-living amoebae are a group of protozoa that are important causes of infectious disease in humans and animals.
Naegleriasis, also known as primary amoebic meningoencephalitis (PAM), is an almost invariably fatal infection of the brain by the free-living unicellular eukaryote Naegleria fowleri. Symptoms are meningitis-like and include headache, fever, nausea, vomiting, a stiff neck, confusion, hallucinations and seizures. Symptoms progress rapidly over around five days, and death usually results within one to two weeks of symptoms.
Naegleria is a genus consisting of 47 described species of protozoa often found in warm aquatic environments as well as soil habitats worldwide. It has three life cycle forms: the amoeboid stage, the cyst stage, and the flagellated stage, and has been routinely studied for its ease in change from amoeboid to flagellated stages. The Naegleria genera became famous when Naegleria fowleri, the causative agent of the usually fatal human and animal disease primary amoebic meningoencephalitis (PAM), was discovered in 1965. Most species in the genus, however, are incapable of causing disease.
Meningoencephalitis, also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain tissue.
Balamuthia mandrillaris is a free-living amoeba that causes the rare but deadly neurological condition granulomatous amoebic encephalitis (GAE). B. mandrillaris is a soil-dwelling amoeba and was first discovered in 1986 in the brain of a mandrill that died in the San Diego Wild Animal Park.
Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as Naegleria fowleri and Balamuthia mandrillaris. This includes the three forms of leishmaniasis: cutaneous, visceral and mucosal. It may be used with liposomal amphotericin B or paromomycin. It is taken by mouth.
Nitroxoline is an antibiotic that has been in use in Europe for about fifty years, and has proven to be very effective at combating biofilm infections. Nitroxoline was shown to cause a decrease in the biofilm density of P. aeruginosa infections, which would allow access to the infection by the immune system in vivo. It was shown that nitroxoline functions by chelating Fe2+ and Zn2+ ions from the biofilm matrix; when Fe2+ and Zn2+ were reintroduced into the system, biofilm formation activity was restored. The biofilm degradation ability is comparable to EDTA derivatives, but this drug has a history of human use in clinical settings and therefore has a precedent with which to allow its use against “slimy” biofilm infections.
The term "brain-eating amoeba" has been used to refer to several microorganisms:
Amoebiasis, or amoebic dysentery, is an infection of the intestines caused by a parasitic amoeba Entamoeba histolytica. Amoebiasis can be present with no, mild, or severe symptoms. Symptoms may include lethargy, loss of weight, colonic ulcerations, abdominal pain, diarrhea, or bloody diarrhea. Complications can include inflammation and ulceration of the colon with tissue death or perforation, which may result in peritonitis. Anemia may develop due to prolonged gastric bleeding.
Sappinia diploidea is a free-living amoeba species.
Amoebic brain abscess is an affliction caused by the anaerobic parasitic protist Entamoeba histolytica. It is extremely rare; the first case being reported in 1849. Brain abscesses resulting from Entamoeba histolytica are difficult to diagnose and very few case reports suggest complete recovery even after the administration of appropriate treatment regimen.
Sappinia is a genus of heterotrophic, lobose amoebae within the family Thecamoebidae. A defining feature of Sappinia, which separates it from its sister genus Thecamoeba, is the presence of two closely apposed nuclei with a central, flattened connection. Sappinia species have two life cycle stages: a trophozoite and a cyst. Up until 2015, only two species had been discovered, Sappinia pedata and Sappinia diploidea. Sequencing of the small subunit rRNA of a particular isolate from a sycamore tree revealed a new species, Sappinia platani.Sappinia species were once thought to be coprozoic, as the first strains were isolated from animal dung. More research has shown that they are typical free-living amoebae, and can be found worldwide in soil, plant litter, and standing decaying plants, as well as freshwater ponds. In 2001, the first and only case of human pathogenesis in Sappinia was confirmed. The patient was a non-immunocompromised 38-year-old male who presented signs of amoebic encephalitis and who patient made a full recovery after treatment with several antimicrobials. The CDC initially classified the causative agent as S. diploidea based on morphological characteristics, but in 2009, Qvarnstrom et al. used molecular data to confirm that the true causative agent was S. pedata.
Cutaneous amoebiasis, refers to a form of amoebiasis that presents primarily in the skin. It can be caused by Acanthamoeba or Entamoeba histolytica. When associated with Acanthamoeba, it is also known as "cutaneous acanthamoebiasis". Balamuthia mandrillaris can also cause cutaneous amoebiasis, but can prove fatal if the amoeba enters the bloodstream It is characterized by ulcers. Diagnosis of amebiasis cutis calls for high degree of clinical suspicion. This needs to be backed with demonstration of trophozoites from lesions. Unless an early diagnosis can be made such patients can develop significant morbidity.
Balamuthia infection is a cutaneous condition resulting from Balamuthia that may result in various skin lesions.
Sappinia pedata is a free living amoeboid organism, first described by Pierre Augustin Dangeard in 1896. It belongs to the genus Sappinia within the Thecamoebida clade of Amoebozoa and is characterized by its unique monopodial locomotion and cell surface morphology. S. pedata has been found in various habitats worldwide, mostly on herbivore dung, decaying plant matter, and soil. The species has gained attention due to its potential medical relevance and has been the subject of most recent and emerging studies in Protistology and Eukaryotic Microbiology as a whole.
Naegleria fowleri, also known as the brain-eating amoeba, is a species of the genus Naegleria. It belongs to the phylum Percolozoa and is classified as an amoeboflagellate excavate, an organism capable of behaving as both an amoeba and a flagellate. This free-living microorganism primarily feeds on bacteria but can become pathogenic in humans, causing an extremely rare, sudden, severe, and almost always fatal brain infection known as naegleriasis or primary amoebic meningoencephalitis (PAM).
Amoebic encephalitis or amoebic meningoencephalitis may refer to several potentially fatal diseases that are infections of the central nervous system by free-living amoebae, often referred to in the media as a "brain-eating amoeba" infection: