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ACS Chemical Neuroscience Apr 2017Brain infections due to Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri often lead to death. Despite differences in the preferential sites of infection...
Brain infections due to Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri often lead to death. Despite differences in the preferential sites of infection in the brain, the mode of delivery of drugs is often intravenous. Here, we discuss targeted therapeutic approach to affect parasite viability without affecting the host cells, with an eye to improve formulation of drugs and/or administration of drugs against brain-eating amoebae.
Topics: Antiprotozoal Agents; Central Nervous System Protozoal Infections; Humans
PubMed: 28225265
DOI: 10.1021/acschemneuro.7b00049 -
Brain Pathology (Zurich, Switzerland) Jan 1997Amebas belonging to the genera Naegleria, Acanthamoeba and Balamuthia are free-living, amphizoic and opportunistic protozoa that are ubiquitous in nature. These amebas... (Review)
Review
Amebas belonging to the genera Naegleria, Acanthamoeba and Balamuthia are free-living, amphizoic and opportunistic protozoa that are ubiquitous in nature. These amebas are found in soil, water and air samples from all over the world. Human infection due to these amebas involving brain, skin, lung and eyes has increased significantly during the last 10 years. The epidemiology, immunology, protozoology, pathology, and clinical features of the infections produced by these protozoa differ strikingly. Infection by the pathogenic Naegleria fowleri is acquired by exposure to polluted water in ponds, swimming pools and man-made lakes. Raised temperatures during the hot summer months or warm water from power plants facilitate the growth of N. fowleri. N. fowleri is a thermophilic ameba that grows well in tropical and subtropical climates. The CNS infection, called Primary Amebic Meningoencephalitis (PAM), produced by N. fowleri is characterized by an acute fulminant meningoencephalitis leading to death 3-7 days after exposure. Victims are healthy, young individuals with a history of recent water-related sport activities. The portal of entry is the olfactory neuroepithelium. The pathologic changes are an acute hemorrhagic necrotizing meningoencephalitis with modest purulent exudate, mainly at the base of the brain, brain-stem and cerebellum. Trophozoites can be seen within the CNS lesions located mainly around blood vessels. Thus far 179 cases have been reported; 81 in the USA alone. Balamuthia mandrillaris and several species of Acanthamoeba are pathogenic "opportunistic" free-living amebas which cause Granulomatous Amebic Encephalitis (GAE) in humans and animals. GAE is an infection, usually seen in debilitated, malnourished individuals, in patients undergoing immunosuppressive therapy for organ transplants and in Acquired Immunodeficiency Syndrome (AIDS). The granulomatous component is negligible, particularly in immunocompromised individuals. Pathologically these amebas produce a patchy, chronic or subacute granulomatous encephalitis with the presence of trophozoites and cysts. The portal of entry is probably through the respiratory tract or an ulceration of the skin reaching the CNS by hematogenous spread. As of October 1, 1996, 166 cases (103 due to Acanthamoeba and 63 due to Balamuthia) of GAE have been reported from around the world. Of these 103 cases due to Acanthamoeba (72 have been reported in the USA alone, > 50 in AIDS). It is well known that several species of Acanthamoeba can also produce, chronic sight threatening ulceration of the cornea called Acanthamoeba keratitis (AK), mostly in contact lens wearers or in individuals with minor corneal abrasions. Hundreds of cases of AK have been documented world wide.
Topics: Acanthamoeba Keratitis; Amebiasis; Amoeba; Animals; Encephalitis; Humans; Meningoencephalitis; Opportunistic Infections
PubMed: 9034567
DOI: 10.1111/j.1750-3639.1997.tb01076.x -
Journal of Neurosurgery. Case Lessons Apr 2022An 80-year-old man presented with subacute mental status change, dizziness, and left-sided vision loss. Magnetic resonance imaging demonstrated a ring-enhancing right...
BACKGROUND
An 80-year-old man presented with subacute mental status change, dizziness, and left-sided vision loss. Magnetic resonance imaging demonstrated a ring-enhancing right parietooccipital lesion.
OBSERVATIONS
Biopsy and laboratory testing demonstrated an amoebic Balamuthia mandrillaris infection. Fewer than 200 cases of this infection have been recognized in the United States, and no standardized treatment regimen currently exists.
LESSONS
Rapid antimicrobial therapy with miltefosine, azithromycin, fluconazole, flucytosine, sulfadiazine, and albendazole was initiated. The pathophysiology, diagnosis, and management of this infection and the patient's course were reviewed. The importance of biopsy for pathologic and laboratory diagnosis and rapid treatment initiation with a multidisciplinary team was reinforced.
PubMed: 36303497
DOI: 10.3171/CASE2268 -
Clinical and Translational Science May 2021Free-living amoebae (FLAs) are protozoa developing autonomously in diverse natural or artificial environments. The FLAs Acanthamoeba spp., Balamuthia mandrillaris, and... (Review)
Review
Free-living amoebae (FLAs) are protozoa developing autonomously in diverse natural or artificial environments. The FLAs Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri represent a risk for human health as they can become pathogenic and cause severe cerebral infections, named granulomatous amoebic encephalitis (GAE), Balamuthia amoebic encephalitis (BAE), and primary amoebic meningoencephalitis (PAM), respectively. Additionally, Acanthamoeba sp. can also rarely disseminate to diverse organs, such as the skin, sinuses, or bones, and cause extracerebral disseminated acanthamebiasis (EDA). No consensus treatment has been established for cerebral FLA infections or EDA. The therapy of cerebral and disseminated FLA infections often empirically associates a large diversity of drugs, all exhibiting a high toxicity. Nevertheless, these pathologies lead to a high mortality, above 90% of the cases, even in the presence of a treatment. In the present work, a total of 474 clinical cases of FLA infections gathered from the literature allowed to determine the frequency of usage, as well as the efficacy of the main drugs and drug combinations used in the treatment of these pathologies. The efficacy of drug usage was determined based on the survival rate after drug administration. The most efficient drugs, drug combinations, and their mechanism of action were discussed in regard to the present recommendations for the treatment of GAE, EDA, BAE, and PAM. At the end, this review aims to provide a useful tool for physicians in their choice to optimize the treatment of FLA infections.
Topics: Amebiasis; Amebicides; Amoeba; Central Nervous System Protozoal Infections; Drug Therapy, Combination; Humans; Survival Rate; Treatment Outcome
PubMed: 33650319
DOI: 10.1111/cts.12955 -
Frontiers in Immunology 2021is one cause of a rare and severe brain infection called granulomatous amoebic encephalitis (GAE), which has a mortality rate of >90%. Diagnosis of GAE is difficult...
is one cause of a rare and severe brain infection called granulomatous amoebic encephalitis (GAE), which has a mortality rate of >90%. Diagnosis of GAE is difficult because symptoms are non-specific. Here, we report a case of amoebic encephalomyelitis (encephalitis and myelitis) in a woman with breast cancer. She sustained trauma near a garbage dump 2 years ago and subsequently developed a skin lesion with a infection. She experienced dizziness, lethargy, nausea and vomiting, inability to walk, and deterioration of consciousness. Next-generation sequencing of cerebrospinal fluid (CSF) samples revealed , and MRI of both brain and spinal cord showed abnormal signals. T-cell receptor (TCR) sequencing of the CSF identified the Top1 TCR. A combination of amphotericin B, flucytosine, fluconazole, sulfamethoxazole, trimethoprim, clarithromycin, pentamidine, and miltefosine was administrated, but she deteriorated gradually and died on day 27 post-admission.
Topics: Adult; Amebiasis; Balamuthia mandrillaris; Breast Neoplasms; Encephalomyelitis; Fatal Outcome; Female; High-Throughput Nucleotide Sequencing; Humans; Magnetic Resonance Imaging
PubMed: 35069540
DOI: 10.3389/fimmu.2021.768065 -
Iranian Journal of Parasitology 2021Free-living amoeba (FLA) belonging to spp, , and are the soil-born protozoa. This study aimed to survey the occurrence of FLA, including spp, , spp., and spp., in...
BACKGROUND
Free-living amoeba (FLA) belonging to spp, , and are the soil-born protozoa. This study aimed to survey the occurrence of FLA, including spp, , spp., and spp., in soil samples collected from various districts of Mazandaran Province (Northern Iran) from July to December 2018.
METHODS
Overall, 118 soil samples from the recreational and public places were surveyed for the existence of spp, , , and using both morphological key and molecular tools with genus-specific primers of JDP1, NA, ITS1, and Bal, respectively. To verify the taxonomic status of isolated amoeba, the phylogenetic tree was made based on sequences of 18S rRNA by MEGA (5.05) software with the maximum likelihood model.
RESULTS
Overall, 61/118 samples (51.6%) were contaminated with FLA, and based on the sequencing data, 29 isolates were successfully sequenced. Among the samples, all isolated (52.4%) belonged to the T4 genotype with amplification of the DF3 region (18S rRNA gene). Internal transcribed spacer (ITS) sequencing revealed the presence of one strain of . Twenty-eight were also confirmed based on Nuclear SSU rDNA. Morphological survey and PCR assay did not show any positive samples for .
CONCLUSION
The present study indicates the occurrence of FLA in soil sources of the recreational and public places in Mazandaran province that it can be a severe risk to human health. Thus, more studies are expected to survey the infection source in patients with FLA-related diseases.
PubMed: 34557245
DOI: 10.18502/ijpa.v16i2.6316 -
Parasitology Research Sep 2018Balamuthia mandrillaris is a free-living amoeba that lives in soil and water near human settlements. B. mandrillaris was first isolated from a mandrill baboon that died...
Balamuthia mandrillaris is a free-living amoeba that lives in soil and water near human settlements. B. mandrillaris was first isolated from a mandrill baboon that died at the San Diego Zoo Wildlife Park in California in 1986, and the first human infection was reported in 1990. Although reported B. mandrillaris infections are often not properly characterized, it appears that B. mandrillaris invades the living body from the soil and water, either via a wound or the nasal cavity. Most confirmed infections have originated in South and North America. B. mandrillaris inhabits warm climates and is recognized as a pathogen in warm areas such as desert climates and tropical climates. B. mandrillaris has been isolated from environmental samples since 2000, most of which originated from warm areas such as step climates, tropical climates, and desert climates. However, B. mandrillaris may survive in diverse environments, although fewer granulomatous amebic encephalitis patients have been reported in colder Japanese and Northern European regions. In the present study, we conducted a survey of 13 soil samples in Aomori Prefecture located at the northernmost tip of Japan Honshu and successfully isolated one strain of B. mandrillaris from soil for the first time in Japan. In addition, B. mandrillaris gene was detected from several soils. This confirms that B. mandrillaris is capable of spreading to a wider climatic region.
Topics: Adult; Aged; Aged, 80 and over; Amebiasis; Animals; Balamuthia mandrillaris; Encephalitis; Female; Humans; Japan; Male; Middle Aged; Sequence Analysis, DNA; Soil
PubMed: 29961176
DOI: 10.1007/s00436-018-5980-x -
Journal of Clinical Microbiology Oct 2021
Retraction for Pietrucha-Dilanchian et al., "Balamuthia mandrillaris and Amebic Encephalitis with Neurotoxoplasmosis Coinfection in a Patient with Advanced HIV Infection".
PubMed: 34664998
DOI: 10.1128/JCM.01838-21 -
Diseases (Basel, Switzerland) Apr 2023Given the opportunity and access, pathogenic protists ( and ) can produce fatal infections involving the central nervous system. In the absence of effective treatments,...
Given the opportunity and access, pathogenic protists ( and ) can produce fatal infections involving the central nervous system. In the absence of effective treatments, there is a need to either develop new antimicrobials or enhance the efficacy of existing compounds. Nanocarriers as drug delivery systems are gaining increasing attention in the treatment of parasitic infections. In this study, novel nanocarriers conjugated with amphotericin B and curcumin were evaluated for anti-amoebic efficacy against and . The results showed that nanocarrier conjugated amphotericin B exhibited enhanced cidal properties against both amoebae tested compared with the drug alone. Similarly, nanocarrier conjugated curcumin exhibited up to 75% cidal effects versus approx. 50% cidal effects for curcumin alone. Cytopathogenicity assays revealed that the pre-treatment of both parasites with nanoformulated-drugs reduced parasite-mediated host cellular death compared with the drugs alone. Importantly, the cytotoxic effects of amphotericin B on human cells alone were reduced when conjugated with nanocarriers. These are promising findings and further suggest the need to explore nanocarriers as a means to deliver medicine against parasitic infections.
PubMed: 37092440
DOI: 10.3390/diseases11020058 -
MBio Oct 2018is a pathogenic free-living amoeba that causes a rare but almost always fatal infection of the central nervous system called granulomatous amoebic encephalitis (GAE)....
is a pathogenic free-living amoeba that causes a rare but almost always fatal infection of the central nervous system called granulomatous amoebic encephalitis (GAE). Two distinct forms of -a proliferative trophozoite form and a nonproliferative cyst form, which is highly resistant to harsh physical and chemical conditions-have been isolated from environmental samples worldwide and are both observed in infected tissue. Patients suffering from GAE are typically treated with aggressive and prolonged multidrug regimens that often include the antimicrobial agents miltefosine and pentamidine isethionate. However, survival rates remain low, and studies evaluating the susceptibility of to these compounds and other potential therapeutics are limited. To address the need for more-effective treatments, we screened 2,177 clinically approved compounds for activity against The quinoline antibiotic nitroxoline (8-hydroxy-5-nitroquinoline), which has safely been used in humans to treat urinary tract infections, was identified as a lead compound. We show that nitroxoline inhibits both trophozoites and cysts at low micromolar concentrations, which are within a pharmacologically relevant range. We compared the efficacy of nitroxoline to that of drugs currently used in the standard of care for GAE and found that nitroxoline is the most potent and selective inhibitor of tested. Furthermore, we demonstrate that nitroxoline prevents -mediated destruction of host cells in cultured fibroblast and primary brain explant models also at pharmacologically relevant concentrations. Taken together, our findings indicate that nitroxoline is a promising candidate for repurposing as a novel treatment of infections. is responsible for hundreds of reported cases of amoebic encephalitis, the majority of which have been fatal. Despite being an exceptionally deadly pathogen, is understudied, leaving many open questions regarding epidemiology, diagnosis, and treatment. Due to the lack of effective drugs to fight infections, mortality rates remain high even for patients receiving intensive care. This report addresses the need for new treatment options through a drug repurposing screen to identify novel inhibitors. The most promising candidate identified was the quinoline antibiotic nitroxoline, which has a long history of safe use in humans. We show that nitroxoline kills at pharmacologically relevant concentrations and exhibits greater potency and selectivity than drugs commonly used in the current standard of care. The findings that we present demonstrate the potential of nitroxoline to be an important new tool in the treatment of life-threatening infections.
Topics: Amebiasis; Amebicides; Balamuthia mandrillaris; Brain; Cell Line; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Fibroblasts; Humans; Models, Biological; Nitroquinolines; Parasitic Sensitivity Tests
PubMed: 30377287
DOI: 10.1128/mBio.02051-18