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Tropical Parasitology 2021is an opportunistic, free-living ameba that is pathogenic to humans. It has a worldwide distribution but is mainly detected in warmer regions. infections are rare but... (Review)
Review
is an opportunistic, free-living ameba that is pathogenic to humans. It has a worldwide distribution but is mainly detected in warmer regions. infections are rare but have been reported in both immunocompetent and immunocompromised individuals of all ages. can enter through wounds on the skin or the nose and cause cutaneous lesions and the usually fatal amebic encephalitis (BAE). Infection usually spreads from the lungs or through nerve fibers, and attacks the central nervous system, forming granulomatous lesions and necrosis in the brain. infection is usually chronic, and patients initially present with nonspecific symptoms, including headache, nausea, myalgia, and low-grade fever. As the disease progresses, the patient becomes paralyzed and comatose, often leading to death. Lack of knowledge of predisposing factors, specific treatment, and standardized detection tools have resulted in a nearly cent percent fatality rate. Although only about 200 cases have been reported worldwide since its characterization in the 1990s, the number of reported cases has increased over the years. BAE is an emerging disease and a major health concern. Few patients have survived infections with antimicrobial treatment that has largely been empirical. Early diagnosis is the key and requires familiarity with the disease and a high degree of suspicion on the part of the diagnostician. There are currently no specific treatment and prevention recommendations. This review highlights our current understanding of in terms of its pathogenicity, genomics, and novel diagnostic and therapeutic approaches against BAE infections.
PubMed: 34765527
DOI: 10.4103/tp.tp_36_21 -
Pathogens and Global Health Mar 2022Pathogenic free-living amoebae affecting the central nervous system are known to cause granulomatous amoebic encephalitis (GAE) or primary amoebic meningoencephalitis...
Pathogenic free-living amoebae affecting the central nervous system are known to cause granulomatous amoebic encephalitis (GAE) or primary amoebic meningoencephalitis (PAM). Although hosts with impaired immunity are generally at a higher risk of severe disease, amoebae such as and can instigate disease in otherwise immunocompetent individuals, whereas species mostly infect immunocompromised people. also cause a sight-threatening eye infection, mostly in contact lens wearers. Although infections due to pathogenic amoebae are considered rare, recently, these deadly amoebae were detected in water supplies in the USA. This is of particular concern, especially with global warming further exacerbating the problem. Herein, we describe the epidemiology, presentation, diagnosis, and management of free-living amoeba infections.
Topics: Acanthamoeba; Amebiasis; Amoeba; Balamuthia mandrillaris; Humans; Naegleria fowleri
PubMed: 34602025
DOI: 10.1080/20477724.2021.1985892 -
Journal of Clinical Microbiology Jan 2022Infections caused by Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris result in a variety of clinical manifestations in humans. These amoebae are found...
Infections caused by Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris result in a variety of clinical manifestations in humans. These amoebae are found in water and soil worldwide. spp. and B. mandrillaris cause granulomatous amoebic encephalitis (GAE), which usually presents as a mass, while N. fowleri causes primary amoebic meningoencephalitis (PAM). spp. can also cause keratitis, and both spp. and can cause lesions in skin and respiratory mucosa. These amoebae can be difficult to diagnose clinically as these infections are rare and, if not suspected, can be misdiagnosed with other more common diseases. Microscopy continues to be the key first step in diagnosis, but the amoeba can be confused with macrophages or other infectious agents if an expert in infectious disease pathology or clinical microbiology is not consulted. Although molecular methods can be helpful in establishing the diagnosis, these are only available in referral centers. Treatment requires combination of antibiotics and antifungals and, even with prompt diagnosis and treatment, the mortality for neurological disease is extremely high.
Topics: Acanthamoeba; Amebiasis; Amoeba; Balamuthia mandrillaris; Humans; Naegleria fowleri
PubMed: 34133896
DOI: 10.1128/JCM.00228-21 -
JAAD International Mar 2022Balamuthia mandrillaris, a free-living amoeba, causes an uncommon infection that is characterized by cutaneous and neurological involvement, which carries a poor...
INTRODUCTION
Balamuthia mandrillaris, a free-living amoeba, causes an uncommon infection that is characterized by cutaneous and neurological involvement, which carries a poor prognosis.
METHODS
This is a retrospective observational study including patients with clinical suspicion of cutaneous balamuthiasis, their skin biopsies, and/or a positive direct immunofluorescence test. The data were collected from the Dermatology and Pathology service of the Hospital Cayetano Heredia and the Instituto Tropical Alexander von Humboldt, Lima, Peru, from January 1985 to June 2007. We identified 60 biopsies from 35 patients, from which clinical data were available in 30.
RESULTS
Twenty-two (73%) patients had centrofacial lesions, mostly located on the nose. The classical lesion was an asymptomatic, erythematous, or violaceous infiltrated plaque. Twenty-two (73%) patients had neurologic involvement. Fifty (83%) biopsies showed granulomatous dermatitis and 75% showed ill-defined tuberculoid granulomas without caseous necrosis. Multinucleated giant cells were observed in 52 (87%) biopsies. Trophozoite forms were identified in the biopsies of 25 (71%) patients. Direct immunofluorescence was positive in 25 (71%) patients.
CONCLUSION
is a pathogen that is capable of inducing a characteristic skin lesion with a reaction pattern of ill-defined tuberculoid granulomas and many giant cells.
PubMed: 35059659
DOI: 10.1016/j.jdin.2021.11.005 -
Antibiotics (Basel, Switzerland) Apr 2022and are free-living, opportunistic protists, distributed widely in the environment. They are responsible for primary amoebic meningoencephalitis (PAM) and...
and are free-living, opportunistic protists, distributed widely in the environment. They are responsible for primary amoebic meningoencephalitis (PAM) and granulomatous amoebic encephalitis (GAE), the fatal central nervous infections with mortality rates exceeding 90%. With the rise of global warming and water shortages resulting in water storage in tanks (where these amoebae may reside), the risk of infection is increasing. Currently, as a result of a lack of awareness, many cases may be misdiagnosed. Furthermore, the high mortality rate indicates the lack of effective drugs available. In this study, secondary metabolites from the plants and were tested for their anti-amoebic properties against and Three of the nine compounds showed potent and significant anti-amoebic activities against both and : ursolic acid, betulinic acid, and betulin. Additionally, all compounds depicted limited or minimal toxicity to human cells and were capable of reducing amoeba-mediated host cell death. Moreover, the minimum inhibitory concentration required to inhibit 50% of amoebae growth, the half-maximal effective concentration, and the maximum non-toxic dose against human cells of the compounds were determined. These effective plant-derived compounds should be utilized as potential therapies against infections due to free-living amoebae, but future research is needed to realize these expectations.
PubMed: 35625183
DOI: 10.3390/antibiotics11050539 -
Antibiotics (Basel, Switzerland) Sep 2022and are opportunistic protists, responsible for fatal central nervous system infections such as primary amoebic meningoencephalitis (PAM) and granulomatous amoebic...
and are opportunistic protists, responsible for fatal central nervous system infections such as primary amoebic meningoencephalitis (PAM) and granulomatous amoebic encephalitis (GAE) with mortality rates higher than 90%. Threatening a rise in cases is the increase in temperature due to global warming. No effective treatment is currently available. Herein, nanotechnology was used to conjugate Zinc oxide with Ampicillin, Ceftrixon, Naringin, Amphotericin B, and Quericitin, and the amoebicidal activity and host cell cytotoxicity of these resulting compounds were investigated. The compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT were found to reduce viability to 35.5%, 39.6%, 52.0%, 50.8%, 35.9%, and 69.9%, respectively, and viability to 40.9%, 48.2%, 51.6%, 43.8%, and 62.4%, respectively, when compared with their corresponding controls. Furthermore, the compounds reduced -mediated and -mediated host cell death significantly. Additionally, the compounds showed limited cytotoxicity against human cells; cell toxicity was 35.5%, 36.4%, 30.9%, 36.6%, and 35.6%, respectively, for the compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT. Furthermore, the minimum inhibitory concentrations to inhibit amoeba growth by 50% were determined for and The MIC for were determined to be 69.52 µg/mL, 82.05 µg/mL, 88.16 µg/mL, 95.61 µg/mL, and 85.69 µg/mL, respectively; the MIC of the compounds for were determined to be 113.9 µg/mL, 102.3 µg/mL, 106.9 µg/mL, 146.4 µg/mL, and 129.6 µg/mL, respectively. Translational research to further develop therapies based on these compounds is urgently warranted, given the lack of effective therapies currently available against these devastating infections.
PubMed: 36289939
DOI: 10.3390/antibiotics11101281 -
Scientific Reports Nov 2021Balamuthia mandrillaris, a pathogenic free-living amoeba, causes cutaneous skin lesions as well as granulomatous amoebic encephalitis, a 'brain-eating' disease. As with...
Balamuthia mandrillaris, a pathogenic free-living amoeba, causes cutaneous skin lesions as well as granulomatous amoebic encephalitis, a 'brain-eating' disease. As with the other known pathogenic free-living amoebas (Naegleria fowleri and Acanthamoeba species), drug discovery efforts to combat Balamuthia infections of the central nervous system are sparse; few targets have been validated or characterized at the molecular level, and little is known about the biochemical pathways necessary for parasite survival. Current treatments of encephalitis due to B. mandrillaris lack efficacy, leading to case fatality rates above 90%. Using our recently published methodology to discover potential drugs against pathogenic amoebas, we screened a collection of 85 compounds with known antiparasitic activity and identified 59 compounds that impacted the growth of Balamuthia trophozoites at concentrations below 220 µM. Since there is no fully annotated genome or proteome of B. mandrillaris, we sequenced and assembled its transcriptome from a high-throughput RNA-sequencing (RNA-Seq) experiment and located the coding sequences of the genes potentially targeted by the growth inhibitors from our compound screens. We determined the sequence of 17 of these target genes and obtained expression clones for 15 that we validated by direct sequencing. These will be used in the future in combination with the identified hits in structure guided drug discovery campaigns to develop new approaches for the treatment of Balamuthia infections.
Topics: Acanthamoeba; Amebiasis; Amoeba; Balamuthia mandrillaris; Base Sequence; Brain; Drug Design; Drug Discovery; Encephalitis; Gene Expression; Naegleria fowleri; Transcriptome; Trophozoites
PubMed: 34737367
DOI: 10.1038/s41598-021-99903-8 -
Parasite (Paris, France) 2021In this review, we focus on the sequenced genomes of the pathogens Naegleria fowleri, Acanthamoeba spp. and Balamuthia mandrillaris, and the remarkable discoveries... (Review)
Review
In this review, we focus on the sequenced genomes of the pathogens Naegleria fowleri, Acanthamoeba spp. and Balamuthia mandrillaris, and the remarkable discoveries regarding the pathogenicity and genetic information of these organisms, using techniques related to the various omics branches like genomics, transcriptomics, and proteomics. Currently, novel data produced through comparative genomics analyses and both differential gene and protein expression in these free-living amoebas have allowed for breakthroughs to identify genes unique to N. fowleri, genes with active transcriptional activity, and their differential expression in conditions of modified virulence. Furthermore, orthologous genes of the various nuclear genomes within the Naegleria and Acanthamoeba genera have been clustered. The proteome of B. mandrillaris has been reconstructed through transcriptome data, and its mitochondrial genome structure has been thoroughly described with a unique characteristic that has come to light: a type I intron with the capacity of interrupting genes through its self-splicing ribozymes activity. With the integration of data derived from the diverse omic sciences, there is a potential approximation that reflects the molecular complexity required for the identification of virulence factors, as well as crucial information regarding the comprehension of the molecular mechanisms with which these interact. Altogether, these breakthroughs could contribute to radical advances in both the fields of therapy design and medical diagnosis in the foreseeable future.
Topics: Acanthamoeba; Balamuthia mandrillaris; Genome, Protozoan; Genomics; Naegleria fowleri; Proteomics; Transcriptome; Virulence
PubMed: 33843581
DOI: 10.1051/parasite/2021033 -
Journal of Pathology and Translational... Sep 2019We present the case of a 71-year-old man who was diagnosed with amoebic encephalitis caused by Balamuthia mandrillaris. He had rheumatic arthritis for 30 years and had...
We present the case of a 71-year-old man who was diagnosed with amoebic encephalitis caused by Balamuthia mandrillaris. He had rheumatic arthritis for 30 years and had undergone continuous treatment with immunosuppressants. First, he complained of partial spasm from the left thigh to the left upper limb. Magnetic resonance imaging revealed multifocal enhancing nodules in the cortical and subcortical area of both cerebral hemispheres, which were suggestive of brain metastases. However, the patient developed fever with stuporous mentality and an open biopsy was performed immediately. Microscopically, numerous amoebic trophozoites, measuring 20 to 25 µm in size, with nuclei containing one to four nucleoli and some scattered cysts having a double-layered wall were noted in the background of hemorrhagic necrosis. Based on the microscopic findings, amoebic encephalitis caused by Balamuthia mandrillaris was diagnosed. The patient died on the 10th day after being admitted at the hospital. The diagnosis of amoebic encephalitis in the early stage is difficult for clinicians. Moreover, most cases undergo rapid deterioration, resulting in fatal consequences. In this report, we present the first case of B. mandrillaris amoebic encephalitis with fatal progression in a Korean patient.
PubMed: 31121998
DOI: 10.4132/jptm.2019.05.14