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BMC Infectious Diseases Apr 2023Balamuthia granulomatous amoebic encephalitis (GAE) is a peculiar parasitic infectious disease of the central nervous system, about 39% of the infected Balamuthia GAE... (Review)
Review
BACKGROUND
Balamuthia granulomatous amoebic encephalitis (GAE) is a peculiar parasitic infectious disease of the central nervous system, about 39% of the infected Balamuthia GAE patients were found to be immunocompromised and is extremely rare clinically. The presence of trophozoites in diseased tissue is an important basis for pathological diagnosis of GAE. Balamuthia GAE is a rare and highly fatal infection for which there is no effective treatment plan in clinical practice.
CASE PRESENTATION
This paper reports clinical data from a patient with Balamuthia GAE to improve physician understanding of the disease and diagnostic accuracy of imaging and reduce misdiagnosis. A 61-year-old male poultry farmer presented with moderate swelling pain in the right frontoparietal region without obvious inducement three weeks ago. Head computed tomography(CT) and magnetic resonance imaging(MRI) revealed a space-occupying lesion in the right frontal lobe. Intially clinical imaging diagnosed it as a high-grade astrocytoma. The pathological diagnosis of the lesion was inflammatory granulomatous lesions with extensive necrosis, suggesting amoeba infection. The pathogen detected by metagenomic next-generation sequencing (mNGS) is Balamuthia mandrillaris, the final pathological diagnosis was Balamuthia GAE.
CONCLUSION
When a head MRI shows irregular or annular enhancement, clinicians should not blindly diagnose common diseases such as brain tumors. Although Balamuthia GAE accounts for only a small proportion of intracranial infections, it should be considered in the differential diagnosis.
Topics: Male; Humans; Middle Aged; Encephalitis; Central Nervous System Protozoal Infections; Infectious Encephalitis; Amebiasis; Brain; Central Nervous System Parasitic Infections; Granuloma; Fatal Outcome
PubMed: 37072710
DOI: 10.1186/s12879-023-08228-6 -
Frontiers in Microbiology 2023species, , and are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living...
species, , and are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical need for effective therapeutics, we screened kinase inhibitor chemotypes against three pFLA using phenotypic drug assays involving CellTiter-Glo 2.0. Herein, we report the activity of the compounds against the trophozoite stage of each of the three amoebae, ranging from nanomolar to low micromolar potency. The most potent compounds that were identified from this screening effort were: ( EC: 0.92 ± 0.3 μM; and EC: 0.43 ± 0.13 μM), and ( ECs: <0.63 μM, and 0.3 ± 0.21 μM), and and ( ECs: 1.0 ± 0.12 μM, and 1.4 ± 0.17 μM, respectively). With several of these pharmacophores already possessing blood-brain barrier (BBB) permeability properties, or are predicted to penetrate the BBB, these hits present novel starting points for optimization as future treatments for pFLA-caused diseases.
PubMed: 37234530
DOI: 10.3389/fmicb.2023.1149145 -
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 -
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 -
Clinical Infectious Diseases : An... May 2019Balamuthia mandrillaris is a free-living ameba that causes rare, nearly always fatal disease in humans and animals worldwide. B. mandrillaris has been isolated from...
BACKGROUND
Balamuthia mandrillaris is a free-living ameba that causes rare, nearly always fatal disease in humans and animals worldwide. B. mandrillaris has been isolated from soil, dust, and water. Initial entry of Balamuthia into the body is likely via the skin or lungs. To date, only individual case reports and small case series have been published.
METHODS
The Centers for Disease Control and Prevention (CDC) maintains a free-living ameba (FLA) registry and laboratory. To be entered into the registry, a Balamuthia case must be laboratory-confirmed. Several sources were used to complete entries in the registry, including case report forms, CDC laboratory results, published case reports, and media information. SAS© version 9.3 software was used to calculate descriptive statistics and frequencies.
RESULTS
We identified 109 case reports of Balamuthia disease between 1974 and 2016. Most (99%) had encephalitis. The median age was 36 years (range 4 months to 91 years). Males accounted for 68% of the case patients. California had the highest number of case reports, followed by Texas and Arizona. Hispanics constituted 55% for those with documented ethnicity. Exposure to soil was commonly reported. Among those with a known outcome, 90% of patients died.
CONCLUSIONS
Balamuthia disease in the United States is characterized by a highly fatal encephalitis that affects patients of all ages. Hispanics were disproportionately affected. The southwest region of the United States reported the most cases. Clinician awareness of Balamuthia as a cause of encephalitis might lead to earlier diagnosis and initiation of treatment, resulting in better outcomes.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amebiasis; Balamuthia mandrillaris; Central Nervous System Protozoal Infections; Child; Child, Preschool; Female; Humans; Infant; Infectious Encephalitis; Male; Middle Aged; Registries; Sequence Analysis, DNA; United States; Young Adult
PubMed: 30239654
DOI: 10.1093/cid/ciy813 -
Journal of Veterinary Diagnostic... May 2023Free-living amoebae are rare causes of morbidity and mortality in humans and animals around the globe. Because the route of exposure and clinical progression of disease... (Review)
Review
Free-living amoebae are rare causes of morbidity and mortality in humans and animals around the globe. Because the route of exposure and clinical progression of disease caused by different species of amoebae may vary in people and animals, determining the species of amoeba present is important. We describe here a fatal infection by the free-living amoeba in a Siberian tiger (). The 17-y-old patient had a rapid clinical decline after a peracute onset of severe lethargy, dull mentation, and anorexia. Autopsy did not identify a cause of death. Histology revealed inflammation associated with amoebic trophozoites in the brain, lungs, and iris of one eye. These amoebae were confirmed to be based on a PCR assay and sequencing. Although there are subtle morphologic differences between cyst stages of spp., , and when present and identified on routine staining, other modalities, including PCR, immunofluorescence, electron microscopy, and immunohistochemistry, are typically utilized to confirm the pathogen involved in these cases. We review the reports of balamuthosis in animals.
Topics: Humans; Animals; Tigers; Amebiasis; Amoeba; Acanthamoeba; Naegleria fowleri; Balamuthia mandrillaris
PubMed: 36908206
DOI: 10.1177/10406387231160771 -
Applied and Environmental Microbiology May 2005Balamuthia mandrillaris is a free-living ameba and an opportunistic agent of granulomatous encephalitis in humans and other mammalian species. Other free-living amebas,...
Balamuthia mandrillaris is a free-living ameba and an opportunistic agent of granulomatous encephalitis in humans and other mammalian species. Other free-living amebas, such as Acanthamoeba and Hartmannella, can provide a niche for intracellular survival of bacteria, including the causative agent of Legionnaires' disease, Legionella pneumophila. Infection of amebas by L. pneumophila enhances the bacterial infectivity for mammalian cells and lung tissues. Likewise, the pathogenicity of amebas may be enhanced when they host bacteria. So far, the colonization of B. mandrillaris by bacteria has not been convincingly shown. In this study, we investigated whether this ameba could host L. pneumophila bacteria. Our experiments showed that L. pneumophila could initiate uptake by B. mandrillaris and could replicate within the ameba about 4 to 5 log cycles from 24 to 72 h after infection. On the other hand, a dotA mutant, known to be unable to propagate in Acanthamoeba castellanii, also did not replicate within B. mandrillaris. Approaching completion of the intracellular cycle, L. pneumophila wild-type bacteria were able to destroy their ameboid hosts. Observations by light microscopy paralleled our quantitative data and revealed the rounding, collapse, clumping, and complete destruction of the infected amebas. Electron microscopic studies unveiled the replication of the bacteria in a compartment surrounded by a structure resembling rough endoplasmic reticulum. The course of intracellular infection, the degree of bacterial multiplication, and the ultrastructural features of a L. pneumophila-infected B. mandrillaris ameba resembled those described for other amebas hosting Legionella bacteria. We hence speculate that B. mandrillaris might serve as a host for bacteria in its natural environment.
Topics: Amoeba; Animals; Encephalitis; Legionella pneumophila; Opportunistic Infections
PubMed: 15870307
DOI: 10.1128/AEM.71.5.2244-2249.2005 -
Free-living amoebae isolated in the Central African Republic: epidemiological and molecular aspects.The Pan African Medical Journal 2017Among the many species of free-living amoebae infecting humans, only , a few species of recently are responsible for human diseases especially deadly encephalitis...
Among the many species of free-living amoebae infecting humans, only , a few species of recently are responsible for human diseases especially deadly encephalitis outside of Acanthamoeba keratitis related. In the Central African Republic (CAR), no studies have previously been conducted about free amoebae and no suspicious cases of encephalitis or amoebic keratitis was reported even though the ecosystem supported the proliferation of these microorganisms. The objective of this study was to identify free-living amoebae present in CAR and to define the molecular characteristic. Bathing sites and cerebrospinal fluid from patients died of bacterial meningitis untagged were explored by culture and PCR and the amplicons were sequenced which allowed to characterize the species found. Only species of the genus and similar to those already described in the world and not pathogenic for humans were found in bathing sites, the cerebrospinal fluid meanwhile remained negative. Although no pathogen species such as or species of have been isolated, this study worth pursuing because this investigation was very limited in space because of the insecurity in the country.
Topics: Amebiasis; Amoeba; Baths; Central African Republic; Central Nervous System Protozoal Infections; Encephalitis; Eye Infections, Parasitic; Female; Humans; Keratitis; Male; Polymerase Chain Reaction
PubMed: 28451034
DOI: 10.11604/pamj.2017.26.57.9021 -
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 -
BioMed Research International 2015Each year, hundreds of millions of people travel across international borders or even oceans, and up to 230 million may remain for long periods. Among these, 3-5 million... (Review)
Review
Each year, hundreds of millions of people travel across international borders or even oceans, and up to 230 million may remain for long periods. Among these, 3-5 million settle permanently in their new homes, with about 1 million migrating permanently to the United States of America. This may result in transport of parasites and other pathogens, which might become established, infecting individuals in the new location. Beyond concern of disease spread, the health of migrants is of concern since the rigors, circumstances, and living conditions surrounding migrations may increase the vulnerability of migrants to infections. International adoptees and refugees are a small subset of these migrants but are of special significance inasmuch as adoptees may be more vulnerable to infection due to their immature immune status, and refugees may be more vulnerable due to substandard living conditions. Both originate from diverse regions, but often from environments of low hygiene and health care standards. This review examines recent examples of infections reported from adoptees and refugees entering the USA through 2010, highlighting the most common origin countries and the diseases most frequently involved, including Chagas disease, Balamuthia amebic meningoencephalitis, giardiasis, microsporidiosis, hepatitis, measles, pertussis, tuberculosis, malaria, intestinal helminths, and syphilis.
Topics: Human Migration; Humans; Infections; Refugees; United States
PubMed: 26583130
DOI: 10.1155/2015/763715