-
Journal of Clinical Microbiology Sep 2015Balamuthia mandrillaris is a rare cause of human infection, but when infections do occur, they result in high rates of morbidity and mortality. A case of disseminated...
Balamuthia mandrillaris is a rare cause of human infection, but when infections do occur, they result in high rates of morbidity and mortality. A case of disseminated Balamuthia infection is presented. Early diagnosis and initiation of recommended therapy are essential for increased chances of successful outcomes.
Topics: Aged, 80 and over; Amebiasis; Balamuthia mandrillaris; Fatal Outcome; Fluorescent Antibody Technique; Hand; Histocytochemistry; Humans; Male; Microscopy; Skin
PubMed: 26135864
DOI: 10.1128/JCM.01549-15 -
BMC Infectious Diseases Jan 2022Granulomatous amoebic encephalitis (GAE) is a rare central nervous system infection caused by the Balamuthia mandrillaris or Acanthamoeba species. Diagnosis is...
BACKGROUND
Granulomatous amoebic encephalitis (GAE) is a rare central nervous system infection caused by the Balamuthia mandrillaris or Acanthamoeba species. Diagnosis is challenging because of the non-specific clinical presentation, cerebrospinal fluid analysis, and radiological features. There is no effective treatment for GAE to date.
CASE PRESENTATION
A 54-year-old male was admitted to hospital after experiencing acute onset of numbness and weakness on his left limb. Due to the initial consideration of intracranial tumor, surgical removal of the right parietal lesion was performed. However, the patient had a headache accompanied by diplopia, difficulty walking and a new lesion was found in the left occipital-parietal lobe two weeks after the first operation. High-throughput next-generation sequencing (NGS) detected the presence of high copy reads of the B. mandrillaris genome sequence in the patient's blood, cerebral spinal fluid (CSF), and brain tissue. Pathological investigation of the brain tissue showed granulomatous changes and amoebic trophozoite scattered around blood vessels under high magnification. The patient was re-operated due to developing progressive confusion caused by subfalcine herniation of the left cerebral hemisphere. The lesions of the right parietal lobe were obviously decreasing in size after the first surgery, and the lesions of the left occipital lobe and the sunfalcine herniation didn't ameliorate two months after the second surgery. The patient was transferred to local hospital for continuous treatment with sulfamethoxazole and azithromycin. After five months of the second surgery, the patient showed good recovery with mild headache.
CONCLUSIONS
This is the first report of a patient with B. mandrillaris encephalitis initially confirmed by NGS and have experienced two excisions, responding favorably to the combination of surgeries and medications. Early surgical resection of intracranial lesions combined with drug treatment may offer the chance of a cure.
Topics: Amebiasis; Balamuthia mandrillaris; Central Nervous System Protozoal Infections; Encephalitis; Humans; Infectious Encephalitis; Male; Middle Aged
PubMed: 35032997
DOI: 10.1186/s12879-021-07020-8 -
Pathogens (Basel, Switzerland) Jun 2020Pathogenic free-living amoebae, , , and several species are the etiological agents of severe brain diseases, with case mortality rates > 90%. A number of constraints...
Pathogenic free-living amoebae, , , and several species are the etiological agents of severe brain diseases, with case mortality rates > 90%. A number of constraints including misdiagnosis and partially effective treatments lead to these high fatality rates. The unmet medical need is for rapidly acting, highly potent new drugs to reduce these alarming mortality rates. Herein, we report the discovery of new drugs as potential anti-amoebic agents. We used the CellTiter-Glo 2.0 high-throughput screening methods to screen the Medicines for Malaria Ventures (MMV) Pandemic Response Box in a search for new active chemical scaffolds. Initially, we screened the library as a single-point assay at 10 and 1 µM. From these data, we reconfirmed hits by conducting quantitative dose-response assays and identified 12 hits against , 29 against , and 14 against ranging from nanomolar to low micromolar potency. We further describe 11 novel molecules with activity against , 22 against , and 9 against . These structures serve as a starting point for medicinal chemistry studies and demonstrate the utility of phenotypic screening for drug discovery to treat diseases caused by free-living amoebae.
PubMed: 32560115
DOI: 10.3390/pathogens9060476 -
Frontiers in Microbiology 2023() is a free-living amoeba that can cause rare yet fatal granulomatous amoebic encephalitis (GAE). However, efficacious treatment for GAE is currently unavailable,...
INTRODUCTION
() is a free-living amoeba that can cause rare yet fatal granulomatous amoebic encephalitis (GAE). However, efficacious treatment for GAE is currently unavailable, especially when genomic studies on are limited.
METHODS
In this study, strain KM-20 was isolated from the brain tissue of a GAE patient, and its mitochondrial genome was assembled using high-coverage Nanopore long reads and Illumina short reads.
RESULTS AND DISCUSSION
Phylogenetic and comparative analyses revealed a range of diversification in the mitochondrial genome of KM-20 and nine other strains. According to the mitochondrial genome alignment, one of the most variable regions was observed in the ribosomal protein S3 (), which was caused by an array of novel protein tandem repeats. The repeating units in the protein tandem region present significant copy number variations (CNVs) among strains and suggest KM-20 as the most divergent strain for its highly variable sequence and highest copy number in . Moreover, mitochondrial heteroplasmy was observed in strain V039, and two genotypes of are caused by the CNVs in the tandem repeats. Taken together, the copy number and sequence variations of the protein tandem repeats enable to be a perfect target for clinical genotyping assay for . The mitochondrial genome diversity of paves the way to investigate the phylogeny and diversification of pathogenic amoebae.
PubMed: 37213512
DOI: 10.3389/fmicb.2023.1162963 -
Dermatology Online Journal Jul 2017Soil and freshwater-dwelling amoebae may opportunistically infect the skin and evoke a granulomatous dermatitis that camouflages their underlying morphology. Amoebic...
Soil and freshwater-dwelling amoebae may opportunistically infect the skin and evoke a granulomatous dermatitis that camouflages their underlying morphology. Amoebic infestations are incredibly rare in the U.S., predominantly occurring in the young, elderly, and immunocompromised. Sadly, because diagnosis is difficult and unsuspected, most cases are diagnosed at autopsy. The following case is of a healthy 84-year-old man with a non-healing nodulo-ulcerative cutaneous lesion on his left forearm that appeared following a gardening injury. Lesional punch biopsies repeatedly showed non-specific granulomatous inflammation with no pathogens evident histologically or by culture. Histopathologic diagnosis was made five months after initial presentation via identification of amoebic trophozoite forms in tissue from a large excisional specimen. Anti-amoebic therapy was initiated immediately. The patient experienced mental status changes three days following lesion excision, with evidence of a cystic mass in the left medial parieto-occipital lobe by CT. Both intraoperative brain biopsies and cutaneous tissue samples tested positive for Balamuthia mandrillaris by indirect immunofluorescent antibody assay performed at the Centers for Disease Control. The patient achieved a full recovery on a triple antibiotic regimen. Clinical suspicion and thorough histopathologic analysis may determine the difference between survival and death for a patient presenting with a treatment-refractory localized granulomatous lesion.
Topics: Aged, 80 and over; Amebiasis; Balamuthia mandrillaris; Brain; Brain Abscess; Central Nervous System Protozoal Infections; Encephalitis; Humans; Magnetic Resonance Imaging; Male
PubMed: 29469695
DOI: No ID Found -
Annals of Laboratory Medicine Mar 2022Identifying the causal pathogen of encephalitis remains a clinical challenge. A 50-year-old man without a history of neurological disease was referred to our department...
BACKGROUND
Identifying the causal pathogen of encephalitis remains a clinical challenge. A 50-year-old man without a history of neurological disease was referred to our department for the evaluation of an intracranial lesion observed on brain magnetic resonance imaging (MRI) scans, and the pathology results suggested protozoal infection. We identified the species responsible for encephalitis using thymine-adenine (TA) cloning, suitable for routine clinical practice.
METHODS
We extracted DNA from a paraffin-embedded brain biopsy sample and performed TA cloning using two universal eukaryotic primers targeting the V4-5 and V9 regions of the 18S rRNA gene. The recombinant plasmids were extracted, and the inserted amplicons were identified by Sanger sequencing and a homology search of sequences in the National Center for Biotechnology Information Basic Local Alignment Search Tool.
RESULTS
The infection was confirmed to be caused by the free-living amoeba . Two of 41 colonies recombinant with 18S V4-5 primers and 35 of 63 colonies recombinant with the 18S V9 primer contained genes; all other colonies contained human genes. Pathogen-specific PCR ruled out , , spp., and infections.
CONCLUSIONS
This is the first report of -induced encephalitis in Korea based on molecular identification. TA cloning with the 18S rRNA gene is a feasible and affordable diagnostic tool for the detection of infectious agents of unknown etiology.
Topics: Adenine; Balamuthia mandrillaris; Cloning, Molecular; Encephalitis; Eukaryota; Humans; Male; Middle Aged; Thymine
PubMed: 34635613
DOI: 10.3343/alm.2022.42.2.196 -
Seminars in Neurology Sep 2005Parasitic infection of the nervous system can produce a variety of symptoms and signs. Because symptoms of infection are often mild or nonspecific, diagnosis can be... (Review)
Review
Parasitic infection of the nervous system can produce a variety of symptoms and signs. Because symptoms of infection are often mild or nonspecific, diagnosis can be difficult. Familiarity with basic epidemiological characteristics and distinguishing radiographic findings can increase the likelihood of detection and proper treatment of parasitic infection of the nervous system. This article discusses the clinical presentation, diagnosis, and treatment for some of the more common infections of the nervous system caused by cestodes, trematodes and protozoans: Echinococcus spp., Spirometra spp. (sparganosis), Paragonimus spp., Schistosoma spp., Trypanosoma spp., Naegleria fowlerii, Acanthamoeba histolytica, and Balamuthia mandrillaris.
Topics: Animals; Cestode Infections; Humans; Nervous System Diseases; Protozoan Infections; Trematode Infections
PubMed: 16170739
DOI: 10.1055/s-2005-917663 -
Cureus Mar 2021Meningoencephalitis caused by free-living amoebas (FLA) has a high mortality rate, and most treatments are ineffective. FLA includes Naegleria, Fowleri, Acanthamoeba,... (Review)
Review
Meningoencephalitis caused by free-living amoebas (FLA) has a high mortality rate, and most treatments are ineffective. FLA includes Naegleria, Fowleri, Acanthamoeba, and Balamuthia mandrillaris (M). We explore the use of miltefosine in the treatment of one of these infections. The concerning mortality of the infection obligates us to look for more effective treatments for meningoencephalitis caused by FLA. During this review, we will consolidate the knowledge of using miltefosine in these three infections. We will investigate the mechanism by which the drug is effective in these infections as well. After this comprehensive review, we should assess if miltefosine improves the mortality and prognosis of the infection with the information collected. We used a Medical Subject Headings (MeSH) search on PubMed. Inclusion criteria included papers written in the English language and human subjects research for the past 25 years. Until today, there are no definitive guidelines to be followed when treating such patients. However, miltefosine has demonstrated promising results. Miltefosine decreases the usual mortality rate in the three infections; however, there are few reports due to the low frequency of these infections. Almost all cases we documented have survived. More information needs to be gathered for the use of miltefosine for these infections.
PubMed: 33833918
DOI: 10.7759/cureus.13698 -
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 -
Emerging Infectious Diseases Jan 2023A patient in California, USA, with rare and usually fatal Balamuthia mandrillaris granulomatous amebic encephalitis survived after receiving treatment with a regimen...
A patient in California, USA, with rare and usually fatal Balamuthia mandrillaris granulomatous amebic encephalitis survived after receiving treatment with a regimen that included the repurposed drug nitroxoline. Nitroxoline, which is a quinolone typically used to treat urinary tract infections, was identified in a screen for drugs with amebicidal activity against Balamuthia.
Topics: Humans; Balamuthia mandrillaris; Amebiasis; Infectious Encephalitis; Granuloma; Brain
PubMed: 36573629
DOI: 10.3201/eid2901.221531