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Govinda S. Visvesvara - One of the best experts on this subject based on the ideXlab platform.
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Assessment of blood–brain barrier penetration of miltefosine used to treat a fatal case of Granulomatous Amebic Encephalitis possibly caused by an unusual Balamuthia mandrillaris strain
Parasitology Research, 2015Co-Authors: Jane T. Atkins, Thomas P. C. Dorlo, Rosemaria Gennuso, Danny Kofos, Rama R. Sriram, Teresa Hayes, Yvonne Qvarnstrom, Zuzana Kucerova, B. Joseph Guglielmo, Govinda S. VisvesvaraAbstract:Balamuthia mandrillaris , a free-living ameba, causes rare but frequently fatal Granulomatous Amebic Encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 μg/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 μg/mL. These are the first results confirming some blood–brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug’s toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities.
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Diagnostic challenges in Balamuthia mandrillaris infections
Parasitology Research, 2013Co-Authors: Stephen A. Lobo, Govinda S. Visvesvara, Kiran Patil, Shilpa Jain, Stephen Marks, Michael Tenner, Alex Braun, Guiqing Wang, Marc Y. KhouryAbstract:Balamuthia mandrillaris is an emerging cause of subacute Granulomatous Amebic Encephalitis (GAE). The diagnosis of this infection has proven to be difficult and is usually made postmortem. Early recognition and treatment may offer some benefit. This report describes a previously healthy woman who died from GAE due to B. mandrillaris .
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Fulminant and fatal Encephalitis caused by Acanthamoeba in a kidney transplant recipient: case report and literature review
Transplant infectious disease : an official journal of the Transplantation Society, 2013Co-Authors: Michael J. Satlin, Govinda S. Visvesvara, J.k. Graham, H. Mena, Kristen M. Marks, Stuart D. Saal, Rosemary SoaveAbstract:Acanthamoeba is the most common cause of Granulomatous Amebic Encephalitis, a typically fatal condition that is classically described as indolent and slowly progressive. We report a case of Acanthamoeba Encephalitis in a kidney transplant recipient that progressed to death within 3 days of symptom onset and was diagnosed at autopsy. We also review clinical characteristics, treatments, and outcomes of all published cases of Acanthamoeba Encephalitis in solid organ transplant (SOT) recipients. Ten cases were identified, and the infection was fatal in 9 of these cases. In 6 patients, Acanthamoeba presented in a fulminant manner and death occurred within 2 weeks after the onset of neurologic symptoms. These acute presentations are likely related to immunodeficiencies associated with solid organ transplantation that result in an inability to control Acanthamoeba proliferation. Skin lesions may predate neurologic involvement and provide an opportunity for early diagnosis and treatment. Acanthamoeba is an under-recognized cause of Encephalitis in SOT recipients and often presents in a fulminant manner in this population. Increased awareness of this disease and its clinical manifestations is essential to attain an early diagnosis and provide the best chance of cure.
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Characterization of a new pathogenic Acanthamoeba Species, A. byersi n. sp., isolated from a human with fatal amoebic Encephalitis.
The Journal of eukaryotic microbiology, 2013Co-Authors: Yvonne Qvarnstrom, Thomas A. Nerad, Govinda S. VisvesvaraAbstract:Acanthamoeba spp. are free-living amoebae that are ubiquitous in natural environments. They can cause cutaneous, nasopharyngeal, and disseminated infection, leading to Granulomatous Amebic Encephalitis (GAE) in immunocompromised individuals. In addition, they can cause amoebic keratitis in contact lens wearers. Acanthamoeba GAE is almost always fatal because of difficulty and delay in diagnosis and lack of optimal antimicrobial therapy. Here, we report the description of an unusual strain isolated from skin and brain of a GAE patient. The amoebae displayed large trophozoites and star-shaped cysts, characteristics for acanthamoebas belonging to morphology Group 1. However, its unique morphology and growth characteristics differentiated this new strain from other Group 1 species. DNA sequence analysis, secondary structure prediction, and phylogenetic analysis of the 18S rRNA gene confirmed that this new strain belonged to Group 1, but that it was distinct from the other sequence types within that group. Thus, we hereby propose the establishment of a new species, Acanthamoeba byersi n. sp. as well as a new sequence type, T18, for this new strain. To our knowledge, this is the first report of a Group 1 Acanthamoeba that is indisputably pathogenic in humans.
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Infections with free-living amebae.
Handbook of Clinical Neurology, 2013Co-Authors: Govinda S. VisvesvaraAbstract:Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri are mitochondria-bearing, free-living eukaryotic amebae that have been known to cause infections of the central nervous system (CNS) of humans and other animals. Several species of Acanthamoeba belonging to several different genotypes cause an insidious and chronic disease, Granulomatous Amebic Encephalitis (GAE), principally in immunocompromised hosts including persons infected with HIV/AIDS. Acanthamoeba spp., belonging to mostly group 2, also cause infection of the human cornea, Acanthamoeba keratitis. Balamuthia mandrillaris causes GAE in both immunocompromised and immunocompetent hosts mostly in the very young or very old individuals. Both Acanthamoeba spp. and B. mandrillaris also cause a disseminated disease including the lungs, skin, kidneys, and uterus. Naegleria fowleri, on the other hand, causes an acute and fulminating, necrotizing infection of the CNS called primary Amebic meningoEncephalitis (PAM) in children and young adults with a history of recent exposure to warm fresh water. Additionally, another free-living ameba Sappinia pedata, previously described as S. diploidea, also has caused a single case of Amebic meningoEncephalitis. In this review the biology of these amebae, clinical manifestations, molecular and immunological diagnosis, and epidemiological features associated with GAE and PAM are discussed.
Vijay Johnson - One of the best experts on this subject based on the ideXlab platform.
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Granulomatous Amebic Encephalitis following hematopoietic stem cell transplantation.
Surgical neurology international, 2015Co-Authors: Ninh Doan, Gregory Rozansky, Ha Son Nguyen, Michael Gelsomino, Saman Shabani, Wade Mueller, Vijay JohnsonAbstract:Granulomatous Amebic Encephalitis (GAE) is rare, but often fatal. The infection has been documented predominantly among the immunocompromised population or among those with chronic disease. To date, however, there have only been eight cases regarding the infection following hematopoietic stem cell transplantation (HSCT). A 62-year-old female with a history of relapsed diffuse large B-cell lymphoma, recently underwent peripheral blood autologous stem cell transplant after BEAM conditioning (day 0). On day +15, she began to exhibit worsening fatigue, generalized weakness, and fever. Symptoms progressed to nausea, emesis, somnolence, confusion, and frontal headaches over the next few days. Imaging demonstrated multifocal ill-defined vasogenic edema with patchy enhancement. The patient was started on broad antibiotics, antifungals, and seizure prophylaxis. Evaluation for bacterial, fungal, mycobacterial, and viral etiologies was fruitless. Her mental status progressively deteriorated. On day +22, she exhibited severe lethargy and went into pulseless electrical activity arrest, requiring chest compressions. The episode lasted <2 min and her pulse was restored. She was taken to the operating room for a brain biopsy. Postoperatively, her right pupil began to dilate compared to the left; she demonstrated extensor posturing in her upper extremities and withdrawal in her lower extremities. Repeat computed tomography demonstrated progressive edema. Given poor prognosis and poor neurological examination, the family opted for withdrawal of care. Final pathology was consistent with Acanthamoeba GAE. The authors report the third case of GAE after autologous stem cell transplant, and the ninth case overall after HSCT. This case is unusual due to its rapid clinical presentation after HSCT compared to prior literature. The case highlights the need for high suspicion of Acanthamoeba infection in this patient population.
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Granulomatous Amebic Encephalitis following hematopoietic stem cell transplantation.
Surgical Neurology International, 2015Co-Authors: Ninh Doan, Gregory Rozansky, Ha Son Nguyen, Michael Gelsomino, Saman Shabani, Wade M. Mueller, Vijay JohnsonAbstract:Background: Granulomatous Amebic Encephalitis (GAE) is rare, but often fatal. The infection has been documented predominantly among the immunocompromised population or among those with chronic disease. To date, however, there have only been eight cases regarding the infection following hematopoietic stem cell transplantation (HSCT).
Francine Marciano-cabral - One of the best experts on this subject based on the ideXlab platform.
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Cannabinoid-mediated exacerbation of brain infection by opportunistic amebae.
Journal of neuroimmunology, 2004Co-Authors: Guy A Cabral, Francine Marciano-cabralAbstract:Recent reports indicate a higher frequency of brain infections with opportunistic amebae of the genus Acanthamoeba among immune compromised individuals, including AIDS patients. We have demonstrated, using a murine model of Granulomatous Amebic Encephalitis (GAE), that the major psychoactive and immune suppressive component in marijuana delta-9-tetrahydrocannabinol (THC) exacerbates infection by these amebae. Mice administered THC and infected with Acanthamoeba exhibited dose-related higher mortalities than infected vehicle controls. The greater severity of disease for THC-treated mice was accompanied by decreased accumulation of macrophage-like cells at focal sites of infection in the brain. Furthermore, THC administration resulted in decreased levels of mRNA for the pro-inflammatory cytokines interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor alpha for neonatal rat microglia co-cultured with Acanthamoeba. These results indicate a potential for marijuana to alter the capacity of brain macrophage-like cells to mount a full complement of immune responsiveness to brain infection by opportunistic amebae.
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Differential stimulation of microglial pro-inflammatory cytokines by Acanthamoeba culbertsoni versus Acanthamoeba castellanii.
The Journal of eukaryotic microbiology, 2004Co-Authors: Francine Marciano-cabral, Christina Ludwick, Robyn A. Puffenbarger, Guy A CabralAbstract:Acanthamoeba spp. are opportunistic pathogens that cause Granulomatous Amebic Encephalitis. We compared the highly pathogenic species A. culbertsoni to the relatively less pathogenic species A. castellanii for its capacity to elicit from neonatal rat microglia the gene expression of pro-inflammatory cytokines. Acanthamoeba culbertsoni elicited a robust cytokine gene response by neonatal rat microglia in vitro as compared to A. castellanii. The preponderant cytokine elicited at the mRNA and protein levels was interleukin-1β. In addition, transmission electron microscopy revealed that microglial cells were capable of phagocytozing A. castellanii. In contrast, A. culbertsoni destroyed microglia. Collectively, these results suggest that a combined action of pro-inflammatory cytokines and destruction of host cells by amebae contribute to the pathology caused by the more pathogenic species.
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Interaction of an Acanthamoeba human isolate harboring bacteria with murine peritoneal macrophages.
Journal of Eukaryotic Microbiology, 2003Co-Authors: Francine Marciano-cabral, Eric Powell, Kathy Han, Tammy J. Ferguson, Guy A CabralAbstract:Acanthamoeba spp. are the causative agents of Granulomatous Amebic Encephalitis (GAE), a chronic progressive fatal infection of the central nervous system. These free-living amebae have been associated, also with cutaneous acanthamoebiasis and sinusitis in immunocompromised patients [8,10,13]. Studies on the biological properties of these amebae have been performed using strains cultured axenically for long periods of time. Virulence in the ameba declines after prolonged culture in vitro [11]. Therefore, a recent clinical isolate obtained from an immune suppressed patient who had undergone a renal transplant was subjected to immediate analysis. The patient was diagnosed post mortem with disseminated acanthamoebiasis based on the presence of trophozoites and cysts in hematoxylin and eosin stained tissue sections [13]. Amebae were isolated from cutaneous lesions at the time of autopsy and cultured axenically in Oxoid medium. The clinical isolate was identified as Acanthamoeba and was shown to harbor bacteria both within trophozoites and cysts. Furthermore, co-culture of these amebae with murine peritoneal macrophages resulted in a robust induction of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFa) at levels, which approximated those elicited by the potent immunomodulator bacterial lipopolysaccharide (LPS).
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The Increasing Importance of Acanthamoeba Infections1
The Journal of eukaryotic microbiology, 2000Co-Authors: Francine Marciano-cabral, Robyn Puffenbarger, Guy A CabralAbstract:Abstract Free-living amebae belonging to the genus Acanthamoeba are the causative agents of Granulomatous Amebic Encephalitis, a chronic progressive disease of the central nervous system, and of Amebic keratitis, a chronic eye infection. Granulomatous Amebic Encephalitis occurs more frequently in immunocompromised patients while keratitis occurs in healthy individuals. The recent increased incidence in Acanthamoeba infections is due in part to infection in patients with acquired immune deficiency syndrome, while that for keratitis is due to the increased use of contact lenses. Understanding the mechanism of host resistance to Acanthamoeba is essential since the amebae are resistant to many therapeutic agents. Studies in our laboratory as well as from others have demonstrated that macrophages from immunocompetent animals are important effector cells against Acanthamoeba. We have demonstrated also that microglial cells, resident macrophages of the brain, elicit cytokines in response to A. castellanii. Neona...
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Amebicidal activity of plant extracts from Southeast Asia on Acanthamoeba spp.
Parasitology research, 1998Co-Authors: Dan-my T. Chu, Denise M. Toney, Howard Miles, Chi Ngyuen, Francine Marciano-cabralAbstract:The effect of 100 polar and 100 nonpolar plant extract materials obtained from Southeast Asia were evaluated for Amebicidal activity in vitro against three species of Acanthamoeba.A. culbertsoni, A. castellanii, and A. polyphaga, the causative agents of Granulomatous Amebic Encephalitis and Amebic keratitis, were studied in vitro to determine whether the plant extracts exhibited Amebicidal activity or induced encystment of the amebae. Of the 200 plant extracts tested, extracts obtained from three plants (Ipomoea sp., Kaempferia galanga, and Cananga odorata) were Amebicidal for all three species of Acanthamoeba and a fourth extract prepared from Gastrochilus panduratum was lytic for A. polyphaga and growth-inhibitory for A. castellanii and A. culbertsoni. Three plant extracts induced encystment of all three species of Acanthamoeba. Select plant extracts were tested as well for tumoricidal activity against B103 neuroblastoma cells. Some plant extracts that exhibited tumoricidal activity for B103 cells were not Amebicidal for Acanthamoeba spp. Additionally, the polar and nonpolar extracts that exhibited Amebicidal activity were also tested for activity against primary murine peritoneal macrophage cultures. Plant extracts that demonstrated tumoricidal or Amebicidal activity were not lytic for normal macrophage cultures.
Yvonne Qvarnstrom - One of the best experts on this subject based on the ideXlab platform.
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Assessment of blood–brain barrier penetration of miltefosine used to treat a fatal case of Granulomatous Amebic Encephalitis possibly caused by an unusual Balamuthia mandrillaris strain
Parasitology Research, 2015Co-Authors: Jane T. Atkins, Thomas P. C. Dorlo, Rosemaria Gennuso, Danny Kofos, Rama R. Sriram, Teresa Hayes, Yvonne Qvarnstrom, Zuzana Kucerova, B. Joseph Guglielmo, Govinda S. VisvesvaraAbstract:Balamuthia mandrillaris , a free-living ameba, causes rare but frequently fatal Granulomatous Amebic Encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 μg/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 μg/mL. These are the first results confirming some blood–brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug’s toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities.
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assessment of blood brain barrier penetration of miltefosine used to treat a fatal case of Granulomatous Amebic Encephalitis possibly caused by an unusual balamuthia mandrillaris strain
Parasitology Research, 2015Co-Authors: Sharon L Roy, Thomas P. C. Dorlo, Rosemaria Gennuso, Danny Kofos, Yvonne Qvarnstrom, Jane Atkins, Rama Sriram, Teresa C Hayes, Zuzana KucerovaAbstract:Balamuthia mandrillaris, a free-living ameba, causes rare but frequently fatal Granulomatous Amebic Encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 μg/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 μg/mL. These are the first results confirming some blood–brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug’s toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities.
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Characterization of a new pathogenic Acanthamoeba Species, A. byersi n. sp., isolated from a human with fatal amoebic Encephalitis.
The Journal of eukaryotic microbiology, 2013Co-Authors: Yvonne Qvarnstrom, Thomas A. Nerad, Govinda S. VisvesvaraAbstract:Acanthamoeba spp. are free-living amoebae that are ubiquitous in natural environments. They can cause cutaneous, nasopharyngeal, and disseminated infection, leading to Granulomatous Amebic Encephalitis (GAE) in immunocompromised individuals. In addition, they can cause amoebic keratitis in contact lens wearers. Acanthamoeba GAE is almost always fatal because of difficulty and delay in diagnosis and lack of optimal antimicrobial therapy. Here, we report the description of an unusual strain isolated from skin and brain of a GAE patient. The amoebae displayed large trophozoites and star-shaped cysts, characteristics for acanthamoebas belonging to morphology Group 1. However, its unique morphology and growth characteristics differentiated this new strain from other Group 1 species. DNA sequence analysis, secondary structure prediction, and phylogenetic analysis of the 18S rRNA gene confirmed that this new strain belonged to Group 1, but that it was distinct from the other sequence types within that group. Thus, we hereby propose the establishment of a new species, Acanthamoeba byersi n. sp. as well as a new sequence type, T18, for this new strain. To our knowledge, this is the first report of a Group 1 Acanthamoeba that is indisputably pathogenic in humans.
Zuzana Kucerova - One of the best experts on this subject based on the ideXlab platform.
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Assessment of blood–brain barrier penetration of miltefosine used to treat a fatal case of Granulomatous Amebic Encephalitis possibly caused by an unusual Balamuthia mandrillaris strain
Parasitology Research, 2015Co-Authors: Jane T. Atkins, Thomas P. C. Dorlo, Rosemaria Gennuso, Danny Kofos, Rama R. Sriram, Teresa Hayes, Yvonne Qvarnstrom, Zuzana Kucerova, B. Joseph Guglielmo, Govinda S. VisvesvaraAbstract:Balamuthia mandrillaris , a free-living ameba, causes rare but frequently fatal Granulomatous Amebic Encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 μg/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 μg/mL. These are the first results confirming some blood–brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug’s toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities.
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assessment of blood brain barrier penetration of miltefosine used to treat a fatal case of Granulomatous Amebic Encephalitis possibly caused by an unusual balamuthia mandrillaris strain
Parasitology Research, 2015Co-Authors: Sharon L Roy, Thomas P. C. Dorlo, Rosemaria Gennuso, Danny Kofos, Yvonne Qvarnstrom, Jane Atkins, Rama Sriram, Teresa C Hayes, Zuzana KucerovaAbstract:Balamuthia mandrillaris, a free-living ameba, causes rare but frequently fatal Granulomatous Amebic Encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 μg/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 μg/mL. These are the first results confirming some blood–brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug’s toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities.
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Serologic survey for exposure following fatal Balamuthia mandrillaris infection
Parasitology Research, 2014Co-Authors: Brendan R. Jackson, Zuzana Kucerova, Sharon L Roy, Rama Sriram, Glenda Aguirre, Joli Weiss, Jonathan Yoder, Rebecca Foelber, Steven Baty, Gordana DeradoAbstract:Granulomatous Amebic Encephalitis (GAE) from Balamuthia mandrillaris , a free-living ameba, has a case fatality rate exceeding 90 % among recognized cases in the USA. In August 2010, a GAE cluster occurred following transplantation of infected organs from a previously healthy landscaper in Tucson, AZ, USA, who died from a suspected stroke. As B. mandrillaris is thought to be transmitted through soil, a serologic survey of landscapers and a comparison group of blood donors in southern Arizona was performed. Three (3.6 %) of 83 serum samples from landscapers and 11 (2.5 %) of 441 serum samples from blood donors were seropositive ( p = 0.47). On multivariable analysis, county of residence was associated with seropositivity, whereas age, sex, and ethnicity were not. Exposure to B. mandrillaris , previously unexamined in North America, appears to be far more common than GAE in Southern Arizona. Risk factors for disease progression and the ameba’s geographic range should be examined.
