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Naveed Ahmed Khan - One of the best experts on this subject based on the ideXlab platform.
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Isoniazid Conjugated Magnetic Nanoparticles Loaded with Amphotericin B as a Potent AntiAmoebic Agent against Acanthamoeba castellanii.
Antibiotics, 2020Co-Authors: Kawish Iqbal, Ayaz Anwar, Areeba Anwar, Sumayah Abdelnasir Osman Abdalla, Kanwal Muhammad Iqbal, Muhammad Raza Shah, Naveed Ahmed KhanAbstract:The pathogenic free-living amoeba, Acanthamoeba castellanii, is responsible for a rare but deadly central nervous system infection, Granulomatous Amoebic Encephalitis and a blinding eye disease called Acanthamoeba keratitis. Currently, a combination of biguanides, amidine, azoles and antibiotics are used to manage these infections; however, the host cell cytotoxicity of these drugs remains a challenge. Furthermore, Acanthamoeba species are capable of transforming to the cyst form to resist chemotherapy. Herein, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with isoniazid, which were further loaded with amphotericin B (ISO-NPs-AMP) to cause potent antiAmoebic effects against Acanthamoeba castellanii. The IC50 of isoniazid conjugated with magnetic nanoparticles and loaded with amphotericin B was found to be 45 μg/mL against Acanthamoeba castellanii trophozoites and 50 μg/mL against cysts. The results obtained in this study have promising implications in drug discovery as these nanomaterials exhibited high trophicidal and cysticidal effects, as well as limited cytotoxicity against rat and human cells.
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AntiAmoebic activity of plant-based natural products and their conjugated silver nanoparticles against Acanthamoeba castellanii (ATCC 50492)
AMB Express, 2020Co-Authors: Areeba Anwar, Naveed Ahmed Khan, Ayaz Anwar, Muhammad Raza Shah, Elaine Lim Siew Ting, Noor Ul Ain, Shaheen Faizi, Ruqaiyyah SiddiquiAbstract:Acanthamoeba spp. are the causative agent of Acanthamoeba keratitis and Granulomatous Amoebic Encephalitis (GAE). The current options to treat Acanthamoeba infections have limited success. Silver nanoparticles show antimicrobial effects and enhance the efficacy of their payload at the specific biological targets. Natural folk plants have been widely used for treating diseases as the phytochemicals from several plants have been shown to exhibit Amoebicidal effects. Herein, we used natural products of plant or commercial sources including quercetin (QT), kolavenic acid (PGEA) isolated from plant extracts of Polyalthia longifolia var pendula and crude plant methanolic extract of Caesalpinia pulcherrima (CPFLM) as antiacanthAmoebic agents. Furthermore, these plant-based materials were conjugated with silver nanoparticles (AgNPs) to determine the effects of the natural compounds and their nanoconjugates against a clinical isolate of A. castellanii from a keratitis patient (ATCC 50492) belonging to the T4 genotype. The compounds were conjugated with AgNPs and characterized by using ultraviolet visible spectrophotometry and atomic force microscopy. Quercetin coated silver nanoparticles (QT-AgNPs) showed characteristic surface plasmon resonance band at 443 nm and the average size distribution was found to be around 45 nm. The natural compounds alone and their nanoconjugates were tested for the viability of amoebae, encystation and excystation activity against A. castellanii. The natural compounds showed significant growth inhibition of A. castellanii while QT-AgNPs specifically exhibited enhanced antiAmoebic effects as well as interrupted the encystation and excystation activity of the amoebae. Interestingly, these compounds and nanoconjugates did not exhibit in vitro cytotoxic effects against human cells. Plant-based compounds and extracts could be an interesting strategy in development of alternative therapeutics against Acanthamoeba infections.
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repositioning of guanabenz in conjugation with gold and silver nanoparticles against pathogenic amoebae acanthamoeba castellanii and naegleria fowleri
ACS Infectious Diseases, 2019Co-Authors: Areeba Anwar, Naveed Ahmed Khan, Mohammad Ridwane Mungroo, Ayaz Anwar, William Sullivan, Ruqaiyyah SiddiquiAbstract:Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating Granulomatous Amoebic Encephalitis and primary Amoebic meningoEncephalitis caused by Acanthamoeba castellanii (A. castellanii) and Naegleria fowleri (N. fowleri), respectively. Here, we report for the first time that guanabenz conjugated to gold and silver nanoparticles has significant antiAmoebic activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles were synthesized by the one-phase reduction method and were characterized by ultraviolet–visible spectrophotometry and atomic force microscopy. Both metals were facilely stabilized by the coating of guanabenz, which was examined by surface plasmon resonance determination. The average size of gold nanoconjugated guanabenz was found to be 60 nm, whereas silver nanoparticles were produced in a larger size ...
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Combating Acanthamoeba spp. cysts: what are the options?
Parasites & Vectors, 2018Co-Authors: Ayaz Anwar, Naveed Ahmed KhanAbstract:Acanthamoeba spp. are protist pathogens and causative agents of serious infections including keratitis and Granulomatous Amoebic Encephalitis. Its ability to convert into dormant and highly resistant cysts form limits effectiveness of available therapeutic agents and presents a pivotal challenge for drug development. During the cyst stage, Acanthamoeba is protected by the presence of hardy cyst walls, comprised primarily of carbohydrates and cyst-specific proteins, hence synthesis inhibition and/or degradation of cyst walls is of major interest. This review focuses on targeting of Acanthamoeba cysts by identifying viable therapeutic targets.
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Brain-Eating Amoebae: Predilection Sites in the Brain and Disease Outcome.
Journal of Clinical Microbiology, 2017Co-Authors: Timothy Yu Yee Ong, Naveed Ahmed KhanAbstract:Acanthamoeba spp. and Balamuthia mandrillaris are causative agents of Granulomatous Amoebic Encephalitis (GAE), while Naegleria fowleri causes primary Amoebic meningoEncephalitis (PAM). PAM is an acute infection that lasts a few days, while GAE is a chronic to subacute infection that can last up to several months. Here, we present a literature review of 86 case reports from 1968 to 2016, in order to explore the affinity of these amoebae for particular sites of the brain, diagnostic modalities, treatment options, and disease outcomes in a comparative manner.
Govinda S. Visvesvara - One of the best experts on this subject based on the ideXlab platform.
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Copyright © 2012 by The American Society of Tropical Medicine and Hygiene Case Report: Treatment of Granulomatous Amoebic Encephalitis with Voriconazole and Miltefosine in an Immunocompetent Soldier
2016Co-Authors: Duncan Webster, Imram Umar, George Kolyvas, Juan M. Bilbao, Marie-christine Guiot, Kevin Duplisea, Yvonne Qvarnstrom, Govinda S. VisvesvaraAbstract:Abstract. A 38-year-old male immunocompetent soldier developed generalized seizures. He underwent surgical debulking and a progressive demyelinating pseudotumor was identified. Serology and molecular testing confirmed a diagnosis of Granulomatous Amoebic Encephalitis caused by Acanthamoeba sp. in this immunocompetent male. The patient was treated with oral voriconazole and miltefosine with Acanthamoeba titers returning to control levels and serial imaging demonstrating resolution of the residual lesion
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sp. Infection with
2013Co-Authors: Er C. Aichelburg, Govinda S. Visvesvara, Julia Walochnik, Ojan Assadian, Andrea Steuer, Horst Aspöck, Helmut Prosch, Gedeon Perneczky, Norbert VetterAbstract:We report on an HIV-negative but immunocompromised patient with disseminated acanthamoebiasis, Granulomatous, Amoebic Encephalitis, and underlying miliary tuberculosis and tuberculous meningitis. The patient responded favorably to treatment with miltefosine, an alkylphosphocholine. The patient remained well with no signs of infection 2 years after treatment cessation. 25-year-old man from India, who had been living in A Austria for 7 years and had no previous history of major illnesses, was brought by ambulance to the hospital for dyspnea, cough, fever, and weight loss. During neurologic examination, a hearing impairment was suspected. The patient was unable to walk because of severe ataxia. Skin examination showed several necrotic ulcers with purulent discharge and black eschars, measuring 0.5 cm to 3 cm, located on the skull, back, neck, and arms (Figure 1, panels A and B). Miliary tuberculosis (TB) of the lungs, liver, spleen, and kidneys was suspected on the basis of chest radiography and computed tomography (CT) of chest and abdomen. Ziehl-Nielsen (ZN) staining for acid-fast bacilli in sputum, bronchial secretions, and lavage obtained through bronchoscopy was negative. PCR for Mycobacterium tuberculosis in bronchial secretions and serum was positive. Culture on Loewenstein agar resulted in growth of nonresistant M. tuberculosis after 31 days. Blood cultures were negative for aerobic/anaerobic bacteria, mycobacteria, and fungi. Results of serologic tests were negative for Aspergillus
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Balamuthia mandrillaris Encephalitis: Survival of a Child With Severe MeningoEncephalitis and Review of the Literature.
Journal of the Pediatric Infectious Diseases Society, 2013Co-Authors: Paul Moriarty, Govinda S. Visvesvara, Mohammad Shekeeb Shahab, Christopher Burke, David Mccrossin, Robert Campbell, Sarah Cherian, Clare NourseAbstract:Balamuthia mandrillaris causes Granulomatous Amoebic Encephalitis, which is frequently fatal. There are few reports of survival in children. A 4-year-old child developed severe meningoEncephalitis with multiple intracranial ring-enhancing lesions. Empiric therapy was commenced after a biopsy was performed, and the patient had a good clinical response. Molecular testing and indirect immunofluorescence later confirmed the diagnosis of Balamuthia Encephalitis. Diagnosis of Balamuthia Encephalitis is often delayed. The literature is reviewed with particular reference to reported survival. Prompt tissue diagnosis and initiation of therapy are common features among survivors. In previous reports, miltefosine was not used to treat children, but it was well tolerated in this case and should be considered as a therapeutic option.
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the mitochondrial genome and a 60 kb nuclear dna segment from naegleria fowleri the causative agent of primary Amoebic meningoEncephalitis
Journal of Eukaryotic Microbiology, 2013Co-Authors: Emily K Herman, Govinda S. Visvesvara, Francine Marcianocabral, Alexander L Greninger, Joel B Dacks, Charles Y ChiuAbstract:Naegleria fowleri is a unicellular eukaryote causing primary Amoebic meningoEncephalitis, a neuropathic disease killing 99% of those infected, usually within 7– 14 days. Naegleria fowleri is found globally in regions including the US and Australia. The genome of the related nonpathogenic species Naegleria gruberi has been sequenced, but the genetic basis for N. fowleri pathogenicity is unclear. To generate such insight, we sequenced and assembled the mitochondrial genome and a 60-kb segment of nuclear genome from N. fowleri. The mitochondrial genome is highly similar to its counterpart in N. gruberi in gene complement and organization, while distinct lack of synteny is observed for the nuclear segments. Even in this short (60-kb) segment, we identified examples of potential factors for pathogenesis, including ten novel N. fowleri-specific genes. We also identified a homolog of cathepsin B; proteases proposed to be involved in the pathogenesis of diverse eukaryotic pathogens, including N. fowleri. Finally, we demonstrate a likely case of horizontal gene transfer between N. fowleri and two unrelated amoebae, one of which causes Granulomatous Amoebic Encephalitis. This initial look into the N. fowleri nuclear genome has revealed several examples of potential pathogenesis factors, improving our understanding of a neglected pathogen of increasing global importance.
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Treatment of Granulomatous Amoebic Encephalitis with voriconazole and miltefosine in an immunocompetent soldier.
The American Journal of Tropical Medicine and Hygiene, 2012Co-Authors: Duncan Webster, Imram Umar, George Kolyvas, Juan M. Bilbao, Marie-christine Guiot, Kevin Duplisea, Yvonne Qvarnstrom, Govinda S. VisvesvaraAbstract:A 38-year-old male immunocompetent soldier developed generalized seizures. He underwent surgical debulking and a progressive demyelinating pseudotumor was identified. Serology and molecular testing confirmed a diagnosis of Granulomatous Amoebic Encephalitis caused by Acanthamoeba sp. in this immunocompetent male. The patient was treated with oral voriconazole and miltefosine with Acanthamoeba titers returning to control levels and serial imaging demonstrating resolution of the residual lesion.
Abdul Mannan Baig - One of the best experts on this subject based on the ideXlab platform.
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A proposed cascade of vascular events leading to Granulomatous Amoebic Encephalitis.
Microbial Pathogenesis, 2015Co-Authors: Abdul Mannan Baig, Naveed Ahmed KhanAbstract:Granulomatous Amoebic Encephalitis due to Acanthamoeba is a chronic disease that almost always results in death. Hematogenous spread is a pre-requisite followed by amoebae invasion of the blood-brain barrier to enter the central nervous system. Given the systemic nature of this infection, a significant latent period of several months before the appearance of clinical manifestations is puzzling. Based on reported cases, here we propose pathogenetic mechanisms that explain the above described latency of the disease.
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Granulomatous Amoebic Encephalitis: ghost response of an immunocompromised host?
Journal of Medical Microbiology, 2014Co-Authors: Abdul Mannan BaigAbstract:Naegleria fowleri, Acanthamoeba and Balamuthia mandrillaris spp. are known to cause fatal Amoebic Encephalitis. Here, I attempt to draw attention to these cases, which are reported as ‘Granulomatous Amoebic Encephalitis’ (GAE), and their occurrence in immunocompromised individuals and patients with AIDS. GAE, like any other Granulomatous inflammation, can occur only in the presence of ample numbers of CD4+ T-lymphocytes. Extensive reviews of manuscripts published over a period of 50 years on this topic and cytokine studies and/or morphological evidence provided in peer-reviewed published studies were evaluated in detail by independent resources to analyse the Granulomatous inflammatory evidence provided to justify the title of GAE in this group of patients. The evidence given in support of GAE did not appear to be convincing enough in the majority of published studies, and in particular its occurrence in patients with AIDS and other immunocompromised states was not justified. The distinction between the early development of type IV hypersensitivity reactions and granuloma/Granulomatous inflammation was found to be vague and inconclusive. It is therefore recommended that this terminology is used only when all the diagnostic criteria have been met, and use of a term such as ‘granulomatoid’ is suggested in cases where there remains an ambiguity in the morphological appearance of the lesions, especially in AIDS and related diseases
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Laboratory testing of clinically approved drugs against Balamuthia mandrillaris
World Journal of Microbiology and Biotechnology, 2014Co-Authors: Huma Kalsoom, Abdul Mannan Baig, Naveed Ahmed KhanAbstract:Balamuthia mandrillaris is a free-living protist pathogen that can cause life-threatening Granulomatous Amoebic Encephalitis. Given the lack of effective available drugs against B. mandrillaris Encephalitis with a mortality rate of more than 90 %, here we screened drugs, targeting vital cellular receptors and biochemical pathways, that are already in approved clinical use for their potential clinical usefulness. Amoebicidal assays were performed by incubating B. mandrillaris with drugs (3 × 10^5 cells/0.5 mL/well) in phosphate buffered saline for 24 h and viability was determined using Trypan blue exclusion staining. For controls, amoebae were incubated with the solvent alone. To determine whether effects are reversible, B. mandrillaris were pre-exposed to drugs for 24 h, washed twice, and incubated with human brain microvascular endothelial cells, which constitute the blood–brain barrier as food source, for up to 48 h. Of the ten drugs tested, amlodipine, apomorphine, demethoxycurcumin, haloperidol, loperamide, prochlorperazine, procyclidine, and resveratrol showed potent Amoebicidal effects, while amiodarone and digoxin exhibited minimal effectiveness. When pre-treated with these drugs, no viable trophozoites re-emerged, suggesting that drugs destroyed parasite irreversibly. Based on the in vitro assay, amlodipine, apomorphine, demethoxycurcumin, haloperidol, loperamide, prochlorperazine, procyclidine, and resveratrol are potential antimicrobials for further testing against B. mandrillaris Encephalitis. These findings may provide novel strategies for therapy but further research is needed to determine clinical usefulness of aforementioned drugs against Granulomatous Amoebic Encephalitis caused by B. mandrillaris , and other free-living amoebae, such as Acanthamoeba spp., and Naegleria fowleri .
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Combined drug therapy in the management of Granulomatous Amoebic Encephalitis due to Acanthamoeba spp., and Balamuthia mandrillaris
Experimental Parasitology, 2014Co-Authors: Huma Kulsoom, Abdul Mannan Baig, Naveed Ahmed KhanAbstract:Granulomatous Amoebic Encephalitis (GAE) is caused by two protist pathogens, Acanthamoeba spp., and Balamuthia mandrillaris. Although rare, it almost always results in death. In the present study, amoebae were treated with various combinations of clinically-approved drugs, targeting vital cellular receptors and biochemical pathways. The results revealed that among the seven different combinations tested, three proved highly effective against both Acanthamoeba castellanii as well as B. mandrillaris at a concentration of 100μM. These combinations included (i) prochlorperazine plus loperamide; (ii) prochlorperazine plus apomorphine; and (iii) procyclidine plus loperamide. In viability assays, none of the drug-treated amoebae emerged as viable trophozoites, suggesting irreversible Amoebicidal effects. Four combinations of drugs tested showed varied potency against A. castellanii and B. mandrillaris at 100μM. The combination of haloperidol and loperamide was highly effective against A. castellanii at 100μM, but potent effects against B. mandrillaris were observed only at 250μM. Digoxin and amlodipine were effective against A. castellanii and B. mandrillaris at 100μM and 250μM, respectively. In contrast, the combination of apomorphine and haloperidol was effective against B. mandrillaris and A. castellanii at 100μM and 250μM, respectively. At 100μM, the combination of procyclidine and amiodarone was effective against neither A. castellanii nor B. mandrillaris. In this case, Amoebicidal properties were observed at 750μM for A. castellanii, and 950μM for B. mandrillaris. As these drugs are used clinically against non-communicable diseases, the findings reported here have the potential to be tested in a clinical setting against Amoebic Encephalitis caused by A. castellanii and B. mandrillaris.
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in vitro efficacies of clinically available drugs against growth and viability of an acanthamoeba castellanii keratitis isolate belonging to the t4 genotype
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Abdul Mannan Baig, Junaid Iqbal, Naveed Ahmed KhanAbstract:The effects of clinically available drugs targeting muscarinic cholinergic, adrenergic, dopaminergic, and serotonergic receptors; intracellular calcium levels and/or the function of calcium-dependent biochemical pathways; ion channels; and cellular pumps were tested against a keratitis isolate of Acanthamoeba castellanii belonging to the T4 genotype. In vitro growth inhibition (amoebistatic) assays were performed by incubating A. castellanii with various concentrations of drugs in the growth medium for 48 h at 30°C. To determine Amoebicidal effects, amoebae were incubated with drugs in phosphate-buffered saline for 24 h, and viability was determined using trypan blue exclusion staining. For controls, amoebae were incubated with the solvent alone. Of the eight drugs tested, amlodipine, prochlorperazine, and loperamide showed potent Amoebicidal effects, as no viable trophozoites were observed (>95% kill rate), while amiodarone, procyclidine, digoxin, and apomorphine exhibited up to 50% Amoebicidal effects. In contrast, haloperidol did not affect viability, but all the drugs tested inhibited A. castellanii growth. Importantly, amlodipine, prochlorperazine, and loperamide showed compelling cysticidal effects. The cysticidal effects were irreversible, as cysts treated with the aforementioned drugs did not reemerge as viable amoebae upon inoculation in the growth medium. Except for apomorphine and haloperidol, all the tested drugs blocked trophozoite differentiation into cysts in encystation assays. Given the limited availability of effective drugs to treat amoebal infections, the clinically available drugs tested in this study represent potential agents for managing keratitis and Granulomatous Amoebic Encephalitis caused by Acanthamoeba spp. and possibly against other meningoEncephalitis-causing amoebae, such as Balamuthia mandrillaris and Naegleria fowleri.
Yuzuru Kanakura - One of the best experts on this subject based on the ideXlab platform.
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A case report of Granulomatous Amoebic Encephalitis by Group 1 Acanthamoeba genotype T18 diagnosed by the combination of morphological examination and genetic analysis.
Diagnostic Pathology, 2018Co-Authors: Takahiro Matsui, Kenji Yagita, Tetsuo Maeda, Shinsuke Kusakabe, Hideyuki Arita, Eiichi Morii, Yuzuru KanakuraAbstract:The diagnosis of Granulomatous Amoebic Encephalitis is challenging for clinicians because it is a rare and lethal disease. Previous reports have indicated that Acanthamoeba with some specific genotypes tend to cause the majority of human infections. We report a case of Granulomatous Amoebic Encephalitis caused by Acanthamoeba spp. with genotype T18 in an immunodeficient patient in Japan after allogenic bone marrow transplantation, along with the morphological characteristics and genetic analysis. A 52-year old man, who had undergone allogenic bone marrow transplantation, suffered from rapid-growing brain masses in addition to pneumonia and died within 1 month from the onset of the symptoms including fever, headache and disorientation. Infection with Acanthamoeba in the brain and lung was confirmed by histological evaluation; immunohistochemical staining and polymerase chain reaction analysis using autopsy samples also indicated the growth of Acanthamoeba in the brain. Gene sequence analysis indicated that this is the second documented case of infection with Acanthamoeba spp. with genotype T18 in a human host. Postmortem retrospective evaluation of cerebrospinal fluid sample in our case, as well as literature review, indicated that some cases of Granulomatous Amoebic Encephalitis caused by Acanthamoeba may be diagnosable by cerebrospinal fluid examination. This case indicates that Acanthamoeba spp. with genotype T18 can also be an important opportunistic pathogen. For pathologists as well as physicians, increased awareness of Granulomatous Amoebic Encephalitis is important for improving the poor prognosis along with the attempt to early diagnosis with cerebrospinal fluid.
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A case report of Granulomatous Amoebic Encephalitis by Group 1 Acanthamoeba genotype T18 diagnosed by the combination of morphological examination and genetic analysis
BMC, 2018Co-Authors: Takahiro Matsui, Kenji Yagita, Tetsuo Maeda, Shinsuke Kusakabe, Hideyuki Arita, Eiichi Morii, Yuzuru KanakuraAbstract:Abstract Background The diagnosis of Granulomatous Amoebic Encephalitis is challenging for clinicians because it is a rare and lethal disease. Previous reports have indicated that Acanthamoeba with some specific genotypes tend to cause the majority of human infections. We report a case of Granulomatous Amoebic Encephalitis caused by Acanthamoeba spp. with genotype T18 in an immunodeficient patient in Japan after allogenic bone marrow transplantation, along with the morphological characteristics and genetic analysis. Case presentation A 52-year old man, who had undergone allogenic bone marrow transplantation, suffered from rapid-growing brain masses in addition to pneumonia and died within 1 month from the onset of the symptoms including fever, headache and disorientation. Infection with Acanthamoeba in the brain and lung was confirmed by histological evaluation; immunohistochemical staining and polymerase chain reaction analysis using autopsy samples also indicated the growth of Acanthamoeba in the brain. Gene sequence analysis indicated that this is the second documented case of infection with Acanthamoeba spp. with genotype T18 in a human host. Postmortem retrospective evaluation of cerebrospinal fluid sample in our case, as well as literature review, indicated that some cases of Granulomatous Amoebic Encephalitis caused by Acanthamoeba may be diagnosable by cerebrospinal fluid examination. Conclusion This case indicates that Acanthamoeba spp. with genotype T18 can also be an important opportunistic pathogen. For pathologists as well as physicians, increased awareness of Granulomatous Amoebic Encephalitis is important for improving the poor prognosis along with the attempt to early diagnosis with cerebrospinal fluid
Ruqaiyyah Siddiqui - One of the best experts on this subject based on the ideXlab platform.
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AntiAmoebic activity of plant-based natural products and their conjugated silver nanoparticles against Acanthamoeba castellanii (ATCC 50492)
AMB Express, 2020Co-Authors: Areeba Anwar, Naveed Ahmed Khan, Ayaz Anwar, Muhammad Raza Shah, Elaine Lim Siew Ting, Noor Ul Ain, Shaheen Faizi, Ruqaiyyah SiddiquiAbstract:Acanthamoeba spp. are the causative agent of Acanthamoeba keratitis and Granulomatous Amoebic Encephalitis (GAE). The current options to treat Acanthamoeba infections have limited success. Silver nanoparticles show antimicrobial effects and enhance the efficacy of their payload at the specific biological targets. Natural folk plants have been widely used for treating diseases as the phytochemicals from several plants have been shown to exhibit Amoebicidal effects. Herein, we used natural products of plant or commercial sources including quercetin (QT), kolavenic acid (PGEA) isolated from plant extracts of Polyalthia longifolia var pendula and crude plant methanolic extract of Caesalpinia pulcherrima (CPFLM) as antiacanthAmoebic agents. Furthermore, these plant-based materials were conjugated with silver nanoparticles (AgNPs) to determine the effects of the natural compounds and their nanoconjugates against a clinical isolate of A. castellanii from a keratitis patient (ATCC 50492) belonging to the T4 genotype. The compounds were conjugated with AgNPs and characterized by using ultraviolet visible spectrophotometry and atomic force microscopy. Quercetin coated silver nanoparticles (QT-AgNPs) showed characteristic surface plasmon resonance band at 443 nm and the average size distribution was found to be around 45 nm. The natural compounds alone and their nanoconjugates were tested for the viability of amoebae, encystation and excystation activity against A. castellanii. The natural compounds showed significant growth inhibition of A. castellanii while QT-AgNPs specifically exhibited enhanced antiAmoebic effects as well as interrupted the encystation and excystation activity of the amoebae. Interestingly, these compounds and nanoconjugates did not exhibit in vitro cytotoxic effects against human cells. Plant-based compounds and extracts could be an interesting strategy in development of alternative therapeutics against Acanthamoeba infections.
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repositioning of guanabenz in conjugation with gold and silver nanoparticles against pathogenic amoebae acanthamoeba castellanii and naegleria fowleri
ACS Infectious Diseases, 2019Co-Authors: Areeba Anwar, Naveed Ahmed Khan, Mohammad Ridwane Mungroo, Ayaz Anwar, William Sullivan, Ruqaiyyah SiddiquiAbstract:Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating Granulomatous Amoebic Encephalitis and primary Amoebic meningoEncephalitis caused by Acanthamoeba castellanii (A. castellanii) and Naegleria fowleri (N. fowleri), respectively. Here, we report for the first time that guanabenz conjugated to gold and silver nanoparticles has significant antiAmoebic activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles were synthesized by the one-phase reduction method and were characterized by ultraviolet–visible spectrophotometry and atomic force microscopy. Both metals were facilely stabilized by the coating of guanabenz, which was examined by surface plasmon resonance determination. The average size of gold nanoconjugated guanabenz was found to be 60 nm, whereas silver nanoparticles were produced in a larger size ...
