Infection Caused by Free Living Amebae
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Inhibition of Fatty Acid Oxidation As a New Target to Treat Primary Amoebic Meningoencephalitis
EXPERIMENTAL THERAPEUTICS crossm Inhibition of Fatty Acid Oxidation as a New Target To Treat Primary Amoebic Meningoencephalitis Maarten J. Sarink,a Aloysius G. M. Tielens,a,b Annelies Verbon,a Robert Sutak,c Jaap J. van Hellemonda a Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands Downloaded from bDepartment of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands cDepartment of Parasitology, Faculty of Science, Charles University, BIOCEV, Vestec, Czech Republic ABSTRACT Primary amoebic meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living amoeba Naegleria fowleri. The amoeba migrates along the ol- factory nerve to the brain, resulting in seizures, coma, and, eventually, death. Previous research has shown that Naegleria gruberi, a close relative of N. fowleri, prefers lipids over glucose as an energy source. Therefore, we tested several already-approved inhibi- http://aac.asm.org/ tors of fatty acid oxidation alongside the currently used drugs amphotericin B and milte- fosine. Our data demonstrate that etomoxir, orlistat, perhexiline, thioridazine, and val- proic acid inhibited growth of N. gruberi. We then tested these compounds on N. fowleri and found etomoxir, perhexiline, and thioridazine to be effective growth inhibitors. Hence, not only are lipids the preferred food source for N. gruberi, but also oxidation of fatty acids seems to be essential for growth of N. fowleri. Inhibition of fatty acid oxida- tion could result in new treatment options, as thioridazine inhibits N. fowleri growth in concentrations that can be reached at the site of infection. It could also potentiate cur- rently used therapy, as checkerboard assays revealed synergy between miltefosine and on August 4, 2020 by guest etomoxir. -
Protistology Mitochondrial Genomes of Amoebozoa
Protistology 13 (4), 179–191 (2019) Protistology Mitochondrial genomes of Amoebozoa Natalya Bondarenko1, Alexey Smirnov1, Elena Nassonova1,2, Anna Glotova1,2 and Anna Maria Fiore-Donno3 1 Department of Invertebrate Zoology, Faculty of Biology, Saint Petersburg State University, 199034 Saint Petersburg, Russia 2 Laboratory of Cytology of Unicellular Organisms, Institute of Cytology RAS, 194064 Saint Petersburg, Russia 3 University of Cologne, Institute of Zoology, Terrestrial Ecology, 50674 Cologne, Germany | Submitted November 28, 2019 | Accepted December 10, 2019 | Summary In this mini-review, we summarize the current knowledge on mitochondrial genomes of Amoebozoa. Amoebozoa is a major, early-diverging lineage of eukaryotes, containing at least 2,400 species. At present, 32 mitochondrial genomes belonging to 18 amoebozoan species are publicly available. A dearth of information is particularly obvious for two major amoebozoan clades, Variosea and Tubulinea, with just one mitochondrial genome sequenced for each. The main focus of this review is to summarize features such as mitochondrial gene content, mitochondrial genome size variation, and presence or absence of RNA editing, showing if they are unique or shared among amoebozoan lineages. In addition, we underline the potential of mitochondrial genomes for multigene phylogenetic reconstruction in Amoebozoa, where the relationships among lineages are not fully resolved yet. With the increasing application of next-generation sequencing techniques and reliable protocols, we advocate mitochondrial -
The Intestinal Protozoa
The Intestinal Protozoa A. Introduction 1. The Phylum Protozoa is classified into four major subdivisions according to the methods of locomotion and reproduction. a. The amoebae (Superclass Sarcodina, Class Rhizopodea move by means of pseudopodia and reproduce exclusively by asexual binary division. b. The flagellates (Superclass Mastigophora, Class Zoomasitgophorea) typically move by long, whiplike flagella and reproduce by binary fission. c. The ciliates (Subphylum Ciliophora, Class Ciliata) are propelled by rows of cilia that beat with a synchronized wavelike motion. d. The sporozoans (Subphylum Sporozoa) lack specialized organelles of motility but have a unique type of life cycle, alternating between sexual and asexual reproductive cycles (alternation of generations). e. Number of species - there are about 45,000 protozoan species; around 8000 are parasitic, and around 25 species are important to humans. 2. Diagnosis - must learn to differentiate between the harmless and the medically important. This is most often based upon the morphology of respective organisms. 3. Transmission - mostly person-to-person, via fecal-oral route; fecally contaminated food or water important (organisms remain viable for around 30 days in cool moist environment with few bacteria; other means of transmission include sexual, insects, animals (zoonoses). B. Structures 1. trophozoite - the motile vegetative stage; multiplies via binary fission; colonizes host. 2. cyst - the inactive, non-motile, infective stage; survives the environment due to the presence of a cyst wall. 3. nuclear structure - important in the identification of organisms and species differentiation. 4. diagnostic features a. size - helpful in identifying organisms; must have calibrated objectives on the microscope in order to measure accurately. -
Primary Amoebic Meningoencephalitis Due to Naegleria Fowleri
56 Case report Primary amoebic meningoencephalitis due to Naegleria fowleri A. Angrup, L. Chandel, A. Sood, K. Thakur, S. C. Jaryal Department of Microbiology,Dr. Rajendra Prasad Government Medical College, Kangra at Tanda, Himachal Pradesh, Pin Code- 176001, India. Correspondence to: Dr. Archana Angrup, Department of Microbiology, Dr. Rajendra Prasad Government Medical College, Kangra, Tanda, Himachal Pradesh, Pin Code-176001, India. Phone no. 09418119222, Facsimile: 01892-267115 Email: [email protected] Abstract The genus Naegleria comprises of free living ameboflagellates found in soil and fresh water. More than 30 species have been isolated but only N. fowleri has been associated with human disease. N. fowleri causes primary amoebic meningoencephalitis (PAM), an acute, often fulminant infection of CNS. Here we report a rare and first case of PAM in an immunocompetent elderly patient from this part of the country. Amoeboid and flagellate forms of N. fowleri were detected in the direct microscopic examination of CSF and confirmed by flagellation test in distilled water, demonstrating plaques /clear areas on 1.5% non nutrient agar and its survival at 42°C. Keywords: Meningitis, Naegleria fowleri, primary amoebic meningoencephalitis Introduction of our knowledge, in India, only eight cases have been reported so far .1, 5-8 Infection of the central nervous system (CNS) in human We hereby report a rare case of PAM in elderly beings with free living amoebae is uncommon. Among the immunocompetent patient from the hilly state of Himachal many different genera of amoebae, Naegleria spp, Pradesh (H.P) in Northern India. Acanthamoeba spp and Balamuthia spp are primarily pathogenic to the CNS. -
Acanthamoeba Spp., Balamuthia Mandrillaris, Naegleria Fowleri, And
MINIREVIEW Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris , Naegleria fowleri , and Sappinia diploidea Govinda S. Visvesvara1, Hercules Moura2 & Frederick L. Schuster3 1Division of Parasitic Diseases, National Center for Infectious Diseases, Atlanta, Georgia, USA; 2Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; and 3Viral and Rickettsial Diseases Laboratory, California Department of Health Services, Richmond, California, USA Correspondence: Govinda S. Visvesvara, Abstract Centers for Disease Control and Prevention, Chamblee Campus, F-36, 4770 Buford Among the many genera of free-living amoebae that exist in nature, members of Highway NE, Atlanta, Georgia 30341-3724, only four genera have an association with human disease: Acanthamoeba spp., USA. Tel.: 1770 488 4417; fax: 1770 488 Balamuthia mandrillaris, Naegleria fowleri and Sappinia diploidea. Acanthamoeba 4253; e-mail: [email protected] spp. and B. mandrillaris are opportunistic pathogens causing infections of the central nervous system, lungs, sinuses and skin, mostly in immunocompromised Received 8 November 2006; revised 5 February humans. Balamuthia is also associated with disease in immunocompetent chil- 2007; accepted 12 February 2007. dren, and Acanthamoeba spp. cause a sight-threatening infection, Acanthamoeba First published online 11 April 2007. keratitis, mostly in contact-lens wearers. Of more than 30 species of Naegleria, only one species, N. fowleri, causes an acute and fulminating meningoencephalitis in DOI:10.1111/j.1574-695X.2007.00232.x immunocompetent children and young adults. In addition to human infections, Editor: Willem van Leeuwen Acanthamoeba, Balamuthia and Naegleria can cause central nervous system infections in animals. Because only one human case of encephalitis caused by Keywords Sappinia diploidea is known, generalizations about the organism as an agent of primary amoebic meningoencephalitis; disease are premature. -
Leishmaniasis in the United States: Emerging Issues in a Region of Low Endemicity
microorganisms Review Leishmaniasis in the United States: Emerging Issues in a Region of Low Endemicity John M. Curtin 1,2,* and Naomi E. Aronson 2 1 Infectious Diseases Service, Walter Reed National Military Medical Center, Bethesda, MD 20814, USA 2 Infectious Diseases Division, Uniformed Services University, Bethesda, MD 20814, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-011-301-295-6400 Abstract: Leishmaniasis, a chronic and persistent intracellular protozoal infection caused by many different species within the genus Leishmania, is an unfamiliar disease to most North American providers. Clinical presentations may include asymptomatic and symptomatic visceral leishmaniasis (so-called Kala-azar), as well as cutaneous or mucosal disease. Although cutaneous leishmaniasis (caused by Leishmania mexicana in the United States) is endemic in some southwest states, other causes for concern include reactivation of imported visceral leishmaniasis remotely in time from the initial infection, and the possible long-term complications of chronic inflammation from asymptomatic infection. Climate change, the identification of competent vectors and reservoirs, a highly mobile populace, significant population groups with proven exposure history, HIV, and widespread use of immunosuppressive medications and organ transplant all create the potential for increased frequency of leishmaniasis in the U.S. Together, these factors could contribute to leishmaniasis emerging as a health threat in the U.S., including the possibility of sustained autochthonous spread of newly introduced visceral disease. We summarize recent data examining the epidemiology and major risk factors for acquisition of cutaneous and visceral leishmaniasis, with a special focus on Citation: Curtin, J.M.; Aronson, N.E. -
Drugs for Amebiais, Giardiasis, Trichomoniasis & Leishmaniasis
Antiprotozoal drugs Drugs for amebiasis, giardiasis, trichomoniasis & leishmaniasis Edited by: H. Mirkhani, Pharm D, Ph D Dept. Pharmacology Shiraz University of Medical Sciences Contents Amebiasis, giardiasis and trichomoniasis ........................................................................................................... 2 Metronidazole ..................................................................................................................................................... 2 Iodoquinol ........................................................................................................................................................... 2 Paromomycin ...................................................................................................................................................... 3 Mechanism of Action ...................................................................................................................................... 3 Antimicrobial effects; therapeutics uses ......................................................................................................... 3 Leishmaniasis ...................................................................................................................................................... 4 Antimonial agents ............................................................................................................................................... 5 Mechanism of action and drug resistance ...................................................................................................... -
Visceral Leishmaniasis: a Global Overview
J Glob Health Sci. 2020 Jun;2(1):e3 https://doi.org/10.35500/jghs.2020.2.e3 pISSN 2671-6925·eISSN 2671-6933 Review Article Visceral leishmaniasis: a global overview Richard G. Wamai ,1 Jorja Kahn ,2 Jamie McGloin ,3 Galen Ziaggi 3 1Department of Cultures, Societies and Global Studies, Northeastern University, College of Social Sciences and Humanities, Integrated Initiative for Global Health, Boston, MA, USA 2Department of Behavioral Neuroscience, Northeastern University, College of Science, Boston, MA, USA 3Department of Health Sciences, Northeastern University, Bouvé College of Health Science, Boston, MA, USA Received: Feb 1, 2020 ABSTRACT Accepted: Mar 14, 2020 Correspondence to The leishmaniases are protozoan infections that are among the neglected tropical diseases Richard G. Wamai (NTDs). Over one billion people are at risk of these diseases in virtually all continents. Department of Cultures, Societies and Global These diseases debilitate large numbers of people, keeping them from full, productive lives. Studies, Northeastern University, College of Visceral leishmaniasis (VL) is the most severe form of these diseases, killing more people Social Sciences and Humanities, Integrated Initiative for Global Health, 360 Huntington than any other parasitic disease except malaria. About 90% of the global burden for VL is Ave., Boston, MA 02115, USA. found in just 7 countries, 4 of which are in Eastern Africa (Sudan, South Sudan, Ethiopia E-mail: [email protected] and Kenya), 2 in Southeast Asia (India, Bangladesh) and Brazil, which carries nearly all of cases in South America. In 2005 the World Health Organization launched a strategy to © 2020 Korean Society of Global Health. -
Accomplishments 2013
National Center for Emerging and Zoonotic Infectious Diseases Accomplishments 2013 The National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) works to improve public health at home and around the world by protecting people from • Foodborne and waterborne illnesses • Deadly diseases like Ebola, anthrax, and rabies • Infections spread by animals, mosquitoes, ticks, and fleas • Infections in healthcare facilities or drug-resistant threats • Illnesses that cross borders and affect refugees, immigrants, and travelers Responding to outbreaks in the United States and across the globe In fiscal year 2013 (FY 2013), NCEZID regularly received requests from states and other countries to assist in the investigation of local, national, and international outbreaks of infectious diseases, known as Epi-Aids (see examples in the boxes on the bottom of pages 2–7). In addition to participating in more than 35 Epi-Aids, NCEZID supported health departments’ response to a variety of outbreaks through epidemiologic investigations, phone consultations, and technical assistance. CDC maintains an up-to-date list of current outbreaks on its website. National Center for Emerging and Zoonotic Infectious Diseases Office of the Director CS241973-A National Center for Emerging and Zoonotic Infectious Diseases Protecting public water systems and the public from Naegleria fowleri (brain-eating ameba) infections After the death of a child staying in St. Bernard Parish, Louisiana, NCEZID laboratories confirmed the presence of the brain-eating ameba Naegleria fowleri in the parish’s treated public water system. NCEZID worked with state public health officials and the US Environmental Protection Agency to develop a plan to rid the system of the ameba and communicate with residents about steps they can take to protect themselves. -
Guidelines for Diagnosis, Treatment and Prevention of Visceral Leishmaniasis in South Sudan
Guidelines for diagnosis, treatment and prevention of visceral leishmaniasis in South Sudan Acromyns DAT Direct agglutination test FDA Freeze – dried antigen IM Intramuscular IV Intravenous KA Kala–azar ME Mercaptoethanol ORS Oral rehydration salt PKDL Post kala–azar dermal leishmaniasis RBC Red blood cells RDT Rapid diagnostic test RR Respiratory rate SSG Sodium stibogluconate TFC Therapeutic feeding centre TOC Test of cure VL Visceral leishmaniasis WBC White blood cells WHO World Health Organization Table of contents Acronyms ...................................................................................................................................... 2 Acknowledgements ....................................................................................................................... 4 Foreword ...................................................................................................................................... 5 1. Introduction ........................................................................................................................... 7 1.1 Background information ............................................................................................... 7 1.2 Lifecycle and transmission patterns ............................................................................. 7 1.3 Human infection and disease ....................................................................................... 8 2. Diagnosis .............................................................................................................................. -
The Epidemiology and Clinical Features of Balamuthia Mandrillaris Disease in the United States, 1974 – 2016
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Clin Infect Manuscript Author Dis. Author manuscript; Manuscript Author available in PMC 2020 August 28. Published in final edited form as: Clin Infect Dis. 2019 May 17; 68(11): 1815–1822. doi:10.1093/cid/ciy813. The Epidemiology and Clinical Features of Balamuthia mandrillaris Disease in the United States, 1974 – 2016 Jennifer R. Cope1, Janet Landa1,2, Hannah Nethercut1,3, Sarah A. Collier1, Carol Glaser4, Melanie Moser5, Raghuveer Puttagunta1, Jonathan S. Yoder1, Ibne K. Ali1, Sharon L. Roy6 1Waterborne Disease Prevention Branch, Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA 2James A. Ferguson Emerging Infectious Diseases Fellowship Program, Baltimore, MD, USA 3Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA 4Kaiser Permanente, San Francisco, CA, USA 5Office of Financial Resources, Centers for Disease Control and Prevention Atlanta, GA, USA 6Parasitic Diseases Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, USA Abstract 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. -
Entamoeba Histolytica?
Amebas Friend and foe Facultative Pathogenicity of Entamoeba histolytica? Confusing History 1875 Lösch correlated dysentery with amebic trophozoites 1925 Brumpt proposed two species: E. dysenteriae and E. dispar 1970's biochemical differences noted between invasive and non-invasive isolates 80's/90's several antigenic and DNA differences demonstrated • rRNA 2.2% sequence difference 1993 Diamond and Clark proposed a new species (E. dispar) to describe non-invasive strains 1997 WHO accepted two species 1 Family Entamoebidae Family includes parasites • Entamoeba histolytica and commensals • Entamoeba dispar • Entamoeba coli Species are differentiated • Entamoeba hartmanni based on size, nuclear • Endolimax nana substructures • Iodamoeba bütschlii Entamoeba histolytica one of the most potent killers in nature Entamoeba histolytica • worldwide distribution (cosmopolitan) • higher prevalence in tropical or developing countries (20%) • 1-6% in temperate countries • Possible animal reservoirs • Amebiasis - Amebic dysentery • aka: Montezuma’s revenge Taxonomy • One parasitic species? • E. histolytica • E. dispar • E. hartmanni 2 Entamoeba Life Cycle - Direct Fecal/Oral transmission Cyst - Infective stage Resistant form Trophozoite - feeding, binary fission Different stages of cyst development Precysts - rich in glycogen Young cyst - 2, then 4 nuclei with chromotoid bodies Metacysts - infective stage Metacystic trophozoite - 8 8 Excystation Metacyst Cyst wall disruption Ameba emerges Nuclear division 48 Cytokinesis Nuclear division