DOCSLIB.ORG

Entamoeba Histos>Fca and Entamoeba Dispar

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Entamoeba Histos>Fca and Entamoeba Dispar Entamoeba histoS>fcaand Entamoeba dispar: Mechanisms of adherence and implications for virulence Dylan Ravindran Pillai A thesis subrnitted in confonnity with the requirements for the degree of Doctor of Philosophy Institute of Medicai Science University of Toronto O Copyright Dylan R. Pillai, 2000 AcquiSiiand Acquisiins et Bblibgtaphic Services services bibliographques The author has granteci a non- L'auteur a accordé une licence non exclusive iicence allowing the exclusive pettantà la National Lïbrary of Canada to BïbIioth&pe nationale du Canada de reproduce, loan, disûibute or seil reproduire, prêter, disniiuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfichef61m, de reproduction sur papier ou sur fotmat electronique. The author retams ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts hmit Ni la thèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimes reproduced without the author's ou autrement reproduits sans son permission. autonsatioa, In 1925, Emile Brumpt had proposed the existence of two morphologically identical species, Entarnoeba hisrolylica (a human pathogen) and Entmoeba dispm (a non-pathogenic human commensal). Recent molecuiar and genetic evidence has supported the two-species concept. The pathogen relies on the galactose/N-Acetyl-O- galactosamine Iecth for adherence that leads to contact-dependent cytolysis of host target ceils, a key step in amebic vinilence. Work presented here explores the structure, fiinction, and expression of the lectin nom E-histoZyticu and E-dispar. We hypothesized that molecular differences between the pathogenic and non-pathogenic lectin homologues would be instructive in understanding the differentid role of each in colonization (E-dispor) versus invasion (E.histolytica). To acheive this, a gene encoding the lectin in E-dispar (dhgI2) was cloned and sequenced. Homologous lectin message and proteh levels in E. histolyrica and E-dispur under axenic culture conditions were compared. A heterologous expression system (in COS 7 cells) was constructed to test anti-lectin monoclonal antibody reactivity for E. histoi'ytica and E-dispar lectin homologues. Lech protein, which was generated in COS7 cells, was used for enzyme-linked immunosorbent assays in which antisera from patients infected with pathogen or non-pathogen were tested. Further experiments were also performed in order to localize the carbohydrate recognition domai@) of the amebic lectin using a newly developed in vitro assay. Taken together, evidence is presented supporthg the view that E.histolylica and E-dispar possess highly conserved lectin molecules that are differentially expressed in pathogen vernis non-pathogen. Additional experùnents were Mormed to isolate and characterize a P2 integrin-like molecuie expressed on the amebic dace* Data supporthg the identification of a distinct B2 integrin on the daceof E. histolytica is presented. A putative role for this molecule in amebic virulence is discussed. Finally, epidemioIogîcaI questions regarding E.histolyticu and E.disp4~infections were revisited, now relying on stool antigen immunoassays. These immunoassays, which are able to distinguish E. histoZyticu fiom E.dispar9demonstrated that the overwhelming majonty of infections in a non-endemic setting are caused by the non-pathogen. These results have broad clinical implications since specific molecdar diagnosis would obviate the need for unnecessary chemotherapy of E-dispar infections, with its attendant costs, nsk of side effects, and danger of drug resistance. iii This work is dedicated to my parents, Sam and Kamala, whose love and sacrince are the source of my energies. Above d,I would like to th& Kevin Kain for the guidance, mentorship, and enthusiasm in his laboratory dining the course ofthis work. I would also Wre to dia& Me1 Silverman for having the vision to pursue and foster the MD/PhD programs in Canada, and for aiiowing me to be a part of it at the University of Toronto in my hometown. 1wouid iike to express my gratitude to members of my advisory cornmittee James Brunton, Ian Crandall, and Keiiy MacDonald. Not least, 1owe a great deal to Seth Bitting, Charles Dela Cruz, Anand Ghanekar, Shankar Karunanithi, Rhona Liridsay, Bryan Lo, Christopher Rickerd, and Mieke va.Zante for their golden companionship in recent years, 1- Introduction: Amebiasis and Entmoeba histolyticu infection................................ 1 1.1 Epidemiology of amebiasis: Entmoeba hisrolyh'cu and E. dispar ....... -2 1.2 Current diagnostic ..approach to E.histoZytica Xection............................ 10 1 -3 Treatment of amebiasis. ......................................................... 17 1.4 Pathogenesis of E-hi~olyrcainfection: the key vinilence factors......... 28 1.5 E. histo&tica infection and immunobiology........O......................... 35 1.6 Lectins: an ove~ew............................................................ 41 1.7 The GaVGdNAc Iectin: adhesin and vinilence factor............................. 47 1 -8 Rationaie and Hypotheses....................................................................... 61 1.9 References ....................................................................... -64 II . The cysteine-rich domain of Entamoeba histolytca adherence lectin is sunicient for hi&-aff?nity GaVGaiNAc-specinc binding in vitro ...................................... -87 2.1 Abstract .................................................................................................. -88 2.2 Introduction .......................................................................................... -89 2.3 .Materials & Methods.............................................................................. -90 2.4 Results ...................................................................................................-99 2.5 Discussion. ...................................................................... 109 2.6 References ....................................................................... -113 III. A gene homologous to hgU of Entmoebu histolytica is present and expressed in E. dispar ................... ... ................................................................................... 1 18 3.1 Abstract ................................................................................................... 119 3-2 Introduction.......................................................................................... 120 3 -3. Materials & Methods ............................................................................... 121 3 -4 Results ...............................................................................................126 3.5 Discussion ........................................................................ 131 3 -6 References ....................................................................... -132 N .Molecula. r characteruaton of the WGaINAc lectin of E.dispm ................ -135 4. f Abstract-.............................................................................................. 136 4.2 Introduction.. ........................................................................................ 137 4.3 .Materials & Methods.............................................................................. 139 4-4 Redts. .................................................................................................... 146 4.5 Discussion ........................................................................ 158 4.6 References ........................................................................ 163 V-A novel PZintegrin (CD 18)-Wre molecule participates in Entmoeba histolylica adherence to endothelid celis.. ................................................................................. -168 5.1 Abstract. ............................................................................................ 169 5.2 Introduction............ ... ................................................................... 170 5.3 .Materials & Methods ............................................................................... 172 5 -4 Results .................................................................................................... 1 76 5.5 Discussion ....................................................................... 185 5.6 References. ....................................................................... 189 VI. Entamoeba histolytica and E.dirpar: rnolecular diagnosis. epidemiology. and treatment implications in a non-endemic setting................... .. ............................. 195 6.1 Absmct................................................................................................... 196 6.2 Introduction.......................................................................................... 197 6.3 .Materials & Methods ............................................................................... 199 6.4 Results ...................................... ,... ....................................... 201 6.5 Discussion ........................................................................ 216 6.6 References ........................................................................ 220 VII .Irnmunochromatographic sîrip based detection of Entamoeba histolytica/ E-dispur and Giardia lamblia coproantigen ......................................................... 226
Load more

Recommended publications
  • (Tea Tree) Oil and Dimethyl Sulfoxide (DMSO) Against Trophozoites and Cysts of Acanthamoeba Strains
    pathogens Article In Vitro Evaluation of the Combination of Melaleuca alternifolia (Tea Tree) Oil and Dimethyl Sulfoxide (DMSO) against Trophozoites and Cysts of Acanthamoeba Strains. Oxygen Consumption Rate (OCR) Assay as a Method for Drug Screening Tania Martín-Pérez *, Irene Heredero-Bermejo , Cristina Verdú-Expósito and Jorge Pérez-Serrano Department of Biomedicine and Biotechnology, Faculty of Pharmacy, University of Alcalá, Alcalá de Henares, 28805 Madrid, Spain; [email protected] (I.H.-B.); [email protected] (C.V.-E.); [email protected] (J.P.-S.) * Correspondence: [email protected] Abstract: Ameobae belonging to the genus Acanthamoeba are responsible for the human diseases Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). The treatment of these illnesses is hampered by the existence of a resistance stage (cysts). In an attempt to add new agents that are effective against trophozoites and cysts, tea tree oil (TTO) and dimethyl sulfoxide (DMSO), separately and in combination, were tested In Vitro against two Acanthamoeba isolates, Citation: Martín-Pérez, T.; T3 and T4 genotypes. The oxygen consumption rate (OCR) assay was used as a drug screening Heredero-Bermejo, I.; Verdú-Expósito, method, which is to some extent useful in amoebicide drug screening; however, evaluation of lethal C.; Pérez-Serrano, J. In Vitro effects may be misleading when testing products that promote encystment. Trophozoite viability Evaluation of the Combination of analysis showed that the effectiveness of the combination of both compounds is higher than when Melaleuca alternifolia (Tea Tree) Oil either compound is used alone. Therefore, the TTO alone or TTO + DMSO in combination were and Dimethyl Sulfoxide (DMSO) against Trophozoites and Cysts of an amoebicide, but most of the amoebicidal activity in the combination’s treatments seemed to be Acanthamoeba Strains.
    [Show full text]
  • 2012 Case Definitions Infectious Disease
    Arizona Department of Health Services Case Definitions for Reportable Communicable Morbidities 2012 TABLE OF CONTENTS Definition of Terms Used in Case Classification .......................................................................................................... 6 Definition of Bi-national Case ............................................................................................................................................. 7 ------------------------------------------------------------------------------------------------------- ............................................... 7 AMEBIASIS ............................................................................................................................................................................. 8 ANTHRAX (β) ......................................................................................................................................................................... 9 ASEPTIC MENINGITIS (viral) ......................................................................................................................................... 11 BASIDIOBOLOMYCOSIS ................................................................................................................................................. 12 BOTULISM, FOODBORNE (β) ....................................................................................................................................... 13 BOTULISM, INFANT (β) ...................................................................................................................................................
    [Show full text]
  • Amoebicidal Drugs Lecturer: Danica B
    Amoebicidal Drugs Lecturer: Danica B. Quijano, MD Date Lectured: November 20, 2015 DLSHSI – College of Medicine: PHARMACOLOGY ö Ariba amoeba! Greetings from the amoebas! Yes, ö Improper hygienic practices we’re gonna be talking a lot about the amoeba o Protozoal infections are common among people but only for the Entameoba histolytica , the in underdeveloped tropical & subtropical pathologic agent responsible for the famous countries, where sanitary conditions, hygienic “amoebiasis” we have all heard about. practices, and control of the vectors of ö We will focus our discussion in the transmission are inadequate. However, with pharmacological treatment for infection caused increased world travel, protozoal diseases are by the protozoa Entamoeba histolytica. But first, no longer confined to specific geographical let’s have a glimpse of the offending pathogen. locations. ö Amoebiasis is an infection caused by the E. ö Speaking of diarrhea and travel.. histolytica likewise amoebiasis is sometimes o Good to know: I believe you have heard the incorrectly used to refer to infection with other term Traveler’s diarrhea. Its diagnosis does not amoebae, but strictly speaking it should be imply a specific organism, but Enterotoxigenic E. reserved for E. histolytica infection. coli (ETEC) is the most commonly isolated pathogen. While Backpacker’s diarrhea is also ö Entamoeba is a genus of amoeboid protozoa that known as Giardiasis or Beaver fever because live in the human intestine. giardiasis, caused by the protozoan Giardia o Some species within this genus are harmless, lamblia, frequently infects persons who spend a while others are pathogenic. lot of time camping, backpacking, or hunting, so o One, especially, has the potential to become it has gained the nicknames.
    [Show full text]
  • Investigating Rad51 and Dmc1 in Entamoeba Histolytica: Homologous Recombinases with Drug Target Potential
    Clemson University TigerPrints All Theses Theses August 2020 Investigating Rad51 and Dmc1 in Entamoeba histolytica: Homologous Recombinases with Drug Target Potential Rachel Evelyn Ham Clemson University, [email protected] Follow this and additional works at: https://tigerprints.clemson.edu/all_theses Recommended Citation Ham, Rachel Evelyn, "Investigating Rad51 and Dmc1 in Entamoeba histolytica: Homologous Recombinases with Drug Target Potential" (2020). All Theses. 3392. https://tigerprints.clemson.edu/all_theses/3392 This Thesis is brought to you for free and open access by the Theses at TigerPrints. It has been accepted for inclusion in All Theses by an authorized administrator of TigerPrints. For more information, please contact [email protected]. INVESTIGATING RAD51 AND DMC1 IN ENTAMOEBA HISTOLYTICA: HOMOLOGOUS RECOMBINASES WITH DRUG TARGET POTENTIAL A Thesis Presented to the Graduate School of Clemson University In Partial Fulfillment of the Requirements for the Degree Master of Science Microbiology by Rachel Evelyn Ham August 2020 Accepted by: Dr. Lesly A. Temesvari, Committee Chair Dr. James C. Morris Dr. Yanzhang Wei ABSTRACT Entamoeba histolytica is the causative agent of amebic dysentery and is prevalent in developing countries. It has a biphasic lifecycle: active, virulent trophozoites and dormant, environmentally-stable cysts. Only cysts are capable of establishing new infections, and are spread by fecal deposition. Many unknown factors influence stage conversion, and synchronous encystation of E. histolytica is not currently possible in vitro. E. histolytica infections are treated with nitroimidazole drugs, such as metronidazole (Flagyl™). However, several clinical isolates have shown metronidazole resistance. Enhancing the amebicidal mechanisms of metronidazole through drug combination therapy may allow for more effective treatment.
    [Show full text]
  • Treatment of Dysentery
    Treatment of Dysentery 2-Antimicrobial agents: 1-Maintain fluid intake using: used against the two most common causes which are oral rehydration therapy or intravenous fluid therapy A-Amebic dysentery (protozoal B-Bacillary dysentery infection mainly by Entameba (bacterial infection mainly by Histolytica). shigella). ANTIAMEBIC DRUGS 1-Fluoroquinolones e.g: Ciprofloxacin 2-Cotrimoxazole (trimethoprim and sulfamethoxazole) A- Luminal Amebicides B-Tissue or systemic amebicides 3-Ceriaxone and cefixime 1-Diloxanide furoate 1-Metronidazole 2-Iodoquinol 2-Tinidazole 3-Antibiotics 3-Emetine +Dehydroemetine Paromomycin+Tetracyclin 5-Chloroquine (liver only) ANTIAMEBIC DRUGS : A- Luminal Amebicides Drugs Diloxanide furoate Iodoquino Paromomycin MOA unknown unknown *Has direct amebicidal action(causes leakage by its action on cell membrane of parasite) * Indirect killing of bacterial flora essential for proliferation of pathogenic amoebae. P.K § Ester of diloxanide + furoic acid § Is given orally § Aminoglycoside antibiotic. + § Given orally. § Not absorbed (90%), excreted in feces. § It is given orally and Not absorbed from GIT other features § It splits in tHe intestine, most of diloxanide is absorbed, § 10% enter circulation, excreted as glucouronide in urine. § Effective against luminal forms of ameba conjugated to form a glucoronide wHich is excreted in § effective against the luminal tropHozoites. § Small amount absorbed is excreted unchanged in urine (90%). urine (may accumulate with renal insufficiency) § The unabsorbed diloxanide is the amoebicidal agent (10%). § Direct amoebicidal action against luminal forms. § NOT active against trophozoites in(intestinal wall or extra-intestinal tissues) USES 1-Drug of choice for asymptomatic intestinal infection 1-luminal amoebicide for asymptomatic amebiasis 1-in chronic amebiasis to eliminate cysts , in cysts (drug of choice in cysts passers).
    [Show full text]
  • Antiprotozoal Activity Against Entamoeba Histolytica of Plants Used in Northeast Mexican Traditional Medicine. Bioactive Compoun
    Molecules 2014, 19, 21044-21065; doi:10.3390/molecules191221044 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Article Antiprotozoal Activity against Entamoeba histolytica of Plants Used in Northeast Mexican Traditional Medicine. Bioactive Compounds from Lippia graveolens and Ruta chalepensis Ramiro Quintanilla-Licea 1,*, Benito David Mata-Cárdenas 2, Javier Vargas-Villarreal 3, Aldo Fabio Bazaldúa-Rodríguez 1, Isvar Kavim Ángeles-Hernández 1, Jesús Norberto Garza-González 3 and Magda Elizabeth Hernández-García 3 1 Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Biológicas, Av. Universidad S/N, Cd. Universitaria, San Nicolás de los Garza, C.P. 66451 Nuevo León, Mexico; E-Mails: [email protected] (A.F.B.-R.); [email protected] (I.K.Á.-H) 2 Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Químicas, Av. Universidad S/N, Cd. Universitaria, San Nicolás de los Garza, C.P. 66451 Nuevo León, Mexico; E-Mail: [email protected] 3 Laboratorio de Bioquímica y Biología Celular, Centro de Investigaciones Biomédicas del Noreste (CIBIN), Dos de abril esquina con San Luis Potosí, C.P. 64720 Monterrey, Mexico; E-Mails: [email protected] (J.V.-V.); [email protected] (J.N.G.-G.); [email protected] (M.E.H.-G.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +52-81-8376-3668; Fax: +52-81-8352-5011. External Editor: Thomas J. Schmidt Received: 12 September 2014; in revised form: 10 December 2014 / Accepted: 11 December 2014 / Published: 15 December 2014 Abstract: Amoebiasis caused by Entamoeba histolytica is associated with high morbidity and mortality is becoming a major public health problem worldwide, especially in developing countries.
    [Show full text]
  • Simaroubaceae Family: Botany, Chemical Composition and Biological Activities
    Rev Bras Farmacogn 24(2014): 481-501 Review Simaroubaceae family: botany, chemical composition and biological activities Iasmine A.B.S. Alvesa, Henrique M. Mirandab, Luiz A.L. Soaresa,b, Karina P. Randaua,b,* aLaboratório de Farmacognosia, Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal de Pernambuco, Recife, PE, Brazil bLaboratório de Farmacognosia, Departamento de Farmácia, Universidade Federal de Pernambuco, Recife, PE, Brazil ARTICLE INFO ABSTRACT Article history: The Simaroubaceae family includes 32 genera and more than 170 species of trees and Received 20 May 2014 brushes of pantropical distribution. The main distribution hot spots are located at tropical Accepted 10 July 2014 areas of America, extending to Africa, Madagascar and regions of Australia bathed by the Pacific. This family is characterized by the presence of quassinoids, secondary metabolites Keywords: responsible of a wide spectrum of biological activities such as antitumor, antimalarial, an- Chemical constituents tiviral, insecticide, feeding deterrent, amebicide, antiparasitic and herbicidal. Although the Simaba chemical and pharmacological potential of Simaroubaceae family as well as its participa- Simarouba tion in official compendia; such as British, German, French and Brazilian pharmacopoeias, Simaroubaceae and patent registration, many of its species have not been studied yet. In order to direct Quassia further investigation to approach detailed botanical, chemical and pharmacological aspects of the Simaroubaceae, the present work reviews
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Antiprotozoal Drugs
    Antiprotozoal Drugs • Protozoal infections are common among people in underdeveloped tropical and subtropical countries, where sanitary conditions, hygienic practices, and control of the vectors of transmission are inadequate. • With increased world travel, protozoal diseases are no longer confined to specific geographic locales. • Because they are unicellular eukaryotes, the protozoal cells have metabolic processes closer to those of the human host than to prokaryotic bacterial pathogens. • Therefore, protozoal diseases are less easily treated than bacterial infections, and many of the antiprotozoal drugs cause serious toxic effects in the host, particularly on cells showing high metabolic activity. • Most antiprotozoal agents have not proven to be safe for pregnant patients. Antiprotozoal Drugs Antiprotozoal Drugs Chemotherapy Amebiasis • Amebiasis (also called amebic dysentery) is an infection of the intestinal tract caused by Entamoeba histolytica. • The disease can be acute or chronic, with varying degrees of illness, from no symptoms to mild diarrhea to fulminating dysentery. • The diagnosis is established by isolating E. histolytica from feces. • Therapy is indicated for acutely ill patients and asymptomatic carriers, since dormant E. histolytica may cause future infections in the carrier and be a potential source of infection for others. • Therapeutic agents for amebiasis are classified according to the site of action as: o Luminal amebicides act on the parasite in the lumen of the bowel. o Systemic amebicides are effective against amebas in the intestinal wall and liver. o Mixed amebicides are effective against both the luminal and systemic forms of the disease, although luminal concentrations are too low for single-drug treatment. Life cycle of Entamoeba histolytica Mixed Amebicides Tinidazole: Metronidazole: • Metronidazole a nitroimidazole, is the mixed amebicide of choice for treating amebic infections.
    [Show full text]
  • IDCM Section 3: Amebiasis
    AMEBIASIS REPORTING INFORMATION • Class B: Report by the close of the next business day in which the case or suspected case presents and/or a positive laboratory result to the local public health department where the patient resides. If patient residence is unknown, report to the local public health department in which the reporting health care provider or laboratory is located. • Reporting Form(s) and/or Mechanism: o The Ohio Disease Reporting System (ODRS) should be used to report lab findings to the Ohio Department of Health (ODH). For healthcare providers without access to ODRS, you may use the Ohio Confidential Reportable Disease form (HEA 3334). o The Ohio Enteric Case Investigation Form may be useful in the local health department follow-up of cases. Do not send this form to the Ohio Department of Health (ODH); information collected from the form should be entered into ODRS where fields are available, and the form should be uploaded in Administration section of ODRS. • Key fields for ODRS reporting include: specimen type (Intestinal Amebiasis: select from stool, tissue, ulcer scrapings; Extra-intestinal Amebiasis: select Extra-intestinal tissue), Test result: for extra-intestinal if antigen test was done select “Positive”, sensitive occupation or attendee of daycare, sensitive occupation of household member, symptoms, travel history, exposure to water and contact information. AGENT Entamoeba histolytica, a one-celled parasite. The parasite has 2 forms: a motile form, called the trophozoite, and a cyst form, responsible for the person-to-person transmission of infection. Infectious dose Low because the cyst is resistant to gastric acid. The cysts are also relatively chlorine resistant.
    [Show full text]
  • Lecture 2 Pharmacology of Anti-Parasitic Drugs Kumar PHARMACOLOGY of ANTI-MALARIA DRUGS
    Lecture 2 Pharmacology of Anti-Parasitic Drugs Kumar PHARMACOLOGY OF ANTI-MALARIA DRUGS: PLASMODIUM SPECIES THAT CAUSE HUMAN MALARIA: CHLOROQUINE (& AMODIAQUINE): Plasmodium One cycle COMMENTS Drug of choice for both treatment and prophylaxis falciparum o Infection ceases spontaneously < 4 wk Rapidly and almost completely absorbed oral administration Responsible for most serious complications Acidic in nature/DNA and deaths SPECTRUM Blood schizonticide – all 4 strains Most likely to become drug resistant Gametocide – P. vivax, P. ovale and P. malariae Plasmodium One cycle MOA Exact pharmacological mechanism still debated but malariae o Infection ceases spontaneously < 4 wk o Changes in metabolic pathway & inhibits reproduction Plasmodium Dormant hepatic stage (hypnozoite) vivax Relapses occur 1. Parasite digests host cell’s hemoglobin to obtain essential AAs Not very common in African population 2. Large amounts of heme is released toxic to parasite Pkasmodium o Lack duffy hemokine receptor on 3. Normally, parasite polymerizes heme to non-toxic hemozoin ovale endothelial cells which transport a. Chloroquine prevents polymerization to hemozoin – parasite into human body accumulation of heme lysis of parasite & host RBC ADRs Pruritis (common) PARASITE LIFE CYCLE: Give after meals to reduce nausea and other GI symptoms 1. Anopheline (females) mosquito initiates infection Hepatic and permanent eye damage (prolonged use) CAUTIONS 2. Sporozoites invade liver Chlorouine can precipitate acute attacks of psoriasis and porphyria
    [Show full text]
  • Metronidazole
    Metronidazole . (me-troe-ni-da-zole) . Flagyl® . Antibiotic, Antiparasitic PRESCRIBER HIGHLIGHTS . Injectable & oral antibacterial (anaerobes) & antiprotozoal agent. Prohibited by the FDA for use in food animals. Contraindications: Hypersensitivity to it or other nitroimidazole derivatives. Extreme caution: in severely debilitated, pregnant or nursing animals; hepatic dysfunction. May be a teratogen, especially in early pregnancy. Adverse Effects: Neurologic disorders, lethargy, weakness, neutropenia, hepatotoxicity, hematuria, anorexia, nausea, vomiting, & diarrhea. Very bitter, metronidazole benzoate may be more palatable when compounded. USES/INDICATIONS Although there are no veterinary-approved metronidazole products, the drug has been used extensively in the treatment of Giardia in both dogs and cats. It is also used clinically in small animals for the treatment of other parasites (Trichomonas and Balantidium coli) as well as treating both enteric and systemic anaerobic infections. It is commonly employed as a perioperative surgical prophylaxis antibiotic where anaerobes are likely (e.g., colon; periodontal). In horses, metronidazole has been used clinically for the treatment of anaerobic infections. PHARMACOLOGY/ACTIONS Metronidazole is a concentration-dependent bactericidal agent against susceptible bacteria. Its exact mechanism of action is not completely understood, but it is taken-up by anaerobic organisms where it is reduced to an unidentified polar compound. It is believed that this compound is responsible for the drug’s antimicrobial activity by disrupting DNA and nucleic acid synthesis in the bacteria. Metronidazole has activity against most obligate anaerobes including Bacteroides spp. (including B. fragilis), Fusobacterium, Veillonella, Clostridium spp., Peptococcus, and Peptostreptococcus. Actinomyces is frequently resistant to metronidazole. Some isolates of C. difficile may be resistant. Metronidazole is also trichomonacidal and amebicidal in action and acts as a direct amebicide.
    [Show full text]