LeiSh Mania

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    HEMOFLAGELLATES

    Dr. R.E. Tan

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    Blood & Tissue Dwelling Protozoa(Hemoflagellates)

    Family : Trypanosomatidae

    Genus :A. Leishmania - tropica

    - braziliensis- donovani

    B. Trypanosoma - gambiense- rhodesiense- cruzi

    C. LeptomonasD. HerpetomonasE. PhytomonasF. CrithidiaG. Blastocrithidia

    Pathogenic toman

    parasitic in insects

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    Protozoan Class Kinetoplasta

    General characteristics of Hemoflagellates:

    Minute, actively motile

    flattened side to side, tapering anterior and blunt posterior end

    Distinguished structures:

    Kinetoplast

    Members of this group are characterized by a single large

    mitochondrion containing a body kinetoplast Located at the base of the flagellum

    A disc-shaped, DNA-containing organelle within themitochondrion

    Undulating membraneThin protoplasmic sheet running along 1 side

    Flagella - single anterior flagellum which travels in a wavy spiralmotion; arising from a kinetoplast near the anterior end

    Nucleus

    reproduce by binary fissionnourishment is attained from blood, plasma, lymph, CSF and

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    Epimastigoteelongate, spindle-shaped body, longer

    single nucleus with central karyosome the kinetoplast is more centrally located,

    usually just anterior to nucleus The single free flagellum emerges from the middle of the parasite and forms a shorter undulating membranerepresented by Genus Crithidia andBlastocrithidia

    Trypomastigote kinetoplast is located at the posterior end the attachment of the flagellum to the body

    forms an undulating membrane that spansthe entire length of the parasite and the

    freeflagellum emerges from the anterior end

    represented by Genus Trypanosoma

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    obligate intracellular parasite capable of causing human disease

    all species are morphologically identical

    differentiation among species causing disease in human is based

    on clinical groundsVarious species are transmitted by sandflies

    Old World: genus Phlebotomus

    New World: genus Lutzomyia

    Vertebrate hosts: primarily mammals (humans, dogs, some

    rodents)

    Causes a complex disease called Leishmaniasis

    Genus

    Leishmania

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    Part of their life cycle is spent in a sand fly gut, where theybecome promastigote; the remainder of their life cycle iscompleted in vertebrate tissues, where only amastigotes arefound

    1) Amastigote

    - present in the vertebrate host (human)

    - always found intracellularly in the cells of thereticuloendothelial system, at times are

    present in the blood stream in large

    mononuclear cells - ovoid / rounded bodies measuring2 3 m wide

    - non-flagellated

    - traditionally known as Leishman-Donovan (L-D)bodies

    - amastigotes cannot be differentiated from otherLeishmania specie on the basis of

    morphology alone

    2) Promastigote

    - present in the invertebrate host (sandfly)- infectious form

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    Life Cycle ofLeishmania

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    ClinicalDisease

    OrganInvolved

    Leishmaniaspecie

    GeographicalLocationCutaneous

    Leishmaniasis

    skin L. Tropica Complex L. tropica

    L. aethiopiaL. major

    L. Mexicana complex L. mexicana

    L. pifanoiL. amazonensis

    L. Braziliensis complexL. peruvianaL. guyanensisL. panamensisL. lainsoni

    L. columbiensisL. InfantumL. chagasi

    Old World

    New World

    New World

    Old WorldNew World

    MucocutaneousLeishmaniasis

    skin & mucousmembrane

    L. Braziliensis complex L. braziliensis

    L. guyanensisL. panamensis

    L. MexicanaL. tropicaL. major

    New World

    New WorldOld WorldOld World

    VisceralLeishmaniasis

    visceral organs L. Donovani complex L. donovani

    L. infantumL. chagasi

    L. TropicaL. amazonensis

    Old WorldOld WorldNew worldOld WorldNew World

    Leishmania Species and the Clinical Diseases TheyCause

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    Old world cutaneous leishmaniasis

    Caused by Leishmania tropica Complex vector: sandfly of genus Phlebotomus (P. papatasi & P.

    sergenti)

    Leishmania major produce an acute infection with a 3-6 months duration, lesions

    occuring in the lower limbs, associated with moist lesionswhich tend to ulcerate very early

    Wet or Rural Cutaneous Leishmaniasis

    seen in Turkmenistan, Iran, Syria, Israel, Jordan, Africa, Egypt,Tunisia, Sudan, Nigeria, Mali and Kenya

    Leishmania tropica produce a chronic disease that if not treated, lasts for a year or

    longer

    characterized by dry lesions that ulcerate only after severalmonths

    usually single and appear in the face

    Dry or Urban Cutaneous Leishmaniasis

    distributed around the Mediterranean littoral, Armenia,Azerbaijan, Turkmenistan, Uzbekistan; also in Afghanistan,

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    New world cutaneous leishmaniasis

    vector: sandfly of genus Lutzomyia

    Caused by species of the Leishmania mexicana Complex:

    Leishmania mexicana

    associated with Chiclero ulcer

    Leishmania pifanoi occurs in Amazon basin, Brazil and Venezuela

    initial lesion is single, and often a period ofmonths or years passes (during which mayulcerate or disappear) before the disease spreadsboth locally or to distant skin areas

    Caused by species of the L. braziliensis complex

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    In South America, the lesions of Cutaneous Leishmaniasis havetheir own names and clinical expressions:

    Uta

    Common in Peru (western Peruvian Andes)

    caused by L. peruviana Appear as a solitary ulcer or a few restricted lesions,

    frequently in the face; necrosis involving the nasal systemand buccal mucosa

    Bush Yaws or pian bois

    Common in Guyana

    Caused by L. guyanensis

    Appear as raspberry-like lesions that resemble yaws

    Chiclero Ulcer or Bay Ulcer

    Common in Mexico,, Yucatan peninsula, and Guatemala

    In Belize - called Bay Ulcer/sore

    Caused by L. mexicana lesions appear single, usually in the ear where they can

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    Symptoms:

    Incubation periodL. tropica & L. aethiopica: couple of months 3 years

    L. major: 2 weeks

    1st sign of infection: small red papule at the site of the bite,which may itch intensely and grows to2cm in diameter or more

    L. tropica & L. aethiopica papule is dry and ulcerate onlyafter several months

    L. major papule is covered with a serous exudate & ulcerateearly

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    Usual cutaneous lesions healsspontaneously

    certain instances such healing does not

    occurAnergic patient

    incapable of mounting a response toinfection which can proliferateindefinitely, forming many lesions

    teeming with parasites Causes Diffuse Cutaneous

    Leishmaniasis

    Due to deficient cell-mediatedimmunity and of some characteristicsof the parasite itself (L. aethopica & L.pifonoi)

    Hypersensitive patient Capable of excellent antibody and

    cellular responses but cannotcompletely eliminate the parasite, so

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    primary lesion:Small red papule

    gradually enlarges

    soft at center

    Rupture

    ulcer formation

    (large, raised w/ indurated edges)Swollen lymph nodes may be present near

    the soresulcer may be single / multiplemost often seen on exposed area of body

    (extremities, face, ear, hands)secondary bacterial infection is commonnew world cutaneous leishmaniasis tends to

    be more

    severe and chronic than old world cutaneous

    leishmaniasis

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    Pathogenesis:

    bite of an infected sandfly

    liberates promastigote into the skin

    the parasite proliferate as amastigotes in the

    macrophages and endothelium of the capiliaries and othersmall blood vessels of the intermediate area

    Lysis of the amastigotes occurs following activation of themacrophages by sensitized lymphocytes

    A granulomatous reaction results in the formation of alocalized nodule, which ulcerates when the blood supply to

    the area is compromised by parasite-induced damage

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    Diagnosis:Diagnosis is usually made in endemic areas on clinical

    grounds, but requires much familiarity with the diseaseDemonstration of parasite from tissue smear or aspirationof

    exudate from ulcer edge

    Wright/ Giemsa stain

    demonstrate amastigote stage

    inside mononuclear cells

    Culture on: NNN medium (Novy-MacNeal-Nicolle)

    Schneiders Drosophila mediumAspirate or biopsy of ulcer may be inoculated

    subcutaneously into the nose of a hamster and the animalwatched for nasal inflammation

    Serology Indirect flourescent Antibody test

    Dermal test (Montenegro skin test) intradermal injection of

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    Treatment:2. Pentavalent Antimonial compounds:

    Sodium stibogluconate (Pentostam)- is the drug of choice for all types of leishmaniasis

    - Given under an experimental protocol atWalter Reed Army Medical Center (WRAMC)

    - 20mg/kg for 20 days of intravenous therapyMeglumine antimonate (Glucantime

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