LeiSh Mania

8/14/2019 LeiSh Mania

1/30

HEMOFLAGELLATES

Dr. R.E. Tan


2/30

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


3/30

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


4/30


5/30

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


6/30

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


7/30

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


8/30

Life Cycle ofLeishmania


9/30

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


10/30


11/30

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,


12/30

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


13/30

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


14/30

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


15/30

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


16/30

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


17/30

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


18/30

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


19/30

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)

- 50mg/kg daily for 10-12 days- used in areas where Pentosam is not available

2. Fluconazole - may increase healing time in L. majorinfection

3. Liposomal amphotericin-B (AmBisome

) used in patientsunresponsive to pentavalent antimonials4. Itraconazole used in India to treat cutaneous leishmaniasis


20/30

Synonyms: Espundia / American leishmaniasis

Most common causative agent: Leishmania braziliensisGeographical Dist. : Central & South America, Brazil, Eastern Peru,

Bolivia, Parugay, Ecuador, Colombia,Venezuela

In Brazil known as Espundia

involves the skin with development of ulcers in the mouth or nasamucosa

not found in the peripheral blood rarely localized in visceral organMode of transmission: bite of a female sandfly

Old world - genus Phlebotomus

OrganInvolved Leishmaniaspecie GeographicalLocationskin & mucous

membraneL. Braziliensis complex L. braziliensis

L. guyanensisL. panamensis

L. MexicanaL. tropicaL. major

New World

New WorldOld WorldOld World


21/30

Primary lesion:

Lesions produced by the parasite appears 1-

4 weeks after the bite Appearance of small red papule at site of the

bite

Becomes itchy, ulcerated vesicle developexactly the same with Oriental sore, but theyare more frequently multiple and maybecome very large

Heals within 6-15months

Secondary lesions:

development of ulcers on the oral or nasal ormucopharyngeal mucosa causing highlydisfiguring tissue destruction & swelling

deformity of the cheeks, lips, soft & hardpalate

symptoms include: fever, weight loss, anemia,weakness, and he atos lenome al

Symptoms:


22/30

Diagnosis :Smear from ulcer demonstrate amastigote stage in

affected tissues

Morphology: similar appearance with other Leishmania specie

Intradermal test (Montenegro test)

Culture NNN medium

Treatment:1. Antimonial compounds:

Sodium stibogluconate (Pentostam)

Meglumine antimonate (Glucantime)

2. Clycoguanil pamoate (Camolar) a folic acid inhibitor

300mg IM single dose (adult)280mg (1-5 years old)

140mg (infants)

3. Amphotericin-B (Fungizone) 0.25-1mg/k IV daily for 8 wks


23/30

Synonyms: Kala-azar/ Death fever / Black disease

Dumdum Fever/Tropicalsplenomegaly

Most common causative agent: Leishmania donovani complex L. donovani - India, Burma, East Pakistan, Sumatra, Thailand,

Southern Russia, East Africa, Ethiopia, Sudan,

North ChinaL. chagasi Cental and South America (vector: Lutzomyia)

L. infantum Europe, Africa, China and Siberia

Insect vector: sand flies (genus Phlebotomus )

Site of involvement: amastigotes live within cells of the

reticuloendothelial system including the spleen, liver,

OrganInvolved

Leishmaniaspecie

GeographicalLocationvisceral organs L. Donovani complex

L. donovaniL. infantumL. chagasi

L. TropicaL. amazonensis

Old WorldOld WorldNew world

Old WorldNew World


24/30

Symptoms:Onset of disease is gradual

incubation period 2weeks-18months or longer

L. donovani does not in most areas cause skin lesionsprimary skin lesion (leishmaniomas) appear as papule

formation at site of bite which may be rarely noted

Later become nodular

Frequently, patient may complain of abdominal swelling withoutdefinite illness on PE: massive splenomegaly andhepatomegaly

Acute onset of fever which mimics malarial attack

weight loss, headache, malaise, anorexia, edema, bleedingmucous membrane, lymphadenopathy

malabsorption syndrome and diarrhea are common

Anemia, leukopenia, and thrombocytopenia are common


25/30

Progressive weight loss as disease pursuesits coarse

Body becomes emaciated with theabdomen hugely swollen by the enlargedliver and spleen

Both organs are soft and non-tender

Ascites may occur in advance cases

Grayish pigmentation / darkening of theskin, most marked on the forehead, overthe temples and around the mouth

Death 75-95% in untreated cases (in 2-3yrs)Post kala-azar dermal leishmanoid

- marked by reddish, depigmented nodules that sometimesbecome quite disfiguring

- usually becomes apparent about 1-2 years after inadequatetreatment


26/30

Pathogenesis:

The various species that cause visceral leishmaniasisparasitize cells of the reticuloendothelial system throughoutthe body

The disease is progressive

Most severe form of leishmaniasis

may be fatal if left untreated

Death usually occurs within 2 years due to intercurrentinfections

Proliferation of the RE cells, particularly of the spleen & liver,leads to massive hypertrophy of these organs, which mayreturn to normal size after successful treatment

Mechanism involved in recovery:

Interaction between T lymphocytes and macrophages

Role of humoral factors in human resistance to reinfection

with L. donovani


27/30

Diagnosis:

Clinical picture maybe suggestivedefinitive diagnosis rests on demonstration of amastigote

( blood & tissue smear, bone marrow, lymph nodes, liver,spleen)

Splenic puncture effective method for securingreticuloendothelial cells for study but procedureis risky

Liver puncture safer but not so productive

Bone marrow aspiration diagnostic procedure of choice

Buffy coat films sometimes of valueCulture - NNN medium

Schneiders Drosophila medium

Animal inoculation intraperitoneal inoculation on hamsters

Serological Fluorescent antibody test , ELISA

- sensitive tests but cannot differentiate between


28/30

Treatment:

1. Antimonial compounds:

Sodium stibogluconate (Pentostam)

Meglumine antimonate (Glucantime)

the drug of choice

28 days of intravenous therapy except Sudanese infections

resistant to Antimonials

Pentamidine 2-4mg/kg IM for 10-15 days

2. Liposomal amphotericin-B

- effective in treating Pentosam resistant visceralleishmaniasis

3. Allopurinol 20mg/kg TID in tx of pts with AIDS

4. Interferon gamma enhance the killing of Leishmania

amastigote


29/30

Prevention:

Suppress the reservoir: dogs, rats, gerbils, other smallmammals and rodents

Suppress the Vector: sandfly

Prevent sandfly bites:

House spraying

Public education

Personal protective measures:

Sleeves down Insect repellents

Permethrin treated uniforms

Permethrin treated bed nests


30/30

THE END!Thank You

Date post:	30-May-2018
Category:	Documents
Upload:	dhainey
View:	220 times
Download:	0 times

LeiSh Mania

Documents