advanced lieshmaniasis2013.pdf

8/13/2019 advanced lieshmaniasis2013.pdf

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phylum

Sarcomastigophora


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Flagellates

Sub kingdom: Protozoa

Phylum: Sarcomastigophora (containing

amoebae and flagellates)

Subphylum: mastigophora (flagella and insome cases undulating membrane)

Class: kinetoplastidea

Order : Trypansomatidae

Genera: Leishmania and Trypansoma


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Leishmania parasite-promastigote


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Leishmania parasite-Amastigote

Infect s Reticulo endothelial

system (i.e. MQ)


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Intestinal, oral and Genital FlagellatesGiardia lamblia (duodenum)

Trichomonas hominis (caecum)

Trichomonas tenax (mouth)

Trichomonas vaginalis (vagina)Enteromonas hominis (large intestine)

Blood and Tissue Flagellates

Leishmania

A- Old World LeishmaniasisLeishmania donovani

Leishmania infantum

Leishmania tropica

Leishmania major

Leishmania aethiopica

B- New World LeishmaniasisLeishmania brazeliensis complex

Leishmania maxicana complex

TrypanosomaTrypanosoma brucei gambiense

Trypanosoma brucei rhodesienseTrypansoma cruzi


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Blood and Tissue Flagellates

Family: Trypansomatida

Possess a single nucleus, a single kinetoplast consists A

kinetoplast is a network of circular DNA (called kDNA) inside a large

mitochondrion that contains many copies of the mitochondrial

genome. The variation in the structures of kinetoplasts could reflect

phylogenic relationships between Kinetoplastids.

Kinetoplasts are usually adjacent to body leading to the thought

that they are tightly bound to the cytoskeleton

The portion of the flagellum extending from the kindetoplast to

the surface of the body of the parasite is Known as axoneme


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Kinetoplast


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The kinetoplast consists of a complex

network of concatenated DNA cirlces

1- Minicircle DNA2- Maxicircle DNA


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Leishmaniases

are a group of clinically diverse

vector-borne diseases whose

etiological agents are speciesbelong to the genus Leishmania


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Clinical Disease /disease phenotype

Selfhealing cutaneous sores

cutaneous (CL)

Leishmanioma

mucocutaneous lesions (MCL)

Mucosal leishmaniasis (ML) visceral leishmaniasis (VL) Kalazar

Post Kalazar dermal leishmaniasis (PKDL)

approx. 50% VL develop PKDL in Sudan

WHO estimates, annual incidence is estimated at 11.5 million cases ofcutaneous leishmaniasis (CL) and 500 000 cases of visceral leishmaniasis

(VL)


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PKDL: Cure after 60 days stibogluconate

Visceral leishmaniasis caused

by L. donovani affecting

mainly childern

Post Kalazar dermal leishmaniasis occurs

in 50% after treatment or with out

treatment

India 5-10%: L. donovani

Cutaneous leishmaniasis

caused by L. major in

Sudan

Mucosal leishmaniasis

Clinical presentation


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Incubation period of VL varies between 2 and 6 months.

On infection, the parasites disseminate through the lymphatic and

vascular systems and infect monocytes and

macrophages in the reticuloendothelial system resulting in

infiltration of the bone marrow, spleen, lymph nodes, and otherorgans.

Most common symptoms are persisting fever, weight loss (a),

epistaxis, anorexia, abdominal pain, cough, diarrhea,

nausea/vomiting.Characteristic signs are fever, splenomegaly (a,b), hepatomegaly (b),

enlarged lymph nodes.

Visceral leishmaniasis (VL) and its Symptoms


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Geographical

distribution of Old

World CutaneousLeishmaniasis (CL):(1) L. infantum CL, (2)

zoonotic CL caused by L.

major, (3) L. tropica CL,

and (4) L. aethiopica CL

Geographical

distribution of VL:(1) low Endemicity area

(2) (2) high Endemicity area.

Guizani et al . 2011


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Balanites aegyptiaca andAcacia seyal

antrees, closely associated with P.orientalis,

in the VL-endemic area in Eastern Sudan

Vector: Phlebotomus papatasi (cutaneous leishmaniasis)

Phlebotomus orientalis (Visceral leishmaniasis)

Sand fly

Phlebotomus

Ecology of leishmaniasis

Cracked cotton soil andtermite hills. Courtesy of Prof El Hassan and A.M Musa


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Leishmania parasites: life cycle

Kaye et al. 2011, nature


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Transmission possibilities

Zoonosis (human-vector-animalreservoir)

Anthroponotic (human-vector-human)


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Promastigote

Found in the digestive tract of sandfly and

in the culture media

Has nucleus and kinetoplast

Flagellum as the same length as the body

of the parasite

No undulating membrane


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Promastigote


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Sandfly: Genus:Phlebotomus

Sexual reproduction does

occur


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Amastigote

Resides in cells of reticuloendothelial

system (MQ, monocytes, leukocytes,

endothelial cells) Non motile round or oval body 2-4 uM

has kinetoplast


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Number of genes ~8400


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Transcription is poly-cistronic in

trypansomes

polycistronic mRNAs (multiple genes ("cistrons") coded in a sngle transcript

The prokaryotic mRNA is usually polycistronic meaning that a single primary transcript will

code for several polypeptides.

The term cistron refers to a sequence which corresponds to 1 polypeptide chain plus the start

and stop signals for translation.


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Trypanosomias

Trypanosomes were firstdescribed in frogs 1855

Griffith Evans identifies T.

evansi as agent of surra (ahorse and camel disease) in1880

David Bruce identifies T. bruceias cause of Nagana anddemonstrates transmission byTse-tse flies

David Bruce, 1855-1931


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Trypanosome biology


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Insect stages and blood stream forms

are very different

Different stages express differentsets of surface proteins

Insect forms have largemitochondria with many cristae

Insect stages have an aerobic

metabolism and a full respiratorychain

Blood stream forms only engage inglycolysis and excrete pyruvate andglycerol

Note that transmission stages do

not replicate and are arrested indevelopment (ladies in waiting)


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Why is trypanosomiasis so deadly?

Infection is

characterized by

periodic waves of

parasitemia Each wave represents

a single antigenically

distinct clone or

serotype

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advanced lieshmaniasis2013.pdf