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Causes: '''''Leishmaniasis'''''
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{{Taxobox
|backcolour =
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|name =''Leishmania spp.''             
|linkpage =Parasites
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|kingdom =Eukaryota           
|linktext =PARASITES
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|sub-kingdom =      
|pagetype=Bugs
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|phylum =Euglenozoa           
|sublink1=Protozoa
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|super-class =      
|subtext1=PROTOZOA
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|class =Kinetoplastea             
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|sub-class =         
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|super-order =       
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|order =Trypanosomatida             
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|sub-order =         
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|super-family =     
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|family =Trypanosomatidae           
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|sub-family =       
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|genus =Leishmania             
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|species =''L. infantum'', ''L. donovani'', ''L.chagasi''           
 
}}
 
}}
<br>
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==Overview==
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[[Image:Leishmania Life Cycle.jpg|thumb|right|150px|Leishmania Life Cycle - Wikimedia Commons]]
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[[Image:Leishmania donovani.jpg|thumb|right|150px|''Leishmania donovani'' in bone marrow cell - Dr. L.L. Moore, Jr.]]
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[[Image:Leishmania tropica.jpg|right|thumb|150px|''L. tropica'' <p> Yutaka TsutsumiWikiMedia Commons]]
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''Leishmania spp.'' are intracellular parasites of [[Macrophage|macrophages]] from the same family as ''[[Trypanosoma]] spp.''. These organisms parasitise human, dogs and wild animals throughout southern Europe, Africa, Asia and South America. The infection is transmitted by [[Psychodidae|sandflies]]. Infection can cause both cutaneous and visceral disease. Clinical disease cause by ''Leishmania'' is termed Leishmaniasis. Three types of ''Leishmania spp.'' are described;
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# '''Hypopylaria''' - found in lizards that ingest the sandfly intermediate host. Development occurs in the hindgut of the fly.
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# '''Peripylaria''' - found in mammals and lizards, development occurs in the fore- and hindgut of the fly.
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# '''Suprapylaria''' - found only in mammals transmitted by the bite of a sandfly, development occurs in the fore- and midgut of the fly.
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==''Trypanosoma''==
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==Recognition==
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''Leishmania spp.'' are ovoid shaped parasites containing a rod shaped 'kinetoplast'. The kinetoplast is associated with a rudimentary flagellum that does not extened beyond the cell margin. The position of the kinetoplast changes as the parasite changes between life stages. Once ingested by a sand fly the parasite takes the promastigote form and the kinetoplast moves to the posterior of the cell.
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*Protozoal parasites found in the blood and tissues of vertebrates
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==Life Cycle==
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The life cycle of ''Leishamania spp.'' requires transmission between mammalian (and occasionally reptile) hosts by a blood sucking fly. The [[Psychodidae|sand flies]] is the intermediate host, in the Old World the flies are of the genus ''Phlebotomus'' and in the New World they are of the genus ''Lutzomyia''.
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*Worldwide distribution
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The promastigote form which lacks a flagella is found in the vertebrate hosts [[Macrophage|macrophages]]. The amistgote is ingested by the sand fly whilst it feeds on the host, once ingested the ''Leishamnia'' will transform into the flagellated promastigote form in the insect gut. Replication by binary fission occurs in the insects gut followed by migration to the proboscis of the insect. The presence of ''Leishamnia'' in the insects proboscis allows inoculation of the next host on which the fly feeds with the ''Leishmania'' parasite. Crushing the sand fly on the skin of a mammal can allow percutaneous transmission.
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*Causes sleeping sickness in humans
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Once inside the vertebrate host the ''Leishmania'' will invade the hosts [[Macrophage|macrophages]] and having done this revert to the amastigote form.
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*Particularly affect sub-Saharan Africa
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==Pathogenesis==
**Affect cattle production
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Infection with ''Leishmania'' can produce either cutaneous or visceral disease as the infected macrophages proliferate in foci. The cutaneous form of the disease produces areas of ulceration on the pinnae of the [[Ear - Anatomy & Physiology|ears]], eyelids or on the [[Lips|lips]]. These ulcerations can also be seen between the digits of the dogs paw. This is a parasitic infection of the [[Protozoal Dermatosis|skin]]. The visceral form causes a chronic wasting condition where generalised excema can be seen. Hair is lost from around the eyes giving the animal a 'spectacled' appearance. These symptoms are accompanied by an intermittent fever and some generalized lymphadenopathy.
**Cause Nagana (depression)
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*Divided into two groups depending on the mode of development of the insect vector
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There is a very long incubation period from infection to pathology, which can take years and therefore many infected dogs either never become symptomatic or remain so for a long period of time. Even once an animal has been treated for leishmaniasis it is not uncommon for clinical symptoms to recur after a lengthy period of remission.
**'''Salivarian'''
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***Multiply in the foregut
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***Transmitted via innoculation via feeding
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**'''Stercorarian'''
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***Multiply in the hindgut
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***Transmitted via contamination of wounds with insect faeces
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'''Life Cycle'''
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==Epidemiology==
*Undergo morphological transformations in intermediate host before becoming infective for the next host
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The spread of the disease relies on the presence of the [[Psychodidae|sand fly]] as a vector. Therfore the regions in which it is found commonly are those in which conditions are suitable for the flies such as the Mediteranean coast, southern Europe as well as in central America and northern Africa. As these flies are very common in these regions, controlling their numbers has limited success, however due to control of [[Culicidae|mosquitos]] to prevent the spread of malaria, the number of sand flies has also been reduced and a reduction in the number of cases of leishmania has been noted. Although this parasite is of primary veterinary importance in dogs, large reservoirs exist in wild animals and stray dogs. This reservoir is easily accessed by the sand fly vector and compounds the issue of controlling the spread of the disease.
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*Blood-sucking [[Biting Flies|flies]] ingest trypanosomes whilst taking a blood meal from an infected animal
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Although the UK is not home to any species of sand fly, leishmaniasis is being observed more frequently in the domestic dog population. This has largely been attributed to the increase in the number of animals that travel to areas of Europe and north Africa where the disease is endemic. These animals often acquire the disease whilst abroad but may not show clinical signs until they have been back in the UK for a considerable length of time. There has however been some evidence to show that close contact between dogs can spread the disease, though this method of transmission is much less common.
**Trypanosomes multiply first in the gut of the [[Biting Flies|fly]]
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*Salivarian trypanosomes are transmitted by [[Biting Flies#Glossinidae|Tsetse flies]]
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==Diagnosis==
**Trypanosomes pass foward to the salivary glands where they transform into the infective stage
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Definitive diagnosis of Leishmaniasis requires combining observation of the clinical signs and the demonstration of ''Leishmania'' organisms in the animal. In the cutaneous disease this may be done by microscopic analysis of skin scrapings from the animals. For diagnosis of the visceral disease samples of joint fluid, [[Lymph Nodes - Anatomy & Physiology|lymph node]] or  [[Bone Marrow - Anatomy & Physiology|bone marrow]] biopsies may all contain macrophages that have been infected by the organisms.
**Innoculated with saliva when [[Biting Flies#Glossinidae|Tsetse fly]] next feeds on a host
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*Stercorarian trypanosomes are transmitted by triatomid bugs, [[Biting Flies#Tabanidae|tabanids]] and [[Biting Flies#Melophagus spp.|keds]]
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Cytological examination of fine needle aspirates should show evidence of [[Lymph Node Abnormalities|reactive hyperplasia]] in the lymph nodes, with increased numbers of lymphoblasts and [[B cell differentiation|plasma cells]].  [[Lymph Node Abnormalities|Reactive hyperplasia]] of [[B cell differentiation|plasma cells]] is especially common in Leishmaniasis cases as it causes chronic antigen stimulation. [[B cell differentiation|Mott cells]], which are [[B cell differentiation|plasma cells]] containing vesicles of accumulated [[Immunoglobulins - Overview|immunoglobulins]] (Russell bodies)  may also be evident. They are also the result of a chronic disease process, such as Leishmaniasis.
**Trypanosomes pass back to the rectum
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As mentioned above, the parasite itself can be identified cytologically within [[Macrophage|macrophages]] to confirm disease.
**Next host is infected when skin wounds are contaminated with infected [[Insecta|insect]] faeces
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'''Pathogenesis'''
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==Treatment and Control==
*Salivarian
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Control of ''Leishmania'' is difficult due to the large environmental pool and the sand flies that transmit the disease. One method is to prevent the sand flies from biting dogs by using collars impregnated with [[Ectoparasiticides|insecticides]] or repellents. These have a limited effect and do not guarantee the safety of the animal. Destruction of infected and stray dogs will decrease the pool from which sand flies may obtain the parasite but this is often morally difficult and due to the infection of wildlife does not stop spread completely.
**Causes wasting disease in cattle (nagana)
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**Sleeping sickness in humans
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*Stercorarian
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Chemotherapy can be used to treat dogs with leishmaniasis; however this will not eliminate the infection completely. It may appear to resolve the infection, but it is not uncommon for clinical sign to return later in the dog's life. It is important to factor in the risks involved with chemotherapy, such as suppression of the immune system, and the expense of prolonged treatment.
**''T. cruzi'' most important in veterinary medicine
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***Occurs in South America
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***Infects armadillos, possums and humans
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***Causes Chagas Disease
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**Transmitted by a triatomid (kissing) bug
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**Chronic infections are often fatal causing heart failure
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**Non-pathogenic species are transmitted by [[Biting Flies#Tabanidae|tabanids]] and [[Biting Flies#Melophagus spp.|keds]]
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***''T. theileria'' and ''T. melophagium''
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*Enlarged [[Lymph Nodes - Anatomy & Physiology|lymph nodes]] and [[Spleen - Anatomy & Physiology|spleen]]
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{{Learning
**Causes lymphoid exhaustion
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|Vetstream = [https://www.vetstream.com/canis/Content/Disease/dis00998.asp Canine leishmaniosis]<br>[https://www.vetstream.com/canis/Content/Freeform/fre00654.asp PET passport travel scheme]
 
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|flashcards = [[Protozoa_Flashcards#Tropical_Protozoa|Tropical Protozoa Flashcards]]
*Anaemia
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[[Cytology Q&A 08]]
**Red blood cells removed from circulation
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|full text = [http://www.cabi.org/cabdirect/FullTextPDF/2005/20053201552.pdf ''' Canine visceral leishmaniasis.''' Gaskin, A.; Seward, R. L.; Knight, D. H.; American Heartworm Society, Batavia, USA, Recent advances in heartworm disease: Symposium 01, San Antonio, Texas, USA, 20-22 April, 2001, 2001, pp 63-65, 35 ref.]
 
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}}
*Degeneration and inflammation of multiple organs
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**E.g. Skeletal muscle, myocardium and CNS
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'''Epidemiology'''
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*Vector distribution
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**[[Biting Flies#Glossinidae|Tsetse flies]] found in riverine, savannah and forest habitats
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**Up to 20% [[Biting Flies|flies]] infected
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**[[Biting Flies|Flies]] infected for life
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*Parasite virulence
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**Some parasitaemic animals survive for long periods of time
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***E.g. ''T. brucei'' and ''T. congolense''
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***Increases the opportunity for infection of [[Biting Flies|flies]]
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**Some trypanosomes kill their host in 1-2 weeks
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***E.g. ''T. vivax''
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***Decreases the chances of [[Biting Flies|fly]] infection
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**Trypanosomes avoid host immune defences by altering glycoprotein coat (surface antigen) before host [[Immunoglobulins - WikiBlood|antibody]] response
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***'''Antigenic variation''' can occur many times over several months causes relapsing parasitaemia
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*Host response
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**Trypanotolerant wild animals remain parasitaemic for prolpnged periods without showing clincial signs of disease
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***Cause lasting reservoirs of infection
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**Most domestic livestock are susceptible to trypanosomosis
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**Some local breeds of sheep, goats and cattle are trypanotolerant
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***E.g. ''Bos indicus''
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'''Diagnosis'''
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*Demonstrate trypanosomes in blood
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**Giemsa stained smears
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**Fresh blood films
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***Motile trypanosomes
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**Haematocrit tube
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***Motile trypanosomes at the plasma/buffy coat interface
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'''Control'''
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*[[Biting Flies#Glossinidae|Tsetse fly]] control
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**Spraying and trapping
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*Prophylactic drug treatment
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**Change drug group periodically to decrease the chances of resistance occuring
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**May lead to protective immunity but livestock will still be susceptible to heterologous challenges
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*Barrier fences and buffer zones
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**Separate livestock and wild animals
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*Trypanotolerant livestock
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'''Other trypanosomes'''
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*Mechanically transmitted by [[Biting Flies|biting flies]]
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**E.g. Surra affecting horses and camels in North Africa, Asia and South America
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**''T. equinum'' in South America
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**''T. evansi'' in Asia
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*Venerally transmitted
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**E.g. Dourine
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***Transmitted by ''T. equiperdum''
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***Causes genital and abdominal oedema, emaciataion and CNS signs
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***Affects horses and donkeys in Africa, Asia, Central and South America
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*Non-pathogenic species occur in the UK
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**In sheep caused by ''T. melophagium''
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**In cattle caused by ''T. theileri''
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==''Leishmania''==
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*''Leishmania'' spp. are intracellular parasites of [[Macrophage|macrophages]]
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*Are closely related to ''Trypanosoma'' spp.
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*Cause diseases in humans, dogs and wild animals
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*Present in southern Europe, Africa, Asia and South America
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'''Life Cycle'''
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*Transmitted by blood sucking [[Biting Flies#Psychodidae|sand flies]]
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**''Phlebotomus'' spp. in the Old World
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**''Lutzomyia'' spp. in the New World
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*The amastigote (morphological form) in found in vertebrate [[Macrophage|macrophages]]
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*Ingested by [[Biting Flies#Psychodidae|sand fly]] during feeding
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**Transforms in [[Insecta|insect]] gut
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*Multiplies and migrates to [[Insecta|insect]] proboscis
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**Innoculated during feeding
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**Can be transmitted percutaneously if [[Biting Flies#Psychodidae|sand fly]] crushed on skin
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*Invades [[Macrophage|macrophages]] and reverts to amastigote
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'''Pathogenesis'''
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*Infection of vertebrate host
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**Produces foci of proliferating ''Leishmania''-infected [[Macrophage|macrophages]] in skin ('''cutaneous''') or internal organs ('''visceral''')
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*Very long incubation periods
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**Months to years
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*Many infected dogs are asymptomatic
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*Cutaneous form
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**Produces areas of ulceration on pinnae of ears
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*Visceral form causes chronic wasting condition
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**Generalised eczema
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***Loss of hair around eyes producing 'spectacle' effect
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**Intermittent fever
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**Generalised lymphadenopathy
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*Involved in [[Parasitic skin infections - Pathology#Protozoa|skin infections]]
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'''Epidemiology'''
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*Disease dependent on [[Biting Flies#Psychodidae|sand fly]] vectors
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**E.g. Common in dogs around the Mediterranean coast, foci around southern Europe and around Madrid
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*Reservoirs of infection
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**E.g. Wild animals such as rodents and stray dogs
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*Mechanisms of transmission
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**Direct contact
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**[[Biting Flies#Psychodidae|sand fly]] bite
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*Leishmaniasis in British dogs
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**Susceptible to infection if exposed whilst abroad in endemic areas as have no immunity
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**No [[Biting Flies#Psychodidae|sand flies]] in Britain but dogs have become infected whilst in contact with infected imported animals
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'''Diagnosis'''
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*Demonstrate ''Leishmania'' organisms
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**In skin scraping or smears
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**In [[Lymph Nodes - Anatomy & Physiology|lymph node]] or [[Bone Marrow - Anatomy & Physiology|bone marrow]] biopsies
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'''Treatment and Control'''
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{{review}}
*Chemotherapy
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**Prolonged treatment, expensive, suppresses infection
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**Does not cure infection
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*Prevent [[Biting Flies#Psychodidae|sand flies]] biting
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{{OpenPages}}
**Collars, sprays containing [[Ectoparasiticides|insecticide]] with repellent effect
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*Destruction of infected and stray dogs
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[[Category:Tropical Protozoa]]
**[[Biting Flies#Psychodidae|Sand flies]] biting infected dogs may spread the disease to to other dogs, humans and wildlife
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[[Category:Dermatological Diseases - Dog]]
**There is a slight possibility of transmission to humans by direct contact
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[[Category:Expert Review]]

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