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==clinical manifestation=====visceral leishmania===
====diagnosis of visceral leishmania====*suspect for >2 weeks fever+splenomegaly with geographical relation*detection of amastigote in smear of bone marrow aspiration, lymph node or spleen aspiration
====post kala-azar dermal leishmanisis (PKDL)====
===cutaneous leishmania===
===mucocutaneous leishmania===*only in new world CL**Bolivia, Brazil, Peru
*Bolivia, Brazil, Peru
====diagnosis of mucocutaneous leishmaniasis====
→sand flly
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==taxonomy==
*phylum ''Sarcomastigophorea'', class ''Zoomastigophorea'', genus ''Leishmania''
==epidemiology==
*700,000 - 1 mil. new cases per year
*20,000-30,000 deaths per year
==life cycle==
*amastigote - 2-4 μm
**transform from promastigote and propagate inside macrophage
**propagetes inside macrophage
**parasitized macrophage finally ruptures and let amasitgote out which eventually by sandfly
**transform to promastigote inside sandfly midgut
*simpler than ''Trypanosoma''
*host: human, dog, rodent
===sand fllysandfly===
*''Phlebotomus'' spp.
**Eurasian
**Latin America
*Feed during night
*Bitten site by sandfly produces asymptomatic papule, eventually enlarges to an ulcerated nodule and will be spontaneously healed
*most serious
*same as Kala-azar
**Latin "black fever"
*incubation 3 weeks to > 2 years**reason of diversity of incubation unknown*symptoms**fever-generally low grade**weight loss**hepatosplenomegaly- extremely substantial***completely subsides rapidly by treatment**cough, diarrhea**anemia, leukopenia, thrombocytopenia*many patients are asymptomatic and cured spontaneously**cell-mediated immunity**mass treatment of asymptomatic patients is very problematic because of lacking of easily taken oral short course drug*50,000-90,000 new cases reported per year 2004-2008*202,200-389,100 new cases estimated per year2004-2008 - underreporting
**mainly children affected
**India, Ethiopia, South Sudan, Uganda, Brazil***South Asia- decreasing trend towards elimination***South Asia- epidemic wave pattern every 15 years***East Africa- no decreasing trends***East Africa-***Latin America-
*''L. donovani''
**India, Africa
*''L. infantum'' (formerly ''L. chagasi'' was thought separated species)
**Mediterranean, China, South America
**dog , cattle is reservoir
**sensitivity 93-99% in spleen aspirate, 53-86% in bone marrow aspirate, 53-65% in lymph node aspirate
***0.1% of life-threatening hemorrhage by spleen aspiration
*culture in NNN media
*immunochromatographical detection of rk39 antigen
**dip stick form
**97-100% sensitivity in Asia, low in Africa
***reason unkown, possibly the difference of subspecies
**cannot distinguish between active or relapse
**unkown sensitivity in HIV co-infection
*in areas of high HIV prevelence all leischmeniasis patients should be screened for HIV
*PCR
*importance of accurate diagnosis
**clinical features of VL resemble
*DDx
**chronic malaria
**schistosomiasis
**typhoid
**tuberculosis - splenomegaly is rare unless miliary TB
**hematological malignancy
*can be verically transmitted - rare
*Treatment
**to reduce parasite burden
**to improve complication
**to help to induce cell-mediated immunity
*Tx in India
**liposomal AMPH-B
***+miltefosine
***+paromomycin
***+
**AMPH-B - adherence is diffucult
**miltefosine - adherence is diffucult; now is only for combination with liposomal AMPH-B
**drug interactions
*Tx in East Africa
**
*Tx for ''L. infantum'' in Latin America
**
*skin manifestation after completion of Tx of visceral leishmaniasis
**macular type, papular type, nodular type
**possibly 5-10% of VL patients
**incidence 4.8/1000 in India
*''Leishmania'' may be detected from skin specimen in some cases
**possible skin is contagious**reservoir*diagnosis**history of VL**rK39*treatment**no good evidence**miltefosine for 12 weeks
*most common
*same as Oriental sore, Chiclero ulcer (in Latin America)
*basically self-limited
*rarely diffuce or disseminated
*600700,000-1 .2 mil. new cases per year*90% of cases are from 7 countries**Afghanistan, Pakistan, Iran, Syria, Saudi Arabia, Algeria, Brazil, Colombia, Iran, Syria***completely different from VL countries but Brazil
**imported in Texas, US in 2015
**cutaneous leishmaniasis by ''L. donovani'' is reported in Sri Lanka
**tends to increase in conflict area, mass displacement, military deployment
***especially in Syria since its civil war
*''L. tropica'', ''L. mexicana'', ''L. amazonensis'' and other species >20
*"old world" Africa and South Asia
*"new world" Latin America
*''Rhombomys opimus'' (great gerbil) is primary reservoir
===transmission===*cutaneous leishmaniasis by anthroponotic (''L. donovanitropica'' is reported ) or zoonotic (other species)*skin contact with active lesion innocuous*risk factors **poor quality housing**male**younger age <15 y/o**proximity to forest**domestic dog ownership**sleeping in Sri Lankatemporary shelters ===clinical features===*no life threatening*significant cosmetic morbidity**stigmatization*old world**dryer, warty, scaly*new world**wet, ulcerative**lymphadenopathy
====diffuse cutaneous leishmaniasis====*rare form of CL*nodular, papular ====disseminated CL====*rare form of CL*>10 mixed type skin lesions*in immunocompromised host ====leishmania recidivans====*by ''L. tropica''*new lesions encircling years-old scar ===diagnosis of cutaneous leishmaniasis====
*smear of fine needle aspirate or biopsy of skin lesion
**specimen from ulcer margin is the highest yield
**fine needle aspiration cytology is generally better
*serological test is of no use; low sensitivity and variable specificity
*NAAT is available
====DDx of CL====
**staphylococcal infection
**streptococcal infection
**mycobacterial ulcer
**fungal ulcer
**cancer
**sarcoidosis
**tropical ulcer -
*same as Espundia, white leprosy
*lyphatic or hematogenous dissemination to mucosa in mouth and/or upper respiratory tract, resulted in destruction and deformity of nose, palate, pharynx
*''L. braziliensis'', ''L. panamensis''
*progressive ever without treatment
*secondary bacterial infection
*worsening nasal congestion, epistaxis or discharge common
*permanent disfigurement of face
**cleft palate, nasal septum destruction, "Tapir" nose
*leishmania is scarce in mucosal lesion
**strong local immune response
*in Thailand
*''L. siamensis'', ''L. martiniquensis''
==treatment==
*majority spontaneously healed in 2-15months
*distinguish simple or complex
**complex -
*new world needs more to identify species to anticipate of progression to mucocutaneous CL
*pentavalent antimonial
**meglumine antimoniate
**sodium stibogluconate
*amphotericin B
**liposomal amphotericin B
*paromomycin
*pentamidine
*miltefosine
*cryotherapy
**liquid nitrogen
*thermotherapy
**40-42℃ for 3min.
***50℃ for 30 sec.
**make second degree burn
*topical application
==vaccine==
*no human vaccine
*canine vaccine has been rolled out
*"leishmanization" in Uzbeskistan
**intradermal inoculation of live wild strain of ''L. major''
==control==
*case detection and treatment for anthroponotic leishmaniasis
*vector control for sandfly-borne leishmaniasis
*destruction of burrows of great gerbil
==GHIT Fund==
Global Health Innovative Technology Fund
*supported by Japanese Government
