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====post kala-azar dermal leishmanisis (PKDL)====
→sand flly
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==taxonomy==
*phylum ''Sarcomastigophorea'', class ''Zoomastigophorea'', genus ''Leishmania''
==morphology==
*single flagellum
*kinetoplast- aggregation of DNA
*similar to ''Trypanosoma''
==epidemiology==
*700,000 - 1 mil. new cases per year
*20,000-30,000 deaths per year
==life cycle==
*promastigote - 10-25 μm
**with flagellum
**transform from amastigote inside sandfly midgut
**proliferate inside midgut
**introduced into human skin directly from sandfly midgut during sandfly bite
**phagocytized by macrophage
*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
==clinical manifestation=sandfly===*''Phlebotomus'' spp.**Eurasian*''Lutzomya'' spp.**Latin America*Feed during night*Bitten site by sandfly produces asymptomatic papule, eventually enlarges to an ulcerated nodule and will be spontaneously healed ===visceral leishmania===
*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 ===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**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 ==cutaneous leishmania==*most common*same as Oriental sore, Chiclero ulcer (in Latin America)*papule, nodule → ulcer → scar*basically self-limited*rarely diffuce or disseminated*700,000-1.2 mil. new cases per year*90% of cases are from 7 countries**Afghanistan, Pakistan, Iran, Syria, Saudi Arabia, Algeria, Brazil, Colombia***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===*anthroponotic (''L. tropica'') 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 temporary 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 - ==mucocutaneous leishmania==*only in new world CL**Bolivia, Brazil, Peru*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 ===diagnosis of mucocutaneous leishmaniasis===*leishmania is scarce in mucosal lesion**strong local immune response*serology or molecular ==emerging novel leishmaniasis==*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=cutaneous leishmania=*no human vaccine*canine vaccine has been rolled out*"leishmanization" in Uzbeskistan**intradermal inoculation of live wild strain of ''L. major'' ==control==*most commoncase detection and treatment for anthroponotic leishmaniasis*vector control for sandfly-borne leishmaniasis*destruction of burrows of great gerbil
===mucocutaneous leishmania=GHIT Fund==Global Health Innovative Technology Fund*supported by Japanese Government
