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Trematode (fluke, distoma)
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taxonomy
- phylum Sarcomastigophorea, class Zoomastigophorea, genus Leishmania
- Plasmodium belongs to phylum Apicomplexa
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
- parasitize in human macrophage
- 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
- vector: sandfly
- host: human, dog, rodent
sandfly
- Phlebotomus spp.
- Lutzomya spp.
- 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
- 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 year 2004-2008 - 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
- anthroponotic = maintained in human-to-human infection
- 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
post kala-azar dermal leishmanisis (PKDL)
- 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
- skin is contagious
- reservoir
- diagnosis
- 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
- old world
- 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
- 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
- new world needs more to identify species to anticipate of progression to mucocutaneous CL
- pentavalent antimonial
- meglumine antimoniate
- sodium stibogluconate
- amphotericin B
- paromomycin
- pentamidine
- miltefosine
- cryotherapy
- thermotherapy
- 40-42℃ for 3min.
- make second degree burn
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