「Leishmaniasis」の版間の差分

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*host: human, dog, rodent
 
*host: human, dog, rodent
  
===sand flly===
+
===sandfly===
 
*''Phlebotomus'' spp.
 
*''Phlebotomus'' spp.
 
**Eurasian
 
**Eurasian
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**Latin America
 
**Latin America
 
*Feed during night
 
*Feed during night
 +
*Bitten site by sandfly produces asymptomatic papule, eventually enlarges to an ulcerated nodule and will be spontaneously healed
  
 
==visceral leishmania==
 
==visceral leishmania==

2022年10月15日 (土) 21:41時点における最新版

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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.
    • 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 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
    • 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

  • 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