Leishmaniasis

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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