Leishmaniasis: Introduction, classification, Pathogenesis, Lab Diagnosis,Treatment and Control

Leishmaniasis due to Leishmania donovani

 Introduction of Leishmaniasis

Leishmaniasis is an infectious disease caused by the unicellular blood parasite, Leishmania. Members of the genus Leishmania pass their life cycle in two hosts- man and the insect vector female sandfly. On the basis of clinical disease production, it is of various types like Visceral leishmaniasis, Cutaneous leishmaniasis, and cutaneous and mucocutaneous leishmaniasis. So, here we discuss visceral leishmaniasis in detail and it is also called Kala-azar, which is the most severe form of Leishmaniasis.

Classification of Leishmaniasis

Classification of Leishmaniasis ( based on disease production )

  • Visceral leishmaniasis
    Leishmania donovani (complex) (VL): L. donovani, L. Infantum, and L. chagas
  •  Cutaneous leishmaniasis of the Old world:

Leishmania tropica
Leishmania major

  • Cutaneous and mucocutaneous leishmaniasis of New world
    Leishmania mexicana (Complex)
    Leishmania brazilliensis (complex)
    Leishmania peruriana

Leishmania donovani

It causes visceral leishmaniasis or kala-azar and also causes post-kala-azar dermal leishmaniasis.

Geographical Distribution

India ( states- Assam, Bengal, Bihar, Orissa, UP)

China

Africa

South America

South Europe

Russia

Habitat:  Amastgote form in the reticuloendothelial system (macrophages): e.g. spleen, bone marrow, liver, etc.
Transmission: Persons to person transmitted by the bite of female sand flies (Phlebotomus or Lutzomyia).

Morphology of Leishmania donovani

It has two forms promastigote and amastigote.

Promastigote
It is long slender, spindle-shaped about 15-20 µm length, 1-2µm width.

The nucleus is centrally placed.

Kinetoplast (blepharoplast and parabasal body ) lies transversely and near the anterior end.

Flagellum projects from the anterior end and may be of the size of the body or even longer.
Habitat: a digestive tract of insect vector (sandfly) or laboratory culture.

Amastigote
Amastigote form is also called LD bodies.
It has shape and size: round or oval body, 2-4 micrometer along the longitudinal axis.

Kinetoplast  (parabasal body and the blepharoplast ) at a right angle to the nucleus.

Axoneme arises from blepharoplast and extends up to the tip of the cell.

Vacuole alongside the axoneme is present.
Habitat: It is present in reticuloendothelial cells of the body.

Life cycle of Leishmania donovani

The life cycle of Leishmania completes in two hosts, human, and sandfly. Sandfly is a bloodsucker, usually feeding at night on sleeping prey. When the fly bites a leishmaniasis patient, the pathogen is ingested along with the prey’s blood. Inside the stomach of the sandfly, the amastigotes quickly transform into elongated and motile forms called the promastigotes. The promastigotes live extracellularly in the alimentary canal, reproducing asexually, then migrate to the proximal end of the gut.  As the fly bites, the promastigotes are released from the proboscis and introduced locally at the bite site. Once in our body, promastigotes invade macrophages where they transform back into the smaller amastigote form. The amastigotes replicate in the macrophage cell, inside the phagolysosome but only when whose normal defensive response they are able to prevent. The daughter cells then migrate to fresh cells or through the bloodstream to find new hosts. In this way the infection is progressive, spreading to our body’s mononuclear phagocyte system, particularly the spleen and liver. The free amastigotes in peripheral tissues are then ingested by sandfly to start another cycle.

Pathogenesis of Visceral leishmaniasis

Infections range from asymptomatic to progressive, fully developed visceral leishmaniasis/ kala-azar. The incubation period is 3-6 months. Progressive wasting, anemia, and protrusion of the abdomen from enlarged liver and spleen. Fatal after 2 – 3 years if not treated. In acute cases with chills, fevers up to 104°F, and vomiting; death may occur within 6 – 12 months. The immediate cause of death is usually an invasion of a secondary pathogen that the body is unable to combat.

Clinical Manifestation of Visceral leishmaniasis

Pyrexia- Low-grade fever ( continuous intermittent in later stages)
Hepato-splenomegaly
Characteristic blackening of skin with dry, rough, harsh
Anemia

Leukopenia

Cachexia
Hypergammaglobulinemia
Epistaxis
Proteinuria,
Hematuria

Hair ( brittle, fallout)

Post-Kala-azar Dermal Leishmaniasis 

Its beief form is PKDL. Normally it develops <2 years after completion of antimonial treatment for the original disease when the visceral infection disappears but the skin infections persist.

Clinical presentation of PKDL

Hypopigmented patches,
Erythematous patches
Yellowish pink nodules

Laboratory diagnosis of  Leishmaniasis 

  • Direct evidence:
    Specimens: Bone marrow biopsy,spleen or liver biopsy (rare ), Blood (common)

Microscopy: Leishman’s/wright or Giemsa stain
Isolation: Culturing of promastigote form in NNN (Novy-Nicolle-McNeal medium)

This medium contains defibrinated rabbit blood (one part) and salt agar ( 2 parts ).

After inoculating the material in the water of condensation of the medium, it is incubated at 22°C to 24°C.

After completion of incubation, it demonstrates promastigote form of parasites.

Schneider’s insect tissue culture medium
Animal inoculation: e.g. Golden hamster
Ag detection: e.g. Immunoblotting and PCR

  • Indirect evidence
    Blood picture: leucopenia, anemia
    Napier’s Aldehyde test
    Chopra’s Antimony test
    Complement fixation test with WKK antigen-non specific as the antigen is prepared from tubercle bacillus by Witebsky, Klingenstein, and Kuhn.
    Immunofluorescence  test

ELISA

Indirect hemagglutination test
Qualitatively detects anti-leishmania circulating antibodies by leishmanial recombinant antigen K39 (rK39)- a product of a gene cloned from L. chagasi containing a 39- amino acid repeat conserved among Leishmania species.

Rapid immunochromatographic tests

Leishmanin skin test
0.2 ml of killed culture intradermal injection- positive in cured cases of Kala-azar and negative result in active leishmaniasis.

Treatment of  Leishmaniasis 

Standard treatment

Pentavalent antimonial sodium stibogluconate intravenously

Pentamidine intramuscularly (used if fail to respond antimonial  sodium stibogluconate )
Amphotericin B may be used in the pentamidine resist cases.

Control of  Leishmaniasis 

Vector control
Reservoir control
Treatment of active cases
Vaccination

Cutaneous leishmaniasis

Its causative agent is Leishmania tropica.

Pathogenesis

Infected sandfly injects promastigote form

The core of the cells parasitized by amastigote form

Acanthosis cellular infiltration

Pressure necrosis and ulceration

Secondary infection

Granulation

Healing with a scar takes 2 to 12 months.

Cutaneous and mucocutaneous leishmaniasis

Its causative agent is Leishmania brazilliensis.

Pathogenesis

Infected sandfly injects promastigote form.

Weeping ulcer (oriental sore)

Spreads to the mucosa of mouth, nose, larynx, pharynx

Parasitized cells inflammatory infiltration necrosis

later on reactive fibrosis

Further Reading

  1. Merkel and Voge’s medical parasitology
    9th edition.
  2. Parasitology: 12th edition
    By K. D. Chatterjee
  3. District laboratory practice in Tropical countries –Part-I.
    By Monica Chesbrough.
  4. Isenberg clinical microbiology procedures Handbook
    2nd edition. Vol. 2
  5. Atlas of Medical Helminthology and protozoology -4th edn  -P.L.  Chiodini, A.H. Moody, D.W. Manser
  6. Medical Parasitology by Abhay R. Satoskar, Gary L. Simon, Peter J. Hotez and Moriya Tsuji
  7. Atlas of Human Parasitology, Lawrence R Ash, Thomas C. Orihel, 3 rd ed, Publisher ASCP Press, Chicago.
  8. Molecular Medical Parasitology. Editors: J. Joseph Marr, Timothy W. Nilsen, and Richard W. Komuniecki, Publisher Academic Press, an imprint of Elsevier Science.
  9. Topley & Wilsons’ Principle of parasitology. Editors: M.T. Parker &amp; L.H. Collier, 8 th ed 1990, Publisher Edward Arnold publication, London.
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