Introduction

• Caused by protozoan parasites that belong to the genus Leishmania and transmitted by the bite of certain species of sand fly (subfamily Phlebotominae).
• Lutzomyia and Phlebotomus genus transmitting Leishmania to humans.
• Most forms of the disease transmissible only from animals (zoonosis), but some can be spread between humans.
• Human infection caused by about 21 of 30 species that infect mammals. These include the L. donovani complex with three species (L. donovani, L. infantum, and L. chagasi); the L. mexicana complex with four main species (L. mexicana, L. amazonensis, and L. venezuelensis); L. tropica; L. major; L. aethiopica; and the subgenus Viannia with four main species (L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) panamensis, and L. (V.) peruviana). The different species are morphologically indistinguishable, but they can be differentiated by isoenzyme analysis, DNA sequence analysis, or monoclonal antibodies.
• Cutaneous leishmaniasis is the most common form of leishmaniasis.
• Visceral leishmaniasis is a severe form in which the parasites have migrated to the vital organs.

History

• In 1917 a case of cutaneous leishmaniasis in the Middle East, known then locally as "Jericho Buttons".
• Descriptions of conspicuous lesions similar to cutaneous leishmaniasis (CL) has been discovered on tablets from King Ashurbanipal from the 7th century BC, some of which may have been derived from even earlier texts from 1500 to 2500 BC.
• Muslim physicians including Avicenna in the 10th century AD gave detailed descriptions of what was called Balkh sore.
• In 1756, Alexander Russell, after examining a Turkish patient, gave one of the most detailed clinical descriptions of the disease.
• Physicians in the Indian subcontinent would describe it as Kala-azar (Hindi phrase for black fever, kālā meaning black and āzār meaning fever or disease).
• As for the new world, evidence of the cutaneous form of the disease was found in Ecuador and Peru in pre-Inca potteries depicting skin lesions and deformed faces dating back to the first century AD.
• 15th and 16th century texts from the Inca period and from Spanish colonials mention "valley sickness", "Andean sickness", or "white leprosy", which are likely to be CL.
• It is possible that Surgeon major Cunningham of the British Indian army saw it first in 1885 without being able to relate it to the disease.
• Peter Borovsky, a Russian military surgeon working in Tashkent, conducted research into the etiology of oriental sore, locally known as Sart sore, and in 1898 published the first accurate description of the causative agent, correctly described the parasite's relation to host tissues and correctly referred it to Protozoa.
• In 1901, Leishman identified certain organisms in smears taken from the spleen of a patient who had died from "dum-dum fever" (Dum Dum is an area close to Calcutta) and proposed them to be trypanosomes, found for the first time in India.
• A few months later Captain Charles Donovan (1863-1951) confirmed the finding of what became known as Leishman-Donovan bodies in smears taken from patients in Madras, India.
• Ronald Ross who proposed that Leishman-Donovan bodies were the intracellular stages of a new parasite, which he named Leishmania donovani.
• The link with the disease kala-azar was first suggested by Charles Donovan, but was conclusively demonstrated by Charles Bentley's discovery of Leishmania donovani in patients with kala-azar.

Epidemiology

• Leishmaniasis can be transmitted in many tropical and sub-tropical countries, and is found in parts of about 88 countries. Approximately 350 million people live in these areas.

Classification

• Cutaneous leishmaniasis

  - the most common form which causes a sore at the bite site, which heals in a few months to a year, leaving an unpleasant looking scar. This form can progress to any of the other three forms.

• Mucocutaneous leishmaniasis

  - commences with skin ulcers which spread causing tissue damage to (particularly) nose and mouth.

• Visceral leishmaniasis

  - the most serious form and potentially fatal if untreated.

• Post-kala-azar dermal leishmaniasis

  - (also known as "Post-kala-azar dermatosis") a cutaneous condition characterized by a macular, depigmented eruption found mainly on the face, arms, and upper part of the trunk.

• Viscerotropic leishmaniasis

  - is a systemic infection reported in soldiers fighting in Operation Desert Storm in Saudi Arabia.

• Diffuse cutaneous leishmaniasis

  - this form produces widespread skin lesions which resemble leprosy and is particularly difficult to treat.

Signs and symptoms

• Skin sores erupting weeks to months after the person affected is bitten by sand flies.
• From a few months to years after infection- fever, damage to the spleen and liver, and anaemia.
• Considered to be one of the classic causes of a markedly enlarged spleen.

A- Sand fly biting the victim, B- Bitten Site, C- Multiple lesions, D- Spleenomegaly

Life cycle of Leishmania

Life cycle of Leishmania

Metacyclic Promastigotes

• Leishmaniasis is transmitted by the bite of female phlebotomine sandflies.
• The sandflies inject the infective stage, metacyclic promastigotes, during blood meals.
• Metacyclic promastigotes that reach the puncture wound are phagocytized by macrophages and transform into amastigotes.
• Amastigotes multiply in infected cells and affect different tissues, depending in part on which Leishmania species is involved.
• These differing tissue specificities cause the differing clinical manifestations of the various forms of leishmaniasis.
• Sandflies become infected during blood meals on an infected host when they ingest macrophages infected with amastigotes.
• In the sandfly's midgut, the parasites differentiate into promastigotes, which multiply, differentiate into metacyclic promastigotes and migrate to the proboscis.

Biochemistry

• In Leishmania protein-coding genes are organized as large polycistronic units in a head-to-head or tail-to-tail manner.
• RNA polymerase II transcribes long polycistronic messages in the absence of defined RNA pol II promoters.
• Leishmania has unique features with respect to the regulation of gene expression in response to changes in the environment.

Diagnosis

• Diagnosed in the haematology laboratory by direct visualization of the amastigotes (Leishman-Donovan bodies).

Laboratory Procedure

• Buffy-coat preparations of peripheral blood or aspirates from marrow, spleen, lymph nodes or skin lesions should be spread on a slide to make a thin smear, and stained with Leishman's or Giemsa's stain (pH 7.2) for 20 minutes.
• Amastigotes are seen with monocytes or, less commonly in neutrophil in peripheral blood and in macrophages in aspirates. They are small, round bodies 2-4μm in diameter with indistinct cytoplasm, a nucleus and a small rod-shaped kinetoplast.
• Occasionally amastigotes may be seen lying free between cells.

Bone marrow aspirate smear: visceral leishmaniasis

Prevention

• Currently there are no vaccines in routine use.
• Prevention of sand fly biting.

Treatment

• Paromomycin is effective treatment for leishmaniasis.
• There are two common therapies containing antimony (known as pentavalent antimonials), meglumine antimoniate (Glucantime) and sodium stibogluconate (Pentostam).
• Drug-resistant leishmaniasis may respond to immunotherapy (inoculation with parasite antigens plus an adjuvant) which aims to stimulate the body's own immune system to kill the parasite.

Research

Several potential vaccines are being developed, under pressure from the World Health Organization, but none is available.

Miasmatic analysis

• The condition starts with activation of Psora.
• After implantation of the disease seeds into the body, the Syphilis becomes active and the Psora is suppressed.
• As soon as the syphilis reaches its youth, the Sycosis marries Syphilis and produces the worst forms of manifestations.
• Thenceforth, the treatment will require polymiasmatic remedies having very deep penetrating powers.

Homoeopathic Treatment

The Homoeopathic remedies for Leishmaniasis - in decreasing order of similarity to the general picture of the Leishmaniasis constitution - 
Ars alb > Nit ac > Lach > Nat m > Sulph > Carb v > Rhus t > Nux v > Con > Plb > Phos > Ph. ac > Calc > Hydr > Squill.

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