Leishmaniasis

Published on 16/03/2015 by admin

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Leishmaniasis

Suhail M. Hadi and Ahmed S. Hadi

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

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Leishmaniasis is a flagellate protozoan disease caused by many species of the genus Leishmania. It can be classified into three clinical forms: visceral (kala azar), which is the most severe, mucocutanous, which can lead to extensive destruction of the mucous membranes, and cutaneous (Old and New World), which involves mainly exposed body parts, causing ulcers and scarring. The manifestations of cutaneous leishmaniasis are broad and may be similar to other inflammatory and neoplastic diseases. Unusual presentations may be seen: e.g., lupoid, sporotrichoid, paronychia-like, psoriasiform, mycetoma-like, erysipeloid, whitlow-like, discoid lupus erythematosus-like, lupus vulgaris-like, squamous cell carcinoma-like, zosteriform, chronic eczema-like, verrucous, palmoplantar, and scar leishmaniasis. Dermatologists and pathologists should be aware of such pitfalls and may utilize polymerase chain reaction (PCR) to confirm the diagnosis.

Generalized, disseminated, and mucosal leishmaniasis may be seen in patients with HIV infection and AIDS. Subclinical forms of cutaneous leishmaniasis do exist. Leishmaniasis is transmitted mainly by the bite of the infected female phlebotomine sandfly. However, other possible routes of transmission exist including transfusion, congenital, needle sharing, sexual, and person-to-person contact. Only the management of cutaneous leishmaniasis is addressed here.

Management strategy

The diagnosis of cutaneous leishmaniasis starts with the finding of a typical lesion and a history of exposure. A skin scraping for microscopic analysis is the simplest test. Cultures from an exudate or scraping show good results. Where available, PCR offers a rapid, highly sensitive, and specific modality of diagnosis. Serological tests can be used and include the indirect immunofluorescent antibody test, direct agglutination test, fast agglutination screening test, and enzyme-linked immunosorbent assay (ELISA).

A new vaccine has been recently studied for its protection against cutaneous leishmaniasis. Results showed durable protective immunity. It has the advantages of a non-invasive nasal route of vaccination and reduced cost.

Treatment is needed to improve the cosmetic outcome, as spontaneous healing may leave scarring.

Pentavalent antimonials are the first-line therapy. Meglumine antimoniate is the drug of choice. It can be given intralesionally with local anesthetic (particularly in children, because of pain) or systemically 10 mg/kg daily for 2 weeks. Leishmania recidivans requires higher doses for longer periods. Sodium stibogluconate can be infiltrated into individual lesions 1–2 mL/week. In widespread, severe cases it can be given intramuscularly or intravenously in a dose of 10 mg/kg/day for 2 weeks.

Pentavalent antimoniate use is complicated by its high incidence rate of side effects, including arthralgia, fatigue, gastrointestinal upset, elevation of amylase, lipase and liver enzyme levels, leukopenia, anemia, and ECG abnormalities. Side effects appear to be dose related, and are more common in patients with renal and liver impairment and those with cardiac arrhythmias. Amphotericin B has been used in antimony-resistant cases.

Pentamidine isethionate (aromatic diamidine) is effective for diffuse cutaneous leishmaniasis. Side effects of pentamidine include hypoglycemia, diabetes mellitus, hypotension (if administered too rapidly), nausea, abdominal pain, vomiting, and headache.

Allopurinol has antileishmanial activity, and other oral drugs such as miltefosine, zinc sulfate, rifampin, doxycycline and azoles are also beneficial. γ-Interferon was shown to be effective as monotherapy treatment for leishmaniasis. Topical preparations such as paramomycin ointment and 5% imiquimod also show considerable therapeutic potential.

Good cure rates have been achieved with both thermotherapy and cryotherapy. Lasers have been used, but further studies are needed to support their role in the treatment of leishmaniasis. Additional treatment modalities are presented below.

Specific investigations

The margin of leishmania lesions contains amastigotes, whereas the center has dead skin and debris. Accordingly, the margin is addressed when performing a slit-skin smear. The aspirate can then be sent for culture, or for histology that shows Leishman–Donovan bodies inside macrophages using Giemsa stain.

In papular and nodular lesions the margin of the lesion is punctured with a hypodermic needle and a syringe containing 0.1 mL saline. The aspirate is drawn up into the needle and is examined microscopically and/or cultured.

The gold standard medium for culture is Novy–MacNeal–Nicolle with positive results in 1 to 3 weeks, or Schneider Drosophila medium, which gives positive results in one week.

Microculture is a new culture medium that has higher carbon dioxide concentrations and lower oxygen and pH, which encourages more rapid amastigote to promastigote differentiation. Culture is not a reliable method in older lesions as the organisms become scarce and difficult to isolate.

Serological tests aim to detect the presence of antibodies against Leishmania. They are particularly valuable in visceral and mucocutaneous leishmaniasis.

PCR is a sensitive and powerful method of diagnosis of cutaneous leishmaniasis, which depends on gene amplification techniques.

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