Microbiology
Leishmania species are extracellular, flagellated promastigotes while dwelling in their sandfly vector, but are obligate intracellular, nonflagellated amastigotes while living in vertebrate hosts, including humans.
- Organisms of the L. donovani complex usually cause visceral leishmaniasis and are present in Asia, the Middle East, the horn of Africa, the Mediterranean, and Central and South America.
- L. tropica, L. major, and L. aethiopica cause Old World cutaneous leishmaniasis and are present in Asia and in northern and sub-Saharan Africa.
- The L. mexicana complex causes New World cutaneous leishmaniasis and is present in Central America and northern South America.
Epidemiology
More than 1.5 million cases of leishmaniasis occur annually worldwide, of which 0.7-1.2 million are cutaneous and 200,000-400,000 are visceral.
Clinical Manifestations
Visceral leishmaniasis (kala-azar): Pts most commonly present with an abrupt onset of moderate- to high-grade fever associated with rigor and chills.
- Splenomegaly, hepatomegaly, and (except in the Indian subcontinent) lymphadenopathy are common.
- Leukopenia, anemia, thrombocytopenia, a polyclonal increase in serum immunoglobulins, and hepatic transaminitis are common.
- Up to 50% of pts in India, East Africa, and the Sudan may develop hypopigmented skin lesions (post-kala-azar dermal leishmaniasis) concurrent with or after cure of visceral leishmaniasis. In some cases, these pts may require unusually long treatment courses.
Cutaneous leishmaniasis: After an incubation period of days or weeks, papular lesions progress to nodules that ulcerate over weeks or months. Lesions usually heal spontaneously after 2-15 months.
- The margins of the ulcer are raised and indurated, and the base of the ulcer is usually painless.
- Disease due to L. tropica may involve leishmaniasis recidivans: development of new scaly, erythematous papules in the area of a healed sore.
Mucosal leishmaniasis: This disfiguring sequela of New World cutaneous leishmaniasis results from dissemination of parasites from the skin to the naso-oropharyngeal mucosa.
- Disease may occur 1-5 years after the initial cutaneous episode.
- Persistent nasal congestion and bleeding are followed by progressive ulcerative destruction.
- These lesions do not resolve spontaneously.
Diagnosis
- Visceral leishmaniasis: Identification of amastigotes in smears of tissue aspirates is the gold standard for diagnosis.
- - The sensitivity of splenic smears is >95%, but splenic aspiration may be very dangerous; smears of bone marrow and lymph node aspirates have sensitivities of 60-85% and 50%, respectively.
- - Several serologic techniques, including a rapid test, are available and offer good sensitivity and specificity.
- Cutaneous and mucosal leishmaniasis: Diagnosis is made by microscopy, culture, or PCR examination of aspirates and biopsy specimens from skin lesions and lymph nodes.
Treatment: Leishmaniasis - Visceral leishmaniasis: The pentavalent antimonial (SbV) compounds sodium stibogluconate and meglumine antimoniate (20 mg/kg per day IV or IM for 28-30 days) are the first-line therapeutic agents and provide cure rates >90%.
- - Amphotericin B (AmB; either deoxycholate or a lipid formulation) is recommended in areas with SbV resistance (e.g., northeastern India) or if initial SbV therapy fails.
- - Paromomycin and the oral agent miltefosine have been approved for the treatment of visceral leishmaniasis in India.
- - Liposomal AmB is the drug of choice for HIV-infected pts.
- Cutaneous leishmaniasis: Although lesions generally resolve spontaneously, treatment may be needed if lesions spread or persist.
- - Topical agents can be effective for a few small lesions. Systemic treatment is needed for multiple lesions; lesions on the face, hands, or joints; and lesions of New World cutaneous leishmaniasis.
- - Administration of SbV (20 mg/kg daily for 20 days) constitutes the most effective treatment. Exceptions include disease due to L. guyanensis (pentamidine isethionate preferred) or L. aethiopica (paromomycin preferred).
- Mucosal leishmaniasis: SbV (20 mg/kg for 30 days) is recommended.
- - Pts require long-term follow-up, and neither relapse nor failure of therapy is uncommon.
- - AmB and potentially miltefosine can be used in cases of relapse or therapy failure.
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