Leishmaniasis is caused by species of Leishmania. Manifestations include cutaneous, visceral, and mucocutaneous syndromes. Cutaneous leishmaniasis causes painless chronic skin lesions ranging from nodules to large ulcers that can persist for months to years but eventually heal. Visceral leishmaniasis causes irregular fever, hepatosplenomegaly, pancytopenia, and polyclonal hypergammaglobulinemia with high mortality in untreated patients. Mucosal disease affects nasopharyngeal tissues and can cause gross mutilation of the nose and palate. Diagnosis is by demonstrating parasites in smears or cultures. Treatment is with liposomal amphotericin B, amphotericin B deoxycholate, pentavalent antimony compounds (sodium stibogluconate, meglumine antimonate), or miltefosine, depending on the causative species and clinical syndrome.
Leishmaniasis is present in scattered areas worldwide. Human infection is caused by about 20 Leishmania sp that are morphologically indistinguishable but can be differentiated by laboratory analysis.
Leishmania promastigotes are transmitted by sand flies (Phlebotomus sp, Lutzomyia sp) to vertebrate hosts. Vector sand flies are infected by biting infected humans or animals. Animal reservoirs vary with the Leishmania sp and location and include canines, rodents, and other animals. In the Indian subcontinent, humans are the reservoir for L. donovani. Rarely, infection is spread by blood transfusion, shared needles, congenitally, or sexually.
After infection, promastigotes from the vector are phagocytized by host macrophages; inside these cells, they transform into amastigotes.
The parasites may remain localized in the skin or spread to internal organs or the mucosa of the nasopharynx, resulting in 3 major clinical forms of leishmaniasis:
Cutaneous leishmaniasis is also known as oriental or tropical sore, Delhi or Aleppo boil, uta or chiclero ulcer, or forest yaws. The causative agents are L. major and L. tropica in southern Europe, Asia, and Africa; L. mexicana and related species in Mexico and Central and South America; and L. braziliensis and related species in Central and South America. Cases have occurred among US military personnel serving in Iraq and Afghanistan and among travelers to endemic areas in Central and South America, Israel, and elsewhere. Uncommonly, L. braziliensis spreads widely in the skin causing disseminated cutaneous leishmaniasis.
Visceral leishmaniasis (kala-azar, Dumdum fever) is typically caused by L. donovani or L. infantum/chagasi and occurs in India, Africa (particularly the Sudan), Central Asia, the Mediterranean basin, South and Central America, and infrequently China. Most cases occur in northeastern India. Parasites disseminate from the site of the sand fly bite in the skin to regional lymph nodes, the spleen, the liver, and bone marrow and cause symptoms. Subclinical infections are common; only a minority of infected patients develop progressive visceral disease. Symptomatic infection with L. infantum/chagasi is more common among children than adults. Visceral leishmaniasis is an opportunistic infection in patients with AIDS or other immunocompromising conditions.
Mucosal leishmaniasis (espundia) is caused mainly by L. braziliensis, but it occasionally occurs with other Leishmania sp in the Americas. The parasites spread from the initial skin lesion through lymphatics and blood to nasopharyngeal tissues. Symptoms and signs of mucosal disease develop months to years later.
Symptoms and Signs
In cutaneous leishmaniasis, a well-demarcated skin lesion develops at the site of a sand fly bite, usually within several weeks to months. Multiple lesions may occur after multiple infective bites or with metastatic spread. The initial lesion is often a papule that slowly enlarges, ulcerates centrally, and develops a raised, erythematous border where intracellular parasites are concentrated. Ulcers are painless and cause no systemic symptoms unless secondarily infected. Lesions typically heal spontaneously after several months but may persist for years. They leave a depressed, burn-like scar. The course depends on the infecting Leishmania sp and the host's immune status. Diffuse cutaneous leishmaniasis results in widespread nodular skin lesions resembling those of lepromatous leprosy. It results from cell-mediated anergy to the organism.
In visceral leishmaniasis, the clinical manifestations usually develop gradually over weeks to months after inoculation of the parasite. Irregular fever, hepatosplenomegaly, pancytopenia, and polyclonal hypergammaglobulinemia with a reversed albumin:globulin ratio occur. In some patients, there are twice-daily temperature spikes. Emaciation and death occur within months to years in patients with progressive infections. Those with asymptomatic, self-resolving infections and survivors (after successful treatment) are resistant to further attacks unless cell-mediated immunity is impaired (eg, by AIDS). Relapse may occur years after initial infection. After treatment for visceral leishmaniasis, patients in the Sudan and India may develop post kala-azar dermal leishmaniasis (PKDL) with flat or nodular cutaneous lesions that contain many parasites. These lesions develop at the end of or within 6 mo of therapy in patients in the Sudan and 1 to 2 yr later in India. The lesions persist for a few months to a year in most patients in the Sudan but can last for years in India. PKDL lesions are thought to contribute to the spread of infection.
Mucosal leishmaniasis starts with a primary cutaneous ulcer. This skin lesion heals spontaneously, but months to years later, mucosal lesions develop, sometimes resulting in gross mutilations of the nose, palate, and face.
A definite diagnosis is made by demonstrating organisms in Giemsa-stained smears or cultures of aspirates from the spleen, bone marrow, liver, or lymph nodes in visceral leishmaniasis or biopsy, aspirates, or touch preparations from the border of a cutaneous lesion. Parasites are usually difficult to isolate from mucosal lesions. Organisms causing simple cutaneous leishmaniasis can be differentiated from those capable of causing mucocutaneous leishmaniasis with specific DNA probes or monoclonal antibodies or by analysis of isoenzyme patterns of cultured parasites.
Serologic tests can help diagnose visceral leishmaniasis; high titers of antibodies to a recombinant leishmanial antigen (rk39) are present in most immunocompetent patients with visceral leishmaniasis. Antibodies may be absent in subclinical cases and in patients with cutaneous leishmaniasis or AIDS.
The leishmanin skin test is available outside the US. It is positive in patients with cutaneous and mucosal leishmaniasis but negative in those with active visceral leishmaniasis.
Supportive measures (eg, adequate nutrition, transfusions, antibiotics for secondary bacterial infection) may be needed for patients with visceral leishmaniasis. Reconstructive surgery may be required if mucocutaneous leishmaniasis grossly distorts the nose or palate, but surgery should be delayed for 6 to 12 mo after therapy to avoid losing grafts because of relapses. This form frequently relapses, as does the visceral form in patients with AIDS. Treatment with highly active antiretroviral therapy (HAART) may reduce risk of relapse.
Drugs are given; selection depends on the form of disease, infecting species, resistance pattern, and geographic location.
Parenteral pentavalent antimonials are often used for Leishmania sp acquired in regions where resistance is low if the lesion is potentially disfiguring or if the infecting species has the potential to disseminate and cause mucosal leishmaniasis. Drugs include sodium stibogluconate and meglumine antimonite. Doses of both are based on their pentavalent antimony content—20 mg/kg IV (slow infusion required) or IM once/day for 20 days. Adverse effects include nausea, vomiting, malaise; elevated amylase, liver enzymes, or both; and cardiotoxicity (arrhythmias, myocardial depression, heart failure, ECG changes, cardiac arrest). The incidence of side effects increases with age. The drug is stopped if patients develop cardiotoxicity.
Alternatively, miltefosine may be effective at a dose of 2.5 mg/kg (maximum, 150 mg/day) po once/day for 28 days. Adverse effects include nausea, vomiting, transient aminotransferase elevations, and dizziness. Fluconazole or itraconazole is effective in some cases. Topical paromomycin 2 times a day for 10 to 20 days has been used for L. major infections.
Diffuse cutaneous leishmaniasis is relatively resistant to treatment.
Liposomal amphotericin B is the drug of choice in the US and wherever the drug is available; other lipid-associated amphotericin preparations have been used successfully. Immunocompetent patients are given liposomal amphotericin B 3 mg/kg IV once/day for 5 days and then once/day on days 14 and 21. Higher doses and longer regimens are used in patients with AIDS.
Pentavalent antimony compounds are used to treat visceral leishmaniasis in Latin America. Dosing is as for cutaneous disease (see Cutaneous leishmaniasis), except the drug is given for 28 days.
Drug resistance is an increasing problem with antimonials, particularly in India in patients with visceral leishmaniasis. In such cases, miltefosine 2.5 mg/kg po once/day (maximum 150 mg/day) for 28 days has been effective, but miltefosine resistance has also been reported. Alternatively, amphotericin B deoxycholate 1 mg/kg IV once/day for 15 to 20 days or every other day for up to 8 wk or paromomycin 15 mg/kg IM once/day for 21 days may be used for antimony-sensitive or -resistant strains.
Pentavalent antimonials (as for visceral leishmaniasis), amphotericin B 0.5 to 1.0 mg/kg once/day or every other day for 8 wk, or miltefosine (as described for visceral leishmaniasis) may be used.
For prevention, treatment of cases in a geographic area where humans are a reservoir, reduction of the vector population by spraying residual insecticide (one that has prolonged duration of action) in sites of domestic transmission, and elimination of nonhuman reservoirs may help. People in endemic areas should use insect repellents containing DEET (diethyltoluamide). Insect screens, bed nets, and clothing are more effective if treated with permethrin or pyrethrum because the small sand flies can penetrate mechanical barriers. Vaccines are not currently available.
Last full review/revision December 2009 by Richard D. Pearson, MD
Content last modified February 2012