Leishmaniasis is caused by species of Leishmania. Manifestations include cutaneous, mucosal, and visceral syndromes. Cutaneous leishmaniasis causes painless chronic skin lesions ranging from nodules to large ulcers that can persist for months to years but eventually heal. Mucosal leishmaniasis affects nasopharyngeal tissues and can cause gross mutilation of the nose and palate. Visceral leishmaniasis causes irregular fever, hepatosplenomegaly, pancytopenia, and polyclonal hypergammaglobulinemia with high mortality in untreated patients. Diagnosis is by demonstrating parasites in smears or cultures and increasingly by PCR-based assays at reference centers. Serologic testing can be helpful in diagnosing visceral but not cutaneous leishmaniasis. Treatment of visceral leishmaniasis is with liposomal amphotericin B. Alternatives include amphotericin B deoxycholate, pentavalent antimony compounds (sodium stibogluconate, meglumine antimonate), and miltefosine. A variety of topical and systemic treatments are available for cutaneous leishmaniasis depending on the causative species and clinical manifestations.
Leishmaniasis is present in scattered areas worldwide. Human infection is caused by 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 geographic location and include dogs, other 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 inoculation by a sand fly, promastigotes 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.
Mucosal leishmaniasis (espundia) is caused mainly by L. braziliensis but occasionally by other Leishmania sp. The parasites are thought to spread from the initial skin lesion through the lymphatics and blood to nasopharyngeal tissues. Symptoms and signs of mucosal leishmaniasis typically develop months to years after the appearance of the skin lesion.
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.
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. Their appearance varies. 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 typically painless and cause no systemic symptoms unless secondarily infected. Lesions usually 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, a rare syndrome,results in widespread nodular skin lesions resembling those of lepromatous leprosy. It results from cell-mediated anergy to the organism.
Mucosal leishmaniasis starts with a primary cutaneous ulcer. This lesion heals spontaneously, but progressive mucosal lesions develop months to years later. Typically, patients have nasal stuffiness, discharge, and pain. Over time, the infection may progress, resulting in gross mutilation of the nose, palate, or face.
In visceral leishmaniasis, the clinical manifestations usually develop gradually over weeks to months after inoculation of the parasite but can be acute. Irregular fever, hepatosplenomegaly, pancytopenia, and polyclonal hypergammaglobulinemia with a reversed albumin:globulin ratio occur. In some patients, there are twice-daily temperature spikes. Cutaneous skin lesions rarely occur. 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.
Post kala-azar dermal leishmaniasis (PKDL) may develop after treatment for visceral leishmaniasis in patients in the Sudan and India. It is characterized by 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 patients in India. The lesions persist for a few months to a year in most patients in the Sudan but can last for many years in patients in India. PKDL lesions are thought to be a reservoir for the spread of infection in these countries.
A definite diagnosis is made by demonstrating organisms in Giemsa-stained smears, by isolating Leishmania in cultures, or by PCR-based assays of aspirates from the spleen, bone marrow, liver, or lymph nodes in patients with visceral leishmaniasis or of biopsy, aspirates, or touch preparations from a skin lesion. Parasites are usually difficult to find or isolate in biopsies of mucosal lesions. Organisms causing simple cutaneous leishmaniasis can be differentiated from those capable of causing mucosal leishmaniasis with specific DNA probes or by analysis 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 patients with AIDS or other immunocompromising conditions. Serologic tests for antileishmanial antibodies are not helpful in the diagnosis of cutaneous leishmaniasis.
The leishmanin skin test is not available in the US. It is typically 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 mucosal leishmaniasis grossly distorts the nose or palate, but surgery should be delayed for 12 mo after successful chemotherapy to avoid losing grafts because of relapses. This form frequently relapses, as does the visceral form in patients with AIDS. Treatment with antiretroviral therapy can reduce risk of relapse.
Drugs are given based on the clinical syndrome, infecting species, resistance pattern, and geographic location.
Treatment may be topical or systemic, depending on the lesion and organism.
Topical treatment is an option for smaller, uncomplicated lesions. Intralesional injection of sodium stibogluconate has been used for many years for simple cutaneous leishmaniasis in Europe and Asia; it is not currently available in the US for intralesional use. Other topical options include heat therapy, which requires a specialized system for administration, and cryotherapy; both can be painful and are practical only when used to treat small lesions. Topical paromomycin is used outside the US as an ointment that contains 15% paromomycin and 12% methylbenzethonium chloride in soft white paraffin.
Systemic therapy is used in patients who are infected by L. braziliensis or related organisms associated with mucosal leishmaniasis; who have multiple, large, widespread, or disfiguring lesions; or whose cell-mediated immunity is compromised. In the US, options include liposomal amphotericin B, amphotericin deoxycholate, and sodium stiboglunconate (only if infection was acquired in areas where resistance to them is not prevalent). Sodium stibogluconate is available from the Centers for Disease Control and Prevention (CDC; call the Emergency Operations Center at 770-488-7100). Meglumine antimoniate (a pentavalent antimonial) is used in Latin America. 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 and/or liver enzymes, and cardiotoxicity (arrhythmias, myocardial depression, heart failure, ECG changes, cardiac arrest). The incidence of adverse effects increases with age. The drug is stopped if patients develop cardiotoxicity.
Alternatives include azoles (eg, fluconazole, itraconazole). Fluconazole 200 mg po once/day for 6 wk is commonly ineffective, leading to the use of higher daily doses. Another alternative is miltefosine 2.5 mg/kg (maximum, 150 mg/day) po once/day for 28 days; however,availability in the US is currently limited. Adverse effects with miltefosine include nausea, vomiting, transient aminotransferase elevations, and dizziness. It is contraindicated during pregnancy.
Diffuse cutaneous leishmaniasis is relatively resistant to treatment.
The optimal treatment is uncertain. Historically, pentavalent antimonials have been used. Another option is liposomal amphotericin or amphotericin deoxycholate 0.5 to 1.0 mg/kg once/day or every other day for 8 wk. Recent studies suggest that miltefosine may be effective.
Liposomal amphotericin B is typically used in the US; other lipid-associated amphotericin preparations have been used successfully but are less well-studied. 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. Antiretroviral therapy can help restore immune function, reducing the likelihood of relapse.
Pentavalent antimony compounds can be used to treat visceral leishmaniasis in Latin America (and in the US after consultation with the CDC). Dosing is 20 mg/kg (based on the antimony content) IV or IM once/day 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. Another alternative is amphotericin B deoxycholate 1 mg/kg IV once/day for 15 to 20 days or every other day for up to 8 wk. Paromomycin 15 mg/kg IM once/day for 21 days has been used to treat resistant strains in India.
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 control 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 January 2014 by Richard D. Pearson, MD
Content last modified January 2014