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 polymerase chain reaction (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 or miltefosine, depending on the
infecting Leishmania species and the geographic area of acquisition. Alternatives
include amphotericin B deoxycholate and pentavalent antimony compounds (sodium
stibogluconate or meglumine antimoniate) if disease was acquired in areas
where Leishmania species are likely to be susceptible. 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 species that are morphologically indistinguishable
but can be differentiated by laboratory analysis.
Etiology of Leishmaniasis
Leishmania promastigotes are transmitted by sand flies (Phlebotomus, Lutzomyia) to
vertebrate hosts. Vector sand flies are infected by biting infected humans or animals.
Animal reservoirs vary with the Leishmania species 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.

Pathophysiology of Leishmaniasis
After inoculation by a sand fly, extracellular promastigotes are phagocytized by host
macrophages; inside these cells, they transform into amastigotes.

eishmaniasis is present in scattered areas worldwide. Human infection is

caused by 20 Leishmania species that are morphologically indistinguishable
but can be differentiated by laboratory analysis.
Etiology of Leishmaniasis
Leishmania promastigotes are transmitted by sand flies (Phlebotomus, Lutzomyia) to
vertebrate hosts. Vector sand flies are infected by biting infected humans or animals.
Animal reservoirs vary with the Leishmania species 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.

Pathophysiology of Leishmaniasis
After inoculation by a sand fly, extracellular promastigotes are phagocytized by host
macrophages; inside these cells, they transform into amastigotes.

The parasites may remain localized in the skin or spread to the mucosa of
the nasopharynx or disseminate to bone marrow, the spleen, the liver, and
occasionally other organs, resulting in 3 major clinical forms of leishmaniasis:

 Cutaneous
 Mucosal
 Visceral

Cutaneous leishmaniasis is also known as oriental or tropical sore, Delhi or

Aleppo boil, uta or chiclero ulcer, or forest yaws. The major causative
species are
 L. major and L. tropica in southern Europe, Asia, and Africa
 L. mexicana and related species in Mexico and Central and South
America
 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 species. 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.
Mucosal Leishmaniasis
Visceral leishmaniasis (kala-azar, Dumdum fever) is typically caused by L.
donovani or L. infantum (previously called L. chagasi in Latin America) 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 systemic symptoms. Subclinical infections are
common; only a minority of infected patients develop progressive visceral
disease. Symptomatic infection with L. infantum is more common among
children than adults. Visceral leishmaniasis is an opportunistic infection in
patients with AIDS or other immunocompromising conditions.

Symptoms and Signs of Leishmaniasis

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 heal
spontaneously after several months but may persist for years. They leave a
depressed, burn-like scar. The course depends on the
infecting Leishmania species 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 due to L. braziliensis and related organisms
typically starts with one or more primary cutaneous ulcers. Spread to the
mucosa via lymphatics and the bloodstream probably occurs early in
infection. The skin lesions heal spontaneously; but progressive mucosal
lesions may not become apparent for months to years. Typically, patients have
nasal stuffiness, discharge, and pain. Over time, the infection may progress, resulting
in gross mutilation of the nose, palate, oral pharynx, 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. In patients in the Sudan, these
lesions develop at the end of or within 6 months of therapy and spontaneously resolve
a few months to a year later. In patients in India and adjacent countries, skin lesions
typically develop 1 to 2 years after therapy ends and can last for many years. PKDL
lesions are thought to be a reservoir for the spread of infection in these areas.
Diagnosis of Leishmaniasis

Light microscopy of Wright-Giemsa or Giemsa-stained tissue samples,
touch preparations, or aspirates
 Antibody titers for visceral leishmaniasis, but not for cutaneous or
mucosal leishmaniasis
 Culture (special media required)
 Polymerase chain reaction–based assays

Parasites are usually difficult to find or isolate in culture from biopsies of

mucosal lesions.

Organisms causing simple cutaneous leishmaniasis can be differentiated

from those capable of causing mucosal leishmaniasis based on the
geographic area of acquisition, specific DNA probes, or 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. But 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.

Polymerase chain reaction (PCR)–based assays of aspirates from bone

marrow, the spleen, or lymph nodes in patients with visceral leishmaniasis or
of biopsy, aspirates, or touch preparations from a skin lesion help diagnose
leishmaniasis.
The leishmanin skin test that detects a delayed-type hypersensitivity response to
leishmanial antigens 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.

Treatment of Leishmaniasis
 Drug therapy depends on the clinical syndrome and other factors
 For cutaneous infection, topical treatment, sodium stibogluconate injection or
topical paromomycin outside the US or heat therapy or cryotherapy
 For systemic treatment of cutaneous, mucosal, or visceral leishmaniasis,
liposomal amphotericin IV or miltefosine orally
  Alternatively, amphotericin B deoxycholate IV or pentavalent antimonials
(sodium stibogluconate, meglumine antimoniate) IV or IM if the
infecting Leishmania species is likely to be susceptible
Treatment of leishmaniasis is complicated. The therapeutic approach depends on the
following:

 Clinical syndrome
 Infecting Leishmania species
 Geographic location of acquisition
 Organism's likelihood of susceptibility to antileishmanial drugs
 Immune status of the host

Detailed recommendations for treatment are available (1, 2).

Sodium stibogluconate is no longer available from the Centers for Disease
Control and Prevention (see Centers for Disease Control and Prevention:
Infectious Diseases Laboratories ).
Cutaneous leishmaniasis
Treatment of cutaneous leishmaniasis may be topical or systemic, depending on the
lesion and organism.

If a lesion is small, spontaneously healing, and not caused by a Leishmania species

associated with mucosal leishmaniasis, it can be closely followed, rather than treated.
Topical treatment is an option for small, 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. In addition, 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 have the following:
 Infection by L. braziliensis or related organisms associated with
mucosal leishmaniasis
 Complex cutaneous leishmaniasis with multiple, large, widespread, or
disfiguring lesions
 Compromised cell-mediated immunity

In the US, systemic options include liposomal amphotericin B, miltefosine,

and amphotericin B deoxycholate. Sodium stibogluconate or meglumine
antimoniate may be used if infection was acquired in areas where antimony-
resistance is not prevalent. Liposomal amphotericin B and amphotericin
B deoxycholate are typically given in the regimens used for visceral
leishmaniasis.

Miltefosine, which has the advantage of oral administration, can be effective

for cutaneous leishmaniasis, particularly when caused by Leishmania
braziliensis, Leishmania guyanensis, and Leishmania
panamensis. Miltefosine is dosed by body weight: patients 30 to 44 kg, 50
mg orally twice a day for 28 days; ≥ 45 kg, 50 mg orally 3 times a day for 28
days. Adverse effects include nausea, vomiting, transient elevations in
aminotransferases, and dizziness. Miltefosine is contraindicated during
pregnancy; women of childbearing age who are taking this drug must use
effective birth control measures.
Pentavalent antimonials (sodium stibogluconate or meglumine antimoniate)
should be used only if the infecting Leishmania species is likely to be
susceptible. 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 a 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). Fluconazole 200 mg orally
once a day for 6 weeks is commonly ineffective, but success has been
reported with higher daily doses in some areas.
Diffuse cutaneous leishmaniasis is relatively resistant to treatment.
Mucosal leishmaniasis
The optimal treatment is uncertain.

Recent studies suggest that liposomal amphotericin B with a cumulative dose ranging

from 20 to 60 mg/kg or miltefosine dosed by body weight: patients 30 to 44 kg, 50 mg
orally twice a day for 28 days; ≥ 45 kg, 50 mg orally 3 times a day for 28 days are
often effective, but data are limited. Adverse effects of miltefosine include nausea,
vomiting, transient elevations in aminotransferases, and dizziness; the drug is
contraindicated during pregnancy so women of childbearing age who are taking this
drug must use effective birth control measures. Historically, pentavalent antimonials
have been used in Latin America. Another alternative is amphotericin B deoxycholate
0.5 to 1.0 mg/kg IV once a day or every other day for a total dose of 20 to 45 mg/kg.
Reconstructive surgery may be required if mucosal leishmaniasis grossly distorts the
nose or palate, but surgery should be delayed for 12 months after successful
chemotherapy to avoid losing grafts because of relapses.
Visceral leishmaniasis
Liposomal amphotericin B and miltefosine are approved by the US Food and Drug
Administration for treatment of visceral leishmaniasis; other lipid-associated
amphotericin preparations may be effective but have been less well studied.
Dosage of liposomal amphotericin B is
 For immunocompetent patients: 3 mg/kg IV once a day for 5 days and then once
a day on days 14 and 21 (total dose of 21 mg/kg)
 For patients with AIDS or other immunocompromising conditions: 4 mg/kg IV
once a day on days 1 to 5, 10, 17, 24, 31, and 38 (total dose of 40 mg/kg)

Miltefosine orally, dosed by body weight: patients 30 to 44 kg, 50 mg twice a day for

28 days or for patients ≥ 45 kg, 50 mg 3 times a day for 28 days can be used to treat
immunocompetent patients who acquired L. donovani in India or adjacent areas of
South Asia, who are > 12 years of age, who weigh > 30 kg, and who are not pregnant
or breastfeeding.
Pentavalent antimonials can be used to treat visceral leishmaniasis acquired in Latin
America or other areas of the world where the infection is not resistant to these drugs.
Dosage is 20 mg/kg (based on the antimony content) IV or IM once a day for 28 days.

An alternative is amphotericin B deoxycholate 1 mg/kg IV once a day for 15 to 20 days

or every other day for up to 8 weeks.
Relapses are common among patients with AIDS or other immunocompromising
conditions. Antiretroviral drugs can help restore immune function in those with AIDS,
reducing the likelihood of relapse. Secondary prophylaxis with an antileishmanial drug
may help prevent relapses in AIDS patients with CD4 counts < 200/mcL.

Supportive measures (eg, adequate nutrition, transfusions, antibiotics for secondary

bacterial infection) are often necessary for patients with visceral leishmaniasis.

Treatment references

Prevention of Leishmaniasis
For prevention of leishmaniasis, the following may help:

 Treatment of leishmaniasis in a geographic area where humans are the

reservoir
 Reduction of the vector population by spraying residual insecticide (one
that has prolonged duration of action) in sites of domestic transmission
 Personal protective measures including insect repellants on exposed
skin and protective clothing
 Control of nonhuman reservoirs
Travelers to endemic areas should use insect repellents containing DEET
(diethyltoluamide) on exposed skin. Insect screens, bed nets, and clothing
are more effective if treated with permethrin because the small sand flies can
penetrate mechanical barriers.
Vaccines are not currently available.

Key Points
 Leishmaniasis is present in scattered areas worldwide and is
transmitted by bites of sand flies.
 The parasites may remain localized in the skin (cutaneous
leishmaniasis), spread to the mucosa (mucosal leishmaniasis), or
disseminate to the liver, the spleen, and bone marrow (visceral
leishmaniasis).
 Diagnose using Wright-Giemsa or Giemsa-stained smears,
cultures, or polymerase chain reaction-based assays; serologic
tests can help diagnose visceral leishmaniasis in
immunocompetent patients but are not helpful in many patients
with AIDS or with cutaneous or mucosal leishmaniasis.
 Treat small, uncomplicated skin lesions with locally applied heat
or cryotherapy or, outside the US, with topical paromomycin or
intralesional sodium stibogluconate.
 Systemic treatment options for complex cutaneous leishmaniasis,
mucosal leishmaniasis, and visceral leishmaniasis include
liposomal amphotericin B, miltefosine, and amphotericin
B deoxycholate; sodium stibogluconate or meglumine antimoniate
may be used if infection is acquired in areas where the
infecting Leishmania species is likely to be susceptible.
 Drug resistance to antimonials is common in India and adjacent
countries and is emerging in other areas.