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Last updated: 04/21/2023
Years published: 2016, 2019, 2023
NORD gratefully acknowledges Henry W. Murray, MD, Arthur R. Ashe Professor of Medicine, Attending Physician, New York Presbyterian Hospital, Weill Cornell Medical College, for assistance in the preparation of this report.
Summary
Leishmaniasis is an infectious disease caused by protozoan parasites of the genus, Leishmania. Protozoa are microscopic, single-cell organisms. The parasites that cause the disease are transmitted to people through the bites of certain species of infected sand flies. In humans, these parasites cause three main forms of infection: cutaneous leishmaniasis, mucosal leishmaniasis and visceral leishmaniasis. In each of these forms, infection ranges from causing no symptoms (asymptomatic infection) to severe, even life-threatening complications. Only a small percentage of people infected by Leishmania parasites will go on to develop disease. Leishmaniasis is seldom encountered in the United States. Most people from the U.S. who become infected do so because of travel to or living in regions around the world where the disease is common. Military personnel and contractors who serve in those areas are also at risk. In rare instances, there have been reports of cutaneous leishmaniasis acquired in the U.S. in Texas and Oklahoma.
Introduction
Leishmaniasis is broadly classified based upon its location in the Western or Eastern hemispheres. In the Western Hemisphere the disease is known as New World leishmaniasis, and is found in some areas of Mexico, Central America and South America. In the Eastern Hemisphere, the disease is known as Old World leishmaniasis, and is found in certain parts of Asia, the Middle East, southern Europe (particularly the Mediterranean area), North Africa and tropical regions of Africa. New World and Old World leishmaniasis are caused by different Leishmania species.
Leishmaniasis can affect people in different ways. Some have truly silent infection, and do not develop any signs or symptoms. Other people develop mild to moderate disease, but some develop severe infection which can lead to permanent damage and potentially life-threatening complications.
CUTANEOUS LEISHMANIASIS
This is the most common form of leishmaniasis. Symptoms may begin within weeks to months after being bitten by an infected sand fly. Affected individuals may develop one or more sores (skin lesions), particularly on exposed parts of the body such as the face, ears and the arms and legs. The lesions form at the site where the bite occurs. The lesions may be papules (bumps) or nodules (solid, raised bumps), plaques (spread out, raised lesions) or ulcers (open, eroded areas like craters). Skin lesions may change in size, becoming smaller but often enlarge and do not heal. Sores may be moist and leak fluid (like pus) or may be dry and crust over and are usually painless. Individuals may develop lesions that are limited to one area of the body and may slowly heal on their own over 6-18 months. Lesions, however, usually leave noticeable scars. Sometimes, individuals also have swollen, adjacent lymph nodes (lymphadenopathy).
Diffuse Cutaneous Leishmaniasis
This very rare form is characterized by an initial skin lesion that spreads to affect the skin of multiple different areas of the body. Individuals often have a poorly functioning immune system, which leaves them susceptible to widespread involvement of the skin, predisposes to a poor response to treatment and permits infection to last indefinitely. Affected individuals may have multiple plaques, ulcers and nodules all over their body. Diffuse cutaneous leishmaniasis progresses slowly but is a chronic condition that routinely recurs after treatment even if treatment appears to have been initially effective.
Leishmaniasis Recidivans
This term is used to define the recurrence of a skin lesion years after the initial lesion healed. Leishmaniasis recidivans often develops on the face, particularly the cheek, with a new ulcer or papule forming over or near the scar of the old lesion. Sometimes this lesion may slowly grow larger.
MUCOSAL LEISHMANIASIS
Parasites can spread from the initial skin lesion via the bloodstream to other distant sites such as the mucous membranes of the nose, mouth and throat. Individuals with mucosal leishmaniasis typically have had a skin lesion that healed on its own or with treatment, only to develop mucous membrane involvement often several years or sometimes decades later. Persistent stuffiness in or bleeding from the nose may be the first signs of the disease. Inflammation and partial to total destruction of the mucous membranes of the mouth, nose and throat can eventually occur. If untreated, mucosal leishmaniasis can cause disfiguring damage and scarring to the nose and mouth. Nasal obstruction and bleeding may result from this damage. Complications can be difficult to treat and progressively worsen. Mucosal leishmaniasis can develop in people who were not treated or were originally inadequately treated for cutaneous leishmaniasis. Known risk factors for the development of mucosal disease include infection with particular parasite species often found in South America; skin lesions which are multiple, large, long-lasting or on the head or neck; a suppressed immune system; or infection acquired in Bolivia.
VISCERAL LEISHMANIASIS
This form of leishmaniasis, usually the most severe form clinically, also develops if certain parasite species escape from the skin, enter the bloodstream and reach internal organs including the spleen, liver and bone marrow. Clinical findings range from asymptomatic infection to mild disease that resolves on its own to a severe, life-threatening infection. If symptoms develop and the full-blown disease is left untreated, visceral leishmaniasis is usually fatal.
Affected individuals may develop repeated bouts of prolonged fever, weakness, unintended weight loss or even severe wasting of the body (cachexia), significant enlargement of the spleen and liver and pancytopenia (low levels of the three main types of blood cells: red blood cells, white blood cells and platelets). A low level of red blood cells is called anemia and can produce fatigue, paleness of the skin (pallor), shortness of breath, lightheadedness, dizziness and a fast or irregular heartbeat. Affected individuals often become progressively worse over weeks to months.
Visceral leishmaniasis is also called kala-azar in India. Kala-azar is Hindi for black fever and usually refers to severe, chronic cases of the disease. A variety of additional names can be used for visceral leishmaniasis including Dum-dum fever, Burdwan fever, Sirkari disease and Sahibโs disease.
Post-Kala-Azar Dermal Leishmaniasis
This form of infection occurs in people who have or have had visceral leishmaniasis. It is most common in Africa and India. In Africa (e.g., Sudan), the disease is present or noted shortly after diagnosis and treatment for visceral leishmaniasis. Individuals may develop a raised rash on the face, buttocks and arms and legs. These lesions heal on their own over time or following treatment for visceral infection.
In India, post-kala-azar dermal leishmaniasis develops several years after treatment for visceral leishmaniasis. Individuals often develop multiple, flat discolored areas of skin (macules). Eventually, these lesions turn into plaques or nodules on the face and trunk. In India, this form requires intensive treatment.
Leishmaniasis-HIV Coinfection
Some people are infected by both the human immunodeficiency virus (HIV) and leishmaniasis. These people have a greater chance of developing severe, life-threatening complications and death. They may develop complications not normally seen in otherwise healthy people with leishmaniasis including involvement of the gastrointestinal tract and other atypical sites. Because of HIV-associated immunodeficiency, treatment may be ineffective, and relapse rates are high even after apparently effective treatment.
Leishmanial infections are caused by > 20 different species of Leishmania parasites. Parasites are microscopic organisms that live in another organism (called the host, e.g., man) and survive by taking nutrients at the hostโs expense. Leishmania are transmitted to humans or animals through the bite of an infected sand fly. Sand flies become infected by biting and sucking the blood of infected people or animals, especially dogs. Sand flies are very small and do not make any noise. Sometimes, their bites can be painful; most often, the bites are painless and go unnoticed. Sand flies are most active from dusk to dawn.
Sand flies can bite and infect anyone of any age in areas where leishmaniasis is found. The disease is much more common in rural areas than in cities. There are several risk factors for leishmaniasis, including socioeconomic status (the disease is common to some of the poorest areas on earth), malnutrition and poor housing, and there is some evidence of genetic predisposition. Additional environmental risk factors include deforestation, mining, building damns, changing or creating new irrigation schemes and other aspects of urbanization, which can lead to increased exposure to sand flies and consequently to leishmanial infection. Migratory patterns (the movements of large populations of people susceptible to leishmaniasis) can lead to an increase in the number of people infected.
Leishmaniasis seldom occurs in the U.S. Most people from the U.S. who become infected do so from travel to or living in regions where the disease is common. Cutaneous infection is periodically reported, however, in Texas and Oklahoma and one case was recently reported further north in North Dakota.
The exact number of people who develop leishmaniasis each year in the world is not known. The Centers for Disease Control and Prevention estimates that for cutaneous leishmaniasis, the number of new, clinically apparent cases each year is about 700,000 to 1.2 million people worldwide. For visceral leishmaniasis, the number is about 200,000 to 400,000 cases. More than 90% of people who develop visceral leishmaniasis live in poor rural regions of Bangladesh, Ethiopia, India, Nepal, South Sudan, Sudan and Brazil. Cutaneous leishmaniasis is much more widespread, in South and Central America, the Middle East and Central Asia.
The diagnosis of leishmaniasis is based upon characteristic symptoms and signs, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A detailed patient history includes whether a person has lived in or traveled to areas where the disease is common. For example, cutaneous leishmaniasis should always be considered with a non-healing or progressive skin lesion in a person who has traveled to or lived in a region where leishmaniasis is found.
Clinical Testing and Workup
Doctors take samples of infected tissue to be studied. They may take biopsy or scrapping samples from skin lesions for suspected cutaneous leishmaniasis from lesions in the nose, mouth or throat for suspected mucosal infection, or from the bone marrow (material found within the bones of the body) for suspected visceral leishmaniasis. These samples are sent to laboratories that can examine them in various ways for the presence of Leishmania parasites.
Blood tests may be performed to detect antibodies against the Leishmania parasites. Antibodies are specialized proteins created by the immune system in response to foreign or invading pathogens in the body. Doctors readily find antibodies against the Leishmania parasites in the blood of people with visceral leishmaniasis. However, sometimes the test can come back negative even when a person has the disease. Antibody blood tests are not often useful for people with the cutaneous or mucosal forms of leishmaniasis.
Treatment
Leishmaniasis is a treatable and curable disease. Specific procedures and therapeutic interventions may vary, depending upon numerous factors, such as the form of the disease (cutaneous, mucosal, visceral); the presence or absence of certain symptoms; geographic location where the person was infected; the specific Leishmania species involved; and an individualโs age and general health. Decisions concerning the use of drug regimens and/or other treatments should be made by physicians experienced in leishmaniasis in consultation with the patient based upon the specifics of his or her case. A thorough discussion of the potential benefits and risks of treatment (including side effects), patient preferences, the potential for scarring in cutaneous infection and other appropriate issues should take place. For example, patients should be clearly informed that initial treatment may be prolonged, more than one course of treatment may be required and given the propensity for relapse in all forms of this infection, that 6-12 months of additional observation after treatment is necessary before considering that โcureโ has been achieved.
According to the Centers for Disease Control and Prevention (CDC), individuals with cutaneous leishmaniasis may or may not require specific treatment, while all symptomatic, clinically expressed cases of visceral leishmaniasis and mucosal leishmaniasis require treatment. Specific people or groups such as young children, pregnant women, women who are lactating, people with poor functioning immune systems or people with other health conditions may require different medications or different dosage regimens.
In 2014, the U.S. Food and Drug Administration (FDA) approved the use of oral miltefosine (Impavido) for the treatment of cutaneous, mucosal and visceral leishmaniasis caused by specific species of Leishmania. This drug should not be used (is contraindicated) in pregnant women.
Cutaneous leishmaniasis can heal on its own, although healing can take a long time and often leaves scars. Treatment in specific instances for small, uncomplicated lesions can include applying heat or cold to the sores to destroy the parasites, or an antibiotic known as paromomycin can be applied as an ointment directly onto the sores. Paromomycin is not commercially available in the U.S.
For people with cutaneous leishmaniasis who have several large skin lesions, a weakened immune system or infected with Leishmania species that can potentially cause mucosal leishmaniasis, treatment can include various medications such as liposomal amphotericin B, miltefosine or sodium stibogluconate, an antimony-containing drug. In regions outside the U.S., skin lesions are also directly injected with antimonial agents.
The best treatment option for mucosal leishmaniasis is not known. Treatments that have been used for this condition are those used in the treatment of visceral infection and include liposomal amphotericin B, miltefosine, and sodium stibogluconate. Surgery may be necessary for people with severe complications of the mucous membranes of the mouth and nose (orofacial surgery).
For people with both leishmaniasis and HIV, treatment for HIV infection with antiretroviral therapy may improve the response to antileishmanial treatment, avoid or delay relapses of leishmaniasis and improve overall survival.
Prevention
Prevention is the most effective means of controlling leishmaniasis. In areas where leishmaniasis is known to be present, steps should be taken to avoid exposure to sand flies, especially from dusk to dawn, by using insect repellent containing DEET and clothing that covers the arms and legs when outside. Travelers should remain in well-screened areas, especially at night when sand flies are most active. Insect screen, netting around the bed, and clothing that is treated with insecticides such as permethrin or pyrethrum should also be used. More information about taking steps to avoid leishmaniasis can be found at the CDCโs travelerโs website (https://wwwnc.cdc.gov/travel).
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, in the main, contact: www.centerwatch.com
For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Various medications to treat specific cases of leishmaniasis are available in the U.S. but are not FDA-approved for this indication. These medications include amphotericin B deoxycholate, pentamidine isethionate and the antifungal drugs, ketoconazole, itraconazole and fluconazole. Despite limited clinical experience, oral treatment with fluconazole is also sometimes used in the U.S. for cutaneous infection. An intravenously (IV)-administered antifungal drug known as liposomal amphotericin B (AmBisome) is often used in the U.S. for treatment of cutaneous leishmaniasis or the rare case of mucosal infection diagnosed in the U.S. although liposomal amphotericin B is currently FDA approved only for the treatment of visceral leishmaniasis.
Compounds called pentavalent antimonials, given IV or intramuscularly, have been used for decades to treat all forms of leishmaniasis. In some parts of the world, cutaneous leishmaniasis is treated by injecting a pentavalent antimony drug, such as sodium stibogluconate, directly into the skin lesion depending on its size and location. Sodium stibogluconate (Pentostam) is available in the United States to U.S.-licensed physicians through the Centers for Disease Control and Prevention Drug Service (404.639.3670) under an Investigational New Drug protocol approved by the FDA.
Researchers are working on vaccines to prevent leishmaniasis. Vaccines are used to stimulate the immune system to kill parasites ideally when they first enter the skin or soon thereafter before parasites have the chance to take hold in the tissues and establish actual infection.
JOURNAL ARTICLES
Murray HW, Eiras DP, Kirkman LA, Chai RL, Caplivski D. Mucosal leishmaniasis in New York City. Am J Trop Med Hyg. 2020 102(6):1319-22.
Boggild AK et al. Cutaneous and mucocutaneous leishmaniasis in travelers and migrants: a 20-year GeoSentinel Surveillance Network analysis. J Trav Med. 2019. doi: 10.1093/jtm/taz055.
Aronson NE, Joya CA. Cutaneous leishmaniasis: updates in diagnosis and management. Infect Dis Clin North Am. 2019 Mar;33(1):101-117. https://www.ncbi.nlm.nih.gov/pubmed/30712756
van Griensven J, Diro E. Visceral leishmaniasis: recent advances in diagnostics and treatment regimens. Infect Dis Clin North Am. 2019 Mar;33(1):79-99. https://www.ncbi.nlm.nih.gov/pubmed/30712769
Alves F, Bilbe G, Blesson S, et al. Recent development of visceral leishmaniasis treatments: successes, pitfalls, and perspectives. Clin Microbiol Rev. 2018 Aug 29;31(4). https://www.ncbi.nlm.nih.gov/pubmed/30158301
Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2016 Dec 15;63(12):1539-1557. https://www.ncbi.nlm.nih.gov/pubmed/27941143
Gillespie PM, Beaumier CM, Strych U, et al. Status of vaccine research and development of vaccines for leishmaniasis. Vaccine. 2016;[Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pubmed/26973063
Mosimann V, Blazek C, Grob H, et al. Miltefosine for mucosal and complicated cutaneous Old World Leishmaniasis: a case series and review of the literature. Open Forum Infect Dis. 2016;3:ofw008. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810230/
Sakkas H, Gartzonika C, Levidiotou S. Laboratory diagnosis of human visceral leishmaniasis. J Vector Borne Dis. 2016;53:8-16. https://www.ncbi.nlm.nih.gov/pubmed/27004573
Seyed N, Taherei T, Rafati S. Post-genomics and vaccine improvement for Leishmania. Front Microbiol. 2016;7:467. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822237/
Copeland NK, Aronson NE. Leishmaniasis: treatment updates and clinical practice guidelines review. Curr Opin Infect Dis. 2015 Oct;28(5):426-37. https://www.ncbi.nlm.nih.gov/pubmed/26312442
Eiras DP, Kirkman LA, Murray HW. Cutaneous leishmaniasis: current treatment practices in the USA for returning travelers. Curr Treat Options Infect Dis. 2015;7:52-62.
Showler AJ, Boggild AK. Cutaneous leishmaniasis in travellers: a focus on epidemiology and treatment in 2015. Curr Infect Dis Rep. 2015 Jul;17(7):489. https://www.ncbi.nlm.nih.gov/pubmed/26031962
Clarke CF, Bradley KK, Wright JH, Glowicz J. Emergence of autochthonous cutaneous leishmaniasis in Northeastern Texas and Southeastern Oklahoma. Am J Trop Med Hyg. 2013;88:157-161. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541728/
Murray HW. Leishmaniasis in the United States: treatment in 2012. Am J Trop Med Hyg. 2012;86:434-440.
Murray HW, Berman JD, Davies CR, Saravia NG. Advances in leishmaniasis. Lancet. 2005;366:1561-1577. https://www.ncbi.nlm.nih.gov/pubmed/16257344
INTERNET
Stark CG, Vidyashankar C. Leishmaniasis. Medscape. Updated: February 18, 2020. Available at: Leishmaniasis: Practice Essentials, Background, Pathophysiology (medscape.com) Accessed Feb 6, 2023.
World Health Organization. Leishmaniasis Fact Sheet. January 8, 2022. Available at: https://www.who.int/mediacentre/factsheets/fs375/en/ Accessed Feb 6, 2023.
Centers for Disease Control and Prevention. Leishmaniasis. February 14, 2020. Available at: https://www.cdc.gov/parasites/leishmaniasis/ Accessed Feb 6, 2023.
Pearson RD. Leishmaniasis. Merck Manual Consumer Version. September 2022. Available at: https://www.merckmanuals.com/home/infections/parasitic-infections-extraintestinal-protozoa/leishmaniasis Accessed Feb 6, 2023.
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