Leishmaniasis is a wide array of clinical manifestations caused by protozoal parasites of the Trypanosomatida genus Leishmania. It is generally spread through the bite of phlebotomine sandflies, Phlebotomus and Lutzomyia, and occurs most frequently in the tropics and sub-tropics of Africa, Asia, the Americas, and southern Europe. The disease can present in three main ways: cutaneous, mucocutaneous, or visceral. The cutaneous form presents with skin ulcers, while the mucocutaneous form presents with ulcers of the skin, mouth, and nose. The visceral form starts with skin ulcers and later presents with fever, low red blood cell count, and enlarged spleen and liver.
Infections in humans are caused by more than 20 species of Leishmania. Risk factors include poverty, malnutrition, deforestation, and urbanization. All three types can be diagnosed by seeing the parasites under microscopy. Additionally, visceral disease can be diagnosed by blood tests.
Leishmaniasis can be partly prevented by sleeping under nets treated with insecticide. Other measures include spraying insecticides to kill sandflies and treating people with the disease early to prevent further spread. The treatment needed is determined by where the disease is acquired, the species of Leishmania, and the type of infection. Recent research in leishmaniasis treatment explores combination therapies, nanotechnology-based drugs, and immunotherapy.
For cutaneous disease, paromomycin, fluconazole, or pentamidine may be effective.
About 4 to 12 million people are currently infected in some 98 countries. About 2 million new cases and between 20 and 50 thousand deaths occur each year. About 200 million people in Asia, Africa, South and Central America, and southern Europe live in areas where the disease is common. The World Health Organization has obtained discounts on some medications to treat the disease. It is classified as a neglected tropical disease. The disease may occur in a number of other animals, including dogs and rodents.
Signs and symptoms
The symptoms of leishmaniasis are skin sores which erupt weeks to months after the person is bitten by infected sandflies.
Leishmaniasis may be divided into the following types: Cutaneous leishmaniasis is the most common form, which causes an open sore at each bite site, which heals in a few months to a year and a half, leaving an unpleasant-looking scar. Diffuse cutaneous leishmaniasis produces widespread skin lesions which resemble leprosy, and may not heal on their own.
Mucocutaneous leishmaniasis causes both skin and mucosal ulcers with damage primarily of the nose and mouth. Visceral leishmaniasis or kala-azar ('black fever') is the most serious form and is generally fatal if untreated. Other consequences, which can occur a few months to years after infection, include fever, damage to the spleen and liver, and anemia.
Cause
Leishmaniasis is transmitted by the bite of infected female phlebotomine sandflies which can transmit the protozoa Leishmania. The sandflies inject the infective stage, metacyclic promastigotes, during blood meals. Metacyclic promastigotes in the puncture wound are phagocytized by macrophages, and transform into amastigotes. Amastigotes multiply in infected cells and affect different tissues, depending in part on the host, and in part on which Leishmania species is involved. These differing tissue specificities cause the differing clinical manifestations of the various forms of leishmaniasis. Sandflies become infected during blood meals on infected hosts when they ingest macrophages infected with amastigotes. In the sandfly's midgut, the parasites differentiate into promastigotes, which multiply, differentiate into metacyclic promastigotes, and migrate to the proboscis.
The genomes of three Leishmania species (L. major, L. infantum, and L. braziliensis) have been sequenced, and this has provided much information about the biology of the parasite. For example, in Leishmania, protein-coding genes are understood to be organized as large polycistronic units in a head-to-head or tail-to-tail manner; RNA polymerase II transcribes long polycistronic messages in the absence of defined RNA pol II promoters, and Leishmania has unique features concerning the regulation of gene expression in response to changes in the environment. The new knowledge from these studies may help identify new targets for urgently needed drugs and aid the development of vaccines.
Vector Although most of the literature mentions only one genus transmitting Leishmania to humans (Lutzomyia) in the New World, a 2003 study by Galati suggested a new classification for New World sand flies, elevating several subgenera to the genus level. Elsewhere in the world, the genus Phlebotomus is considered the vector of leishmaniasis.
Possible non-human reservoirs Some cases of infection of non-human animals of human-infecting species of Leishmania have been observed. In one study, L. major was identified in twelve out of ninety-one wild western lowland gorilla fecal samples and in a study of fifty-two captive non-human primates under zoo captivity in a leishmaniasis endemic area, eight (all three chimpanzees, three golden lion tamarins, a tufted capuchin, and an Angolan talapoin), were found to be infected with L. infantum and capable of infecting Lutzomyia longipalpis sand flies, although "parasite loads in infected sand flies observed in this study were considered low".
Organisms Visceral disease is usually caused by Leishmania donovani, L. infantum, or L. chagasi, but occasionally these species may cause other forms of disease. The cutaneous form of the disease is caused by more than 15 species of Leishmania.
Risk factors Risk factors include malnutrition, deforestation, lack of sanitation, suppressed immune system, and urbanization.
Socioeconomic conditions: Poor living conditions like overcrowded housing and inadequate sanitation are associated with increased human exposure to sandflies. Poor waste management and open sewage create ideal breeding grounds for sandflies in rural and low-income urban areas. Limited access to healthcare may delay diagnosis and treatment, which can contribute to more severe disease outcomes. Poor individuals may face a financial barrier to treatment, increasing their risk of severe disease. Malnutrition: Deficiencies in protein, iron, vitamin A, and zinc weaken the immune system, making it harder to fight Leishmania infections. This increases the risk of both cutaneous and visceral leishmaniasis, leading to more severe illness and poor treatment outcomes. Population Mobility: Migration and displacement due to conflict, economic hardship, or environmental changes contribute to the spread of leishmaniasis, particularly when non-immune individuals enter endemic areas. Refugees and seasonal agricultural workers are at higher risk due to limited access to vector control measures. Human activity in previously uninhabited lands may increase exposure to infected sandflies and wildlife reservoirs. Environmental and Climate Change: Temperature, humidity, and rainfall changes affect the sandfly population. Rising temperatures have been linked to higher sandfly survival and breeding rates, allowing the disease to spread into higher altitudes and previously unaffected regions, such as Southern Europe and North America. Deforestation, urbanization, and dam construction disturb sandfly habitats, creating new transmission hotspots and increasing the risk of outbreaks.
Diagnosis
Leishmaniasis is diagnosed in the hematology laboratory by direct visualization of the amastigotes (Leishman–Donovan bodies). Buffy-coat preparations of peripheral blood or aspirates from marrow, spleen, lymph nodes, or skin lesions should be spread on a slide to make a thin smear and stained with Leishman stain or Giemsa stain (pH 7.2) for 20 minutes. Amastigotes are seen within blood and spleen monocytes or, less commonly, in circulating neutrophils and in aspirated tissue macrophages. They are small, round bodies 2–4 μm in diameter with indistinct cytoplasm, a nucleus, and a small, rod-shaped kinetoplast. Occasionally, amastigotes may be seen lying free between cells. However, the retrieval of tissue samples is often painful for the patient and identification of the infected cells can be difficult. So, other indirect immunological methods of diagnosis are developed, including enzyme-linked immunosorbent assay, antigen-coated dipsticks, and direct agglutination test. Although these tests are readily available, they are not the standard diagnostic tests due to their insufficient sensitivity and specificity.
Several different polymerase chain reaction (PCR) tests are available for the detection of Leishmania DNA. With this assay, a specific and sensitive diagnostic procedure is finally possible. The most sensitive PCR tests use minicircle kinetoplast DNA found in the parasite. Kinetoplast DNA contains sequences for mitochondrial proteins in its maxicircles (~25–50 per parasite), and guide RNA in its minicircles (~10,000 per parasite) of the kinetoplast. With this specific method, one can still detect Leishmania even with a very low parasite load. When needing to diagnose a specific species of Leishmania, as opposed to only detection, other PCR methods have been superior.
Most forms of the disease are transmitted only from nonhuman animals, but some can be spread between humans. Infections in humans are caused by about 21 of 30 species that infect mammals; the different species look the same, but they can be differentiated by isoenzyme analysis, DNA sequence analysis, or monoclonal antibodies.
Prevention Prevention of leishmaniasis focuses on reducing sandfly vector biting rates and treatment of human cases for predominantly human parasites like Leishmania donovani and Leishmania tropica, though the latter species has an important reservoir in rock hyraxes in Israel and possibly Saudi Arabia. Treatment of survivors of visceral leishmaniasis who develop presumably infectious cutaneous lesions associated with post-kala azar dermal leishmaniasis may prevent onward transmission. However, certain Leishmania species can be zoonotic, like Leishmania infantum, an important cause of visceral leishmaniasis in the Americas and Mediterranean region that affects both dogs and humans. Other species follow sylvatic cycles, with diverse wild animal reservoir hosts like rodents, armadillos or sloths. Thus, prevention strategies depend on the predominant Leishmania and sandfly species and the transmission cycles they mediate regionally.
Personal protection Using insect repellent on exposed skin and under the ends of sleeves and pant legs. Follow the instructions on the label of the repellent. The most effective repellents generally are those that contain the chemical DEET (N,N-diethylmetatoluamide) Leishmaniasis can be partly prevented by using nets treated with insecticide or insect repellent while sleeping. To provide good protection against sandflies, fine mesh sizes of 0.6 mm or less are required, but a mosquito net with 1.2mm mesh will provide a limited reduction in the number of sandfly bites. Finer mesh sizes have the downside of higher cost and reduced air circulation which can cause overheating. Many Phlebotomine sandfly attacks occur at sunset rather than at night, so it may also be useful to put nets over doors and windows or to use insect repellents. Use of insecticide-impregnated dog collars and treatment or culling of infected dogs. Spraying houses and animal shelters with insecticides.* Prevention and control of leishmaniasis requires a multifaceted approach. Insecticide spraying, treated nets, and case management are commonly used strategies, while additional approaches are being explored for long-term disease control.
Vector control An integrated vector management (IVM) approach is key to reducing sand fly populations. Some of the latest strategies include: