Affects: Dogs
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.
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.
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.
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.
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.
Treatment: The treatment is determined by where the disease is acquired, the species of Leishmania, and the type of infection.
For visceral leishmaniasis in India, South America, and the Mediterranean, liposomal amphotericin B is the recommended treatment and is often used as a single dose. Rates of cure with a single dose of amphotericin-B have been reported as 95%. In India, almost all infections are resistant to pentavalent antimonials. In Africa, a combination of pentavalent antimonials and paromomycin is recommended. These, however, can have significant side effects. Miltefosine, an oral medication, is effective against both visceral and cutaneous leishmaniasis. Side effects are generally mild, though it can cause birth defects if taken within three months of getting pregnant. It does not appear to work for L. major or L. braziliensis. Trifluralin, a herbicide, is shown to be effective treatment as ointment, without hemolytic or cell-toxic side-effects.
Recent research in leishmaniasis treatment explores combination therapies, nanotechnology-based drugs, and immunotherapy. Combination treatments, such as liposomal amphotericin B (L-AmB) with miltefosine or paromomycin, have shown high cure rates for visceral leishmaniasis while reducing treatment time and side effects. The WHO recommends miltefosine-based combination therapy for specific cases of visceral leishmaniasis. Nanotechnology-based treatments, including lipid and metallic nanoparticles, improve drug delivery by targeting parasites more precisely and reducing toxicity. Immune-modulating therapies, such as interferon-gamma (IFN-γ), are under investigation for their potential in enhancing immune responses against Leishmania infections.
The evidence around the treatment of cutaneous leishmaniasis is poor. Several topical treatments may be used for cutaneous leishmaniasis. Which treatments are effective depends on the strain, with topical paromomycin effective for L. major, L. tropica, L. mexicana, L. panamensis, and L. braziliensis. Pentamidine is effective for L. guyanensis. Oral fluconazole or itraconazole appears effective in L. major and L. tropica. There is limited evidence to support the use of heat therapy in cutaneous leishmaniasis as of 2015.
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.