Leishmaniasis is a parasitic disease caused by the protozoa belonging to the genus, Leishmania . Human leishmaniasis is not a disease, but a group of diseases. While several ways to classify leishmaniasis (eg, by geography or taxonomy) are available, clinically, it can present itself in various ways, and is more easily classified as cutaneous, mucocutaneous, and visceral leishmaniasis.

Classification Eukaryota (organisms with nucleated cells), Kingdom Protista, Phylum Protozoa, Class Flagellates, Genus Leishmania.

Species, Reservoirs, and Clinical Diseases Leishmaniasis Species (Possible reservoir) Geographic Location Cutaneous leishmaniasis L. tropica complex L. tropica (dog) L. aethiopica (rock hyrax) L. major (gerbils & rodents) Old World L. mexicana complex L. mexicana (woodrats, cat, and others) L. pifanoi L. amazonensis (small forest mammals, rodents, marsupials, and foxes) L. garnhami L. venezuelensis New World L. braziliensis complex L. peruviana (domestic dog and probably a wild rodent) L. guyanensis (arboreal sloths and anteaters) L. panamensis (sloths, rodents, monkeys, procyonids) L. lainsoni (agouti) L. colombiensis (sloth)

Species, Reservoirs, and Clinical Diseases Cutaneous leishmaniasis L. infantum Old World L. chagasi New World Mucocutaneous leishmaniasis L. braziliensis complex L. braziliensis L. guyanensis L. panamensis L. mexicana L. tropica L. major

Species, Reservoirs, and Clinical Diseases Visceral leishmaniasis L. donovani complex L. donovani (no reservoir in Indian or Kenyan area, various rodents in Sudan , dogs in China ) L. infantum (human is accidental host, natural infection in dogs, other Canidae, and porcupines) Old World L. chagasi (domestic dogs and cats, foxes) New World L. tropica L. amazonensis

During blood meal, infected sandflies inject the infective stage, the so-called promastigote parasite, into the human host. Injected promastigotes are first phagocytized by macrophages and transform into so-called amastigote parasites. These multiply in the infected cells and also affect different tissues, depending on the Leishmania species, which causes the corresponding clinical manifestation of the disease.

When sandflies take blood meals from an infected host, they take up parasitized macrophages. In the vector fly's midgut, these parasites differentiate into the so-called promastigote form, which multiplies and finally migrates to the fly's proboscis.

Clinical forms CUTANEOUS VISCERAL MUCOCUTANEOUS

Visceral Leishmaniasis (Kala-azar) Etiology The L. donovani species complex includes several species: L. infantum and L. chagasi

Epidemiology The species of visceral leishmaniasis are endemic in areas of India, China, Central and South America, East and West Africa, and the countries surrounding the Mediterranean. In India, no extrahuman reservoirs are known, but in other regions, infection may involve several mammalian species, including dogs, foxes, and wild rodents. Sandflies of the genus Phlebotomus are the insect vectors that spread L. donovani.

Pathogenesis The flagellated promastigotes of L. donovani are introduced by an insect bite. After entering macrophages of the reticuloendothelial system, these forms change into amastigotes, which multiply in phagocytic cells. Released amastigotes disseminate hematogenously and invade reticuloendothelial cells in the spleen, liver, lymph nodes, bone marrow, and skin.

Incubation and Clinical Symptoms Incubation period is 6-8 months. Symptoms: weakness, dizziness, weight loss, diarrhea, and constipation. Fever, may spike twice daily; chills and sweating. hepatosplenomegaly anemia and leukopenia. bleeding from the gingivae, nose, or GI tract, ecchymoses and petechiae on the skin.

Cutaneous and Mucocutaneous Leishmaniasis Etiology and Epidemiology Old World cutaneous leishmaniasis is caused by three species of Leishmania that belong to the L. tropica complex: L. tropica is present in the Middle East and the Mediterranean littoral; L. major is found in the Middle East, Arabia, India, and sub-Saharan Africa; L. aethiopica is found principally in Ethiopia and Kenya. Phlebotomus sandflies are the principal vectors. Infections that are caused by Leishmania can be acquired by travelers, as well as by military and other personnel residing in endemic areas. Military personnel in the Middle East have acquired cutaneous leishmaniasis with L. major and viscerotropic infections with L. tropica.

Cutaneous and Mucocutaneous Leishmaniasis New World cutaneous leishmaniasis arises from infection with parasites belonging to the L. mexicana group or the L. braziliensis (Viannia subgenus) group. The patterns of illness vary with the nature of the infecting leishmanial organisms, which are found in different regions of North, Central, and South America. Infections with strains of L. viannia, which are endemic in various areas of South America, cause cutaneous leishmaniasis and, in a small percentage of those infected, result in the later development of mucocutaneous leishmaniasis. Such mucocutaneous disease (espundia) involves the nasal or oropharyngeal mucosa, or both, and may prove fatal. All of these New World leishmanial parasites are transmitted principally by sandfly vectors, although direct human contact may also bring about infection. Various mammals are naturally infected reservoirs of the organisms.

Pathogenesis Both Old World and New World forms of leishmaniasis are initiated when the bite of an infected sandfly injects promastigotes into the human host. The organisms enter tissue macrophages and capillary endothelial cells, become amastigotes, and multiply. A granulomatous inflammatory response develops at the bite site. With local ischemia, the lesion ulcerates; a bacterial infection of the necrotic area may extend the ulceration.

Incubation and Clinical Symptoms Incubation period is from 2-8 months to 1,5 years and more. In Old World symptoms of cutaneous leishmaniasis: a papule (at the inoculation site). papule ulcerates and a shallow circular lesion appears that is several centimeters in diameter and has a raised margin. lymphadenopathy. Healing of the lesions is slow, sometimes requiring more than a year.

Clinical Symptoms of New World leishmaniasis Incubation period is 2-3 weeks to 1-3 mounths. L. viannia lesions on the skin or mucous membranes. progressive ulcerations of lymphatic nodes and mucous membranes. the infection metastasizes to the nasal or oral mucosa. Metastatic lesions can erode the nasal septum or the hard palate or soft palate. Some patients die of malnutrition or bacterial infection. L. mexicana single lesion or a few lesions on exposed surfaces of the body such as the face and ear, which heals spontaneously over 6 months. extensive destruction of the pinna.

Immunity In visceral leishmaniasis (Kala-Azar) cellular immunity is responsible for resolving mild disease. High levels of antibodies are found. In cutaneous and mucocutaneous leishmaniasis host defense relies on cell-mediated immunity; antibody titers are low. The response ranges from a local granuloma with few parasites to a histiocytoma with many parasites.

Laboratory Diagnostics of visceral leishmaniasis Demonstration of the organism in host tissues cultured on a Novy-MacNeal-Nicolle (NNN) or other medium or detection of Leishman-Donovan bodies (amastigotes) in stained tissue samples. PCR can be performed using genus- or species-specific oligonucleotides. Established by examining bone marrow aspirates. Splenic aspirates have the highest yields but may be risky. Liver biopsy or aspiration of enlarged lymph nodes can also provide diagnostic material.

Laboratory Diagnostics of cutaneous and mucocutaneous leishmaniasis Demonstrating amastigotes on stained smears of a biopsy or of scrapings from the border of an ulcer. Culturing amastigotes on NNN medium inoculated with lesion material. PCR targeting parasite kinetoplast DNA has allowed detection of organisms that might be missed on histologic section or culturing.

Laboratory Diagnostics of cutaneous and mucocutaneous leishmaniasis Except in diffuse cutaneous leishmaniasis, the leishmanin skin test is usually positive.

Treatment There are two common therapies containing antimony, meglumine antimoniate (Glucantim®) and sodium stibogluconate (Pentostam®). Unfortunately, in many parts of the world, the parasite has become resistant to antimony and for visceral or mucocutaneous leishmaniasis, amphotericin is now the treatment of choice. Miltefosine (Impavido®), is a new drug for visceral, mucocutaneous and cutaneous leishmaniasis. Drug-resistant leishmaniasis may respond to immunotherapy (inoculation with parasite antigens plus an adjuvant) which aims to stimulate the body's own immune system to kill the parasite.

Prevention: Preventing sandfly bites is the most immediate form of protection. Insect repellent, appropriate clothing, screening of windows, and fine mesh netting around the bed (in endemic areas) will reduce exposure. Public health measures to reduce the sandfly population and animal reservoirs are important. There are no preventive vaccines or drugs for leishmaniasis.