• Leishmaniasis is a parasitic disease spreadintroduction by the bite of infected sand flies. There are several different forms of leishmaniasis. The most common are cutaneous and visceral. The cutaneous type causes skin sores. The visceral type affects internal organs such as the spleen, liver and bone marrow. People with this form usually have fever, weight loss and an enlarged spleen and liver. • Leishmaniasis is found in parts of about 88 countries. Most of these countries are in the tropics and subtropics. It is possible but very unlikely that you would get this disease in the United States. But you should be aware of it if you are traveling to the Middle East or parts of Central America, South America, Asia, Africa or southern Europe.
Types• Infection with Leishmania species can result in 3 main types of disease depending on the species, geographic region and host immune response.• Leishmania donovani produces visceral leishmaniasis (kala-azar). Symptoms include fever (often 2 fever spikes per day), enlargement of the spleen and liver, weakness, and progressive emaciation. The disease is often fatal without treatment, but survivors often develop immunity.• Leishmania tropica and L. mexicana produce cutaneous leishmaniasis which is characterized by skin lesions (oriental sore). Infected macrophages containing amastigotes are found primarily at the site of infection around the sores. The sores are chracterized by an elevated rim encircling the lesion.• Leishmania braziliensis produces mucocutaneous leishmaniasis, characterized by lesions near mucosal membranes. The intitial site if infection is a small red papule that ulcerates in a few weeks. The lesions are flat (no raised rim) and often oozing. Infections of the ear, nose and mouth area lead to degeneration of the cartilage and soft tissues, resulting in disfigurement.
Types• Cutaneous leishmaniasisAmericas -Leishmania tropica mexicana, Leishmaniabraziliensis, and Leishmania amazonensisOld World -Leishmania tropica, Leishmania major, Linfantum, and Leishmania aethiopica• Mucocutaneous leishmaniasis Americas -L braziliensis Old World -L aethiopica• Visceral leishmaniasisIndia, Kenya -Leishmania donovaniSouth Europe and North Africa -L infantumAmericas -Leishmania chagasi
• Amastigote of leishmania are spherical to ovoid .Leishmania measure 1-5 µm long by 1-2 µm wide They possess a large nucleus, a prominent kinetoplast, and a short axoneme The organisms reside in macrophages of the host and can be found throughout the body.
• promastigate: Promastigote 10-20 X 7-4 micrometers inLeptomonad stage size, fusiform in shape, it has one nucleus.central in position, and one anterior flagellum which is just as long as its body length. Promastigotes are found in the digestive tract of sandflies. which serve as an arthropod vector, and they can also be found in culture medium.
Leishmaniasis Life Cycle Infection occurs when infected sandfly regurgitates infective promastigotes into the blood whilefeeding. The promatigotes are phagocytized by macrophages and transform into amastigotes. The amastigoteThe life cycle is continued when a sandfly feeds on an infected person andingests the amastigotes in the macrophages.multiply by binary fission in the macrophages.
transmission• Human Stages• Sand fly injects promastigotes into the skin during a blood meal. *infective stage• Promastigotes are phagocytized by neutrophils that are rapidly recruited to the bite site.• Infected neutrophils release the parasites which are then consumed by macrophages.• Promastigotes transform into amastigotes inside macrophages. *diagnostic stage• Amastigotes multiply in cells (including macrophages) of various tissues. *diagnostic stage• Sand Fly Stages• Sand fly ingests infected macrophages when it takes a blood meal. Ingestion of parasitized cell.• Amastigotes transform into promastigotes in midgut.• Promastigotes divide and migrate to the anterior midgut and foregut.• Sand fly injects promastigotes into the skin during a blood meal. *infective stage
Risk factors• Children are at greater risk than adults in endemic areas.• Malnutrition has been shown to contribute to the development of disease.• Persons with AIDS are at 100-1000 times greater risk of developing visceral leishmaniasis in certain areas.• Incomplete therapy of initial disease is a risk factor for recurrence of leishmaniasis.• Some studies have shown protection against cutaneous leishmaniasis with vaccination of killed Leishmania promastigotes and live bacillus Calmette-Guérin (BCG). However, this does not seem to be protective against visceral leishmaniasis.• Of note, the bite of one infected sandfly is sufficient to cause the disease, since a sandfly can egest more than 1000 parasites per bite.
Cutaneous leishmania Leishmania tropica MostCutaneous leishmaniasis common form Characterized by one or more sores, or nodules on the skin Sores can change in size and appearance over time. Often described as looking somewhat like a volcano with a raised edge and central crater Sores are painless or painful
Cutaneous leishmaniasis• After the bite of an infected sandfly, the incubation period is usually several weeks after inoculation, but this incubation period is variable. Initial lesions can appear immediately after a bite, or the incubation period may last for several months. These lesions are usually painless.• Skin trauma can result in activation of seemingly latent cutaneous infection long after the initial bite.• Over a period of weeks to years, some lesions may resolve spontaneously without pharmacotherapy
Cutaneous leishmaniasis• Systemic signs usually are absent.• Initially, the lesion is a small, red papule up to 2 cm in diameter. Over several weeks, the papule becomes darker and will crust in the center, eventually ulcerating to present a typical appearance of an ulcer with raised edges and surrounding dusky red skin. The ulcers can be moist or open with seropurulent exudate or dry with a crusted scab.
Sores usually are found on exposed areas of skin, especially the extremities and face.
Cutaneous leishmaniasis • Regional adenopathy, satellite lesions, and subcutaneous nodules can be present. • Untreated sores can leave depigmented retracted scars.
• Mucotaneous leishmaniasis (MCL) cases are focused in South America, especially inMucotaneous leishmaniasis Brazil, Paraguay, Ecaudor, Bolivia, Peru, Colombia, andVenezuela. Ninety percent of the cases occur in Brazil, Bolivia, and Peru. Twenty percent of leishmaniasis patients in Brazil develop MCL. In Ecuador, many of the cases seem to be focused in the Amazon region. During the 1990-2003 period, there were 21,805 reports of MCL mostly from the Amazonian lowlands, some inter-Andean valleys, and throughout the Pacific coastal region. Other infections caused by various Leishmania species have occurred in Ethiopia, Kenya, Namibia, Central America, Guyana, Surinam, Panam, an d Sudan.
Mucocutaneous leishmaniasis• The incubation period is from 1-3 months. Mucocutaneous leishmaniasis can be the primary manifestation of the disease, but the primary lesions may also be limited to cutaneous manifestations, with mucosal lesions appearing only later in the course of disease when untreated cutaneous lesions progress to involve the oral and nasal surfaces. Cases in which the time between the primary lesion and the appearance of mucosal involvement is up to 2 decades have been reported.• Initial symptoms related to mucosal lesions may include nasal obstruction and bleeding.• Mucosal lesions become painful gradually and can become sites of infection, sometimes leading to sepsis.
Mucocutaneous leishmaniasis• Mucosal lesions can progress to involve the entire nasal mucosa and the hard and soft palates. Without treatment, the entire nasal mucosa and palates become deformed with ulceration and erosion of the nasal septum, lips, and palate. The disease attacks cartilaginous areas (as depicted below) but usually spares bony structures, and it can leave extreme disfigurement.
Mucocutaneous leishmaniasis• Cutaneous lesions can be single or multiple.• Secondary mucosal lesions often develop after the primary lesion has healed.• Signs include gingival edema, periodontitis, and adenopathy.
single or multpile lesions and ulcers develop at the mucosal regions (nose, mouth, throat cavities) and in the adjacent tissueextensive disfiguring of the nasal septum, lips, and palate (does not include the bones)
• L. donovani produces visceral leishmaniasis or Kala-azar.Visceral leishmaniasis Kala-azar is an Indian name, meaning "black fever" (darkening of the skin). • Most severe form of the disease, usually fatal if left untreated Usually associated with fever, weight loss, and an enlarged spleen and liver.
• Habitat:- internal organ (liver, lymph nodes, spleenVisceral leishmaniasis ,bone marrow) Disease- Visceral leishmaniasis, Kala azar, Dum Dum fever Transmission- VL. is transmitted chiefly by female Sandflies (Phlebotomus spp.)
visceral leishmaniasis• Kala azar is the Indian name for visceral leishmaniasis. The term means "black disease," which is a reference to the characteristic darkening of the skin that is seen in patients with the disease.• Many subclinical cases occur and go unrecognized for each clinically recognized case.• Malnutrition has been shown to contribute to the development of clinical disease.• Like cutaneous leishmaniasis, visceral leishmaniasis can take different forms ranging from asymptomatic or self-resolving disease to fulminant disease.• Onset can be insidious or sudden.• In endemic areas, kala azar may be suspected in a patient with persistent, irregular, or remittent fever; leukopenia; and splenomegaly. Other accompanying symptoms may be lymphadenopathy and weight loss.• Fever can be continuous, intermittent, or remittent, and it can recur at irregular intervals.
visceral leishmaniasis• Bouts of fever occur.• Hepatosplenomegaly occurs secondary to compensatory production of phagocytic blood cells.• Wasting and weakness are observed.• Darkening of the skin is characteristic (thus, the name kala azar or black fever).• Diarrhea may occur.• Lymphadenopathy is often present.• In visceral leishmaniasis, patients may die of hemorrhage (secondary to infiltration of the hematopoietic system), severe anemia, secondary bacterial infections of mucous membranes, bacterial pneumonia, septicemia, tuberculosis, dysentery, or measles
Mucocutaneous leishmaniasis• Diagnosis preferably is made by culture of the organism, but organisms are often scant.• Results from the leishmanin skin test are positive after 2-3 months of infection.• Serologic tests are available in some centers and, as in the cutaneous form, PCR is becoming more common as a method of diagnosing the disease.• Because the organisms often are scarce, the diagnosis often is epidemiologic (travel to endemic area, clinical picture coupled with laboratory data).
Visceral leishmaniasis• Definitive diagnosis is made by observing the parasite (more specifically, amastigotes in tissue) on stained Giemsa smears or by observing the culture of bone marrow, splenic, hepatic, or lymph node aspirates.• Cultures are grown on NNN medium• Serologic testing is useful with the indirect fluorescent antibody test• An enzyme-linked immunosorbent assay (ELISA)• Obtain a complete blood count. Bone marrow infiltration may cause anemia, thrombocytopenia, and leukopenia with a relative monocytosis and lymphocytosis.• Perform liver function tests (LFTs).• Run a coagulation panel.
Cutaneous leishmaniasis• Diagnosis usually is based on the appearance of the lesion.• microscopy of the parasite in Giemsa stains or histological section can reveal the parasite and should be attempted first.• The leishmaniasis skin test (Montenegro test) produces positive results 3 months after the appearance of lesions.• polymerase chain reaction (PCR) is being used more frequently and is more accurate in determining new- onset leishmaniasis than serum tests.
Cutaneous leishmaniasis• Treatment of cutaneous leishmaniasis differs according to the etiology and geographic location of the infection. For certain types of cutaneous leishmaniasis where the potential for mucosal spread is low, topical paromycin can be used. If only one or a few small lesions are present (excluding face or over a joint), careful follow- up without drug treatment may be appropriate.• For more invasive lesions (eg, those failing to respond to topical treatment; metastatic spread to the lymph nodes; or large, disfiguring, and multiple skin lesions, especially those on the face, near mucosal surfaces, or near joints), sodium stibogluconate or pentamidine can be used.• Other reported treatments include topical imiquimod cream, cryotherapy, thermotherapy, ketoconazole, photodynamic therapy, itraconazole, allopurinol, and miltefosine (not FDA approved, requires Investigation New Drug [IND] application and local Institutional Review Board [IRB] approval).
Mucosal leishmaniasis• Amphotericin B deoxycholate may be first-line therapy for advanced mucosal disease.• Pentavalent antimony for a course of 4 weeks has been recommended.• Miltefosine is the only oral medication approved for both VL and ML.
Visceral leishmaniasis• Be alert for complications related to reticuloendothelial system failure. Patients may have bleeding or neutropenia leading to infectious conditions such as pneumonia or diarrhea. Transfusions may be necessary for severe bleeding or anemia. Antibiotics are indicated to treat intercurrent infectious conditions.• Outside of India, treatment with a pentavalent antimonial compound usually is effective. The use of an alternative parenteral agent should be considered even for first-line therapy in areas where resistance to pentavalent antimony therapy is prevalent, as it is in India, or if nonantimonial therapy would be advantageous for other reasons (eg, toxicity profile, duration of therapy).• A major advance has been the advent of liposomal formulations of amphotericin B, in which various alternative lipids have replaced deoxycholate.• Other parenteral alternatives that have merit include amphotericin B (not only in deoxycholate form but also in liposomal forms) and have generally replaced pentamidine. Miltefosine, a chemotherapeutic agent, is the first extremely effective oral agent for visceral leishmaniasis but is not currently available in the United States. Injectable paromycin has also been reported to be noninferior to amphotericin B but also is not currently FDA approved.