LEC3Leish.pdf

LEC.3 Blood and tissue flagellates Dr. Maysoon A.Merdaw Leishmania spp. Leishmania spp. caused Leishmaniasis disease spread by the bite of certain types of sandflies. Geographical distribution divided the disease to 1- Old world leishmaniasis caused by L. donovani, L. infantum, L. tropica, L. major,...

LEC.3 Blood and tissue flagellates Dr. Maysoon A.Merdaw Leishmania spp. Leishmania spp. caused Leishmaniasis disease spread by the bite of certain types of sandflies. Geographical distribution divided the disease to 1- Old world leishmaniasis caused by L. donovani, L. infantum, L. tropica, L. major, L. aethiopica are transmitted by the sandflies genus Phlebotomus; 2- New world leishmaniasis caused by L. mexicana, L. braziliensis and etc... are transmitted by the sandflies genus Lutzomyia and Psychodopygus. The term ‘New World’ refers to the Americas and the ‘Old World’ is used for the rest of the world. Morphology and Life cycle The life cycle of Leishmania is completed in two hosts, humans and sandflies. Two stages are known; the amastigote which is spherical or subspherical and the promastigote which is pyriform or spindle shape with flagellum. Natural reservoir hosts humans, dogs and wild rodents. The adult female sandfly is a bloodsucker, usually feeding at night. When the fly bites a reservoir host or infected person with Leishmania, the pathogen reaches the stomach of the sandfly, the amastigotes quickly transform into elongated and motile forms called the promastigotes. The promastigotes live extracellularly in the alimentary canal, reproducing asexually, then migrate to the proximal end of the 1 gut. As the fly bites, the promastigotes are released from the proboscis and introduced locally at the bite site. Once inside the human host, promastigotes invade macrophages. Inside the cells they transform back into the smaller amastigote form. The amastigotes replicate in the macrophage cell. After repeated multiplication, they break down their host cell by complete pressure of mass. The daughter cells protozoans then migrate to fresh cells (Cutaneous or mucocutaneous leishmaniasis) or through the bloodstream (visceral leishmaniasis) to find new hosts. In this way the infection is progressive, spreading to the host's mononuclear phagocyte system, particularly the spleen and liver. The free amastigotes in peripheral tissues are then ingested by sandfly to enter another cycle. Risk factors include poverty, malnutrition, deforestation, lack of sanitation and urbanization. Leishmaniasis is mainly a zoonotic disease. 2 Old world leishmaniasis - Cutaneous leishmaniasis (oriental sore) Is the most common form caused by L. tropica, L. major, L. aethiopica, found in 88 tropical and subtropical countries which causes an open sore at the bite sites, which heals in a few months to a year and half, leaving an unpleasantlooking scar. Diffuse cutaneous leishmaniasis produces widespread skin lesions which resemble leprosy, and may not heal on its own. Habitat is inside reticuloendothelial cells of the skin. Pathogenesis: Leishmania invades human macrophages and replicates intracellularly. A raised, red lesion develops at the site of the bite (Incubation period varies from a few weeks to 6 months and in some cases it may be 1–2 years). Clinically, the lesion begins as a raised papule about 2.5 cm in diameter. The lesion then ulcerates and may become secondarily infected with bacteria. One factor restricting the parasites causing cutaneous leishmaniasis to the skin may simply be temperature. Diagnosis -A skin scraping with microscopic analysis using Wright or Giemsa stain. -Needle aspiration of tissue fluid from the margin of a lesion can yield fluid for culture (can be on NNN medium) to isolate the organism and identify the species. -DNA testing (PCR). -Leishmanin skin test (Montenegro test) delayed-type hypersensitivity reaction to intradermal crude Leishmania antigen. - Visceral leishmaniasis (kala-azar) Also known as black fever, and Dumdum fever, is the most severe form of leishmaniasis and, without proper diagnosis and treatment, is associated with 3 high fatality. Caused by obligate intracellular parasite Leishmania donovani, L. infantum (infantile visceral leishmaniasis) Habitat: reticuloendothelial cells, predominately of liver, spleen, bone marrow and lymph nodes of man and dogs. Pathogenesis: The parasite spreads from the site of inoculation to multiply in reticuloendothelial cells, especially in the liver, spleen, bone marrow and lymph nodes. This leads to progressive enlargement of these organs. The most typical symptoms are fever and the enlargement of the spleen, liver and lymph nodes, anaemia, leucopenia, and skin changes. Death is due to secondary infections. Sometime after successful treatment—generally a few months with African kala-azar, or as much as several years with the Indian strain—a secondary form of the disease may set in, called post kala-azar dermal leishmaniasis, or PKDL. This condition caused by the reversal of L.donovani from viscerotropic to dermatotropic, manifests first as small, measle-like skin lesions on the face, which gradually increase in size and spread over the body. PKDL is not seen with L. infantum infection. Diagnosis Non specific tests: blood count, haemoglobin and serum protein estimation. Parasitological diagnosis: blood film stained with Leishman or Giemsa stain, culture in specific media, visualization of the amastigotes in splenic or bone marrow aspirate, PCR (polymerase chain reaction) tests for the detection of Leishmania DNA. Immunological tests: Serological testing is much more frequently used in areas where leishmaniasis is endemic. Leishmanin test is negative in active cases of kala-azar because the Cellmediated immunity is impaired in active kala-azar patients who consequently lack a delayed hypersensitivity response. 4 Diagnosis of PKDL can be established by demonstration of amastigote form of L. donovani by a microscope of Leishman-stained smear prepared from the biopsy material obtained from nodular lesions. New world leishmaniasis - Mucocutaneous leishmaniasis (espundia) It causes both skin and mucosal ulcers with damage primarily of the nose and mouth. It can be highly disfiguring if not promptly treated. Caused by L. braziliensis and, L. mexicana, which are mainly found in certain South America, and Central America respectively. Pathogenesis: Habitat of these parasites occur as intracellular parasites (amastigote form) inside the macrophages of the skin and mucous membrane of the nose and buccal cavity. Leishmania invades human macrophages and replicates intracellularly. A raised, red lesion develops at the site of the bite. The lesion may spontaneously heal with scarring, but then reappear elsewhere (especially as destructive mucocutaneous lesions). Diagnosis: as in cutaneous leishmaniasis Treatments: The treatment needed is determined by where the disease is acquired, the species of Leishmania, and the type of infection. Some possible medications used for visceral disease include liposomal amphotericin B, a combination of pentavalent antimonials and paromomycin, and miltefosine. For cutaneous disease, paromomycin, fluconazole, or pentamidine may be effective. Prevention Leishmaniasis can be partly prevented by: -sleeping under nets treated with insecticide. 5 -spraying insecticides to kill sandflies. -treating people with the disease early to prevent further spread. -reservoir control programs. Vaccination: leishmania is an intracellular pathogen since it requires strong cell mediated immunity to be controlled. However most of vaccines trials provide humoral response. 6