Leishmaniasis & Malaria: PDF

OTHER Haemoflagellates Leishmaniasis  Leishmania Parasites and Diseases SPECIES Disease Leishmania tropica Leishmania major Cutaneous leishmaniasis Leishmania braziliensis Mucocutaneous leishmaniasis Leishmania donovani...

OTHER Haemoflagellates Leishmaniasis  Leishmania Parasites and Diseases SPECIES Disease Leishmania tropica Leishmania major Cutaneous leishmaniasis Leishmania braziliensis Mucocutaneous leishmaniasis Leishmania donovani Visceral leishmaniasis Phylum: Sarcomastigophora Order: Kinetoplastida  HETEROXENEUOS Life Cycle Amastigote Promastigote Mammalian stage Insect (sand fly) Non-motile Motile Intracellular Midgut  Leishmaniasis Life-Cycle Sand fly Stages Human Stages Sand fly takes a blood meal Divide in midgut and 1 (Injects promastigote Promastigotes are 8 migrate to proboscis stage into the tissue) 2 Phagocytized by macrophages i Promastigotes transfer Amastigotes transform 3 7 Into promastigote into amastigotes inside macrophages stage in midgut d 6 Ingestion of 4 Amastigotes multiply in cells Parasitized cell (Including macrophages) of Sand fly takes 5 Various tissues i Infective stage a blood meal (ingest macrophages Diagnostic d stage Infected with amastigotes ) Sand fly  Clinical types of cutaneous leishmaniasis Leishmania major: Zoonotic cutaneous (animal- vector-human) leishmaniasis: wet lesions with severe reaction Leishmania tropica: Anthroponotic(human- vector-human) cutaneous leishmaniasis: Dry lesions with minimal ulceration Oriental sore (most common) classical self- limited ulcer  Impact of Leishmania infection on immune cells. Mast cells collaborate in disease progression by secreting IL-4 and IL-13 fostering Th2 responses and parasite survival (panel 1). Neutrophils, macrophages, and DCs can either eliminate or promote parasite survival. Recruited neutrophils eliminate leishmanial parasites through phagocytosis, ROS, and NETs release. Leishmania can survive transiently within neutrophils by inhibiting phagolysosome biogenesis and oxidative stress, and by delaying neutrophil apoptosis.  Infected neutrophils also secrete IL-8 and MIP1β, which attract additional neutrophils and other phagocytic cells, favoring Leishmania survival and pathology (panel 2). Macrophages can be differentiated in M1 or M2 during leishmaniasis. M1 macrophages produce proinflammatory cytokine and chemokines, NO and ROS, booster Th1 responses, and favor disease control. Diagnosis: Smear of skin ulcer : Wright’s or Giemsa stain – microscopy for LD bodies (amastigotes). Biopsy: microscopy for LD bodies or culture in nutirtional medium for promastigotes  Visceral leishmaniasis There are geographical variations. The diseases is called kala-azar (Dum Dum fever in India) Leishmania infantum mainly affect children Leishmania donovani mainly affects adults  PATHOGENESIS Fever & malaise(fatigue). Weight loss & Anaemia Abdomen Protrusion - hepatosplenomegaly Edema in face, nosebleed and difficulty in breathing vomiting and Diarrhea - Secondary bacterial infection leads to death. - Untreated disease can be fatal. - After recovery it might produce a condition called post kala-azar dermal leishmaniasis (PKDL) is common in India. - It is marked by reddish, depigmented nodules in the skin. hepatosplenomegaly mucocutaneous PKDL  Visceral leishmaniasis Diagnosis (1) Parasitological diagnosis: METHOD Bone marrow aspirate 1. microscopy Splenic aspirate 2. culture in NNN medium Lymph node Tissue biopsy Bone marrow aspiration Bone marrow amastigotes (2) Immunological Diagnosis: Specific serologic tests: Direct Agglutination Test (DAT), ELISA, IFAT Skin test (leishmanin test) for survey of populations and follow-up after treatment.  Phylum Apicmplexa Haemosporiids Plasmodium There are four species of Plasmodium: P. falciparum, P. vivax, P.ovale and P. malariae. P. falciparum causes severe often fatal malaria and is responsible for most deaths, with most victims being children.  Malaria Species 1-Plasmodium falciparum: malignant tertian malaria 2-Plasmodium vivax: benign tertian malaria 3-Plasmodium ovale:benign tertian malaria 4- Plasmodium malariae: quartan malaria  Life cycle of malaria Plasmodium has two hosts: mosquitoes (female Anopheles ) and humans. Sexual reproduction takes place in the mosquito and the parasite is transmitted to humans when the mosquito takes a blood meal.  Life cycle of malaria: humans The mosquito injects Plasmodium into a human in the form of sporozoites. The sporozoites first invade liver cells and asexually reproduce to produce huge numbers of merozoites which spread to red blood cells where more merozoites are produced through more asexual reproduction. Some parasites transform into sexually reproducing gametocytes and these if ingested by a mosquito continue the cycle.  Life cycle of malaria: mosquitoes As soon as the mosquito hits a blood vessel to take blood meal, the host’s body responds by clotting the wound. Platelets clump around the proboscis and release chemicals which cause the platelets to clot together. To slow clotting and speed feeding, mosquitoes inject anticoagulants including one called apyrase that unglues the platelets. They also inject other chemicals that expand the blood vessels.  Gametocytes ingested by a mosquito mature into macro- and microgametes and combine in the mosquito’s stomach to produce zygotes. These zygotes develop into motile elongated ookinates. The ookinates invade the mosquito’s midgut wall where they ultimately produce sporozoites, which make their way to the salivary glands where they can be injected into a new human host.  Behavior of Plasmodium in humans The parasite must avoid the host’s immune system. To do so while in the body it moves from one hiding place to another. The parasite moves first to the liver. Can get there in about 30 minutes, which is usually fast enough to avoid triggering the immune system. At the liver Plasmodium enters a liver cell. The cell responds by grabbing Plasmodium proteins and displaying the antigens on its cell surface in a special cup the major histocompatibility complex or MHC.  The immune system recognizes the Plasmodium antigens and mounts an immune response. However, in a week before the immune system has mounted its full response, the parasite has produced about 40,000 copies of itself, and these burst out of the liver to seek red blood cells. The parasites leave the liver, reenter the bloodstream, and find a red blood cell to enter. Each parasite spends two days in a red blood cell consuming the hemoglobin and reproducing. Red blood cell infected with malaria Plasmodium in red blood cell  The parasite uses a set of organelles concentrated at its apical end to gain entry (apical complex). A suite of proteins are produced that cause the red blood cell’s membrane to open and let the parasite squeeze in. It takes only about 15 seconds for the parasite to get in. Inside the red blood cell, the Plasmodium consumes the hemoglobin. It takes in a small amount of hemoglobin, slices it apart with enzymes and harvests the energy released. The toxic core of the hemoglobin molecule is processed into an inert molecule called hemozoin (malaria pigment). Infected cells clump up in capillaries.  After another day the contents of the cell have been used up. The cell ruptures and 16 new parasites burst out to infect other red blood cells. Some of these parasites transform into sexually reproducing gametocytes and these if ingested by a mosquito will continue the cycle. In the red blood cells Plasmodium is invisible to the immune system because the red blood cells have no MHC and cannot alert the immune system.  The latch proteins however stimulate the immune system. The latch protein is made by a single gene, but Plasmodium has over 100 such genes each of which produces a unique latch. In each generation some of the new parasites switch on a new latch gene and so the immune system is always playing catch up.  Malarial Paroxysm Cold stage feeling of intense cold vigorous shivering lasts 15-60 minutes Hot stage intense heat dry burning skin throbbing headache lasts 2-6 hours Sweating stage profuse sweating declining temperature exhausting and weak ness→ sleep - lasts 2-4 hours Laboratory diagnosis of malaria Laboratory diagnosis of malaria  Laboratory diagnosis of malaria The Malaria Parasite Trophozoites Three developmental stages seen in blood films: CCMOVBD CCMOVBD Schizont Gametocyte 1. Trophozoite 2. Schizont 3. Gametocyte CCMOVBD CCMOVBD Laboratory diagnosis of malaria Laboratory diagnosis of malaria Rapid diagnostic tests detect malaria antigens Rapid diagnostic tests detect malaria antigens  Main Malaria Control Measures 1. Early diagnosis and treatment of cases 2. Vector control : adult mosquitoes :insecticides mosquito larvae: draining breeding sites 3. Reducing vector-human contact: bed nets , repellents 4. Early detection and control of epidemics. 5. Mosquito nets save lives.  Apicomplexa in tissues FAMILY SARCOCYSTIDAE e.g. Toxoplasma gondii Toxoplasma is an intracellular parasite of many kinds of tissues, including muscle and intestinal epithelium. The life cycle includes enteroepithelial and extraintestinal stages in domestic cats and other felines, but extraintestinal stages only in other hosts. Sexual reproduction occur only in cat.  Toxoplasma gondii exists in three forms All parasite stages are infectious. 1. TACHYZOITES 2. TISSUE CYSTS (BRADYZOIT) 3. OOCYSTS Oocysts  Tachyzoite stage Rapidly growing stage observed in the early stage of infection inhabits in the body fluid. Crescent-shaped. One end is more pointed than the other subterminal placed nucleus. Asexual form. It can infect phagocytic and non-phagocytic, cells.  Bradyzoites Are slow-growing stage inside the tissue cysts. Protective cyst wall is dissolved and bradyzoites infect tissue and transform into tachyzoites. Bradyzoites are released in the intestine and are highly infective if ingested.  THE OOCYST The oocyst is noninfectious before sporulation.. Sporulated oocysts are subspherical to ellipsoidal. Each oocyst has two ellipsoidal sporocysts. Each Sporocyst contains four sporozoites. Shedding occurs 3-5 days after ingestion of tissue cysts Sporulated oocyst remain infective for months. Unsporulated oocysts Two sporocysts Sporulated oocysts  Oocysts in the feces of cat Cat ingests tissue cysts containing bradyzoites. Gametocytes develop in the small intestine. Sexual cycle produces the oocyst which is excreted in the feces. Oocysts appear in the cat’s feces 3-5 days after infection by cysts. Oocysts require oxygen and they sporulate in 1- 5 days.  Oocytes do not become infectious until they sporulate, sporulation occurs Tissue phase (accidental host). 1- 5 days after that the oocyte is excreted in the feces. Intermediate host gets infected by ingesting sporulated oocysts. Human, cattle, birds, rodents, pigs, and sheep. Intermediate host  Disease: Toxoplasmosis 1) Acquired toxoplasmosis painful, swollen lymph glands in the cervical. This symptom may be associated with fever, headache, muscle pain, anemia, and sometimes lung complications. Cysts and cyst rupture in the retina can also lead to blindness. 2) Congenital toxoplasmosis About 98% of cases of Toxoplasmosis are acquired through Congenital Toxoplasmosis.  Congenital Toxoplasmosis 1. Intracerebral calcification. toxoplasmic encephalitis 2. Chorioretinitis. Ocular toxoplasmosis 3. Convulsions. 4. Mental retardation. 5. Cardiomegaly.  Lab Diagnosis of Toxoplasmosis: 1) The demonstration of the Toxoplasma gondii organism in blood, body fluids, or tissue. 2) Detection of T. gondii antigen in blood or body fluids by enzyme-linked immunosorbent assay (ELISA) technique. 3) Polymerase Chain Reaction on body fluids, including CSF, amniotic fluid, and blood.