Leishmania Infection

Leishmania

Leishmaniasis is a disease caused by protozoan parasites that belong to the genus Leishmania and is transmitted by the bite of certain species of sand fly (subfamily Phlebotominae). Two genera transmit Leishmania to humans: Lutzomyia in the New World and Phlebotomus in the Old World.[1]

Most forms of the disease are transmissible only from animals (zoonosis), but some can be spread between humans. Human infection is caused by about 21 of 30 species that infect mammals. These include the L. donovani complex with three species (L. donovani, L. infantum, and L. chagasi); the L. mexicana complex with 3 main species (L. mexicana, L. amazonensis, and L. venezuelensis); L. tropica; L. major; L. aethiopica; and the subgenus Viannia with four main species (L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) panamensis, and L. (V.) peruviana). The different species are morphologically indistinguishable, but they can be differentiated by isoenzyme analysis, DNA sequence analysis, or monoclonal antibodies.

Cutaneous leishmaniasis is the most common form of leishmaniasis. Visceral leishmaniasis is a severe form in which the parasites have migrated to the vital organs.

Classification:
Leishmaniasis may be divided into the following types:[2]:422–428

Cutaneous leishmaniasis
Mucocutaneous leishmaniasis
Visceral leishmaniasis
Post-kala-azar dermal leishmaniasis
Viscerotropic leishmaniasis

Life cycle:
Leishmaniasis is transmitted by the bite of female phlebotomine sandflies. The sandflies inject the infective stage, metacyclic promastigotes, during blood meals (1). Metacyclic promastigotes that reach the puncture wound are phagocytized by macrophages (2) and transform into amastigotes (3). Amastigotes multiply in infected cells and affect different tissues, depending in part on which Leishmania species is involved (4). These differing tissue specificities cause the differing clinical manifestations of the various forms of leishmaniasis. Sandflies become infected during blood meals on an infected host when they ingest macrophages infected with amastigotes (5,6). In the sandfly's midgut, the parasites differentiate into promastigotes (7), which multiply, differentiate into metacyclic promastigotes and migrate to the proboscis (8)

Signs and symptoms:
The symptoms of leishmaniasis are skin sores which erupt weeks to months after the person affected is bitten by sand flies. Other consequences, which can become manifest anywhere from a few months to years after infection, include fever, damage to the spleen and liver, and anaemia.

In the medical field, leishmaniasis is one of the famous causes of a markedly enlarged spleen, which may become larger even than the liver. There are four main forms of leishmaniasis:

Visceral leishmaniasis – the most serious form and potentially fatal if untreated.
Cutaneous leishmaniasis – the most common form which causes a sore at the bite site, which heal in a few months to a year, leaving an unpleasant looking scar. This form can progress to any of the other three forms.
Diffuse cutaneous leishmaniasis – this form produces widespread skin lesions which resemble leprosy and is particularly difficult to treat.
Mucocutaneous leishmaniasis – commences with skin ulcers which spread causing tissue damage to (particularly) nose and mouth

Diagnosis:
Leishmaniasis is diagnosed in the haematology 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's or Giemsa's stain (pH 7.2) for 20 minutes. Amastigotes are seen with monocytes or, less commonly in neutrophil in peripheral blood and in macrophages in aspirates. They are small, round bodies 2-4μm in diameter with indistinct cytoplasm, a nucleus and a small rod-shaped kinetoplast. Occasionally amastigotes may be seen lying free between cells.[15]

Treatment:
There are two common therapies containing antimony (known as pentavalent antimonials), meglumine antimoniate (Glucantime) and sodium stibogluconate (Pentostam). It is not completely understood how these drugs act against the parasite; they may disrupt its energy production or trypanothione metabolism. Unfortunately, in many parts of the world, the parasite has become resistant to antimony and for visceral or mucocutaneous leishmaniasis,[16] but the level of resistance varies according to species.[17] Amphotericin (AmBisome) is now the treatment of choice;[18] its failure in some cases to treat visceral leishmaniasis (Leishmania donovani) has been reported in Sudan,[19] but this may be related to host factors such as co-infection with HIV or tuberculosis rather than parasite resistance.

Miltefosine (Impavido), is a new drug for visceral and cutaneous leishmaniasis. The cure rate of miltefosine in phase III clinical trials is 95%; Studies in Ethiopia show that it is also effective in Africa. In HIV immunosuppressed people who are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment. Clinical trials in Colombia showed a high efficacy for cutaneous leishmaniasis. In mucocutaneous cases caused by L.brasiliensis it has shown to be more effective than other drugs. Miltefosine received approval by the Indian regulatory authorities in 2002 and in Germany in 2004. In 2005 it received the first approval for cutaneous leishmaniasis in Colombia. Miltefosine is also currently being investigated as treatment for mucocutaneous leishmaniasis caused by Leishmania braziliensis in Colombia,[16] and preliminary results are very promising. It is now registered in many countries and is the first orally administered breakthrough therapy for visceral and cutaneous leishmaniasis.[20](More, et al., 2003). In October 2006 it received orphan drug status from the US Food and Drug administration. The drug is generally better tolerated than other drugs. Main side effects are gastrointestinal disturbance in the 1–2 days of treatment which does not affect the efficacy. Because it is available as an oral formulation, the expense and inconvenience of hospitalisation is avoided, which makes it an attractive alternative.

The Institute for OneWorld Health has reintroduced the drug paromomycin for treatment of leishmaniasis, results with which led to its approval as an orphan drug. The Drugs for Neglected Diseases Initiative is also actively facilitating the search for novel therapeutics. A treatment with paromomycin will cost about $10. The drug had originally been identified in 1960s, but had been abandoned because it would not be profitable, as the disease mostly affects poor people.[21] The Indian government approved paromomycin for sale in August 2006.[22] A 21-day course of paromomycin produces a definitive cure in >90% of patients with visceral leishmaniasis.[23]

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.[24]

Several potential vaccines are being developed, under pressure from the World Health Organization, but as of 2006[update] none is available. The team at the Laboratory for Organic Chemistry at the Swiss Federal Institute of Technology (ETH) in Zürich are trying to design a carbohydrate-based vaccine [1]. The genome of the parasite Leishmania major has been sequenced,[25] possibly allowing for identification of proteins that are used by the pathogen but not by humans; these proteins are potential targets for drug treatments.

The compound vasicine (peganine), found in the plant Peganum harmala, has been tested in vitro against the promastigote stage of Leishmania donovani, the causative agent of visceral leishmaniasis. It was shown that this compound induces apoptosis in Leishmania promastigotes. "Peganine hydrochloride dihydrate, besides being safe, was found to induce apoptosis in both the stages of L. donovani via loss of mitochondrial transmembrane potential."[26]

Another alkaloid harmine found in Peganum harmala, ". . .because of its appreciable efficacy in destroying intracellular parasites as well as non-hepatotoxic and non-nephrotoxic nature, harmine, in the vesicular forms, may be considered for clinical application in humans."[27]

HIV Protease inhibitors have been found to be active against Leishmania species in two in vitro studies in Canada and India. The study reported that the intracellular growth of Leishmania parasites was controlled by nelfinavir and ritonavir in a human monocyte cell line and also in human primary monocyte-derived macrophages.[28]

Leishmania Infection
Heart Murmur Adenoids Bursitis Eye Infections Hepatitis C Glomerulonephritis (GN) Male And Female Infertility - Causes Escherichia Coli O157 Clostridium Epstein-Barr virus Cervical cancer Allergy-Immunology Glossary Mumps Cancer Head And Neck Blood Coagulation Disorders Sickle-Cell Disease Gastrointestinal Disorders Common cold Warts - Causes, Symptoms, And Treatment What Causes Acne Clarithromycin Leishmania Infection Angiostrongylus Infection Tuberculosis Addison's disease Coming Soon Headaches And Allergies Hay fever Hand, Foot, & Mouth Disease Pubic Lice Infestation Psoriasis Protein Suppresses Allergy Prostate Cancer Prenatal Testing Prader-Willi Syndrome Post-Traumatic Stress Disorder (PTSD) Poison Plants Pneumococcal Disease Plague Pet Allergy Penicillin Allergy Patent Ductus Arteriosus (PDA) Polio Disease Pinworm Infection Pheochromocytoma Phenylketonuria Pertussis Disease PAD (Peripheral Arterial Disease) Peanut Allergy Symptoms Parvovirus B19 (Fifth Disease) Pacemaker	Leishmania Leishmaniasis is a disease caused by protozoan parasites that belong to the genus Leishmania and is transmitted by the bite of certain species of sand fly (subfamily Phlebotominae). Two genera transmit Leishmania to humans: Lutzomyia in the New World and Phlebotomus in the Old World.[1] Most forms of the disease are transmissible only from animals (zoonosis), but some can be spread between humans. Human infection is caused by about 21 of 30 species that infect mammals. These include the L. donovani complex with three species (L. donovani, L. infantum, and L. chagasi); the L. mexicana complex with 3 main species (L. mexicana, L. amazonensis, and L. venezuelensis); L. tropica; L. major; L. aethiopica; and the subgenus Viannia with four main species (L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) panamensis, and L. (V.) peruviana). The different species are morphologically indistinguishable, but they can be differentiated by isoenzyme analysis, DNA sequence analysis, or monoclonal antibodies. Cutaneous leishmaniasis is the most common form of leishmaniasis. Visceral leishmaniasis is a severe form in which the parasites have migrated to the vital organs. Classification: Leishmaniasis may be divided into the following types:[2]:422–428 Cutaneous leishmaniasis Mucocutaneous leishmaniasis Visceral leishmaniasis Post-kala-azar dermal leishmaniasis Viscerotropic leishmaniasis Life cycle: Leishmaniasis is transmitted by the bite of female phlebotomine sandflies. The sandflies inject the infective stage, metacyclic promastigotes, during blood meals (1). Metacyclic promastigotes that reach the puncture wound are phagocytized by macrophages (2) and transform into amastigotes (3). Amastigotes multiply in infected cells and affect different tissues, depending in part on which Leishmania species is involved (4). These differing tissue specificities cause the differing clinical manifestations of the various forms of leishmaniasis. Sandflies become infected during blood meals on an infected host when they ingest macrophages infected with amastigotes (5,6). In the sandfly's midgut, the parasites differentiate into promastigotes (7), which multiply, differentiate into metacyclic promastigotes and migrate to the proboscis (8) Signs and symptoms: The symptoms of leishmaniasis are skin sores which erupt weeks to months after the person affected is bitten by sand flies. Other consequences, which can become manifest anywhere from a few months to years after infection, include fever, damage to the spleen and liver, and anaemia. In the medical field, leishmaniasis is one of the famous causes of a markedly enlarged spleen, which may become larger even than the liver. There are four main forms of leishmaniasis: Visceral leishmaniasis – the most serious form and potentially fatal if untreated. Cutaneous leishmaniasis – the most common form which causes a sore at the bite site, which heal in a few months to a year, leaving an unpleasant looking scar. This form can progress to any of the other three forms. Diffuse cutaneous leishmaniasis – this form produces widespread skin lesions which resemble leprosy and is particularly difficult to treat. Mucocutaneous leishmaniasis – commences with skin ulcers which spread causing tissue damage to (particularly) nose and mouth Diagnosis: Leishmaniasis is diagnosed in the haematology 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's or Giemsa's stain (pH 7.2) for 20 minutes. Amastigotes are seen with monocytes or, less commonly in neutrophil in peripheral blood and in macrophages in aspirates. They are small, round bodies 2-4μm in diameter with indistinct cytoplasm, a nucleus and a small rod-shaped kinetoplast. Occasionally amastigotes may be seen lying free between cells.[15] Treatment: There are two common therapies containing antimony (known as pentavalent antimonials), meglumine antimoniate (Glucantime) and sodium stibogluconate (Pentostam). It is not completely understood how these drugs act against the parasite; they may disrupt its energy production or trypanothione metabolism. Unfortunately, in many parts of the world, the parasite has become resistant to antimony and for visceral or mucocutaneous leishmaniasis,[16] but the level of resistance varies according to species.[17] Amphotericin (AmBisome) is now the treatment of choice;[18] its failure in some cases to treat visceral leishmaniasis (Leishmania donovani) has been reported in Sudan,[19] but this may be related to host factors such as co-infection with HIV or tuberculosis rather than parasite resistance. Miltefosine (Impavido), is a new drug for visceral and cutaneous leishmaniasis. The cure rate of miltefosine in phase III clinical trials is 95%; Studies in Ethiopia show that it is also effective in Africa. In HIV immunosuppressed people who are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment. Clinical trials in Colombia showed a high efficacy for cutaneous leishmaniasis. In mucocutaneous cases caused by L.brasiliensis it has shown to be more effective than other drugs. Miltefosine received approval by the Indian regulatory authorities in 2002 and in Germany in 2004. In 2005 it received the first approval for cutaneous leishmaniasis in Colombia. Miltefosine is also currently being investigated as treatment for mucocutaneous leishmaniasis caused by Leishmania braziliensis in Colombia,[16] and preliminary results are very promising. It is now registered in many countries and is the first orally administered breakthrough therapy for visceral and cutaneous leishmaniasis.[20](More, et al., 2003). In October 2006 it received orphan drug status from the US Food and Drug administration. The drug is generally better tolerated than other drugs. Main side effects are gastrointestinal disturbance in the 1–2 days of treatment which does not affect the efficacy. Because it is available as an oral formulation, the expense and inconvenience of hospitalisation is avoided, which makes it an attractive alternative. The Institute for OneWorld Health has reintroduced the drug paromomycin for treatment of leishmaniasis, results with which led to its approval as an orphan drug. The Drugs for Neglected Diseases Initiative is also actively facilitating the search for novel therapeutics. A treatment with paromomycin will cost about $10. The drug had originally been identified in 1960s, but had been abandoned because it would not be profitable, as the disease mostly affects poor people.[21] The Indian government approved paromomycin for sale in August 2006.[22] A 21-day course of paromomycin produces a definitive cure in >90% of patients with visceral leishmaniasis.[23] 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.[24] Several potential vaccines are being developed, under pressure from the World Health Organization, but as of 2006[update] none is available. The team at the Laboratory for Organic Chemistry at the Swiss Federal Institute of Technology (ETH) in Zürich are trying to design a carbohydrate-based vaccine [1]. The genome of the parasite Leishmania major has been sequenced,[25] possibly allowing for identification of proteins that are used by the pathogen but not by humans; these proteins are potential targets for drug treatments. The compound vasicine (peganine), found in the plant Peganum harmala, has been tested in vitro against the promastigote stage of Leishmania donovani, the causative agent of visceral leishmaniasis. It was shown that this compound induces apoptosis in Leishmania promastigotes. "Peganine hydrochloride dihydrate, besides being safe, was found to induce apoptosis in both the stages of L. donovani via loss of mitochondrial transmembrane potential."[26] Another alkaloid harmine found in Peganum harmala, ". . .because of its appreciable efficacy in destroying intracellular parasites as well as non-hepatotoxic and non-nephrotoxic nature, harmine, in the vesicular forms, may be considered for clinical application in humans."[27] HIV Protease inhibitors have been found to be active against Leishmania species in two in vitro studies in Canada and India. The study reported that the intracellular growth of Leishmania parasites was controlled by nelfinavir and ritonavir in a human monocyte cell line and also in human primary monocyte-derived macrophages.[28]
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