Cutaneous Leishmaniasis And Pathogenesis Biology Essay

epidermal leishmaniosis And Pathogenesis Biology endeavor kala azar is a tropical, protozoan complaint caused exclusively by intracellular sponges belonging to the genus Leishmania. kala azar is a worldwide problem and due to the assorted species of Leishmania, target manifest in humans as 3 principal(prenominal) clinical forms cutaneous kala azar, Muco cutaneous kala azar, or Visceral kala azar. Consequently, the severity of the transmittal and symptoms differ from self healing corruptions that produce satisfying scars to the fatal infections.PathogenesisLeishmaniasis is transmitted by the bite of female insect vector guts flies of the species Phlebotomus in the Old World and Luzomyia in the reinvigorated World (Figure 1). The life pedal for all Leishmania species is relatively impartial and similar (Figure 2).When the mainstay aerify takes a blood meal, it inoculates the source with the 2-3 mm long parasite. At this stage, the Leishmania parasite is known as a promastigote as it contains a singular flagellum. Promastigotes atomic number 18 injected into the host skin, after which they seclude themselves to the hosts macrophages, and argon induced by phagocytosis. These white blood cells argon represent at the vaccination site because of the hosts natural immune response to the rachis fly bite. Once inside the macrophages, the promastigotes transform into their non-flagellate form, known as amastigotes. From here(predicate) the amastigotes reproduce by binary fission and continue to proliferate in spite of appearance the white blood cells until the cell bursts. The parasites are then free to infect and invade other reticulo-endothelial cells, which share the same fate and are done for(p) due to the reproduction of amastigotes within. The amastigotes and septic macrophages enter the blood circulation.The life cycle of Leishmania is continued when a female rachis fly feeds on the give hosts blood and the amastigotes are taken up by the sand flies. Amastigotes transform into promastigotes, which proliferate by binary fission in the midgut of the sand fly everywhere a period of 4-25 days (WHO, 2010). Hereafter, the promastigotes migrate to the fly proboscis or mouthparts, where the parasite can infect a parvenu host during feeding (Murray et al, 2009) and thus the Leishmania lifecycle is continued.Mammals are much frequently reservoirs for infection. As well as humans dogs, rodents, wolves and foxes are examples of common reservoirs (Neuber, 2008) and thus, can suffer from kala azar diseases too.Figure 2 The life cycle of Leishmania. equal from Chappuis et al (2007).Figure 1 A Sand fly vector of Leishmania parasites. Extracted from Neuber (2008).EpidemiologyLeishmaniasis is endemic in 88 countries, 72 of which are developing countries. An estimated 12 million people are infected with leishmaniasis and 70,000 people die each year (Reithinger et al, 2007). There are before long about 350 million peop le worldwide that are at risk of exposure and threatened by leishmaniasis because they sleep together within 40 brotherhood and south of the equator (Jones et al., 2005 Neuber, 2008) and according to the World Health Organisation (2010), there are an estimated 1-2 million new cases each year.There are approximately 20 species of Leishmania which are pathogenic for humans (Chappuis et al., 2007). These species vary in their geographic location and overhear an effect on the leishmaniasis which manifests (Table 1).Cutaneous leishmaniasis is the most common form of leishmaniasis and is endemic in over 70 countries worldwide (Figure 3). It is found throughout Africa and the Middle East in Afghanistan, Algeria, Iran, Iraq, Kabul, Pakistan, Saudi Arabia, Syria however, more particularly in confederation the States, in brazil nut and Peru (Reithinger et al, 2007 Murray et al, 2009).Over 90% mucocutaneous leishmaniasis often occurs in Bolivia, brazil and Peru and the majority (over 90% ) of visceral leishmaniasis cases, the most dangerous form, is localised to 6 countries Bangladesh, Brazil, Ethiopia, India, Nepal and Sudan. There are an estimated 500,000 new cases of visceral leishmaniasis each year (WHO, 2010 Chappuis et al., 2007).Figure 3 geographic distribution of Cutaneous Leishmaniasis. Extracted from Reithinger et al (2007).Main Clinical PresentationLeishmania ParasiteMain Geographical DistributionCutaneous LeishmaniasisL. tropica*Africa, Asia, Middle East, Mediterranean subjectCutaneous LeishmaniasisL. major*Middle East, AfricaCutaneous LeishmaniasisL. aethiopia*Ethiopia, KenyaCutaneous LeishmaniasisL. amazonesis randomness America (Brazil, Venezuela)Cutaneous LeishmaniasisL .columbiensis Northern South America (Columbia, Panama)Cutaneous LeishmaniasisL. garnhami South America (Venezuela)Cutaneous LeishmaniasisL. peruviana Peru, Panama, Costa Rica, ColumbiaCutaneous LeishmaniasisL. venezuelensis Northern South America (Venezuela)Mucocutaneous Leishmania sisL. braziliensis Central and South AmericaVisceral LeishmaniasisL. donovani*Africa, AsiaVisceral LeishmaniasisL. infantum (L. chagasi)Europe, north Africa, Central and South America, Mediterranean playing fieldTable 1 Overview of clinical presentation and geographical distribution of species of Leishmaniasis that cause human disease. L. = Leishmania. * Leishmania species of the Old World. Leishmania species of the New world. information adapted from Reithinger et al (2007), Neuber (2008) and Murray et al (2009).Clinical PresentationCutaneous LeishmaniasisCutaneous leishmaniasis is a localised reaction at the inoculation site, which tends to be uncovered areas such(prenominal) as the face, hands and lower legs. mingled with 2 weeks and 2 months after the sand flys bite, a red papule forms. The area begins to swell and become irritated and after 3-4 weeks, flat ulcers form which in the end harden and form crusted margins. The volcano-like lesions that form can heal without int erposition however, sick persons are unremarkably left with significant, disfiguring scars.Mucocutaneous LeishmaniasisMucocutaneous leishmaniasis, also known as espundia, is most often caused by Leishmania viannia braziliensis and has a similar incubation time as cutaneous leishmaniasis. However, this form causes more devastating disfigurement to disease sufferers as the parasites metastasise towards to the mucosal membranes and prohibit them and nearby unrelated tissue structures also (Murray et al, 2009). This form is more commonly seen after a primary infection of cutaneous leishmaniasis, where the lesions have in conclusion healed. Un interact lesions can transform into mucocutaneous forms and year later the oral and nasal mucosas become infected. Inflammation of the nose, mouth, oropharynx and trachea cause sever mutilation and facial disfigurement. Death can nearlytimes arise as mucosal lesions do not self-heal and prolonged infection compromises both immune and respirat ory systems.Visceral LeishmaniasisVisceral leishmaniasis, also known as, kala-azar, dumdum pyrexia or black fever, is the most frightful form of leishmaniasis, and if left untreated, those infected will die. It is the most dangerous because parasites leave the skin and colonise the complete reticulo-endothelial system (Neuber, 2008) and spread to internal organs. Incubation period may be from several weeks to a year and can present as a rapidly fatal disease or as an asymptomatic, self-limiting infection (Murray et al, 2009). As the parasites proliferate and destroy the hosts cells, sufferers present with a marked enlargement of the liver, lien lymph nodes as well as fatigue, weight loss, fever chills, severe genus Anemia and kidney damage. Death is caused by haemorrhage, complications relating to anaemia or a weakened immune system which cannot treat with bacterial co-infections (Chappuis et al, 2007).As is the case with all forms of leishmaniasis, the chances of the sufferer developing a secondary infection, such as a bacterial infection, are very high and doing so, can complicate the disease come on and may lead to death.To join on one photo for each CL, ML and VL.Canine LeishmaniasisLeishmania infantum not only cause severe disease in humans, but in dogs also. Millions of dogs in Europe, Asia, North Africa, and South America are affected by the parasite. There are some clinical manifestations of the disease in dogs which re similar to that of humans including cutaneous alterations, enlargement of lymph nodes, liver and spleen, weight loss and glomerulopathy. As well as this, ocular lesions, epistaxis (nose bleeds), onycogryphosis (abnormal curving of claws) and lameness (disability in walking) are classical symptoms found in infected dogs (Maia and Campino, 2008). As with visceral leishmaniasis, canine leishmaniasis may also present as an asymptomatic infection, thus delaying demand discourse.DiagnosisDue to the clinical presentations of the dise ase, a diagnosis can be made however, for a definitive diagnosis the Leishmania parasite must(prenominal) be detected to confirm the diagnosis. Parasitological techniques are routinely used and fill demonstrating promastigotes in a direct examination of tissue aspirates, or spying amastigotes in biopsy specimens, which are then, examined using a microscope.Serological techniques to diagnose leishmaniasis are based upon indirectly identifying specific host humoural and cell-mediated responses after inoculation of the parasite. Diagnostic methods include direct agglutination examination (DAT), the immunofluorescence antibody test (IFAT), the enzyme-linked immunosorbent verification (ELISA), immunoblotting and antigen detection.Molecular techniques involve detecting leishmanial DNA or RNA have been beneficial in not only diagnosis, but species identification also. The molecular(a) techniques include using various versions of polymerase chain reactions (PCR) to amplify species spe cific parasite sequences, DNA probes, monoclonal antibodies (MAbs) and isoenzyme electrophoresis.TreatmentAll forms of leishmaniasis should be treated due to their mortality and morbidity consequences. Drugs are available to treat the disease and choice for all forms is the pentavalent antimonial compound sodium stibogluconate (Pentostam).Cutaneous leishmaniasis is also treated with injections of other antimonial compounds, such as fluconazole and litefosine, directly into the infected lesions (* Figure). Miltefosine has also proven to be an effective treatment for visceral leishmaniasis (Murray et al, 2009).However, as with all medicine treatments, the development of dose resistance is a huge issue and over use of this drug in previous years could lead to Leishmania species becoming resistant. As well as this, there are considerable side set up associated with most drugs (Neuber, 2008). A safe and effective vaccine against the various species is urgently required particularly in endemic areas however, there is currently no vaccine available although work to develop one is still ongoing.(To add * Figure of such treatment)Social and Economical ImplicationsLeishmaniasis is found in developing countries or the poorer regions of a country and thus commonly affects the poorest of the poor. Having such a disease can cause many problems in the lives of those infected and their families as they become poorer due to the direct and high costs of diagnosis and treatment of the disease, and the indirect costs such as loss of income (Chappuis et al, 2007). other impact of the disease is the social and psychological stigma associated with leishmaniasis, because of the disfigurement and significant scarring caused. Thus, even after the disease has been treated or self-healed, patients must deal with a constant reminder of what they had to endure.Cheap, rapid and accurate diagnostic methods are needed to allow all those infected, especially the poor, to get the medical at tention they need, and to also allow treatment to start as soon as possible thus ensuring symptoms may not be as detrimental. protrusion AimsThe aim of this project is to compare the different methods for diagnosis of leishmaniasis in humans and dogs. These methods will be critically analysed in order to test the following hypothesis A Leishmania infection can be detected unequivocally. In doing so, the necessary requirements for a correct diagnosis for those who live in endemic areas and for those whom leishmaniasis is a threat, will also be discussed.