History, Impact and EpidemiologyIn 1908, untold numbers of slaves and laborers working the railroads connecting Rio, Brazil to the nitty-gritty of the Amazon rendered to malaria, yellow fever and other mysterious, undiagnosed illnesses. Having been antecedently achievementful at reducing malarial indisposition contagion clay in the Santos shipping industry four succession earlier, Carlos Chagas was establish the challenge of alleviating the taintious indisposition burden be typesetters case in the Brazilian interior. Upon relocating to the un au accordinglytic, rural bea of Lassance, he encountered droves of individuals kick about irregular vegetable marrowbeats, atypical arrythmias, cardiac insufficiencies and inexplicable cases of sharp end. Chagas had received training in palm of e very(prenominal)day health and parasitology from renowned physician, Oswaldo Cruz, and wisely deduced a progress to between the autochthonality of myocardial reverse and the triatomine bug. While unheard of on the more checked Brazilian coast, these large black insects would very much emerge from barmy mud walls and thatch roofs to work on the broth of inhabitants end-to-end the night. They were often referred to as ? cuddling bugs? for the trademark swollen bit stations often left conterminous the eyelids and lips of their victims. Upon dissection of the triatomine bug, Chagas discovered a eukaryotic, lash-like protozoal similar to Trypanosoma brucei, earlier identify as the element of Afri toilet sleeping sickness. aft(prenominal) conclusion this sponge in the line of productsstream of young girl who had experienced fever, lymphadenopathy, hepatosplenomegaly and fancy unwrapure prior to death, by and by being been bitten by the reduvvid bug, Chagas confirmed the link between his novel trypano round discovery and ailment by infecting monkeys with triatomine guck and observing identical clinical symptoms(Prata, 1994) Chagas named the protozoan after his mentor, Trypanosoma! cruzi, and the associated disease eventually bore his own name. After nearly a century of its identification, Chagas disease continues a epochal public health issue and a major ca custom of execrable and death in Latin America. The Centers for malady Control estimates that 8 ? 11 million people in Mexico, Central and randomness America need Chagas disease and m whatsoever are incognizant they are even tump over (http://www.cdc.gov/chagas/factsheet.html). The large numbers of presently septic individuals, along with the estimated degree Celsius million at take chances in 21 countries and imagine 50,000 annual fatalities, energise T. cruzi transmission system one of the track ca economic consumptions of heart disease and cardiovascular-related deaths in endemic areas (1-3). Public health efforts geared toward limiting transmitterborne transmission concur significantly decreased the number of newly infected individuals, hardly the cases now being identified out lie u of the typical endemic regions from change magnitude incidences of blood transmission (4) and organ transplantation (5) distillery make Chagas one of the most important diseases to understand cod to its memorial of morbidity and mortality (6). Despite its obvious clinical wideness and the efforts of some(prenominal) investigators, the pathogenesis of Chagas heart disease is still insidious repayable to the complex nature of the host poriferan interrelationship and numerous infective mechanisms that contain been proposed over the travel century of research(Moncayo, 1999). Trypanosoma cruzi ? Life circle and TransmissionThe manners cycle of T. cruzi involves two intermediate hosts (triatomine insects and mammals) and three exculpated morphologic and functional developmental coiffes: epimastigotes, trypomastigotes and amastigotes. As illustrated in depend 1, the epimastigote crops take over in the midgut of the reduviid bug insect vector and develop into nonreplica tive metacyclic trypomastigote forms residing in the ! vector hindgut. When the insects feed on blood, they poke their elimination containing metacyclic trypomastigotes that subsequently penetrate the mammalian host finished every scratching of the bite wound or bailable mucosa or conjunctival membranes and initiate electric cellular invasion. Trypomastigotes gag the acid parasitophorous vacuole and freely enter the host-cell cytoplasm where they differentiate into the replicative amastigote form. adjacent many rounds of multiplication by binary fission, the cell cytosol fills with amastigotes which ultimately vary into bloodform trypomastigotes. A integraly parasitized cell will then rupture, releasing trypomastigotes to the blood stream where they can either infect adjacent cells, beam through the blood, or be taken up by a new reduviid bug, gum olibanum terminate the cycle. A less common, yet increasingly significant, avenue of bloodsucker transmission is through transfusion of blood products(Revelli, 1999). As such , Chagas disease has become a potential problem associated with migration of infected individuals from endemic areas to the United States, Canada, Eastern Europe, Australia and Japan. Fortunately, the appropriate selection of blood donors, the use of more sensitive and accurate advanced molecular diagnostic tests and the application of a mandatory quality arrogance system have improved the safety of blood banks in Latin American and have reduced the overall encounter of acquirement of blood-borne Chagas disease. Acute and inveterate Chagas diseaseThere are typically two typifys of contagion in human Chagas heart disease: the sharp stage which occurs shortly after the contagious disease and the degenerative stage which appears after a silent period that may last many years. The discriminating stage of the disease, generally seen in children, is characterized by fever, lymphadenopathy and hepatosplenomegaly, muscularity and joint pains, malaise, respiratory disturbances an d local inflammation at the site of infection. Focal ! cardiac inflammation and heart enlargement, attri anded to mononucleate cell, mast cell and neutrophil infiltration, has also been discovered (16). In nearly 95% of cases, clinical symptoms are either absent or lenient and non-specific (6), making it difficult to diagnose disease in the acute stage of infection. In instances when symptoms manifest, less than 5% of individuals can succumb to infection, typically of either myocarditis or meningoencephalitis. more(prenominal) comm and, acute cases with or without symptoms progress to a degenerative stage, where T. cruzi establishes a lifelong, low-grade infection which can present in any age multitude (6). Interestingly, two thirds of individuals harboring degenerative parasite infection, often termed ?indeterminate?, fail to demonstrate any detectable clinical signs and do not die of Chagas disease. However, in about triad of cases(Prata, 1994), a degenerative form of disease develops, ca use permanent damage to the heart, esophagus and colon, with dilatation and disorders of nerve conduction of these organs. The riddle in chronic Chagas heart disease primarily consists of lymph cells with humiliate numbers of macrophages, eosinophils, germ plasm cells, neutrophils and mast cells . While studies on myocardial biopsy fragments from chronic Chagasic patients indicate a predominance of CD8+ over CD4+ T cells T.
cruzi infection also causes a decrease in expression of lymphocyte surface molecules including CD3, CD8, and CD4 in order to circumvent host immunity. Questions remain pertaining to the cytokine environment produced during chronic infection. While some argue that heart-infiltrating T cells yield compl etely a significant production of IFN-γ and TNF-! α, bring to IL-12 synthesis and gibe of the infection, others claim that macrophage IL-10 production facilitates the replication and survival of the fittest of the fittest of the pathogen. Interestingly, parasites are rarely found in the hearts of chronic Chagasic patients, yet parasite DNA can be find in some inflammatory lesions. Through an uncertain mechanism, myocyte expiry continues throughout the run away of disease, causing the gradual accumulation of fibrosis and rock-bottom contractility of the heart. The diminished go across mass, rhythm irregularity (arrhythmia or ventricular tachycardia), and ultimate heart failure is the leading cause of death in chronic Chagas patients. In fact, 10% of all T. cruzi infected patients will die from refractory, end-stage heart failure or ascetical arrhythmia (26, 27), cock-a-hoop chronic Chagas disease patients a shorter survival and worse prospect than cardiomyopathies of non-inflammatory etiology. Current chemotherape utic approaches for the specific interposition of Chagas disease are considered to be unsatisfactory because of frequent poisonous side effectuate and overall limited efficacy, particularly in the chronic form of the disease(Revelli, 1999). In fact, the irreversible nature of the diminished cardiac contractility observed in the chronic phase of Chagas makes heart transplantation the only viable therapeutic option. The frequent side effects of presently accepted discussions, benznidazole and nifurtimox, likely result from bystander subtractive or aerobic damage in mammalian tissues that is mean to specifically figure out the deficiency of detoxification mechanisms in T. cruzi. While the use of these nitroderivatives has had limited success in the performment of acute infection, physicians have been hesitant to place such treatment since complete annihilation of T. cruzi is uncommon using such measures. When employed for the treatment of chronic Chagas disease, these thera pies were unable to embarrass lesions of the heart a! nd digestive tract and had no impact on mortality after 10 years of administration. Unfortunately, rather than prescribing what is clearly an insufficient treatment for chronic Chagas, physicians are forced to treat symptoms as they appear instead of the disease itself. ReferencesRevelli, S., C. Le Page, E. Piaggio, J. Wietzerbin, and O. Bottasso. 1999. Benznidazole, a drug employed in the treatment of Chagas disease, down-regulates the synthesis of nitrite and cytokines by murine stimulated macrophages. Clin Exp Immunol 118:271-277. Murta, S. M., C. Ropert, R. O. Alves, R. T. Gazzinelli, and A. J. Romanha. 1999. In-vivo treatment with benznidazole enhances phagocytosis, parasite destruction and cytokine let go of by macrophages during infection with a drug-susceptible but not with a derived drug-resistant Trypansoma cruzi population. Parasite Immunol 21:535-544. Prata, A. 1994. Chagas Disease. Infect Dis Clin northernmost Am 8:61-77. Moncayo, A. 1999. Progress towards interrupti on of transmission of Chagas disease. Mem exigent Oswaldo Cruz 94 Suppl 1:401-404. If you want to get a full essay, order it on our website:
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