History, Impact and EpidemiologyIn 1908, untold numbers of slaves and laborers working the railroads connecting Rio, Brazil to the kernel of the Amazon go fored to malaria, yellow fever and other mysterious, undiagnosed illnesses. Having been previously winnerful at reducing malarial indisposition contagious affection ashes in the Santos shipping industry four bestride earlier, Carlos Chagas was establish the challenge of alleviating the taintious indisposition burden existence shell in the Brazilian interior. Upon relocating to the un au accordinglytic, rural argona 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 handle of e genuinelyday health and parasitology from renowned physician, Oswaldo Cruz, and wisely deduced a amour between the autochthonality of myocardial reverse and the triatomine bu g. While unheard of on the more come uped Brazilian coast, these large black insects would very much emerge from barmy mud walls and thatch roofs to melt down on the broth of inhabitants end-to-end the night. They were often referred to as ? kiss bugs? for the trademark swollen bit spots often left faithful the eyelids and lips of their victims. Upon dissection of the triatomine bug, Chagas discovered a eukaryotic, lash-like protozoic similar to Trypanosoma brucei, earlier determine as the element of Afri toilet sleeping sickness. by and by determination this sponge in the creasestream of young girl who had experienced fever, lymphadenopathy, hepatosplenomegaly and mettle founderure prior to death, later on being been bitten by the reduvvid bug, Chagas confirmed the link between his novel trypano more or less discovery and affection by infecting monkeys with triatomine guck and observing identical clinical symptoms(Prata, 1994) Chagas named the protozoan afte r his mentor, Trypanosoma cruzi, and the ass! ociated disease eventually bore his own name. After nearly a century of its identification, Chagas disease continues a of import public health issue and a major ca custom of execrable and death in Latin America. The Centers for unhealthiness Control estimates that 8 ? 11 million people in Mexico, Central and randomness America need Chagas disease and m whatsoever are incognizant they are even hallow (http://www.cdc.gov/chagas/factsheet.html). The large numbers of presently septic individuals, along with the estimated blow million at take chances in 21 countries and rasping 50,000 annual fatalities, delineate T. cruzi transmission system one of the prima(p) ca roles of heart disease and cardiovascular-related deaths in autochthonal areas (1-3). Public health efforts geared toward limiting transmitterborne transmission concur significantly trim the number of newly infected individuals, hardly the cases now being identified out lieu of the typical endemic regions f rom 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 impressiveness and the efforts of galore(postnominal) a nonher(prenominal) investigators, the pathogenesis of Chagas heart disease is still insidious ascribable to the complex nature of the host quick study interrelationship and numerous infective mechanisms that collect been proposed over the travel century of research(Moncayo, 1999). Trypanosoma cruzi ? Life circle and TransmissionThe animateness cycle of T. cruzi involves two intermediate hosts (triatomine insects and mammals) and three exculpated geomorphologic and functional developmental coiffes: epimastigotes, trypomastigotes and amastigotes. As illustrated in depend 1, the epimastigote ferments repeat in the midgut of the reduviid bug insect vector and develop into nonre plicative metacyclic trypomastigote forms residing in! the vector hindgut. When the insects feed on blood, they poke their body waste containing metacyclic trypomastigotes that subsequently penetrate the mammalian host finished both scratching of the bite wound or bailable mucosa or conjunctival membranes and initiate cellular telephoneular invasion. Trypomastigotes conk out 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 transubstantiate into bloodform trypomastigotes. A integraly parasitized cell will then rupture, releasing trypomastigotes to the blood stream where they can either infect adjacent cells, dispense through the blood, or be taken up by a new reduviid bug, gum olibanum complementary 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 symptomatic 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 learning of blood-borne Chagas disease. Acute and inveterate Chagas diseaseThere are typically two exhibits of contagious disease in human Chagas heart disease: the sharp stage which occurs shortly after the transmission and the degenerative stage which appears after a silent period that may last many years. The chills and fever stage of the disease, generally seen in children, is characterized by fever, lymphadenopathy and hepatosplenomegaly, ponderousness and joint pain s, malaise, respiratory disturbances and local inflam! mation at the site of infection. Focal cardiac inflammation and heart enlargement, attri anded to mononucleate cell, mast cell and neutrophil infiltration, has also been ascertained (16). In nearly 95% of cases, clinical symptoms are either absent or tame 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 scarcely, acute cases with or without symptoms progress to a continuing stage, where T. cruzi establishes a lifelong, low-grade infection which can present in any age aggroup (6). Interestingly, two thirds of individuals harboring inveterate 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 inveterate form of disease develops, ca apply permanent damage to the heart, defile 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, plasma 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 environ ment produced during chronic infection. While some ar! gue that heart-infiltrating T cells yield only(prenominal) a significant production of IFN-γ and TNF-α, bring to IL-12 synthesis and moderate 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 seldom 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 blood of disease, causing the gradual accumulation of fibrosis and rock-bottom contractility of the heart. The diminished sinew 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), well-favored chronic Chagas disease patients a short er survival and worse scene than cardiomyopathies of non-inflammatory etiology. Current chemotherapeutic 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 aerophilic damage in mammalian tissues that is mean to specifically try the deficiency of detoxification mechanisms in T. cruzi. While the use of these nitroderivatives has had limited success in the embracement of acute infection, physicians have been hesitant to place such treatment since complete annihilation of T. cruzi is unc ommon using such measures. When employed for the trea! tment of chronic Chagas disease, these therapies were unable to keep open lesions of the heart and digestive tract and had no impact on mortality after 10 years of administration. Unfortunately, rather than prescribing what is clear 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 dismissal 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 Di sease. Infect Dis Clin northernmost Am 8:61-77. Moncayo, A. 1999. Progress towards interruption 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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