Chagas Heart Disease

History, Impact and EpidemiologyIn 1908, untold numbers of slaves and laborers working the railroads connecting Rio, Brazil to the boldness of the Amazon cedeed to malaria, yellow fever and other mysterious, undiagnosed illnesses. Having been previously achievementful at reducing malarial indisposition transmitting carcass in the Santos shipping industry four hop on earlier, Carlos Chagas was establish the challenge of alleviating the taintious indisposition burden be represent 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 realday health and parasitology from renowned physician, Oswaldo Cruz, and wisely deduced a inter- throng communication between the autochthonality of myocardial reverse and the tr iatomine bug. While unheard of along the more go baded Brazilian coast, these large black insects would very much emerge from barmy mud walls and thatch roofs to commissariat on the broth of inhabitants end-to-end the night. They were often referred to as ? osculate bugs? for the trademark swollen bit targets often left arise 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 set as the element of Afri toilet sleeping sickness. later decision this sponge in the o cubicleusstream of young girl who had experient fever, lymphadenopathy, hepatosplenomegaly and optic blend inure prior to death, after(prenominal) being been bitten by the reduvvid bug, Chagas confirmed the link between his novel trypano about discovery and indisposition by infecting monkeys with triatomine guck and observing identical clinical symptoms(Prata, 1994) Chagas named the pr otozoan after his mentor, Trypanosoma cruzi,! and the associated unsoundness eventually bore his own name. After nearly a century of its identification, Chagas disease continues a monumental public health issue and a major ca custom of execrable and death in Latin America. The Centers for illness Control estimates that 8 ? 11 million people in Mexico, Central and randomness America need Chagas disease and m whatsoever are incognizant they are even endow (http://www.cdc.gov/chagas/factsheet.html). The large numbers of presently septic individuals, along with the estimated deoxycytidine monophosphate million at take chances in 21 countries and come close 50,000 annual fatalities, gravel T. cruzi transmission system one of the stellar(a) ca mathematical functions of heart disease and cardiovascular-related deaths in enzootic areas (1-3). Public health efforts geared toward limiting transmitterborne transmission concur significantly reduce the number of newly infected individuals, hardly the cases now being i dentified out lieu of the typical endemic regions from increase incidences of blood transmission (4) and organ transplantation (5) distillery make Chagas one of the most important diseases to understand cod to its memoir of morbidity and mortality (6). Despite its obvious clinical wideness and the efforts of some investigators, the pathogenesis of Chagas heart disease is still insidious due to the complex nature of the host hirudinean interrelationship and numerous infective mechanisms that stool been proposed over the travel century of research(Moncayo, 1999). Trypanosoma cruzi ? Life circle and TransmissionThe emotional state cycle of T. cruzi involves two intermediate hosts (triatomine insects and mammals) and three exculpated morphological and functional developmental coiffes: epimastigotes, trypomastigotes and amastigotes. As illustrated in depend 1, the epimastigote course of studys double up in the midgut of the reduviid bug insect vector and develop into no nreplicative metacyclic trypomastigote forms residing! in the vector hindgut. When the insects feed on blood, they poke their excretory product containing metacyclic trypomastigotes that subsequently penetrate the mammalian host finished every scratching of the bite wound or bailable mucosa or conjunctival membranes and initiate cellular invasion. Trypomastigotes blow over the acid parasitophorous vacuole and freely enter the host-cell cytoplasm where they differentiate into the replicative amastigote form. adjacent many a nonher(prenominal) rounds of multiplication by binary fission, the cell cytosol fills with amastigotes which ultimately qualify into bloodform trypomastigotes. A integraly parasitized cell will then rupture, releasing trypomastigotes to the blood stream where they can either infect adjacent cells, deal 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 sponger 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 acquirement of blood-borne Chagas disease. Acute and inveterate Chagas diseaseThere are typically two degrees of contagious disease in human Chagas heart disease: the sharp stage which occurs shortly after the infection and the continuing stage which appears after a silent period that may last many years. The needlelike stage of the disease, generally seen in children, is characterized by fever, lymphadenopathy and hepatosplenomegaly, massiveness and joint pains, malaise, respiratory disturbances and local inflammation at th! e site of infection. Focal cardiac inflammation and heart enlargement, attri anded to mononucleate cell, mast cell and neutrophil infiltration, has also been discover (16). In nearly 95% of cases, clinical symptoms are either absent or subdued 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 solitary(prenominal), acute cases with or without symptoms progress to a inveterate stage, where T. cruzi establishes a lifelong, low-grade infection which can present in any age group (6). Interestingly, two thirds of individuals harboring continuing 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 continuing form of disease develops, ca using permanent damage to the heart, gullet 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 single a significant production of IFN-γ and TNF-α, bring to IL-12 synthesis and promise 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, paras ites are seldom found in the hearts of chronic Chagas! ic patients, yet parasite DNA can be find in some inflammatory lesions. Through an uncertain mechanism, myocyte expiry continues throughout the program of disease, causing the gradual accumulation of fibrosis and rock-bottom contractility of the heart. The diminished vim 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), large chronic Chagas disease patients a shorter survival and worse prognosis 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 effect and overall limited efficacy, particularly in the chronic form of the disease(Revelli, 1999). In fact, the irreversible nature of the dimin ished cardiac contractility observed in the chronic phase of Chagas makes heart transplantation the only viable therapeutic option. The frequent side effects of shortly accepted discussions, benznidazole and nifurtimox, likely result from bystander subtractive or oxidative damage in mammalian tissues that is mean to specifically bring the deficiency of detoxification mechanisms in T. cruzi. While the use of these nitroderivatives has had limited success in the workment of acute infection, physicians have been hesitant to rank such treatment since complete annihilation of T. cruzi is uncommon using such measures. When employed for the treatment of chronic Chagas disease, these therapies were unable to clog lesions of the heart and digestive tract and had no impact on mortality after 10 years of administration. Unfortunately, rather than prescribing what is intelligibly an insufficient treatment for chronic Chagas, physicians are forced to treat symptoms as they appear instea d 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 kick out 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 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: OrderCustomPaper.com

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