Chagas Heart Disease

History, Impact and EpidemiologyIn 1908, untold numbers of slaves and laborers working the railroads connecting Rio, Brazil to the mettle of the Amazon succumbed to malaria, yellow fever and other mysterious, undiagnosed illnesses. Having been antecedently successful at reducing malarial indisposition transmission system in the Santos shipping industry four age earlier, Carlos Chagas was establish the challenge of alleviating the taintious indisposition burden being face in the Brazilian interior. Upon relocating to the un au accordinglytic, rural area 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 fields of everyday health and parasitology from renowned physician, Oswaldo Cruz, and wisely deduced a contact between the autochthonality of myocardial reverse and the triatomine bug. While unheard of along the more developed Brazilian coast, these large black insects would very much emerge from barmy mud walls and thatch roofs to feed on the broth of inhabitants end-to-end the night. They were often referred to as ?kissing bugs? for the trademark swollen bit sites often left near the eyelids and lips of their victims. Upon dissection of the triatomine bug, Chagas discovered a eukaryotic, lash-like protozoan similar to Trypanosoma brucei, earlier identified as the element of Afri toilet sleeping sickness. After finding this sponge in the bloodstream of young girl who had experienced fever, lymphadenopathy, hepatosplenomegaly and heart failure prior to death, after being been bitten by the reduvvid bug, Chagas confirmed the link between his novel trypanosome discovery and disease 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 significant public health issue and a major ca custom of execrable and death in Latin America. The Centers for Disease Control estimates that 8 ? 11 million people in Mexico, Central and randomness America need Chagas disease and m whatsoever are incognizant they are even give (http://www.cdc.gov/chagas/factsheet.html). The large numbers of presently septic individuals, along with the estimated 100 million at take chances in 21 countries and approximate 50,000 annual fatalities, make T. cruzi transmission system one of the leading causes of heart disease and cardiovascular-related deaths in endemic areas (1-3). Public health efforts geared toward limiting transmitterborne transmission concur significantly reduced the number of newly infected individuals, hardly the cases now being identified out lieu of the typical endemic regions from increasing incidences of blood transmission (4) and organ transplantation (5) distillery make Chagas one of the most important diseases to understand cod to its history of morbidity and mortality (6). Despite its obvious clinical importance and the efforts of many investigators, the pathogenesis of Chagas heart disease is still insidious due to the complex nature of the hostparasite interrelationship and numerous infective mechanisms that have been proposed over the travel century of research(Moncayo, 1999).

Trypanosoma cruzi ? Life circle and TransmissionThe life 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 forms replicate in the midgut of the reduviid bug insect vector and develop into nonreplicative metacyclic trypomastigote forms residing in the vector hindgut. When the insects feed on blood, they poke their excreta containing metacyclic trypomastigotes that subsequently penetrate the mammalian host finished either scratching of the bite wound or bailable mucosa or conjunctival membranes and initiate cellular invasion. Trypomastigotes die the acidic 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 transform into bloodform trypomastigotes. A integraly parasitized cell will then rupture, releasing trypomastigotes to the blood stream where they can either infect adjacent cells, disseminate through the blood, or be taken up by a new reduviid bug, gum olibanum completing the cycle. A less common, yet increasingly significant, avenue of parasite 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 acquisition of blood-borne Chagas disease.

Acute and inveterate Chagas diseaseThere are typically two stages of infection in human Chagas heart disease: the sharp stage which occurs shortly after the infection and the chronic stage which appears after a silent period that may last many years. The acute stage of the disease, generally seen in children, is characterized by fever, lymphadenopathy and hepatosplenomegaly, muscle and joint pains, malaise, respiratory disturbances and 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 observed (16). In nearly 95% of cases, clinical symptoms are either absent or mild 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) commonly, acute cases with or without symptoms progress to a chronic stage, where T. cruzi establishes a lifelong, low-grade infection which can present in any age group (6). Interestingly, two thirds of individuals harboring chronic 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 chronic form of disease develops, causing 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, 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 environment produced during chronic infection. While some argue that heart-infiltrating T cells yield only a significant production of IFN-γ and TNF-α, bring to IL-12 synthesis and control 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 course of disease, causing the gradual accumulation of fibrosis and rock-bottom contractility of the heart. The diminished muscle 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), giving 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 effects 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 currently accepted discussions, benznidazole and nifurtimox, likely result from bystander subtractive or oxidative damage in mammalian tissues that is mean to specifically exploit the deficiency of detoxification mechanisms in T. cruzi. While the use of these nitroderivatives has had limited success in the treatment of acute infection, physicians have been hesitant to prescribe 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 prevent lesions of the heart and 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 release 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



If you want to get a full essay, wisit our page: write my paper