Infecciones por protozoos flagelados hemotisulares II. Enfermedad de Chagas. Tripanosomosis africana

Medicine - Programa de Formación Médica Continuada Acreditado 04/2010; 10(54). DOI: 10.1016/S0304-5412(10)70094-9
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    ABSTRACT: Chagas' disease (American trypanosomiasis) is an endemic parasitic disease in some areas of Latin America. About 16-18 million persons are infected with the aetiological agent of the disease, Trypanosoma cruzi, and more than 100 million are living at risk of infection. There are different modes of infection: (1) via blood sucking vector insects infected with T. cruzi, accounting for 80-90% of transmission of the disease; (2) via blood transfusion or congenital transmission, accounting for 0.5-8% of transmission; (3) other less common forms of infection, eg, from infected food or drinks or via infected organs used in transplants. The acute phase of the disease can last from weeks to months and typically is asymptomatic or associated with fever and other mild nonspecific manifestations. However, life-threatening myocarditis or meningoencephalitis can occur during the acute phase. The death rate for persons in this phase is about 10%. Approximately 10-50% of the survivors develop chronic Chagas' disease, which is characterized by potentially lethal cardiopathy and megacolon or megaoesophagus. There are two drugs available for the aetiological treatment of Chagas' disease: nifurtimox (Nfx) and benznidazole (Bz). Nfx is a nitrofurane and Bz is a nitroimidazole compound. The use of these drugs to treat the acute phase of the disease is widely accepted. However, their use in the treatment of the chronic phase is controversial. The undesirable side effects of both drugs are a major drawback in their use, frequently forcing the physician to stop treatment. The most frequent adverse effects observed in the use of Nfx are: anorexia, loss of weight, psychic alterations, excitability, sleepiness, digestive manifestations such as nausea or vomiting, and occasionally intestinal colic and diarrhoea. In the case of Bz, skin manifestations are the most notorious (e.g., hypersensitivity, dermatitis with cutaneous eruptions, generalized oedema, fever, lymphoadenopathy, articular and muscular pain), with depression of bone marrow, thrombocytopenic purpura and agranulocytosis being the more severe manifestations. Experimental toxicity studies with Nfx evidenced neurotoxicity, testicular damage, ovarian toxicity, and deleterious effects in adrenal, colon, oesophageal and mammary tissue. In the case of Bz, deleterious effects were observed in adrenals, colon and oesophagus. Bz also inhibits the metabolism of several xenobiotics biotransformed by the cytochrome P450 system and its reactive metabolites react with fetal components in vivo. Both drugs exhibited significant mutagenic effects and were shown to be tumorigenic or carcinogenic in some studies. The toxic side effects of both nitroheterocyclic derivatives require enzymatic reduction of their nitro group. Those processes are fundamentally mediated by cytochrome P450 reductase and cytochrome P450. Other enzymes such as xanthine oxidoreductase or aldehyde oxidase may also be involved.
    Human &amp Experimental Toxicology 09/2006; 25(8):471-9. · 1.41 Impact Factor
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    ABSTRACT: This review gives an account of central nervous system (CNS) involvement in Chagas disease, as confirmed by pathological studies. The fundamental histopathological finding associated with the acute nervous form of the disease is nodular encephalitis in multiple foci. CNS involvement probably does not occur in patients with the mild symptomatic acute form; or, in some cases, mild encephalitis in sparse foci may be present. Reactivation of chronic Chagas disease (reactivated acute nervous form), although uncommon, has been reported in immunosuppressed patients with malignant neoplasms of the hematopoietic-lymphoid system, after renal, heart and bone marrow transplantation and especially after the emergence of AIDS. Three aspects differentiate CNS involvement in immunosuppressed chagasic patients from the neuropathological picture described in the acute nervous form: the encephalitis in multiple foci tends to acquire a necrotizing feature; numerous amastigotes are always present; and many patients have the tumoral or pseudotumoral form (brain 'chagoma'). Ischemic cerebral changes associated with chronic chagasic cardiopathy (e.g. cerebral infarcts) are common. These changes, which are similar to those found in heart diseases with other causes, are considered secondary to hypoxemia following congestive heart failure, abrupt transitory fall of systemic arterial pressure and cerebral blood flow, cardiac arrhythmias and thromboembolism.
    Transactions of the Royal Society of Tropical Medicine and Hygiene 06/2009; 103(10):973-8. · 1.93 Impact Factor
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    ABSTRACT: African trypanosomes (the prototype of which is Trypanosoma brucei brucei) are protozoan parasites that infect a wide range of mammals. Human blood, unlike the blood of other mammals, has efficient trypanolytic activity, and this needs to be counteracted by these parasites. Resistance to this activity has arisen in two subspecies of Trypanosoma brucei - Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense - allowing these parasites to infect humans, and this results in sleeping sickness in East Africa and West Africa, respectively. Study of the mechanism by which T. b. rhodesiense escapes lysis by human serum led to the identification of an ionic-pore-forming apolipoprotein - known as apolipoprotein L1 - that is associated with high-density-lipoprotein particles in human blood. In this Opinion article, we argue that apolipoprotein L1 is the factor that is responsible for the trypanolytic activity of human serum.
    Nature Reviews Microbiology 07/2006; 4(6):477-86. · 23.32 Impact Factor