Leishmaniasis is a chronic disease caused by parasites from Leishmania genus and still represents a severe public health problem in the world and the incidence is increasing (Desjeux, 2004). There is no effective vaccine for prevention of any form of leishmaniasis and programs of prevention and drug therapy are the main mechanisms for disease control. On the other hand, current chemotherapy is the only way to treat cases of leishmaniasis. Since the 1940s, the pentavalent antimony compounds (e.g., Glucantime, Pentostam, or branded pentavalent formulations) have been the mainstays of antileishmanial therapy (Ait-Oudhia et al., 2011). Although these drugs are usually effective, they produce serious side effects, present difficulties of administration and high cost, the parasite persists in the scars of clinically cured patients (Schubach et al., 1998), and drug resistance has been observed (Castillo et al., 2010). Second-line drugs are used in areas with high rates of unresponsiveness to antimonial treatment or when it was not possible to administrate it. However, these drugs are even more toxic than antimony compounds and expensive, and these include pentamidine, amphotericin B, anti-fungal, allopurinol, and more recently, miltefosine, paramomicine and sitamaquine. Furthermore, they have low therapeutic index when compared to antimonial compounds (Almeida and Santos, 2011). Instead of determining treatment based on rational therapeutic indications, treatment of choice is frequently dictated by economic considerations and in a large majority of countries, chemotherapeutic approaches for all forms of leishmaniasis rely on the use of pentavalent antimonial compounds (Ait-Oudhia et al., 2011). The mechanism of pentavalent antimony compounds action is the inhibition of glycolytic pathway and ┚-oxidation enzymes of the parasites (Baiocco et al., 2009), but being a heavy metal it is non-selective and it is believed to interfere with other metabolic pathways of parasites and hosts. Furthermore, these drugs can interact with the zinc finger domain of proteins, and many proteins have this motif in their tridimensional structures (Demicheli et al., 2008).
Immunocytochemistry of Proteases in the Study of Leishmania Physiology and Host-Parasite Interaction
Published 2012 in Unknown venue
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2012
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Unknown venue
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2012-03-09
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Biology, Medicine
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