are the drugs of choice for the treatment of leishmaniasis over 90 years, a disease that currently affects 12 million people worldwide. Its introduction was based on 19 th century concepts of therapeutic effects of metal salts as arsenicals and other metals, most of them abandoned due to toxic effects or better drugs. In the last three decades, there was a great improvement in the knowledge of cell biology and immunology of those infections, but chemotherapy has not been improved in the same strength. The structure and mechanism of action of the two pentavalent antimonial drugs of choice, meglumine antimoniate and sodium stibogluconate, are not well known and the contamination of those pharmaceutical by toxic contaminants have been verified. Keywords: antimony; leishmaniasis; therapy. INTRODUÇÃO LeishmanioseA leishmaniose é uma doença infecciosa zoonótica, amplamente distribuída em todo mundo, que afeta o homem e os animais. Esta parasitose ocorre na Ásia, Europa, África e Américas, sendo que existem relatos sobre a doença, no continente americano, desde a época colonial. Em 1571, Pedro Pizarro relatou que os povos situados nos vales quentes do Peru eram dizimados por uma doença que desfigurava o nariz, a qual foi posteriormente caracterizada como leishmaniose 1 . A importância desta doença era tamanha, que as deformações provocadas 2 chegaram a ser registradas em peças cerâmi-cas por artistas da época.A Em 1993, a Organização Mundial da Saúde considerou a Leishmaniose como a segunda doença de importância pública, causada por protozoário. VETORESOs vetores da leishmaniose são dípteros da família Psychodida, hematófagos pertencentes aos gêneros Phlebotomus (Velho Mundo) e Lutzomyia (Novo Mundo), com vasta distribuição nos climas quentes e temperados. Somente as fêmeas são hematófagas. Pertencem ao tipo dos dípteros de atividade crepuscular e pós-crepuscular, abrigando-se durante o dia em lugares úmidos, sombrios e bem protegidos dos ventos. São encontrados em tocas de animais silvestres, buracos de pau, ocos de bambu 4 . Os flebótomos, dos gêneros Lutzomyia e Psychopopygus, infectam-se ao picar o animal portador da doença, aspirando macró-fagos parasitados ou amastigotas livres no sangue ou tecidos e podem, assim, transmitir a doença ao homem 5 . Os mamíferos portadores da leishmaniose são geralmente animais silvestres como a preguiça, o tamanduá, roedores, raposas e outros, sendo que grande parte das lesões nestes não é aparente. No Brasil, o mais importante reservatório animal é o cão e a raposa 6 . A partir de estudos patofisiológicos foi verificado que a Leishmania se desenvolve no tubo intestinal do hospedeiro invertebrado, na forma promastigota, e essa, uma vez introduzida nos mamíferos através da picada, transforma-se na forma amastigota. Enquanto a forma promastigota é flagelada e extracelular, a forma amastigota é intracelular e sem movimento. A multiplicação dos amastigotas ocorre no interior de vacúolos parasi-

INTRODUCTION Performance variation among PCR systems in detecting Toxoplasma gondii has been extensively reported and associated with target genes, primer composition, amplification parameters, treatment during pregnancy, host genetic susceptibility and genotypes of different parasites according to geographical characteristics. PATIENTS A total of 467 amniotic fluid samples from T. gondii IgM- and IgG-positive Brazilian pregnant women being treated for 1 to 6 weeks at the time of amniocentesis (gestational ages of 14 to 25 weeks). METHODS One nested-B1-PCR and three one-round amplification systems targeted to rDNA, AF146527 and the B1 gene were employed. RESULTS Of the 467 samples, 189 (40.47%) were positive for one-round amplifications: 120 (63.49%) for the B1 gene, 24 (12.69%) for AF146527, 45 (23.80%) for both AF146527 and the B1 gene, and none for rDNA. Fifty previously negative one-round PCR samples were chosen by computer-assisted randomization analysis and re-tested (nested-B1-PCR), during which nine additional cases were detected (9/50 or 18%). DISCUSSION The B1 gene PCR was far more sensitive than the AF146527 PCR, and the rDNA PCR was the least effective even though the rDNA had the most repetitive sequence. Considering that the four amplification systems were equally affected by treatment, that the amplification conditions were optimized for the target genes and that most of the primers have already been reported, it is plausible that the striking differences found among PCR performances could be associated with genetic diversity in patients and/or with different Toxoplasma gondii genotypes occurring in Brazil. CONCLUSION The use of PCR for the diagnosis of fetal Toxoplasma infections in Brazil should be targeted to the B1 gene when only one gene can be amplified, preferably by nested amplification with primers B22/B23.

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BackgroundToxoplasmosis is a zoonosis caused by an obligate intracellular parasite, Toxoplasma gondii, which affects warm-blooded animals including humans. Its prevalence rates usually vary in different regions of the planet.MethodsIn this study, an analysis of the seroprevalence of toxoplasmosis among Brazilian students was proposed by means of IgG specific antibodies detection. The presence of anti-Toxoplasma gondii antibodies by indirect fluorescent antibody test (IFAT) was also evaluated in order to compare it with enzyme-linked immunosorbent assay (ELISA) and to assess the use of 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and o-phenylenediamine dihydrochloride chromogens.ResultsThe IFAT method showed a seroprevalence of 22.3%. These results were similar to those obtained by ELISA (24.1%). The seroprevalence was directly estimated from the IgG avidity, which showed that in a sample of 112 students, three of them had acute infection, an incidence of 1.6% in the studied population.ConclusionIn this study, the use of different chromogenic substrates in immunoenzymatic ELISA assays did not display different sensitivity in the detection of T. gondii-reagent serum. The extrapolation of results to this population must be carefully considered, since the investigation was conducted on a reduced sample. However, it allows us to emphasize the importance of careful and well prepared studies to identify risk factors for toxoplasmosis, to adopt preventive measures and to offer guidance to at-risk populations about the disease.

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Leishmaniasis is a parasitic disease caused by the intramacrophage protozoa Leishmania spp. and may be fatal if left untreated. Although pentavalent antimonials are toxic and their mechanism of action is unclear, they remain the first-line drugs for treatment of leishmaniasis. An effective therapy could be achieved by delivering antileishmanial drugs to the site of infection. Compared with free drugs, antileishmanial agent-containing liposomes are more effective, less toxic and have fewer adverse side effects. The aim of this study was to develop novel meglumine antimoniate (MA)-containing liposome formulations and to analyse their antileishmanial activity and uptake by macrophages. Determination of the 50% inhibitory concentration (IC(50)) values showed that MA-containing liposomes were ≥10-fold more effective than the free drug, with a 5-fold increase in selectivity index, higher activity and reduced macrophage toxicity. The concentration required to kill 100% of intracellular amastigotes was ≥40-fold lower when MA was encapsulated in liposomes containing phosphatidylserine compared with the free drug. Fluorescence microscopy analysis revealed increased uptake of fluorescent liposomes in infected macrophages after short incubation times compared with non-infected macrophages. In conclusion, these data suggest that MA encapsulated in liposome formulations is more effective against Leishmania-infected macrophages than the non-liposomal drug. Development of liposome formulations is a valuable approach to the treatment of infectious diseases involving the mononuclear phagocyte system.

We conducted a retrospective analysis of Toxoplasma encephalitis patients from Instituto de Infectologia Emílio Ribas, the main AIDS hospital of São Paulo, Brazil, during two different stages of the HIV epidemics, in 1988 (38 patients) and 1991 (33 patients). There were AIDS-related demographic differences, but the clinical presentation and diagnostic efficiency were similar, usually based on tomography and clinical response to therapy, with a clear distinction from other CNS infections, based on clinical and laboratory findings. Specific serologic studies were performed less often in 1991, with a high frequency of therapy change. The direct acute death rate from Toxoplasma encephalitis was high during both periods, i.e. 8/38 in 1988 and 10/33 in 1991. The direct acute death rate for the patients from the two periods as a whole was 25.4% (18/71), related to the time of HIV infection, absence of fever and presence of meningeal irritation at presentation, blood leukocytes higher than 10,000/mm3 and blood lymphocytes lower than 350/mm3. Toxoplasma encephalitis is a preventable disease when adequate prophylactic therapy is used and is relatively easy to treat in diagnosed HIV patients. Unfortunately, this severe and deadly disorder is the HIV diagnostic disease in several patients, and our data support the need for careful management of these patients, especially in those countries with a high toxoplasmosis prevalence where AIDS is concurrent with economic and public health problems.