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S M Di Santi

Publications and source records attributed to S M Di Santi.

12 recordsLinked to original sources

Molecular typing of Plasmodium falciparum from Giemsa-stained blood smears confirms nosocomial malaria transmission.

In this report, we describe the partial molecular characterisation of Plasmodium falciparum isolates obtained from two individuals who were involved in a probable case of accidental malaria transmission after admission to a hospital in the metropolitan area of São Paulo, Brazil. Molecular analysis of polymorphic stretches of the merozoite surface protein 1 and 2 genes using PCR-typing and nucleotide sequencing revealed that the two isolates were identical and that the identified msp-1 gene was different from all others published to date. Additional anamnestic data supported our findings and made all other possible routes of infection unlikely. The methodology used here is simple to perform and needs as little as one Giemsa-stained blood smear as starting material.

Adult↗

Prevalence of the dihydrofolate reductase Asn-108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the Brazilian Amazon.

Pyrimethamine resistance in cultivated laboratory isolates of Plasmodium falciparum is linked to the dihydrofolate reductase mutation Asn-108, a mutation that acts by interrupting drug binding within the active site of the enzyme. To determine the prevalence of this mutation in endemic regions harboring pyrimethamine-resistant malaria, we used a mutation-specific polymerase chain reaction assay to survey P. falciparum strains from a wide section of the Brazilian Amazon. Mutations were identified directly from blood samples without intervening steps of in vitro cultivation. Of 42 samples collected from four states in Brazil, 38 (90%) contained the Asn-108 codon AAC that confers pyrimethamine resistance, four samples contained only the wild-type Ser-108 codon AGC, and none contained the Thr-108 codon ACC found in cycloguanil-resistant pyrimethamine-sensitive strains. These findings indicate that a very high incidence of the Asn-108 DHFR mutation is responsible for pyrimethamine resistance in the Amazon, and they are consistent with recent failure rates reported for Fansidar (pyrimethamine-sulfadoxine). We suggest that limited use of proguanil be evaluated as an alternative to pyrimethamine.

Animals↗

Plasmodium falciparum: restricted polymorphism of T cell epitopes of the circumsporozoite protein in Brazil.

We examined the extent of variation of the 3' region of the circumsporozoite gene among Plasmodium falciparum isolates through amplification of a selected DNA fragment followed by DNA sequencing. A total of 32 isolates were analyzed, of which 24 were from Amazon endemic areas in Brazil and 8 from widely separated geographical regions in the world. Among Brazilian isolates only 2 variants were detected: 19 displayed the same sequence of strain 7G8 whereas the 4 remaining isolates differed from the 7G8 strain at five nucleotide positions which also led to amino acid changes. Variation was restricted to one of the T-helper epitopes while the sequence identified as a cytotoxic T cell epitope was conserved in all Brazilian isolates. P. falciparum samples from other geographical regions in the world showed sequences distinct from those of Brazilian isolates. However, some constancy could be observed within that variation. For instance, the most frequent nucleotide substitutions, from A and C at nucleotide positions 1015 and 1024, were the same in all isolates.

Amino Acid Sequence↗

Antimalarial effect in vitro and lack of modulating effect of desipramine and imipramine.

Based on previous studies in vitro of the modulating effect of desipramine on chloroquine-resistance of Plasmodium falciparum, the effect of desipramine and imipramine on freshly isolated resistant Brazilian strains of the parasite was investigated. Both drugs in therapeutic doses showed an unexpected antimalarial effect in vitro in duplicate tests (IC50 = 44.26 and 46.53 micrograms/L for desipramine, and 83.93 and 41.26 micrograms/L for imipramine), but no reversal of resistance when added to cultures together with chloroquine.

Animals↗

In vitro evaluation of erythromycin in chloroquine resistant brazilian P. falciparum freshly isolates: modulating effect and antimalarial activity evidence.

Erythromycin, a reversal agent in multidrug-resistant cancer, was assayed in chloroquine resistance modulation. The in vitro microtechnique for drug susceptibility was employed using two freshly isolates of Plasmodium falciparum from North of Brazil. The antimalarial effect of the drug was confirmed, with an IC50 estimates near the usual antimicrobial therapy concentration, and a significant statistical modulating action was observed for one isolate.

Animals↗

In vitro evaluation of quinidine sensitivity in Brazilian Plasmodium falciparum isolates: comparative analysis to quinine and chloroquine.

Falciparum malaria represents a serious and an increasing world public health problem due to the acquired parasite's resistance to the most available drugs. In some endemic areas, quinidine, a diastereoisomer of the antimalarial quinine, has been employed for replacing the latter. In order to evaluate the use of quinidine as an alternative to the increasing loss of quinine effectiveness in Brazilian P. falciparum strains, as has been observed in the Amazon area, we have assayed quinidine, quinine and chloroquine. The in vitro microtechnique was employed. All isolates showed to be highly resistant to chloroquine. Resistance to quinine was not noted although high MIC (minimal inhibitory concentration) values have been observed. These data corroborate the decreasing sensitivity to quinine in strains from Brazil. Quinidine showed IC50 from 0.053 to 4.577 micromol/L of blood while IC50 from 0.053 to 8.132 micromol/L of blood was estimated for quinine. Moreover, clearance of the parasitemia was observed in concentrations lower than that used for quinidine in antiarrhythmic therapy, confirming our previous data. The results were similar to African isolate.

Animals↗

[Control of blood transfusion malaria in an endemic and in a non-endemic region in Brazil].

The aim of the present work was to establish appropriate criteria for screening of donor blood from regions with distinct Malaria epidemiological characteristics. Three locations with different screening criteria were studied: São Paulo, SP (with no vectorial transmission), Belém, PA (with low active transmission) and Matupá and Peixoto de Azevedo, MT (with high active transmission). The Malaria parasite--Plasmodium sp--was searched for by "thick film", QBC Test and antigen Immunofluorescence test, and was not detected in any of the samples. There was, however, a great variation in the positivity of anti-plasmodial antibodies, as determined by IIF-IgG anti-P. vivax and -P. falciparum, between accepted donors in the 3 studied locations and between rejected and accepted donors in São Paulo (1.98% accepted, 22.3% rejected--p < 0.01) and Belém (17.2% accepted, 58.3% rejected--p < 0.01). These data endorse the use of the applied clinical and epidemiological screening. In Matupá and Peixoto de Azevedo, where there was no rejected donor, the serological positivity was 80.6%. We, therefore, consider that the Malaria screening in blood banks should follow clinical and epidemiological criteria suitable to each region. The laboratorial screening techniques should then detect either the parasites (thick film/QBC Test or the parasite antigens.

Blood Donors↗

[Frequency of malaria relapse due to Plasmodium vivax in a non-endemic region (São Paulo, Brazil)].

Very few well-established information is available about the frequency and timeliness of relapses in cases of Plasmodium vivax malaria acquired in Brazil. So, we analysed a series of correctly treated patients observed out of endemic areas. The rate of relapses seen in São Paulo, which may represent that of the parasitosis in the whole country, was high, ranging from 7.5% to 24.5%, and early in most cases, i.e. appearing by three months, what anticipates a high endemicity.

Brazil↗