RESUMO
Efforts have been made to establish sensitive diagnostic tools for malaria screening in blood banks in order to detect malaria asymptomatic carriers. Microscopy, the malaria referencetest in Brazil, is time consuming and its sensitivity depends on microscopist experience. Although molecular tools are available, some aspects need to be considered for large-scale screening: accuracy and robustness for detecting low parasitemia, afford ability for application to large number of samples and flexibility to perform on individual or pooled samples...
Assuntos
Humanos , Doadores de Sangue , Malária/transmissão , Portador SadioRESUMO
Anti-malarial resistance in Plasmodium falciparum remains an obstacle for malaria control. Resistance-associated genes were analysed in Brazilian samples over four decades to evaluate the impact of different treatment regimens on the parasite genetic profile. Methods: Samples were collected on filter paper from patients infected in the Amazon region from 1984 to 2011.DNA was extracted with Chelex® 100 and monoinfection confirmed by PCR. SNPs in the pfcrt, pfmdr1, pfdhfr and pfdhpsgenes were assessed by PCR-RFLP. The pfmdr1 copy number was estimated using real time quantitative PCR with SYBR®Green. Parasite response was assessed ex vivo with seven concentrations of each anti-malarial. Patients were treatedaccording to Brazilian guidelines: quinine plus tetracycline or mefloquine in period 1 and ACT in period 2...
Assuntos
Humanos , Plasmodium falciparum , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/genéticaRESUMO
Leishmaniasis, Chagas disease, and malaria affectthe poorest population around the world, with an elevatedmortality and morbidity. In addition, the therapeutic alternativesare usually toxic or ineffective drugs especially thoseagainst the trypanosomatids. In the course of selection of newanti-protozoal compounds from Brazilian flora, the CH2Cl2phase from MeOH extract obtained from the leaves ofPentacalia desiderabilis (Vell.) Cuatrec. (Asteraceae)showed in vitro anti-leishmanial, anti-malarial, and antitrypanosomalactivities. The chromatographic fractionationof the CH2Cl2 phase led to the isolation of thebioactive compound, which was characterized as jacaranone[methyl (1-hydroxy-4-oxo-2,5-cyclohexandienyl)acetate], by spectroscopic methods. This compoundshowed activity against promastigotes of Leishmania (L.)chagasi, Leishmania (V.) braziliensis, and Leishmania(L.). amazonensis showing an IC50 of 17.22, 12.93, and11.86 μg/mL, respectively. Jacaranone was also tested invitro against the Trypanosoma cruzi trypomastigotes andPlasmodium falciparum chloroquine-resistant parasites(K1 strain) showing an IC50 of 13 and 7.82 μg/mL,respectively, and was 3.5-fold more effective than benznidazolein anti-Trypanosoma cruzi assay. However, despiteof the potential against promatigotes forms, this compoundwas not effective against amastigotes of L. (L.) chagasiand T. cruzi. The cytotoxicity study using Kidney Rhesusmonkey cells, demonstrated that jacaranone showedselectivity against P. falciparum (21.75 μg/mL) and aselectivity index of 3. The obtained results suggested thatjacaranone, as other similar secondary metabolites orsynthetic analogs, might be useful tolls for drug designfor in vivo studies against protozoan diseases...