In order to obtain more information about the population structure of Chilean Trypanosoma cruzi, and their genetic relationship with other Latino American counterparts, we performed the study of T. cruzi samples detected in the midgut content of Triatoma infestans insects from three endemic regions of Chile. The genetic characteristics of these samples were analysed using microsatellite markers and PCR conditions that allow the detection of predominant T. cruzi clones directly in triatomine midgut content. Population genetic analyses using the Fisher's exact method, analysis of molecular variance (AMOVA) and the determination of F(ST) showed that the northern T. cruzi population sample was genetically differentiated from the two southern population counterparts. Further analysis showed that the cause of this genetic differentiation was the asymmetrical distribution of TcIII T. cruzi predominant clones. Considering all triatomines from the three regions, the most frequent predominant lineages were TcIII (38%), followed by TcI (34%) and hybrid (8%). No TcII lineage was observed along the predominant T. cruzi clones. The best phylogenetic reconstruction using the shared allelic genetic distance was concordant with the population genetic analysis and tree topology previously described studying foreign samples. The correlation studies showed that the lineage TcIII from the III region was genetically differentiated from the other two, and this differentiation was correlated with geographical distance including Chilean and mainly Brazilian samples. It will be interesting to investigate whether this geographical structure may be related with different clinical manifestation of Chagas disease.

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The growth inhibitory effects of six guanine and guanosine analogs, 3-deazaguanine (compound 1); 3-deazaguanosine (compound 2); 6-aminoallopurinol (compound 3); 9-I-xylofuranosyl guanine (compound 4); a ribosylated derivative of compound 3, 6-aminopyrazolo(3,4-d)pyrimidin-4-one (compound 5); and 5-aminoformycin B (compound 6), were tested against some pathogenic members of the family of American Trypanosomatidae. Compounds 1 and 2 were highly active against Trypanosoma cruzi, Trypanosoma rangeli, and American Leishmania spp. in in vitro culture forms. Both compounds also showed antiprotozoal activity in T. cruzi-infected mice, with the optimal dose being about 30 mg/kg of body weight per day given as 10 consecutive doses. Compound 3 was the most active compound in vitro, inhibiting all of the American Trypanosomatidae culture forms tested. It was also highly inhibitory in mice that were acutely infected with T. cruzi, with the optimal dose being about 10 mg/kg of body weight per day. Ribosylation of compound 3 resulted in a derivative that showed decreased inhibitory activity on Trypanosomatidae multiplication. Compound 6 was highly inhibitory of in vitro multiplication of American Leishmania and T. rangeli but had no effect on T. cruzi epimastigotes and on mice that were acutely infected with T. cruzi. Compound 4 showed only a slight effect on T. cruzi epimastigotes.Recent reviews on the chemotherapy of Chagas' disease and American cutaneous leishmaniasis have emphasized the deficiencies of currently available therapeutic agents and the need for new ones (1, 31). These diseases are still important health problems in the Western Hemisphere, while Trypanosoma rangeli, which is apparently a harmless parasite of humans and a variety of birds and domestic animals, infects about 52% of exposed people in endemic areas (23).With regard to purine metabolism, with the exception of adenine, the incorporation of purine bases by Trypanosoma cruzi is similar to that of Leishmania spp. (11). Because purine bases are incorporated more readily than their respective ribonucleosides, it appears that the major biosynthetic pathway from a purine base to its ribonucleoside is direct, via purine phosphoribosyltransferases, rather than a sequential conversion from base to ribonucleoside to ribonucleotide (11). In contrast to Leishmania spp. (19,22) and African trypanosomes (15), which have very high nucleosidecleaving activities, purine ribonucleosides are remarkably stable in T. cruzi (11).With regard to guanine metabolism in members of the family Trypanosomatidae, data are consistent with a direct conversion of guanine to GMP which could be converted sequentially to IMP and AMP by GMP reductase (EC 1.6.6.8) and the adenylosuccinate synthetase (EC 6.3.4.4) to GTP. For guanosine analogs to reach the nucleotide stage, they must be modified by purine nucleoside-cleaving enzymes, which have been demonstrated in several Trypanosomatidae (16,21,24), to produce the parent heterocyclic compound, which then acts as a substrate for hypoxanthin...

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Syphilis during pregnancy has a high risk of congenital transmission with disastrous fetal consequences. Penicillin (PNC) is the only effective antimicrobial for the treatment of pregnant women with syphilis. Chilean guidelines do not consider desensitization to PNC in these women. We report two cases of pregnant women aged 32 and 23 years, with immediate allergy to PNC and syphilis who were safely and successfully desensitized using a four-hour intravenous protocol in the critical care unit and who subsequently received benzathine G PNC. An electronic survey was conducted among approximately 100 Clinical Pharmacists (CP) in the country. Of these, 16 answered and 13 reported having experience in drug desensitization, in at least five cases with PNC and none reported deaths or cardiorespiratory arrest. Desensitization to PNC can be carried out safely and in Chile, this alternative should be incorporated to the management of pregnant women with syphilis and immediate allergy to PNC, instead of using erythromycin.