Showing papers by "Bruno de Sousa published in 2013"

Therapeutic potential of caspofungin combined with trimethoprim-sulfamethoxazole for pneumocystis pneumonia: a pilot study in mice.

Abstract: Pneumocystis pneumonia (PcP) is a major cause of mortality and morbidity in immunocompromised patients. There are limited alternative therapeutic choices to trimethoprim-sulfamethoxazole (TMP-SMX) which is the standard first line therapy/prophylaxis for PcP. The efficacy of low doses of caspofungin and caspofungin in association with TMP-SMX standard-prophylactic dose was evaluated in an experimental model of Pneumocystis. Susceptibility of Pneumocystis spp. to low doses of caspofungin and caspofungin/TMP-SMX was evaluated in Balb/c immunosuppressed mice, infected intranasally with P. murina. Caspofungin was administered once daily at 0.1 mg/kg, 0.05 mg/kg, and 0.001 mg/kg and TMP-SMX was administered by oral gavage (12.25 mg/62.5 mg/day), for 21 days. Efficacy was calculated based on the reduction in organism burden determined through quantitative fluorescent-based real-time PCR (qPCR). Serum β-1,3-D-glucan was measured as an additional marker of infection. The present data showed that caspofungin demonstrated anti-Pneumomocystis effect. However, the doses administrated were too low to achieve Pneumocystis eradication, which suggests that echinocandin treatment should not be administrated as mono-therapy. After 21 days of treatment, P. murina was not detected in the lungs of mice with either TMP-SMX or caspofungin/TMP-SMX. The results showed that, even at the lowest concentrations tested, the efficacy of caspofungin in association with TMP-SMX was higher than the efficacy of either drug used alone. The administration of caspofungin/TMP-SMX was at least 1.4 times more effective against P. murina infection than TMP-SMX used alone. The most promising result was achieved with the combination of caspofungin 0.05 mg/kg/day with TMP-SMX 12.5 mg-62.5 mg/day, which reduced the parasite burden to undetectable levels immediately at the 14(th) day of treatment, showing a highly marked anti-Pneumomocystis effect. These data suggest that the administration of low doses of caspofungin in combination with low doses of TMP-SMX may provide an improved treatment protocol for Pneumocystis infection clearance.

Nonclassic metallointercalators with dipyridophenazine: DNA interaction studies and leishmanicidal activity.

Abstract: Complexes [Cu(CH3COO)(dppz)2]CH3COO (1) and [Zn(dppz)2](BF4)2 (2) with the intercalator dipyridophenazine (dppz) were prepared to obtain metallointercalators with increased geometrical flexibility compared to octahedral ones. Biophysical results (thermal denaturation, circular dichroism, rheometry, atomic force microscopy) indicate a strong interaction with DNA by intercalation and the existence of a positive cooperative effect with groove binding being preferred at low concentration of complexes. Induced circular dichroism (ICD) studies with DNA show that compounds 1 and 2 have a preferred orientation when binding to DNA. Since the compounds lack functional groups to permit hydrogen bonds, a combined intercalation/covalent binding mode is plausible. Further studies by QTof-ESI-MS and tandem experiments with GC oligonucleotides strongly support this dual-binding mode, since binding requires loss of one dppz unit with the copper center remaining attached to DNA even after another dppz loss. DNA saturation ...

Genetic diversity and signatures of selection of drug resistance in Plasmodium populations from both human and mosquito hosts in continental Equatorial Guinea

Abstract: Background In Plasmodium, the high level of genetic diversity and the interactions established by co-infecting parasite populations within the same host may be a source of selection on pathogen virulence and drug resistance. As different patterns have already been described in humans and mosquitoes, parasite diversity and population structure should be studied in both hosts to properly assess their effects on infection and transmission dynamics. This study aimed to characterize the circulating populations of Plasmodium spp and Plasmodium falciparum from a combined set of human blood and mosquito samples gathered in mainland Equatorial Guinea. Further, the origin and evolution of anti-malarial resistance in this area, where malaria remains a major public health problem were traced.

Population dynamics and spatial structure of human-biting mosquitoes, inside and outside of houses, in the Chockwe irrigation scheme, southern Mozambique

Abstract: Focal control of malaria vectors, a potentially cost-effective alternative to conventional control, requires a spatio-temporal understanding of the mosquitoes. Trapping of African malaria vectors has generally been limited to inside houses making distribution estimates dependent on the location of dwellings. The development of tent-traps to sample outdoor biting mosquitoes has enabled more independent estimates. Here we describe both temporal and spatial variation in mosquito movements in an irrigation project village in southern Mozambique. Six hundred and ninety-three tent-trap collections (525 of which were paired with light-trap collections), 552 exit collections and 391 collections of mosquitoes resting inside houses were undertaken from March 2005 to April 2006. Fifteen species of mosquito were collected (five exclusively as larvae). Mansonia africana was the most common finding, numbers being greatest away from the village. Only Anopheles funestus, An. tenebrosus and Culex quinquefasciatus were collected in greater numbers in light-traps compared to tent-traps. Among the common mosquitoes, correlations in numbers of mosquito collected in paired tent and in light-traps were significant for all but An. tenebrosus. Inverse distance weighting was used to produce raster density maps of the most common mosquitoes. All species, with minor variations, in both hot and cool seasons, were collected in greatest numbers close to the edges of the village where water suitable for larval development was available. All exophilic anophelines species tested negative for sporozoites. It is suggested that focal control of larvae, applied by the villagers themselves, could be a suitable alternative to conventional control in this and similar villages.

[Giardia duodenalis and chronic malnutrition in children under five from a rural area of Guinea-Bissau].

Abstract: Introduction: Malnutrition and infections by intestinal parasites such as Giardia duodenalis coexist in the same geographical regions, reaching the highest prevalence in developing countries. The cycle of malnutrition and infection implies that both conditions can aggravate each other and compromise the growth and development of children with special relevance for under-five. The aim of this study was to investigate the association between chronic malnutrition and infection by G. duodenalis in children under five in a rural community in Guinea-Bissau. Material and Methods: A case-control study that included 109 children aged 0 to 59 months of a rural community in Guinea-Bissau was conducted. The anthropometric assessment of children in the study identified 31 cases of chronic malnutrition (z-score height for age < -2) and 78 controls (z-score height for age ≥ -2). Microscopic examination of stools was performed for detection and identification of G. duodenalis and other parasites. Results: The microscopic analysis of stool samples revealed G. duodenalis infection in 29.0% (9/31) of cases and 35.9% (28/78) of controls. No association between the infection with G. duodenalis and chronic malnutrition in children under study could be established. Discussion and Conclusion: The results reinforce the interest in designing further studies exploring this association in different regions and epidemiological settings, while direct to the importance of the criteria for malnutrition definition which influences the subsequent analysis.

Cell phenotypic change due to Cryptosporidium parvum infection in immunocompetent mice

Abstract: Cryptosporidium parvum is an intracellular parasite causing enteritis which can become life-threatening in immunocompromised host. Immunoregulatory T cells play a central role in the regulatory network of the host. Here, we proposed to characterize the populations of immune cells during infection and reinfection with C. parvum. Four-week-old BALB/C mice were inoculated with oocysts of C. parvum at days 0 and 22. Fecal and blood samples, spleens, and small intestines were collected for analysis. Peripheral blood and spleen cell populations were characterized by flow cytometry. After infection (days 0 to 21), mice presented higher values of neutrophils, eosinophils, NK cells and CD4(+)CD25(high) T cells in peripheral blood. After reinfection, this upward trend continued in the following days for all four populations in infected mice. At day 35, infected mice presented similar values to the control group, except for CD4(+)CD25(high) T cells, which remained higher in infected mice. A possible correlation between alterations in blood and spleen cell populations was also studied, but no consistent association could be established. Small intestine sections were screened for intracellular stages of the parasite but no evidence of pathology was observed. Here, we report information which may be important for the understanding of the specific cell-mediated response in immunocompetent mice to C. parvum infection. Although some questions remain unanswered and complementary studies are needed, our results are expected to contribute to a better understanding of innate and Treg cells role in the clearance process of this parasite.

Healthcare access and the patterns of maternal health care utilization among poor and non-poor women living in urban areas in Portugal

Abstract: Introduction: Studies on attitudes and practices are increasingly used but not specifically related to the motivations for the use of reproductive health care among women of fertile age, living in urban areas and in different social contexts. Objectives: The aim of this study was to estimate the associations between the variables of social status (degree of poverty in the studied groups) and the variables of fecundity (representations, tensions, practices and control of fertility) and, in addition, to compare access to health care in the different studied groups, assessing the association between use of maternal health care and poverty in urban areas. Design: A case-control study was conducted in the Municipality of Lisbon, Portugal, with a total sample of 1513 women of fertile age: 499 cases of women considered very poor were selected from the database of beneficiaries of RSI (Social Welfare Payment for Inclusion); 1014 controls (two controls for each selected case), divided as 507 poor women selected from the other beneficiaries of Santa Casa da Misericordia in Lisbon and 507 non-poor women selected from four Health Centers from the Municipality of Lisbon, Portugal. A total of 1054 women answered the questionnaire: 304 cases (response rate of 61%) and 750 (response rate of 74%) controls. The statistical analysis involved descriptive analysis and multinomial logistic regression. Results: The analysis confirms the association between poverty and patterns and representations of fecun dity regarding pregnancy planning. The results of this study thus show the existence of different distributions on several variables and the gradients of poverty. Regarding access to health care, the major impact of poverty on women is limiting access to pharmaceuticals. The incapacity to afford the cost of health care appears as a central aspect of access to health care. Conclusion: A number of factors seem to be associated with poverty in women, such as ethnicity, single motherhood, low household income, low household size, low educational level of women and marital status. The association of poverty with not planning the pregnancy of the last child on one hand and large household size on the other hand points to a vicious circle that sustains poverty and leads to extreme poverty. Limited financial access to health care seems to mediate the association between women’s poverty and low coverage with family planning as well as the lack of access to safe termination of pregnancy.

Giardia Duodenalis e Desnutrição Crónica em Crianças Menores de Cinco Anos de uma Região Rural da Guiné-Bissau.

Abstract: INTRODUCTION Malnutrition and infections by intestinal parasites such as Giardia duodenalis coexist in the same geographical regions, reaching the highest prevalence in developing countries. The cycle of malnutrition and infection implies that both conditions can aggravate each other and compromise the growth and development of children with special relevance for under-five. The aim of this study was to investigate the association between chronic malnutrition and infection by G. duodenalis in children under five in a rural community in Guinea-Bissau. MATERIAL AND METHODS A case-control study that included 109 children aged 0 to 59 months of a rural community in Guinea-Bissau was conducted. The anthropometric assessment of children in the study identified 31 cases of chronic malnutrition (z-score height for age < -2) and 78 controls (z-score height for age = -2). Microscopic examination of stools was performed for detection and identification of G. duodenalis and other parasites. RESULTS The microscopic analysis of stool samples revealed G. duodenalis infection in 29.0% (9/31) of cases and 35.9% (28/78) of controls. No association between the infection with G. duodenalis and chronic malnutrition in children under study could be established. DISCUSSION AND CONCLUSION The results reinforce the interest in designing further studies exploring this association in different regions and epidemiological settings, while direct to the importance of the criteria for malnutrition definition which influences the subsequent analysis.

EVA: Enhancing VoIP applications

Abstract: This paper introduces EVA, a mechanism that enhances VoIP applications by optimizing path selection, taking into consideration multihoming, traffic performance and application performance criteria. These criteria are hierarchically organized according to their type, which can be classified as benefits or costs. EVA solves the NP-hard path selection problem through a MADM technique that employs a new distance function and a stability factor to select paths with optimal quality, while assuring the highest quality of experience during the VoIP call. The EVA solution mitigates unstable scoring, commonly found in MADM techniques, while keeping the same complexity O(m·n). EVA is evaluated analytically using data from a wireless testbed with multihomed hosts. Results demonstrate that EVA selects paths with high quality of experience levels and it is able to maintain the quality levels throughout the sessions. Moreover, when compared to similar techniques, the proposed approach demonstrates higher flexibility and adaptability to heterogeneous scenarios with different characteristics.

Genetic diversity and signatures of selection of drug resistance in Plasmodium populations from both human and mosquito hosts in continental

Abstract: Background: In Plasmodium, the high level of genetic diversity and the interactions established by co-infecting parasite populations within the same host may be a source of selection on pathogen virulence and drug resistance. As different patterns have already been described in humans and mosquitoes, parasite diversity and population structure should be studied in both hosts to properly assess their effects on infection and transmission dynamics. This study aimed to characterize the circulating populations of Plasmodium spp and Plasmodium falciparum from a combined set of human blood and mosquito samples gathered in mainland Equatorial Guinea. Further, the origin and evolution of anti-malarial resistance in this area, where malaria remains a major public health problem were traced. Methods: Plasmodium species infecting humans and mosquitoes were identified by nested-PCR of chelex-extracted DNA from dried blood spot samples and mosquitoes. Analysis of Pfmsp2 gene, anti-malarial-resistance associated genes, Pfdhps, Pfdhfr, Pfcrt and Pfmdr1, neutral microsatellites (STR) loci and Pfdhfr and Pfdhps flanking STR was undertaken to evaluate P. falciparum diversity. Results: Prevalence of infection remains high in mainland Equatorial Guinea. No differences in parasite formula or significant genetic differentiation were seen in the parasite populations in both human and mosquito samples. Point mutations in all genes associated with anti-malarial resistance were highly prevalent. A high prevalence was observed for the Pfdhfr triple mutant in particular, associated with pyrimethamine resistance. Analysis of Pfdhps and Pfdhfr flanking STR revealed a decrease in the genetic diversity. This finding along with multiple independent introductions of Pfdhps mutant haplotypes suggest a soft selective sweep and an increased differentiation at Pfdhfr flanking microsatellites hints a model of positive directional selection for this gene. Conclusions: Chloroquine is no longer recommended for malaria treatment in Equatorial Guinea but sulphadoxinepyrimethamine (SP) remains in use in combination with artesunate and is the only drug recommended in preventive chemotherapy in pregnancy. The high prevalence of point mutations in Pfdhfr and Pfdhps points to the danger of an eventual reduction in the efficacy of SP combined therapy in P. falciparum populations in Equatorial Guinea and to the essential continuous monitoring of these two genes.

[Health system in the Health Region of Lisbon and Tagus Valley: beyond health centers and hospitals].

Abstract: Introducao: A intencao deste trabalho e conhecer melhor, na Regiao de Saude de Lisboa e Vale do Tejo (RSLVT), a dimensao daatividade empresarial associada a producao de saude e bem-estar.Material e Metodos: Analisaram-se bases de dados do Gabinete de Estrategia e Planeamento do Ministerio do Emprego e SolidariedadeSocial, relativas ao ano de 2007 com dados sobre empresas e estabelecimentos nao publicos dos sectores associados asaude e dos recursos humanos associados a esses estabelecimentos, referentes so a Regiao de Lisboa e Vale do Tejo. Em relacaoa mesma Regiao, analisaram-se tambem dados, disponibilizados pelo Instituto Nacional de Estatistica, dos inqueritos, aos hospitaise centros de saude do Servico Nacional de Saude, referentes a 2008. Os dados foram submetidos a analise estatistica descritiva egeorreferenciada.Resultados: Os resultados permitem uma primeira descricao do complexo economico da saude da Regiao de Saude de Lisboa e Valedo Tejo na sua plenitude de empresas, estabelecimentos e recursos humanos dedicados a atividades de saude nos sectores publicoe nao publico.Na Regiao de Saude de Lisboa e Vale do Tejo existem 7180 empresas, 8504 estabelecimentos e 127 430 recursos humanos associadosa atividades de saude. Existem quatro grandes grupos de atividades associadas a saude: prestacao de cuidados, apoio social,comercializacao de produtos de saude e outras categorias. Destas, as tres ultimas categorias estao quase que exclusivamente nosector nao publico, enquanto a prestacao de cuidados, o maior grupo, esta grandemente concentrado no sector publico.Conclusao: Um sector de saude pensado de uma forma ampla e nao so como o Servico Nacional de Saude identifica uma capacidadeinstalada importante nao so do ponto de vista da prestacao de servicos mas tambem de capacidade economica com elevado potencialde internacionalizacao.