Uncovering the role of IFNAR1 in Experimental Cerebral malaria

Dissertation presented the Ph.D degree in Biology

Efficacy of sulfadoxine-pyrimethamine and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria in the Amazon basin of Peru

In vivo antimalarial drug efficacy studies of uncomplicated Plasmodium falciparum malaria at an isolated site in the Amazon basin of Peru bordering Brazil and Colombia showed >50% RII/RIII resistance to sulfadoxine-pyrimethamine but no evidence of resistance to mefloquine.

Durability to marine environment of innovative products for consolidation and chromatic reintegration of historical renders

9th International Masonry Conference 2014, 7-9 July, Universidade do Minho, Guimarães

Evaluation of an immunochromatography test for malaria diagnosis under different storage conditions

This study aimed to evaluate the second-generation OptiMal test for malaria diagnosis under various storage conditions. It detected all the positive samples, except for two Plasmodium malariae samples. Further research evaluating diverse environmental conditions are important for ICT test applicability in Brazilian malaria areas.

Dynamics and kinetics of natural killer cell cytotoxicity in human malaria as evaluated by a novel stepwise cytotoxicity assay

Malaria causes important functional alterations of the immune system, but several of them are poorly defined. To evaluate thoroughly the natural killer cell cytotoxicity in patients with malaria, we developed a technique capable to assess both the dynamics and the kinetics of the process. For the kinetics assay, human peripheral blood mononuclear cells were previously incubated with K562 cells and kept in agarose medium, while for the dynamics assay both cells were maintained in suspension. NK activity from patients with vivax malaria presented a kinetics profile faster than those with falciparum malaria. NK cytotoxicity positively correlated with parasitemia in falciparum malaria. The dynamics of NK cytotoxicity of healthy individuals was elevated at the beginning of the process and then significantly decreased. In contrast, malaria patients presented successive peaks of NK activity. Our results confirmed the occurrence of alteration in NK cell function during malaria, and added new data about the NK cytotoxicity process.

Malaria outbreaks in a non-endemic area of Brazil, 2005

In March 2005, a resident of the municipality of Monte Alegre de Minas, State of Minas Gerais, without any history of traveling to endemic areas for malaria, was diagnosed with Plasmodium vivax infection and local mosquito-borne transmission was suspected. The epidemiological investigation identified another 10 cases with local transmission and all of them were related to the imported malaria case that was detected in this region. The potential exposure site was the banks of the river Tejuco, an area frequented by mineral prospectors. Some of these prospectors were known to have come from states with malaria transmission. In the autochthonous cases, Plasmodium vivax and Plasmodium falciparum were diagnosed. Entomological investigation identified Anopheles (Nyssorhynchus) darlingi, Anopheles (Nyssorhynchus) albitarsis, Anopheles (Nyssorhynchus) triannulatus and Anopheles (Nyssorhynchus) parvus. After the first outbreak, another three autochthonous cases were notified in municipality of Monte Alegre de Minas, in the same year. The occurrence of these outbreaks highlights the importance of surveillance systems in areas that are nonendemic for malaria.

Consolidation and chromatic reintegration of historical renders with lime-based pozzolanic products

Historical renders are exposed to several degradation processes that can lead to a wide range of anomalies,such as scaling, detachments, and pulverization. Among the common anomalies, the loss of cohesion and of adhesion are usually identified as the most difficult to repair; these anomalies still need to be deeply studied to design compatible, durable, and sustainable conservation treatments. The restitution of render cohesion can be achieved using consolidating products. Nevertheless, repair treatments could induce aesthetic alterations, and, therefore, are usually followed by chromatic reintegration. This work aims to study the effectiveness of mineral products as consolidants for lime-based mortars and simultaneously as chromatic treatments for pigmented renders. The studied consolidating products are prepared by mixing air lime,metakaolin, water, and mineral pigments. The idea of these consolidating and coloring products rises from a traditional lime-based technique, the limewash, widely diffused in southern Europe and in the Mediterranean area. Consolidating products were applied and tested on lime-based mortar specimens with a low binder–aggregate ratio and therefore with reduced cohesion. A physico-mechanical, microstructural, and mineralogical characterization was performed on untreated and treated specimens, in order to evaluate the efficacy and durability of the treatments. Accelerated aging tests were also performed to assess consolidant durability, when subjected to aggressive conditions. Results showed that the consolidants tested are compatible, effective, and possess good durability.

Artesunate + amodiaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in the Colombian Pacific region: a noninferiority trial

INTRODUCTION: In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. METHODS: A randomized, controlled, open-label, noninferiority (Δ≤5%) clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28‑day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. Safety: assessed through adverse events. RESULTS: A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval) adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%). There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group), typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group) was significantly shorter (p=0.002). Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68) and 1% and 13.3% after treatment (p<0.001). CONCLUSIONS: Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.

Historical analysis of the records of sylvan yellow fever in the State of Amazonas, Brazil, from 1996 to 2009

IntroductionYellow fever is a non-contagious infectious disease, highly lethal, transmitted by the Aedes, Haemagogus and Sabethes.MethodsDescriptive retrospective study of the yellow fever cases in Amazonas, between 1996 and 2009.ResultsForty two cases of yellow fever were confirmed, with 30 deaths, 10% of which were foreigners.ConclusionsThe presence of Aedes aegypti and Aedes albopictus in both rural Amazonas and its capital demonstrates the dispersion of these vectors and underscores the need for better and continuous epidemiological and entomological control.

Possible artemisinin-based combination therapy-resistant malaria in Nigeria: a report of three cases

Artemisinin-based combination therapy-resistant malaria is rare in Sub-Saharan Africa. The World Health Organization identifies monitoring and surveillance using day-3 parasitaemia post-treatment as the standard test for identifying suspected artemisinin resistance. We report three cases of early treatment failure due to possible artemisinin-based combination therapy-resistant Plasmodium falciparum malaria. All cases showed adequate clinical and parasitological responses to quinine. This study reveals a need to re-evaluate the quality and efficacy of artemisinin-based combination therapy agents in Nigeria and Sub-Saharan Africa.

Historical trajectories of currently shrinking Portuguese cities: A typology of urban shrinkage

Cities develop according to different patterns, undergoing population growth during some periods and decline (shrinkage) during others. Theories attempting to understand these behaviours include: 1) shrinkage is a natural process in the life cycle of a city, alternating with periods of growth, or 2) shrinkage is an extreme event that places cities into a continuous decline process with no return to population growth. We use retrospective data over a period of 130 years to study 25 Portuguese cities currently facing population decline, and show that both theories coexist in time and space. Five types of shrinking city are revealed: “Persistent Early Shrinkage” due to exodus fromthe rural periphery, “Metropolitan Shrinkage” due to the challenges of urban sprawl, “Recent Shrinkage” in de-industrialisation hotspots, “Cyclic Shrinkage” occurring in political transformation cores, and “Mild Shrinkage” due to life-style disamenity. As diversity of city population trajectories appears to be the norm in both Portugal and other Western European countries, the incorporation of this range into the management of urban transitions is recommended in order to reinforce city resilience.

A historical overview of leprosy epidemiology and control activities in Amazonas, Brazil

Leprosy is an ancient infectious disease caused by Mycobacterium leprae. According to comparative genomics studies, this disease originated in Eastern Africa or the Near East and spread with successive human migrations. The Europeans and North Africans introduced leprosy into West Africa and the Americas within the past 500 years. In Brazil, this disease arrived with the colonizers who disembarked at the first colonies, Rio de Janeiro, Salvador and Recife, at the end of the sixteenth century, after which it was spread to the other states. In 1854, the first leprosy cases were identified in State of Amazonas in the north of Brazil. The increasing number of leprosy cases and the need for treatment and disease control led to the creation of places to isolate patients, known as leprosaria. One of them, Colonia Antônio Aleixo was built in Amazonas in 1956 according to the most advanced recommendations for isolation at that time and was deactivated in 1979. The history of the Alfredo da Matta Center (AMC), which was the first leprosy dispensary created in 1955, parallels the history of leprosy in the state. Over the years, the AMC has become one of the best training centers for leprosy, general dermatology and sexually transmitted diseases in Brazil. In addition to being responsible for leprosy control programs in the state, the AMC has carried out training programs on leprosy diagnosis and treatment for health professionals in Manaus and other municipalities of the state, aiming to increase the coverage of leprosy control activities. This paper provides a historical overview of leprosy in State of Amazonas, which is an endemic state in Brazil.

Factors associated with non-adherence to the treatment of vivax malaria in a rural community from the Brazilian Amazon Basin

Abstract: INTRODUCTION We investigated the association between demographic and behavioral factors and non-adherence to antimalarial therapy. METHODS A demographic questionnaire and 5-item self-reported questionnaire regarding non-adherence were completed by 135 patients after treatment for Plasmodium vivax. RESULTS Treatment interruption, but not demographic factors, was significantly associated with non-adherence to therapy. The likelihood of non-adherence was 5.16 times higher when the patients felt better than when they felt worse. The relative risk of parasitic resurgence was 3.04 times higher in non-adherent patients. CONCLUSIONS Treatment interruption is significantly associated with treatment adherence.

Historical reconstructions of raw materials based on a blue smalt coating applied to a seventeenth-century altarpiece

Based on samples cross-sections from the Main Altarpiece of the Coimbra Old Cathedral, where a blue coating performed in 1685 is observed (that was partly covered with a Prussian blue-containing overpaint), the raw materials present in this coating were reproduced and studied. Blue areas were painted with smalt in oil, according to the contract signed by Manoel da Costa Pereira in 1684 and the analysis by Le Gac in 2009. Based on these, three batches of cobalt-based glasses (S1, S2 and S3) were heated and melted in alumina crucibles in the kiln. S1 contained 6.03 % of cobalt oxide, S2 contained 2.10 %, with the addition of 1.49 % of magnesium oxide, and S3 contained 6.82 % of cobalt oxide, with the addition of 4.63% of antimony trioxide. These batches were ground mechanically with water and manually with different vehicles stated in recipes. The results were studied by means of OM, SEM-EDS, X-Ray CT, Colorimetry and Vickers HT. Different binders were also produced and analyzed by means of μ-FTIR, in order to perform their characterization and obtain Standard Spectra. Since anhydrite was identified in the ground layers, gypsum from Óbidos was also characterized by XRD. The main goal of this thesis was to study all the raw materials present in the 1685-blue coating, in order to allow the historically accurate reconstruction of the layers build-up in the next future.