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The Asian tiger mosquito (Aedes albopictus), a vector of dengue, Zika and other diseases, was introduced in Europe in the 1970s, where it is still widening its range. Spurred by public health concerns, several studies have delivered predictions of the current and future distribution of the species for this region, often with differing results. We provide the first joint analysis of these predictions, to identify consensus hotspots of high and low suitability, as well as areas with high uncertainty. The analysis focused on current and future climate conditions and was carried out for the whole of Europe and for 65 major urban areas. High consensus on current suitability was found for the northwest of the Iberian Peninsula, southern France, Italy and the coastline between the western Balkans and Greece. Most models also agree on a substantial future expansion of suitable areas into northern and eastern Europe. About 83% of urban areas are expected to become suitable in the future, in contrast with ~ 49% nowadays. Our findings show that previous research is congruent in identifying wide suitable areas for Aedes albopictus across Europe and in the need to effectively account for climate change in managing and preventing its future spread.

La presente investigación tuvo como objetivo determinar la prevalencia de Toxoplasma gondii en estudiantes de la cerrera de Medicina Veterinaria de la Universidad Politécnica Salesiana de la ciudad de Cuenca, mediante la técnica de Elisa Indirecta. Las muestras sanguíneas fueron tomadas a cada uno de los estudiantes de diferentes ciclos y docentes. Con el objetivo de obtener resultados, que nos permitan identificar que tan expuestos están los estudiantes de Medicina Veterinaria a este parásito. The objective of this research was to determine the prevalence of Toxoplasma gondii, in students of the Veterinary Medicine school of the Salesian Polytechnic University of the city of Cuenca, through the Elisa Indirecta technique. Blood samples were taken from each of the students from different cycles and teachers. In order to obtain results that allow us to identify how exposed Veterinary Medicine students are to this parasite.

Publisher Copyright: © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. Identification of partial sweeps, which include both hard and soft sweeps that have not currently reached fixation, provides crucial information about ongoing evolutionary responses. To this end, we introduce partialS/HIC, a deep learning method to discover selective sweeps from population genomic data. partialS/HIC uses a convolutional neural network for image processing, which is trained with a large suite of summary statistics derived from coalescent simulations incorporating population-specific history, to distinguish between completed versus partial sweeps, hard versus soft sweeps, and regions directly affected by selection versus those merely linked to nearby selective sweeps. We perform several simulation experiments under various demographic scenarios to demonstrate partialS/HIC's performance, which exhibits excellent resolution for detecting partial sweeps. We also apply our classifier to whole genomes from eight mosquito populations sampled across sub-Saharan Africa by the Anopheles gambiae 1000 Genomes Consortium, elucidating both continent-wide patterns as well as sweeps unique to specific geographic regions. These populations have experienced intense insecticide exposure over the past two decades, and we observe a strong overrepresentation of sweeps at insecticide resistance loci. Our analysis thus provides a list of candidate adaptive loci that may be relevant to mosquito control efforts. More broadly, our supervised machine learning approach introduces a method to distinguish between completed and partial sweeps, as well as between hard and soft sweeps, under a variety of demographic scenarios. As whole-genome data rapidly accumulate for a greater diversity of organisms, partialS/HIC addresses an increasing demand for useful selection scan tools that can track in-progress evolutionary dynamics. publishersversion published

Publisher Copyright: © 2022 The Authors Leishmanioses are of public health concern in Morocco, mainly the Zoonotic Cutaneous Leishmaniasis (ZCL) endemic in the Moroccan pre-Saharian area. Transmission of this disease depends on eco-epidemiological and socio-economic conditions. Therefore, a multivariable approach is required to delineate the risk and intensity of transmission. This will help outline main disease risk factors and understand interactions between all underlying factors acting on disease transmission at a local and regional scale. In this context, we propose a new conceptual model, the Biophysical-Drivers-Response-Zoonotic Cutaneous Leishmaniasis (BDRZCL), adapted to the Pre-Saharian area. The proposed model highlights how the physical and human drivers affect the environment and human health. The incidence of ZCL is linked to human activity and biophysical changes or by their interactions. The human response added to risk drivers are the main components that influence the biophysical part. This model improves our understanding of the cause-effect interactions and helps decision-makers and stakeholders react appropriately. publishersversion published

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsmedchemlett.1c00589. Malaria, leishmaniasis, and sleeping sickness are potentially fatal diseases that represent a real health risk for more than 3,5 billion people. New antiparasitic compounds are urgent leading to a constant search for novel scaffolds. Herein, pyrazino[2,1-b]quinazoline-3,6-diones containing indole alkaloids were explored for their antiparasitic potential against Plasmodium falciparum, Trypanosoma brucei, and Leishmania infantum. The synthetic libraries furnished promising hit compounds that are species specific (7, 12) or with broad antiparasitic activity (8). Structure-activity relationships were more evident for Plasmodium with anti-isomers (1S,4R) possessing excellent antimalarial activity, while the presence of a substituent on the anthranilic acid moiety had a negative effect on the activity. Hit compounds against malaria did not inhibit β-hematin, and in silico studies predicted these molecules as possible inhibitors for prolyl-tRNA synthetase both from Plasmodium and Leishmania. These results disclosed a potential new chemotype for further optimization toward novel and affordable antiparasitic drugs. publishersversion published

Maria Callas’ diet, also known as the tapeworm diet, is a non-food-based hazardous treatment. This study aims to justify whether Maria Callas used this treatment for weight loss. To investigate this, we searched in the ‘white’, ‘grey’, and ‘black’ literature. The historical facts about the use of tapeworm pills seem to be inconsistent and include fake news. In the case of Maria Callas, it has been confirmed by her biography and personal communications that she was diagnosed with a beef tapeworm due to eating uncooked meat. This discredits the hypothesis that she consumed tapeworm pills.

Funding Information: T.P.V., P.G.K., and A.A.A. acknowledge financial support from the German Center for Infection Research (DZIF), Clinical Research Group, Lambarene, and a German Science Foundation grant (DFG Ku 775/17-1) for the German African Cooperation Project in Infectiology. Work was supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT, Portugal (to BioISI). L.P.-L. is the recipient of a fellowship from BioSys Ph.D. program PD65-2012 (reference number SFRH/BD/142860/2018) from FCT (Portugal). V.M.L. receives support from the Swedish Research Council (grant agreement numbers 2016-01153, 2016-01154, and 2019-01837), the EU/EFPIA/OICR/McGill/KTH/Diamond Innovative Medicines Initiative 2 Joint Undertaking (EUbOPEN grant number 875510), the Swedish Strategic Research Programmes in Diabetes (SFO Diabetes), Stem Cells and Regenerative Medicine (SFO StratRegen), as well as the European Union’s Horizon 2020 research and innovation program U-PGx (grant agreement number 668353). Publisher Copyright: © 2021 American Society for Microbiology. Malaria remains one of the deadliest diseases in Africa, particularly for children. While successful in reducing morbidity and mortality, antimalarial treatments are also a major cause of adverse drug reactions (ADRs). Host genetic variation in genes involved in drug disposition or toxicity constitutes an important determinant of ADR risk and can prime for parasite drug resistance. Importantly, however, the genetic diversity in Africa is substantial, and thus, genetic profiles in one population cannot be reliably extrapolated to other ethnogeographic groups. Gabon is considered a high-transmission country, with more than 460,000 malaria cases per year. Yet the pharmacogenetic landscape of the Gabonese population or its neighboring countries has not been analyzed. Using targeted sequencing, here, we profiled 21 pharmacogenes with importance for antimalarial treatment in 48 Gabonese pediatric patients with severe Plasmodium falciparum malaria. Overall, we identified 347 genetic variants, of which 18 were novel, and each individual was found to carry 87.369.2 (standard deviation [SD]) variants across all analyzed genes. Importantly, 16.7% of these variants were population specific, highlighting the need for high-resolution pharmacogenomic profiling. Between one in three and one in six individuals harbored reduced-activity alleles of CYP2A6, CYP2B6, CYP2D6, and CYP2C8 with important implications for artemisinin, chloroquine, and amodiaquine therapy. Furthermore, one in three patients harbored at least one G6PD-deficient allele, suggesting a considerably increased risk of hemolytic anemia upon exposure to aminoquinolines. Combined, our results reveal the unique genetic landscape of the Gabonese population and pinpoint the genetic basis for interindividual differences in antimalarial drug responses and toxicity. publishersversion published

Funding Information: We acknowledge the participants in the study, without whom this research could not have been done. For laboratorial support the authors wish to show their appreciation to Gabriel Barbosa de Abreu (in memorian). To Norman Ratcliffe for the English revision of this manuscript. Part of this work is described in a Master?s Dissertation by PS, conducted at the Applied Microbiology and Parasitology Post-graduation Program, Federal Fluminense University. Publisher Copyright: © Copyright © 2021 Salles, Perce-da-Silva, Rossi, Raposo, Ramirez Ramirez, Pereira Bastos, Pratt-Riccio, Cassiano, Baptista, Cardoso, Banic and Machado. Genetic variability was linked with individual responses to treatment and susceptibility to malaria by Plasmodium vivax. Polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. The aim of the study was to investigate whether or not CYP2D6 single nucleotide polymorphisms rs1065852, rs38920-97, rs16947 and rs28371725 are unequally distributed in malaria by Plasmodium vivax individuals from the Brazilian Amazon region. The blood samples were collected from 220 unrelated Plasmodium vivax patients from five different endemic areas. Genotyping was performed using SNaPshot® and real-time polymerase chain reaction methods. In all five areas, the rs1065852 (CYP2D6*10, C.100C > T), rs3892097 (CYP2D6*4, 1846C > T) and rs16947 (CYP2D6*2, C.2850G > A), as a homozygous genotype, showed the lowest frequencies. The rs28371725 (CYP2D6*41, 2988G > A) homozygous genotype was not detected, while the allele A was found in a single patient from Macapá region. No deviations from Hardy-Weinberg equilibrium were found, although a borderline p-value was observed (p = 0.048) for the SNP rs3892097 in Goianésia do Pará, Pará state. No significant associations were detected in these frequencies among the five studied areas. For the SNP rs3892097, a higher frequency was observed for the C/T heterozygous genotype in the Plácido de Castro and Macapá, Acre and Amapá states, respectively. The distribution of the CYP2D6 alleles investigated in the different areas of the Brazilian Amazon is not homogeneous. Further investigations are necessary in order to determine which alleles might be informative to assure optimal drug dosing recommendations based on experimental pharmacogenetics. publishersversion published

Malaltia de Chagas; Trypanosoma cruzi; Variabilitat genètica Chagas disease; Trypanosoma cruzi; Genetic variability Enfermedad de Chagas; Trypanosoma cruzi; Variabilidad genética Background: Trypanosoma cruzi has a high rate of biological and genetic variability, and its population structure is divided into seven distinct genetic groups (TcI-TcVI and Tcbat). Due to immigration, Chagas disease (ChD), caused by T. cruzi, has become a serious global health problem including in Europe. Therefore, the aim of this study was to evaluate the existence of genetic variability within discrete typing unit (DTU) TcV of T. cruzi in Bolivian patients with chronic ChD residing in Barcelona, Spain. Methods: The DNA was extracted from the peripheral blood of 27 patients infected with T. cruzi DTU TcV and the fragments of the genetic material were amplificated through the low stringency single primer-polymerase chain reaction (LSSP-PCR). The data generated after amplification were submitted to bioinformatics analysis. Results: Of the 27 patients evaluated in the study, 8/27 (29.6%) were male and 19/27 (70.4%) female, 17/27 (62.9%) were previously classified with the indeterminate clinical form of Chagas disease and 10/27 (37.1%) with Chagas cardiomyopathy. The LSSP-PCR detected 432 band fragments from 80 to 1,500 bp. The unweighted pair-group method analysis and principal coordinated analysis data demonstrated the existence of three distinct genetic groups with moderate-high rates of intraspecific genetic variability/diversity that had shared parasite's alleles in patients with the indeterminate and cardiomyopathy forms of ChD. Conclusions: This study demonstrated the existence of a moderate to high rate of intra-DTU TcV variability in T. cruzi. Certain alleles of the parasite were associated with the absence of clinical manifestations in patients harboring the indeterminate form of ChD. These results support the need to search for increasingly specific targets in the genome of T. cruzi to be correlated with its main biological properties and clinical features in patients with chronic ChD. This work was supported by São Paulo Research Foundation (FAPESP)- fapesp.br/en (Grant No. 2018/22093-4), São Paulo Research Foundation (FAPESP)- fapesp.br/en (Grant No. 2019/11943-0), São Paulo Research Foundation (FAPESP)- fapesp.br/en (Grant No. 2016/25403-9), and Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, PROSICS Barcelona, Spain.

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In Spain, PCR is the tool of choice for the diagnosis of congenital Chagas disease (CD) and serology for diagnosing chronic CD. A loop-mediated isothermal amplification test for Trypanosoma cruzi DNA detection showed good analytical performance and ease of use., In Spain, PCR is the tool of choice for the diagnosis of congenital Chagas disease (CD) and serology for diagnosing chronic CD. A loop-mediated isothermal amplification test for Trypanosoma cruzi DNA detection showed good analytical performance and ease of use. We aimed to evaluate the performance of the Loopamp Trypanosoma cruzi detection kit (Eiken Chemical Co. Ltd., Japan) (Tcruzi-LAMP) for congenital and chronic CD diagnosis using well-characterized samples. We included samples from 39 congenital and 174 chronic CD cases and from 48 uninfected children born to infected mothers and 34 nonchagasic individuals. The sensitivity, specificity, and accuracy of Tcruzi-LAMP were estimated using standard case definitions for congenital CD (positive result by parasitological or PCR tests or serology after 9 months of age) and chronic CD (positive serology by at least two tests). The Tcruzi-LAMP results were read by visual examination and a real-time fluorimeter. For congenital CD, Tcruzi-LAMP sensitivity was 97% for both types of reading; specificity was 92% by visual examination and 94% by fluorimeter. For chronic CD, sensitivity was 47% and specificity 100%. The accuracy in congenital CD was >94% versus 56% in chronic CD. The agreement of Tcruzi-LAMP with PCR tests was better in congenital CD (kappa, 0.86 to 0.91) than in chronic CD (kappa, 0.67 to 0.83). The Loopamp Trypanosoma cruzi detection kit showed good performance for the diagnosis of congenital CD. Tcruzi-LAMP, like PCR, can be useful for the screening and early diagnosis of congenital infection.

Schistosomiasis is a chronic neglected tropical disease saddling millions of people in the world, mainly children living in poor rural areas. Praziquantel (PZQ) is currently the only drug used for the treatment and control of this disease. However, the extensive use of this drug has brought concern about the emergence of PZQ-resistance/tolerance bySchistosoma mansoni. Studies ofSchistosomaspp. genome, transcriptome, and proteome are crucial to better understand this situation. In thisin vitrostudy, we compare the proteomes of aS. mansonivariant strain stably resistant to PZQ and isogenic to its fully susceptible parental counterpart, identifying proteins from male and female adult parasites of PZQ-resistant and PZQ-susceptible strains, exposed and not exposed to PZQ. A total of 60Schistosomaspp. proteins were identified, some of which present or absent in either strain, which may putatively be involved in the PZQ-resistance phenomenon. These proteins were present in adult parasites not exposed to PZQ, but some of them disappeared when these adult parasites were exposed to the drug. Understanding the development of PZQ-resistance inS. mansoniis crucial to prolong the efficacy of the current drug and develop markers for monitoring the potential emergence of drug resistance.

Soil-transmitted helminths (STH) represent a significant public health problem. However, Strongyloides stercoralis is not yet integrated into the control strategy against STH, given limitations to accurately assess its burden. Considering that S. stercoralis shares biological and epidemiological characteristics with hookworms, we describe a new approach for an improved estimation of the burden of infections by S. stercoralis based on the prevalence and burden of hookworms and the relationship between these species. A systematic review of publications reporting prevalence rates for S. stercoralis and hookworms was carried out. The data was classified into two categories: 1) “Community”, with surveys including all age groups, and 2) “SAC”, with surveys limited to school-aged children. The relationship between S. stercoralis and hookworms was characterized in order to estimate the global burden of S. stercoralis infections. The study is registered in PROSPERO (CRD42019131127). Spearman correlation coefficient between S. stercoralis and hookworms was estimated and the global burden of S. stercoralis infections was estimated using a regression model. A total of 119 articles were included, and a significant positive correlation between the burden of S. stercoralis and hookworms was identified. Spearman’s coefficient for Community surveys was 0.94 and for SAC surveys it was 0.63. Based on the linear model, the global burden of S. stercoralis infections was estimated at 386 million (95%CI 324–449 million) people, including 22 million (95%CI 20–24 million) SAC. The significant relationship between S. stercoralis and hookworms allows an estimation of the global burden of S. stercoralis infections in most epidemiologic settings using hookworm burden and justifies the search of integrated control activities. Trial registration PROSPERO (registration code CRD42019131127)., Author summary Evidence on epidemiologic similarities between Strongyloides stercoralis and hookworms was confirmed by our group. A systematic bibliographic search of surveys published between 2001 and 2018 was carried out. Results suggested that the prevalence and burden of infections by hookworms could be used as a proxy to estimate S. stercoralis infections. This approach is based on a linear relationship between the burden of these species. In addition, the models and linearity showed a better fit for surveys using diagnostic methods with high sensitivity for both species. Our estimate of 386 million people infected with S. stercoralis globally, provides an update of the burden of S. stercoralis. This implies an estimate of almost four times higher than what was estimated previously. Our approach allows evidence-based approximation to the estimations of the global burden of S. stercoralis infections, for different age groups and geographic regions. This information highlights the hidden burden of S. stercoralis while also contributing in the estimation of the potential need for ivermectin for the treatment of neglected tropical diseases.

descripción no proporcionada por scopus, ISGlobal work is supported by the Departament d’Universitats i Recerca de la Generalitat de Catalunya, Spain (AGAUR; 017SGR00924) and by the Instituto de Salud Carlos III (ISCIII) RICET Network for Cooperative Research in Tropical Diseases (ISCIII; RD16/0027/0004 - PI1290) and FEDER. MJP research is supported by the Ministry of Health, Government of Catalonia (PERIS 2016-2010 SLT008/18/00132). ICA, JG, and FT are supported by the grant number U01AI129783 from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). ICA is also partly supported by the grant number 5U54MD007592 from the National Institute on Minority Health and Health Disparities (NIMHD), NIH. MCL and MCT were supported by ISCIII RICET grant RD16/0027/0005 - PI1290 and FEDER and by grants SAF2016-81003-R and SAF2016-80998-R from the Spanish “Programa Estatal I+D+i (MINECO)”. AA's work was supported by the Italian Ministry of Health “Fondi Ricerca Corrente - Linea 3, progetto 9” to IRCCS Sacro Cuore Don Calabria Hospital. JR was supported by CONACyT Fossis grant #261006. The Drugs for Neglected Diseases initiative (DNDi) is grateful to its donors, public and private, who have provided funding to DNDi since its inception in 2003. A full list of DNDi's donors can be found at http://www.dndi.org/donate/donors/. FIND is grateful to its donors, public and private, who have helped bring innovative new diagnostics for diseases of poverty. A full list of FIND’s donors can be found at: https://www.finddx.org/partners-donors/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Data sources The authors of this rapid review did not disclose which electronic databases were included in their literature search. The inclusion and exclusion criteria for the data sources are not reported in the manuscript. Study selection The authors included six studies on the effectiveness of hydroxychloroquine or chloroquine for the prevention and treatment of COVID-19 in humans. Studies comprised of two randomised controlled trials, two non-randomised trials both of which were non-blinded and open-label and one that was uncontrolled, a prospective cohort study and an interim report. The authors did not report details of any studies that were excluded. Data extraction and synthesis The data extraction methodology was not reported and it is unclear if the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. Treatment regimens and the study outcomes were extracted where available and overall findings were presented in a table. There were no comparable outcome measures; therefore, results were deemed unsuitable to combine and no statistical analyses were carried out. A narrative synthesis of each study is presented. Results The results of the studies in this rapid review are difficult to quantify as each study had different outcome parameters. Due to the heterogeneity of the studies, results were not combined, and no statistical analysis was carried out. Narrative synthesis of each of the included studies identified important and significant limitations, precluding the studies from demonstrating a statistically significant difference in outcomes. Conclusions This review highlights the urgent need for more high quality evidence on the use of hydroxychloroquine and chloroquine in the prevention and treatment of COVID-19. The results of the studies included should be interpreted with caution due to the weak supporting data and numerous methodological limitations. The authors suggested that the studies be viewed as hypothesis-generating and should not be used in decision making around the recommendations and guidelines in the prevention and treatment of COVID-19. There are currently several ongoing randomised controlled trials looking at the effectiveness and efficacy of these drugs on COVID-19. It is hoped the outcome of these studies can help guide future recommendations and national guidelines.

Objetivo: Determinar a epidemiologia e a distribuição espacial das parasitoses intestinais no município de Teresina, Brasil. Métodos: Foi realizado um estudo transversal com base nos resultados dos exames parasitológicos de fezes executados no laboratório Raul Bacelar, entre janeiro de 2014 e julho de 2017. Além da prevalência de parasitoses intestinais e de poliparasitismo, verificou-se a associação destas doenças com sexo, zona e período do ano, por meio do teste do qui-quadrado, enquanto a relação com a idade foi analisada pelos testes de Mann-Kendall e comparações múltiplas de faixas etárias. A distribuição espacial foi realizada utilizando o software de georreferenciamento QGIS. Resultados: A prevalência de enteroparasitoses em Teresina foi de 17,8%, sendo Ascaris lumbricoides a espécie mais comum. A prevalência de indivíduos com poliparasitismo foi de 3,1%, na qual foi encontrada uma associação entre as espécies Entamoeba coli e Entamoeba histolytica/dispar. Não houve relação entre parasitoses intestinais e sexo, mas verificou-se que indivíduos na zona rural foram mais suscetíveis a essas doenças. As espécies Ascaris lumbricoides e Entamoeba histolytica/dispar ocorreram com maior frequência, respectivamente, no primeiro e no segundo semestre. Observou-se que houve aparente tendência de aumento de casos de E. histolytica/dispar e de redução de casos de Giardia sp. de acordo com o envelhecimento. O mapeamento das parasitoses intestinais demostrou que houve uma prevalência entre 1 e 20% na maioria dos bairros de Teresina, e a ascaridíase representou pelo menos 40% dos casos de enteroparasitose nesses bairros. Conclusões: Investimentos em saneamento básico e novas investigações epidemiológicas devem ser realizados para o controle das parasitoses intestinais em Teresina, enfatizando que crianças e idosos devem ser considerados grupos prioritários nessas ações

Objectives The aim of this study is to assess the efficacy of the use of pre-exposure prophylaxis (PrEP) with hydroxychloroquine against placebo in healthcare workers with high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in reducing their risk of coronavirus disease 2019 (COVID-19) disease during an epidemic period. As secondary objectives, we would like to: i) assess the efficacy of the use of PrEP with hydroxychloroquine against placebo in healthcare workers with high risk of SARS-CoV-2 infection in reducing their risk of exposure to SARS-CoV-2 (defined by seroconversion) during an epidemic period, ii) evaluate the safety of PrEP with hydroxychloroquine in adults, iii) describe the incidence of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 infection, iv) identify clinical, analytical and microbiological predictors of COVID-19 among healthcare workers at high risk of SARS-CoV-2 infection, v) set up a repository of serum samples obtained from healthcare workers at high risk of SARS-CoV-2 infection for future research on blood markers to predict SARS-CoV-2 infection. Trial design Multicentre double-blind parallel design (ratio 1:1) randomized controlled clinical trial. Participants Approximately 440 healthcare workers of four Spanish hospitals (Hospital Clínic of Barcelona, Hospital de la Santa Creu i Sant Pau of Barcelona, Hospital Plató of Barcelona, Hospital General de Granollers, Barcelona) will be recruited. Participants are considered to be at high-risk of SARS-CoV-2 infection due to their frequent contact with suspected and confirmed cases of COVID-19. For eligibility, healthcare workers with 18 years old or older working at least 3 days a week in a hospital with both negative SARS-CoV-2 polymerase chain reaction (PCR) assays and serological COVID-19 rapid diagnostic tests (RDT) are invited to participate. Participants with any of the following conditions are excluded: pregnancy, breastfeeding, ongoing antiviral, antiretroviral or corticosteroids treatment, chloroquine or hydroxychloroquine uptake the last month or any contraindication to hydroxychloroquine treatment. Intervention and comparator Eligible participants will be allocated to one of the two study groups: Intervention group (PrEP): participants will receive the standard of care and will take 400mg of hydroxychloroquine (2 tablets of 200 mg per Dolquine® tablet) daily the first four consecutive days, followed by 400 mg weekly for a period of 6 months. Control group: participants will receive placebo tablets with identical physical appearance to hydroxychloroquine 200 mg (Dolquine®) tablets following the same treatment schedule of the intervention group. Both groups will be encouraged to use the personal protection equipment (PPE) for COVID-19 prevention according to current hospital guidelines. Main outcomes The primary endpoint will be the number of confirmed cases of a COVID-19 (defined by a positive PCR for SARS-CoV-2 or symptoms compatible with COVID-19 with seroconversion) in the PrEP group compared to the placebo group at any time during the 6 months of the follow-up in healthcare workers with negative SARS-CoV-2 PCR and serology at day 0. As secondary endpoints, we will obtain: i) the SARS-CoV-2 seroconversion in the PrEP group compared to placebo during the 6 months of follow-up in healthcare workers with negative serology at day 0; ii) the occurrence of any adverse event related with hydroxychloroquine treatment; iii) the incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers in the non-PrEP group, among the total of healthcare workers included in the non-PrEP group during the study period; iv) the risk ratio for the different clinical, analytical and microbiological conditions to develop COVID-19; v) a repository of serum samples obtained from healthcare workers confirmed COVID-19 cases for future research on blood markers to predict SARS-CoV-2 infection. Randomisation Participants meeting all eligibility requirements will be allocated to one of the two study arms (PrEP with hydroxychloroquine or non-PrEP control group) in a 1:1 ratio using simple randomisation with computer generated random numbers. Blinding (masking) Participants, doctors and nurses caring for participants, and investigators assessing the outcomes will be blinded to group assignment. Numbers to be randomised (sample size) Each intervention group will have 220 participants, giving a total of 440 participants. Trial Status The current protocol version is 1.5, 2nd of June 2020. Two hundred and seventy-fiveparticipants were recruited and completed first month follow-up until date. The estimated sample size could not be reached yet due to the declining national epidemic curve. Thus, 275 is the total number of participants included until date. The study has been suspended (26th of June) until new epidemic curve occurs. Trial registration This trial was registered on April 2nd 2020 at clinicaltrials.gov with the number NCT04331834. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Portugal, Velho Mundo, e Brasil, Novo Mundo, são países endémicos de Leishmaniose humana e canina, transmitida por flebotomíneos vetores, sendo o agente patogénico, desta zoonose, o protozoário Leishmania infantum, e o cão o principal reservatório. Em Portugal, as espécies flebotomínicas comprovadamente vetoras de L. infantum são Phlebotomus perniciosus e P. ariasi. Contudo, existem várias regiões que ainda não foram estudadas em termos entomológicos, ou não foram monitorizadas há mais de uma década, como é o caso do Alentejo. Já no que diz respeito ao Brasil, no Município de Volta Redonda, casos autóctones de Leishmaniose, humana e canina, foram somente reportados, pela primeira vez, em 2014, e nunca tinham sido realizadas prospeções flebotomínicas. Com este trabalho, pretendeu-se determinar aspetos bioecológicos e vetoriais, quer no Alentejo, quer em Volta Redonda, tendo como objetivo contribuir para o esclarecimento da ocorrência de espécies vetoras de Leishmaniose nas referidas regiões do Velho e Novo Mundo. Em ambos os países, determinaram-se: a abundância relativa das espécies capturadas por armadilha CDC, a razão dos sexos, as densidades, a variação sazonal, as infeções naturais das fêmeas por Leishmania sp., e as refeições sanguíneas das fêmeas ingurgitadas, por técnicas moleculares. Em 2016/2017 (14 meses), nos Distritos de Évora e Beja, capturaram-se 431 exemplares, correspondentes às cinco espécies assinaladas em Portugal. A abundância relativa foi (ordem decrescente): 47,80% P. perniciosus, 35,96% Sergentomyia minuta, 12,76% P. sergenti, 2,55% P. ariasi, e 0,93% P. papatasi. P. perniciosus foi capturado em todas as localidades positivas para a presença de flebotomíneos, sendo a espécie com maior distribuição geográfica. A densidade total mais elevada foi 6,78, em julho. Em Volta Redonda as capturas realizaram-se entre outubro de 2016 e abril de 2018, (18 meses). Dos 165 exemplares capturados, por ordem decrescente de abundância, foram assinaladas as espécies: 86,06% Lutzomyia longipalpis, 10,91% Evandromyia sallesi, 2,42% Nyssomyia whitmani, e 0,60% Ev. lenti. A densidade total mais elevada foi 5,72, em abril.Pela primeira vez, no Alentejo, foram assinaladas espécies naturalmente infetadas por L. infantum: uma P. perniciosus e quatro S. minuta. A ocorrência de S. minuta infetada por esta espécie de Leishmania foi, com este trabalho, assinalada pela primeira vez na Europa. Verificou-se que P. perniciosus e S. minuta se alimentaram em seres humanos, também igualmente demonstrado, pela primeira, vez nesta região. Relativamente aos exemplares capturados em Volta Redonda, Brasil, uma Lu. longipalpis e duas Ev. sallesi foram capturadas naturalmente infetadas por L. infantum. Este facto é de especial interesse, uma vez que Lu. longipalpis é o principal vetor de Leishmaniose visceral no Novo Mundo. Ainda que vários aspetos de risco e vetoriais tenham sido observados, pela primeira vez, nas duas regiões dos dois países, a monitorização flebotomínica deverá ser continuada, não só devido às alterações climáticas e ambientais, que cada vez mais se manifestam, mas também para que medidas de controlo possam ser implementadas de forma eficaz ao conhecer-se, em tempo real, os parâmetros vetoriais, os reservatórios locais e a doença, humana e canina. Portugal-Old World and Brazil-New World are endemics countries for human and canine Leishmaniosis, transmitted by phlebotomine sand flies. The pathogenic agent of this zoonosis is the protozoa Leishmania infantum, and dog the main reservoir. The proven vectors of L. infantum are Phlebotomus perniciosus and P. ariasi in Portugal. However, several areas have not been entomologically studied, or haven´t been monitored for more than a decade, such as Alentejo region. Concerning Brazil, in Volta Redonda Municipality, autochthonous human and canine cases were only reported for the first time in 2014, and there had never been phlebotomine surveys. With this work, it was intended to determine biological and vectorial aspects, both in Alentejo and Volta Redonda, with the goal of contributing for the clarification, of the occurrence of vector species of Leishmaniosis, in said regions of the Old and New World. In both countries, it was determined the following entomological parameters: the relative abundance of the captured species by CDC light trap, sex ratio, densities, seasonal variation, natural infection of the females by Leishmania sp. and blood meals (by molecular techniques). In 2016/2017 (14 months), in Évora and Beja Districts, 431 specimens were captured, corresponding to the five species reported in Portugal. The relative abundance was (in descending order): 47,80% P. perniciosus, 35,96% Sergentomyia minuta, 12,76% P. sergenti, 2,55% P. ariasi, and 0,93% P. papatasi. P. perniciosus was captured in all positive localities for sand fly presence and the species with the highest geographical distribution. The highest density was 6,78, in july. In Volta Redonda captures were performed from october 2016 until april 2018 (18 months). From 165 specimens captured, the following species were pointed out (in descending order): 86,06% Lutzomyia longipalpis, 10,91% Evandromyia sallesi, 2,42% Nyssomyia whitmani, and 0,60% Ev. lenti. The highest density was 5,72, in april. For the first time in Alentejo, naturally infected species by L. infantum were found: one P. perniciosus and four S. minuta. With this study, the occurrence of infected S. minuta by L. infantum was recorded for the first time in Europe. It was also verified that P. perniciosus and S. minuta fed on humans, also equally demonstrated for the first time in this region.In what concerns to the sand fly species in Volta Redonda, Brazil, one Lu. longipalpis and two Ev. sallesi, were captured being naturally infected by L. infantum. This is an especially interesting fact, given that Lu. longipalpis is the main vector of visceral Leishmaniosis in the New World. Even though, several risk and vectorial aspects were observed and reported for the first time in the two regions of both countries, the phlebotomine monitoring should continue, not only due to climate and environmental changes, which manifest evermore frequently nowadays, but also so that control measures may be implemented efficiently by knowing, in real time, the vectorial parameters, reservoirs locations and the disease itself (human and canine).

Nas últimas décadas, tem havido um grande interesse na utilização de plantas e dos seus princípios ativos no campo da medicina com a pesquisa de novos fármacos. Neste trabalho foram testadas 22 plantas medicinais da Guiné-Bissau, com o objetivo de fracionar e identificar os extratos de plantas com atividade biológica (antibacteriana, antiparasitária e quimiopreventiva) contra microrganismos patogénicos. O metanol foi utilizado principalmente como solvente de extração nas 22 plantas que deram origem a 29 amostras incluindo folhas, ramos, cascas e raízes. Além deste solvente de extração foram utilizados mais quatro solventes para fazer o fracionamento, nomeadamente, isopropanol, acetona, clorofórmio e éter nas 29 amostras de plantas. Estas amostras foram testadas em cinco microrganismos: Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa e Toxoplasma gondii, de forma a determinar a existência de atividade antibacteriana e antiparasitária. Os extratos também foram testados sobre células Vero e 3T3, de modo a determinar a sua atividade citotóxica. A quantidade de polifenóis e a capacidade antioxidante dos extratos também foram estudados. Os resultados obtidos foram analisados, avaliando-se quais os extratos das expécies de plantas que demonstravam atividade antibacteriana, anti-parasitária (anti-T. gondii) e quimiopreventiva. Com este estudo, a principal observação foi que os extratos das espécies de plantas: Abrus precatorius, Diospyros heudelotii e Zanthoxylum leprieuri foram os que demonstraram atividade antibacteriana, atividade antiparasitária contra T. gondii, e boa atividade antioxidante, embora tenham apresentado toxicidade nas células VERO e 3T3 para as concentrações estudadas. Concluiu-se que, no futuro, estes extratos poderão ter forte potencial, para o desenvolvimento de novos fármacos. In the last decades, there has been a great interest in the use of plants and their active principles in the field of medicine with the research of new drugs. In this work, 22 medicinal plants from Guinea-Bissau were tested, with the objective of fractionating and identifying extracts of plants with biological activity (antibacterial, antiparasitic and chemopreventive) against pathogenic microorganisms. Methanol was used primarily as extraction solvent in the 22 plants that gave rise to 29 samples including leaves, branches, barks and roots. In addition to this extraction solvent, four other solvents to do the fractionation, namely isopropanol, acetone, chloroform and ether were used in the 29 plant samples. Their action was observed against five microorganisms: Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Toxoplasma gondii, in order to determine the existence of antibacterial and antiparasitic activity. The extracts were also tested on Vero and 3T3 cells in order to determine their cytotoxic activity. The amount of polyphenols and the antioxidant capacity of the extracts were also studied. The results obtained were analyzed, evaluating the extracts of the plant species that showed antibacterial, anti-parasitic (anti-T. gondii) and chemopreventive activity. In the present study, the extracts of the plant species Abrus precatorius, Diospyros heudelotii and Zanthoxylum leprieuri showed antibacterial activity, antiparasitic activity against T. gondii, and good antioxidant activity, although they showed toxicity in VERO and 3T3 cells for the concentrations studied. It was concluded that in the future these extracts may have a strong potential for the development of new drugs.

OBJETIVO: A palavra “miíase” é derivada do grego myio (mosca) e ase (doença), e descreve a infestação em humanos e animais vertebrados vivos por larvas de dípteros, no qual se alimentam de tecidos sadios ou mortos do hospedeiro. O diagnóstico é clinico com base na presença dos vermes, e seu tratamento consiste na remoção total destas larvas. Os autores relatam um caso de desbridamento cirúrgico como opção segura para o tratamento de miíase cavitária em face. DESCRIÇÃO DO CASO: Paciente, 58 anos, sexo masculino, foi admitido com lesão cavitária em face do lado direito contendo larvas de mosca. Foi realizado desbridamento cirúrgico em duas fases, sem associação de medicamentos ou manobras menos invasivas, com a remissão total do quadro, no entanto o paciente faleceu após um mês e meio do início do tratamento oncológico devido a um carcinoma de células escamosas na região posterior de língua e orofaringe. CONCLUSÃO: A utilização de medicamentos antiparasitários é controversa na literatura, que em situações específicas, podem colocar o paciente em risco de vida. Prevenção ainda é a melhor maneira de combater a infestação por miíase. Os autores relataram um caso de miíase cavitária em face utilizando somente o desbridamento cirúrgico como tratamento

Cystoseira is a common brown algal genus widely distributed throughout the Atlantic and Mediterranean regions whose taxonomical assignment of specimens is often hampered by intra- and interspecific morphological variability. In this study, three mitochondrial regions, namely cytochrome oxidase subunit 1 (COI), 23S rDNA (23S), and 23S-tRNAVal intergenic spacer (mt-spacer) were used to analyse the phylogenetic relationships of 22 Cystoseira taxa (n = 93 samples). A total of 135 sequences (48 from COI, 43 from 23S and 44 from mt-spacer) were newly generated and analysed together with Cystoseira sequences (9 COI, 31 23S and 35 mt-spacer) from other authors. Phylogenetic analysis of these three markers identified 3 well-resolved clades and also corroborated the polyphyletic nature of the genus. The resolution of Cystoseira taxa within the three clades improves significantly when the inclusion of specimens of related genera was minimized. COI and mt-spacer markers resolved the phylogeny of some of the Cystoseira taxa, such as the C. baccata, C. foeniculacea and C. usneoides. Furthermore, trends between phylogeny, embryonic development and available chemotaxonomic classifications were identified, showing that phylogenetic, chemical and morphological data should be taken into account to study the evolutionary relationships among the algae currently classified as Cystoseira. The resolution of Cystoseira macroalgae into three well supported clades achieved here is relevant for a more accurate isolation and identification of natural compounds and the implementation of conservation measures for target species. Fundação para a Ciência e a Tecnologia SFRH/BD/78062/2011 SFRH/BD/105541/2014 IF/00866/2014 CCMAR/Multi/04326/2013 PEst-OE/EQB/LA0023/2011 Spanish Ministry of Education info:eu-repo/semantics/publishedVersion

Desde o final da Segunda Guerra Mundial e o início dos anos 90, século XX, os percevejos, ou cimicídeos, com importância em Medicina humana, deixaram de ter relevância no que diz respeito às ectoparasitoses humanas a que dão origem, através das suas picadas. Estes insetos são estritamente hematófagos e os humanos são os seus hospedeiros preferenciais, quer em relação ao comportamento trófico, quer à disseminação passiva por bagagens/mobílias. A partir de 2000, verificou-se uma reemergência global, particularmente no que diz respeito à espécie Cimex lectularius, com todas as graves consequências, quer a nível de saúde pública, quer em termos económicos, uma vez que as desinfestações têm que ser efetuadas por empresas de controlo de pragas, devidamente habilitadas. Em países como os Estados Unidos, Canadá, França, Reino Unido, Brasil, China e outros, as infestações ocorrem em todos os locais em que possam pernoitar seres humanos, tais como hotéis, apartamentos, lares, transportes, hospitais, escolas e outros, o que tem levado à necessidade da realização de estudos epidemiológicos para se verificar o grau de infestação e atuar de forma célere e eficaz. Em Portugal, nenhum estudo sobre percevejos, com importância médica, tinha sido realizado e a Região Metropolitana de Lisboa (RML) é uma das regiões que mais mobilidade de pessoas apresenta, nomeadamente turistas, congressistas, estudantes, empresários, imigrantes, emigrantes e outros. Tendo em conta a possibilidade da ocorrência de infestações cimicídicas, em diferentes variedades de habitações humanas, com a colaboração da Empresa bio 2 health, efetuou-se um estudo, por conveniência, cujos objetivos foram identificar as espécies de percevejos com importância em Medicina humana, capturados em diferentes variedades de habitações, tais como “apartamento”, “hostel”, “hotel” e “lar”, em três concelhos (Lisboa, Oeiras e Cascais) e em 11 freguesias da RML, e determinar o grau de infestação dos quartos/salas observados. Em relação aos 45 quartos/salas prospetados e infestados, 35,55% (16/45) encontravam-se no grau 5 (grau máximo de infestação); 2,22% (1/45), no grau 4; 6,67% (3/45), no grau 3; 6,67% (3/45), no grau 2; 48,89% (22/45), no grau 1. Dos 16 quartos que se encontraram no grau máximo de infestação, 62,5% (10/16) pertenciam a variedade apartamento, 18,75% (3/16) à variedade hotel, 12,5% (2/16) à variedade lar, e 6,25% (1/16) à variedade hostel. As freguesias onde se observaram quartos/salas no grau máximo de infestação foram as seguintes: Lumiar, S. Vicente, Arroios, Alcântara, Misericórdia, e Cascais e Estoril. Todos os cimicídeos capturados foram identificados como pertencentes à espécie Cimex lectularius. Pelos resultados obtidos, conclui-se que: diferentes habitações, independentemente do grau socioeconómico e freguesias prospetadas, estavam infestadas por C. lectularius; estes insetos causaram picadas nos residentes/hóspedes e eventualmente podem ter sido disseminados para outros locais/regiões através das bagagens/mobílias; as habitações infestadas apresentavam graus de infestação de 1 a 5. É de referir que, após as prospeções, as habitações infestadas foram todas desinfestadas pela Empresa que apoiou este primeiro estudo cimicídico realizado em Portugal. After the end of World War II and the early 1990s, bedbugs or cimicids of human medicine importance, ceased to be relevant for the human ectoparasitoses they originate through their bites. These insects are strictly hematophagous and humans are their preferred hosts, both in terms of trophic behavior and passive spread in luggage/furniture. From 2000 onwards there has been a global reemergence, particularly regarding the species Cimex lectularius, with serious consequences both in public health and in economic terms, as disinfestations must be carried out by competent pest control companies. In Countries such as the United States, Canada, France, United Kingdom, Brazil, China, and others, infestations occur wherever humans may stay, such as hotels, apartments, nursing homes, transports, hospitals, schools, and others. These have led to the need for epidemiological studies to verify the degree of infestation and to act quickly and effectively. In Portugal, no study on bed bugs, with medical importance, had been carried out previously and Lisbon Metropolitan Region (LMR) is one of the regions with the greatest mobility of people, such as tourists, congress participants, students, businesspersons, immigrants, emigrants and others. Taking into account the possibility of occurrence of bed bug infestations in different varieties of human dwellings, and with the collaboration of the pest control Company bio 2 health, a convenience study was conducted aiming to identify the species of bed bugs of medical importance, captured in different varieties of housing, namely "apartment", "hostel", "hotel" and " nursing homes ", in 3 municipalities (Lisbon, Oeiras and Cascais) and 11 parishes of LMR, and to determine the degree of infestation of the rooms/halls observed. From the 45 prospected and infested rooms/halls, 35.55% (16/45) were in degree 5 (maximum degree of infestation); 2.22% (1/45) in degree 4; 6.67% (3/45) in degree 3; 6.67% (3/45) in degree 2; 48.89% (22/45) in degree 1. Of the 16 rooms/halls that were found to have the highest degree of infestation, 62.5% (10/16) belong to the apartment variety, 18.75% (3/16) to hotel variety, 12.5% (2/16) to the nursing home variety and 6.25% (1/16) to the hostel variety. The parishes with the highest degree of infestation were: Lumiar, S. Vicente, Arroios, Alcântara, Misericórdia, and Cascais and Estoril. All captured bed bugs were identified as belonging to the species Cimex lectularius. Considering the results obtained, it can be concluded that: different dwellings, regardless of socioeconomic status and prospective parishes, were infested by C. lectularius. These insects caused bites on residents/guests and may eventually have been spread to other locations/regions in luggage/furniture. The infested dwellings presented infestation degrees from 1 to 5. It should be noted that infested dwellings were subjected to pest control by the Company that helped this first cimicidic study conducted in Portugal.

Introducción: El uso de las aplicaciones electrónicas (apps) en la enseñanza médica ha demostrado que facilita el aprendizaje, ya que permiten tener acceso inmediato al conocimiento a cualquier hora y en cualquier lugar. Objetivo: Desarrollar y evaluar una aplicación electrónica (app) para estudiar la morfología y el ciclo biológico del parásito Toxoplasma gondii, para los alumnos del módulo de Parasitología de la asignatura de Microbiología y Parasitología de la Facultad de Medicina UNAM, para reforzar e integrar la información de la enfermedad toxoplasmosis, que es una de las parasitosis más complejas que se estudian en el módulo. Método: La aplicación se desarrolló en el Departamento de Visualización y Realidad Virtual (DVRV) de la Dirección de Cómputo y Tecnologías de Información y Comunicación (DGTIC), UNAM y se evaluó mediante un cuestionario de satisfacción de usuario que se aplicó a los estudiantes del módulo, utilizando una variable criterial de satisfacción correspondiente a la escala de Satisfacción de la versión española del Cuestionario Distance Education Learning Survey. La consistencia interna para el instrumento se calculó con la prueba Alpha de Cronbach. Para identificar la estructura del Instrumento, se utilizó el Análisis de componentes principales (ACP), con rotación Varimax y Normalización Kaiser. Resultados: Los resultados en el ACP indicaron una apropiada adecuación muestral y elementos pertinentes en el instrumento analizado. La consistencia interna para el instrumento mostró un valor estandarizado de 0.87, lo cual aporta evidencia para afirmar que los reactivos miden el mismo constructo relacionando su patrón de respuestas entre sí. Conclusión: La app fue bien aceptada por los estudiantes y cumplió con el objetivo. Las respuestas de los estudiantes permitirán mejorar el diseño de futuras aplicaciones electrónicas para el estudio de la parasitología médica.

Thesis (Magister in Immunology) - University of Cartagena. Institute of Immunological Research. Master's Degree in Immunology, 2018 Background: Helminth infections can modify the immune response of the host and exert risk and protective effects on allergic diseases depending on the chronicity and intensity of the infection. Blood populations such as eosinophils and regulatory B cells have been independently associated with helminth infection and allergic diseases, with eosinophils being used as biomarkers for severity. However, the effects of helminth infections in these blood populations, and the predictive role of eosinophils in asthma severity is unclear in humans from endemic settings. Objectives: To characterize the effects of Ascaris lumbricoides infection in eosinophils, regulatory B cells and asthma severity in asthmatic patients from a helminth endemic population. Methods: In a rural community from the Colombia tropics, asthmatic patients were recruited and evaluated with a clinical questionnaire, specific and total IgE, complete blood counts, skin prick test, serial coprologicals and spirometry. Regulatory B cell subsets were evaluated in a subset of asthmatic patients and controls from the community. Results: A total of 82 patients with wheezing symptoms in the last year were recruited. Complete blood counts showed a mean eosinophil count of 654 (±SD 634) cells/uL, with 48,7% (n=40) of patients having eosinophils greater than 400 cells/uL. The frequency of active A.lumbricoides and T.trichiura infection were 46,3% (n=38) and 18,2% (n=15) respectively. In the multivariate analysis, A.lumbricoides sensitization was associated with a 6.9-fold increase in the odds of having eosinophils greater than 400 cells/uL (p=0.002) and House Dust Mite (HDM) sensitization was also associated with a 5,4-fold increase (p=0.008). Helminth infection was associated with higher log-transformed eosinophils independently of age and HDM sensitization.We found lower percentage of CD24+CD38+ B cells in asthmatic patients compared to control subjects and no significant differences between infected and uninfected patients for CD1dhighCD5+ and CD24highCD38high B cell subsets. Conclusion: In a rural community from the Colombian tropics, where helminths are endemic, sensitization to A.lumbricoides was more predictive of eosinophilia than sensitization to house dust mites. The frequency of regulatory B cell subsets was lower in asthmatic patients than in controls. Further research should evaluate larger cohorts and determine the basal level of eosinophils in this population and focus on the cellular function of regulatory B cells.

Em 2016 a malária foi considerada endémica em 91 países e apesar do decréscimo, estima-se que em 2017 terão ocorrido cerca de 219 milhões de novos casos de malária a nível mundial. Face à propagação da resistência do Plasmodium falciparum à maioria dos antimaláricos disponíveis, a Organização Mundial de Saúde (OMS) recomenda a utilização de terapêuticas combinadas à base de artemisinina (ACT) como tratamento da malária não complicada. Em Timor-Leste os ACTs foram implementados em 2007, sendo o artemeter-lumefantrina (AL) usado como tratamento de primeira linha da malária desde então. A resistência à artemisinina e seus derivados foi confirmada no Sudeste Asiático, por isso o risco de aparecimento e propagação de resistência à artemisinina e seus derivados tem levado a esforços no sentido de serem realizados estudos de resistência em todas as regiões endémicas para a malária. Assim sendo estudos contínuos através do uso de marcadores moleculares que permitam a determinação de resistência aos antimaláricos são muito importantes de forma a detetar precocemente o aparecimento e evitar o alastramento de parasitas P. falciparum resistentes/tolerantes aos ACTs. Neste estudo pretendeu-se optimizar a técnica de Polymerase Chain Reaction (PCR) e desenhar novos primers para detecção de polimorfismos pontuais nos genes pfmdr2 e pfarps10 bem como determinar a frequência de polimorfismos, nos genes pfk13, pfmdr1, pfmdr2 e pfarps10, associados à resposta aos ACTs em isolados de P. falciparum provenientes de Timor-Leste. As amostras utilizadas foram recolhidas entre 2012 e 2013, correspondendo a um período depois da introdução dos ACTs em Timor-Leste. Os polimorfismos nos codões 86, 184 e 1246 do gene pfmdr1, no gene pfmdr2 os codões 423, 484, 492 e por último no gene pfarps10 o codão 127 foram analisados através de amplificação de DNA pela técnica de PCR e sequenciação. Em relação ao gene pfmdr1 verificou-se uma prevalência do alelo selvagem (wild-type) N86 (85%), assim como nos alelos F184 (54,2%) e D1246 (100%). Em relação ao gene pfmdr2 para os codões 484 e 492 mantém-se esta tendência (T484 81,8%; I492 90,9%), já no codão 423 o alelo mais prevalente é 423Y, mutante (81,8%). Por último, no gene pfarps10 apenas se verificou a presença do alelo selvagem (V127 100%). Assim sendo é extremamente importante manter uma vigilância molecular sobre o país uma vez que este se encontra numa fase de pré-eliminação da doença. In 2016 malaria was considered endemic in 91 countries and despite this decrease, uptdated estimates indicate that 219 million malaria new cases occurred globally in 2017. In view of the spread of Plasmodium falciparum resistance to most available antimalarials, the World Health Organization (WHO) recommends the use of combination artemisinin-based therapy (ACT) as a treatment for uncomplicated malaria. In East-Timor, ACTs were implemented in 2007, with artemether-lumefantrine (AL) being used as first-line malaria treatment ever since. Resistance to artemisinin and its derivatives has been confirmed in Southeast Asia, so the risk of emerge and spread of resistance to artemisinin and its derivatives has led to efforts to carry out resistance studies in all endemic regions to malaria. Thus, continuous studies through the use of molecular markers that allow the determination of resistance to antimalarials are very important in to monitor the emergence and avoid the spread of parasites P. falciparum resistant/tolerant to ACTs. The aim of this study was to optimize the Polymerase Chain Reaction (PCR) technique and to design new primers to detect point polymorphisms in the pfmdr2 and pfarps10 genes as well as to determine the frequency of polymorphisms in the pfk13, pfmdr1, pfmdr2 and pfarps10 genes associated with the response to ACTs in P. falciparum isolates from Timor-Leste. The samples used were collected between 2012 and 2013, corresponding to a period after the introduction of ACTs in East-Timor. Polymorphisms at codons 86, 184 and 1246 of the pfmdr1 gene, in the pfmdr2 gene codons 423, 484, 492 and lastly in the pfarps10 codon 127 gene were analyzed by amplification of DNA using a PCR method and sequencing. In relation to the pfmdr1 gene, a prevalence of the wild-type N86 (85%) was observed, as well as in the F184 (54.2%) and D1246 (100%) alleles. In relation to the pfmdr2 gene at codons 484 and 492, this trend remains (T484 81.8%, I492 90.9%), at codon 423 the most prevalent allele is 423Y, mutant (81.8%). Finally, was only found the presence of the wild allele (V127 100%) in the pfarps10 gene. Therefore, it is extremely important to maintain a molecular surveillance of the country once it is in a phase of pre-elimination of the disease.

A partir dos anos 90 do século XX, houve uma reemergência dos percevejos, ou cimicídeos, com importância em Medicina humana, tornando-se estes ectoparasitas uma verdadeira pandemia, e ocorrendo desde os Estados Unidos da América do Norte, ao Canadá, Reino Unido, França, Nigéria e outros. Estes insetos, estritamente hematófagos, encontram-se em hotéis, apartamentos, vivendas, meios de transporte e todos os locais onde possam pernoitar seres humanos. A disseminação passiva deve-se, fundamentalmente, à frequente deslocação das pessoas, individualmente e/ou em massa, com as suas bagagens. Devido às graves repercussões na saúde pública, aos elevados custos, e tendo em vista uma luta eficaz, os estudos epidemiológicos tornam-se cada vez mais necessários. Em Angola, com 24,3 milhões de habitantes, e que por diferentes motivos as pessoas se deslocam, quer internamente, quer para o exterior, nunca se tinha realizado um estudo sobre percevejos. Assim, de outubro de 2017 a fevereiro de 2018, realizaram-se capturas cimicídicas em 5 Províncias (Luanda, Bengo, Malange, Huambo e Huila), tendo como objetivo determinar as espécies cimicídicas, a distribuição, e a taxa e grau de infestação dos quartos e salas de diferentes tipos e variedades de habitações humanas. 60% (3/5) das Províncias (Luanda, Huambo e Huila) foram positivas para percevejos nos quartos/salas das habitações prospetadas. Na Província de Luanda, a taxa e o grau de infestação do tipo/variedade Hotel foi de 10,61% (7/66), e 0/59 - 1/1 - 5/6 respetivamente. As variedades Vivenda, onde se constatou a maior taxa e grau de infestação, e Casa tijolo, foram também positivas, contrariamente às variedades Apartamento, Casa cimento e Casa adobe. Nas outras Províncias positivas, a taxa e grau de infestação foram maiores para as variedades Casa cimento e Vivenda, respetivamente no Huambo e Huila. Capturaram-se 608 percevejos, dos quais 98,19% (597/608) pertencem à espécie Cimex lectularius e a 1,81% (11/608) não foi possível identificar a espécie (características morfológicas não se enquadram nas chaves para cimicídeos com importância em Medicina humana). Estes, foram capturados no Huambo, numa habitação humana da variedade Casa cimento. Com este trabalho, realizado pela primeira vez em Angola, conclui-se que: A espécie C. lectularius está presente em todas as Províncias positivas para cimicídeos; A espécie C. hemipterus não foi encontrada; Os tipos/variedades de habitações humanas onde se capturaram percevejos são variados, desde vivendas, a hotéis, casas de cimento, tijolo e outros; A taxa total de infestação dos quartos/salas das habitações foi de 12,10% (15/124); O grau de infestação variou entre 0, 1 e 5. A maioria dos quartos/salas não estavam infestados (109-grau 0), mas os que estavam, apresentavam o grau máximo de infestação (14-grau 5). Um quarto apresentou somente diurese (grau 1). Assim, as habitações prospetadas, ou eram negativas ou estavam no grau máximo de infestação, o que mostrou que só quando há grandes infestações é que chamam empresas de controlo de pragas. Porém, as condições económicas nem sempre o permitem. Since the 1990s, bed bugs, or cimicids, with human medical importance, re-emerged, turning these ectoparasites into a serious pandemic, occuring from the United States of America to Canada, United Kingdom, France, Nigeria and others. These insects, wich are exclusively hematophagus, i.e., blood feeders, can be found in hotels, apartments, villas, transports, and all over locations where humans may stay overnight. Passive dissemination occurs mostly related to the increase in the movement of people, with their luggage, individually, and/or mass movements. Duo to the serious repercussions on public health, high costs and the need for effective control measures, epidemiological studies are essential. In Angola, with a population of 24.3 million, and where people migrate (for different reasons) both internally and abroad, a survey on bed bugs has never been conducted. Therefore, from October 2017 to February 2018, cimicidic captures were performed in 5 Provinces (Luanda, Bengo, Malange, Huambo and Huila), aiming to determine the bedbug species, their distribution, and the rate and degree of infestation in rooms and halls of different types and varieties of human dwellings. 60% (3/5) of the Provinces (Luanda, Huambo and Huila) were positive for bed bugs in rooms/halls, of the surveyed dwellings. In Luanda Province, the rate and the degree of infestation of the variety/type Hotel were 10.61% (7/66), and 0/59 - 1/1 - 5/6, respectively. The varieties Villa presented the highest rate and degree of infestation. Brick House was positive for the presence of cimicids, unlike the varieties Apartement, Cement House and Adobe House. In the other positive Provinces, the rate and degree of infestation were higher for the varieties Cement House and Villa, in Huambo and Huila, respectively. 608 bed bugs were captured, 98.19% (597/608) of which belonging to the Cimex lectularius species and 1.81% (11/608) could not be identified (morphological characteristics did not fit the keys for Cimidae with human medical importance). These 11 specimens were captured in Huambo, in a human dwelling of the Ciment House variety. With this study, carried out for the first time in Angola, it was possible to conclude the following: Cimex lectularius is present in all bed bugs positive Provinces; The species Cimex hemipterus was not found; The type/varieties of human dwellings where bed bugs were captured are heterogeneous from villas to hotels, cement, brick houses and others; The total cimicids infestation rate of rooms/halls was 12.10% (15/124); The degree of cimicids infestation ranged from 0, 1 and 5; Most of the rooms/halls were not infested (109-degree 0), but those that were, had the highest infestation degree (14-degree 5). One room only presented diuresis (degree 1). Thus, surveyed dwellings were either negative or at the highest degree of infestation, showing that only when there are large infestations the pest control companies are called. However, economic conditions do not always allow it.

There is ever-increasing anticipation for the potential of mass drug administration of endectocides (also known as systemic insecticides) to reduce malaria transmission, with ivermectin emerging as the most likely first-in-class endectocide. More than half of the 46 papers published on this subject in the past decade appeared in the past 2 years. 23 projects are registered in the MESA Track database, of which seven are active today; and, more importantly, trial mapping by the Malaria Ivermectin Roadmap shows that abundant new evidence on the topic will be available by 2020. Why is there so much interest in repurposing ivermectin? After achieving remarkable advances from 2000 to 2015, the global fight against malaria has stalled. Beyond funding and access gaps, residual transmission—driven by mosquito behavioural adaptations that allow avoidance of home-based insecticides—has become a key liability for vector control, and challenges achievement of the global goals set forth by WHO.

Os ftirápteros, ou piolhos, com importância em Medicina Humana, nomeadamente Pediculus humanus capitis são insetos agentes causadores da pediculose da cabeça, com particular relevância em crianças de idade escolar. Dada a verdadeira pandemia que se tem verificado nas últimas décadas, o estudo destes ectoparasitas permanentes torna-se de extrema importância não só pela incomodidade que provocam mas também pelos vários aspetos socioeconómicos que a sua presença pode causar nas pessoas infestadas nos diferentes países, independentemente dos continentes em que se encontram. Este trabalho tem como principal objetivo determinar a prevalência de P. h. capitis em crianças de idade escolar, em três Escolas da Província de Luanda, Angola (duas públicas e uma privada), e determinar também os conhecimentos e fatores associados a esta ectoparasitose em Escolas dos Distritos da Maianga, Samba e Cacuaco. A prevalência da infestação determinou-se a partir da observação e colheita manual e observação laboratorial dos exemplares colhidos. Os conhecimentos e fatores associados foram determinados através de questionários aos Professores, Encarregados de Educação e Alunos após as devidas autorizações e Parecer do Conselho de Ética do IHMT. Neste estudo anónimo, só participaram os intervenientes que se disponibilizaram a colaborar. Dos 210 Alunos observados, verificou-se uma prevalência total de 28,10%. Nas crianças do género feminino a prevalência foi de 43,85% (52/130) e 2,5% (2/80) no género masculino. Perante os resultados obtidos, através das observações e respostas, os fatores associados, ou de risco, foram: ser criança do género feminino (p = 0,000), ter alguém em casa com piolhos (p = 0,000) e partilhar escovas e pentes (p = 0,042). Para além das cartas de diagnóstico, positivo ou negativo, para as crianças entregarem aos Encarregados de Educação, distribuíram-se folhetos informativos, devidamente elaborados para o efeito, para que pudessem realizar melhores práticas, quer para evitar a infestação por P. h. capitis, quer para quando se encontrassem infestados. Os conhecimentos dos Professores, Encarregados de Educação e Alunos, acerca desta problemática, desde a forma de transmissão ao tipo de tratamento utilizado, são também apresentados neste trabalho The lice (Phthiraptera), with importance in Human Medicine, namely Pediculus humanus capitis are agents of the pediculosis of the head, with particular relevance in school-age children. Given the true pandemic that has occurred in the last decades, the study of these permanent ectoparasites becomes of extreme importance not only because of the discomfort they cause but also because of the various socioeconomic aspects that their presence may cause in people infected in different countries, regardless of continents in which they are. The main objective of this study is to determine the prevalence of P. h. capitis in school-age children, in three Schools of the Province of Luanda, Angola (two publics and one private), and to determine also the knowledge and variables associated with this ectoparasitosis in Schools of the Districts of Maianga, Samba and Cacuaco. The prevalence of the infestation was determined from the examination of children’ hair (head) and laboratory observation of the collected specimens. The knowledge and associated variables were determined through questionnaires to the Teachers, Parents/Guardians and Students after the due authorizations and approval from the Ethics Council of the IHMT. In this anonymous study, only those agreeing to participate were included. Of the 210 students studied, there was a total prevalence of 28.10%. In the female gender the prevalence was 43.85% (52/130) and 2.5% (2/80) in the male gender. Based on observations and responses, the risk factors were: being a female child (p = 0.000), having someone at home with head lice (p = 0.000), and sharing brushes and combs (p = 0.042). In addition to the diagnostic letters, positive or negative, delivered to Parents/Guardians, informative leaflets were distributed, duly elaborated for this purpose. Teachers, Parents/Guardians and Students’ Knowledge about this problem, from the transmission to treatment, are also described in this work.

As doenças transmitidas por vetores são de grande relevância na saúde pública da Guiné-Bissau, constituindo a principal causa de morbilidade e mortalidade principalmente em grávidas e crianças menores de cinco anos. Com a ameaça global de doenças transmitidas por mosquitos, e a inexistência de vacinas, é imprescindível promover a adesão da comunidade a práticas preventivas. Uma vez confirmada a presença de Aedes aegypti e Anopheles gambiae na Guiné-Bissau, este estudo teve como objetivo geral: Descrever conhecimentos e perceções dos residentes de três áreas da cidade de Bissau e arredores, sobre os vetores Aedes aegypti e Anopheles gambiae, e as principais doenças transmitidas pelos mesmos, identificando também os criadouros larvares domésticos e peridomesticos do vector Aedes aegypti. Foi realizado um inquérito com 26 perguntas de 19 de setembro a 29 de outubro de 2016 em duas áreas da cidade de Bissau e uma em região de Biombo (urbana, semiurbana e rural), selecionando aleatoriamente 544 indivíduos, com idades compreendidas entre 18 aos 85 anos, e responsáveis pelas tarefas domésticas das suas habitações (a maioria de sexo feminino). O estudo revelou que, entre as doenças transmitidas por vetores consideradas no estudo malária, dengue, chikungunya e zika), a mais conhecida é a malária, sendo as restantes doenças desconhecida pela maioria dos inquiridos. malária foi também o eventual diagnóstico mais referido, num episódio de febre. No que se refere às medidas preventivas eficazes, a mais referida foi o uso da rede mosquiteira (medida preventiva da malária) mas a remoção de criadouros (medida preventiva de dengue, chikungunya e zika) foi considerada ineficaz para a maioria dos inquiridos. Os criadouros mais frequentemente encontrados foram os pneus, blocos de cimento bidões, baldes e latas presentes nas três áreas de estudo. Constituindo assim uma vantagem no caso de uma campanha para remoção de criadouros. Vector-borne diseases are of great relevance to public health in Guinea-Bissau, and are the main cause of morbidity and mortality, especially among pregnant women and children under five years of age. In the country there are a number of risk factors, ranging from the existence of several infectious agents involved, to the lack of efficient laboratory support, to the difficulty of implementing and maintaining educational and health measures. With the global threat of mosquito-borne diseases and the scarcity of information about vector mosquitoes in Guinea-Bissau, it is essential to gather information that supports the choice of educational and sanitary measures. Thus, after confirming the presence of Aedes aegypti and Anopheles gambiae in Guinea-Bissau, this study aimed to: describe knowledge and perceptions of residents of three areas of the city of Bissau and surrounding areas, on the vectors Aedes aegypti and Anopheles gambiae, and the major diseases transmitted by them. A survey was carried out with 26 questions from September 19 to October 29, 2016 in two areas of the city of Bissau and one in Biombo region (urban, semi-urban and rural), randomly selecting 544 individuals, aged 18 to 85 household chores (most of them female). The study revealed that among the vector-borne diseases considered in the study (malaria, dengue, chikungunya and zika), malaria is the most known, with the remaining diseases being unknown by most respondents. Malaria was also the most frequent diagnosis in an episode of fever. Regarding effective preventive measures, the most mentioned was the use of the mosquito net (preventive measure of malaria), but the removal of breeding sites (preventive measure of dengue, chikungunya and zika) was considered ineffective for most of the respondents. The most frequent breeding sites were the tires, cement blocks, buckets and cans present in the three study areas. This is an advantage in the case of a campaign to stop breeding.

Aedes (Stegomyia) aegypti (Linnaeus, 1762), é uma espécie de mosquito de distribuição cosmotropical, e tem grande importância epidemiológica, visto que é principal vetor de algumas arboviroses nomeadamente dengue, Zika, chikungunya e febre-amarela. O arquipélago de Cabo Verde enfrentou epidemias de dengue e de Zika em 2009 e 2015, respetivamente. Medidas de controlo desse vetor têm sido implementadas usando Temephos como larvicida, e o piretróide deltametrina, como adulticida, em pulverizações intra-domiciliares. O objetivo do presente estudo foi avaliar os níveis de sensibilidade a inseticidas químicos em populações locais de Ae. aegypti das ilhas do Maio (concelho do Maio) e de Santiago (concelho da Praia e São Lourenço dos Órgãos), em Cabo Verde. Foram feitos bioensaios para determinação do status de suscetibilidade das populações, e adicionalmente, testes moleculares para deteção de mutações do tipo Knockdown (Kdr) no gene que codifica para o canal de sódio, o alvo destes inseticidas. Por fim, o efeito residual das pulverizações intra-domiciliares no concelho da Praia, ilha de Santiago também foi avaliado. De acordo com os bioensaios, a população de Ae. aegypti do concelho do Maio é resistente a deltametrina, mas sensível à permetrina, enquanto que a população do concelho de São Lourenço dos Órgãos mostrou-se sensível para os dois piretróides. A população de Ae. aegypti do concelho da Praia, a capital do país, mostrou-se sensível a todos os inseticidas, exceto ao DDT. Com relação às mutações Kdr, a mutação F1534C foi detetada em baixa frequência, em mosquitos colhidos nos três concelhos, mas em maior frequência nos exemplares provenientes da cidade da Praia e considerados resistentes ao DDT. A mutação V1016I só foi observada em mosquitos de São Lourenço dos Órgãos. A mutação V410L não foi encontrada em nenhuma das populações investigadas. A bioeficácia das pulverizações intra-domiciliares, avaliada de acordo com os critérios da OMS, foi considerada baixa numa maioria esmagadora de casas. Este trabalho regista pela primeira vez o aparecimento de mutações do tipo Kdr em Ae. aegypti de Cabo Verde. Estes dados reportam pela primeira vez, a potencial existência de populações de Ae. aegypti resistentes a inseticidas o que, a confirmar-se, representa um problema real para os programas de controlo de vetores. Os resultados aqui apresentados podem, no entanto, servir de base para o desenho de novas estratégias para o combate aos mosquitos. Aedes (Stegomyia) aegypti (Linnaeus, 1762), is a mosquito species of cosmotropical distribution, and has great epidemiological importance, since it is the main vector of some arboviruses namely dengue, Zika, chikungunya and yellow fever. The Cape Verde archipelago faced dengue and Zika epidemics in 2009 and 2015, respectively. Control measures of this vector have been implemented using Temephos as larvicide, and the pyrethroid deltamethrin, as adulticide, in intra-household sprays. The objective of the present study was to evaluate the levels of sensitivity to chemical insecticides in Ae. aegypti of the islands of Maio (county of Maio) and Santiago (municipality of Praia and São Lourenço dos Órgãos) in Cape Verde. Bioassays were performed to determine the susceptibility status of the populations, and in addition, molecular tests for the detection of Knockdown (Kdr) mutations in the gene encoding the sodium channel, the target of these insecticides. Finally, the residual effect of intra-household sprays in the city of Praia, Santiago Island was also evaluated. According to the bioassays, the population of Ae. aegypti on the island of Maio is resistant to deltamethrin but sensitive to permethrin, whereas the population of the county of São Lourenço dos Órgãos was sensitive for both pyrethroids. The population of Ae. aegypti in the city of Praia, the country's capital, was sensitive to all insecticides except DDT. Regarding Kdr mutations, the F1534C mutation was detected at low frequency in mosquitoes collected in the three municipalities, but more frequently in the samples from the city of Praia and considered resistant to DDT. The mutation V1016I was only observed in mosquitoes of São Lourenço dos Órgãos. The V410L mutation was not found in any of the populations investigated. The bioefficacy of intra-domiciliary sprays, assessed according to WHO criteria, was considered low an overwhelming majority of households. This work records for the first time the appearance of mutations of the Kdr type in Ae. aegypti of Cape Verde. These data report for the first time, the potential existence of Ae. aegypti resistant insecticides which, if confirmed, represents a real problem for vector control programs. The results presented here can however, serve as a basis for the design of new strategies for combating mosquitoes.

A schistosomose urinária é a forma mais prevalente de schistosomose em humanos, e é causada pelo tremátode Schistosoma haematobium. Pode resultar em graves patologias urinárias e genitais. É altamente endémico em Moçambique, mas os programas de controlo tiveram um sucesso limitado e os hospedeiros intermediários têm sido pouco estudados. Um inquérito na Província da Zambézia tinha encontrado uma prevalência de S. haematobium em crianças de 73%, através de filtração de urina e PCR. A prevalência de infeção nos hospedeiros intermediários dos caracóis coletados, Bulinus sp, em Gurué tinha sido de 1,9 a 7,7%, respetivamente no rio Mutxora e Barragem, pelo teste de eliminação de cercárias. O objetivo deste estudo foi determinar a taxa de infeção não patente de Bulinus sp e caracterizar e comparar as populações de caracóis em Gurué. O DNA foi extraído da massa cefalopodal e do hepatopâncreas de 105 caracóis de dois locais (Barragem e rio Mutxora), provenientes de grupos sem libertação de cercárias. A qualidade do DNA foi avaliada por amplificação e sequenciamento de ITS2 e COI para confirmar a espécie de Bulinus. O DNA de parasita foi detetado por PCR da região repetitiva DraI e PCR multiplex (simples e nested) de COI. As duas populações de caracóis apresentaram diversidade genética entre si em ITS2 e COI e foram filogeneticamente mais semelhantes entre si e a sequências de Bulinus globosus da Tanzânia. A PCR DraI teve uma sensibilidade de 89 % na deteção do parasita. A taxa de prevalência pré-patente determinada por PCR de DraI foi de 0 e 17 %, respetivamente, para o rio Mutxora e a Barragem, sendo que nesta última foi de 13 % para região cefalopodal e 4 % hepatopâncreas. As taxas de infeção maiores na massa cefalopodal, sugerem infeções recentes. Por PCR multiplex e sequenciação de COI confirmou-se a presença de apenas S. haematobium. Estes resultados mostram que a infeção não patente de moluscos nesta região pode ser muito maior do que o esperado a partir da eliminação de cercárias, com uma alta taxa de infeções recentes. A deteção de infeção do hospedeiro intermediário por métodos moleculares é, portanto, importante em levantamentos epidemiológicos e monitorização de programas de controle em Moçambique. Urinary schistosomiasis is the most prevalent form of schistosomiasis in humans, and it is caused by the trematode Schistosoma haematobium. It can result in severe urinary and genital pathologies. It is highly endemic in Mozambique, but control programs have had limited success and intermediate hosts have been poorly studied. A survey in the Province of Zambézia had found a prevalence of S. haematobium in children of 73%, through urine filtration and PCR. The prevalence of infection in the snail intermediate hosts collected, Bulinus sp, in Gurué had been 1.9 to 7.7%, respectively in the Mutxora River e Barragem, by the cercarial elimination test. The objective of this study was to determine the non-patent infection rate of Bulinus sp and to characterize and compare the snail populations in Gurué DNA was extracted from the cephalopodal mass and hepatopancreas of 105 snails from two sites (Barragem and Mutxora River) from groups without cercarial release. DNA quality was assessed by amplification and sequencing of ITS2 and COI to confirm the Bulinus species. Parasite DNA was detected by PCR of the repetitive region DraI and multiplex PCR (simple and nested) of COI. The two snail populations showed genetic diversity between each other in ITS2 and COI and were phylogenetically more similar to each other and to the sequences of Bulinus globosus from Tanzania. The DraI PCR had a sensitivity of 89% for parasite detection. The pre-patent prevalence rate was 0 and 17%, respectively, for the Mutxora River and Barragem, and in the latter it was 13% for the cephalopodal region and 4% for the hepatopancreas. The higher infection rates in the cephalopodal mass suggest recent infections. Multiplex PCR and sequencing of COI confirmed the presence of only S. haematobium. These results show that the non-patent infection of snails in this region may be much higher than expected from the elimination of cercariae alone, with a high rate of recent infections. Detection of host infection by molecular methods is, therefore, important in epidemiological surveys and monitoring of control programs in Mozambique.

Introdução: A disponibilização de redes mosquiteiras impregnadas com insecticida de longa duração (REMILDs) é uma das intervenções principais no controlo vectorial da malária. O uso de REMILDs está associado a uma redução da transmissão da malária. Moçambique disponibiliza as REMILDs através de dois canais: consulta pré natal e em campanhas para a cobertura universal. Este estudo testa novas estratégias de distribuição de REMILDs (intervenção) em campanha e compara os seus resultados com o das estratégias anteriores (controlo). O objetivo geral é o de comparar os dois modelos de distribuição de redes mosquiteiras em distritos rurais de Moçambique. Métodos: Os distritos de intervenção foram: Gurue e Sussundenga; os distritos de controlo foram: Alto-Molócuè e Machaze. Usando uma abordagem quantitativa, três estudos tiveram lugar: i) antes e depois entre os meses de Outubro e Dezembro de 2015; ii) antes e depois, do tipo observacional e transversal, entre os meses de Junho e Julho de 2016; iii) análise de custo-efectividade entre os meses de Outubro e Dezembro de 2015. Três principais estratégias de implementação foram testadas: uso de cupões durante o registo das famílias (AFs), uso de autocolantes para identificar as casas registadas e um novo critério de atribuição de redes. Os principais indicadores medidos foram: i) percentagem de REMILDs distribuídas; ii) cobertura da posse e uso de REMILDs; iii) percentagem de AFs que alcançaram a cobertura universal; iv) razão incremental de custo-efectividade (RICE); iv) benefício líquido incremental. Resultados: Cerca de 88% (302.648) de REMILDs foram distribuídas nos distritos de intervenção em comparação com 77% (219.613) nos distritos de controlo [OR: 2.14 (IC 95%: 2,11–2,16)]. Seis meses após a campanha de 2015, dos 760 AFs inqueridos nos distritos de intervenção, 98,8% tinha pelo menos uma REMILD; dos 787 AFs inqueridos nos distritos de control, 89,6% tinha pelo menos uma REMILD [OR: 9,7, (IC 95%: 5,25 – 22,76)]. Cerca de 95% e 87% dos inqueridos que tinham pelo menos uma REMILD reportaram ter dormido debaixo da mesma na noite anterior nos distritos de intervenção e controlo, respectivamente [OR: 3,2; (IC 95%: 2,12-4,69)]; 71% dos AFs inqueridos alcançaram a cobertura universal nos distritos de intervenção contra 59.6% nos distritos de controlo [OR: 1,6; (IC 95%: 1,33 – 2,03)]. A RICE por REMILD distribuída foi de US$ 0,68. O benefício líquido incremental foi positivo. Conclusões: Os distritos de intervenção tiveram maior disponibilização de REMILDs, maior cobertura de posse e uso, e um melhor progresso para o alcance de cobertura universal. A nova estratégia foi mais custo-efectiva do que a estratégia anterior. A nova estratégia poderá acelerar o passo no controlo vectorial para a redução da morbi-mortalidade por malária e alcançe dos objectivos da Estratégia Técnica Global para a Malária 2016 – 2030. Introduction: The provision of long lasting insecticidal nets (LLINs) has been pointed out as one of the core malaria vector control interventions. The use of LLINs is associated with a reduction in malaria transmission. LLINs delivery in Mozambique has been carried out through two delivery channels: prenatal care service and universal coverage campaigns. This study tests new delivery strategies (intervention) in universal coverage campaign and compares its results with previous strategies (control). The general objective of the thesis is to compare two bed nets delivery models in rural districts of Mozambique. Methods: The intervention districts were: Gurue and Sussundenga; the control districts were: Alto-Molocue and Machaze. Using a quantitative approach, three studies took place: i) before and after study between October and December 2015; ii) before and after, observational and cross-sectional study, between June and July 2016; and iii) cost-effectiveness analysis between October and December 2015. Three core implementation strategies were tested: use of coupons during household (HH) registration, use of stickers to identify registered houses and a new LLINs allocation criterion. The main endpoints measured were: i) percentage of distributed LLINs; ii) LLINs ownership and use coverage; iii) percentage of HHs that achieved universal coverage; iv) incremental cost-effectiveness ratio (ICER); iv) incremental net benefit (INB). Results: Approximately 88% (302,648) of LLINs were distributed in intervention districts compared to 77% (219,613) in control districts [OR: 2.14 (95% CI: 2.11-2.16)]. Six months after the 2015 campaign, of the 760 HHs surveyed in the intervention districts, 98.8% had at least one LLIN; of the 787 HHs surveyed in the control districts, 89.6% had at least one LLIN [OR: 9.7, (95% CI: 5.25 - 22.76)]. Near 95% and 87% of respondents who had at least one LLIN reported having slept under the LLIN the previous night in the intervention and control districts, respectively [OR: 3.2; (95% CI 2.12-4.69)]; 71% of the HHs surveyed achieved universal coverage in the intervention districts against 59.6% in the control districts [OR: 1.6; (95% CI: 1.33-2.03)]. ICER per distributed LLIN was US$ 0.68. INB was positive. Conclusions: Intervention districts had greater LLINs availability, greater LLINs ownership and use coverage, and a better progression toward reaching universal coverage targets. The new strategy was more cost-effective than the previous strategy. The new strategy might well accelerate the pace in vector control for reducing malaria morbidity and mortality and achieving the goals of the Global Technical Strategy for malaria 2016-2030.

Parasitic diseases affect billions of people and are considered a major public health issue. Close to 400 species are estimated to parasitize humans, of which around 90 are responsible for great clinical burden and mortality rates. Unfortunately, they are largely neglected as they are mainly endemic to poor regions. Of relevance to this review, there is accumulating evidence of the release of extracellular vesicles (EVs) in parasitic diseases, acting both in parasite parasite inter-communication as well as in parasite host interactions. EVs participate in the dissemination of the pathogen and play a role in the regulation of the host immune systems. Production of EVs from parasites or parasitized cells has been described for a number of parasitic infections. In this review, we provide the most relevant findings of the involvement of EVs in intercellular communication, modulation of immune responses, involvement in pathology, and their potential as new diagnostic tools and therapeutic agents in some of the major human parasitic pathogens., National Council for Scientific and Technological Development (CNPq), United States Department of Health & Human Services National Institutes of Health (NIH) - USA R01AI070655-A5 R01AI070655-A5S1 2G12MD007592, European Union (EU), Ministerio Español de Economía y Competitividad

Nas últimas décadas tem-se assistido a uma redução do número de casos de malária em muitos países da África Subsariana. No entanto, o sobrediagnóstico de malária em zonas endémicas é frequente. É desconhecida a relevância clínica das arboviroses no diagnóstico diferencial da malária em Angola. Historicamente a principal arbovirose descrita em Angola tem sido a febre amarela. No entanto, existiu evidência de circulação de outros arbovírus como o vírus chikungunya durante o período colonial. Após a independência do país, que ocorreu em 1975, foram registados em vários países casos esporádicos de dengue importados de Angola. Deste modo, até 2012, o desconhecimento sobre a prevalência de arboviroses, como dengue e chikungunya era uma realidade. Foi realizado um estudo observacional e transversal com o objectivo de identificar a presença do vírus dengue e do vírus chikungunya. Incluíram-se doentes com síndroma febril (temperatura corporal ≥37,5ºC à admissão e/ou história de febre) e com clínica compatível com malária. Foram aplicados testes de diagnóstico rápido (TDR) [SD BIOLINE®], que são ensaios imunocromatográficos para detecção de: Ag NS1 e anticorpos IgG / IgM contra o vírus dengue; Ig M contra o vírus chikungunya; Ag HRPII- P.f e pLDH-P.v de Plasmodium spp. Foram ainda colhidas amostras para realização de técnicas de biologia molecular (PCR ou RT-PCR) para Plasmodium spp., dengue e chikungunya. O estudo decorreu em duas fases, a primeira, de Fevereiro a Abril de 2012, na província do Huambo e a segunda, de Maio a Junho de 2015, na província de Benguela, tendo sido incluídos um total de 542 doentes. Na primeira fase incluíram 242 doentes, maioritariamente do sexo feminino (59,9%). A média de idades foi de 16 anos. A clínica mais frequente foi a respiratória, nomeadamente tosse (60,7%) e corrimento nasal (48,3%) seguida das queixas álgicas, cefaleias (40,1%), dores abdominais (36,4%), artralgias (33,9%) e mialgias (30,6%). As taxas de positividade do TDR foram as seguintes: malária (2,1%), chikungunya (1,7%) e dengue (0,8%). Verificou-se um caso de positividade concomitante para dengue (Ag NS1+) e chikungunya. Na segunda fase foram incluídos 300 doentes, também maioritariamente do sexo feminino (61%). A média de idades foi de 19 anos. A clínica mais frequente foi a álgica, cefaleias (53%), mialgias (45%), artralgias (43,3%), dores abdominais (38,3%) seguida da respiratória, tosse (26,3%) e corrimento nasal (16,3%). As taxas de positividade do TDR foram as seguintes: malária (36,7%), chikungunya (18,3%) e dengue (3,3%). Verificaram-se 28 casos de positividade concomitante para malária e chikungunya e 4 para malária e dengue (1 com Ag NS1+ e 3 com IgM+). Nesta segunda fase foi ainda identificada por RT-PCR uma sequência genómica do vírus chikungunya que revelou uma elevada identidade com uma estirpe circulante nos Camarões em 2006. Este estudo foi pioneiro na investigação recente de arbovírus em Angola, documentando a sua circulação, assim como também possibilitou, pela primeira vez, a aplicação em larga escala de TDR para dengue e chikungunya neste país. In recent decades, there has been a reduction in the number of malaria cases in many sub- Saharan African countries. However, the overdiagnosis of malaria in endemic areas is frequent. The clinical relevance of arboviruses in the differential diagnosis of malaria in Angola is unknown. Historically the main arbovirosis described in Angola has been Yellow Fever. However, there was evidence of circulation of other arboviruses such as the Chikungunya virus during the colonial period. After the country's independence, which occurred in 1975, sporadic dengue cases imported from Angola were registered in several countries. Thus, until 2012, the lack of knowledge about the prevalence of arboviruses, such as Dengue and Chikungunya, was a reality. An observational and cross - sectional study was carried out to identify the presence of Dengue virus and Chikungunya virus. Patients with febrile syndrome (body temperature at admission ≥37.5 ° C and / or history of fever) and clinically compatible with malaria were included. Rapid diagnostic tests (TDR) [SD BIOLINE®], which are immunochromatographic assays for the detection of: Ag NS1 and IgG / IgM antibodies against Dengue virus have been applied; Ig M against the Chikungunya virus; Ag HRPII- P.f and pLDH-P.v from Plasmodium spp. Biological samples were also collected for molecular biology techniques (PCR or RT-PCR) for Plasmodium spp., Dengue and Chikungunya. The study was conducted in two phases, the first from February to April 2012 in Huambo province and the second from May to June 2015 in Benguela province, with a total of 542 patients. In the first phase 242 patients were included, mostly female (59.9%). The average age was 16 years. The most common symptoms were respiratory such as cough (60.7%) and nasal discharge (48.3%) followed by painful complaints, headache (40.1%), abdominal pain (36.4%), arthralgia (33 , 9%) and myalgias (30.6%). The rates of positive TDR were as follows: malaria (2.1%), Chikungunya (1.7%) and Dengue (0.8%). There was a case of concomitant positivity for Dengue (Ag NS1 +) and Chikungunya. In the second phase 300 patients were included, also mostly female (61%). The average age was 19 years. The most frequent clinic complaints were headaches (53%), myalgias (45%), arthralgia (43.3%), abdominal pains (38.3%) followed by cough (26.3%) and runny nose (16.3%). The rates of positive TDR were as follows: malaria (36.7%), Chikungunya (18.3%) and Dengue fever (3.3%). There were 28 cases of concomitant positivity for malaria and Chikungunya and 4 cases for malaria and Dengue (1 with Ag NS1 + and 3 with IgM +). In this second phase a Chikungunya genomic sequence was also identified by RT-PCR which revealed a high identity with a circulating strain in Cameroon in 2006. This study was relevant for the recent investigation of arbovirus in Angola, documenting its circulation, as well as for allowing for the first time the large-scale application of TDR to Dengue and Chikungunya in this country.

A leishmaniose é uma das doenças mais negligenciadas em todo o Mundo, de acordo com a OMS, sendo todos os anos registados 300 000 novos casos. A doença afecta, sobretudo, indivíduos de países em vias de desenvolvimento, onde o acesso ao diagnóstico e ao tratamento se torna extremamente complicado. Para além disso, a quimioterapia disponível apresenta uma eficácia progressivamente menor devido ao aparecimento de estirpes resistentes. Com tudo isto, torna-se imperativo o desenvolvimento de novos compostos antileishmania e de novas estratégias para diminuir o impacto da doença. As proteínas pertencentes à família ATP-binding cassette (ABC) são transportadores que se encontram presentes numa grande variedade de células (desde procariotas a eucariotas) e que são responsáveis pelo efluxo de moléculas. Muitas vezes, estes transportadores originam fenótipos resistentes, como é o caso do fenótipo multidrug resistant (MDR). Uma forma de ultrapassar esta resistência é recorrendo ao uso de inibidores destas bombas de efluxo. O principal objectivo deste trabalho é determinar a acção de bombas de efluxo num contexto em que macrófagos de uma linha celular (P388D1) são infectados com promastigotas mais resistentes pertences a diferentes espécies de Leishmania (Leishmania infantum, Leishmania amazonensis, Leishmania shawi e Leishmania guyanensis) e são expostos simultaneamente a fármacos/compostos experimentais antileishmania e inibidores das bombas de efluxo. No presente trabalho, o primeiro passo foi obter estirpes susceptíveis ao Glucantime (GLUC), à Miltefosina (MILT), ao ácido ursólico (URS), à chalcona-8 (CH8) e à quercetine (QC). Para as estirpes que se conseguiram obter, foi determinado o valor de IC50 para os compostos experimentais URS, CH8 e QC. Por último, num contexto em que macrófagos foram infectados com diferentes estirpes mais resistentes, foi determinado o efeito na taxa de infecção relativa de um tratamento constituído por um composto antileishmania e por um inibidor das bombas de efluxo (EPI), como o verapamil (VER), o ortovanadato de sódio (ORT) e o Phe-Arg β-naftilamida (PaβN). Todos os tratamentos foram capazes de reduzir a taxa de infecção relativa de macrófagos infectados com as estirpes susceptíveis de Leishmania infantum, à excepção do tratamento com CH8 e VER feito à estirpe INF CH8. Para as diferentes estirpes de Leishmania amazonensis, todos os tratamentos apresentaram resultados positivos, à excepção daqueles que incluíam ORT, que parece ser inofensivo para esta espécie. No extremo oposto, encontram-se as estirpes de Leishmania shawi e Leishmania guyanensis, em que nenhum dos tratamentos reduziu a taxa de infecção. Os inibidores das bombas de efluxo (EPI) conseguem reduzir a actividade das bombas de efluxo e aumentar a eficácia dos fármacos antileishmania, e, por causa disso, o seu uso pode constituir um bom tratamento alternativo para a leishmaniose. Leishmaniasis is one of the most neglected diseases in the World, according to the WHO, with new registered 300 000 cases every year. This disease affects mainly individuals from low income countries, where the access to diagnosis and treatment is very difficult. Besides this, the available chemotherapy is losing efficacy due to the emergence of resistant strains. So, there is a need for the development of new antileishmanial compounds and new strategies to refrain the impact of the disease. The proteins belonging to the ATP-binding cassette (ABC) family are transporters present in a wide variety of cells (from prokaryotes to eukaryotes) involved in the efflux of molecules. In many cases, these transporters become responsible for multidrug resistant (MDR) phenotypes and other resistance events in cells. One of the strategy to overcome this resistance is to use efflux pump inhibitors (EPI). The general goal of the present work is determine the action of efflux pumps in a context where macrophages from a cellular line (P388D1) get infected with more resistant Leishmania promastigotes from several species (Leishmania infantum, Leishmania amazonensis, Leishmania shawi and Leishmania guyanensis) and are exposed simultaneously to antileishmanial drugs/experimental compounds and efflux pump inhibitors. In this work, the first step was to differentiate different strains susceptible to Glucantime (GLUC), Miltefosine (MILT), ursolic acid (URS), chalcone-8 (CH8) and quercetine (QC). For the resistant strains obtained, the IC50 of the experimental compounds URS, CH8 and QC were then calculated. At last, in a context of macrophages infected with the different more resistant strains, it was evaluated the effect in their relative infection rate of a treatment consisting in experimental compounds combined with EPI, such as verapamil (VER), sodium orthovanadate (ORT) and Phe-Arg β-naphthylamide (PAβN). All the treatments could significantly reduce the relative infection rate of macrophages infected with the susceptible strains of Leishmania infantum, with the exception of the treatment with CH8 and VER in INF CH8 strain. For the several strains of Leishmania amazonensis, all treatments reduced the relative infection rate, with the exception for the treatments containing ORT, which seems to be harmless to this species. On the opposite side are the strains of Leishmania shawi and Leishmania guyanensis, where none of the treatments was able to reduce the relative infection rate of the macrophages. The EPI can effectively decrease the activity of efflux pumps activity and increase the efficacy of antileishmanial drugs, and because of this, its use can be a possible alternative treatment for leishmaniasis.

A giardíase é uma doença causada pelo protozoário intestinal Giardia duodenalis. Esta doença tem uma distribuição ubíqua e afeta todos os grupos etários apesar de apresentar uma maior incidência nos países de baixo e médio rendimento, bem como em crianças. Este protozoário intestinal inclui oito genótipos (A-H), dos quais apenas A e B são infeciosos para o homem. Vários estudos têm sido realizados no sentido de esclarecer a sua relação com a gravidade da doença diarreica. No entanto, existem poucas publicações onde se explora a sua associação com o estado nutricional e menos ainda com a infeção pelo VIH, em crianças com menos de cinco anos de idade. Este trabalho teve como objetivo principal o estudo da associação entre a infeção por G. duodenalis e o estado nutricional, diarreia e infeção pelo VIH em crianças dos 0 aos 59 meses de idade no Hospital Central de Nampula (HCN), Moçambique. Para tal, foram incluídas 831 crianças internadas ou assistidas nas consultas externas do HCN, das quais se obteve uma amostra de fezes, os seus dados socio-demográficos, clínicos e antropométricos (comprimento/estatura e peso). A análise parasitológica de fezes foi efetuada por exame direto e concentração de Ritchie e a deteção de antigénio de G. duodenalis por teste imunocromatográfico rápido. As amostras com identificação positiva para G. duodenalis em qualquer um dos métodos foram conservadas para posterior extração de DNA e análise molecular. A caraterização genotípica foi realizada através do estudo de polimorfismos únicos de posição para o gene da β-giardina (bg), tendo sido realizada a análise estatística através da regressão logística binária e regressão logística múltipla. O diagnóstico parasitológico revelou que G. duodenalis foi o parasita intestinal mais comum na população estudada (23,9%, 199/831). Os resultados obtidos não demonstraram nenhuma associação estatisticamente significativa entre o estado nutricional, diarreia ou infeção pelo VIH e a infeção pelos genótipos de G. duodenalis. No entanto, verificou-se que as crianças que viviam em habitações com três ou mais pessoas por divisão eram mais suscetíveis à infeção total e simples por G. duodenalis (p=0,034 e p=0,048, respetivamente). Em relação ao estado nutricional observou-se que as crianças com infeção simples por G. duodenalis apresentavam uma menor probabilidade de terem desnutrição aguda (p=0,041). Para além disso, as crianças com idades inferiores a 24 meses pareciam ser mais suscetíveis a terem desnutrição por baixo-peso e aguda, a apresentarem diarreia, dor abdominal e falta de apetite (p

As infeções parasitárias intestinais encontram-se entre as infeções mais frequentes a nível mundial, sendo as crianças em idade pré-escolar e escolar um dos principais grupos de risco da população. Estima-se que cerca de 3,5 mil milhões de indivíduos estejam infetados, e que cerca de 450 milhões se encontrem doentes. A distribuição e a prevalência das espécies de parasitas intestinais variam de região para região, afetando maioritariamente os países de baixa renda, com clima tropical ou subtropical e com baixo grau de saneamento. O objetivo principal deste trabalho foi determinar a ocorrência de infeções parasitárias intestinais em crianças (sintomáticas e assintomáticas) dos 0 aos 10 anos, seguidas em ambulatório ou no internamento do Hospital Agostinho Neto (HAN), na cidade da Praia (Cabo Verde), e a sua relação com fatores sociodemográficos e clínicos. No HAN, a recolha de dados clínicos, epidemiológicos, sociodemográficos e a colheita das amostras fecais, decorreram nos meses de novembro e dezembro de 2015, e janeiro de 2016, e no Laboratório do Grupo de Protozoários Oportunistas/VIH e Outros Protozoários, do Instituto de Higiene e Medicina Tropical (IHMT), foi efetuado o diagnóstico parasitológico e molecular. Para a deteção de DNA dos seguintes parasitas: Giardia duodenalis, Cryptosporidium spp. e do microsporídeo- Enterocytozoon bieneusi foram utilzadas as técnicas de nested-PCR. No presente estudo, no total das técnicas aplicadas, verificou-se que o número de crianças parasitadas foi bastante superior (74,0%) ao número de crianças não parasitadas (26,0%). Das espécies encontradas nas amostras fecais, Blastocystis hominis foi a espécie observada em maior percentagem (69.3%), seguida por G. duodenalis (10.7%), E. bieneusi (5.3%), Ascaris lumbricoides (4.7%), Entamoeba coli (4%), Hemynolepis nana (3.3%), Entamoeba histolytica/dispar (2.7%), Cryptosporidium spp. (1.3%) e Enteromonas hominis e Iodamoeba butschlii (0.7% cada). Os potenciais fatores de risco observados durante o estudo foram: idade, tipo de abastecimento de água e hábitos de defecação da criança. Do total de crianças parasitadas constatou-se que 7,2% encontravam-se infetadas por rotavírus. Os resultados e os dados epidemiológicos obtidos, neste estudo, reforçam a importância do diagnóstico e controlo das enteroparasitoses na população infantil de Cabo Verde. Intestinal parasitic infections are among the more frequent infections worldwide, being children in preschool and school ages one of main risk groups of the population. We estimate that around 3,5 billions of individuals are infected, and that around 450 million are ill. Distribution and prevalence of intestinal parasites’ species vary from region to region, affecting mostly developing countries with tropical and subtropical climate and with low sanitation level. The main objective of this srudy was to determinate the occurrence of parasitic intestinal infections in children (symptomatic and asymptomatic) from 0 to 10 years old, in ambulatory or as inpatient at Agostinho Neto Hospital (HAN), at Cidade da Praia (Cabo Verde), and their relation with socio-demographic and clinical factors. In HAN, clinical data, epidemiological, socio-demographic and fecal samples collection took place during November and December 2015, and January 2106, and parasitological and molecular diagnosis was performed at the Laboratory of the Group of Opportunists Protozoa / HIV and Others Protozoa of the Institute of Hygiene and Tropical Medicine (IHMT), in Lisboa, Portugal. DNA detection of Giardia duodenalis, Cryptosporidium spp. and microsporidia - Enterocytozoon bieneusi was performed applying applied nested-PCR techniques. Tanking, consideration the parasitological abd molecular techniques applied, we observed that the number of parasitized children was quite superior (74,0%) to the number of non-parasitized children (26,0%). Blastocystis hominis was the predominant parasite found (69,3%), followed by G. duodenalis (10.7%), E. bieneusi (5.3%), Ascaris lumbricoides (4.7%), Entamoeba coli (4%), Hymenolepis nana (3.3%), Entamoeba histolytica/dispar (2.7%), Cryptosporidium spp. (1.3%) and Enteromonas hominis and Iodamoeba butschlii (0.7% each). Potential risk factors observed during the study were: age, type of water supply and children’s defecation habits. Of the total of parasitized children, 7,2 were infected with rotavirus. Results and epidemiological data obtained in this study reinforce the importance of diagnosis and control of enteroparasitoses in the infant population of Cabo Verde.

A leishmaniose causada pelo parasita Leishmania infantum é uma doença zoonótica com uma importância grande para a população humana e animal devido à elevada morbidade e mortalidade em regiões endémicas. Apesar do cão ser o principal hospedeiro e reservatório do parasita, o papel do gato doméstico na epidemiologia da doença tem vindo a adquirir um interesse crescente. A presente dissertação baseia-se num rastreio epidemiológico da infeção por Leishmania infantum em gatos errantes do distrito de Faro. A amostra total foi de 75 gatos. Foram utilizados cinco métodos de diagnóstico, três serológicos (IFI, CIE e ELISA) e dois moleculares (PCR e “Nested”-PCR). Tendo em conta que foram considerados como expostos ou infetados pelo parasita os animais cujas amostras se revelaram positivas para pelo menos uma das técnicas utilizadas no estudo, a prevalência da infeção por Leishmania foi de 29,3% (22/75). Os resultados obtidos reforçam a necessidade de alertar os proprietários e os médicos veterinários para o risco de infeção da população felina por este parasita, e a necessidade de implementação de medidas profiláticas para proteger animais e pessoas. Leishmaniasis caused by the parasite Leishmania infantum is a zoonotic disease of great importance to the human and animal population due to its high morbidity and mortality in endemic regions. Although the dog is the main host and reservoir of the parasite, the role of domestic cat in the epidemiology of the disease has been argued. The present dissertation is based on an epidemiological survey of Leishmania infantum infection in stray cats in the Faro district. The total sample consisted of 75 cats. Five diagnostic methods, three serological (IFAT, CIE and ELISA) and two molecular (PCR and “Nested”-PCR) were used. As the animals whose samples were positive for at least one of the techniques used in the study were considered as exposed to or infected by the parasite, the prevalence of Leishmania infection obtained in this study was 29.3% (22/75). This study reinforces the need of both owners and veterinarians to be aware of the risk of infection by this parasite in the feline population, and to the need to implement prophylactic measures to protect animals and people.

Tesis por compendio de publicaciones, [ES] Han pasado unos 160 años desde que Theodor von Siebold y Theodor Bilharz hicieron la primera descripción de una de las especies del género Schistosoma, S. haematobium (Cox et al., 2004) hasta que un grupo de investigadores liderados por Matt Berriman del Sanger Institute (UK) anotaran la primera secuencia del genoma de otra especie de Schistosoma, S. mansoni (Berriman et al., 2009). Durante este recorrido en el tiempo, Fujiro Katsurada descubre S. japonicum en el valle de Katayama y lo encuadra como una especie zoonótica. En la década de los sesenta se describieron otras especies de esquistosomas humanos como S. intercalatum y S. mekongi (Ohmae et al., 2004). En los últimos años se ha identificado una nueva especie en humanos denominada S. guineensis (Webster et al., 2006). La esquistosomiasis es adquirida por contacto con agua dulce contaminada con larvas natatorias -cercarias- del parásito, emitidas por diferentes especies de caracoles (hospedadores intermediarios), que penetran activamente por la piel. Tras su penetración, la cercaria pierde la cola transformándose en esquistosómula, la cual realiza una migración necesaria para su pre-maduración, pasando por los pulmones y volviendo a la circulación general para llegar finalmente a los vasos sanguíneos de diferentes localizaciones donde termina su maduración. Los vermes adultos de S. mansoni, S. japonicum, S. mekongi y S. intercalatum se asientan en los vasos mesentéricos, y los de S. haematobium llegan a los vasos que irrigan la vejiga urinaria. En estas localizaciones, los vermes macho y hembra entran en contacto para su total maduración y comienzo de la oviposición. Los huevos del parásito comienzan a ser eliminados con la orina (S. haematobium) o las heces (otras especies) del individuo infectado tras un período que oscila entre 35 y 70 días, alcanzando el agua y liberando los miracidios que penetran en los caracoles de diversos géneros para transformarse y multiplicarse en su interior hasta convertirse en cercarias y así cerrar el ciclo biológico. Una minoría se quedan atrapados en diferentes tejidos, formando los granulomas que es el hecho patogénico principal y el que da lugar a los síntomas y signos clínicos que se presentan en la fase crónica de esta infección. Los datos epidemiológicos indican que 779 millones de personas viven en 76 países endémicos de esquistosomiasis. Además, se estima que existen 250 millones de personas infectadas (80% en África subsahariana), 120 millones con sintomatología, 20 millones con enfermedad grave y una mortalidad anual de 280.000. La incapacidad ponderada por año de vida (DALY) es de 1,35 millones (King et al., 2005). La mayor prevalencia en áreas endémicas es en los adolescentes y disminuye generalmente en edad adulta. Se estima entre 60-80% de infección activa en niños de edad escolar y del 20-40% en adultos (Colley et al., 2014). Respecto a su distribución geográfica, se conoce que en el continente americano solo existe S. mansoni. En África conviven S. haematobium, S. intercalatum y S. guineensis y en Asia habitan S. japonicum y S. mekongi. En Europa era considerada una enfermedad importada, aunque en los últimos años se han registrado casos autóctonos en Córcega (Francia) debidos a S. haematobium (Holtfreter et al., 2014), si bien algunos investigadores apuntan a la existencia de híbridos S. haematobium/S. bovis. Desde el punto de vista clínico, la esquistosomiasis puede debutar con prurito en las primeras 24 horas siguientes a la penetración de las cercarias a través de la piel. Este cuadro es más llamativo en personas infectadas por parásitos aviares. Se observa más en viajeros y pasa desapercibida en personas residentes en áreas endémicas (Meltzer et al., 2006). La fase aguda o también denominada “Fiebre de Katayama” (Ross et al., 2007) se produce entre las 2-8 semanas después de la exposición y se debe a la reacción inmunológica desencadenada frente a la fase de migración del parásito. Se caracteriza por presentar fiebre, lesiones cutáneas (exantema, urticaria), afectación pulmonar (tos, disnea) y eosinofilia. En general es autolimitada, aunque en algunas ocasiones los síntomas pueden persistir más de diez semanas presentando diarrea, pérdida de peso, dolor abdominal, hepatoesplenomegalia, etc. La fase crónica de la esquistosomiasis aparece meses o años después de la infección y se debe a la reacción granulomatosa formada en torno a los huevos atrapados en hígado, bazo, intestino y otras localizaciones más lejanas como pulmones y sistema nervioso. Se presenta con más frecuencia en personas residentes en áreas endémicas de la enfermedad. Los métodos de diagnóstico parasitológico directo Kato-katz (Katz et al., 1972) y filtración de orina son los más utilizados para detectar estos parasitosis sin embargo poseen escasa sensibilidad y no son efectivos en la fase aguda de a enfermedad. Se han desarrollado diferentes métodos serológicos tanto de detección de antígeno como de anticuerpos (Pardo et al., 2007). La detección de anticuerpos tiene la limitación de presentar reactividad cruzada con otras infecciones producidas por helmintos. En los últimos años se han desarrollado técnicas moleculares (PCR, LAMP, etc…) utilizando diferentes muestras biológicas (heces, orina,..) (Sandoval et al., 2006). El fármaco de elección para el tratamiento de la esquitosomosis es el praziquantel, la dosis recomendada es 20mg/Kg cada 12 horas. Este fármaco es muy efectivo frente a vermes adultos pero tiene poca efectividad frente a esquistosómulas. Esta puede ser la razón de la aparición de resistencias en zonas endémicas. No obstante, en estas zonas existen reinfecciones continuas por la exposición de la población a aguas contaminadas con la fase infectiva del parásito. Estas son las principales razones para desarrollar una vacuna efectiva contra esta importante parasitosis. En la actualidad no existe ninguna vacuna disponible y los escasos estudios con determinadas moléculas no han llegado a fases clínicas avanzadas.

146 páginas. Maestría en Ciencias e Ingeniería Ambientales. Las enfermedades causadas por parásitos reciben el nombre de parasitosis y constituyen un problema de salud pública que, a pesar de los adelantos en la tecnología, continúan afectando la calidad de vida de los individuos y los animales que los adquieren. El ozono (O3) y el peróxido de hidrógeno (H2O2), así como la combinación de ambos (O3/H2O2) son poderosos oxidantes que se aplican exitosamente desde hace mucho tiempo como desinfectantes de agua de tipo residual y potable, por lo que es de interés evaluar su actividad parasiticida a diferentes tiempos de contacto, pH y concentraciones. Se utilizaron quistes de Giardia lamblia y huevos de Toxocara canis, ambos agentes zoonóticos, cosmopolitas, que comúnmente contaminan aguas residuales y suelo. El contacto hasta por 120 min de soluciones de H2O2 a diferentes concentraciones y pH inactiva el 52.2% de los huevos de T. canis y disminuye el 71.9% de viabilidad de los quistes de G. lamblia. El tratamiento con O3 inactivó al 98% de los quistes a pH 10, con los huevos alcanzó el 83.9% a pH 5. La oxidación con agua saturada con ozono de manera individual o combinada con peróxido de hidrógeno a diferentes valores de pH no eliminó el riesgo de transmisión de la giardiosis ya que solo alcanzó valores máximos de 35.5% de actividad giardicida, Sin embargo, la actividad del ozono aplicado en el reactor semi-bach fue 2.6 veces más eficiente en la inactivación de quistes de G. lamblia. La oxidación por el ozono en combinación con peróxido de hidrógeno y la acción de los radicales hidroxilo formados en el ambiente alcalino presentaron mayor inactivación de quistes de G. lamblia (99.4%) y huevos de helminto (89.4%) en comparación con la inactivación en reacciones a pH neutro y ácido. El sinergismo que se tiene con la combinación oxidante de O3/H2O2 y la presencia de radicales hidroxilo formados en el pH alcalino permitió obtener mayores porcentajes de inactivación lo que disminuye de manera importante el riesgo de transmisión de ambas parasitosis, por lo que se demostró que los procesos de oxidación a avanzada son una alternativa para inactivar quistes del protozoario G. lamblia así como huevos de helminto T. canis. Parasitic diseases are a public health problem that despite the advances in technology continues to affect the quality of life of individuals and animals. Ozone and hydrogen peroxide as well as the combination of both (O3/H2O2) are powerful oxidants successfully that have been applied for a long time as disinfectants of waste water and potable type, so it is interesting to evaluate its parasitical activity at different contact times, pH and concentrations of O3 and H2O2. Giardia lamblia cysts and Toxocara canis eggs were used, both zoonotic cosmopolitan agents, commonly contaminate wastewater and soil. Contact up to 120 min of H2O2 solutions at different concentrations and pH inactivates the 52.2% of the T. canis eggs and only decreases 71.9% viability of G. lamblia cysts. The treatment with O3 inactivated the 98% of the cysts with a pH 10, with the eggs only reached 83.9 % at a pH of 5. The oxidation with water saturated with ozone individually or in combination with hydrogen peroxide in different values of pH didn’t eliminate the risk of transmission of the Giardiosis as it only reached higher values of 35.54% of giardicidal activity. Even though the activity of the ozone applied in the reactor was 2.6 times more efficient in the inactivation of G. lamblia. Oxidation by ozone in combination with hydrogen peroxide and the action of the hydroxyl radicals formed by the alkaline environment presented a higher inactivation of the G. lamblia cysts (99.4%) and the helminth eggs (89.4%) compared to the inactivation of the reactions of a neutral and an acid pH. The synergism that is obtain with the oxidant combination of O3/H2O2 and the presence of hydroxyl radicals formed in the alkaline pH allowed higher percentages of inactivation which significantly reduces the risk of the transmission of both parasitosis, it was shown that the advanced oxidation processes are an alternative to inactivate cysts of the protozoan G. lamblia as well as the eggs of the helminth T. canis. Consejo Nacional de Ciencia y Tecnología (México).