IHMT: PM - Artigos em revista internacional com arbitragem científica
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- Insect-specific viruses in the Parvoviridae familyPublication . Morais, Paulo; Trovão, Nídia S; Abecasis, Ana B; Parreira, Ricardo; TB, HIV and opportunistic diseases and pathogens (THOP); Global Health and Tropical Medicine (GHTM); Instituto de Higiene e Medicina Tropical (IHMT); Vector borne diseases and pathogens (VBD); ElsevierThe analysis of the viruses allocated to the recently established Brevihamaparvovirus genus (Parvoviridae family), which includes all previously known brevidensoviruses, has not yet been carried out on an extensive basis. As a result, no detailed genetic lineage characterization has ever been performed for this group of insect-specific viruses. Using a wide range of molecular tools, we have explored this taxon by calculating Shannon entropy values, intra- and inter-taxon genetic distances, analysed sequence polymorphisms, and evaluated selective pressures acting on the viral genome. While the calculated Brevihamaparvovirus mutation rates were within the range of those of other parvoviruses, their genomes look to be under strong purifying selection, and are also characterized by low diversity and entropy. Furthermore, even though recombination events are quite common among parvoviruses, no evidence of recombination (either intra or intergenic) was found in the Brevihamaparvoviruses sequences analyzed. An extended taxonomic analysis and reevaluation of existing Brevihamaparvoviruses sequences, many still unclassified, was performed using cut-off values defining NS1 identity between viral sequences from the Parvovirus family. Two existing genetic lineages, Dipteran Brevihamaparvovirus 1 and Dipteran Brevihamaparvovirus 2, were rearranged and the creation of a new one, Dipteran Brevihamaparvovirus 3, was suggested. Finally, despite the uncertainties associated with both the time estimates of the most recent common ancestors, which could span from twenty thousand years before the current era to way earlier (in the last century), and the dispersal routes proposed for Brevihamaparvoviruses sequences by phylodynamic reconstruction, the analyses here presented could help define how future studies should be conducted as more isolates continue to be identified in the future, and contribute to eliminating possible analytical biases.
- Surveillance of leishmaniasis cases from 15 European centres, 2014 to 2019Publication . Cortes, Sofia; Cristovão, José Manuel; LeishMan Surveillance network; Vector borne diseases and pathogens (VBD); Global Health and Tropical Medicine (GHTM); Instituto de Higiene e Medicina Tropical (IHMT); Universidade NOVA de Lisboa; European Centre for Disease Prevention and ControlBackground: Surveillance of human leishmaniasis in Europe is mostly limited to country-specific information from autochthonous infections in the southern part. As at the end of 2021, no integrated analysis has been performed for cases seen across centres in different European countries. Aim: To provide a broad perspective on autochthonous and imported leishmaniasis cases in endemic and non-endemic countries in Europe. Methods: We retrospectively collected records from cutaneous, mucosal and visceral leishmaniasis cases diagnosed in 15 centres between 2014 and 2019. Centres were located in 11 countries: Belgium, France, Germany, Italy, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom. Data on country of infection, reason for travelling, infecting species, age and sex were analysed. Results: We obtained diagnostic files from 1,142 cases, of which 76%, 21% and 3% had cutaneous, visceral, and mucosal disease, respectively. Of these, 68% were men, and 32% women, with the median age of 37 years (range: 0–90) at diagnosis. Visceral leishmaniasis was mainly acquired in Europe (88%; 167/190), while cutaneous leishmaniasis was primarily imported from outside Europe (77%; 575/749). Sixty-two percent of cutaneous leishmaniasis cases from outside Europe were from the Old World, and 38% from the New World. Geographic species distribution largely confirmed known epidemiology, with notable exceptions. Conclusions: Our study confirms previous reports regarding geographic origin, species, and traveller subgroups importing leishmaniasis into Europe. We demonstrate the importance of pooling species typing data from many centres, even from areas where the aetiology is presumably known, to monitor changing epidemiology.
- Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones Active against Plasmodium and TrypanosomatidsPublication . Long, Solida; Duarte, Denise; Carvalho, Carla; Oliveira, Rafael; Santarém, Nuno; Palmeira, Andreia; Resende, Diana I. S. P.; Silva, Artur M. S.; Moreira, Rui; Kijjoa, Anake; Cordeiro Da Silva, Anabela; Nogueira, Fátima; Sousa, Emília; Pinto, Madalena M. M.; Vector borne diseases and pathogens (VBD); Global Health and Tropical Medicine (GHTM); Instituto de Higiene e Medicina Tropical (IHMT); ACS - American Chemical SocietyMalaria, 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.
- Human seroprevalence of Toscana virus and Sicilian phlebovirus in the southwest of PortugalPublication . Maia, Carla; Ayhan, Nazli; Cristóvão, José Manuel; Pereira, André; Charrel, Remi; Vector borne diseases and pathogens (VBD); Instituto de Higiene e Medicina Tropical (IHMT); Global Health and Tropical Medicine (GHTM); SpringerToscana virus (TOSV) is emergent in the Mediterranean region and responsible for outbreaks of encephalitis or meningoencephalitis. Sicilian phlebovirus (SFSV) cause epidemics of febrile illness during the summer. The aim of this study was to evaluate the presence of antibodies against TOSV and SFSV in humans in the southwest of Portugal. Neutralizing antibodies to TOSV and SFSV were respectively detected in 5.3% and 4.3% out of 400 human sera tested highlighting the need to increase public health awareness regarding phleboviruses and to include them in the differential diagnosis in patients presenting with fever of short duration and neurological manifestations.
- Enzyme immunoassays (EIA) for serodiagnosis of human leptospirosisPublication . Fortes-Gabriel, Elsa; Guedes, Mariana Soares; Shetty, Advait; Gomes, Charles Klazer; Carreira, Teresa; Vieira, Maria Luísa; Esteves, Lisa; Mota-Vieira, Luísa; Gomes-Solecki, Maria; Instituto de Higiene e Medicina Tropical (IHMT); Global Health and Tropical Medicine (GHTM); Vector borne diseases and pathogens (VBD); PLOS - Public Library of ScienceThe laborious microscopic agglutination test (MAT) is the gold standard serologic test for laboratory diagnosis of leptospirosis. We developed EIA based serologic assays using recombinant proteins (rLigA, rLigB, rLipL32) and whole-cell extracts from eight Leptospira serovars as antigen and assessed the diagnostic performance of the new assay within each class, against MAT positive (MAT+) human sera panels from Portugal/PT (n = 143) and Angola/AO (n = 100). We found that a combination of recombinant proteins rLigA, rLigB and rLipL32 correctly identified antigen-specific IgG from patients with clinical and laboratory confirmed leptospirosis (MAT+) with 92% sensitivity and ~ 97% specificity (AUC 0.974) in serum from the provinces of Luanda (LDA) and Huambo (HBO) in Angola. A combination of whole cell extracts of L. interrogans sv Copenhageni (LiC), L. kirschneri Mozdok (LkM), L. borgpetersenii Arborea (LbA) and L. biflexa Patoc (LbP) accurately identified patients with clinical and laboratory confirmed leptospirosis (MAT+) with 100% sensitivity and ~ 98% specificity for all provinces of Angola and Portugal (AUC: 0.997 for AO/LDA/HBO, 1.000 for AO/HLA, 0.999 for PT/AZ and 1.000 for PT/LIS). Interestingly, we found that MAT+ IgG+ serum from Angola had a significantly higher presence of IgD and that IgG3/IgG1 isotypes were significantly increased in the MAT+ IgG+ serum from Portugal. Given that IgM/IgD class and IgG3/IgG1 specific isotypes are produced in the earliest course of infection, immunoglobulin G isotyping may be used to inform diagnosis of acute leptospirosis. The speed, ease of use and accuracy of EIA tests make them excellent alternatives to the laborious and expensive MAT for screening acute infection in areas where circulating serovars of pathogenic Leptospira are well defined.
- Erratum toPublication . Corbel, Vincent; Fonseca, Dina M.; Weetman, David; Pinto, João; Achee, Nicole L.; Chandre, Fabrice; Coulibaly, Mamadou B.; Dusfour, Isabelle; Grieco, John; Juntarajumnong, Waraporn; Lenhart, Audrey; Martins, Ademir J.; Moyes, Catherine; Ng, Lee Ching; Raghavendra, Kamaraju; Vatandoost, Hassan; Vontas, John; Muller, Pie; Kasai, Shinji; Fouque, Florence; Velayudhan, Raman; Durot, Claire; David, Jean Philippe; Vector borne diseases and pathogens (VBD); Instituto de Higiene e Medicina Tropical (IHMT); Global Health and Tropical Medicine (GHTM); BioMed Central (BMC)
- A conceptual model for understanding the zoonotic cutaneous leishmaniasis transmission risk in the Moroccan pre-Saharan areaPublication . Karmaoui, Ahmed; Sereno, Denis; Maia, Carla; Campino, Lenea; El Jaafari, Samir; Taybi, Abdelkhaleq Fouzi; Hajji, Lhoussain; Vector borne diseases and pathogens (VBD); Instituto de Higiene e Medicina Tropical (IHMT); Global Health and Tropical Medicine (GHTM); ElsevierLeishmanioses 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.
- Trypanosoma cruzi discrete typing unit TcIV implicated in a case of acute Chagas disease in a domiciliated dog in the western AmazonPublication . Vasconcelos, Luciene Almeida Siqueira de; Oliveira, Josué Costa; Silva Junior, Rubens Celso Andrade da; Justiniano, Silvia Cássia Brandão; Souza, Éder Dos Santos; Magalhães, Laylah Kelre Costa; Silveira, Henrique; Silva, George Allan Villarouco da; Guerra, Jorge Augusto de Oliveira; Guerra, Maria das Graças Vale Barbosa; Vector borne diseases and pathogens (VBD); Global Health and Tropical Medicine (GHTM); Instituto de Higiene e Medicina Tropical (IHMT); Sociedade Brasileira de Medicina TropicalChagas disease is caused by the protozoan Trypanosoma cruzi. Seven lineages have been identified based on different molecular markers, namely TcI, TcII, TcIII, TcIV, TcV, TcVI, and TcBat. Dogs play the role of epidemiological sentinels being domestic reservoirs of T. cruzi. The aim of the current study was to report the first case of CD in a domestic dog in Manaus, Amazonas, Brazil, infected with T. cruzi DTU TcIV. We hope our report encourages veterinarians and surveillance professionals to a take a deeper look at T. cruzi infection in domestic animals.
- CYP2D6 Allele Frequency in Five Malaria Vivax Endemic Areas From Brazilian Amazon RegionPublication . Salles, Paula Ferreira; Perce-da-Silva, Daiana Souza; Rossi, Atila Duque; Raposo, Luisa Riehl; Ramirez Ramirez, Aina Danaisa; Pereira Bastos, Otílio Machado; Pratt-Riccio, Lilian Rose; Cassiano, Gustavo Capatti; Baptista, Andrea Regina Souza; Cardoso, Cynthia Chester; Banic, Dalma Maria; Machado, Ricardo Luiz Dantas; Vector borne diseases and pathogens (VBD); Global Health and Tropical Medicine (GHTM); Instituto de Higiene e Medicina Tropical (IHMT); Frontiers MediaGenetic 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.
- Discovery of Ongoing Selective Sweeps within Anopheles Mosquito Populations Using Deep LearningPublication . Ag1000g Consortium; Instituto de Higiene e Medicina Tropical (IHMT); Global Health and Tropical Medicine (GHTM); Vector borne diseases and pathogens (VBD); Oxford University PressIdentification 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.