Institute of Hygiene and Tropical Medicine
Recent publications
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) still poses a challenge for biomedicine and public health. To advance in developing effective diagnostic, prognostic, and preventive interventions our study focused on high throughput antibody binding epitope mapping of SARS‐CoV‐2 Spike RBD protein by IgA, IgM and IgG antibodies in saliva and sera of different cohorts from healthy uninfected individuals to SARS‐CoV‐2‐infected unvaccinated and vaccinated asymptomatic, recovered, nonsevere and severe patients. Identified candidate diagnostic (455‐LFRKSNLKPFERD‐467), prognostic (395‐VYADSFVIRGDEV‐407‐C‐KLH, 332‐ITNLCPFGEV‐342‐C‐KLH, 352‐AWNRKRI‐358‐C‐KLH, 524‐VCGPKKSTNLVKN‐536‐KLH), and protective (MKLLE‐487‐NCYFPLQSYGFQPTNGVG‐504‐GGGGS‐446‐GGNYNYLYRLFRKSNLKPFERD‐467) epitopes were validated with sera from pre‐vaccine and post‐vaccine cohorts. The results identified neutralizing epitopes and support that antibody recognition of linear B‐cell epitopes in RBD protein is associated with antibody isotype and disease symptomatology. The findings in asymptomatic individuals suggest a role for anti‐RBD antibodies in the protective response against SARS‐CoV‐2. The possibility of translating results into diagnostic interventions for the early diagnosis of asymptomatic individuals and prognosis of disease severity provides new tools for COVID‐19 surveillance and evaluation of risks in hospitalized patients. These results together with other approaches may contribute to the development of new vaccines for the control of COVID‐19 and other coronavirus‐related diseases using a quantum vaccinomics approach through combination of protective epitopes. This article is protected by copyright. All rights reserved
Nanotechnology is a crucial technology in recent years has resulted in new and creative applications of nanomedicine. Polymeric nanoparticles have increasing demands in pharmaceutical applications and require high reproducibility, homogeneity, and control over their properties. Work explores the use of cashew phthalate gum (PCG) as a particle-forming polymer. PCG exhibited a pH-sensitive behavior due to the of acid groups on its chains, and control drug release. We report the development of nanoparticles carrying benznidazole. Formulations were characterized by DLS, encapsulation efficiency, drug loading, FTIR, pH-responsive behavior, release, and in vitro kinetics. Interaction between polymer and drug was an evaluated by molecular dynamics. Morphology was observed by SEM, and in vitro cytotoxicity by MTT assay. Trypanocidal effect for epimastigote and trypomastigote forms was also evaluated. NPs responded to the slightly basic pH, triggering the release of BNZ. In acidic medium, they presented small size, spherical shape, and good stability. It was indicated NP with enhanced biological activity, reduced cytotoxicity, high anti T. cruzi performance, and pH-sensitive release. This work investigated properties related to the development and enhancement of nanoparticles. PCG has specific physicochemical properties that make it a promising alternative to drug delivery, however, there are still challenges to be overcome.
Background Tuberculosis (TB) in prisons usually occurs at higher rates than in the general population, especially in developing countries. TB has been reported as the most common cause of death among prisoners. Studies have shown limitations for early detection of TB in prisons that seem to result from mistaken concepts about TB, delayed diagnosis mainly due to the naturalization of lack of healthcare for this population Methods A scoping review was performed using the methodology of the Joanna Briggs Institute to assess “What are the scientific evidences on the epidemiology of TB in the prison system?”. Then, a meta-analysis was performed to assess the prevalence of TB (active and latent) TB in prisoners. The results are presented as prevalence, in percentage, through random effects models, with a confidence interval of 95%. Results Regarding active TB, the results of the metanalysis showed that countries with a high burden of TB had a prevalence of 3.54% [2.71; 4.63], countries not considered to be high burden TB countries had a prevalence of 1.43% [0.86; 2.37]. Latent TB had a prevalence of 51.61% [39.46; 63.58] in high TB burden countries and a prevalence of 40.24% [23.51; 59.61] in countries with low TB burden. In terms of development, in low- and lower-middle-income countries, the prevalence of active TB was 3.13% [1.84; 5.29] and in high- and upper-middle income countries the prevalence was 2.25% [1.70; 2.99]. The prevalence of latent TB in high- and middle-income countries was 43.77% [28.61; 60.18] and of 49.42% [45.91; 52.94] in low and lower middle-income countries. Conclusion Our analysis suggests that TB, and probably other infectious diseases, find fertile ground in prisons where previous acquire social disadvantages seem to thrive—therefore, TB in prisons is a global public health problem and effective strategies are needed to control the disease are needed targeting the prison environment, including rapid health assessments to understand each context and to implement tailored and precision interventions.
Background Understanding the correlation between the methods of monitoring surface cleaning and disinfection (SCD) is fundamental for better infection control. Purpose This study aims to correlate the SCD monitoring methods in a Brazilian pediatric unit. This is an exploratory, longitudinal, and correlational study. Methods The study was conducted in a pediatric hospitalization unit of a medium-sized hospital from December 2020 to March 2021. Four high-contact surfaces were analyzed before and after the cleaning and disinfection process by means of visual inspection, quantification of adenosine triphosphate (ATP), and colony-forming unit (CFU) count. The study consisted of three stages: stage I involving situational diagnosis of the SCD process; stage II referring to the implementation of the Surface Cleaning and Disinfection Standardization Program (SCDSP); and stage III involving long-term assessment after implementing the program. A total of 192 assessments were performed in each stage, totaling 576 in the three study stages. Conclusions A significant correlation was found between the ATP quantification methods and microbial count in the bed railing ( p = 0.009) and companion’s armchair ( p = 0.018) surfaces. In both cases, Spearman’s correlation coefficients were positive, indicating a positive correlation between ATP and microbial count scores, that is, the higher the ATP values (in RLUs), the greater the microbial counts (in CFUs/cm ² ). The analysis of the ROC curves suggests that the surfaces presenting ATP below 108 RLUs can be considered approved. The ATP method yielded 78.6% sensitivity; in turn, microbial count presented a sensitivity of 85.7%. It is important to use different methods to monitor the cleaning and disinfection of surfaces, as each one has different sensitivity and specificity.
Introduction The use of digital health interventions has expanded, particularly in home-based primary care (HBPC), following the increase in the older adult population and the need to respond to the higher demand of chronic conditions, weakness and loss of autonomy of this population. There was an even greater demand with COVID-19 and subsequent isolation/social distancing measures for this risk group. The objective of this study is to map and identify the uses and types of digital health interventions and their reported impacts on the quality of HBPC for older adults worldwide. Methods and analysis This is a scoping review protocol which will enable a rigorous, transparent and reliable synthesis of knowledge. The review will be developed from the theoretical perspective of Arksey and O'malley, with updates by Levac and Peters and respective collaborators based on the Joanna Briggs Institute manual, and guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Data from white literature will be extracted from multidisciplinary health databases such as: the Virtual Health Library, LILACS, MEDLINE/PubMed, Scopus, Web of Science, Cinahl and Embase; while Google Scholar will be used for gray literature. No date limit or language restrictions will be determined. The quantitative data will be analyzed through descriptive statistics and qualitative data through thematic analysis. The results will be submitted to stakeholder consultation for preliminary sharing of the study and will later be disseminated through publication in open access scientific journals, scientific events and academic and community journals. The full scoping review report will present the main impacts, challenges, opportunities and gaps found in publications related to the use of digital technologies in primary home care. Discussion The organization of this protocol will increase the methodological rigor, quality, transparency and accuracy of scoping reviews, reducing the risk of bias.
A study on fasciolosis prevalence, gross pathological lesions, fluke genetic identification and coprological analysis was carried out in slaughtered cattle from one abattoir in Cape Verde. Of the 131 cattle inspected over two months, 12 (9.0%) presented fasciolosis-compatible lesions (FCL) that resulted in liver condemnation. The genetic characterization of the flukes collected, through restriction fragment length polymorphism analysis of PCR-amplified fragments (PCR-RFLP), confirmed the presence of Fasciola gigantica; therefore, being the first identification of this species in cattle from Cape Verde. Animals that released Fasciola spp. eggs and, thus, responsible for environment contamination (positive shedders), were identified through coprological analysis (natural sedimentation technique). Of the 12 animals with FCL, samples from 11 were submitted to coprological analysis and 7 (63.6%) were found to be positive shedders. Furthermore, of the 82 animals with non-FCL, randomly selected for coprological analysis, 4 (4.9%) were also found to be positive shedders for Fasciola spp. The results of this study, regarding species identification and coprological analysis, are epidemiologically important to update the information regarding fasciolosis in Cape Verde. The new data could help implement effective strategies for disease control and mitigation, consequently reducing economic loss and the level of animal and human infection from the One Health perspective.
We analyzed the knowledge, attitudes and practices (KAP) of schistosomiasis mansoni prevention in an endemic area of Brazil. This cross-sectional study was conducted between March and May 2021, with 412 participants living in the municipality of Feira Grande, Alagoas, Brazil. Data collection occurred through visits to the Health Center Urbano II and Massapê, through an interview with a structured questionnaire to identify the levels of KAP regarding schistosomiasis prevention. Of all respondents, 70.87% lived in rural areas, 22.66% reported a history of past schistosomiasis and 52.71% never participated in schistosomiasis control program actions. Factors associated with better KAP scores were being part of an older age group, not using rainwater and having no history of past schistosomiasis. Specifically, among the domains, attitude was the highest score and knowledge was the lowest. Participation in a health intervention program, knowing someone who had schistosomiasis and having been informed through a public health program seemed to have an important impact on the population’s KAP. Our results contributed to broadening perceptions about schistosomiasis prevention, highlighting the positive impacts that health programs and interventions have on disease control.
Over the past two decades, a considerable expansion of malaria interventions has occurred at the national level in Angola, together with cross-border initiatives and regional efforts in southern Africa. Currently, Angola aims to consolidate malaria control and to accelerate the transition from control to pre-elimination, along with other country members of the Elimination 8 initiative. However, the tremendous heterogeneity in malaria prevalence among Angolan provinces, as well as internal population movements and migration across borders, represent major challenges for the Angolan National Malaria Control Programme. This review aims to contribute to the understanding of factors underlying the complex malaria situation in Angola and to encourage future research studies on transmission dynamics and population structure of Plasmodium falciparum , important areas to complement host epidemiological information and to help reenergize the goal of malaria elimination in the country.
Objective: To study the prevalence of transmitted drug resistance (TDR) to INSTIs and NRTIs, and of clinically relevant resistance (CRR), in newly-diagnosed people with HIV (PWH) naïve to antiretroviral therapy (ART) in Europe. Methods: MeditRes HIV is a consortium that includes ART naïve PWH newly diagnosed in France, Greece, Italy, Portugal, and Spain during the years 2018-2021. Reverse transcriptase (RT) and Integrase (INSTI) sequences were provided by participating centers. To evaluate the prevalence of surveillance drug resistance mutations (SDRM) we used the CPR tools from Stanford HIV-website. To evaluate clinically relevant resistance (CRR), defined as any resistance level >= 3, we used the Stanford v.9.1HIVDB Algorithm. Results: We included 2705 PWH, 72% men, median age of 37 (IQR, 30-48); 43.7% infected by non-B subtypes. The prevalence of INSTI-SDRMs was 0.30% (T66I, T66A, E92Q, E138T, E138K, Y143R, S147G and R263K, all n = 1), and of NRTI-SDRMs was 5.77% (M184V n = 23, 0.85%; M184I n = 5, 0.18%; K65R/N n = 3, 0.11%; K70E n = 2, 0.07%; L74V/I n = 5, 0.18%; any TAMs n = 118, 4.36%). INSTI-CRR was 2.33% (0.15% dolutegravir/bictegravir; 2.29% raltegravir/elvitegravir), and 1.74% to first-line NRTIs (0.89% tenofovir/tenofovir alafenamide fumarate; 1.74% abacavir; 1.07% lamivudine/emtricitabine). Conclusions: We present the most recent data on TDR to integrase based first-line regimens in Europe. Given the low prevalence of CRR to second generation integrase inhibitors and to first-line NRTIs, in the years 2018-2021 it is unlikely that newly diagnosed PWH in MeditRes countries would present with baseline resistance to a first-line regimen based on second generation integrase inhibitors.
Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P. vivax genomes from 21 countries, we identified 33-SNP, 50-SNP and 55-SNP barcodes (GEO33, GEO50 and GEO55), with high capacity to predict the infection’s country of origin. The Matthews correlation coefficient (MCC) for an existing, commonly applied 38-SNP barcode (BR38) exceeded 0.80 in 62% countries. The GEO panels outperformed BR38, with median MCCs > 0.80 in 90% countries at GEO33, and 95% at GEO50 and GEO55. An online, open-access, likelihood-based classifier framework was established to support data analysis (vivaxGEN-geo). The SNP selection and classifier methods can be readily amended for other use cases to support malaria control programs. An online, amendable classifier for detecting malaria parasite country of origin from genomic data is developed using a machine learning approach.
In Portugal, the genetic diversity, origin of HBV and the Portuguese role in the dissemination of HBV worldwide were never investigated. In this work, we studied the epidemic history and transmission dynamics of HBV genotypes that are endemic in Portugal. HBV pol gene was sequenced from 130 patients followed in Lisbon. HBV genotype A was the most prevalent (n = 54, 41.5%), followed by D (n = 44, 33.8%), and E (n = 32, 24.6%). Spatio-temporal evolutionary dynamics was reconstructed in BEAST using a Bayesian Markov Chain Monte Carlo method, with a GTR nucleotide substitution model, an uncorrelated lognormal relaxed molecular clock model, a Bayesian skyline plot, and a continuous diffusion model. HBV subgenotype D4 was the first to be introduced in Portugal around 1857 (HPD 95% 1699-1931) followed by D3 and A2 a few decades later. HBV genotype E and subgenotype A1 were introduced in Portugal later, almost simultaneously. Our results indicate a very important role of Portugal in the exportation of subgenotypes D4 and A2 to Brazil and Cape Verde, respectively, in the beginning of the XX century. This work clarifies the epidemiological history of HBV in Portugal and provides new insights in the early and global epidemic history of this virus.
Rhipicephalus microplus is the only tick species known to serve as a biological vector of Theileria equi for horses and other equids in Brazil. The protozoan T. equi is one of the causal agents of equine piroplasmosis, a major threat in horse breeding systems. Vector competence is closely linked to the pathogens’ ability to evade tick defense mechanisms. However, knowledge of tick immune response against infections by hemoparasites of the Theileria genus is scarce. In the present study, the expression of genes involved in immune signaling pathways of R. microplus adults’ guts when challenged with a high or low parasitic load of T. equi was evaluated. This research demonstrates divergences in the immune gene expression pattern linked to T. equi infection in R. microplus since the Toll, IMD, and JNK signaling pathways were transcriptionally repressed in the guts of adult ticks infected with T. equi. Moreover, the results showed that different infectious doses of T. equi induce differential gene expression of key components of immune signaling cascades in R. microplus gut, suggesting a link between the intensity of infection and the activation of tick immunity response. The present study adds knowledge to elucidate the gut immune signaling response of R. microplus to T. equi infection. In addition, the generated data can serve as a basis for further investigations to develop strategies for controlling and preventing equine piroplasmosis.
This Comment piece summarises current challenges regarding routine vaccine uptake in the context of the COVID-19 pandemic and provides recommendations on how to increase uptake. To implement these recommendations, the article points to evidence-based resources that can support health-care workers, policy makers and communicators.
NorA is one of the main native MDR efflux pumps of Staphylococcus aureus, contributing to reduced susceptibility towards fluoroquinolones and biocides, but little is known about its variability within S. aureus or its distribution and conservation among other staphylococci. We screened for sequences homologous to S. aureus norA and found it in 61 out of the 63 Staphylococcus species described. To the best of our knowledge, this is the first study to report the occurrence of norA across the Staphylococcus genus. The norA phylogenetic tree follows the evolutionary relations of staphylococci and the closely related Mammalliicoccus genus. Comparative analyses suggest a conservation of the NorA function in staphylococci. We also analyzed the variability of norA within S. aureus, for which there are several circulating norA alleles, differing up to 10% at the nucleotide level, which may hamper proper norA detection. We demonstrate the applicability of a PCR-based algorithm to detect and differentiate norA alleles in 52 S. aureus representing a wider collection of 89 isolates from different hosts. Our results highlight the prevalence of norAI and norAII in different settings and the association of norA alleles with specific S. aureus clonal lineages. Ultimately, it confirms the applicability of our PCR-based algorithm to rapidly detect and assign the different norA alleles, a trait that may impact antimicrobial efflux capacity and the search for potential NorA inhibitors.
Background Inadequate leadership capacity compounds the world's workforce lack of preparedness for outbreaks of all sizes, as illustrated by the COVID-19 pandemic. Traditional human resources for health (HRH) leadership has focused on determining the health workforce requirements, often failing to fully consider the unpredictability associated with issues such as public health emergencies (PHE). Main arguments The current COVID-19 pandemic demonstrates that policy-making and relevant leadership have to be effective under conditions of ethical uncertainty and with inconclusive evidence. The forces at work in health labor markets (HLM) entail leadership that bridges across sectors and all levels of the health systems. Developing and applying leadership competencies must then be understood from a systemic as well as an individual perspective. To address the challenges described and to achieve universal health coverage (UHC) by 2030, countries need to develop effective HRH leaderships relevant to the complexity of HLM in the most diverse contexts, including acute surge events during PHE. In complex and rapidly changing contexts, such as PHE, leadership needs to be attentive, nimble, adaptive, action oriented, transformative, accountable and provided throughout the system, i.e., authentic, distributed and participatory. This type of leadership is particularly important, as it can contribute to complex organizational changes as required in surge events associated with PHE, even in in the absence of formal management plans, roles, and structures. To deal with the uncertainty it needs agile tools that may allow prompt human resources impact assessments. Conclusions The complexity of PHE requires transformative, authentic, distributed and participatory leadership of HRH. The unpredictable aspects of the dynamics of the HLM during PHE require the need to rethink, adapt and operationalize appropriate tools, such as HRH impact assessment tools, to redirect workforce operations rapidly and with precision.
Background In Europe, data on population health is fragmented, difficult to access, project-based and prone to health information inequalities in terms of availability, accessibility and especially in quality between and within countries. This situation is further exacerbated and exposed by the recent COVID-19 pandemic. The Joint Action on Health Information (InfAct) that builds on previous works of the BRIDGE Health project, carried out collaborative action to set up a sustainable infrastructure for health information in the European Union (EU). The aim of this paper is to present InfAct’s proposal for a sustainable research infrastructure, the Distributed Infrastructure on Population Health (DIPoH), which includes the setup of a Health Information Portal on population health to be maintained beyond InfAct’s time span. Methods The strategy for the proposal was based on three components: scientific initiatives and proposals to improve Health Information Systems (HIS), exploration of technical acceptability and feasibility, and finally obtaining high-level political support.. The technical exploration (Technical Dialogues—TD) was assumed by technical experts proposed by the countries, and political guidance was provided by the Assembly of Members (AoM), which gathered representatives from Ministries of Health and Science of EU/EEA countries. The results from the AoM and the TD were integrated in the sustainability plan compiling all the major outputs of InfAct. Results The InfAct sustainability plan was organized in three main sections: a proposal of a new research infrastructure on population health (the DIPoH), new health information tools and innovative proposals for HIS, and a comprehensive capacity building programme. These activities were carried out in InfAct and are being further developed in the Population Health Information Research Infrastructure (PHIRI). PHIRI is a practical rollout of DIPoH facilitating and generating the best available evidence for research on health and wellbeing of populations as impacted by COVID-19. Conclusions The sustainability plan received wide support from Member States and was recognized to have an added value at EU level. Nevertheless, there were several aspects which still need to be considered for the near future such as: (i) a commitment of stable financial and political support by Member States (MSs), (ii) the availability of resources at regional, national and European level to deal with innovations, and (iii) a more direct involvement from EU and international institutions such as the European Centre for Disease Prevention and Control (ECDC), the World Health Organization (WHO) and the Organisation for Economic Cooperation and Development OECD for providing support and sustainable contributions.
Background Miltefosine treatment failure in visceral leishmaniasis in Brazil has been associated with deletion of the miltefosine susceptibility locus (MSL) in Leishmania infantum. The MSL comprises four genes, 3′-nucleotidase/nucleases (NUC1 and NUC2); helicase-like protein (HLP); and 3,2-trans-enoyl-CoA isomerase (TEI). Methods In this study CRISPR-Cas9 was used to either epitope tag or delete NUC1, NUC2, HLP and TEI, to investigate their role in miltefosine resistance mechanisms. Additionally, miltefosine transporter genes and miltefosine-mediated reactive oxygen species homeostasis were assessed in 26 L. infantum clinical isolates. A comparative lipidomic analysis was also performed to investigate the molecular basis of miltefosine resistance. Findings Deletion of both NUC1, NUC2 from the MSL was associated with a significant decrease in miltefosine susceptibility, which was restored after re-expression. Metabolomic analysis of parasites lacking the MSL or NUC1 and NUC2 identified an increase in the parasite lipid content, including ergosterol; these lipids may contribute to miltefosine resistance by binding the drug in the membrane. Parasites lacking the MSL are more resistant to lipid metabolism perturbation caused by miltefosine and NUC1 and NUC2 are involved in this pathway. Additionally, L. infantum parasites lacking the MSL isolated from patients who relapsed after miltefosine treatment were found to modulate nitric oxide accumulation in host macrophages. Interpretation Altogether, these data indicate that multifactorial mechanisms are involved in natural resistance to miltefosine in L. infantum and that the absence of the 3'nucleotidase/nuclease genes NUC1 and NUC2 contributes to the phenotype. Funding MRC GCRF and FAPES.
Human immunodeficiency virus (HIV) can develop resistance to all antiretroviral drugs. Multi‐drug resistance however is a rare event in modern HIV treatment, but can be life‐threatening, particular in patients with very long therapy histories and in areas with limited access to novel drugs. To understand the evolution of multi‐drug resistance, we analyzed the EuResist database to uncover the accumulation of mutations over time. We hypothesize that accumulation of resistance mutations is not acquired simultaneously and randomly across viral genotypes but rather tends to follow a predetermined order. The knowledge of this order might help to elucidate potential mechanisms of multi‐drug resistance. Our evolutionary model shows an almost monotonic increase of resistance with each acquired mutation, including less well known NRTI‐related mutations like K223Q, L228H and Q242H. Mutations within the integrase (IN) (T97A, E138A/K G140S, Q148H, N155H) indicate high probability of multi‐drug resistance. Hence, these IN mutations also tend to be observed together with mutations in the protease (PR) and reverse transcriptase (RT). We followed up with an analysis of the mutation‐specific error rates of our model given the data. We identified several mutations with unusual rates (PR: M41L, L33F, IN: G140S). This could imply the existence of previously unknown virus variants in the viral quasispecies. In conclusion, our bioinformatics model supports the analysis and understanding of multi‐drug resistance. This article is protected by copyright. All rights reserved.
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214 members
João Piedade
  • Unit of Medical Microbiology
Ana Gama
  • Saúde Pública Internacional e Bioestatística
Sofia Cortes
  • Global Health and Tropical Medicine (GHTM)
Ana Paula Arez
  • Medical Parasitology
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Paulo Ferrinho (Full Professor)
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