After its first kick-off meeting in mid-June in Entebbe, Uganda, the PROTECT consortium has started its work to support the implementation of maternal vaccination against Group B Streptococcus (GBS) in Africa. The project, co-funded by the European Union (EDCTP3), is coordinated by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation, in collaboration with Makerere University - John Hopkins University Joint Collaboration (MUJHU), Uganda, and brings together up to ten African and European institutions.

In addition, "the project has received strong support from the World Health Organisation (WHO), main regulatory authorities and key international stakeholders, so it has the potential to significantly influence healthpolicy recommendations for GBS maternal vaccination strategies at a global level," stresses Azucena Bardají, coordinator of PROTECT and Associate Research Professor at ISGlobal - Maternal, Child and Reproductive Health Initiative.

A vaccine that could save thousands of lives

The initiative aims to develop pregnancy registries for maternal vaccines safety assessment, establish sentinel sites for GBS infection surveillance, and monitor vaccine confidence in Kenya, Malawi, Mozambique and Uganda, to support the next phases of the maternal GBS vaccine clinical trial and accelerate its development, evaluation and licensure.

Although GBS is normally a harmless bacterium that can form part of our microbiota, it can pose a risk during pregnancy and childbirth, as pregnant women colonised with GBS can spread the bacteria to their infants before or during childbirth and cause serious infection. Today, it remains a major cause of death, disease and disability in newborns and infants, particularly in low- and middle-income countries, as can cause sepsis and meningitis.

The GBS maternal vaccines, currently in development, could save thousands of lives each year by preventing mother-to-child transmission of GBS infection. However, according to the WHO Full Value of Vaccines Assessment (FVVA) for GBS vaccines, there are a number of challenges that need to be addressed before the next phases of the vaccine clinical trial can proceed: the lack of background data on burden of disease and birth outcomes in Africa. It also advocates for capacity building for the maternal GBS vaccine trials at sites across Africa.

PROTECT's decisive role

This is where PROTECT can play a crucial role. It will define the burden of infant GBS in representative populations in sub-Saharan Africa. The consortium will also develop robust pregnancy episode registries with detailed information on pregnancy and infant outcomes to monitor the safety and effectiveness of GBS vaccines.

"Recruiting mothers in vaccine trials is always a challenge. We will work to overcome this through community engagement and education," adds Bardají. "In addition, we will set up a multi-country tracking system to monitor the level of vaccine confidence and develop toolkits to improve knowledge about vaccines and ensure equitable participation in vaccine trials."

As a result of the project, an African network of sites capable of conducting pre- and post-licensure studies of maternal vaccines will be established, providing the necessary baseline data of GBS burden for policy makers to consider the introduction of GBS vaccines in sub-Saharan Africa. In addition, the strengthening of capacities could contribute to the surveillance of other diseases and evaluation of other new vaccines, thereby improving overall health outcomes in the region.

A team from the Barcelona Institute for Global Health, a centre supported by the "la Caixa" Foundation, and the French National Institute of Health and Medical Research (Inserm), has carried out an analysis of hospital admissions related to high summer temperatures in Spain over more than a decade. The study concludes that the causes of hospitalisation in which the heat has the most notable impact are:

• Metabolic disorders and obesity
• Renal failure
• Urinary tract infection
• Sepsis
• Urolithiasis
• Poisoning by drugs and other non-medicinal substances 

The research, published in Environmental Health Perspectives, included data of more than 11.2 million of hospital admissions between 2006 and 2019. Those data were restricted to emergency hospital admissions from 48 provinces in mainland Spain and the Balearic Islands and were provided by the Spanish National Institute of Statistics. The team also calculated the values of daily mean temperatures, daily mean relative humidity and concentrations of different air pollutants (PM_2.5, PM₁₀, NO₂ and O₃). With the help of different models, they estimated the relationships between temperature and the different causes of hospitalisation for the summer season (June to September) and by province.

As expected, the statistical analysis showed that high temperature had “a generalised impact on cause-specific hospitalisations”. Even though heat increased the risk of hospitalization in all age groups, children of less than 1 year of age and adults beyond 85 years were the most vulnerable groups, with higher risk of hospital admission. Differences by sex were also found, since in hotter days men showed a higher risk of hospitalization from injuries than women, while women had a higher risk of admission from parasitic, endocrine and metabolic, respiratory or urinary diseases.

“The underlying mechanisms by which heat triggers adverse health outcomes remain unclear, but they seem to be related to how our body regulates its own temperature”, says Hicham Achebak, researcher at INSERM and ISGlobal and holder of a Marie Sklodowska-Curie postdoctoral fellowship from the European Commission. “Under conditions of heat stress, the body activates cutaneous vasodilation and sweat production in order to lose heat. The subsequent reactions can affect people differently depending on a series of factors, such as age, sex or pre-existing health conditions. We know, for example, that women have a higher temperature threshold above which sweating mechanisms are activated and are more susceptible to the effects of heat”, he adds.

Obesity and metabolic disorders

The group of diseases more largely affected by heat were metabolic disorders and obesity. The risk of hospital admission for this type of diseases on the hottest days nearly duplicated compared to the days of optimum or comfort temperature. “There are a number of reasons to explain this. For example, in people with obesity, heat loss responses work less efficiently, as body fat acts as an insulator, making them more susceptible to heat disorders”, says Hicham Achebak.

Relative humidity, air pollution and heat waves

Regarding other variables included in the study, relative humidity didn’t seem to play a relevant role on the relationship of heat with emergency hospital admissions, except for the risk of acute bronchitis and bronchiolitis, which was stronger on days with lower relative humidity.

In addition, high air pollution days appeared to exacerbate the risk of hospitalization from heat for metabolic disorders and obesity, as well as from diabetes, but not for the rest of the health outcomes.

“We observed that the added effects of heat waves —or extreme high temperatures over consecutive days—were small and specific for a subset of diseases, mainly non-respiratory infectious diseases, endocrine and metabolic disorders or nervous system diseases, among others. For this reason, we believe that current Heat-Health Early Warning Systems should be activated not only during heat waves, but also during non-persistent extreme temperatures”, says Joan Ballester Claramunt, ISGlobal researcher and senior author of the study.

Check the data

Reference

Hicham Achebak, Grégoire Rey, Zhao-Yue Chen, Simon J Lloyd, Marcos Quijal-Zamorano, Raúl Fernando Méndez-Turrubiates, Joan Ballester. Heat exposure and cause-specific hospital admissions in Spain: a nationwide cross-sectional study. Environmental Health Perspectives. 2024. https://doi.org/10.1289/EHP13254

A study led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation, provides new evidence on the adverse effects of prenatal exposure to ethylene oxide (EO) on foetal development. The results, published in Epidemiology, show that increased EO exposure in utero is associated with a reduction in birth weight and head circumference in newborns.

Ethylene oxide is a chemical used in various industrial processes and in hospitals, is known for its mutagenic and carcinogenic properties. Human exposure to EO is mainly through inhalation of tobacco smoke and air pollution produced from various household products, including cleaning and personal care products. Workers in the healthcare and chemical industries are particularly exposed to this substance, which is commonly used in sterilisation processes. Previous studies have found that women exposed to higher levels of EO at work during pregnancy had a higher risk of miscarriage and premature birth than those with lower exposure. 

This new study focused on pregnant women and newborns in the general population, rather than a specific population with known high levels of EO exposure. The research team looked at the levels of EO hemoglobin (Hb) adducts in the cord blood of 1,106 newborns from 5 countries: Greece, Spain, Norway, UK and Denmark. This measurement provides valid information on the amount of EO the foetus was exposed to during the last three months of pregnancy, which may help to better understand potential adverse effects on foetal development and birth outcomes.

The study used data from the NewGeneris project, which aimed to study genotoxic exposures in the environment on children's health by measuring several biomarkers in cord blood. Information on birth weight, head circumference, sex and gestational age was obtained from maternity records. 

Higher exposure, lower birth weight and smaller head circumference

The results of the study showed that median levels of EO-Hb adducts in the umbilical cord were higher in smoking mothers compared to non-smoking mothers. Higher levels of hemoglobin adducts were associated with lower birth weight. Specifically, mean birth weight decreased by 3.30 grams with each 10 pmol/g increase in hemoglobin adducts. Increasing levels of hemoglobin adducts were also associated with a decrease in head circumference.

“Reduced head circumference has been linked to delayed neurodevelopment, and reduced birth weight increases the risk of cardiovascular disease, type 2 diabetes mellitus and osteoporosis,” says Barbara Harding, ISGlobal researcher and first author of the study.

The team found no evidence of an association between EO Hb adduct levels and the risk of being small for gestational age (SGA), a condition that can compromise a baby's short and long-term health.

"The study results highlight the importance of addressing EO exposure in both occupational and non-occupational settings. Policy changes to reduce EO exposure in vulnerable populations, such as women of childbearing age, could protect foetal health and improve birth outcomes," says Manolis Kogevinas, ISGlobal researcher and senior author of the study.

Reference

Harding BN, Agramunt, S., Pedersen, M., Knudsen, LE., Nielsen, JKS, Wright, J, Vafeiadi, M., Merlo, DF., Stayner, L., Kelly-Reif, K., Espinosa, A., Bustamante, M., Gützkow, KB., Granum, B., von Stedingk, H., Rydberg, P., Alexander, J., Törnqvist, M., Kogevinas, M. Ethylene oxide hemoglobin adducts in cord blood and offspring’s size at birth: The NewGeneris European Cohort Study. Epidemiology. 2024. DOI: 10.1097/EDE.0000000000001767

Ambient temperatures are associated with over 5 million premature deaths worldwide every year, more than 300,000 of which in Western Europe alone. In a context of rapidly warming temperatures that successively broke previous records during the last two decades , it is essential to use epidemiological models to develop novel, impact-based early warning systems predicting the health effects of forecast temperatures.

This is precisely what the Adaptation group at the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation, has done: Forecaster.health is the first pan-European, open-access platform using sex- and age-specific epidemiological models to predict the actual mortality risks of ambient temperatures for different segments of the population.

The tool allows users to enter the date for which they want to obtain the health predictions within a window of up to two weeks, as well as the population subgroup for which they want to obtain the prediction of temperature related mortality . Once these variables have been selected, the system displays a map showing warnings for 580 regions in 31 European countries with colour codes corresponding to four levels of heat and cold related mortality risk: low, moderate, high and extreme.

Change in paradigm: from meteorology to epidemiology

"Until now, temperature warnings have been solely based on the physical information of weather forecasts, and therefore, they ignore the differences in vulnerability to heat and cold among population groups. Our system changes this paradigm by shifting the focus from meteorology to epidemiology and the social determinants of vulnerability to the environmental factors", says Joan Ballester Claramunt, principal investigator of the Adaptation group at ISGlobal. " Forecaster.health does not only forecast the temperatures themselves, but also the actual risks that these temperatures have on the population as a whole, and especially, on specific population subgroups based on sex and age", he adds.

More precise than weather forecasts

The team used the mortality database of the project EARLY-ADAPT (https://www.early-adapt.eu), which currently includes data for 580 regions in 31 European countries by sex, age and cause of death, to fit separate epidemiological models for population groups. Every day, the tool obtains temperature records and forecasts, and uses the epidemiological models to quantify the risk of temperature related mortality by sex and age group for any given date within the following 15 days.

“We know that vulnerability to heat is influenced by a number of factors, including sex and age. We know, for example, that women are more susceptible to heat than men, and that the risk of death for both heat and cold increases with age. For that reason, our tool separately fits epidemiological models for each sex and age group, which allows us to issue independent warnings accounting for the real impacts on the population”, says Marcos Quijal-Zamorano, researcher at ISGlobal and one of the authors of the system.

The first step towards a multi-hazard platform

Always based on epidemiological evidence and models, Forecaster.health will be expanded in the next months and years in different directions. To begin with, new countries and smaller regions will be added to the platform, as soon as new data is acquired by the team. The tool is also expected to develop new epidemiological models to incorporate health warnings for several air pollutants, such as particulate matter, ozone or nitrogen dioxide. Finally, the platform will also issue warnings for specific causes of death, such as cardiovascular and respiratory diseases, and for other health outcomes, such as hospital admissions and occupational accidents.

“Our approach crucially depends on the availability of health data to fit our epidemiological models. We are eager to add additional health outcomes for more countries or smaller regions, either from Europe or in other continents, if data is provided to us”, emphasises Joan Ballester Claramunt .

Proof-of-Concept Grants of the European Research Council

Forecaster.health has been funded by the Proof-of-Concept Grants HHS-EWS and FORECAST-AIR of the European Research Council (ERC). These grants are aimed at transforming the basic research and resources generated in the ERC Consolidator Grant EARLY-ADAPT into innovative tools to address societal challenges. In that regard, EARLY-ADAPT is studying how populations are adapting to the public health challenge of climate change, and consequently, HHS-EWS and FORECAST-AIR are offering real solutions to increase the resilience of societies to environmental threats such as ambient temperatures and air pollutants.

The team that developed the platform is composed by Joan Ballester Claramunt, Mireia Beas-Moix, Nadia Beltrán-Barrón, Raúl Fernando Méndez Turrubiates, Fabien Peyrusse andMarcos Quijal-Zamorano.

Date

25/09/2024

Hour

9.30 - 14.00 h

Place

PRBB
(Dr. Aiguader, 88) Barcelona

This event aims to facilitate the sharing of knowledge, ideas, and resources within the exposome research community in the Barcelona area. Whether you're a seasoned exposomics researcher or a newcomer to the field, this symposium invites you to join us in building a supportive community dedicated to advancing exposome research. With a series of invited presentations, abstract-selected presentations and posters, it will provide a panorama of exposome research across different institutions in the Barcelona area.

The exposome represents the comprehensive set of environmental exposures that an individual encounters throughout their life. The exposomics field aims to evaluate how the exposome impacts on  biology and health through discovery-based analytical approaches. This local-level symposium is part of a larger initiative to build an International Human Exposome Network.

The symposium is expected to cover the following topics:

1. Technological Innovations and Methodologies in Exposomics

• Advanced Analytical Techniques: Innovations in non-targeted chemical exposome characterization, including anthropogenic pollutants and diet related compounds.
• Computational Methods and Data Science: Application of big data, artificial intelligence, and machine learning in exposome studies
• Novel Biomarkers and Detection Methods: Development of new biomarkers and tools for measuring environmental exposures, e.g. microplastics, accurately and comprehensively
• Sensors and Geospatial Modeling Applications: to collect and analyze spatial data on environmental exposures. This includes wearable sensors, remote sensing, and GIS for mapping and analyzing the spatial distribution of exposures and their health impacts.

2. Exposome and Human Health

• Social and physical environment in Low and Middle Income Countries' contexts.
• Early-life Exposures and Child Health: Research on multiple early-life exposures and their effects on child health and development.
• Chronic Diseases and Aging: The role of cumulative environmental exposures in the development of chronic diseases such as cancer, respiratory diseases, and neurodegenerative disorders.
• Precision Medicine: Utilising exposome data to advance precision medicine and improve health outcomes in clinical settings.

3. Biological Impacts and Experimental Modeling in Exposomics

• Molecular and Cellular Responses: Investigating how environmental exposures influence molecular and cellular processes, including gene expression, epigenetic modifications, and metabolic pathways.
• Animal and In Vitro Models: Use of animal models and in vitro systems to study the biological effects of environmental exposures and to identify potential mechanisms of toxicity.
• Integrative Omics Approaches: Combining genomics, proteomics, metabolomics, and other omics data to understand the comprehensive biological impact of the exposome.

4. Translational Research: Bridging experimental findings with clinical and epidemiological studies to better understand the health implications of exposome-related findings​.

Key Dates

• Abstract Call Deadline: July 1st 2024 — SUBMIT YOUR ABSTRACT! (Further details below)
• Abstract Selection Disclosure: July 26th 2024
• Registration Deadline: Sept 13th 2024 — REGISTER NOW!

Scientific Core Committee

• ISGlobal - Exposome Hub (Léa Maitre, Martine Vrijheid, Mariona Bustamente)
• CSIC - Institute of Environmental Assessment and Water Research (Pablo Gago-Ferrero)
• University of Barcelona - Biomarkers & Nutritional and Food Metabolomics Group (Cristina Andres-Lacueva)
• University of Barcelona - Artificial Intelligence in Medicine Lab (Karim Lekadir)
• EMBL, Barcelona - Organoid models of neuroendocrine development and cancer (Talya L. Dayton)

Agenda Outline

• 09.30 - 10.00 h — Welcome Coffee - Networking
• 10.00 - 10.30 h — Introduction local and global exposome research landscape (ISGlobal)
• 10.30 - 11.30 h — Part 1: Invited scientific presentations
• 11.30 - 12.30 h — Coffee Break - Poster session for early career researchers (selected based on abstract selection before the event)
• 12.30 - 13.30 h — Part 2: Invited and abstract-selected scientific presentations

The detailed programme of the symposium will be available soon (to be published in July 2024). Regarding participation format, the event will be in-person and presentations need to be in this format. Livestream option will be available, but just to follow presentations only.

Abstract Submission and Review Process

Abstracts submitted to the Barcelona Exposome Symposium will undergo a streamlined review process, starting with an initial screening and coordination by the core team, followed by a detailed evaluation by committee members. The scientific committee will then select the final abstracts. Authors of accepted abstracts will be notified by July 27th. The selection criteria focus on relevance to the symposium's topics, scientific rigour, clarity of presentation, interdisciplinary merit, and potential public health impact. This thorough and fair evaluation ensures that the symposium features high-quality discussions that are both impactful and informative.

Oral presentations (12 min) and Posters are invited for broadly defined exposomics and environmental health related topics. Posters can cover a wide range of subjects within these fields.

Poster Dimensions (to be added soon).

Submission Guidelines: Abstracts should be 200 words max.

Submit your abstract by 1 July 2024.

Coordinated by:

Support provided by:

Brain scans of more than 2,000 preadolescents suggests that early life exposure to heat and cold may have lasting effects on the microstructure of white matter in the brain, especially when living in poorer neighbourhoods. The study, published in Nature Climate Change, highlights the vulnerability of foetuses and children to extreme temperatures. This research has been  led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the “la Caixa” Foundation, and IDIBELL, in collaboration with the Erasmus University Medical Center Rotterdam (ERASMUS MC) and the Centro de Investigación Biomédica en Red (CIBER): areas of Epidemiology Public Health (CIBERESP), and Mental Health (CIBERSAM).

In the current climate emergency, the impact of extreme temperatures on human health is a major concern for the scientific community and society. Children are particularly vulnerable to temperature changes, as their thermoregulation mechanisms are still immature.

“We know that the developing brain of foetuses and children is particularly susceptible to environmental exposures, and there is some preliminary evidence suggesting that exposure to cold and heat may affect mental well-being and cognitive performance in children and adolescents”, says Mònica Guxens, researcher at ISGlobal, Erasmus MC and CIBERESP. “However, there is a lack of studies evaluating potential changes in brain structure as a result of these exposures,” she adds.

In this study, a team led by Guxens looked at the white matter structure in the brains of preadolescents to identify windows of susceptibility to cold and heat exposure in early life. The analysis included 2,681 children from the Generation R Study, a birth cohort in Rotterdam, who underwent magnetic resonance imaging (MRI) between 9 and 12 years of age. The MRI protocol assessed brain connectivity by measuring the magnitude and direction of water diffusion within the brain’s white matter. In more mature brains, water flows more in one direction than in all directions, which gives lower values for a marker called mean diffusivity and higher values for another marker called fractional anisotropy. The research team used an advanced statistical approach to estimate, for each participant, exposure to monthly mean temperatures from conception until 8 years of age, and their effect on these MRI connectivity parameters (mean diffusivity and fractional anisotropy) measured at 9-12 years.

Susceptibility window between pregnancy and age three

The results show that exposure to cold during pregnancy and the first year of life, and exposure to heat from birth until 3 years of age were associated with higher mean diffusivity at preadolescence, pointing to slower white matter maturation. 'Cold' and 'heat', in this case, are defined as those temperatures that are at the lower and upper end, respectively, of the temperature distribution in the study region.

"The fibres of the white matter are responsible for connecting the different areas of the brain, enabling communication between them. As the white matter develops, this communication becomes faster and more efficient. Our study is like a photograph at a particular moment in time and what we see in that image is that participants more exposed to cold and heat show differences in a parameter - the mean diffusivity - which is related to a lower level of maturation of the white matter," explains Laura Granés, IDIBELL and ISGlobal researcher and first author of the study. "In previous studies, the alteration of this parameter has been associated with poorer cognitive function and certain mental health problems," she adds.

“The largest changes in connectivity parameters are observed in the first years of life,” says co-author and IDIBELL, UB and CIBERSAM researcher Carles Soriano. “Our results suggest that it is during this period of rapid brain development that exposure to cold and heat can have lasting effects on the microstructure of white matter.”

No association was found between temperature exposure in early life and fractional anisotropy at 9-12 years. The authors argue that a possible explanation is that these two metrics reflect different microstructural changes, and that mean diffusivity may be a more robust indicator of white matter maturation, compared to fractional anisotropy.

Poorer children more at risk

A stratified analysis by socioeconomic conditions showed that children living in poorer neighbourhoods were more vulnerable to cold and heat exposure. In these children, the windows of susceptibility to cold and heat were similar than those identified in the overall cohort, but started earlier. These differences may be related to housing conditions and energy poverty.

One important mechanism that could explain the effect of ambient temperature on neurodevelopment could be related to poorer sleep quality.  Other possible mechanisms include disruption of placental functions, activation of the hormonal axis leading to higher cortisol production, or inflammatory processes.

“Our findings help to raise awareness of the vulnerability of foetuses and children to changing temperatures,” says Guxens. The findings also stress the need of designing public health strategies to protect the most vulnerable communities in the face of the looming climate emergency. 

Reference

Granés L, Essers E, Ballester J, Petricola S, Tiemeier H, Iñiguez C, Soriano-Mas C and Guxens M. Cold and heat exposure in early life and white matter microstructure in preadolescents. Nat Climate Change. 2024. Doi: 10.1038/s41558-024-02027-w

Researchers from the Institut d’Investigació en Atenció Primària Jordi Gol (IDIAPJGol) and the Barcelona Institute for Global Health (ISGlobal), a center promoted by “la Caixa” Foundation, have led a study on the effectiveness of vaccines against COVID-19 among cancer patients in Catalonia. The research, recently published in the journal Nature Communications, recommends administering additional doses of the vaccine among this risk population.

Cancer patients are at increased risk of death from COVID-19, especially those who have lung cancer, hematological malignancies or are undergoing systemic treatment, such as chemotherapy.

The participation of patients with active cancer in clinical trials that have been carried out to test the effectiveness of vaccines against COVID-19 has been very limited, so it has not been possible to know exactly the effectiveness of immunization against the SARS-CoV-2 virus among this risk group. However, prospective data from several studies show that cancer patients may develop fewer protective antibodies to COVID-19 virus than the general population, especially after receiving a single dose of the vaccine.

Real world data

The study that has just been published in Nature Communications confirms these results, based on the analysis of massive data obtained from clinical registries. This is the most comprehensive work yet on this issue and the first of this kind with information from real-world data, providing a more realistic view of how vaccines are working in everyday clinical practice among people with cancer.

The researchers have analyzed the data of 184,744 patients with neoplasia included in the information system for the development of research in primary care (SIDIAP), the database that includes people treated at the first level of care in Catalonia. Half of the individuals included in the study (92,372) had received at least the first complete immunization (two inoculations of the vaccine) and the other half (92,372) had not been vaccinated at the time of the work.

Researchers have compared the mortality data and serious complications derived from COVID-19 among the immunized group after receiving the first and second doses of the vaccine with those of the unvaccinated group. Next, the researchers compared the results of the members of the experimental group after having received the booster dose of the vaccine (which was 54,267 patients) with an equivalent sample of people in the control group who had only received the first two inoculations.

The results of the study show that the rate of mortality and serious complications among cancer patients not vaccinated against COVID-19 is twice that of those who have received the full first dose. However, this difference is smaller than the observed data among the general population immunized against SARS-CoV-2 and the non-immunized population.

“Our results clearly demonstrate that vaccination against COVID-19 significantly reduces mortality and serious complications among cancer patients, especially those who have received the booster dose,” highlighted ISGlobal researcher Otavio Ranzani, who supervised the study together with Talita Duarte-Sallés from IDIAPJGol.

For her part, this researcher explained that “this work provides essential information to understand the impact of vaccination against COVID-19 on cancer patients, and helps to design public health policies that protect this vulnerable population.”

Reference

Lazar, F., Mercadé-Besora N., Raventós B., Pérez-Crespo L., Castro G., Ranzani O., Duarte-Salles T. Effectiveness of COVID-19 Vaccines Against Severe COVID-19 Among Patients with Cancer in Catalonia, Spain. Nature Communications. 2024. https://doi.org/10.1038/s41467-024-49285-y

In the ongoing fight against tuberculosis (TB), a newly launched Global TB Dictionary aims to provide a common language for researchers, policymakers, funders and affected communities. Developed through a systematic approach and guided by evidence and expert review, the dictionary aims to unify TB-related terminology and promote clearer communication in the field.

Tuberculosis remains a major global challenge, causing an estimated number of 10.6 million new disease episodes and 1.3 million TB-related deaths in 2022 alone. Scientific output on TB has grown exponentially since the 1990s. Advances in research and treatment have broadened the understanding of the TB spectrum from exposure to infection to disease, challenging long-held concepts and introducing new terminology for use in research and control efforts.

The need for a standardised TB lexicon is evident in the evolving landscape of TB research, where new discoveries and evolving concepts are constantly reshaping our understanding of the disease. Terms such as “subclinical TB”, “incipient TB”, and even “tuberculosis” itself have been used ambiguously, prompting some professionals to advocate for clearer terminology. Similarly, case definitions for paediatric TB have undergone several revisions, contributing to inconsistencies in reporting and analysis.

Unifying terms and definitions through a consensus process

To address these challenges, a diverse group of researchers, public health officials and TB survivors worked together to create the first edition of the Global TB Dictionary. The development process, led by ISGlobal, involved a comprehensive review of TB-related literature, including publications from the Global TB Programme (WHO), the International Union Against Tuberculosis and Lung Disease (The Union), and the Centers for Disease Control and Prevention (CDC) in the United States. In addition, a systematic search of PubMed was conducted to identify articles discussing TB terms and concepts or containing glossaries. Expert input from a panel of TB experts ensured the inclusion of relevant terms and definitions.

The glossary underwent multiple review iterations, with terms and definitions assessed by multiple reviewers to ensure accuracy and coherence. Extensive discussion within the editorial team resolved discrepancies and ensured alignment with current scientific knowledge and non-stigmatising language. 

Furthermore, individuals affected by tuberculosis have also been included in developing the dictionary, "ensuring that the language used in the dictionary is widely accepted and appropriate for all individuals in the TB community. The participation of patients not only ensured the inclusivity of the language used in the dictionary but also provided valuable insight into how the disease affects their lives," emphasized Joanna Ehrlich, project manager at ISGlobal and coordinator of the dictionary.

The dictionary aims to include regular updates to reflect advances in TB research and the inclusion of new terms suggested by the TB community. Users can access the document online and contribute suggestions for future editions, ensuring that it remains a dynamic and evolving resource.

"We hope that this open-access glossary will be a useful resource that allows the community of TB researchers, policymakers, funders and people affected by TB to unite around a common understanding of TB-related vocabulary," said Alberto García-Basteiro, ISGlobal researcher and co-editor of the TB dictionary's together with Prof Marcel Behr from Mcgill University, in Canada.

The development of the Global TB Dictionary is a step towards improving communication and collaboration in TB research and control efforts. By providing a common reference point, the dictionary facilitates clearer communication among stakeholders and improves the overall coherence of TB-related discourse.

Access the dictionary: www.tbdictionary.org

Read the commentary in The Lancet Global Health here.

The second edition of the International Spring School in Global Health, held from 27 to 31 March, attracted a thousand participants, double the number of the first edition. Organised through the Severo Ochoa Programme at ISGlobal, an institution supported by "la Caixa" Foundation, this edition addressed key issues in the field of global health such as implementation science, endemic and pandemic infectious diseases, the health impact of climate change, global occupational epidemiology, the analysis of time series data collected with digital technologies, and knowledge translation. 

The International Spring School in Global Health contributes to the achievement of Sustainable Development Goals (SDGs) 3 (health and well-being) and 4 (inclusive, equitable and quality education) through the transfer of knowledge by our faculty of research professionals and their collaborators. In this way, access to training and learning is promoted through an educational programme aimed at postgraduate and masters students, doctoral students and researchers, as well as other professionals interested in global health. Sessions are synchronous, participatory and interactive, using examples and success stories relevant to different parts of the world. 

In this second edition of the Spring School, two modules were taught in Spanish and with a timetable more accessible to people from Latin America, with the aim of opening up the training to more people from this geographical area, which is one of the priority regions for Spanish development cooperation. Participants were able to access the modules free of charge thanks to the support of the Ministry of Foreign Affairs, European Union and Cooperation, the Ministry of Science and Innovation and the Spanish National Research Agency.

Participants from 98 countries 

Of the 1,000 participants registered this year, 91% were international students (from 98 countries), 81% came from low and middle income countries and 21% had participated in previous editions of the Spring School or Summer School. Half of the participants came from 26 of the 37 countries considered as priority by the Spanish Agency for International Development Cooperation (AECID), which has supported the project through the Ministry of Foreign Affairs, European Union and Cooperation.

In addition to the 6 modules, the participants were invited to the opening event - a roundtable on contrasting visions of the transformation of global health governance, moderated by Leire Pajin and Rafael Vilasanjuan- and to two keynote lectures by Cathryn Tonne and Jeffrey Lazarus.

A collaborative and inclusive platform 

"The second edition of the Spring School has once again demonstrated ISGlobal's commitment to inclusive and equitable global health education and learning. The participation of students from all over the world has provided a valuable platform for the exchange of knowledge and experiences to address the challenges in the field," points out Núria Casamitjana, Training and Education Director. 

"It has been very satisfying to see how, throughout the course, participants have been able to establish new interactions that could be the starting point for new collaborations and professional networks," says Giulia Pollarolo, coordinator of the Spring School. 

Exposure to current levels of ground-level ozone (O₃) in Europe is one of the main causes of premature mortality due to air pollution, especially in summer. A study led both by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation, in collaboration with the French National Institute of Health and Medical Research (Inserm), and the Barcelona Supercomputing Center - Centro Nacional de Supercomputación (BSC-CNS), has quantified for the first time the impact of imported (non-national) O₃ on mortality. The results, published in Nature Medicine, have important implications for air quality and public health policies in the continent and within the European Union.

Ground-level ozone is a harmful air pollutant formed in the troposphere by the interaction of sunlight with several precursor gases, mainly nitrogen oxides (NOx) and volatile organic compounds (VOCs) from natural and anthropogenic sources. High O₃ levels are associated with a range of adverse respiratory health effects, including aggravation of asthma, chronic obstructive pulmonary disease, lower lung function and infections, leading in the most severe cases to hospitalisation and death.

The research team quantified both national and imported O₃ contributions to mortality across 35 European countries between 2015 and 2017, covering 813 regions and around 530 million people. The results show that imported O₃ contributed to 88.3% of all deaths attributable to this pollutant. Most of this transboundary O₃ came from outside the study domain (from hemispheric sources and transport), accounting for 56.7% of the total attributable mortality. O₃ imported from the other 34 European countries also had a significant effect on mortality, accounting for 20.9%.

The concentration of O₃ in a given location greatly depends on the tropospheric transport of the pollutant itself. “The health effects of O₃, and of any air pollutant in general, are far from being a local issue. In this study, we found that 11.7% of deaths attributable to O₃ were caused by national sources," says Hicham Achebak, a researcher at Inserm (France) and ISGlobal and holder of a Marie Sklodowska-Curie postdoctoral fellowship from the European Commission. "This fact underlines the need for coordinated actions at local, continental and global scales by all countries to reduce O₃ concentrations and their impact on health," adds the first author of the study.

The analysis was based on data from the warm season (May to October), which is the season of highest O₃ values. To track O₃ concentrations, the study used the CALIOPE air quality system developed at BSC-CNS, which covers Europe and surrounding areas. This system tracks both O₃ and its precursors (i.e. NOx and VOCs) that are formed or emitted in each region. To obtain data outside the study area, the researchers used a modelling approach that allowed them to track the dispersion and transport of air pollutants over long distances. The method also included emissions from both land and sea.

The average O₃ concentration over all countries and the study period was 101.9 μg/m³, ranging from 76.7 μg/m³ in Finland to 130.1 μg/m³ in Malta. The estimated number of deaths attributable to O₃ during the study period was 114,447 (estimated based on the whole range of O₃ concentrations), resulting in an attributable mortality rate of 72 deaths per million population per year.

Most industrialised and populous countries contribute most to mortality

As expected, as warmer temperatures in the south favour the formation of O₃, the concentrations of this pollutant decrease in the north of the continent. The highest mortality burdens were estimated in the most populated countries (Germany, Italy, France, the United Kingdom, Spain and Poland), whereas the highest mortality rates were found in the south-eastern countries (Bulgaria, Serbia, Croatia, Hungary, Greece and Romania).

The analysis also showed that within Europe the most industrialised countries were the major contributors to the mortality attributable to transported transboundary O₃, especially France, with an estimated 4,003 deaths between 2015 and 2017, and Germany, with 3,260 deaths. O₃ originating from France had a significant impact on neighbouring countries such as Luxembourg (32.3% of deaths attributable to O3), Switzerland (29.3%), Belgium (24.4%) or Spain (16.8%). O₃ from Germany also significantly affected neighbouring countries such as Luxembourg (24.2% of deaths), the Czech Republic (23.3%) or the Netherlands (21.5%).

The results highlight the importance of westerly winds, with countries downwind towards the east having a higher number of deaths attributable to imported O₃ from other European countries. South-western European countries were the least affected by the health effects of imported O₃ from other European countries. In fact, Spain, France and Portugal were the countries with the largest fraction of attributable mortality caused by national O₃ with respect to contributions from other European countries, accounting for 53.7%, 47.1% and 46.2% of deaths respectively, and the smallest imported/exported ratio of attributable deaths.

In some coastal regions and small Mediterranean countries, the contribution of shipping emissions was significant, such as Malta (24% of deaths) and Cyprus (14%).

Local, continental and global action to reduce pollution

The study underlines the need for a systematic quantification of national, EU and non-EU contributions to air pollution levels and associated health impacts as an essential step prior to the elaboration of regulation and mitigation plans, especially for air pollutants such as O₃ that are easily transported across political borders. 

"Thus far, mitigation efforts have focused primarily on national and regional scales, lacking a comprehensive, transboundary assessment of the associated health effects," says Joan Ballester Claramunt, ISGlobal researcher and co-senior author of the study. "Our study is a first step towards this in-depth analysis, which would help achieve WHO air quality standards to prevent premature deaths and other health impacts such as hospitalisations and chronic diseases," he adds.

Given the large non-national contributions to average O₃ in each location, the study emphasizes that the results should not be interpreted by local air quality authorities as a justification for local inaction. "During the highest O₃ episodes the local/national contributions can increase substantially, and local mitigation actions can contribute to considerably reduce daily exceedances of the regulated thresholds. Additionally, local mitigation strategies are key towards reducing the export of O₃ to other regions and countries” argues Carlos Pérez García-Pando, ICREA and AXA Research Professor at the Earth Sciences Department of BSC-CNS and co-senior author of the study.

Climate warming will reinforce the conditions for tropospheric O3 formation in the future, as the photochemical mechanisms of O₃ formation are favoured during heat waves and periods of high solar radiation. "Tackling climate change is key to improving air quality and, in turn, a key element to consider when designing and implementing long-term, long-lasting policies on a global scale. Also, future research should refine our results by analysing the contribution to mortality of the different economic sectors and natural sources, which are impacted by climate change." argues Oriol Jorba, Researcher and co-group leader of the Atmospheric Composition Group at the Earth Sciences Department of BSC-CNS.

Reference

Achebak, H., Garatachea, R., Pay, MT., Jorba, O., Guevara, M., Pérez García-Pando, C., Ballester, J. Geographic sources of ozone air pollution and mortality burden in Europe. Nature Medicine, 2024. Doi: 10.1038/s41591-024-02976-x

Human adenovirus (HAdV) is a common pathogen that can cause life-threatening disease in bone marrow transplant recipients, particularly among paediatric patients. There are currently no specific treatments for HAdV infections, but a new study led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by “la Caixa” Foundation, and the Instituto de Biomedicina de Sevilla (IBiS) has identified four promising compounds that bring hope to the fight against these infections.

Metal-based compounds have received much attention as potential drugs against a wide range of pathogens due to the diverse structures and mechanisms of action associated with metal ions. “For example, there has been a lot of interest in studying gold-based complexes as antibacterial, anti-inflammatory or even anticancer agents, but few studies have investigated these compounds for antiviral purposes,” says Sara Soto, ISGlobal researcher and senior author of the study together with Javier Sánchez- Céspedes, from IBiS.

Broad antiviral activity with low toxicity

In this study, the research team analysed the anti-adenoviral activity of four gold(III)-based compounds that are highly stable under different conditions. Experiments with cell lines showed that all four compounds inhibited HAdV replication in a dose-dependent manner, and at very low (sub-micromolar) concentrations that were not toxic to the cells.

The research team also carried out studies to identify the mechanisms of action of these compounds. They found that these molecules act at late stages of the HAdV replication cycle, after it has replicated its DNA. This suggests that they could effectively inhibit the virus at crucial points in its lifecycle, thereby curbing its ability to spread and cause disease.

Additionally, all four compounds significantly inhibited the replication of another human virus (cytomegalovirus), indicating their potential as broad-spectrum antivirals.

“One of our compounds showed particularly high activity and low cytotoxicity,” explains Soto. “This complex can be considered a promising candidate for deriving new, improved compounds that could enter preclinical studies,” she adds.

Reference

Manzanero-Balsera M, Soengas RG, Carretero-Ledesma M et al. Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents. Heliyon. 2024. Doi: 10.1016/j.heliyon.2024.e27601

In a significant step towards bolstering efforts to mitigate climate change impacts on public health, the Catalan Institute of Health, along with the Barcelona Institute for Global Health (ISGlobal), a centre supported by the ”la Caixa” Foundation, and the UNESCO Chair in Life Cycle and Climate Change from ESCI-UPF, have joined forces under the auspices of the CATALYSE project . This collaboration marks a four-year commitment aimed at fortifying the Catalan Health System's resilience against the effects of climate change.

CATALYSE, a flagship initiative of an international consortium, is dedicated to bridging the gap between knowledge and action to accelerate climate change response and safeguard public health across Europe. This five-year project, spearheaded by ISGlobal and funded by the European Commission under the Horizon Europe programme, has three main lines of action: provide evidence on the effects of climate change on health and how to reduce negative impacts; produce new knowledge to accelerate climate change action in Europe; and help health systems adapt to climate change and reduce their carbon footprints.

In Catalonia, the UNESCO Chair will serve as the focal point for project activities, working in tandem with the Catalan Institute of Health to develop and implement strategies tailored to the region's specific needs. At the heart of this partnership lies the signing of a Memorandum of Understanding (MoU), signaling a shared commitment to devising contemporary guidelines for climate change mitigation within the Catalan health sector.

The initial phase of collaboration will focus on assessing the carbon footprint of the Catalan Health System, pinpointing areas of significant greenhouse gas emissions. These insights will inform the design of targeted mitigation policies aligned with stakeholder priorities. Given the unique challenges inherent to reducing carbon footprints in the healthcare sector, the project will also produce a tailored educational program for healthcare professionals aimed at fostering climate change awareness and adaptation within the sector.

This assessment will benefit from the experience and the methodology of a previous assessment on ISGlobal’s own carbon footprint conducted by both the Barcelona Institute for Global Health and ESCI-UPF.

Through the implementation of these measures, the project envisages enhancing the Catalan Health System's resilience to future climate change occurrences while simultaneously alleviating its environmental footprint.

The implementation of primary health care (PHC) over the last two decades has prevented more than 300,000 child deaths in four Latin American countries, and could prevent more than 140,000 by 2030 in a scenario of economic crisis. This is the main conclusion of a study coordinated by the Barcelona Institute for Global Health (ISGlobal), a centre supported by “la Caixa” Foundation.

The 2018 Astana Declaration highlighted the critical role of PHC in ensuring that everyone enjoys the highest possible standard of health, and in achieving universal health coverage. The Declaration also stressed the urgent need to assess the effectiveness of PHC strategies in low and middle-income countries (LMICs), in order to make them more effective and sustainable.

A multi-country assessment

“Ours is the first comprehensive attempt to assess the impact of PHC as a macro-strategy in four countries representing the majority of the population (62%) in Latin America,” says ISGlobal researcher Davide Rasella, who leads the Health Impact Assessment group. He and his team conducted a retrospective impact evaluation in Brazil, Colombia, Ecuador, and Mexico from 2000 to 2019, using data on PHC coverage and mortality between birth and five years of age. They also used forecasting models up to 2030 under different economic scenarios.

The analysis shows that high PHC coverage was associated with significant reductions in mortality among newborns (of almost 30%), and children under five. The PHC effects were particularly strong for poverty-related conditions (such as anemia and malnutrition) and vaccine-preventable diseases. The models predict that in a scenario of moderate economic crisis, 142,285 child deaths could be avoided by 2030 in the four countries by increasing PHC coverage.

Latin American countries are among those that have suffered the most from the socioeconomic consequences of the COVID-19 pandemic and may be forced to implement fiscal austerity measures. “However, our findings show that expanding PHC to protect the growing number of vulnerable populations is an effective strategy to mitigate the health impact of the current economic crisis and to achieve the Sustainable Development Goals related to child health,” says Ana Moncayo, first author of the study and researcher at the Center for Research on Health In Latin America (CISeAL).

The authors also stress the importance of having sufficient and high-quality administrative data, (demographic, socioeconomic, and health-related information) to enable robust studies that can guide decision-making.

Reference

Moncayo AL, Cavalcanti D, Ordoñez JA et al. Can Primary Health Care mitigate the effects of economic crises on child health? An integrated multi-country evaluation and forecasting analysis in Latin America. Lancet Global Health. 2024.  

The term ‘metabolic syndrome’ (MetS) encompasses a group of factors, such as abdominal obesity, hypertension and insulin resistance, that together increase the risk of cardiovascular disease and type 2 diabetes. A new study suggests that prenatal exposure to a combination of endocrine disrupting chemicals (EDCs) is associated with a poorer metabolic health in childhood, which in turn may contribute to an increased risk of metabolic syndrome in adulthood. The research, led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation, has been published in Jama Network Open.

EDCs are chemical substances that are so named because of their ability to interfere with the functioning of our hormonal system, growth, energy balance and metabolism and whose exposure, given their ubiquity in our environment, is difficult to escape. Previous studies have already shown a link between individual exposure to some of these compounds during the prenatal phase and some of the factors that make up the metabolic syndrome, particularly obesity and blood pressure. This time, as part of the ATHLETE project, the team set out to assess the combined impact of these substances on all metabolic syndrome factors.

The study involved 1,134 mothers and their children from six European countries (Spain, France, Greece, Lithuania, Norway and the United Kingdom), all volunteers from the HELIX (Human Early Life Exposome) cohort. Prenatal exposure to a total of 45 endocrine disruptors was analysed through blood and urine samples collected from the mothers during pregnancy or from the umbilical cord after birth.

Later, when the children were between 6 and 11 years old, they were followed up, including a clinical examination, interview and collection of biological samples. This yielded data on waist circumference, blood pressure, cholesterol, triglycerides and insulin levels, which were aggregated to obtain a risk index for metabolic syndrome.

Mercury, PFAS, organochlorine pesticides and PBDEs

Statistical analysis showed that mixtures of metals, perfluoroalkylated and polyfluoroalkylated substances (PFAS), organochlorine pesticides and flame retardants (or PBDEs) were associated with a higher risk of metabolic syndrome. In the case of metals, the association observed was mainly due to the effect of mercury, the main source of which is the intake of large fish. 

PFASs are one of the most widely used families of chemical compounds, being used in pesticides, paints, non-stick pans or fast food packaging, among many other common uses. Because of their persistence, they are also known as the ‘forever chemicals’. Also very persistent are organochlorine pesticides, which were already banned in Europe in the 1970s, but to which we are still widely exposed due to their permanence in the environment.

Different results according to sex

"We also observed that associations were stronger in girls for mixtures of PFASs and polychlorinated biphenyls (PCBs), while boys were more susceptible to exposure to parabens. Since endocrine disruptors interfere with sex steroid hormones, these differences fall within what would be expected", explains Nuria Güil Oumrait, ISGlobal researcher and first author of the study.

"Our results suggest that exposure to widespread mixtures of endocrine disruptors during pregnancy may be associated with adverse metabolic health in both boys and girls. This association may contribute to the current increase in the prevalence of lifetime metabolic syndrome, which currently affects 1/4 of the adult population, with upward trends evident even among young people", concludes Martine Vrijheid, co-director of ISGlobal's Environment and Health over the Lifespan programme and senior author of the study.

Reference

Güil-Oumrait N, Stratakis N, Maitre L, Anguita A, Urquiza J, Fabbri L, Basagaña X, Heude B, Småstuen Haug L, Kaur Sakhi A, Iszatt N, Keun H.C, Wright J, Chatzi L, Vafeiadi M, Bustamante M, Grazuleviciene R, Andrušaitytė S, Slama R, McEachan R, Casas M, Vrijheid M. Prenatal Exposure to Chemical Mixtures and Metabolic Syndrome Risk in Children. JAMA Network Open. 2024; 7(5):e2412040. doi:10.1001/jamanetworkopen.2024.12040

A new study led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the ‘la Caixa’ Foundation, and the Germans Trias i Pujol Research Institute (IGTP), provides new information on the role of the spleen and extracellular vesicles in latent infections caused by Plasmodium vivax.

Malaria caused by P. vivax is widespread worldwide, with nearly 77 million cases in 2022. While there is no sustained local transmission in Catalonia or most of Europe, it is estimated that more than 2 billion people are at risk of contracting the disease in endemic regions such as Southeast Asia and Latin America.

P. vivax infection is transmitted by mosquito bites. Once infected, a person may develop an acute infection – with symptoms including fever, chills, sweats, and muscle aches – or the parasite may remain in a latent state. This poses a significant challenge to the diagnosis and global eradication of the disease, as up to 90% of chronic P. vivax infections are asymptomatic and many go undetected by current diagnostic methods.

The role of the spleen in P. vivax infections

Carmen Fernández-Becerra and Hernando A del Portillo, who lead the Plasmodium vivax and Exosome Research (PvREX) group at ISGlobal and IGTP, have been studying for years how the parasite manages to hide and evade immune responses and conventional treatments. Their focus is on the spleen, where recent studies have shown that over 95% of the parasite's biomass is concentrated.

Previous research by the PvREx group has shown that the spleen not only filters out old and defective red blood cells but also serves as a hiding place for malaria-infected red blood cells. They have also shown that extracellular vesicles – small structures secreted by infected cells – facilitate this hiding process. These vesicles promote the adherence of infected cells to spleen cells, a crucial mechanism for the survival of the parasite.

Cellular events in a P. vivax infection

In collaboration with researchers from the Josep Carreras Leukaemia Research Institute, the Institut Pasteur du Cambodge, and the Microbiological and Biomedical Research Group of the Universidad de Córdoba, the PvREX team provides new details on the cellular processes involved in P. vivax infection.

Using advanced genetic techniques, the researchers show that a P. vivax gene, whose expression is dependent on the spleen, is associated with the parasite's adherence to spleen cells. This adherence is enhanced in the presence of extracellular vesicles derived from the plasma of infected patients.

By analysing individual cells, they show for the first time that extracellular vesicles signal spleen cells to express proteins that facilitate the parasite's adherence. "These results open new avenues for identifying signalling pathways induced by extracellular vesicles in human spleen cells, a critical step in interrupting the transmission of the parasite", says del Portillo.

Asymptomatic chronic infections are a major challenge to malaria eradication. This study provides valuable information on how malaria parasites hide in the human spleen, and highlights the importance of understanding the interactions between the parasite and its host. "Identifying these interactions is essential to combat this global health challenge", says Fernández-Becerra.

Reference

Ayllon-Hermida A, Nicolau-Fernandez M, Larrinaga AM, Aparici-Herraiz I, Tintó-Font E, Llorà-Batlle O, Orban A, Yasnot MF, Graupera M, Esteller M, Popovici J, Cortés A, Del Portillo HA, Fernandez-Becerra C. Plasmodium vivax spleen-dependent protein 1 and its role in extracellular vesicles-mediated intrasplenic infections. Front Cell Infect Microbiol. 2024 May 17;14:1408451. DOI: 10.3389/fcimb.2024.1408451.