The effect of environmental degradation and land use change on malaria re-emergence in south Venezuela: a spatiotemporal modelling study

Background: Malaria transmission is highly dependent on environmental conditions. The association between climatic variables and malaria transmission is well established, but the interaction between variations in climate and land use change, such as deforestation, is less well understood. Earth observation data provide a valuable and accessible resource to investigate these environment–malaria associations, in particular where little ground truth data are available. Progress towards malaria elimination in Latin America is being hindered by a surge of cases in Venezuela, a country that accounted for 53% of cases in the region in 2019. The country's economic and political crisis has fuelled economic migration to gold mining areas in the south, where extraction activities are expanding malaria vector habitats and sustaining disease transmission. Methods: In this spatiotemporal modelling study, we used multisource Earth observation data, including meteorological, land use change, and socioeconomic factors, and data on mining activity, to investigate how changes in the ecological landscape might have facilitated increases in the incidence of malaria in the past 20 years. We modelled spatiotemporal malaria case data for 1996–2016 using a Bayesian hierarchical mixed-model framework for Bolívar state in Venezuela, a malaria foci where approximately 60% of national cases occur annually. We examined how mining activities were associated with malaria hotspots and also considered the potential effects of climate variation, seasonality, and spatial dependency structures. Findings: We found that malaria risk was increased in mining hotspots, which were important in sustaining transmission in Bolívar state. We also found that the effect of temperature and rainfall variation differed depending on the level of deforestation in Bolívar, where the increased risk of malaria with temperature was greatest in areas that were more deforested. Interpretation: Our findings provide important evidence of environmentally driven re-emergence of malaria and highlight the advantages of using Earth observation data for understanding malaria dynamics in areas with sparse or incomplete data records

Climate services for health: From global observations to local interventions.

Despite the wealth of available climate data available, there is no consensus on the most appropriate product choice for health impact modelling and how this influences downstream climate-health decisions. We discuss challenges related to product choice, highlighting the importance of considering data biases and co-development of climate services between different sectors

The Relative Role of Climate Variation and Control Interventions on Malaria Elimination Efforts in El Oro, Ecuador: A Modeling Study

Malaria is a vector-borne disease of significant public health concern. Despite widespread success of many elimination initiatives, elimination efforts in some regions of the world have stalled. Barriers to malaria elimination include climate and land use changes, such as warming temperatures and urbanization, which can alter mosquito habitats. Socioeconomic factors, such as political instability and regional migration, also threaten elimination goals. This is particularly relevant in areas where local elimination has been achieved and consequently surveillance and control efforts are dwindling and are no longer a priority. Understanding how environmental change, impacts malaria elimination has important practical implications for vector control and disease surveillance strategies. It is important to consider climate change when monitoring the threat of malaria resurgence due to socioeconomic influences. However, there is limited assessment of how the combination of climate variation, interventions and socioeconomic pressures influence long-term trends in malaria transmission and elimination efforts. In this study, we used Bayesian hierarchical mixed models and malaria case data for a 29-year period to disentangle the impacts of climate variation and malaria control efforts on malaria risk in the Ecuadorian province of El Oro, which achieved local elimination in 2011. We found shifting patterns of malaria between rural and urban areas, with a relative increase of Plasmodium vivax in urbanized areas. Minimum temperature was an important driver of malaria seasonality and the association between warmer minimum temperatures and malaria incidence was greater for Plasmodium falciparum compared to P. vivax malaria. There was considerable heterogeneity in the impact of three chemical vector control measures on both P. falciparum and P. vivax malaria. We found statistically significant associations between two of the three measures [indoor residual spraying (IRS) and space spraying] and a reduction in malaria incidence, which varied between malaria type. We also found environmental suitability for malaria transmission is increasing in El Oro, which could limit future elimination efforts if malaria is allowed to re-establish. Our findings have important implications for understanding environmental obstacles to malaria elimination and highlights the importance of designing and sustaining elimination efforts in areas that remain vulnerable to resurgence

Synergies between environmental degradation and climate variation on malaria re-emergence in southern Venezuela: a spatiotemporal modelling study.

BACKGROUND: Environmental degradation facilitates the emergence of vector-borne diseases, such as malaria, through changes in the ecological landscape that increase human-vector contacts and that expand vector habitats. However, the modifying effects of environmental degradation on climate-disease relationships have not been well explored. Here, we investigate the rapid re-emergence of malaria in a transmission hotspot in southern Venezuela and explore the synergistic effects of environmental degradation, specifically gold-mining activity, and climate variation. METHODS: In this spatiotemporal modelling study of the 46 parishes of the state of Bolívar, southeast Venezuela, we used data from the Venezuelan Ministry of Health including population data and monthly cases of Plasmodium falciparum malaria and Plasmodium vivax malaria between 1996 and 2016. We estimated mean precipitation and temperature using the ERA5-Land dataset and used monthly anomalies in sea-surface temperature as an indicator of El Niño events between 1996 and 2016. The location of suspected mining sites in Bolívar in 2009, 2017, and 2018 were sourced from the Amazon Geo-Referenced Socio-Environmental Information Network. We estimated measures of cumulative forest loss and urban development by km2 using annual land cover maps from the European Space Agency Climate Change Initiative between 1996 and 2016. We modelled monthly cases of P falciparum and P vivax malaria using a Bayesian hierarchical mixed model framework. We quantified the variation explained by mining activity before exploring the modifying effects of environmental degradation on climate-malaria relationships. FINDINGS: We observed a 27% reduction in the additional unexplained spatial variation in incidence of P falciparum malaria and a 23% reduction in P vivax malaria when mining was included in our models. The effect of temperature on malaria was greater in high mining areas than low mining areas, and the P falciparum malaria effect size at temperatures of 26·5°C (2·4 cases per 1000 people [95% CI 1·78-3·06]) was twice as high as the effect in low mining areas (1 case per 1000 people [0·68-1·49]). INTERPRETATION: We show that mining activity in southern Venezuela is associated with hotspots of malaria transmission. Increased temperatures exacerbated malaria transmission in mining areas, highlighting the need to consider how environmental degradation modulates climate effect on disease risk, which is especially important in areas subjected to rapidly rising temperatures and land-use change globally. Our findings have implications for the progress towards malaria elimination in the Latin American region. Our findings are also important for effectively targeting timely treatment programmes and vector-control activities in mining areas with high rates of malaria transmission. FUNDING: Biotechnology and Biological Sciences Research Council, Royal Society, US National Institutes of Health, and Global Challenges Research Fund. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

TGFBR1 Intralocus Epistatic Interaction as a Risk Factor for Colorectal Cancer

In colorectal cancer (CRC), an inherited susceptibility risk affects about 35% of patients, whereas high-penetrance germline mutations account for <6% of cases. A considerable proportion of sporadic tumors could be explained by the coinheritance of multiple low-penetrance variants, some of which are common. We assessed the susceptibility to CRC conferred by genetic variants at the TGFBR1 locus. We analyzed 14 polymorphisms and the allele-specific expression (ASE) of TGFBR1 in 1025 individuals from the Spanish population. A case-control study was undertaken with 504 controls and 521 patients with sporadic CRC. Fourteen polymorphisms located at the TGFBR1 locus were genotyped with the iPLEX Gold (MassARRAY-Sequenom) technology. Descriptive analyses of the polymorphisms and haplotypes and association studies were performed with the SNPator workpackage. No relevant associations were detected between individual polymorphisms or haplotypes and the risk of CRC. The TGFBR1*9A/6A polymorphism was used for the ASE analysis. Heterozygous individuals were analyzed for ASE by fragment analysis using cDNA from normal tissue. The relative level of allelic expression was extrapolated from a standard curve. The cutoff value was calculated with Youden's index. ASE was found in 25.4% of patients and 16.4% of controls. Considering both bimodal and continuous types of distribution, no significant differences between the ASE values of patients and controls were identified. Interestingly, a combined analysis of the polymorphisms and ASE for the association with CRC occurrence revealed that ASE-positive individuals carrying one of the most common haplotypes (H2: 20.7%) showed remarkable susceptibility to CRC (RR: 5.25; 95% CI: 2.547–5.250; p<0.001) with a synergy factor of 3.7. In our study, 54.1% of sporadic CRC cases were attributable to the coinheritance of the H2 haplotype and TGFBR1 ASE. These results support the hypothesis that the allelic architecture of cancer genes, rather than individual polymorphisms, more accurately defines the CRC risk

The Streptococcus pneumoniae Pilus-1 Displays a Biphasic Expression Pattern

The Streptococcus pneumoniae pilus-1 is encoded by pilus islet 1 (PI-1), which has three clonal variants (clade I, II and III) and is present in about 30% of clinical pneumococcal isolates. In vitro and in vivo assays have demonstrated that pilus-1 is involved in attachment to epithelial cells and virulence, as well as protection in mouse models of infection. Several reports suggest that pilus-1 expression is tightly regulated and involves the interplay of numerous genetic regulators, including the PI-1 positive regulator RlrA. In this report we provide evidence that pilus expression, when analyzed at the single-cell level in PI-1 positive strains, is biphasic. In fact, the strains present two phenotypically different sub-populations of bacteria, one that expresses the pilus, while the other does not. The proportions of these two phenotypes are variable among the strains tested and are not influenced by genotype, serotype, growth conditions, colony morphology or by the presence of antibodies directed toward the pilus components. Two sub-populations, enriched in pilus expressing or not expressing bacteria were obtained by means of colony selection and immuno-detection methods for five strains. PI-1 sequencing in the two sub-populations revealed the absence of mutations, thus indicating that the biphasic expression observed is not due to a genetic modification within PI-1. Microarray expression profile and western blot analyses on whole bacterial lysates performed comparing the two enriched sub-populations, revealed that pilus expression is regulated at the transcriptional level (on/off regulation), and that there are no other genes, in addition to those encoded by PI-1, concurrently regulated across the strains tested. Finally, we provide evidence that the over-expression of the RrlA positive regulator is sufficient to induce pilus expression in pilus-1 negative bacteria. Overall, the data presented here suggest that the observed biphasic pilus expression phenotype could be an example of bistability in pneumococcus

Genetic modifiers of CHEK2*1100delC-associated breast cancer risk

Purpose: CHEK2*1100delC is a founder variant in European populations that confers a two-to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Methods: Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. Results: The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.212.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average. Conclusion: Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Peer reviewe

Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(−07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10(−05)). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci

Smoking cessation opportunities in severe mental illness (tobacco intensive motivational and estimate risk — TIMER—): study protocol for a randomized controlled trial

There is an increased risk of premature death in people with severe mental illness (SMI). Respiratory disorders and cardiovascular disease are leading causes of increased mortality rates in these patients, and tobacco consumption remains the most preventable risk factor involved. Developing new tools to motivate patients towards cessation of smoking is a high priority. Information on the motivational value of giving the lung age and prevention opportunities is unknown in this high-risk population. In the context of community care, screening and early detection of lung damage could potentially be used, together with mobile technology, in order to produce a prevention message, which may provide patients with SMI with a better chance of quitting smoking.This study receives funding by the Spanish Ministry of Economy, Industry and Competitiveness, Instituto Carlos III (FIS PI16/00802)