Epidemiological Link Research Articles

Exploring the impact of obesity and community health programs on enhancing endometrial cancer detection among low-income and native American women through a public health lens

This review examines the intricate relationship between obesity, endometrial cancer detection, and the role of community health programs, with a particular focus on low-income and Native American populations. Obesity is identified as a significant modifiable risk factor for endometrial cancer, disproportionately affecting vulnerable communities, which exacerbates existing health disparities. The paper explores the epidemiological link between obesity and endometrial cancer, highlighting disparities in detection and the compounded risks faced by underserved populations. It also reviews the effectiveness of public health initiatives aimed at improving cancer screening rates and obesity prevention among these groups. Despite the progress made through various community health programs, substantial gaps remain, particularly in ensuring culturally competent, accessible, and sustainable care. A lack of longitudinal studies evaluating the long-term impact of these programs on cancer detection and obesity management underscores the need for more robust research. Additionally, social, psychological, and systemic barriers continue to hinder screening uptake, further perpetuating health inequities. This review concludes by emphasizing the need for integrated public health approaches that combine obesity prevention with cancer screening, as well as policy reforms to enhance healthcare access and provider availability in underserved communities. Recommendations are provided for future research that addresses these gaps, with the goal of improving early detection and overall health outcomes for low-income and Native American women.

Investigating Transmission Patterns and Genome Sequencing of SARS-CoV-2 in University College Dublin

Abstract Background This study describes the investigation and management of multiple outbreaks of SARS-Cov2 during the second and third wave of the pandemic at University College Dublin, Ireland from September 2020 to September 2021. Methods Relevant data were gathered as part of the public health outbreak investigations led by the UCD Internal Covid Control Team (ICCT) in collaboration with the public health teams of the Health Service Executive (HSE). Results are presented for PCR (polymerase chain reaction) confirmed cases and their close contacts, reported to the UCD ICCT between September 2020 to September 2021. Results There were 214 cases notified to ICCT. Among these, 153 cases were in residence on-campus cases. 73 epidemiologically linked clusters identified, where the number of cases linked with each cluster varied between 1 to 27. Additional cases during this period had no obvious epidemiological link to the identified clusters. Of 902 close contacts with PCR test results, 31.5% (n = 284) tested positive. 77% (n = 219) self-reported with mild to moderately symptoms while 23% (n = 65) self-reported as asymptomatic. Retrospective Whole Genome Sequence (WGS) analysis was undertaken after the outbreaks had subsided. The test positive cases were grouped into 6 clusters, and it was shown that many of the apparent sporadic cases were included in these clusters. Conclusions The proportion of close contacts testing positive varied significantly throughout the pandemic, with testing policy and type of exposure having the greatest impact. Whole genome sequencing can give a better understanding of webs of transmission to complement epidemiological investigations. It is now possible to undertake sequencing in real time where it can make a contribution to outbreak control and resolution. Public Health professionals should become familiar with WGS and bioinformatics as useful tools in their armory for the control of all communicable diseases not only SARS-CoV-2. Key messages • Combined epidemiological investigations and Whole Genome Sequencing (WGS) provide crucial insights into campus COVID-19 outbreaks, guiding effective control measures. • WGS integration enhances understanding of transmission patterns, identifies clusters, and equips public health professionals with data-driven approaches for outbreak management beyond SARS-CoV-2.

Nonalcoholic fatty liver disease worsens cardiac repair after myocardial infarction

Abstract Background There is a strong epidemiological link between nonalcoholic fatty liver disease (NAFLD) and ischemic heart disease such as myocardial infarction (MI). Yet, a causal relationship between liver injury and post-MI cardiac repair remains to be established. Purpose NAFLD impairs post-MI myocardial repair processes. In particular, we hypothesized that the pathological liver could transmit deleterious signals shaping the inflammatory reaction in the infarcted milieu. Methods To characterize post-MI cardiac function and remodeling in three mouse models of liver damage mimicking different stages of NAFLD without cardiovascular (CV) risk factors : i) choline-deficient, L-amino-acid-defined, high fat diet (CDA-HFD) causing severe non-alcoholic steatohepatitis; ii) NEMOLPC-KO mice deficient for NF-κB in liver parenchymal cells, exhibiting liver inflammation and fibrosis, but mild steatosis; and ATGLLPC-KO animals deficient for Adipose Triglyceride Lipase in liver parenchymal cells displaying strong steatosis. Results In our three experimental models, liver damages were characterized by inflammation, steatosis and fibrosis but were not associated with metabolic syndrome. More interestingly, left ventricular ejection fraction were reduced by 1.2-fold, 1.3-fold and 1.3-fold in CDA-HFD, NEMOLPC-KO and ATGLLPC-KO male and female mice, respectively when compared to their respective controls, at 35 days post-MI (n=12-25 per group). NAFLD-induced cardiac dysfunction was not associated with worsen cardiac remodeling as infarct size, fibrosis and vascular density were not significantly affected. On the same note, flow cytometry experiments, at 7- and 14-days post-MI, showed no changes in the number or type of inflammatory cells, particularly that of cardiac resident macrophages, in CDAHFD, ATGLLPC-KO and NEMOLPC-KO mice. We next hypothesized that reduced left ventricular function could be induced by altered cardiomyocyte contractility. To corroborate this hypothesis, we isolated cardiomyocytes from hearts of infarcted mice with or without NAFLD and assessed cell contractility using IonOptix technology. Our preliminary results, in the CDAHFD model, showed that there was a reduction in contraction amplitude, defining by the ratio of the difference in sarcomere length during contraction/relaxation to the sarcomere length at the time of relaxation. The speed of contraction and relaxation were also decreased in CDAHFD mice compared with control animals. Conclusions NAFLD favors cardiac dysfunction post-MI. We now aim to identify molecular and cellular entities participating to such pathogenic dialogue between the dysfunctional liver and the infarcted heart.

‘Freeze the measles’: how to improve backward tracing with a new digital tool

Abstract Background A measles outbreak occurred in Tuscany, between January and April 2024. There were 37 cases (Incidence: 40,5 per million) with 32 cases (24 confirmed) in the Health District of Pisa. Even if bidirectional tracing showed a better effectiveness in pandemics, there aren’t ready-to-use standardized tools for backward tracing. Methods Pisa Public Health Unit created a digital tool based on a spreadsheet and called “Freeze the measles” which records measles cases and the locations where they passed through (hotspots). These were uploaded on a cloud shared with all the tracers. Hotspots have an expiry date of 21 days. Hotspots and home address case were plotted on a digital map. In a new investigation, tracers could find out if the case visited some hotspots before getting sick and check the distance between home address and hotspots, reducing recall bias. Every case was interviewed about 21 days before rash onset (backward) and plus or minus 4 days of rash onset (forward). The tool matched data to identify contacts and exposure. Results Since the index case wasn’t found, the first 5 unrelated cases were considered index cases for this outbreak. Second and third wave involved 17 cases. The tool allows to find an epidemiological link for 16 of them, while 1 case remained unrelated. A super-spreader was identified with 12 secondary cases occurred at hospital emergency room (7), at a near home minimarket (4) and in a large furniture store (1). In second and third waves, tool was able to link 94% of cases. 2 additional cases were imported. When the last hotspot became frozen without new cases occurring, the outbreak was considered ended. The outbreak lasted 33 days. Conclusions The “Freeze the measles” tool allows to identify transmission chains through an interactive map built on cases and their mobility. Key messages • Contact tracing needs an appropriate backward investigation to be more effective. • New digital tools as ‘Freeze the measles’ could improve preparedness and management of outbreaks.

Mediterranean Diet and Risk of Hip Fracture: A Systematic Review and Dose-Response Meta-Analysis.

Hip fractures are a major public health concern. Understanding their epidemiologic and biological links with diet and cardiovascular risk may have important implications for prevention. To assess the dose-response association of Mediterranean diet (MD) adherence with the risk of hip fracture. A systematic search was conducted in the PubMed, Scopus, and Web of Science databases for prospective studies. Search terms were "Mediterranean Diet" and "Fracture." Data were extracted from 8 studies, encompassing 15 cohorts that included 503 174 individuals. Methodological quality was assessed using the Risk of Bias in Nonrandomized Studies of Interventions. The "meta" and "dosresmeta" packages were used in R Studio Software. The results demonstrated that high and moderate MD adherence were associated with a reduced risk of hip fracture (relative risk [RR] = 0.71 [95% CI, 0.55-0.91]; and RR = 0.78[(95% CI, 0.65-0.93], respectively). The effect of the association was similar in men and women. The dose-response pattern of the association was linear: each point increase in MD adherence was associated with a 5.25% reduction in hip fracture risk. Adherence to MD is associated with a reduction in hip fracture risk, following a linear dose-response pattern. This supports the promotion of this dietary pattern for improving bone health. PROSPERO registration no. CRD42023402284.

Genomic Analysis of Aeromonas salmonicida ssp. salmonicida Isolates Collected During Multiple Clinical Outbreaks Supports Association with a Single Epidemiological Unit.

Outbreaks of furunculosis cause significant losses in salmonid aquaculture worldwide. With a recent rise in antimicrobial resistance, regulatory measures to minimize the use of antibiotics in animal husbandry, including aquaculture, have increased scrutiny and availability of veterinary medical products to control this disease in production facilities. In such a regulatory environment, the utility of autogenous vaccines to assist with disease prevention and control as a veterinary-guided prophylactic measure is of high interest to the producers and veterinary services alike. However, evolving concepts of epidemiological units and epidemiological links need to be considered during approval and acceptance procedures for the application of autogenous vaccines in multiple aquaculture facilities. Here, we present the results of solid-state nanopore sequencing (Oxford Nanopore Technologies, ONT) performed on 54 isolates of Aeromonas salmonicida ssp. salmonicida sampled during clinical outbreaks of furunculosis in different aquaculture facilities from Bavaria, Germany, from 2017 to 2020. All of the performed analyses (phylogeny, single nucleotide polymorphism and 3D protein modeling for major immunogenic proteins) support a high probability that all studied isolates belong to the same epidemiological unit. Simultaneously, we describe a cost/effective method of whole genome analysis with the usage of ONT as a viable strategy to study outbreaks of other pathogens in the field of aquatic veterinary medicine for the purpose of developing the best autogenous vaccine candidates applicable to multiple aquaculture establishments.

Identifying Candida auris transmission in a hospital outbreak investigation using whole-genome sequencing and SNP phylogenetic analysis.

Candida auris poses a global public health challenge, causing multiple outbreaks within healthcare facilities. Despite advancements in strain typing for various infectious diseases, a consensus on the genetic relatedness threshold for identifying C. auris transmission in local hospital outbreaks remains elusive. We investigated genetic variations within our local isolate collection using whole-genome-based single nucleotide polymorphism (SNP) phylogenetic analysis. A total of 74 C. auris isolates were subjected to whole-genome sequencing (WGS) and SNP phylogenetic analysis via the QIAGEN CLC Genomics Workbench. Isolates included known related strains from the same patient, strains from different hospitals, strains from our hospital patients with no epidemiological link, and 19 patient isolates from a recent C. auris outbreak. All but three isolates were identified to be Clade IV. By examining the genetic diversities of C. auris within patients and between patients, we identified a SNP variation range of 0-13 for identifying related isolates. During an outbreak investigation, utilizing this range, maximum likelihood phylogenetic analysis revealed two distinct clusters that aligned with the epidemiological links. Determining a SNP variation range to delineate genetic relatedness among isolates is crucial for the application of WGS and SNP phylogenetic analysis in identifying C. auris transmission during hospital outbreak investigations. The use of WGS SNP phylogenetic analysis via the CLC Genomics Workbench has emerged as a valuable method for typing C. auris in clinical microbiology laboratories.

Epidemiological trends of SARS-CoV-2 infections during pregnancy in Chicago

Abstract Background The epidemiology of SARS-CoV-2 has varied significantly across age groups, specifically children. Immune and physiologic changes in pregnancy can lead to increased susceptibility to infection. Pregnant people were at increased risk of severe COVID-19 infections and obstetric complications, particularly before vaccine availability. We investigated epidemiologic trends of SARS-CoV-2 cases in pregnant people over time compared to trends in the general population and various age subgroups. We hypothesized that rates of SAR-CoV-2 infection in pregnant people may show a similar pattern to children rather than nonpregnant adults. Methods Cases of pregnant persons with SARS-CoV-2 infection who delivered at Prentice Women’s Hospital (Chicago, IL) were identified through the electronic medical record (March 2020-November 2022). Prentice has ~12,000 births annually. Clinical data collection for SARS-CoV-2 cases included the date of positive test, maternal demographics, vaccination status, severity, and latency (days between SARS-CoV-2 infection and delivery). SARS-CoV-2 cases rates in Chicago (cases/100,000; total; age 0-17 years, ≥18 years) were obtained from the Chicago Department of Public Health. Monthly average SARS-CoV-2 rates were calculated to visualize trends over the study period using Microsoft Excel. Results A total of 3,474 SARS-CoV-2 cases in pregnancy were included in the final dataset; 497 cases were excluded from analyses due to incomplete data to pinpoint timing of infection. The median maternal age was 33 years (IQR 30-36) with a median latency of 72 days (IQR 22-143.75). Over half (2206) of pregnant persons received COVID-19 vaccination. In terms of timing, 514 people (15%) tested positive during their 1st trimester, 1017 (29%) in 2nd trimester, and 1943 (56%) in 3rd trimester. The trends of SARS-CoV-2 cases over time among pregnant persons coincide closely with trends among children in Chicago rather than adults [Figure 1]. A steep spike and higher SARS-CoV-2 rates were observed in pregnancy during the initial Omicron variant surge (December 2021-January 2022) and in April-July 2022, during which children also led case rates. Earlier in the pandemic, pregnant people and children were less affected than non-pregnant adults. Conclusion We observed an interesting trend of SARS-CoV-2 cases among pregnant persons aligning with rates in children in Chicago rather than adults. Possible explanations include: 1) pregnant people exercising an abundance of caution prior to vaccine availability and knowledge about COVID-19 in pregnancy and 2) epidemiologic link of maternal exposure to children. This information may inform public health strategies and effective precautions in future epidemics/pandemics to keep patients safe during pregnancy. Figure 1. Cases of SARS-CoV-2 in age and pregnancy subgroups in Chicago. Blue bars represent SARS-CoV-2 positive cases among pregnant people who later delivered at Prentice Women’s Hospital [left y-axis] March 2020-November 2022. Colored lines represent case rate (cases/100,000) in Chicago according to Chicago Department of Public Health data (yellow = total, purple = adults ≥18 years, red = children 0-17 years) [right y-axis].

Genomic epidemiology of Clostridioides difficile Sequence Type 35 reveals intraspecies and interspecies clonal transmission

ABSTRACT Clostridioides difficile sequence type (ST) 35 has been found in humans and animals worldwide. However, its genomic epidemiology and clonal transmission have not been explored in detail. In this study, 176 C. difficile ST35 isolates from six countries were sequenced. Genomic diversity, clonal transmission and epidemiological data were analyzed. Sporulation and virulence capacities were measured. Four ribotypes (RT) were identified including RT046 (97.2%), RT656 (1.1%), RT427 (0.6%), and RT AI-78 (1.1%). Phylogenetic analysis of 176 ST35 genomes, along with 50 publicly available genomes, revealed two distinctive lineages without time-, region-, or source-dependent distribution. However, the distribution of antimicrobial resistance genes differed significantly between the two lineages. Nosocomial and communal transmission occurred in humans with the isolates differed by ≤ two core-genome single-nucleotide polymorphism (cgSNPs) and clonal circulation was found in pigs with the isolates differed by ≤ four cgSNPs. Notably, interspecies clonal transmission was identified among three patients with community acquired C. difficile infection and pigs with epidemiological links, differed by ≤ nine cgSNPs. Toxin B (TcdB) concentrations were significantly higher in human isolates compared to pig isolates, and ST35 isolates exhibited stronger sporulation capacities than other STs. Our study provided new genomic insights and epidemiological evidence of C. difficile ST35 intraspecies and interspecies clonal transmission, which can also be facilitated by its strong sporulation capacity.

Genomic Surveillance for Enhanced Healthcare Outbreak Detection and Control.

Current methods are insufficient alone for outbreak detection in hospitals. Real-time genomic surveillance using offers the potential to detect otherwise unidentified outbreaks. We initiated and evaluated the Enhanced Detection System for Healthcare-associated Transmission (EDS-HAT), a real-time genomic surveillance program for outbreak detection and mitigation. This study was conducted at UPMC Presbyterian Hospital from November 2021 to October 2023. Whole genome sequencing (WGS) was performed weekly on healthcare-associated clinical bacterial isolates to identify otherwise undetected outbreaks. Interventions were implemented in real-time based on identified transmission. A clinical and economic impact analysis was conducted to estimate infections averted and net cost savings. There were 3,921 bacterial isolates from patient healthcare-associated infections that underwent WGS, of which 476 (12.1%) clustered into 172 outbreaks (size range 2-16 patients). Of the outbreak isolates, 292 (61.3%) had an identified epidemiological link. Among the outbreaks with interventions, 95.6% showed no further transmission on the intervened transmission route. The impact analysis estimated that, over the two-year period, 62 infections were averted, with gross cost savings of $1,011,146, and net savings of $695,706, which translates to a 3.2-fold return on investment. Probabilistic sensitivity analysis showed EDS-HAT was cost-saving and more effective in 98% of simulations. Real-time genomic surveillance enabled the rapid detection and control of outbreaks in our hospital and resulted in economic benefits and improvement in patient safety. This study demonstrates the feasibility and effectiveness of integrating genomic surveillance into routine infection prevention practice, offering a paradigm shift in healthcare outbreak detection and control.

Outbreak-associated Salmonella Baildon found in wastewater demonstrates how sewage monitoring can supplement traditional disease surveillance.

Non-typhoidal Salmonella is a common cause of gastroenteritis worldwide, but current non-typhoidal Salmonella surveillance is suboptimal. Here, we evaluated the utility of wastewater monitoring to enhance traditional surveillance for this foodborne pathogen. In June 2022, we tested raw sewage collected twice a week from two treatment plants in central Pennsylvania for non-typhoidal Salmonella and characterized isolates using whole-genome sequencing. We recovered 43 Salmonella isolates from wastewater samples, differentiated by genomic analysis into seven serovars: 16 Panama (37.2%), 9 Senftenberg (20.9%), 8 Baildon (18.6%), and 3 or fewer of four other serovars. We assessed genetic relatedness and epidemiologic links between these wastewater isolates with those from patients with salmonellosis. All S. Baildon isolates from wastewater were genetically similar to those associated with a known contemporaneous salmonellosis outbreak. S. Baildon from wastewater and 42 outbreak-related isolates in the national outbreak detection database had the same core genome multilocus sequence typing, and outbreak code differed by zero or one single polynucleotide polymorphism. One of the 42 outbreak-related isolates was obtained from a patient residing in the wastewater sample collection catchment area, which serves approximately 17000 people. S. Baildon is a rare serovar (reported in <1% cases nationally, over five years). Our study underscores the value of monitoring sewage from a defined population to supplement traditional surveillance methods for the evidence of Salmonella infections and to determine the extent of outbreaks.IMPORTANCEDuring the COVID-19 pandemic, monitoring for SARS-CoV-2 in wastewater was highly effective in identifying the variants of concern earlier than clinical surveillance methods. Here, we show that monitoring domestic sewage can also augment traditional reporting of foodborne illnesses to public health authorities. Our study detected multiple Salmonella enterica serovars in samples from two wastewater treatment plants in central Pennsylvania. Using whole-genome sequencing, we demonstrated that the isolates of variant S. Baildon clustered with those from a foodborne salmonellosis outbreak that occurred in a similar time frame. Cases were primarily from Pennsylvania, and one individual lived within the wastewater treatment catchment area. This study highlights the effectiveness of domestic sewage testing as a proactive public health strategy to track and respond to infectious disease outbreaks.

Exploring the Link Between Genetic Predictors of Cardiovascular Disease and Psoriasis.

The epidemiological link between immune-mediated diseases (IMIDs) and cardiovascular disease has often been attributed to systemic inflammation. However, the direction of causality and the biological mechanisms linking cardiovascular disease with IMIDs are incompletely understood. Given the robust epidemiological association and the growing body of supportive mechanistic evidence, psoriasis is an exemplary IMID model for exploring this relationship. To assess the bidirectional relationships between genetic predictors of psoriasis and the 2 major forms of cardiovascular disease, coronary artery disease (CAD) and stroke, and to evaluate the association between genetic predictors of cardiovascular disease with 9 other IMIDs. This was a genetic association study using mendelian randomization (MR), a powerful genetic tool to help distinguish causation from associations observed in epidemiological studies, to provide supportive evidence for causality between traits. The study conducted 2-sample MR analyses using summary-level data from large-scale genome-wide association meta-analysis studies (GWAS) for each trait. The analysis focused on individuals of European descent from GWAS meta-analyses, involving CAD, stroke, psoriasis, and 9 other IMIDs. Data were analyzed from January 2023 to May 2024. Genetic predictors of CAD, stroke, psoriasis, and 9 other IMIDs. The primary outcomes were the associations of genetic predictors of CAD and stroke with the risk of psoriasis and 9 other IMIDs, determined using inverse-variance weighted (IVW) MR estimates. This study included 181 249 cases and 1 165 690 controls with CAD, 110 182 cases and 1 503 898 controls with stroke, 36 466 cases and 458 078 controls with psoriasis, for a total of approximately 3 400 000 individuals, and 9 other IMIDs. In contrast to previous assumptions, genetic predictors of psoriasis were found to have no association with CAD or stroke. In the reverse direction, genetic predictors of both CAD (MR estimate IVW odds ratio [OR], 1.07; 95% CI, 1.04-1.10; P = .003) and stroke (IVW OR, 1.22; 95% CI, 1.05-1.41; P = .01) were found to have risk-increasing associations with psoriasis. Adjusting for stroke rendered the associations of genetically predicted CAD with psoriasis risk nonsignificant (and vice versa), suggesting that a shared effect underlying genetic risk for CAD and stroke associates with increased psoriasis risk. No risk-increasing associations were observed for genetic predictors of cardiovascular disease with other common IMIDs, including rheumatoid arthritis and inflammatory bowel disease. Findings of this mendelian randomization study indicate that genetic predictors of cardiovascular disease were associated with increased psoriasis risk with no reciprocal effect or association with other IMIDs. Elucidating mechanisms underpinning this association could lead to novel therapeutic approaches in both diseases.

Multidrug-resistant tuberculosis clusters and transmission in Taiwan: a population-based cohort study.

Multidrug-resistant tuberculosis (MDR-TB) remains a challenge in the TB program of Taiwan, where 0.5% of new cases and 2.1% of previously treated cases were resistant to at least rifampin (RIF) and isoniazid (INH). Since >80% of our MDR-TB are new cases, genotyping of MDR Mycobacterium tuberculosis is implemented to facilitate contact investigation, cluster identification, and outbreak delineation. This is a population-based retrospective cohort study analyzing MDR-TB cases from 2019 to 2022. Whole genome sequencing (WGS) was performed using the Illumina MiSeq and analyzed using the TB Profiler. A single nucleotide polymorphism (SNP) threshold of ≤ 12 and phylogenetic methods were used to identify putative transmission clusters. An outbreak was confirmed using genomic data and epidemiologic links. Of the 297 MDR-TB cases, 246 (82.8%), 45 (15.2%), and 6 (2.0%) were simple MDR, extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), respectively. The sublineage 2.2 modern Beijing was the predominant (48.8%) MDR-TB strain in Taiwan. Phylogenetic analysis identified 25.3% isolates in 20 clusters, with cluster sizes ranging from 2 to 13 isolates. Nevertheless, only 2 clusters, one household and one community, were confirmed as outbreaks. In this study, we found that males had a higher risk of MDR-TB transmission compared to females, and those infected with the sublineage 2.1-proto-Beijing genotype isolates were at a higher risk of transmission. Furthermore, 161 (54.2%) isolates harbored compensatory mutations in the rpoC and non-rifampicin resistant determinant region (non-RRDR) of the rpoB gene. MDR-TB strains containing rpoB S450L and other compensatory mutations concurrently were significantly associated with clusters, especially the proto-Beijing genotype strains with the compensatory mutation rpoC E750D or the modern Beijing genotype strains with rpoC D485Y/rpoC E1140D. Routine and continuous surveillance using WGS-based analysis is recommended to warn of risks and delineate transmission clusters of MDR-TB. We proposed the use of compensatory mutations as epidemiological markers of M. tuberculosis to interrupt putative MDR-TB transmission.

Phenotype wide association study links bronchopulmonary dysplasia with eosinophilia in children

Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Despite this, genetic drivers of BPD are poorly understood. The objective of this study is to better understand the impact of single nucleotide polymorphisms (SNPs) previously associated with BPD by examining associations with other phenotypes. We drew pediatric subjects from the biorepository at the Center for Applied Genomics to identify associations between these SNPs and 2,146 imputed phenotypes. Methylation data, external cohorts, and in silico validation methods were used to corroborate significant associations. We identified 60 SNPs that were previously associated with BPD. We found a significant association between rs3771150 and rs3771171 and mean eosinophil percentage in a European cohort of 6,999 patients and replicated this in external cohorts. Both SNPs were also associated with asthma, COPD and FEV1/FVC ratio. These SNPs displayed associations with methylation probes and were functionally linked to ST2 (IL1RL1) levels in blood and lung tissue. Our findings support a genetic justification for the epidemiological link between BPD and asthma. Given the well-established link between ST2 and type 2 inflammation in asthma, these findings provide a rationale for future studies exploring the role of type 2 inflammation in the pathogenesis of BPD.

Increased levels of anti-Encephalitozoon intestinalis antibodies in patients with colorectal cancer.

The prevalence of microsporidiosis in the general population, or within specific groups of individuals/patients, is largely underestimated. The absence of specific seroprevalence tools limits knowledge of the epidemiology of these opportunistic pathogens, although known since the 1980s. Since microsporidia hijack the machinery of its host cell and certain species multiply within intestinal cells, a potential link between the parasite and colorectal cancer (CRC) has been suggested. To explore a potential epidemiological link between microsporidia and CRC, we evaluated the seroprevalence of Encephalitozoon intestinalis among CRC patients and healthy subjects using ELISA assays based on two recombinant proteins, namely rEiPTP1 and rEiSWP1, targeting polar tube and spore wall proteins. ELISA were performed in 141 CRC patients and 135 healthy controls. Patients with CRC had significantly higher anti-rEiPTP1 IgG levels than subjects in the control group. Anti-rEiPTP1 IgG, anti-rEiSWP1 IgG and anti-rEiPTP1 IgA levels were significantly increased among men with CRC compared to healthy men. Women with CRC who had died had higher rEiSWP1 IgG levels than those who were still alive. These higher antibody levels against microsporidia in patients with CRC suggest a relationship between microsporidia and pathophysiology of CRC.

Transmission of tuberculosis in rural Henan, China: a prospective population-based genomic spatial epidemiological study

ABSTRACT The incidence of tuberculosis (TB) has declined more slowly in rural than urban areas in China, and data on the patterns of transmission and the high-risk populations in rural areas remains scarce. We conducted a population-based study of culture-positive pulmonary TB patients diagnosed in rural Linzhou City, Henan Province from July 2018 to February 2023. Genomic clusters were defined based on whole-genome sequencing and risk factors for clustering were identified by logistic regression. Transmission events were inferred with phybreak and transmission links were sought through epidemiological investigation of clustered patients. Logistic regression was used to explore the relationship between genomic differences of patient isolates and geographical distances of patient residences. Spatial hotspots were defined using kernel density estimation. Of 455 culture-positive patients, 430 were included in the final analysis. Overall, 192 (44.7%,192/430) patients were grouped into 49 clusters. Clusters containing ≥5 patients accounted for 18.4% (9/49) of the clusters and clustering was highest in student patients. No super-spreaders were detected. Confirmed epidemiologic links were identified for only 18.2% of clustered patients. The clustering risk decreased rapidly with increasing distances between patient residences, but 77.6% of clustered patient pairs lived ≥5.0 km apart. Both the Central Subdistrict and Rencun Township were identified as hotspots for TB transmission. Recent transmission appears to be an important driver of the TB burden in Linzhou. The formulation of effective strategies to reduce TB incidence in rural areas will require further studies to identify high-risk populations and venues where local inhabitants congregate and transmit the infection.

Tracking Measles and Rubella Elimination Progress-World Health Organization African Region, 2022-2023.

Measles or rubella elimination is verified when endemic transmission of the corresponding virus has been absent for over 36 months in a defined area, in the presence of a well-performing surveillance system. This report updates the progress by 47 countries in the WHO African Region towards the goal of attaining verification of measles and rubella elimination in at least 80% of the countries of the region by 2030. We reviewed the WHO-UNICEF vaccination coverage estimates for the first and second doses of measles- and measles-rubella-containing vaccines, as well as the available coverage data for measles supplementary immunization activities, during 2022-2023. We also reviewed the measles-surveillance performance and analyzed the epidemiological trends of measles and rubella as reported in the case-based surveillance database. The WHO-UNICEF estimates of first measles vaccine dose (MCV1) and second measles vaccine dose (MCV2) coverage for the African Region for 2022 were 69% and 45%, respectively. Rubella-containing vaccines have been introduced in the routine immunization program in 32 of 47 (68%) countries as of the end of 2022, with no introductions during 2023. In 2022 and 2023, a total of 144,767,764 children were vaccinated in the region with measles or MR vaccines in 24 countries through 32 mass vaccination campaigns. The administrative coverage target of 95% was reached in only 15 (49%) of the 32 vaccination campaigns. In 2023, a total of 125,957 suspected cases of measles were reported through the case-based surveillance system, and 73,625 cases (58%) were confirmed to be measles, either by laboratory testing, by epidemiological linkage, or based on clinical compatibility. A total of 4805 confirmed rubella cases were reported, though this total represents substantial under-ascertainment. The regional incidence of measles was 60.3 cases per million population. Twenty-six countries (55%) met the targets for the two principal surveillance system performance-monitoring indicators. No country in the region has attained the verification of measles or rubella elimination as of the end of 2023. Addressing systemic problems with routine immunization and using tailored approaches to reach unvaccinated children can contribute to progress towards measles and rubella elimination. In addition, periodic and timely high-quality preventive SIAs remain a critical programmatic strategy to reach unvaccinated children.

HIV, HCV and HIV-HCV Coinfections in the General Population versus Inmates from Romania.

The objective of this study was to analyze the epidemiological links of the human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV-HCV coinfections to less studied types of transmission in certain populations. We performed an observational, prospective study on 903 patients aged between 15-87 years who took part in the Open Test Project. They were divided in two subgroups: general population vs. individuals from prisons who were questioned about multiple risk factors. A chi-square independence test was used to establish correlations between risk factors and results of screening tests. Logistic regression was used to calculate the probability of a reactive screening test based on each independent risk factor and age. HIV was very strongly associated with unprotected sexual intercourse with HIV-positive partners (the strongest association), unprotected sexual intercourse with sex workers, newly diagnosed sexually transmitted diseases (STDs), intravenous drug users (IDUs) and sharing injecting materials. In the case of HCV reactive tests, very strong associations have been established with IDUs (the strongest association), unprotected sex with IDUs and sharing injecting materials. Our study indicates the need for implementing targeted public health programs, tailored to the local epidemiology that can ultimately lead to micro-elimination of hepatitis and HIV infections in this area.

Analysis of management factors influencing Anaplasma marginale transmission

The aim of this study was to identify factors that play a key role in the epidemiology of bovine anaplasmosis by adapting a model primarily developed for cattle babesiosis. A cross-sectional observational study was conducted to study the proportion of calf herds in endemic stability/instability for A. marginale in a semi-arid area of Argentina. The A. marginale inoculation rate (h) was calculated from age-specific seroprevalence using double-antigen sandwich ELISA in 58 herds of 4.5–8.5-month–old calves. Herds were considered to be in endemic instability (EI) at h < 0.005 and, therefore, at risk of anaplasmosis outbreaks. A generalized linear model was performed to explore husbandry practices associated with differences in A. marginale transmission. Additionally, spatial clustering of herds with the same immunological status was analyzed using spatial scan statistics (SatScan, Bernoulli model). Spearman's correlation was used to explore a possible association between A. marginale h and Babesia bovis and B. bigemina h (data obtained in previous works). Almost half (43 %) of the herds were in the EI zone for A. marginale. Calves raised under forage combinations had a greater risk of being in EI (OR = 5.41, CI95 %OR = 1.43–20.41) than those reared exclusively on permanent pastures, where cattle density is higher (P = 0.01). Moreover, calves from herds treated only with pyrethroids to control ticks had more chances of being in EI (OR = 4.16, CI95 %OR = 1.12–15.38) than calves from herds receiving different acaricide combinations (P = 0.03). Calves from herds subjected to more than two treatments against Haematobia irritans had higher odds for EI (OR = 5.69, CI95 %OR = 1.24–26.11) than those from herds using fewer than two treatments (P = 0.02). The spatial analysis revealed no spatial clustering of the immune status of the herds (P = 0.67 and P = 0.74 for low and high incidence rates, respectively). A significant variation between farms was observed in A. marginale h (CV = 90.38 %). The correlation analysis revealed a strong epidemiological link of A. marginale h with B. bovis h (Rho=0.794, P<0.001) and B. bigemina h (Rho=0.839, P<0.001). Given that R. microplus is the only vector of B. bovis and B. bigemina in the region, the results of this work strongly suggest an active and significant role of R. microplus in the transmission of A. marginale.

Abstract Mo087: A shared gene regulatory network underlies atrial pathophysiology in atrial fibrillation and heart failure mouse models

Atrial fibrillation and heart failure have a strong epidemiologic link, however the mechanisms underlying their mutual risk remain unresolved. We revealed a remarkable correlation of both gene expression and genomic features in the atria of atrial fibrillation (AF, Tbx5 deletion) and heart failure (HF, TAC banding) mouse models. Tbx5 - and TAC-dependent gene expression in the left atria demonstrated a correlation coefficient of 0.8. Remarkably, 118 transcription factors were dysregulated in both models and 109 shared directionality in both cases, suggesting a shared transcriptional response. Differential non-coding transcriptional profiling to identify altered cis -regulatory regions demonstrated a correlation coefficient of 0.81 between the models, including ~1,800 shared differentially expressed ncRNAs, of which ~400 emanated from accessible candidate regulatory elements. Integration with chromatin architecture allowed identification of lineage-specific shared AF and HF gene regulatory networks. A TBX5-driven ncRNA-defined regulatory element drives expression of Klf15, an inhibitor of cardiac hypertrophy, in the wild-type cardiomyocytes that is downregulated in both mouse and human heart failure. Whereas in mouse HF and AF a disease-specific ncRNA-defined regulatory element is upregulated with Sox9 , an important transcriptional regulator of fibroblast activation. This work indicates that AF and HF initiate a shared atrial pathological genomic response, including downregulation of a wild-type GRN that normally prevents injury-based disease signaling and upregulation of a disease GRN that promotes atrial remodeling, uncovering a common genomic underpinning of atrial disease.