Transmission Patterns Research Articles

Borealpox Virus: a Comprehensive Review of its Emergence and Global Recommendations

The emergence of the Borealpox virus (BRPV), formerly known as the Alaskapox virus (AKPV), in 2015 poses an intriguing scientific challenge. Despite being first discovered in Alaska, BRPV is a potential global threat, and reports of instances have raised questions about how serious it can be; especially in those with impaired immune systems. The unique characteristics of BRPV have been clarified through genomic characterization, providing insight into its evolutionary lineage and transmission dynamics. A recent death linked to BRPV highlights the difficulties presented by newly developing infectious illnesses, particularly for individuals who are already at risk. The implications of BRPV for public health call for all-encompassing management approaches; such as creating efficient treatments and customized interventions for various clinical presentations. Research and surveillance initiatives are vital for comprehending ecological reservoirs and patterns of transmission. Additionally, biosafety regulations and immunization programs are critical for controlling outbreaks and reducing the worldwide effects of BRPV. Prioritizing vaccination drive approaches, implementing stringent infection control measures, and reinvigorating disease surveillance systems are imperative for preventing BRPV. In addition, enhancing the training of frontline healthcare professionals and implementing the One Health concept are crucial measures that foster robust cooperation and adaptability, while confronting new public health concerns. A comprehensive review of the emergence and consequences of the Borealpox virus is necessary to direct future investigations and global public health campaigns. By utilizing interdisciplinary approaches and promoting global collaboration, we may successfully alleviate the danger presented by BRPV and protect public health across borders.

Insights into the molecular network characteristics of major HIV-1 subtypes in developed Eastern China: a study based on comprehensive molecular surveillance data.

This study aimed to conduct a comprehensive molecular epidemiology study of major HIV-1 subtypes in developed Eastern China (Zhejiang Province). Plasma samples and epidemiological information were collected from 4180 newly diagnosed HIV-1 positive patients in Zhejiang Province in 2021. Pol sequences were obtained to determine the subtypes via multiple analytical tools. HIV-1 molecular networks were constructed on the basis of genetic distances to analyze transmission patterns among major subtypes. Furthermore, the birth-death skyline (BDSKY) model was utilized to estimate the transmission risks associated with large clusters (LCs). In 4180 patients, 3699 (88.49%) pol sequences were successfully obtained and classified into four subtype groups. In the networks under an optimal genetic distance of 0.01 substitutions/site, the majority of links (74.52%, 1383/1856) involved individuals within the same city, highlighting the predominant role of local transmission in driving the HIV-1 epidemic. In the CRF07_BC, CRF01_AE, and others/URFs networks, men who have sex with men (MSM) were the primary sexual transmission population, with the younger MSM group (< 30 years old) exhibiting higher linkage frequencies. Within the CRF08_BC network, 93.98% of individuals were infected primarily through heterosexual contact and had a significantly greater risk of localized clustering than other subtypes did. Moreover, fifteen identified LCs were predominantly transmitted through commercial heterosexual contact (CHC), exhibiting localized clustering and high potential for sustained diffusion. Overall, our findings reveal a diverse and heterogeneous distribution of HIV-1 subtypes in Zhejiang Province, with noticeable variations in hotspots across different geographic areas and populations.

Characterizing HIV-1 transmission by genetic cluster analysis among newly diagnosed patients in the China-Myanmar border region from 2020 to 2023

ABSTRACT Cluster analysis of HIV sequence can provide insights into viral transmission patterns in border regions. This study aims to illuminate the HIV-1 subtype distribution and transmission dynamics among newly diagnosed individuals in Dehong prefecture, a region along the China-Myanmar border. Among 948 participants with pol gene sequences, 36 HIV-1 subtypes were identified, with URFs (18.8%, 178/948) being the dominant strain, followed by CRF01_AE (18.5%, 175/948) and CRF07_BC (10.9%, 103/948). Additionally, 287 sequences (30.3%, 287/948) were grouped into 91 clusters, 31 of which contained both Chinese and Burmese individuals. Multivariable logistic regression indicated that men who have sex with men (MSM), CD4 + cell count of 200∼499 cells/μl, and 500 cells/μl and above, and CRF01_AE were risk factors for entering the network. Through Chord diagram, we found frequent transmission relationships among heterosexual China male group, especially those over 35 years of age. Additionally, the correlation between heterosexual Myanmar female group and heterosexual China male group among cross-risk groups deserved to be emphasized. Furthermore, the network exhibited a growing trend over time, with the largest active transmission cluster identified in Ruili county. In conclusion, the HIV-1 subtype landscape in Dehong has become increasingly complex, and the region has faced risks of transmission from both domestic and international sources. Targeted intervention strategies should be implemented for MSM, heterosexual Chinese middle-aged and elderly men, and heterosexual Burmese young adults to mitigate these risks. These findings provided evidence-based insights for local government to formulate coordinated transnational intervention approaches.

Prevalence of SARS-CoV-2 and Associated Factors Among Individuals During the Second Wave of Infection in Yaounde, Cameroon

Background: The first case of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in Cameroon on March 5, 2020, in Yaounde. Since then, viral propagation occurred nationwide with a higher burden in urban settings and limited evidence on transmission patterns. Our objective was to determine the prevalence of SARS-CoV-2 and associated factors among individuals in urban settings of Cameroon during the second wave of the pandemic. Methods: a population-based cross-sectional survey was conducted from January 18 to April 26, 2021, among 807 consenting individuals living in four major districts of the city of Yaoundé. Out of 711 nasopharyngeal swabs collected, 671 tests were performed by SARS-CoV-2 ribonucleic acid (RNA) extraction and real time-polymerase chain reaction (RT-PCR) at the National Public Health Laboratory (NPHL). Data were analysed using SPSS v21.0, with p &lt; 0.05 considered statistically significant. Results: overall SARS-CoV-2 RNA positivity rate was 11.62% (78/671), without any significant difference between males and females with 10.9% versus 12.20% respectively (OR = 0.87, p = 0.5). However, clinical status was associated with SARS-CoV-2 RNA positivity rate in symptomatic (26.3%) vs. asymptomatic (9.7%) individuals (Odds Ratio [OR] = 3.30, p = 0.0001). Other factors associated with SARS-CoV-2 RNA positivity include exposure to more than 15min with confirmed cases, wearing a non-conventional facemask (p ˂ 0.05), the practice of occasional hand hygiene before and after contact with patients (OR = 3.60, p &lt; 0.0001) or always as recommended (OR = 0.28, p = 0.0001), hand hygiene before and after occasional contact with objects (OR = 2.05, p = 0.0043) or always as recommended (OR = 0.48, p = 0.0027), surgical mask (OR = 0.17, p = 0.013) and standard mask (p = 0.026). Conclusion: From this urban setting of Cameroon, coronavirus disease 2019 (COVID-19) reached an alert burden (10-20%) during the second wave of the pandemic at the district level. Interestingly, SARS-CoV-2 infection was driven by the presence of symptoms, close contact with confirmed cases, limited adherence to recommended barrier measures, and the use of non-conventional facemasks.

Exploring the use of deep learning models for accurate tracking of 3D zebrafish trajectories.

Zebrafish are ideal model organisms for various fields of biological research, including genetics, neural transmission patterns, disease and drug testing, and heart disease studies, because of their unique ability to regenerate cardiac muscle. Tracking zebrafish trajectories is essential for understanding their behavior, physiological states, and disease associations. While 2D tracking methods are limited, 3D tracking provides more accurate descriptions of their movements, leading to a comprehensive understanding of their behavior. In this study, we used deep learning models to track the 3D movements of zebrafish. Videos were captured by two custom-made cameras, and 21,360 images were labeled for the dataset. The YOLOv7 model was trained using hyperparameter tuning, with the top- and side-view camera models trained using the v7x.pt and v7.pt weights, respectively, over 300 iterations with 10,680 data points each. The models achieved impressive results, with an accuracy of 98.7% and a recall of 98.1% based on the test set. The collected data were also used to generate dynamic 3D trajectories. Based on a test set with 3,632 3D coordinates, the final model detected 173.11% more coordinates than the initial model. Compared to the ground truth, the maximum and minimum errors decreased by 97.39% and 86.36%, respectively, and the average error decreased by 90.5%.This study presents a feasible 3D tracking method for zebrafish trajectories. The results can be used for further analysis of movement-related behavioral data, contributing to experimental research utilizing zebrafish.

Genomic epidemiology demonstrates spatially clustered, local transmission of Plasmodium falciparum in forest-going populations in southern Lao PDR.

While there has been significant progress in controlling falciparum malaria in the Lao People's Democratic Republic (PDR), sporadic cases persist in southern provinces where the extent and patterns of transmission remain largely unknown. To assess parasite transmission in this area, 53 Plasmodium falciparum (Pf) positive cases detected through active test and treat campaigns from December 2017 to November 2018 were sequenced, targeting 204 highly polymorphic amplicons. Two R packages, MOIRE and Dcifer, were applied to assess the multiplicity of infections (MOI), effective MOI (eMOI), within-host parasite relatedness, and between-host parasite relatedness ([Formula: see text]). Genomic data were integrated with survey data to characterize the temporal and spatial structures of identified clusters. The positive cases were mainly captured during the focal test and treat campaign conducted in 2018, and in the Pathoomphone area, which had the highest test positivity and forest activity. About 30% of the cases were polyclonal infections, with over half of theses (63%) showing within-host relatedness greater than 0.6, suggesting that cotransmission rather than superinfection was primarily responsible for maintaining polyclonality. A large majority of cases (81%) were infected by parasites genetically linked to one or more other cases. We identified five genetically distinct clusters in forest fringe villages within the Pathoomphone district, characterized by a high degree of genetic relatedness between parasites (mean [Formula: see text] = 0.8). Four smaller clusters of 2-3 cases linked Moonlapamok and Pathoomphone districts, with an average [Formula: see text] of 0.6, suggesting cross-district transmission. Most of the clustered cases occurred within 20 km and 2 months of each other, consistent with focal transmission. Transmission clusters identified in this study confirm the role of ongoing focal parasite transmission occurring within the forest or forest-fringe in the highly mobile population.

Vector competence of Aedes albopictus field populations from Reunion Island exposed to local epidemic dengue viruses

Dengue virus (DENV) is the most prevalent mosquito-borne Flavivirus that affects humans worldwide. Aedes albopictus, which is naturally infected with the bacteria Wolbachia, is considered to be a secondary vector of DENV. However, it was responsible for a recent DENV outbreak of unprecedented magnitude in Reunion Island, a French island in the South West Indian Ocean. Moreover, the distribution of the cases during this epidemic showed a spatially heterogeneous pattern across the island, leading to questions about the differential vector competence of mosquito populations from different geographic areas. The aim of this study was to gain a better understanding of the vector competence of the Ae. albopictus populations from Reunion Island for local DENV epidemic strains, while considering their infection by Wolbachia. Experimental infections were conducted using ten populations of Ae. albopictus sampled across Reunion Island and exposed to three DENV strains: one strain of DENV serotype 1 (DENV-1) and two strains of DENV serotype 2 (DENV-2). We analyzed three vector competence parameters including infection rate, dissemination efficiency and transmission efficiency, at different days post-exposition (dpe). We also assessed whether there was a correlation between the density of Wolbachia and viral load/vector competence parameters. Our results show that the Ae. albopictus populations tested were not able to transmit the two DENV-2 strains, while transmission efficiencies up to 40.79% were observed for the DENV-1 strain, probably due to difference in viral titres. Statistical analyses showed that the parameters mosquito population, generation, dpe and area of sampling significantly affect the transmission efficiencies of DENV-1. Although the density of Wolbachia varied according to mosquito population, no significant correlation was found between Wolbachia density and either viral load or vector competence parameters for DENV-1. Our results highlight the importance of using natural mosquito populations for a better understanding of transmission patterns of dengue.

Exploring the Relationship Between COVID-19 Transmission and Population Mobility over Time

This study explores the dynamic relationship between COVID-19 transmission and transportation mobility, with an emphasis on understanding the time-varying bidirectional interplay across the different phases of the pandemic. To gain insight into this relationship, we analyzed county-level data on transmission and mobility patterns from the United States over a 74-week period using a comprehensive list of factors including: temporal factors, socio-demographics, health indicators, health care infrastructure attributes, and spatial factors. For our analysis, we proposed a simultaneous econometric model system that explicitly accounts for the bidirectional relationship between COVID-19 transmission and mobility patterns while also accounting for the influence of common unobserved factors on the two variables. The model results strongly support our hypothesis that COVID-19 transmission and mobility patterns are interconnected. Further, our findings show distinct phases of the bidirectional relationship influenced by behavior changes, vaccine availability, and the emergence of new variants. Additionally, we conducted a validation exercise on a hold-out sample to assess the robustness of our model. The results confirm the superiority of the simultaneous model system with enhanced interpretability and prediction capability. By analyzing data from several weeks for the COVID-19 pandemic, our study provides valuable insights into the evolving dynamics and potential strategies for future pandemics.

Multidimensional data visualization and synchronization for revealing hidden pandemic information

Visualization is integral to uncovering hidden information in data and providing users with intuitive feedback for decision-making. Data visualization is crucial for transforming complex data into actionable insights across various domains. In recent years, coronavirus disease vaccines have become increasingly available to much of the population. However, the CDC (Centers for Disease Control and Prevention) often fails to consider multidimensional coronavirus pandemic data from a side-by-side perspective, limiting the ability of medical professionals and individuals to compare and interact with comprehensive data visualizations. Effectively displaying coronavirus and vaccination data collected from multiple sources is essential for interpreting pandemic transmission patterns and vaccine efficiency. This paper presents a new platform for innovative data visualizations that offers users intuitive feedback and a complete data story. We designed algorithms to seamlessly combine multiple parameters, synchronize attributes, and dynamically visualize data over time on a single webpage. Instead of integrating all attributes into a single plot, which can be overwhelming due to space limitations and make it difficult to extract crucial information from overcrowded display components, we developed algorithms to classify, enhance, and group all parameters based on their relationships and similarities. Furthermore, a side-by-side visualization method was created to dynamically link all parameters in multiple images for data exploration, trend comparison, hidden information detection, and correspondence analysis. Our platform provides real-time performance, enabling healthcare professionals to make informed decisions, communicate findings effectively, and uncover patterns that might not be apparent in raw data. The proposed multidimensional data visualization algorithms have broad applications in general data exploration and revealing hidden information.

Analyzing the dynamics and optimal control of a vector-borne model with dual vertical transmission and multiple serotypes

Abstract Transmission and contact patterns have an important influence on the intensity and trend of disease transmission. Taking into account two different serotypes and the vertical transmission of the disease in both humans and mosquitoes, this paper proposes a novel vector-borne disease model. In order to explore the evolution mechanisms of the model and the impacts of contact pattern on disease transmission. The basic regeneration number of the proposed model is obtained via the next-generation matrix approach. Subsequently, we analyze the conditions of the stabilities and existences of the equilibrium points. Further, the sensitivity of the parameters is studied using numerical simulations. It is observe that the increase of vertical transmission rate of mosquitoes leads to the increase of the basic reproduction number. In addition, we develop vaccination and insecticide control strategies and derive the existence and expression of the optimal solution. Our numerical results show that vaccination has a little effect on preventing the spread of disease among mosquitoes. However, insecticide spraying is effective in reducing the spread of disease between humans and mosquitoes.&amp;#xD;

Combining molecular transmission network analysis and spatial epidemiology to reveal HIV-1 transmission pattern among the older people in Nanjing, China

BackgroundIn China, the problem of HIV infection among the older people has become increasingly prominent. This study aimed to analyze the pattern and influencing factors of HIV transmission based on a genomic and spatial epidemiological analysis among this population.MethodsA total of 432 older people who were aged ≥ 50 years, newly diagnosed with HIV-1 between January 2018 and December 2021 and without a history of ART were enrolled. HIV-1 pol gene sequence was obtained by viral RNA extraction and nested PCR. The molecular transmission network was constructed using HIV-TRACE and the spatial distribution analyses were performed in ArcGIS. The multivariate logistic regression analysis was performed to analyze the factors associated with clustering.ResultsA total of 382 sequences were successfully sequenced, of which CRF07_BC (52.3%), CRF01_AE (32.5%), and CRF08_BC (6.8%) were the main HIV-1 strains. A total of 176 sequences entered the molecular network, with a clustering rate of 46.1%. Impressively, the clustering rate among older people infected through commercial heterosexual contact was as high as 61.7% and three female sex workers (FSWs) were observed in the network. The individuals who were aged ≥ 60 years and transmitted the virus by commercial heterosexual contact had a higher clustering rate, while those who were retirees or engaged other occupations and with higher education degree were less likely to cluster. There was a positive spatial correlation of clustering rate (Global Moran I = 0.206, P < 0.001) at the town level and the highly aggregated regions were mainly distributed in rural area. We determined three large clusters which mainly spread in the intra-region of certain towns in rural areas. Notably, 54.5% of cases in large clusters were transmitted through commercial heterosexual contact.ConclusionsOur joint analysis of molecular and spatial epidemiology effectively revealed the spatial aggregation of HIV transmission and highlighted that towns of high aggregation were mainly located in rural area. Also, we found vital role of commercial heterosexual contact in HIV transmission among older people. Therefore, health resources should be directed towards highly aggregated rural areas and prevention strategy should take critical persons as entry points.

Evolution and mutational landscape of highly pathogenic avian influenza strain A(H5N1) in the current outbreak in the USA and global landscape

The emergence of highly pathogenic avian influenza strain A (H5N1) in the USA is a high concern. Here, we illustrated the evolution, divergence, transmission pattern, infection pattern, entropy diversity, nucleotide diversity, and mutational landscape of HPAI(H5N1). We depicted three phylogenetic trees, i.e., from three perspectives: considering the HPAI H5N1 genome of the current outbreak in the USA (n = 971), considering the HPAI H5N1 spared in different hosts (cattle, hunan, avian, and nonhuman primates) and using the global genome sequences (n = 3154). We found that the clade 2.3.4.4b was responsible for the present infection. We noted that the USA's divergence rate is 3.43e-3 subs per site per year, and the global divergence rate is 5.21e-3 subs per site per year. We reported significant nucleotide changes to illustrate the genome.Similarly, we observe several point mutations in some proteins, such as PB2, PA, HA, NA, and NS1. Among point mutations, some common mutations are noted in PB2 (E362G, M631L) and PA (L219I, K497R). However, elimination strategies should be a high priority for dairy farm workers, domestic cattle, and poultry birds to limit future outbreaks.

Circulating dengue virus serotypes, demographics, and epidemiology in the 2023 dengue outbreak in Chittagong, Bangladesh.

Dengue is a serious epidemic for Bangladesh affecting thousands of lives. This study aimed to identify and determine the prevalence of the circulating variants of dengue virus (DENV) and their association with demographics and clinical manifestations among the dengue-infected patients. A total of 711 participants with NS1 antigen positivity were enrolled, followed by viral RNA extraction from the collected blood samples and a multiplex real-time reverse transcription-polymerase chain reaction (RT-PCR) assay to determine the dengue virus serotypes. Of 711 dengue-infected patients, 503 (70.7%) were male. Among different age groups, most of the patients were 21-30 years old (n = 255, 35.9%). The DENV2 (n = 483, 67.9%) serotype was more prevalent than the DENV3 (n = 144, 20.3%) and DENV1 (n = 84, 11.8%). The duration of fever was highest in the DENV-1 patients (4.79 ± 1.84 days) in contrast to DENV-3 (4.48 ± 1.68 days) and DENV-2 (4.33 ± 1.45 days) (P = 0.039). Importantly, five highly populated areas were identified as dengue hotspots in Chittagong metropolitan city. Our results provide crucial insights into the patterns of dengue virus transmission and severity among southern Bangladeshi population, thereby aiding in the development of targeted public health interventions and management strategies to combat future outbreaks.

Spatiotemporal patterns and socioeconomic determinants of pulmonary tuberculosis in Dongguan city, China, during 2011–2020: an ecological study

ObjectivePulmonary tuberculosis (PTB) is a critical challenge worldwide, particularly in China. This study aimed to explore the spatiotemporal transmission patterns and socioeconomic factors of PTB in Dongguan city, China.Methods/designAn ecological...

Characterizing school-linked and non-school linked SARS-CoV-2 cases in children and households: a retrospective cohort study using linked population-level administrative data from Manitoba, Canada

ObjectiveTo identify directionality of SARS-CoV-2 cases within households and schools, and characterize school, household, and neighbourhood factors associated with school and non-school linked cases. ApproachUsing linked administrative data housed at the Manitoba Centre for Health Policy, a cohort of 449,425 individuals from 126,670 households with school-aged children enrolled in Manitoba public schools between September 1, 2020-June 30, 2021 was created. Using population-based SARS-CoV-2 laboratory test results, education enrolment and household composition data, index and transmission cases were counted and categorized at an individual and household level as school or non-school linked. Logistic regression models examined school, household and neighbourhood factors associated with school- and non-school linked households. Results143280 individuals were tested for SARS-CoV-2 during the study period; 14712 individuals (10.3%) tested positive. Amongst positive cases, 1695 (11.5%) were school-linked; the remaining 13017 (88.5%) were non-school linked. 13.7% of SARS-CoV-2 positive households had ≥1 case linked to school; 86.3% did not. Preliminary results found higher incomes quintiles had lower odds of being a school-linked household, as did living outside the Winnipeg region. Having more children in a grade and more household members resulted in higher odds of being a school-linked transmission household. No associations were observed for having a child under age five in the household. ConclusionsTaken together, these data suggest schools were not a large source of SARS-CoV-2 cases in Manitoba and factors associated with school-linked households largely mirrored broader community transmission patterns. ImplicationsThese findings may influence public health approaches to future pandemic control.

Prevalence and genomic characteristics of becAB-carrying Clostridium perfringens strains

Clostridium perfringens, as a foodborne pathogen, can cause various intestinal diseases in both humans and animals according to its repertoire of toxins. In recent years, a multitude of studies have highlighted its threat to infants and young children. C. perfringens carries numerous toxins, with the newly identified BEC toxin confirmed as the second toxin to cause diarrheal illness, after CPE. However, the global dissemination of C. perfringens strains carrying becAB genes, which encode BEC toxins, has not been extensively studied. Following epidemiological surveillance of the prevalence of C. perfringens from different sources in various provinces of China, we identified two becAB-carrying strains and one strain carrying a sequence similar to becAB from distinct provinces and sources. When combined with genomic analysis of other becAB-carrying C. perfringens strains from public databases, we found that becAB was present in strains from different lineages. Our analysis of the plasmid and genetic environment corroborates previous findings on becAB-carrying strains, confirming that it currently achieves horizontal transmission through one type of evolutionarily conserved Pcp plasmid. This study provides a comprehensive analysis of the prevalence and transmission patterns of the newly emerged toxin gene locus, becAB, in C. perfringens. Despite the relatively low identification rate of becAB-carrying strains, their potential impact requires ongoing surveillance and investigation of their features, particularly their antimicrobial resistance.

Genomic characterization and cluster analysis of Carbapenem-resistant Klebsiella pneumoniae

To investigate the genomic features and perform cluster analysis of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to provide an experimental basis for guiding the prevention and treatment of CRKP infections.A retrospective case-cohort study was conducted on 19 non-redundant CRKP strains isolated from the Tenth Affiliated Hospital of Southern Medical University between January and June 2023. Whole genome sequencing (WGS) and multilocus sequence typing (MLST) were performed to compare genomic features and analyze the resistance genes and homology of the strains.The results showed that the 19 CRKP strains were isolated from 8 different clinical departments, mainly from respiratory specimens. The whole genome sequencing revealed that the genomic lengths of CRKP ranged from 4.90 to 5.85 Mbp, with contigs N50 values>20 kb for each genome. The median overall GC content was 57.0% (50.4%-57.1%). Comparative genomic analysis identified three regions with high genomic variability. WGS detected 32 resistance genes across 11 categories. All 19 strains carried carbapenem resistance genes (blaKPC-2 and blaOXA-48), blaTEM-1B extended-spectrum β-lactamase resistance genes, qnrS1 quinolone resistance gene, and fosA fosfomycin resistance gene, with each strain carrying only one carbapenemase gene. The detection rate of blaKPC-2 was 94.7% (18/19). MLST identified three sequence types: ST11, ST437 and ST147, with ST11 being predominant (89.5%, 17/19). Clustering analysis based on acquired resistance genes revealed three clonal transmission patterns among strains 72 and 90, and strains 88, 84, 66 and 79.In conclusion, CRKP strains carry multiple resistance genes, and clustering analysis indicating that nosocomial clonal transmission is closely related to acquired resistance genes. The ST11-blaKPC-2 type strain is the predominant clone. Strengthened surveillance and effective control strategies are necessary to reduce nosocomial transmission of CRKP.

Exploring first-degree family history in a cohort of Portuguese Alzheimer’s disease patients: population evidence for X-chromosome linked and recessive inheritance of risk factors

BackgroundAlzheimer’s disease (AD) heritability is estimated to be around 70–80%. Yet, much of it remains to be explained. Studying transmission patterns may help in understanding other factors contributing to the development of AD.ObjectiveIn this study, we aimed to search for evidence of autosomal recessive or X- and Y-linked inheritance of risk factors in a large cohort of Portuguese AD patients.MethodsWe collected family history from patients with AD and cognitively healthy controls over 75 years of age. We compared the proportions of maternal and paternal history in male and female patients and controls (to search for evidence of X-linked and Y-linked inherited risk factors). We compared the risk of developing AD depending on parents’ birthplace (same vs. different), as a proxy of remote consanguinity. We performed linear regressions to study the association of these variables with different endophenotypes.ResultsWe included 3090 participants, 2183 cognitively healthy controls and 907 patients with AD. Men whose mother had dementia have increased odds of developing AD comparing to women whose mother had dementia. In female patients with a CSF biomarker-supported diagnosis of AD, paternal history of dementia is associated with increased CSF phosphorylated Tau levels. People whose parents are from the same town have higher risk of dementia. In multivariate analysis, this proxy is associated with a lower age of onset and higher CSF phosphorylated tau.ConclusionsOur study gives evidence supporting an increased risk of developing AD associated with an X-linked inheritance pattern and remote consanguinity.

Asymptomatic carriage of Plasmodium falciparum in children living in a hyperendemic area occurs independently of IgG responses but is associated with a balanced inflammatory cytokine ratio

BackgroundAsymptomatic carriage of infected red blood cells (iRBCs) can be prevalent in communities regardless of transmission patterns and can occur with infection of different Plasmodium species. Clinical immunity dampens the inflammatory responses leading to disease symptoms in malaria. The aim of this study was to define the immunological correlates of asymptomatic carriage of Plasmodium falciparum in a highly exposed population.Methods142 asymptomatic Plasmodium-infected individuals greater than 2 years of age without fever (body temperature <37.5 ℃) were followed weekly for 10 weeks before being treated with artemisinin-based combination therapy (ACT). Plasma levels of 38 cytokines were measured at baseline by Luminex and the quantity and growth inhibitory activities of circulating parasite-reactive antibodies measured. The Plasmodium antigen tested included P. falciparum merozoite extract (ME) and schizont extract (SE), and the recombinant proteins erythrocyte binding antigen 175 (EBA-175) and merozoite surface protein 1 (MSP-119).ResultsMedian levels of IgG against P. falciparum EBA-175 and MSP-119 at baseline were significantly higher in those older than 20 years of age compared with the younger age group and appeared to correlate with better parasite control. Amongst all participants there were no discernible changes in IgG levels over time. Parasite density was higher in the younger age group and associated with IL-10, TNF and MCP-1 levels. A balanced IL-10:TNF ratio was associated with asymptomatic malaria regardless of age, and balanced ratios of IL-10/TNF and IL-10/IFN-γ were the only significant correlate of maintenance of asymptomatic malaria over the course of the study in individuals 20 years of age and younger.ConclusionThe above findings indicate that asymptomatic carriage of P. falciparum in children living in a hyperendemic area occurs independently of IgG but is associated with a balanced inflammatory cytokine ratio.

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.