Infectious Research Articles

Multidisciplinary Effort Leading to Effective Tuberculosis Community Outbreak Containment in Israel

Tuberculosis (TB) is the second-most prevalent cause of mortality resulting from infectious diseases worldwide. It is caused by bacteria belonging to the Mycobacterium tuberculosis complex (MTBC). In Israel, TB incidence is low, acknowledged by the WHO as being in a pre-elimination phase. Most cases occur among immigrants from high TB incidence regions like the Horn of Africa and the former Soviet Union (FSU), with occasional outbreaks. The outbreak described in this report occurred between 2018 and 2024, increasing the incidence rate of TB in the region. Control of this outbreak posed challenges due to factors including a diverse population (including Ethiopian immigrants, Israeli-born citizens, and immigrants from other countries), economic and social barriers, and hesitancy to disclose information. The unique multidisciplinary team formed to address these challenges, involving the local TB clinic, district health ministry, health maintenance organization (HMO) infectious disease consultant, neighborhood clinic, and National Mycobacterium Reference Laboratory (NMRL), achieved effective treatment and containment. Whole genome sequencing (WGS) proved pivotal in unraveling patient connections during the outbreak. It pinpointed those patients overlooked in initial field investigations, established connections between patients across different health departments, and uncovered the existence of two distinct clusters with separate transmission chains within the same neighborhood. This study underscores collaborative efforts across sectors that successfully contained a challenging outbreak.

Antibiotics Utilization Pattern in a Children’s Medical Center in North of Iran

Background: The development of a system for rational use of antimicrobials seems mandatory. Furthermore, since hospitals do not share the same bacterial flora and have different patterns of antibiotic therapy the purpose of the present study is to perform a Drug Utilization Evaluation (DUE) on the pattern of antibiotic administration in patients hospitalized in 17 Shahrivar Pediatric Hospital, RASHT, Iran. Methods: In this descriptive cross-sectional study that was conducted in a one-year period (2021-2022), 560 patients were randomly selected and their medication data were collected based on the gender and age as well as the type, dose, duration of antibiotic therapy and the results of bacterial cultures and also susceptibility of the infectious microorganisms. Results: The average age of patients was 53.56 months with 46.9% of them being less than 24 months old. The highest rate of antibiotics administration belonged to the infectious diseases ward (30%) and 33% of antibiotics were prescribed by pediatric infectious diseases specialists. The result of most of the cultures was reported as negative (98.38%), the most prevalent microorganism was Escherichia Coli from urine cultures (2.38%) and Staphylococcus Aureus from sputum cultures (14.28%). The highest prescribed antibiotics were ceftriaxone (51.2%) and vancomycin (45.6%). It was determined the antibiotic stipend was 15.6% of the whole budget for purchasing medicine. Conclusions: It is necessary to develop a guideline regarding the prescription of antibiotics in children's departments, which reduces empiric treatment and the requirement to adjust the drug after a negative culture.

Nanogel: A versatile drug delivery system for the treatment of various diseases and their future perspective.

Nanogel (NG) drug delivery systems have emerged as promising tools for targeted and controlled drug release, revolutionizing treatment approaches across various diseases.Their unique physicochemical properties, such as nano size, high surface area,biocompatibility, stability, and tunable drug release, make themideal carriers for a wide range of therapeutic agents. Nanogels (NGs), characterized by their 3D network of crosslinked polymers, offer unique edges like high drug loading capacity, controlled release, and targeted delivery. Additionally, the diverse applications of NGs in medical therapeutics highlight their versatility and potential impact on improving patient outcomes. Their application spans cancer treatment, infectious diseases, and chronic conditions, allowing for precise drug delivery to specific tissues or cells, minimizing side effects, and enhancing therapeutic efficacy. Despite their potential, challenges such as scalability, manufacturing reproducibility, and regulatory hurdles must be addressed. Achieving clinical translation requires overcoming these obstacles to ensure therapeutic payloads' safe and efficient delivery. Strategies such as surface modification and incorporating stimuli-responsive elements enhanced NG performance and addressed specific therapeutic challenges. Advances in nanotechnology, biomaterials, and targeted drug design offer opportunities to improve the performance of NGs and address current limitations. Tailoring NGs for exploring combination therapies and integrating diagnostics for real-time monitoring represent promising avenues for future research. In conclusion, NG drug delivery systems have demonstrated tremendous potential in diverse disease applications. Overcoming challenges and leveraging emerging technologies will pave the way for their widespread clinical implementation, ushering in a new era of precision medicine and improved patient care.

Dental and microbiological status of COVID-19 convalescent patients with simple marginal gingivitis

The pattern of dental morbidity in the population of the Russian Federation evidences about a high incidence of inflammatory periodontal diseases, which varies based on patient age and comorbidity. The negative age-related dynamics of dental health emphasizes the problem of concomitant pathology and requires constant monitoring of risk factors for inflammatory periodontal diseases. Insufficient attention is paid to endogenous risk factors, such as neurodystrophic disorders, diseases of the cardiovascular system, leukemia, anemia, gastrointestinal tract diseases, infections, etc. At the same time, the growth of “new” infections (HIV-infection, HCV-infection, Ebola fever, new coronavirus infection) is recorded with elevating level of other infectious diseases. The aim of the study is to assess dental and microbiological status of COVID-19 convalescent patients. A survey of 100 patients diagnosed with simple marginal gingivitis (ICD-10 code: K 05.10) was carried out consisting of the following groups: main group — 75 COVID-19 convalescent patients, control group — 25 COVID-19-negative subjects. All individuals underwent microbiological diagnostics for gingival groove contents and an assessed dental status. The index assessment was performed using the simplified Green-Vermillion Oral Hygiene Index (OHI-S), the PMA index (Parma) and the gingival papilla blood flow index (PBI). In the laboratory, the collected material was seeded onto expanded list of dense nutrient media. The identification of isolated microorganisms was carried out using MALDI-ToF mass spectrometry. Our analysis of the index assessment in both groups showed that the average values of the indices 1 month after the diagnosis of new coronavirus infection (ICD-10 code: U07.1) in main group are higher than in control group. Based on the results of a microbiological study, significant differences in the frequency of microbial species isolation were identified for 12 species. Thus, it is important to develop approaches to predicting development of chronic gingivitis and its exacerbation in COVID-19 patients.

Empowerment Tuberculosis Cadres with Participatory Socialization as Effort to Improve The TB Suspect's Achievements at The Sempu’s Public Health Center

Background: Tuberculosis (TB) is an infectious disease with high mortality and morbidity rates in Indonesia, caused by the bacterium Mycobacterium tuberculosis. The Case Detection Rate (CDR) in Banyuwangi is still relatively low at 54% compared to the set target. In Banyuwangi, one of the Non-Governmental Organizations (NGOs), Yayasan Bhanu Yasa Sejahtera Yabhysa, supports the TB control program in the region. Since 2021, this community has collaborated with the Banyuwangi Health Department to implement community-based TB interventions in 28 Community Health Centers (Puskesmas) spread across 16 districts, with a total of 66 active TB cadres. The aim of this community service is to train Tuberculosis (TB) cadres through socialization to improve the performance of TB suspects in Sempu Banyuwangi Community Health Center. Methods: The analysis of knowledge improvement data used a paired T-test with a 95% Confidence Interval. The test was conducted to evaluate the difference in knowledge improvement before and after education. Results: From the results of this community service, there was an increase in knowledge before and after socialization by 0.06 or 6%. The formation of TB cadres through contact investigation simulation carried out in community service activities resulted in the formation of four cadres. Conclusion: Based on the pre-test and post-test results, respondents showed a 6% increase in knowledge. The hope of this community service is to improve the achievement of TB suspect cases and reduce TB cases in Sempu Community Health Center.

Estimating the risk of gastrointestinal illness associated with drinking tap water in Norway: a prospective cohort study

BackgroundThe delivery of safe drinking water has high public health relevance, as reflected in the Sustainable Development Goals (SDG6). Several precautionary actions have reduced the burden associated with infectious diseases in high-income countries; however, pollution in source waters, inadequate disinfection, and premise plumbing, along with an increased awareness that intrusion in the drinking water distribution system, represents risk factors for gastrointestinal illness linked to consume of drinking water. Sporadic cases of waterborne infections are expected to be underreported since a sick person is less likely to seek healthcare for a self-limiting gastrointestinal infection. Hence, knowledge on the true burden of waterborne diseases is scarce. The primary aim with the present study was to estimate the risk of gastrointestinal illness associated with drinking tap water in Norway.MethodsWe conducted a 12-month prospective cohort study where participants were recruited by telephone interview after invitation based on randomised selection. A start up e-survey were followed by 12 monthly SMS questionnaires to gather information on participants characteristics and drinking tap water (number of 0.2L glasses per day), incidence, duration and symptoms associated with gastrointestinal illness. Associations between the exposure of drinking tap water and the outcome of risk of acute gastrointestinal illness (AGI) were analysed with linear mixed effects models. Age, sex, education level and size of the drinking water supply were identified as potential confounders and included in the adjusted model.ResultsIn total, 9,946 persons participated in this cohort study, accounting for 11.5% of all invited participants. According to the data per person and month (99,446 monthly submissions), AGI was reported for 5,508 person-months (5.5 per 100 person-months). Severe AGI was reported in 819 person-months (0.8 per 100 person-months). Our study estimates that 2–4% of AGI in Norway is attributable to drinking tap water.ConclusionsThis is the largest cohort study in Norway estimating the burden of self-reported gastrointestinal infections linked to the amount of tap water drunk in Norway. The data indicate that waterborne AGI is not currently a burden in Norway, but the findings need to be used with caution. The importance of continued efforts and investments in the maintenance of drinking water supplies in Norway to address the low burden of sporadic waterborne cases and to prevent future outbreaks needs to be emphasised.

Personal hygiene practice and associated factors among elementary school students in Fiche Town, Oromia, Ethiopia

BackgroundStudents in school are more likely to be sick from communicable diseases like diarrheal illnesses, acute respiratory infections, and other illnesses linked to poor personal hygiene. Poor hygiene practices are common among school children and put their health at risk, which in turn has several consequences. These include significant school absences, transmission of infectious diseases to other students, and missed workdays for parents and guardians. However, there is limited evidence on the level of personal hygiene practice and its associated factors among school students. Thus, this study was aimed at determining personal hygiene practice level and its associated factors among elementary school grade (5–8) students in Fiche town, Oromia, Ethiopia, in 2022.MethodsA cross-sectional study design was conducted from April 29 to May 29, 2022, in Fiche town, Oromia regional state, among 534 elementary school students. A multi-stage probability sampling technique was used to select the individual students. A structured questionnaire was used to collect the data. The data was entered into epi-data version 4.6 and analyzed by SPSS version 26.0. Variables that scored a p-value less than 0.2 during bivariate analysis were included in multilevel logistic regression models to determine factors associated with personal hygiene practice. The odds ratio with a 95% confidence interval was estimated, and the level of significance was set at \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\le\\:$$\\end{document} 0.05.ResultsThe magnitude of good personal hygiene (scored above the mean) was 59.2% (95% confidence interval (CI)) (55.1–63.0). A considerable proportion of students scored more than 50% in latrine use (62.5%), regular hand-washing (55.4%), and oral hygiene (55.20%) practices. Being female, having good personal hygiene knowledge, doing hygiene inspections at school, and having latrine accessibility was significantly associated with good personal hygiene among elementary school students.ConclusionConsiderable proportion of elementary school students in Fiche town have score poor personal hygiene practice. Interventions aimed that target improving knowledge of personal hygiene and hygiene inspection at school are crucial to enhance the personal hygiene among elementary school students.

Evaluation of the immune responses of biological adjuvant bivalent vaccine with three different insertion modes for ND and IBD

ABSTRACT Infectious bursal disease (IBD) is a widespread problem in the poultry industry, and vaccination is the primary preventive method. However, moderately virulent vaccines may damage the bursa, necessitating the development of a safe and effective vaccine. The Newcastle disease virus (NDV) has been explored as a vector for vaccine development. In this study, reverse genetic technology was used to obtain three recombinant viruses, namely, rClone30-VP2L (P/M)-chGM-CSF (NP), rClone30-chGM-CSF (P/M)-VP2L (NP), and rClone30-VP2L-chGM-CSF (P/M). Animal experiments showed that the three biological adjuvant bivalent vaccines effectively increased anti-NDV and anti-infectious bursal disease virus (IBDV) titres, enhancing both humoral and cellular immune responses in chickens without leading to any harm. Amongst the three biological adjuvant bivalent vaccines, the rClone30-chGM-CSF (P/M)-VP2L (NP) group had higher levels of anti-NDV antibodies at 14 days after the first immunization and stimulated a greater humoral immune response in 7–10 days. While, the rClone30-VP2L (P/M)-chGM-CSF (NP) group was the most effective in producing a higher level of IBDV antibody response. In conclusion, these three vaccines can induce immune responses more rapidly and effectively, streamline production processes, be cost-effective, and provide a new avenue for the development of Newcastle disease (ND) and IBD bivalent vaccines

Toward precision medical education: Characterizing individual residents' clinical experiences throughout training.

Despite the central role of experiential learning in residency training, the actual clinical experiences residents participate in are not well characterized. A better understanding of the type, volume, and variation in residents' clinical experiences is essential to support precision medical education strategies. We sought to characterize the entirety of the clinical experiences had by individual internal medicine residents throughout their time in training. We evaluated the clinical experiences of medicine residents (n = 51) who completed training at NYU Grossman School of Medicine's Brooklyn campus between 2020 and 2023. Residents' inpatient and outpatient experiences were identified using notes written, orders placed, and care team sign-ins; principal ICD-10 codes for each encounter were converted into medical content categories using a previously described crosswalk tool. Of 152,426 clinical encounters with available ICD-10 codes, 132,284 were mapped to medical content categories (94.5% capture). Residents' clinical experiences were particularly enriched in infectious and cardiovascular disease; most had very little exposure to allergy, dermatology, oncology, or rheumatology. Some trainees saw twice as many cases in a given content area as did others. There was little concordance between actual frequency of clinical experience and expected content frequency on the ABIM certification exam. Individual residents' clinical experiences in training vary widely, both in number and in type. Characterizing these experiences paves the way for exploration of the relationships between clinical exposure and educational outcomes, and for the implementation of precision education strategies that could fill residents' experiential gaps and complement strengths with targeted educational interventions.

Incidence and risk factors of SARS-CoV-2 breakthrough infection in the early Omicron variant era among vaccinated and boosted individuals in Chicago.

SARS-CoV-2 vaccines are safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. This study was performed to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. A retrospective clinical cohort study was performed utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. The primary outcome was the incidence and time to the first positive SARS-CoV-2 molecular test in the Omicron predominant era. Multivariable Cox modeling analyses to determine the hazard of SARS-CoV-2 infection were stratified by calendar time (Period 1: January 1 -June 30, 2022; Period 2: July 1 -December 31, 2022) due to violations in the proportional hazards assumption. In total, 133,191 patients were analyzed. During Period 1, having 3+ comorbidities was associated with increased hazard for breakthrough (HR = 1.16 CI 1.08-1.26). During Period 2 of the study, having 2 comorbidities (HR = 1.45 95% CI 1.26-1.67) and having 3+ comorbidities (HR 1.73, 95% CI 1.51-1.97) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in Period 1 of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age plays an important role in breakthrough infection with the highest incidence among young adults, which may be due to age-related behavioral factors. These findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

Impact of twelve immunization-preventable infectious diseases on population health using disability-adjusted life years (DALYs) in Spain

BackgroundThe objective of this study is to estimate the burden of selected immunization-preventable infectious diseases in Spain using the Burden of Communicable Diseases in Europe (BCoDE) methodology, as well as focusing on the national immunization programme and potential new inclusions.MethodsThe BCoDE methodology relies on an incidence and pathogen-based approach to calculate disease burden via disability-adjusted life year (DALY) estimates. It considers short and long-term sequelae associated to an infection via outcome trees. The BCoDE toolkit was used to populate those trees with Spanish-specific incidence estimates, and de novo outcome trees were developed for four infections (herpes zoster, rotavirus, respiratory syncytial virus [RSV], and varicella) not covered by the toolkit. Age/sex specific incidences were estimated based on data from the Spanish Network of Epidemiological Surveillance; hospitalisation and mortality rates were collected from the Minimum Basic Data Set. A literature review was performed to design the de novo models and obtain the rest of the parameters. The methodology, assumptions, data inputs and results were validated by a group of experts in epidemiology and disease modelling, immunization and public health policy.ResultsThe total burden of disease amounted to 163.54 annual DALYs/100,000 population. Among the selected twelve diseases, respiratory infections represented around 90% of the total burden. Influenza exhibited the highest burden, with 110.00 DALYs/100,000 population, followed by invasive pneumococcal disease and RSV, with 25.20 and 10.57 DALYs/100,000 population, respectively. Herpes zoster, invasive meningococcal disease, invasive Haemophilus influenza infection and hepatitis B virus infection ranked lower with fewer than 10 DALYs/100,000 population each, while the rest of the infections had a limited burden (< 1 DALY/100,000 population). A higher burden of disease was observed in the elderly (≥ 60 years) and children < 5 years, with influenza being the main cause. In infants < 1 year, RSV represented the greatest burden.ConclusionsAligned with the BCoDE study, the results of this analysis show a persisting high burden of immunization-preventable respiratory infections in Spain and, for the first time, highlight a high number of DALYs due to RSV. These estimates provide a basis to guide prevention strategies and make public health decisions to prioritise interventions and allocate healthcare resources in Spain.

High-Level Isolation: A Landscape Analysis of Global Capabilities and Opportunities to Advance the Field.

High-level isolation units (HLIUs) have been established by countries to provide safe and optimal medical care for patients with high-consequence infectious diseases. We aimed to identify global high-level isolation capabilities and determine gaps and priorities of global HLIUs, using a multiple method approach that included a systematic review of published and gray literature and a review of Joint External Evaluations and Global Health Security Index reports from 112 countries. A follow-up electronic survey was distributed to identified HLIUs. The landscape analysis found 44 previously designated/self-described HLIUs in 19 countries. An additional 33 countries had potential HLIUs; however, there were not enough details on capabilities to determine if they fit the HLIU definition. An electronic survey was distributed to 36 HLIUs to validate landscape analysis findings and to understand challenges, best practices, and priorities for increased networking with a global HLIU cohort; 31 (86%) HLIUs responded. Responses revealed an additional 30 confirmed HLIUs that were not identified in the landscape analysis. To our knowledge, this was the first mapping and the largest ever survey of global HLIUs. Survey findings identified major gaps in visibility of HLIUs: while our landscape analysis initially identified 44 units, the survey unveiled an additional 30 HLIUs that had not been previously identified or confirmed. The lack of formalized regional or global coordinating organizations exacerbates these visibility gaps. The unique characteristics and capabilities of these facilities, coupled with the likelihood these units serve as core components of national health security plans, provides an opportunity for increased connection and networking to advance the field of high-level isolation and address identified gaps in coordination, build an evidence base for HLIU approaches, and inform HLIU definitions and key components.

Molecular characterisation of Histoplasma capsulatum sensu lato from Ethiopian horses reveals two distinct phylogenetic clades.

Epizootic lymphangitis (EL) is a highly prevalent and contagious infectious disease affecting horses in many parts of Ethiopia caused by Histoplasma capsulatum sensu lato ('var. farciminosum'). In this study, 12 suspected isolates of H. capsulatum sensu lato or yeasts unidentified by conventional biochemical tests isolated from Ethiopian horses with EL were characterised by ITS sequencing. Six of the 12 isolates were identified to be members of H. capsulatum sensu lato and the other six were Pichia kudriavzevii (synonym: Candida krusei) (n=3), Trichosporon asahii (n=1), Geotrichum silvicola (n=1) and Moesziomyces aphidis (n=1), respectively. The six H. capsulatum sensu lato isolates were further characterised by multilocus sequence analysis. Four distinct gene loci [arf (462 bases), H-anti (410 bases), ole1 (338 bases) and tub1 (272 bases)] of these six isolates as well as those of two H. capsulatum sensu lato ('var. farciminosum') reference strains (ATCC 58332 and ATCC 28798) were PCR-amplified and sequenced. Phylogenetic analyses of their concatenated nucleotide sequences showed that three of the isolates and the reference strain ATCC 58332 were identical and belonged to the Eurasia clade within Latin American (LAm) A (H. suramericanum), and those of the other three isolates and the reference strain ATCC 28798 were identical and belonged to the Africa clade. At least two distinct phylogenetic clades of Histoplasma capsulatum sensu lato were circulating in Ethiopian horses with EL. Advanced molecular technologies and bioinformatics tools are crucial for accurate identification and typing of pathogens as well as discovery of novel microorganisms in veterinary microbiology.

Visual analysis of hot spots and trends in research of meteorology and hemorrhagic fever with renal syndrome: a bibliometric analysis based on CiteSpace and VOSviewer

Objective: We here displayed the global research trends of meteorology and hemorrhagic fever with renal syndrome (HFRS) as a visual knowledge map by using bibliometrics and revealed the research directions, hotspots, trends, and frontiers in this field.Methods: Using Web of Science core collection as the data source and with CiteSpace and VOSviewer software, we collected and analyzed the annual number of papers, cooperative relationships (countries, institutions, authors, etc.), citations (literature citation, literature co-citation, literature publication, etc.), keywords (emergence, clustering, etc.) of meteorology, and HFRS-related research data for the past 30 years, and drew a visual map.Results: In total, this study included 313 papers investigating the relationship between meteorology and HFRS. The first paper was published in 1992. Globally, United States had the largest number of publications in this field, and the Chinese Center for Disease Control and Prevention was the most influential institution conducting related research (20 articles published, and the mediation centrality was 0.24). Several small author cooperation clusters were formed; however, the number of papers published by the same scholar and the co-citation frequency were low. Cazelles Bernard (7 articles) published the highest number of articles in this field, and Gubler DJ was the author with the most co-citations (55 times). The most frequently cited journal was Emerging Infectious Diseases. In this field, the top three high-frequency keywords were “hemorrhagic fever,” “transmission,” and “temperature.” According to keyword cluster analysis, the top three themes were dengue, dechlorane plus, and bank voles. The timeline spectrum exhibited that dengue clustering had a good temporal continuity. The trend analysis of emergent words revealed that the research on “temperature,” “meteorological factors” and “Puumala hantavirus” has gradually appeared in recent years.Conclusion: This study represents the first comprehensive exploration of global trends, hotspots, frontiers, and developments in the relationship between meteorology and HFRS, utilizing CiteSpace and VOSviewer software. The findings of this study are crucial for elucidating the influence of climate change on disease transmission patterns and offering novel insights for forthcoming epidemiological research and public health interventions.

Building a network with assortative mixing starting from preference functions, with application to the spread of epidemics

Compartmental models of disease spread have been well studied on networks built according to the Configuration Model, i.e., where the degree distribution of individual nodes is specified, but where connections are made randomly. Dynamics of spread on such “first order” networks were shown to be profoundly different compared to epidemics under the traditional mass action assumption. Assortativity, i.e., the preferential mixing of nodes according to degree, is a second order property that is thought to impact epidemic trajectory. We first show how assortative mixing can come about from individual preferences to connect with others of lower or higher degree, and propose an algorithm for constructing such a network. We then investigate via simulation how this network structure favors or inhibits diffusion processes, such as the spread of an infectious disease.

Therapeutic applications of synthetic gene/genetic circuits: a patent review

A significant limitation of numerous current genetic engineering therapy approaches is their limited control over the strength, timing, or cellular context of their therapeutic effect. Synthetic gene/genetic circuits are synthetic biology approaches that can control the generation, transformation, or depletion of a specific DNA, RNA, or protein and provide precise control over gene expression and cellular behavior. They can be designed to perform logical operations by carefully selecting promoters, repressors, and other genetic components. Patent search was performed in Espacenet, resulting in 38 selected patents with 15 most frequent international classifications. Patent embodiments were categorized into applications for the delivery of therapeutic molecules, treatment of infectious diseases, treatment of cancer, treatment of bleeding, and treatment of metabolic disorders. The logic gates of selected genetic circuits are described to comprehensively demonstrate their therapeutic applications. Synthetic gene circuits can be customized for precise control of therapeutic interventions, leading to personalized therapies that respond specifically to individual patient needs, enhancing treatment efficacy and minimizing side effects. They can be highly sensitive biosensors that provide real-time therapy by accurate monitoring various biomarkers or pathogens and appropriately synthesizing a therapeutic molecule. Synthetic gene circuits may also lead to the development of advanced regenerative therapies and to implantable biodevices that produce on-demand bioactive molecules. However, this technology faces challenges for commercial profitability. The genetic circuit designs need adjustments for specific applications, and may have disadvantages like toxicity from multiple regulators, homologous recombination, context dependency, resource overuse, and environmental variability.

Modeling tuberculosis transmission flow in China, 2010–2012

BackgroundChina has the third largest number of TB cases in the world, and the average annual floating population in China is more than 200 million, the increasing floating population across regions has a tremendous potential for spreading infectious diseases, however, the role of increasing massive floating population in tuberculosis transmission is yet unclear in China.Methods29,667 tuberculosis flow data were derived from the new smear-positive pulmonary tuberculosis cases in China. Spatial variation of TB transmission was measured by geodetector q-statistic and spatial interaction model was used to model the tuberculosis flow and the regional socioeconomic factors.ResultsTuberculosis transmission flow presented spatial heterogeneity. The Pearl River Delta in southern China and the Yangtze River Delta along China’s east coast presented as the largest destination and concentration areas of tuberculosis inflows. Socioeconomic factors were determinants of tuberculosis flow. Some impact factors showed different spatial associations with tuberculosis transmission flow. A 10% increase in per capita GDP was associated with 10.2% in 2010 or 2.1% in 2012 decrease in tuberculosis outflows from the provinces of origin, and 1.2% in 2010 or 0.5% increase in tuberculosis inflows to the destinations and 18.9% increase in intraprovincial flow in 2012. Per capita net income of rural households and per capita disposable income of urban households were positively associated with tuberculosis flows. A 10% increase in per capita net income corresponded to 14.0% in 2010 or 3.6% in 2012 increase in outflows from the origin, 44.2% in 2010 or 12.8% increase in inflows to the destinations and 47.9% increase in intraprovincial flows in 2012. Tuberculosis incidence had positive impacts on tuberculosis flows. A 10% increase in the number of tuberculosis cases corresponded to 2.2% in 2010 or 1.1% in 2012 increase in tuberculosis inflows to the destinations, 5.2% in 2010 or 2.0% in 2012 increase in outflows from the origins, 11.5% in 2010 or 2.2% in 2012 increase in intraprovincial flows.ConclusionsTuberculosis flows had clear spatial stratified heterogeneity and spatial autocorrelation, regional socio-economic characteristics had diverse and statistically significant effects on tuberculosis flows in the origin and destination, and income factor played an important role among the determinants.

Oral Leishmaniasis in HIV-Positive and HIV-Negative Patients: A Comparative Analysis with Two New Case Reports.

This case report examines the clinical presentation, diagnosis, treatment, and outcomes of mucocutaneous leishmaniasis with primary oral involvement in HIV-positive and HIV-negative patients diagnosed in Brazil. We discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, highlighting the clinical and histopathologic diagnostic features and distinct progression patterns based on HIV status. Our findings are compared with patterns observed in other countries, emphasizing the differences between the Americas and Europe, Asia, and Africa. In the Americas, particularly in Brazil, mucocutaneous leishmaniasis often presents with localized oral lesions, even in the presence of systemic immunosuppression, whereas in the Europe, Asia, and Africa, oral involvement is typically associated with visceral leishmaniasis in immunocompromised patients. These differences were due to variations in the parasite species involved. This comparison underscores the importance of regional and immunological factors in diagnosing and managing this neglected infectious disease.

Assessing molecular genetic and immunological predictors of COVID-19 course in healthcare worker risk group

Relevance. Studying features of innate and adaptive mechanisms of immune response in medical workers (MW), the most vulnerable social group with a high risk of infection, is an urgent research task. The aim of the study: Comprehensive study of innate and adaptive immune mechanisms and analyzing relationships between clinically significant polymorphisms (SNPs) in TLR2, TLR4 genes, TLR2 expression level on peripheral blood monocytes, peripheral blood cytokine profile (IL-1β, IL-10, IL-6, IFNγ, platelet activation marker) and SARS-CoV-2-specific humoral immune response in medical workers (MW) at a temporary infectious disease hospital in early and late COVID-19 convalescence. Materials and methods. immunologic, cytofluorimetric and molecular-genetic research methods were applied. Adaptive immune response in medical workers — COVID-19 convalescent subjects. Results. Early post-COVID-19 convalescence period in MW was linked to higher TLR2 monocyte expression; the mean fluorescence intensity was significantly elevated by 1.5-fold compared to control group. Late convalescence period (7 months post-COVID-19) was characterized by lowered serum IFNγ level. A decline in IFNγ production was significant: decreased by 82-fold in MR that was markedly stronger compared to control group (59 times). The imbalance of cytokines controlling antiviral innate and adaptive immune response was revealed in MW with identified combination of polymorphisms rs5743708 and rs4986790 in TLR2, TLR4 genes with the rate not exceeding 6.7%. It was found that 7 months after COVID-19 there was a markedly decreased IFNγ, IL-1β and IL-10 levels. The studies indicate both altered innate and adaptive immune mechanisms and a need to optimize therapeutic and prophylactic measures aimed at increasing patient-intrinsic resistance, protection of respiratory tract mucosal barriers and identification of genetic predictors of defects in innate and adaptive immune response in medical workers — COVID-19 convalescent subjects.

Impact of educational interventions on hepatitis B and C awareness among school students of Delhi NCR, India

BackgroundViral hepatitis, particularly B and C, is a major cause of liver cirrhosis and cancer, leading to about 1.4 million deaths annually. Alarmingly, less than 20% of those with hepatitis are aware of their status, with only 6.3% receiving treatment. School children can play a pivotal role in raising awareness and preventing the spread of infections. This intervention study focuses on understanding and enhancing the knowledge, attitudes, and practices related to Hepatitis B and C, among school children in Delhi NCR to foster dialogue and awareness.MethodsAn intervention study was conducted in selected schools across Delhi NCR between September and October 2022 to assess baseline knowledge, attitudes, and practices related to Hepatitis B and C. Three of seven schools were randomly selected by probability sampling, representing 9–12 grade students, and 901 students participated. Following this, an educational interventional program was conducted using educational material, interactive sessions, and audiovisual aids. Post-intervention assessments were done to measure the impact on knowledge improvement.ResultsThe study is expected to provide insights into the current level of awareness regarding Hepatitis B and C. Furthermore, the intervention’s effectiveness was analysed using the pre-formed questionnaire. The average pre-test knowledge score was 8.9 ± 3.2, while the post-test average was 15.6 ± 4.4, indicating a substantial increase of 6.7 ± 4.7 points (+ 75.2%). There was a positive correlation of 0.240 between pre and post-test scores. Attitude change before and after the session showed a positive percentage change of + 38.0% with a correlation of 0.351. The study indicated substantial improvements in knowledge about hepatitis B and C, notably regarding awareness about transmission methods and risk factors.ConclusionThis interventional study seeks to bridge the knowledge gap among school children regarding Hepatitis B and C in Delhi NCR, fostering a proactive approach towards prevention, detection, and treatment. The considerable rise in awareness and favourable changes in perspectives post-intervention say that specific health education initiatives are pivotal in raising awareness and comprehension of infectious diseases, ultimately contributing to improving community health.