Front Neurosci. 2025 Mar 10;19:1498981. doi: 10.3389/fnins.2025.1498981. eCollection 2025.

ABSTRACT

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War Syndrome (GWS), and Fibromyalgia (FM) are complex, chronic illnesses with overlapping clinical features. Symptoms that are reported across these conditions include post-exertional malaise (PEM), fatigue, and pain, yet the etiology of these illnesses remains largely unknown. Diagnosis is challenging in patients with these conditions as definitive biomarkers are lacking; patients are required to meet clinical criteria and often undergo lengthy testing to exclude other conditions, a process that is often prolonged, costly, and burdensome for patients. The identification of reliable validated biomarkers could facilitate earlier and more accurate diagnosis and drive the development of targeted pharmacological therapies that might address the underlying pathophysiology of these diseases. Major driving forces for biomarker identification are the advancing fields of metabolomics and proteomics that allow for comprehensive characterization of metabolites and proteins in biological specimens. Recent technological developments in these areas enable high-throughput analysis of thousands of metabolites and proteins from a variety of biological samples and model systems, that provides a powerful approach to unraveling the metabolic phenotypes associated with these complex diseases. Emerging evidence suggests that ME/CFS, GWS, and FM are all characterized by disturbances in metabolic pathways, particularly those related to energy production, lipid metabolism, and oxidative stress. Altered levels of key metabolites in these pathways have been reported in studies highlighting potential common biochemical abnormalities. The precise mechanisms driving altered metabolic pathways in ME/CFS, GWS, and FM remain to be elucidated; however, the elevated oxidative stress observed across these illnesses may contribute to symptoms and offer a potential target for therapeutic intervention. Investigating the mechanisms, and their role in the disease process, could provide insights into disease pathogenesis and reveal novel treatment targets. As such, comprehensive metabolomic and proteomic analyses are crucial for advancing the understanding of these conditions in-order to identify both common, and unique, metabolic alterations that could serve as diagnostic markers or therapeutic targets.

PMID:40129725 | PMC:PMC11931034 | DOI:10.3389/fnins.2025.1498981

Food Sci Biotechnol. 2024 Dec 27;34(7):1605-1616. doi: 10.1007/s10068-024-01802-x. eCollection 2025 Apr.

ABSTRACT

Ensuring the viability and accurate stratification of Lacticaseibacillus group (LCG) species after freeze-drying is essential for their effective use as probiotics. This study investigates the use of reconstituted skim milk (RSM) as a cryoprotectant base, supplemented with fructans such as inulin and diverse forms of levan from Halomonas smyrnensis, to maintain the viability of Lacticaseibacillus casei ATCC 334, Lacticaseibacillus paracasei ATCC 25302, and Lacticaseibacillus rhamnosus ATCC 53103. Cellular viability was enhanced with levan-based cryoprotectants, motivating the use of levan-based hydrogels (gHLs) for freeze-drying LCG species. Throughout freeze-drying, the species-specific molecular masses (m/z) were preserved irrespective of the cryoprotectant used, with markers 3445 and 6664 m/z identified as potential species-specific molecular mass indicators for Lc. paracasei and Lc. rhamnosus, respectively. This study is the first to utilize levan in various forms as a cryoprotective agent alongside RSM, highlighting its promise as an effective cryoprotectant for LCG and potentially other probiotics.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-024-01802-x.

PMID:40129716 | PMC:PMC11929659 | DOI:10.1007/s10068-024-01802-x

Microbiome. 2025 Mar 24;13(1):82. doi: 10.1186/s40168-025-02079-w.

ABSTRACT

BACKGROUND: Extraintestinal bacterial infections (EBIs), e.g., urinary tract infection, bacteremia, and meningitis, occur in approximately 10% of febrile infants younger than 60 days. Although many EBI-causing species commonly reside in the infant gut, proof that the digestive system is a pre-infection habitat remains unestablished.

RESULTS: We studied a cohort of febrile term infants < 60 days old who presented to one of thirteen US emergency departments in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Forty EBI cases and 74 febrile controls matched for age, sex, and race without documented EBIs were selected for analysis. Shotgun sequencing was performed of the gut microbiome and of strains cultured from the gut and extraintestinal site(s) of EBI cases, including blood, urine, and/or cerebrospinal fluid. Using a combination of EBI isolate genomics and fecal metagenomics, we detected an intestinal strain presumptively isogenic to the EBI pathogen (> 99.999% average nucleotide identity) in 63% of infants with EBIs. Although there was no difference in gut microbiome diversity between cases and controls, we observed significantly increased Escherichia coli relative abundance in the gut microbiome of infants with EBIs caused by E. coli. Infants with E. coli infections who were colonized by the putatively isogenic pathogen strain had significantly higher E. coli phylogroup B2 abundance in their gut, and their microbiome was more likely to contain virulence factor loci associated with adherence, exotoxin production, and nutritional/metabolic function.

CONCLUSIONS: The intestine plausibly serves as a reservoir for EBI pathogens in a subset of febrile term infants, prompting consideration of new opportunities for surveillance and EBI prevention among colonized, pre-symptomatic infants. Video Abstract.

PMID:40128855 | DOI:10.1186/s40168-025-02079-w

BMC Public Health. 2025 Mar 24;25(1):1129. doi: 10.1186/s12889-025-22262-w.

ABSTRACT

BACKGROUND: Early and risky adolescent alcohol use have each been associated with adult alcohol consumption. However, it remains unclear whether these behaviours independently predict later-life substance use when considered jointly, and research examining links with substances other than alcohol is limited. This study addresses these gaps by examining longitudinal associations between age at first alcohol and risky adolescent alcohol use, with alcohol, tobacco, cannabis and other drug use in early adulthood, and aims to identify critical periods for public health interventions.

METHODS: Growing Up in Ireland is a nationally representative cohort (recruited aged 9 [Wave 1], born 1997-1998). Survey-weighted logistic regression examined whether age at first alcoholic drink and risky alcohol use at age 17 (Alcohol Use Disorders Identification Test scores) independently predict high-risk alcohol (AUDIT > 15), tobacco, cannabis and other drug use at age 20. Models were adjusted for age, sex, academic ability, personality, psychological factors, socioeconomic status, familial, peer and neighbourhood substance use.

RESULTS: The study included 4554 participants (49.8% female). Early alcohol use was common, with 27% reporting use aged 14 or younger. By age 20, 14% reported high-risk alcohol, 38% tobacco, 24% cannabis and 28% other drug use. Older age at first alcohol was associated with dose-response reductions in the odds of high-risk alcohol, tobacco, cannabis and other drug use at age 20, relative to those initiating alcohol at 14 or younger. Adolescents with high-risk alcohol use had double the odds of tobacco (adjusted odds ratio (aOR) 2.1, 95% confidence intervals (CI) 1.3-3.30) and other drug use (aOR 2.5, 95% CI 1.6-4.1) and an 11-fold increase in the odds of continued high-risk alcohol use (aOR 11.5, 95% CI 7.0-18.6) at age 20, relative to adolescents with low-risk alcohol use.

CONCLUSIONS: Age at first alcohol and risky adolescent alcohol use independently predict substance use in early adulthood when considered jointly in extensively adjusted models. These findings highlight the continued urgent need for public health interventions that address factors associated with early alcohol use and support adolescents who use alcohol in a high-risk manner given their elevated risk of progression to more serious substance use as adults.

PMID:40128701 | DOI:10.1186/s12889-025-22262-w

Nat Metab. 2025 Mar 24. doi: 10.1038/s42255-025-01284-z. Online ahead of print.

NO ABSTRACT

PMID:40128614 | DOI:10.1038/s42255-025-01284-z

Nat Commun. 2025 Mar 24;16(1):2870. doi: 10.1038/s41467-025-58288-2.

NO ABSTRACT

PMID:40128545 | DOI:10.1038/s41467-025-58288-2

Sci Data. 2025 Mar 24;12(1):492. doi: 10.1038/s41597-025-04832-0.

ABSTRACT

Spheroids are widely used in oncology for testing drugs, but models composed of a single cell line do not fully capture the complexity of the in vivo tumours targeted by chemotherapy. Developing 3D in vitro models that better mimic tumour architecture is a crucial step for the scientific community. To enable more reliable drug testing, we generated multiculture spheroids and analysed cell morphology and distribution over time. This dataset is the first publicly available single-cell light-sheet fluorescence microscopy image collection of 3D multiculture tumour models comprising of three different cell lines analysed at different time points. Specifically, we created models composed of one cancer cell line (melanoma, breast cancer, or osteosarcoma) alongside two stromal cell lines (fibroblasts and endothelial cells). Then, we acquired single-cell resolution light-sheet fluorescence 3D images of the spheroids to analyse spheroid morphology after 24, 48, and 96 hours. The image collection, whole spheroid annotations, and extracted features are publicly available for further research and can support the development of automated analysis models.

PMID:40128531 | DOI:10.1038/s41597-025-04832-0

Discov Oncol. 2025 Mar 25;16(1):386. doi: 10.1007/s12672-025-02121-1.

ABSTRACT

Growth differentiation factor-15 (GDF15) is a cytokine/growth factor that belongs to the Transforming growth factor-ß (TGF-ß) protein family. The expression of GDF15 is low in most human organs under normal conditions. GDF15 is a stress-responsive cytokine primarily produced by macrophages in response to inflammatory stimuli. The altered expression of GDF15 is associated with many cancers due to the inflammation caused by the disease. GDF15 triggers the activity through its receptor Glial-derived neurotrophic factor-family receptor α-like (GFRAL) and mediates multiple downstream signaling cascades, which are involved in the progression of cancers. Considering the biological importance of GDF15 in different cancers, we applied data mining techniques to systematically compile and analyze the signaling events associated with GDF15 using NetPath criteria. This resulted in constructing a detailed GDF15-mediated signaling pathway map, enhancing our understanding of its molecular mechanisms in cancer. Furthermore, proteins linked to colorectal and breast cancer identified in our pathway map were cross-referenced with established cancer pathway databases to identify unannotated proteins, highlighting gaps in the current annotations. To investigate potential therapeutic strategies, we performed molecular docking simulations and identified Vitisifuran B as a novel inhibitor that could block the GDF15-GFRAL interaction. These findings suggest that Vitisifuran B could effectively modulate GDF15 signaling, offering a promising avenue for cancer therapeutics. This study underscores the power of computational approaches, such as data mining and molecular docking, in enhancing our understanding of GDF15 signaling in cancer and identifying potential inhibitors for therapeutic development.

PMID:40128491 | DOI:10.1007/s12672-025-02121-1

EMBO Rep. 2025 Mar 24. doi: 10.1038/s44319-025-00415-7. Online ahead of print.

ABSTRACT

Actin-based motility is required for the transmission of malaria sporozoites. While this has been shown biochemically, filamentous actin has remained elusive and has not been directly visualised inside the parasite. Using focused ion beam milling and electron cryo-tomography, we studied dynamic actin filaments in unperturbed Plasmodium falciparum cells for the first time. This allowed us to dissect the assembly, path and fate of actin filaments during parasite gliding and determine a complete 3D model of F-actin within sporozoites. We observe micrometre long actin filaments, much longer than expected from in vitro studies. After their assembly at the parasite's apical end, actin filaments continue to grow as they are transported down the cell as part of the glideosome machinery, and are disassembled at the basal end in a rate-limiting step. Large pores in the IMC, constrained to the basal end, may facilitate actin exchange between the pellicular space and cytosol for recycling and maintenance of directional flow. The data also reveal striking actin bundles in the nucleus. Implications for motility and transmission are discussed.

PMID:40128412 | DOI:10.1038/s44319-025-00415-7

Nat Methods. 2025 Mar 24. doi: 10.1038/s41592-025-02632-3. Online ahead of print.

ABSTRACT

Maintenance of genome integrity is paramount to molecular programs in multicellular organisms. Throughout the lifespan, various endogenous and environmental factors pose persistent threats to the genome, which can result in DNA damage. Understanding the functional consequences of DNA damage requires investigating their preferred genomic distributions and influences on gene regulatory programs. However, such analysis is hindered by both the complex cell-type compositions within organs and the high background levels due to the stochasticity of damage formation. To address these challenges, we developed Paired-Damage-seq for joint analysis of oxidative and single-stranded DNA damage with gene expression in single cells. We applied this approach to cultured HeLa cells and the mouse brain as a proof of concept. Our results indicated the associations between damage formation and epigenetic changes. The distribution of oxidative DNA damage hotspots exhibits cell-type-specific patterns; this selective genome vulnerability, in turn, can predict cell types and dysregulated molecular programs that contribute to disease risks.

PMID:40128288 | DOI:10.1038/s41592-025-02632-3

Nat Commun. 2025 Mar 24;16(1):2879. doi: 10.1038/s41467-025-58200-y.

ABSTRACT

Inorganic phosphate (Pi) is essential for life, and its intracellular levels must be tightly regulated to avoid toxicity. XPR1, the sole known phosphate exporter, is critical for maintaining this balance. Here we report cryo-EM structures of the human XPR1-KIDINS220 complex in substrate-free closed and substrate-bound outward-open states, as well as an XPR1 mutant in a substrate-bound inward-facing state. In the presence of inositol hexaphosphate (InsP6) and phosphate, the complex adopts an outward-open conformation, with InsP6 binding the SPX domain and juxtamembrane regions, indicating active phosphate export. Without phosphate or InsP6, the complex closes, with transmembrane helix 9 blocking the outward cavity and a C-terminal loop obstructing the intracellular cavity. XPR1 alone remains closed even with phosphate and InsP6. Functional mutagenesis shows that InsP6, whose levels vary with Pi availability, works with KIDINS220 to regulate XPR1 activity. These insights into phosphate regulation may aid in developing therapies for ovarian cancer.

PMID:40128258 | DOI:10.1038/s41467-025-58200-y

Kidney Int. 2025 Mar 22:S0085-2538(25)00255-8. doi: 10.1016/j.kint.2025.02.027. Online ahead of print.

ABSTRACT

Human kidney organoids derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) have become novel tools for studying various kidney pathologies. Here, we transplanted ESC-derived kidney organoids into humanized mice with a mature human adaptive immune system developed through thymic education. As judged by histology and immunophenotyping, the transplanted HLA-mismatched kidney organoids trigged a robust alloimmune response, characterized by a dense immune cell infiltrate and enhanced memory T cell phenotype in the allograft 30 days post-transplantation. Multiplexed immunofluorescence revealed expression of functional markers of various immune cell infiltrates in response to organoid allografts, mimicking the T cell-mediated rejection process in humans. This validated our model as a novel platform to study various therapeutic strategies to control alloimmunity. Splenocytes isolated from organoid-transplanted hosts showed an alloantigen-specific memory response against 2D kidney organoids ex vivo. Overall, our study indicates that transplanting kidney organoids in humanized mice may be a valuable tool for studying human allogeneic immunity.

PMID:40127865 | DOI:10.1016/j.kint.2025.02.027

Biotechnol Adv. 2025 Mar 22:108567. doi: 10.1016/j.biotechadv.2025.108567. Online ahead of print.

ABSTRACT

Parasitic nematodes represent a substantial global burden, impacting animal health, agriculture and economies worldwide. Of these worms, Haemonchus contortus - a blood-feeding nematode of ruminants - is a major pathogen and a model for molecular and applied parasitology research. This review synthesises some key advances in understanding the molecular biology, genetic diversity and host-parasite interactions of H. contortus, highlighting its value for comparative studies with the free-living nematode Caenorhabditis elegans. Key themes include recent developments in genomic, transcriptomic and proteomic technologies and resources, which are illuminating critical molecular pathways, including the ubiquitination pathway, protease/protease inhibitor systems and the secretome of H. contortus. Some of these insights are providing a foundation for identifying essential genes and exploring their potential as targets for novel anthelmintics or vaccines, particularly in the face of widespread anthelmintic resistance. Advanced bioinformatic tools, such as machine learning (ML) algorithms and artificial intelligence (AI)-driven protein structure prediction, are enhancing annotation capabilities, facilitating and accelerating analyses of gene functions, and biological pathways and processes. This review also discusses the integration of these tools with cutting-edge single-cell sequencing and spatial transcriptomics to dissect host-parasite interactions at the cellular level. The discussion emphasises the importance of curated databases, improved culture systems and functional genomics platforms to translate molecular discoveries into practical outcomes, such as novel interventions. New research findings and resources not only advance research on H. contortus and related nematodes but may also pave the way for innovative solutions to the global challenges with anthelmintic resistance.

PMID:40127743 | DOI:10.1016/j.biotechadv.2025.108567

Arch Biochem Biophys. 2025 Mar 22:110398. doi: 10.1016/j.abb.2025.110398. Online ahead of print.

ABSTRACT

Acute lung injury (ALI) is a severe condition characterized by acute inflammation and respiratory distress, often leading to significant morbidity and mortality. The complex pathophysiology of ALI involves alterations in various molecular and cellular processes, including those regulated by the miR-200 family. This study aims to investigate the regulatory function of miR-200 family members on the fibrinolytic system using three different agents: Bleomycin, IL-17A, and TGF-β, in both in vitro (A549 cells) and in vivo (C57BL/6 mice) models. The role of miR-200a and miR-200b in modulating the fibrinolytic system was assessed through mRNA and protein expression analyses. The results show that in both in vitro and in vivo models, treatment with miR-200a and miR-200b mimics greatly reduced the abnormalities caused by the three drugs. Treatments were given during the inflammatory phase of ALI at two different time points for the in vivo studies: 3 and 7 days. This was evidenced by increased uPA and uPAR mRNA levels and decreased PAI-1 mRNA and protein expression. The inverse regulatory roles of miR-200 family members, particularly miR-200a and miR-200b, suggest potential therapeutic targets in ALI. Furthermore, our study highlights how IL-17A and TGF-β modulate the fibrinolytic system and EMT pathway by influencing the expression of the miR-200 family in ALI. It elucidates the regulatory function of the miR-200 family in restoring the fibrinolytic system and the EMT pathway during lung injury, underscoring the significant therapeutic potential of miR-200 in treating ALI.

PMID:40127710 | DOI:10.1016/j.abb.2025.110398

Proc Natl Acad Sci U S A. 2025 Apr;122(13):e2420343122. doi: 10.1073/pnas.2420343122. Epub 2025 Mar 24.

ABSTRACT

Congenital heart disease (CHD) is a leading cause of infant mortality. We analyzed de novo mutations (DNMs) and very rare transmitted/unphased damaging variants in 248 prespecified genes in 11,555 CHD probands. The results identified 60 genes with a significant burden of heterozygous damaging variants. Variants in these genes accounted for CHD in 10.1% of probands with similar contributions from de novo and transmitted variants in parent-offspring trios that showed incomplete penetrance. DNMs in these genes accounted for 58% of the signal from DNMs. Thirty-three genes were linked to a single CHD subtype while 12 genes were associated with 2 to 4 subtypes. Seven genes were only associated with isolated CHD, while 37 were associated with 1 or more extracardiac abnormalities. Genes selectively expressed in the cardiomyocyte lineage were associated with isolated CHD, while those widely expressed in the brain were also associated with neurodevelopmental delay (NDD). Missense variants introducing or removing cysteines in epidermal growth factor (EGF)-like domains of NOTCH1 were enriched in tetralogy of Fallot and conotruncal defects, unlike the broader CHD spectrum seen with loss of function variants. Transmitted damaging missense variants in MYH6 were enriched in multiple CHD phenotypes and account for ~1% of all probands. Probands with characteristic mutations causing syndromic CHD were frequently not diagnosed clinically, often due to missing cardinal phenotypes. CHD genes that were positively or negatively associated with development of NDD suggest clinical value of genetic testing. These findings expand the understanding of CHD genetics and support the use of molecular diagnostics in CHD.

PMID:40127276 | DOI:10.1073/pnas.2420343122

Microb Biotechnol. 2025 Mar;18(3):e70132. doi: 10.1111/1751-7915.70132.

ABSTRACT

Beyond the rational construction of genetic determinants to encode target functions, complex phenotype engineering requires the contextualisation of their expression within the metabolic and genetic background of the host strain. Furthermore, wherever metabolic complexity is involved, phenotype engineering demands standard, reliable, plug-and-play tools. We introduce GENIO (GENome Integration and fitness Optimization platform for Pseudomonas putida), a framework to optimise genetic circuit performance by means of (i) chromosome-location-based differential gene expression and (ii) subsequent fitness improvement through evolutionary engineering if needed. Using gene expression strength and cell-to-cell variation, we characterised 10 P. putida chromosomal loci (ppLPS) to show that genome context rather than distance to ORI is the main factor driving differential expression performance. We further contextualised ppLPS gene expression against well-known chromosomal integration sites and plasmids displaying different copy numbers. GENIO supports comprehensive exploration of the gene expression space across P. putida's genome while unlocking performance optimization of complex heterologous metabolic pathways through evolutionary engineering. To demonstrate the usability of GENIO, we restored P. putida's aromatic hydrocarbon metabolism by (de)constructing the toluene/m-xylene catabolic pathway coded in the pWW0 plasmid. We also showed that engineering complex phenotypes requires accurate contextualisation of the synthetic pathways involved, a process that benefits from biological robustness.

PMID:40126873 | DOI:10.1111/1751-7915.70132

Elife. 2025 Mar 24;13:RP93373. doi: 10.7554/eLife.93373.

ABSTRACT

Obesity is a major risk factor for type 2 diabetes, dyslipidemia, cardiovascular disease, and hypertension. Intriguingly, there is a subset of metabolically healthy obese (MHO) individuals who are seemingly able to maintain a healthy metabolic profile free of metabolic syndrome. The molecular underpinnings of MHO, however, are not well understood. Here, we report that CTRP10/C1QL2-deficient mice represent a unique female model of MHO. CTRP10 modulates weight gain in a striking and sexually dimorphic manner. Female, but not male, mice lacking CTRP10 develop obesity with age on a low-fat diet while maintaining an otherwise healthy metabolic profile. When fed an obesogenic diet, female Ctrp10 knockout (KO) mice show rapid weight gain. Despite pronounced obesity, Ctrp10 KO female mice do not develop steatosis, dyslipidemia, glucose intolerance, insulin resistance, oxidative stress, or low-grade inflammation. Obesity is largely uncoupled from metabolic dysregulation in female KO mice. Multi-tissue transcriptomic analyses highlighted gene expression changes and pathways associated with insulin-sensitive obesity. Transcriptional correlation of the differentially expressed gene (DEG) orthologs in humans also shows sex differences in gene connectivity within and across metabolic tissues, underscoring the conserved sex-dependent function of CTRP10. Collectively, our findings suggest that CTRP10 negatively regulates body weight in females, and that loss of CTRP10 results in benign obesity with largely preserved insulin sensitivity and metabolic health. This female MHO mouse model is valuable for understanding sex-biased mechanisms that uncouple obesity from metabolic dysfunction.

PMID:40126547 | DOI:10.7554/eLife.93373

Cancer Sci. 2025 Mar 24. doi: 10.1111/cas.70056. Online ahead of print.

ABSTRACT

Tumor-derived exosomes (TDEs) have emerged as vital biomarkers of multiple cancers. However, the diagnostic and stage-predicting effects of exosomal pyruvate kinase isoenzyme type M2 (PKM2) in peripheral blood and its mechanism in promoting gastric cancer (GC) remain unclear. Here, we analyzed plasma exosomal PKM2 in 216 blood samples collected from GC patients and healthy donors (HD). The area under the curve (AUC) of plasma exosomal PKM2 demonstrated superior performance in early GC diagnosis compared with that of widely used clinical biomarkers. Kaplan-Meier analysis revealed that high exosomal PKM2 expression was associated with poor prognosis in patients with GC (HR = 1.623, p = 0.029). Single-cell transcriptome sequencing analysis showed that PKM2 was enriched in tumor-associated macrophages (TAM). We further confirmed that the polarization of TAM to the pro-tumoral M2 phenotype induced by exosomal PKM2 promoted the proliferation, migration, and invasion of GC cells. Mechanistically, exosomal PKM2 enhanced lipid synthesis in TAM by inhibiting SCAP polyubiquitination, which triggered the nuclear accumulation of SREBP1, thereby upregulating fatty acid synthesis enzymes, such as FASN, ACACA, and ACLY. In conclusion, plasma exosomal PKM2 is a promising novel biomarker for the clinical diagnosis of GC. Importantly, exosomal PKM2 shapes the tumor microenvironment by activating the SREBP1-related lipid synthesis pathway in macrophages, thereby contributing to GC development.

PMID:40126044 | DOI:10.1111/cas.70056

New Phytol. 2025 Mar 24. doi: 10.1111/nph.70100. Online ahead of print.

NO ABSTRACT

PMID:40125595 | DOI:10.1111/nph.70100

Lancet Reg Health West Pac. 2025 Mar 6;56:101509. doi: 10.1016/j.lanwpc.2025.101509. eCollection 2025 Mar.

ABSTRACT

BACKGROUND: The incidence of tuberculosis (TB) decreased significantly in recent years in China. However, the declining in the burden of tuberculosis infection (TBI) have not been systematically evaluated. The aim of this study was to elucidate the changes of TBI prevalence during the past decade.

METHODS: Based on a population-based, multicenter cohort study (LATENTTB-NSTM), a 10-year follow-up survey was conducted among registered residents (≥18 years old) at two study sites (Zhongmu and Danyang) using open-cohort design. After excluding active TB, tuberculin skin test (TST) and interferon-γ release assay (IGRA) were used to determine TBI status of each participant.

FINDINGS: Overall, 5924 eligible participants who completed the follow-up survey were included in the analysis. Compared to the age- and gender-standardized TBI prevalence determined by IGRA in 2013, the prevalence of TBI was observed to be decreased by 22·24% (from 15·11% to 11·75%) in Danyang site and by 40·86% (from 16·57% to 9·80%) in Zhongmu site in 2023. A consistently declining trend was observed as well for TBI prevalence determined by TST test. The acquisition of TBI in 10 years was assessed by the conversion rate of IGRA result in 4648 participants who participated in both the 2013 and 2023 surveys. The IGRA conversion rate in Danyang site was significantly higher than that in Zhongmu site (4% vs. 2%, p < 0·0001). The reversion rate of IGRA result was assessed as well, and no statistically significant difference was observed between the two study sites (29% in Danyang site vs. 31% in Zhongmu site, p = 0·577). Male gender was found to be associated with an increased risk of IGRA conversion as compared to female, with adjusted odds ratio (OR) of 1·46 (95% confidence interval [CI]: 1·00-2·13). In addition, never smokers were observed to be associated with significantly higher IGRA reversion rates (OR = 2·91, 95% CI: 1·52-5·57) (p = 0.001) as compared to current smokers. We also found the influence of BCG vaccination at birth on TST positivity was non-significant among individuals aged 15 and above.

INTERPRETATION: Our findings suggest that the prevalence of TBI in rural residents from China has significantly decreased along with the declining of TB incidence in the last decade. The downward trend shows regional differences, which might be partly explained by the difference in new infection rates across regions.

FUNDING: The CAMS Innovation Fund for Medical Sciences and the National Natural Science Foundation of China.

PMID:40125311 | PMC:PMC11930089 | DOI:10.1016/j.lanwpc.2025.101509