Recent Publications

Infect Prev Pract. 2024 Dec 26;7(1):100435. doi: 10.1016/j.infpip.2024.100435. eCollection 2025 Mar.

ABSTRACT

Antibiograms have been used during outbreak investigations for decades as a surrogate for genetic relatedness of Methicillin-resistant Staphylococcus aureus (MRSA). In this study, we evaluate the accuracy of antibiograms in detecting transmission, using genomic epidemiology as the reference standard. We analysed epidemiological and genomic data from 1,465 patients and 1,465 MRSA isolates collected at a single clinical microbiology laboratory in the United Kingdom over a one-year period. A total of 132 unique antibiograms (AB) were identified based on VITEK 2 susceptibility testing, with two profiles (AB1 and AB2) accounting for 698 isolates (48%). We identified MRSA-positive patients with a known hospital or community contact and evaluated the prediction of MRSA transmission based on identical antibiograms. The sensitivity and specificity of identical antibiograms to infer genetically related MRSA isolates (≤25 SNPs) within hospital contacts (presumed transmission events) was 66.4% and 85.5% respectively and 73.8% and 85.7% within community contacts. Reanalysis, where any single drug mismatch in susceptibility results was allowed, increased sensitivity but reduced specificity: 95.2% and 58.8%, respectively, for hospital contacts; and 91.7% and 62.6% for community contacts. Overall, the sensitivity and specificity of identical antibiograms for inferring genetically related MRSA isolates (≤25 SNPs), regardless of epidemiological links, were 49.1% and 87.5%, respectively. We conclude that using an antibiogram with one mismatch can detect most transmission events; however, its poor specificity may lead to an increased workload through the evaluation of numerous pseudo-outbreaks. This study further supports the integration of genomic epidemiology into routine practice for the detection and control of MRSA transmission.

PMID:39877244 | PMC:PMC11772957 | DOI:10.1016/j.infpip.2024.100435

Chemistry. 2025 Jan 21:e202404413. doi: 10.1002/chem.202404413. Online ahead of print.

ABSTRACT

The ability to release a molecule from a larger construct in a controlled manner is of great importance to produce effective prodrugs, antibody-drug conjugates, and chemical probes. Amides are ubiquitous functional groups and yet methods to utilise them as molecular release handles are seldom reported. This concept article highlights the advances made in amide release strategies and how these approaches have been utilised.

PMID:39836098 | DOI:10.1002/chem.202404413

Lancet Infect Dis. 2025 Jan 17:S1473-3099(24)00729-1. doi: 10.1016/S1473-3099(24)00729-1. Online ahead of print.

ABSTRACT

Antimicrobial resistance continues to be a growing threat globally, specifically in health-care settings in which antimicrobial-resistant pathogens cause a substantial proportion of health-care-associated infections (HAIs). Next-generation sequencing (NGS) and the analysis of the data produced therein (ie, bioinformatics) represent an opportunity to enhance our capacity to address these threats. The 3rd Geneva Infection Prevention and Control Think Tank brought together experts to identify gaps, propose solutions, and set priorities for the use of NGS for HAIs and antimicrobial-resistant pathogens. The major deliverable recommendation from this meeting was a proposed framework for implementing the sequencing of HAI pathogens, specifically those harbouring antimicrobial-resistance mechanisms. The key components of the proposed framework relate to wet laboratory quality, sequence data quality, database and tool selection, bioinformatic analyses, data sharing, and NGS data integration, to support public health and actions for infection prevention and control. In this Personal View we detail and discuss the framework in the context of global implementation, specifically in low-income and middle-income countries.

PMID:39832513 | DOI:10.1016/S1473-3099(24)00729-1

Nat Commun. 2025 Jan 17;16(1):759. doi: 10.1038/s41467-025-55931-w.

ABSTRACT

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal ("predicted-at-exposure") titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate.

PMID:39824819 | DOI:10.1038/s41467-025-55931-w

Environ Sci Technol. 2025 Jan 16. doi: 10.1021/acs.est.4c11368. Online ahead of print.

ABSTRACT

The emergence of mobile colistin resistance gene mcr-1 has attracted global attention. The prevalence of mcr-1-positive Escherichia coli (MCRPEC) in humans largely decreased following the ban of colistin as an animal growth promoter in China. However, the prevalence of MCRPEC in the hospital environment and the relationship between disinfectants and mcr-1 remain unclear. We found that MCRPEC prevalence was low in the feces of healthy humans attending physical examinations in six hospitals (4.6%, 71/1532) but high in hospital wastewater (50.0%, 27/54). mcr-1 was mainly located on IncI2 (63.0% in wastewater and 62.0% in feces) and IncHI2 plasmids (18.5% in wastewater and 21.1% in feces). High similarity of the mcr-1 context and its carrying plasmids was observed in human and wastewater MCRPEC, with several isolates clustering together. The coexistence of the ESBL gene blaCTX-M with mcr-1 occurred in 19.7% of IncI2 plasmids. Notably, 60.0% of IncHI2 plasmids exhibited co-occurrence of mcr-1 with the disinfectant resistance gene (DRG) qacEΔ1, conferring resistance to quaternary ammonium compounds (QACs). We revealed that QACs, rather than the other two types of disinfectants─ortho-phthalaldehyde (OPA) and povidone-iodine (PVP-I)─select for plasmids carrying both qacEΔ1 and mcr-1 and elevate their conjugative transfer frequency. Monitoring of DRGs in MCRPEC and managing disinfectant use are urgently needed in healthcare settings to mitigate the spread of colistin resistance from hospital environments to inpatients.

PMID:39818750 | DOI:10.1021/acs.est.4c11368

EMBO J. 2025 Jan 15. doi: 10.1038/s44318-024-00328-6. Online ahead of print.

ABSTRACT

Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant. AT2 dysfunction underlies many lung diseases, including interstitial lung disease (ILD), in which some inherited forms result from the mislocalization of surfactant protein C (SFTPC) variants. Lung disease modeling and dissection of the underlying mechanisms remain challenging due to complexities in deriving and maintaining human AT2 cells ex vivo. Here, we describe the development of mature, expandable AT2 organoids derived from human fetal lungs which are phenotypically stable, can differentiate into AT1-like cells, and are genetically manipulable. We use these organoids to test key effectors of SFTPC maturation identified in a forward genetic screen including the E3 ligase ITCH, demonstrating that their depletion phenocopies the pathological SFTPC redistribution seen for the SFTPC-I73T variant. In summary, we demonstrate the development of a novel alveolar organoid model and use it to identify effectors of SFTPC maturation necessary for AT2 health.

PMID:39815007 | DOI:10.1038/s44318-024-00328-6

J R Soc Interface. 2025 Jan;22(222):20240866. doi: 10.1098/rsif.2024.0866. Epub 2025 Jan 15.

NO ABSTRACT

PMID:39809334 | DOI:10.1098/rsif.2024.0866

bioRxiv [Preprint]. 2024 Dec 3:2024.10.28.620643. doi: 10.1101/2024.10.28.620643.

ABSTRACT

Mycobacterium tuberculosis (Mtb) is the world's most deadly infectious pathogen and new drugs are urgently required to combat the emergence of multi- (MDR) and extensively- (XDR) drug resistant strains. The bacterium specifically upregulates sterol uptake pathways in infected macrophages and the metabolism of host-derived cholesterol is essential for Mtb's long-term survival in vivo. Here, we report the development of antitubercular small molecules that inhibit the Mtb cholesterol oxidases CYP125 and CYP142, which catalyze the initial step of cholesterol metabolism. An efficient biophysical fragment screen was used to characterize the structure-activity relationships of CYP125 and CYP142, and identify a non-azole small molecule 1a that can bind to the heme cofactor of both enzymes. A structure-guided fragment-linking strategy was used to optimize the binding affinity of 1a, yielding a potent dual CYP125/142 inhibitor 5m (KD CYP125/CYP142 = 0.04/0.16 μM). Compound 5m potently inhibits the catalytic activity of CYP125 and CYP142 in vitro (KI values < 0.1 μM), and rapidly depletes Mtb intracellular ATP (IC50 = 0.15 μM). The compound has antimicrobial activity against both drug susceptible and MDR Mtb (MIC99 values 0.4 - 1.5 μM) in extracellular assays, and inhibits the growth of Mtb in human macrophages (MIC = 1.7 μM) with good selectivity over mammalian cytotoxicity (LD50 ≥ 50 μM). The combination of small molecule inhibitors and structural data reported here provide useful tools to study the role of cholesterol metabolism in Mtb and are a promising step towards novel antibiotics targeting bioenergetic pathways, which could be used to help combat MDR-TB.

PMID:39803573 | PMC:PMC11722527 | DOI:10.1101/2024.10.28.620643

Nat Commun. 2025 Jan 13;16(1):302. doi: 10.1038/s41467-024-55186-x.

ABSTRACT

Staphylococcus aureus is an important human pathogen and a commensal of the human nose and skin. Survival and persistence during colonisation are likely major drivers of S. aureus evolution. Here we applied a genome-wide mutation enrichment approach to a genomic dataset of 3060 S. aureus colonization isolates from 791 individuals. Despite limited within-host genetic diversity, we observed an excess of protein-altering mutations in metabolic genes, in regulators of quorum-sensing (agrA and agrC) and in known antibiotic targets (fusA, pbp2, dfrA and ileS). We demonstrated the phenotypic effect of multiple adaptive mutations in vitro, including changes in haemolytic activity, antibiotic susceptibility, and metabolite utilisation. Nitrogen metabolism showed the strongest evidence of adaptation, with the assimilatory nitrite reductase (nasD) and urease (ureG) showing the highest mutational enrichment. We identified a nasD natural mutant with enhanced growth under urea as the sole nitrogen source. Inclusion of 4090 additional isolate genomes from 731 individuals revealed eight more genes including sasA/sraP, darA/pstA, and rsbU with signals of adaptive variation that warrant further characterisation. Our study provides a comprehensive picture of the heterogeneity of S. aureus adaptive changes during colonisation, and a robust methodological approach applicable to study in host adaptive evolution in other bacterial pathogens.

PMID:39805814 | DOI:10.1038/s41467-024-55186-x

Alzheimers Dement. 2024 Dec;20 Suppl 2:e089538. doi: 10.1002/alz.089538.

ABSTRACT

BACKGROUND: Outdoor air pollution is a global issue which poses a significant health risk. Modern neuroimaging techniques have revealed the detrimental impact of air pollution on brain health, in particular the development and progression of neurodegenerative diseases such as Alzheimer's disease (AD).(1) We conducted a systematic review to evaluate the effects of long-term (months to years) exposure to outdoor air pollutants on the development and progression of AD using neuroimaging data.

METHOD: This review followed PRISMA guidelines and registered in PROSPERO (CRD42023482979). Four large databases (MEDLINE, Embase, Scopus, and CINAHL) were systematically searched using words relating to "air pollution", "neuroimaging", and "Alzheimer's disease". The population researched was kept broad to include all ages. There were no geographical limits applied, and so included all countries. Articles were exported to Endnote (Endnote X9.3.3, Clarivate US), where duplicate articles were removed. Remaining articles were uploaded to the Rayyan and screened for eligibility. The Newcastle Ottawa Scale was used to assess the quality of included papers. A narrative synthesis was conducted, which involved grouping papers that focused on the same neuroimaging outcome and comparing and contrasting between studies.

RESULT: Our search yielded 397 results, after removing duplicated (n=172), articles were removed at the title (n=192), abstract (n=8), and full text (n=17) stages. Eight articles met our inclusion criteria and focused on changes to white matter (n= 5), cortical thickness (n= 6), and grey matter (n= 2). Specific air pollutants (e.g., PM2.5) were associated with white matter reductions, and PM10 and NO2 with reduced cortical thickness. However, higher exposure to NOx and NO2 was linked to better performance in cognition tests. Exposure to PM2.5 was associated with reduced grey matter, with study participants showing greater cognitive impairment. Air pollution exposure was associated with brain structure changes which are commonly seen in AD-related pathology.

CONCLUSION: Our results highlighted significant associations between specific air pollutant exposure and changes in different brain structures. Future research is needed to further investigate the relationship between air pollution exposure and cognitive decline. References: Block ML, Calderón-Garcidueñas L. Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci. 2009;32(9):506-16.

PMID:39785598 | DOI:10.1002/alz.089538

R Soc Open Sci. 2025 Jan 8;12(1):240763. doi: 10.1098/rsos.240763. eCollection 2025 Jan.

ABSTRACT

The influence of landscape structure on epidemic invasion of agricultural crops is often underestimated in the construction and analysis of epidemiological models. Computer simulations of individual-based models (IBMs) are widely used to characterize disease spread under different management scenarios but can be slow in exploring large numbers of different landscape configurations. Here, we address the problem of finding an analytical measure of the impact of the spatial structure of a crop landscape on the invasion and spread of plant pathogens. We explore the potential of using an analytical approximation for the rate, r , at which susceptible crop fields become infected at the start of an epidemic to predict the effect that the spatial structure of a host landscape will have on an epidemic. We demonstrate the validity of this approach using two models: (i) a general IBM of the invasion and spread of a pathogen through an abstract host landscape; and (ii) an IBM of a real-life example for a virus disease spreading through a cassava landscape. Finally, we demonstrate that the analytical approach based on an estimate of the rate, r , can be used to identify spatial structures that effect deceleration of an invading pathogen.

PMID:39780974 | PMC:PMC11706665 | DOI:10.1098/rsos.240763

J Equine Vet Sci. 2025 Jan 6:105346. doi: 10.1016/j.jevs.2025.105346. Online ahead of print.

ABSTRACT

This prospective, controlled field trial aimed to determine the effect of dietary supplementation of mares in late pregnancy with a commercial stud feed balancer on the transfer of passive immunity to their foals. Eighty-two pregnant mares on a single stud farm that were eligible for inclusion were assigned into two groups (Intervention and Control) based primarily on existing social groupings. Between 64-224 days prepartum, all mares received the same forage-based diet but mares in the Intervention group received an in-feed commercial stud feed balancer and mares in the Control group received the stud's home-mix concentrate. Data from 68 mare and foal pairs were analysed according to Intention To Treat (ITT) principles and sensitivity analysis was performed on 57 mare and foal pairs who fulfilled the study protocol. The primary outcome of interest was failure of passive transfer of immunity (FPT), defined as foal IgG <8g/l at 12-36 hours after first suckle. Foals of mares in the Intervention group were significantly less likely to develop FPT compared to those in the Control group. Colostral quality (Brix ≥23.0) was also significantly greater in mares in the Intervention compared to the Control group. Group (Intervention vs. Control) and sex of foal were the only variables that were significantly associated with FPT in a multivariable model that explored the effect of other potential risk factors for FPT.

PMID:39778725 | DOI:10.1016/j.jevs.2025.105346

Foodborne Pathog Dis. 2025 Jan 6. doi: 10.1089/fpd.2023.0017. Online ahead of print.

ABSTRACT

Klebsiella quasipneumoniae is a recently described species that can be differentiated from Klebsiella pneumoniae. However, in clinical settings, they are frequently misidentified as K. pneumoniae. In this study, our objective was to conduct genomic characterization and bioinformatics analysis of K. quasipneumoniae subsp. quasipneumoniae (KpII-A) isolated from a sample obtained from a retail fish market in Assam, India. Notably, this particular isolate was identified as K. pneumoniae when identified using BD Pheonix™ M50 (BD Difco, USA). This represents a serious pitfall of conventional microbiological methods for distinguishing between K. pneumoniae and K. quasipneumoniae. In this connection, identifying differences in nuclear gene content is key to avoid misidentification. The isolate was confirmed to be KpII-A using species identification by Mash Screen and whole-genome sequencing by the Illumina platform. We report the draft genome sequence of this strain, comprising of 53 contigs with an average GC content of 58.11%. The annotation revealed 5,095 protein coding sequences, 69 tRNA genes, and 4 rRNA genes. The isolated strain acknowledges the presence of oqxA, oqxB, fosA, and blaOKP-A-3 antimicrobial resistance genes (ARGs). Additionally two phage genomes were detected in contigs 3 and 19 of the bacterial genome. Based on the multilocus sequence typing and genome sequencing, the isolate was identified as a novel sequence type, ST5655, within the species K. quasipneumoniae under the phylogroup KpII-A. The presence of antimicrobial resistance genes in KpII-A, isolated from retail fish samples, raises concerns regarding transmission across barriers in ecological niches and possible transmission to consumers. Given that fish may serve as a potential vehicle for ARG transmission, our findings are highly relevant and paramount to human health. Moreover, our study supports the robustness of the sequence-based microbial identification.

PMID:39761073 | DOI:10.1089/fpd.2023.0017

Cell Rep. 2025 Jan 3;44(1):115140. doi: 10.1016/j.celrep.2024.115140. Online ahead of print.

ABSTRACT

Virus neutralization profiles against primary infection sera and corresponding antigenic cartography are integral part of the COVID-19 and influenza vaccine strain selection processes. Human single variant exposure sera have previously defined the antigenic relationships among SARS-CoV-2 variants but are now largely unavailable due to widespread population immunity. Therefore, antigenic characterization of future SARS-CoV-2 variants will require an animal model, analogous to using ferrets for influenza virus. We evaluated neutralization profiles against 23 SARS-CoV-2 variants in nonhuman primates (NHPs) after single variant exposure and generated an NHP-derived antigenic map. We identified a distant antigenic region occupied by BA.2.86, JN.1, and the descendants KP.2, KP.3, and KZ.1.1.1. We also found that the monovalent XBB.1.5 mRNA vaccine induced broad immunity against the mapped antigenic space. In addition, substantial concordance was observed between our NHP-derived and two human antigenic maps, demonstrating the utility of NHPs as a surrogate for antigenic cartography in humans.

PMID:39754717 | DOI:10.1016/j.celrep.2024.115140

Pediatr Crit Care Med. 2025 Jan 3. doi: 10.1097/PCC.0000000000003682. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess characteristics and outcomes of children with suspected or confirmed infection requiring emergency transport and PICU admission and to explore the association between the 2024 Phoenix Sepsis Score (PSS) criteria and mortality.

DESIGN: Retrospective analysis of curated data from a 2014-2016 multicenter cohort study.

SETTING: PICU admission following emergency transport in South East England, United Kingdom, from April 2014 to December 2016.

PATIENTS: Children 0-16 years old (n = 663) of whom 444 (67%) had suspected or confirmed infection.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The PSS was calculated as a sum of four individual organ subscores (respiratory, cardiovascular, neurological, and coagulation) using the worst values during transport (i.e., from referral until the time of PICU admission). A score cutoff of greater than or equal to 2 points was used to define sepsis; and septic shock was defined as sepsis plus 1 or more cardiovascular subscore points. Sepsis occurred in 260 of 444 children (58.6%) with suspected or confirmed infection, with septic shock occurring in 177 of 260 (68.1%) of those with sepsis. A PSS score greater than or equal to 2 points occurred in 37 of 67 bronchiolitis cases, 19 of 35 meningoencephalitis cases, 30 of 47 pneumonia/empyema cases, 38 of 46 septic/toxic shock cases, nine of 15 severe sepsis cases, and 58 of 118 definite viral infections. Overall, 14 of 444 children died (3.2%). There were 12 deaths in the 260 children with PSS greater than or equal to 2, and two deaths in the 184 children with PSS less than 2 (4.6% vs. 1.1%; absolute difference, 3.5%; 95% CI, 0.1-6.9%; p = 0.04).

CONCLUSIONS: In 2014-2016, over half of the critically ill children undergoing emergency transport to PICU with presumed or confirmed infection, and meeting retrospectively applied PSS criteria for sepsis, had a range of clinical diagnoses including bronchiolitis, meningoencephalitis, and pneumonia/empyema. Furthermore, the PSS criteria for categorization of sepsis and septic shock were associated with outcome and may be of value in future risk-stratification in clinical trials.

PMID:39750062 | DOI:10.1097/PCC.0000000000003682

Nature. 2025 Jan 1. doi: 10.1038/s41586-024-08309-9. Online ahead of print.

ABSTRACT

The dynamics of the genetic diversity of pathogens, including the emergence of lineages with increased fitness, is a foundational concept of disease ecology with key public-health implications. However, the identification of such lineages and estimation of associated fitness remain challenging, and is rarely done outside densely sampled systems1,2. Here we present phylowave, a scalable approach that summarizes changes in population composition in phylogenetic trees, enabling the automatic detection of lineages based on shared fitness and evolutionary relationships. We use our approach on a broad set of viruses and bacteria (SARS-CoV-2, influenza A subtype H3N2, Bordetella pertussis and Mycobacterium tuberculosis), which include both well-studied and understudied threats to human health. We show that phylowave recovers the main known circulating lineages for each pathogen and that it can detect specific amino acid changes linked to fitness changes. Furthermore, phylowave identifies previously undetected lineages with increased fitness, including three co-circulating B. pertussis lineages. Inference using phylowave is robust to uneven and limited observations. This widely applicable approach provides an avenue to monitor evolution in real time to support public-health action and explore fundamental drivers of pathogen fitness.

PMID:39743587 | DOI:10.1038/s41586-024-08309-9

PLoS Genet. 2024 Dec 26;20(12):e1011456. doi: 10.1371/journal.pgen.1011456. Online ahead of print.

ABSTRACT

Inhibitory killer cell immunoglobulin-like receptors (iKIRs) are a family of inhibitory receptors that are expressed by natural killer (NK) cells and late-stage differentiated T cells. There is accumulating evidence that iKIRs regulate T cell-mediated immunity. Recently, we reported that T cell-mediated control was enhanced by iKIRs in chronic viral infections. We hypothesized that in the context of autoimmunity, where an enhanced T cell response might be considered detrimental, iKIRs would have an opposite effect. We studied Type 1 diabetes (T1D) as a paradigmatic example of autoimmunity. In T1D, variation in the Human Leucocyte Antigen (HLA) genes explains up to 50% of the genetic risk, indicating that T cells have a major role in T1D etiopathogenesis. To investigate if iKIRs affect this T cell response we asked whether HLA associations were modified by iKIR genes. We conducted an immunogenetic analysis of a case-control T1D dataset (N = 11,961) and found that iKIR genes, in the presence of genes encoding their ligands, have a consistent and significant effect on protective HLA class II genetic associations. Our results were validated in an independent data set. We conclude that iKIRs significantly decrease HLA class II protective associations and suggest that iKIRs regulate CD4+ T cell responses in T1D.

PMID:39724143 | DOI:10.1371/journal.pgen.1011456

Cell Rep. 2024 Dec 20;44(1):115079. doi: 10.1016/j.celrep.2024.115079. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa produces a wealth of virulence factors whose production is controlled via an intricate regulatory systems network. Here, we uncover a major player in the evolution and regulation of virulence that enhances host colonization and antibiotic resistance. By characterizing a collection of mutants lacking the stringent response (SR), a system key for virulence, we show that the loss of the central regulator MexT bypasses absence of the SR, restoring full activation of virulence pathways. Notably, mexT mutations were associated with resistance to aminoglycosides and the last-resort antibiotic, colistin. Analysis of thousands of P. aeruginosa genomes revealed that mexT mutations are widespread in isolates linked to aggressive antibiotic treatment. Furthermore, in vivo experiments in a murine pulmonary model revealed that mexT mutants display a hypervirulent phenotype associated with bacteremia. Altogether, these findings uncover a key regulator that acts as a genetic switch in the regulation of virulence and antimicrobial resistance.

PMID:39708318 | DOI:10.1016/j.celrep.2024.115079

PLoS Comput Biol. 2024 Dec 19;20(12):e1012562. doi: 10.1371/journal.pcbi.1012562. eCollection 2024 Dec.

ABSTRACT

There is an urgent need for mathematical models that can be used to inform the deployment of surveillance, early warning and management systems for transboundary pest invasions. This is especially important for desert locust, one of the most dangerous migratory pests for smallholder farmers. During periods of desert locust upsurges and plagues, gregarious adult locusts form into swarms that are capable of long-range dispersal. Here we introduce a novel integrated modelling framework for use in predicting gregarious locust populations. The framework integrates the selection of breeding sites, maturation through egg, hopper and adult stages and swarm dispersal in search of areas suitable for feeding and breeding. Using a combination of concepts from epidemiological modelling, weather and environment data, together with an atmospheric transport model for swarm movement we provide a tool to forecast short- and long-term swarm movements. A principal aim of the framework is to provide a practical starting point for use in the next upsurge.

PMID:39700069 | DOI:10.1371/journal.pcbi.1012562

BMC Public Health. 2024 Dec 18;24(1):3520. doi: 10.1186/s12889-024-21029-z.

ABSTRACT

BACKGROUND: Our primary focus was Schistosoma mansoni infection and schoolchildren. Within communities the social environment may promote individual risk of infection for the school-aged children. There will also be demographic groups who are not targeted or reached by preventive chemotherapy campaigns. The behaviours of these other groups will interact with those of school-aged children, resulting in further infection risk through exposure-related behaviours. Furthermore, perception of the disease may significantly influence the schoolchildren's lived experience of the infection and associated disease. It is therefore crucial to document the daily experiences of schoolchildren living in schistosomiasis high transmission areas along Lake Albert, Hoima District.

METHODS: An ethnographic study explored schoolchildren's perspectives and daily life organisations that shape their risk of schistosomiaisis and their perceptions of the disease. The study was conducted between November 2022 and August 2023. It involved in-depth interviews with schoolchildren and their parents, key informant interviews, focus group discussions with schoolchildren, and participant observations. Data was analysed using a reflexive thematic analysis. Code reports were generated inductively using ATLAS.ti (Version 7).

RESULTS: The study revealed a significant level of knowledge and awareness about schistosomiasis among schoolchildren. They had understanding of the risk factors, continued exposure, and experiences of illness, though they had little autonomy to address these through their own behaviour as they were influenced by the behaviour of others and macro-factors such as WASH provision and economic need. Study participants experienced individual-level effects of schistosomiasis such as educational impacts and isolation as a significant form of stigma.

CONCLUSIONS: There is a need for continued community sensitisation and awareness campaigns to address social stigma, educational impact, and contamination and exposure-related behaviours. National and regional policies and programmes on WASH, livelihood and poverty eradication programmes need to be revisited in schistosomiasis high transmission areas to help provide alternatives and improve schoolchildren's lived experiences.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:39695523 | DOI:10.1186/s12889-024-21029-z