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An Interdisciplinary Research Centre at the University of Cambridge

Light management by algal aggregates in living photosynthetic hydrogels

Tue, 28/05/2024 - 11:00

Proc Natl Acad Sci U S A. 2024 Jun 4;121(23):e2316206121. doi: 10.1073/pnas.2316206121. Epub 2024 May 28.


Rapid progress in algal biotechnology has triggered a growing interest in hydrogel-encapsulated microalgal cultivation, especially for the engineering of functional photosynthetic materials and biomass production. An overlooked characteristic of gel-encapsulated cultures is the emergence of cell aggregates, which are the result of the mechanical confinement of the cells. Such aggregates have a dramatic effect on the light management of gel-encapsulated photobioreactors and hence strongly affect the photosynthetic outcome. To evaluate such an effect, we experimentally studied the optical response of hydrogels containing algal aggregates and developed optical simulations to study the resultant light intensity profiles. The simulations are validated experimentally via transmittance measurements using an integrating sphere and aggregate volume analysis with confocal microscopy. Specifically, the heterogeneous distribution of cell aggregates in a hydrogel matrix can increase light penetration while alleviating photoinhibition more effectively than in a flat biofilm. Finally, we demonstrate that light harvesting efficiency can be further enhanced with the introduction of scattering particles within the hydrogel matrix, leading to a fourfold increase in biomass growth. Our study, therefore, highlights a strategy for the design of spatially efficient photosynthetic living materials that have important implications for the engineering of future algal cultivation systems.

PMID:38805271 | DOI:10.1073/pnas.2316206121

Investigating the Interactions of the Cucumber Mosaic Virus 2b Protein with the Viral 1a Replicase Component and the Cellular RNA Silencing Factor Argonaute 1

Sat, 25/05/2024 - 11:00

Viruses. 2024 Apr 25;16(5):676. doi: 10.3390/v16050676.


The cucumber mosaic virus (CMV) 2b protein is a suppressor of plant defenses and a pathogenicity determinant. Amongst the 2b protein's host targets is the RNA silencing factor Argonaute 1 (AGO1), which it binds to and inhibits. In Arabidopsis thaliana, if 2b-induced inhibition of AGO1 is too efficient, it induces reinforcement of antiviral silencing by AGO2 and triggers increased resistance against aphids, CMV's insect vectors. These effects would be deleterious to CMV replication and transmission, respectively, but are moderated by the CMV 1a protein, which sequesters sufficient 2b protein molecules into P-bodies to prevent excessive inhibition of AGO1. Mutant 2b protein variants were generated, and red and green fluorescent protein fusions were used to investigate subcellular colocalization with AGO1 and the 1a protein. The effects of mutations on complex formation with the 1a protein and AGO1 were investigated using bimolecular fluorescence complementation and co-immunoprecipitation assays. Although we found that residues 56-60 influenced the 2b protein's interactions with the 1a protein and AGO1, it appears unlikely that any single residue or sequence domain is solely responsible. In silico predictions of intrinsic disorder within the 2b protein secondary structure were supported by circular dichroism (CD) but not by nuclear magnetic resonance (NMR) spectroscopy. Intrinsic disorder provides a plausible model to explain the 2b protein's ability to interact with AGO1, the 1a protein, and other factors. However, the reasons for the conflicting conclusions provided by CD and NMR must first be resolved.

PMID:38793558 | DOI:10.3390/v16050676

Intratumoral antigen signaling traps CD8<sup>+</sup> T cells to confine exhaustion to the tumor site

Fri, 24/05/2024 - 11:00

Sci Immunol. 2024 May 24;9(95):eade2094. doi: 10.1126/sciimmunol.ade2094. Epub 2024 May 24.


Immunotherapy advances have been hindered by difficulties in tracking the behaviors of lymphocytes after antigen signaling. Here, we assessed the behavior of T cells active within tumors through the development of the antigen receptor signaling reporter (AgRSR) mouse, fate-mapping lymphocytes responding to antigens at specific times and locations. Contrary to reports describing the ready egress of T cells out of the tumor, we find that intratumoral antigen signaling traps CD8+ T cells in the tumor. These clonal populations expand and become increasingly exhausted over time. By contrast, antigen-signaled regulatory T cell (Treg) clonal populations readily recirculate out of the tumor. Consequently, intratumoral antigen signaling acts as a gatekeeper to compartmentalize CD8+ T cell responses, even within the same clonotype, thus enabling exhausted T cells to remain confined to a specific tumor tissue site.

PMID:38787961 | DOI:10.1126/sciimmunol.ade2094

Ectoparasite and bacterial population genetics and community structure indicate extent of bat movement across an island chain

Fri, 24/05/2024 - 11:00

Parasitology. 2024 May 24:1-53. doi: 10.1017/S0031182024000660. Online ahead of print.


PMID:38785194 | DOI:10.1017/S0031182024000660

Ten-Year Risk Equations for Incident Heart Failure in Established Atherosclerotic Cardiovascular Disease Populations

Thu, 23/05/2024 - 11:00

J Am Heart Assoc. 2024 May 23:e034254. doi: 10.1161/JAHA.124.034254. Online ahead of print.


BACKGROUND: Ten-year risk equations for incident heart failure (HF) are available for the general population, but not for patients with established atherosclerotic cardiovascular disease (ASCVD), which is highly prevalent in HF cohorts. This study aimed to develop and validate 10-year risk equations for incident HF in patients with known ASCVD.

METHODS AND RESULTS: Ten-year risk equations for incident HF were developed using the United Kingdom Biobank cohort (recruitment 2006-2010) including participants with established ASCVD but free from HF at baseline. Model performance was validated using the Australian Baker Heart and Diabetes Institute Biobank cohort (recruitment 2000-2011) and compared with the performance of general population risk models. Incident HF occurred in 13.7% of the development cohort (n=31 446, median 63 years, 35% women, follow-up 10.7±2.7 years) and in 21.3% of the validation cohort (n=1659, median age 65 years, 25% women, follow-up 9.4±3.7 years). Predictors of HF included in the sex-specific models were age, body mass index, systolic blood pressure (treated or untreated), glucose (treated or untreated), cholesterol, smoking status, QRS duration, kidney disease, myocardial infarction, and atrial fibrillation. ASCVD-HF equations had good discrimination and calibration in development and validation cohorts, with superior performance to general population risk equations.

CONCLUSIONS: ASCVD-specific 10-year risk equations for HF outperform general population risk models in individuals with established ASCVD. The ASCVD-HF equations can be calculated from readily available clinical data and could facilitate screening and preventative treatment decisions in this high-risk group.

PMID:38780153 | DOI:10.1161/JAHA.124.034254

Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children

Sat, 18/05/2024 - 11:00

Nat Commun. 2024 May 18;15(1):4227. doi: 10.1038/s41467-024-48699-y.


Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vβ21.3+ T-cell subgroup. Here we apply muti-single cell omics to compare the inflammatory process in children with acute respiratory COVID-19 and those presenting with non SARS-CoV-2 infections in children. Here we show that in Multi-Inflammatory Syndrome in Children (MIS-C), the natural killer cell and monocyte population demonstrate heightened CD95 (Fas) and Interleuking 18 receptor expression. Additionally, TCR Vβ21.3+ CD4+ T-cells exhibit skewed differentiation towards T helper 1, 17 and regulatory T cells, with increased expression of the co-stimulation receptors ICOS, CD28 and interleukin 18 receptor. We observe no functional evidence for NLRP3 inflammasome pathway overactivation, though MIS-C monocytes show elevated active caspase 8. This, coupled with raised IL18 mRNA expression in CD16- NK cells on single cell RNA sequencing analysis, suggests interleukin 18 and CD95 signalling may trigger activation of TCR Vβ21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.

PMID:38762592 | DOI:10.1038/s41467-024-48699-y

Direct comparison of SARS-CoV-2 variant specific neutralizing antibodies in human and hamster sera

Sat, 18/05/2024 - 11:00

NPJ Vaccines. 2024 May 18;9(1):85. doi: 10.1038/s41541-024-00888-y.


Antigenic characterization of newly emerging SARS-CoV-2 variants is important to assess their immune escape and judge the need for future vaccine updates. To bridge data obtained from animal sera with human sera, we analyzed neutralizing antibody titers in human and hamster single infection sera in a highly controlled setting using the same authentic virus neutralization assay performed in one laboratory. Using a Bayesian framework, we found that titer fold changes in hamster sera corresponded well to human sera and that hamster sera generally exhibited higher reactivity.

PMID:38762525 | DOI:10.1038/s41541-024-00888-y

A novel family of defensin-like peptides from Hermetia illucens with antibacterial properties

Thu, 16/05/2024 - 11:00

BMC Microbiol. 2024 May 16;24(1):167. doi: 10.1186/s12866-024-03325-1.


BACKGROUND: The world faces a major infectious disease challenge. Interest in the discovery, design, or development of antimicrobial peptides (AMPs) as an alternative approach for the treatment of bacterial infections has increased. Insects are a good source of AMPs which are the main effector molecules of their innate immune system. Black Soldier Fly Larvae (BSFL) are being developed for large-scale rearing for food sustainability, waste reduction and as sustainable animal and fish feed. Bioinformatic studies have suggested that BSFL have the largest number of AMPs identified in insects. However, most AMPs identified in BSF have not yet undergone antimicrobial evaluation but are promising leads to treat critical infections.

RESULTS: Jg7197.t1, Jg7902.t1 and Jg7904.t1 were expressed into the haemolymph of larvae following infection with Salmonella enterica serovar Typhimurium and were predicted to be AMPs using the computational tool ampir. The genes encoding these proteins were within 2 distinct clusters in chromosome 1 of the BSF genome. Following removal of signal peptides, predicted structures of the mature proteins were superimposed, highlighting a high degree of structural conservation. The 3 AMPs share primary sequences with proteins that contain a Kunitz-binding domain; characterised for inhibitory action against proteases, and antimicrobial activities. An in vitro antimicrobial screen indicated that heterologously expressed SUMO-Jg7197.t1 and SUMO-Jg7902.t1 did not show activity against 12 bacterial strains. While recombinant SUMO-Jg7904.t1 had antimicrobial activity against a range of Gram-negative and Gram-positive bacteria, including the serious pathogen Pseudomonas aeruginosa.

CONCLUSIONS: We have cloned and purified putative AMPs from BSFL and performed initial in vitro experiments to evaluate their antimicrobial activity. In doing so, we have identified a putative novel defensin-like AMP, Jg7904.t1, encoded in a paralogous gene cluster, with antimicrobial activity against P. aeruginosa.

PMID:38755524 | DOI:10.1186/s12866-024-03325-1

Comparative analysis of SARS-CoV-2 neutralization titers reveals consistency between human and animal model serum and across assays

Wed, 15/05/2024 - 11:00

Sci Transl Med. 2024 May 15;16(747):eadl1722. doi: 10.1126/scitranslmed.adl1722. Epub 2024 May 15.


The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires ongoing monitoring to judge the ability of newly arising variants to escape the immune response. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal serum samples. We compared 18 datasets generated using human, hamster, and mouse serum and six different neutralization assays. Datasets using animal model serum samples showed higher titer magnitudes than datasets using human serum samples in this comparison. Fold change in neutralization of variants compared to ancestral SARS-CoV-2, immunodominance patterns, and antigenic maps were similar among serum samples and assays. Most assays yielded consistent results, except for differences in fold change in cytopathic effect assays. Hamster serum samples were a consistent surrogate for human first-infection serum samples. These results inform the transition of surveillance of SARS-CoV-2 antigenic variation from dependence on human first-infection serum samples to the utilization of serum samples from animal models.

PMID:38748773 | DOI:10.1126/scitranslmed.adl1722

An ovine model for investigation of the microenvironment of the male mammary gland

Sun, 12/05/2024 - 11:00

J Anat. 2024 May 12. doi: 10.1111/joa.14055. Online ahead of print.


The specific biology of the male breast remains relatively unexplored in spite of the increasing global prevalence of male breast cancer. Delineation of the microenvironment of the male breast is restricted by the low availability of human samples and a lack of characterisation of appropriate animal models. Unlike the mouse, the male ovine gland persists postnatally. We suggest that the male ovine mammary gland constitutes a promising adjunctive model for the male breast. In this study, we evaluate the male ovine mammary gland microenvironment, comparing intact and neutered males. Assessment of the glandular histo-anatomy highlights the resemblance of the male gland to that of neonatal female sheep and confirms the presence of rudimentary terminal duct lobular units. Irrespective of neutered status, cell proliferation in epithelial and stromal compartments is similarly low in males, and cell proliferation in epithelial cells and in the intralobular stroma is significantly lower than in pubertal female sheep. Between 42% and 72% of the luminal mammary epithelial cells in the male gland express the androgen receptor and expression is significantly reduced by neutering. Luminal epithelial cells within the intact and neutered male gland also express oestrogen receptor alpha, but minimal progesterone receptor expression is observed. The distribution of leukocytes within the ducts and stroma is similar to the mammary gland of female sheep and females of other species. Both macrophages and T lymphocytes are intercalated in the epithelial bilayer and are more abundant in the intralobular stroma than the interlobular stroma, suggesting that they may have a protective immunological function within the vestigial glandular tissue of the male sheep. Mast cells are also observed within the stroma. These cells cluster near the glandular tissue and are frequently located adjacent to blood vessels. The abundance of mast cells is significantly higher in intact males compared to neutered males, suggesting that hormone signalling may impact mast cell recruitment. In this study, we demonstrate the utility of the male ovine mammary gland as a model for furthering our knowledge of postnatal male mammary biology.

PMID:38735860 | DOI:10.1111/joa.14055

Lessons from birth to decline of pig-adapted Salmonella

Fri, 10/05/2024 - 11:00

Nat Food. 2024 May 10. doi: 10.1038/s43016-024-00986-z. Online ahead of print.


PMID:38730272 | DOI:10.1038/s43016-024-00986-z

A synoptic review of plant disease epidemics and outbreaks published in 2022

Thu, 09/05/2024 - 11:00

Phytopathology. 2024 May 9. doi: 10.1094/PHYTO-01-24-0042-RVW. Online ahead of print.


This scientometric study reviews the scientific literature and CABI distribution records published in 2022 to find evidence of major disease outbreaks and first reports of pathogens in new locations or on new hosts. This is the second time we have done this, and this study builds on our work documenting and analysing reports from 2021. Pathogens with three or more articles identified in 2022 literature were: Xylella fastidiosa, Bursaphelenchus xylophilus, Meloidogyne species complexes, Candidatus Liberibacter asiaticus, Raffaelea lauricola, Fusarium oxysporum formae specialis and Puccinia graminis f. sp. tritici. Our review of CABI distribution records found 29 pathogens with confirmed first reports in 2022. Pathogens with four or more first reports were: Meloidogyne species complexes, Pantoea ananatis, grapevine red globe virus and Thekopsora minima. Analysis of the proportion of new distribution records from 2022 indicated that grapevine red globe virus, sweet potato chlorotic stunt virus and Ca. Phytoplasma vitis may have been actively spreading. As we saw last year, there was little overlap between the pathogens identified by reviewing scientific literature versus distribution records. Strikingly, too, there was also no overlap between species assessed to be actively spreading in this year's study and those identified last year. In general, introduction of new pathogens and outbreaks of extant pathogens threaten food security and ecosystem services. Continued monitoring of these threats is essential to support phytosanitary measures intended to prevent pathogen introductions and management of threats within a country.

PMID:38723169 | DOI:10.1094/PHYTO-01-24-0042-RVW

A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma

Thu, 09/05/2024 - 11:00

Nat Commun. 2024 May 9;15(1):3900. doi: 10.1038/s41467-024-48034-5.


By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.

PMID:38724552 | DOI:10.1038/s41467-024-48034-5

Towards the Targeted Protein Degradation of PRMT1

Thu, 09/05/2024 - 11:00

ChemMedChem. 2024 May 9:e202400269. doi: 10.1002/cmdc.202400269. Online ahead of print.


Targeting the protein arginine methyltransferase 1 (PRMT1) has emerged as a promising therapeutic strategy in cancer treatment. The phase 1 clinical trial for GSK3368715, the first PRMT1 inhibitor to enter the clinic, was terminated early due to a lack of clinical efficacy, extensive treatment-emergent effects, and dose-limiting toxicities. The incidence of the latter two events may be associated with inhibition-driven pharmacology as a high and sustained concentration of inhibitor is required for therapeutic effect. The degradation of PRMT1 using a proteolysis targeting chimera (PROTAC) may be superior to inhibition as proceeds via event-driven pharmacology where a PROTAC acts catalytically at a low dose. PROTACs containing the same pharmacophore as GSK3368715, combined with a motif that recruits the VHL or CRBN E3-ligase, were synthesised. Suitable cell permeability and target engagement were shown for selected candidates by the detection of downstream effects of PRMT1 inhibition and by a NanoBRET assay for E3-ligase binding, however the candidates did not induce PRMT1 degradation. This paper is the first reported investigation of PRMT1 for targeted protein degradation and provides hypotheses and insights to assist the design of PROTACs for PRMT1 and other novel target proteins.

PMID:38724444 | DOI:10.1002/cmdc.202400269

Enhanced diagnosis of severe bacterial and fungal respiratory infection in children using a rapid syndromic array-case report

Wed, 08/05/2024 - 11:00

Transl Pediatr. 2024 Apr 30;13(4):697-703. doi: 10.21037/tp-23-525. Epub 2024 Apr 11.


BACKGROUND: A microbiological cause of infection is infrequently identified in critically unwell children with a respiratory infection. Molecular diagnostic arrays provide an alternative. These tests are becoming more broadly available, but little is known about how clinicians interpret the results to impact clinical decision making.

CASE DESCRIPTION: Here we describe three cases of bacterial and fungal lower respiratory tract infection (LRTI) diagnosed in the paediatric intensive care unit (PICU) using a custom 52 respiratory pathogen TaqMan array card (TAC). Firstly, an early diagnosis of Candida albicans pneumonia was made with the support of the TAC in a trauma patient who received prolonged mechanical ventilation. The pathogen was only identified on microbiological cultures after further clinical deterioration had occurred. Secondly, a rare case of psittacosis was identified in an adolescent with acute respiratory distress, initially suspected to have multisystem inflammatory syndrome in children (MIS-C). Finally, Haemophilus influenzae pneumonia was identified in an infant with recurrent apnoeas, initially treated for meningitis. Two diagnoses would not have been established using commercially available arrays, and pathogen-specific diagnoses were established faster than that of routine microbiological culture.

CONCLUSIONS: The pathogens included on molecular arrays and interpretation by a multidisciplinary team are crucial in providing value to PICU diagnostic services. Molecular arrays have the potential to enhance early pathogen-specific diagnosis of LRTI in the PICU.

PMID:38715674 | PMC:PMC11071030 | DOI:10.21037/tp-23-525

MVMRmode: Introducing an R package for plurality valid estimators for multivariable Mendelian randomisation

Tue, 07/05/2024 - 11:00

PLoS One. 2024 May 7;19(5):e0291183. doi: 10.1371/journal.pone.0291183. eCollection 2024.


BACKGROUND: Mendelian randomisation (MR) is the use of genetic variants as instrumental variables. Mode-based estimators (MBE) are one of the most popular types of estimators used in univariable-MR studies and is often used as a sensitivity analysis for pleiotropy. However, because there are no plurality valid regression estimators, modal estimators for multivariable-MR have been under-explored.

METHODS: We use the residual framework for multivariable-MR to introduce two multivariable modal estimators: multivariable-MBE, which uses IVW to create residuals fed into a traditional plurality valid estimator, and an estimator which instead has the residuals fed into the contamination mixture method (CM), multivariable-CM. We then use Monte-Carlo simulations to explore the performance of these estimators when compared to existing ones and re-analyse the data used by Grant and Burgess (2021) looking at the causal effect of intelligence, education, and household income on Alzheimer's disease as an applied example.

RESULTS: In our simulation, we found that multivariable-MBE was generally too variable to be much use. Multivariable-CM produced more precise estimates on the other hand. Multivariable-CM performed better than MR-Egger in almost all settings, and Weighted Median under balanced pleiotropy. However, it underperformed Weighted Median when there was a moderate amount of directional pleiotropy. Our re-analysis supported the conclusion of Grant and Burgess (2021), that intelligence had a protective effect on Alzheimer's disease, while education, and household income do not have a causal effect.

CONCLUSIONS: Here we introduced two, non-regression-based, plurality valid estimators for multivariable MR. Of these, "multivariable-CM" which uses IVW to create residuals fed into a contamination-mixture model, performed the best. This estimator uses a plurality of variants valid assumption, and appears to provide precise and unbiased estimates in the presence of balanced pleiotropy and small amounts of directional pleiotropy.

PMID:38713711 | DOI:10.1371/journal.pone.0291183

How are Trypanosoma brucei receptors protected from host antibody-mediated attack?

Tue, 07/05/2024 - 11:00

Bioessays. 2024 May 7:e2400053. doi: 10.1002/bies.202400053. Online ahead of print.


Trypanosoma brucei is the causal agent of African Trypanosomiasis in humans and other animals. It maintains a long-term infection through an antigenic variation based population survival strategy. To proliferate in a mammal, T. brucei acquires iron and haem through the receptor mediated uptake of host transferrin and haptoglobin-hemoglobin respectively. The receptors are exposed to host antibodies but this does not lead to clearance of the infection. Here we discuss how the trypanosome avoids this fate in the context of recent findings on the structure and cell biology of the receptors.

PMID:38713161 | DOI:10.1002/bies.202400053

Utility of decision tools for assessing plant health risks from management strategies in natural environments

Mon, 06/05/2024 - 11:00

Ecol Evol. 2024 May 2;14(5):e11308. doi: 10.1002/ece3.11308. eCollection 2024 May.


Increased imports of plants and timber through global trade networks provide frequent opportunities for the introduction of novel plant pathogens that can cross-over from commercial to natural environments, threatening native species and ecosystem functioning. Prevention or management of such outbreaks relies on a diversity of cross-sectoral stakeholders acting along the invasion pathway. Yet, guidelines are often only produced for a small number of stakeholders, missing opportunities to consider ways to control outbreaks in other parts of the pathway. We used the infection of common juniper with the invasive pathogen Phytophthora austrocedri as a case study to explore the utility of decision tools for managing outbreaks of plant pathogens in the wider environment. We invited stakeholders who manage or monitor juniper populations or supply plants or management advice to participate in a survey exploring their awareness of, and ability to use, an existing decision tree produced by a coalition of statutory agencies augmented with new distribution maps designed by the authors. Awareness of the decision tree was low across all stakeholder groups including those planting juniper for restoration purposes. Stakeholders requested that decision tools contain greater detail about environmental conditions that increase host vulnerability to the pathogen, and clearer examples of when management practices implicated in pathogen introduction or spread should not be adopted. The results demonstrate the need to set clear objectives for the purpose of decision tools and to frame and co-produce them with many different stakeholders, including overlooked groups, such as growers and advisory agents, to improve management of pathogens in the wider environment.

PMID:38706934 | PMC:PMC11066480 | DOI:10.1002/ece3.11308

Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization

Sun, 05/05/2024 - 11:00

Lancet. 2024 May 2:S0140-6736(24)00850-X. doi: 10.1016/S0140-6736(24)00850-X. Online ahead of print.


BACKGROUND: WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception.

METHODS: In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period.

FINDINGS: Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood.

INTERPRETATION: Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality.


PMID:38705159 | DOI:10.1016/S0140-6736(24)00850-X

Effect of pooled tracheal sample testing on the probability of Mycoplasma hyopneumoniae detection

Fri, 03/05/2024 - 11:00

Sci Rep. 2024 May 3;14(1):10226. doi: 10.1038/s41598-024-60377-z.


Tracheal pooling for Mycoplasma hyopneumoniae (M. hyopneumoniae) DNA detection allows for decreased diagnostic cost, one of the main constraints in surveillance programs. The objectives of this study were to estimate the sensitivity of pooled-sample testing for the detection of M. hyopneumoniae in tracheal samples and to develop probability of M. hyopneumoniae detection estimates for tracheal samples pooled by 3, 5, and 10. A total of 48 M. hyopneumoniae PCR-positive field samples were pooled 3-, 5-, and 10-times using field M. hyopneumoniae DNA-negative samples and tested in triplicate. The sensitivity was estimated at 0.96 (95% credible interval [Cred. Int.]: 0.93, 0.98) for pools of 3, 0.95 (95% Cred. Int: 0.92, 0.98) for pools of 5, and 0.93 (95% Cred. Int.: 0.89, 0.96) for pools of 10. All pool sizes resulted in PCR-positive if the individual tracheal sample Ct value was < 33. Additionally, there was no significant decrease in the probability of detecting at least one M. hyopneumoniae-infected pig given any pool size (3, 5, or 10) of tracheal swabs. Furthermore, this manuscript applies the probability of detection estimates to various real-life diagnostic testing scenarios. Combining increased total animals sampled with pooling can be a cost-effective tool to maximize the performance of M. hyopneumoniae surveillance programs.

PMID:38702379 | DOI:10.1038/s41598-024-60377-z