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Shigella flexneri evades septin-mediated cell-autonomous immunity via protein ADP-riboxanation.
No full textCell-autonomous immunity represents evolutionarily conserved defense mechanisms present in both immune and non-immune cells. One of such mechanisms is mediated by cytoskeletal septins that entrap cytosolic bacterial pathogens within cage-like structures. To promote infection, Shigella flexneri delivers effector proteins directly into host cells via a type III secretion system. Here we demonstrate that OspC effectors enable Shigella flexneri to evade septin cage entrapment. Mechanistically, OspC catalyzes ADP-riboxanation of SEPT9 at Arg561, a site essential for stabilizing septin hetero-oligomers. Notably, Arg561 ADP-riboxanation impairs septin polymerization and hence assembly of higher-order structures, including filaments and cage-like structures. Furthermore, we provide evidence that OspC effectors act synergistically with OspG to antagonize septin cage entrapment via two distinct post-translational modifications, thereby facilitating cell-to-cell spread and intracellular replication. Overall, our work reveals the elegant strategies of bacterial pathogens to evade septin-mediated cell-autonomous immunity and offers avenues for therapeutic intervention
Exploring the cause of the pertussis resurgence in England following the COVID-19 pandemic: a mathematical modelling study.
Get PDFBACKGROUND: In 2024 England, in common with many other countries, experienced a pertussis resurgence the cause of which is unclear. We used a pertussis transmission model, previously developed to investigate the cause of the pertussis resurgence in England in 2012, to explore potential factors contributing to the increase in pertussis cases observed in England in 2024.
METHODS: An age-stratified dynamic transmission model fitted to pertussis notification data from England between 1953 and 2013 was run until 2034 with and without changes in social mixing as estimated from Google mobility and school attendance data during the COVID-19 pandemic. The model assumes vaccination protects better against disease than pertussis infection, and that infected vaccinees can transmit if asymptomatic or with only mild/atypical symptoms. Infection is assumed to result in protection against clinical symptoms and infection, and provide more durable immunity than vaccination. Counterfactual scenarios were run to explore the effect of reductions in vaccine coverage during the pandemic and of the addition in 2014 of boosters in the 2nd year of life and in adolescence.
RESULTS: A resurgence was only generated with reduced social mixing and could not be explained by short-term reductions in vaccine coverage. Additional boosters from 2014 would not have prevented a resurgence. Peaks of increased pertussis incidence are predicted over the next decade. The parameter sets that generated a resurgence in 2024 had the shortest duration of acellular vaccine protection, median 5 years with 90% protection against infection.
CONCLUSION: This modelling study implicates reduced mixing in England during the COVID-19 pandemic as the cause of the pertussis resurgence in 2024 together with the short duration of protection from acellular vaccine. Interruption of the background rate of natural boosting during the pandemic increased the pool of susceptible individuals resulting in increased transmission post-pandemic with clinical cases in those with waned vaccine–induced protection and the unvaccinated, including infants of unvaccinated mothers. In countries using acellular pertussis vaccines, infection continues to play an important role in maintaining population immunity around an endemic equilibrium. Improved pertussis vaccines that provide more complete and more durable protection against infection are needed to improve pertussis control.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-026-12521-5
Characteristics Influencing Support for the National Health Service COVID-19 App in England and Wales: Findings From a Longitudinal Survey.
Get PDFBACKGROUND: The use of proximity (contact) tracing mobile phone apps during the COVID-19 pandemic to support manual contact tracing was novel. Uptake of the app was lower than expected. OBJECTIVE: We sought to identify distinct subgroups of individuals based on their level of support for the National Health Service (NHS) COVID-19 app in the first 15 months of the app's implementation, and to identify the attitudes and characteristics associated with membership of more and less supportive groups. METHODS: We conducted 8 waves of a longitudinal survey data of smartphone users, recruited from an online panel (n=2023 at baseline and n=1198 at survey wave 6) between October 14, 2020, and December 13, 2021. We used latent class analysis to identify subgroups of individuals with different inclinations of support for the NHS COVID-19 app. Sankey diagram analysis was used to assess individuals whose subgroup changed over the study period. We estimated population-weighted multinomial logistic regression models using sociodemographic characteristics as independent variables. RESULTS: We identified 4 subgroups in survey waves 1 to 4-"not supportive" (1765/7210, 25%), "ambivalent" (2124/7210, 30%), "somewhat supportive" (1421/7219, 20%), and "completely supportive" (1900/7210, 26%). At wave 5, a total of 3 subgroups of support for the app emerged-"not supportive" (549/1613, 34%), "ambivalent" (497/1613, 31%), and "supportive" (567/1613, 35%). From wave 6 onward, the results showed 4 subgroups emerging-"least supportive" (1568/6952, 23%), "less supportive" (1179/6952, 17%), "ambivalent" (2105/6952, 30%), and "supportive" (2100/6952, 29%). The majority of respondents remained within their identified subgroups between survey waves. Among those who moved into different subgroups, most moved into a less supportive subgroup. Exceptions to this were from waves 2 to 3 and from waves 3 to 4, when higher percentages of respondents moved into more supportive subgroups. The biggest movement to less supportive subgroups occurred after wave 1 (October 2020), when 38% (2740/7210) of respondents moved into a less supportive subgroup. The biggest movement to more supportive subgroups, on the other hand, occurred after wave 2, when 22% (1586/7210) of respondents moved into more supportive subgroups. Over the course of the 8 waves, the percentage of respondents in supportive subgroups declined from 56% (3353/5988) to 29% (1737/5988). Key characteristics of more supportive individuals included having higher levels of trust in the government to control the spread of COVID-19 and having the app installed, while those less concerned about the risk COVID-19 posed to the country were more likely to be unsupportive (P<.05). CONCLUSIONS: When the app was launched, just over half of respondents were supportive, but this declined over the following 15 months. The attrition in support poses important challenges for governments to the use of apps in future pandemics. A potential reason was mistrust in the government's handling of the pandemic
Multidrug-resistant non-typhoidal Salmonella and Escherichia coli in imported poultry products in the Maldives
Get PDFAntimicrobial resistance (AMR) increasingly compromises food safety and public health worldwide. Poultry products are major vectors for AMR bacteria in the food supply. We conducted the first preliminary survey of non-typhoidal Salmonella (NTS) and Escherichia coli on imported poultry in the Maldives. A total of 30 frozen whole chicken samples (15 processed as whole and 15 separated into meat and skin) and 3 pooled egg samples (10 eggs per pool) were obtained from supermarkets and grocery stores in Greater Malé between June 2022 and July 2022. Standard culture methods (Food and Drug Administration Bacteriological Analytical Manual) were used to isolate NTS and E. coli, and isolates were tested for susceptibility to five antibiotics (ampicillin, ceftriaxone, ciprofloxacin, tetracycline and trimethoprim-sulphamethoxazole) by disc diffusion [European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines]. NTS was recovered from 10 of 30 (33.3%) chicken samples, predominantly from skin (9/15) versus meat (3/15); E. coli was found in 15 of 30 (50%) samples, more often in meat. One pooled egg sample (33%) was positive for E. coli. Among 13 NTS isolates, 69% (9/13) were resistant to tetracycline, and 38% (5/13) to ciprofloxacin, ampicillin and ceftriaxone. Thirty-eight per cent (5/13) of NTS were classified by EUCAST as susceptible, increased exposure to ciprofloxacin. Overall, 9 of 13 (69.2%) NTS isolates were multidrug-resistant (MDR; non-susceptible to ≥3 classes). In E. coli, resistance was most common to ampicillin (8/19; 42.1%), followed by tetracycline (5/19; 26.3%), trimethoprim-sulphamethoxazole (4/19; 21.1%), ciprofloxacin (1/19; 5.3%) and ceftriaxone (1/19; 5.3%), with 26.3% (5/19) of E. coli being MDR. These results indicate a substantial prevalence of MDR foodborne bacteria in imported poultry and underscore critical food safety and One Health concerns. Strengthened microbiological surveillance, risk-based import inspection and enhanced regulatory coordination (aligned with the Maldives’ AMR Action Plan) are urgently needed to protect public health
A Novel Clinical Nomogram for Predicting Unfavorable Tuberculosis Treatment Outcomes: A Logistic Regression Risk Model.
Get PDFIntroduction: Communicable diseases remain one of the major public health challenges in Sub-Saharan Africa, with tuberculosis (TB) ranking among the leading causes of morbidity, mortality, and significant economic impact. Mozambique is among the countries with the highest TB burden in the region. This study aimed to develop a clinical prediction model, in the form of a nomogram, to predict the probability of unfavorable treatment outcomes (UTO) among TB patients treated at a district health center in Nacarôa, Nampula Province, Mozambique.
Methods: A retrospective cohort study was conducted using secondary data from patients diagnosed and treated for TB between 2021 and 2023. A multivariable logistic regression analysis was performed to identify factors associated with UTO, and a predictive nomogram was subsequently constructed. Model performance was assessed using the receiver operating characteristic (ROC) curve, accuracy, Brier Score (BS), calibration plot, and the Hosmer–Lemeshow goodness-of-fit test. Clinical utility was evaluated through decision curve analysis (DCA) and clinical impact curves.
Results: UTO were observed in 26.8% of patients (55/205). The multivariable analysis identified as significant predictors of UTO being previously treated for TB, not receiving directly observed therapy (DOT), having a clinical or radiological diagnosis, and having a positive smear microscopy result. The nomogram showed good performance, with an AUC of 83.2% and an accuracy of 84.9%. The Hosmer–Lemeshow test indicated good model fit (p = 0.132), and the calibration plot demonstrated strong agreement between predicted and observed outcomes (BS = 0.119). DCA and clinical impact analyses confirmed the model’s potential to support and optimize clinical decision-making in TB management.
Conclusion: The nomogram developed in this study represents a promising and practical tool for estimating the individual risk of UTO in tuberculosis care and may contribute to improved clinical management and resource allocation in high-burden settings
A study protocol for a baseline community-based cross-sectional study to investigate malaria and dengue transmission dynamics in a development area of new capital city, Indonesia.
Get PDFBACKGROUND: The relocation of Indonesia's capital to Ibu Kota Nusantara (IKN) in East Kalimantan, a malaria and dengue hotspot, presents new risks of infectious disease transmission due to land-use changes and population movements. Current knowledge on the impact of these changes on vector-borne diseases, especially Plasmodium knowlesi malaria and other arboviruses, is limited. Serological surveillance offers a robust method for assessing population exposure. METHOD: A community-based cross-sectional study will be conducted in IKN and its surrounding area, in East Kalimantan. Approximately 2,000 individuals aged >1 year will be enrolled. Finger-prick blood samples will be collected for serological analysis (multiplex bead-based assays for malaria species, and dengue virus serotypes) and malaria RDTs. Demographic, clinical, environmental, and geolocation data will also be collected. Statistical and geostatistical models will be used to assess seroprevalence, spatial patterns, and risk factors of exposure to malaria and dengue
Leptotrombidium imphalum Chiggers as Vector for Scrub Typhus in Human Settlements, India, 2022-2023.
Get PDFScrub typhus is a common bacterial infection in many parts of Asia. The causative agent, Orientia tsutsugamushi, is transmitted by trombiculid mite (chigger) larvae that require small mammals as maintaining hosts. We studied the prevalence of O. tsutsugamushi infection in mites and small mammals in villages and land surrounding them in South India to determine high-risk settings. We identified 12,431 mite larvae on 883 small mammals, 32% of which were bandicoot rats, 31% black rats, and 31% Asian house shrews. Leptotrombidium imphalum was the most common mite species and the only species associated with O. tsutsugamushi infection (prevalence 3.6%). Orientia infection increased with mite population size on a host. Host numbers, the L. imphalum index, and the prevalence of Orientia infection in chiggers were considerably higher within human settlements than in surrounding fields, suggesting that most human scrub typhus infection occurs inside villages rather than during agricultural work
The effect of prenatal balanced energy and protein supplementation on small vulnerable newborn types in low- and middle-income countries: A systematic review and meta-analysis of individual participant data.
Get PDFBACKGROUND: Small vulnerable newborn (SVN) types, defined by combinations of being born too soon or too small, have distinct determinants, health consequences, and prevention strategies. The effects of prenatal balanced energy and protein (BEP) supplementation on SVN types remain unknown.
METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of individual participant data from eight randomized controlled trials of prenatal BEP supplements (N = 10,252, with 5,164 in the BEP arm and 5,088 in the control arm) in low- and middle-income countries were used. The control arms varied across studies and included context-specific standards of care, iron and folic acid supplements, or multiple micronutrient supplements. Newborns were classified into 10 groups through the combinations of preterm birth, small for gestational age (SGA) birth, and low birthweight (LBW), such as term-appropriate-for-gestational-age (AGA)-nonLBW, preterm-SGA-LBW, preterm-large-for-gestational-age-LBW, term-SGA-LBW, preterm-AGA-nonLBW, and other permutations. Newborns were also analyzed using a four-group categorization that included term-nonSGA, preterm-nonSGA, term-SGA, and preterm-SGA. Log-binomial models were used to estimate study-specific risk ratios (RRs), which were pooled using meta-analyses. Subgroup analyses were conducted by maternal age, parity, gestational age at enrollment, early pregnancy body mass index, and maternal anemia status. In the 10-group categorization of SVNs, on average, prenatal BEP supplementation led to a 30% lower risk of preterm-SGA-LBW (RR: 0.70; 95% CI [0.53, 0.91]; P = 0.009), a 25% lower risk of preterm-AGA-LBW (RR: 0.75; 95% CI [0.60, 0.93]; P = 0.009), and a 20% lower risk of term-SGA-LBW (RR: 0.80; 95% CI [0.72, 0.90]; P < 0.001). In the four-group categorization, prenatal BEP supplementation led to a 31% lower risk of preterm-SGA (RR: 0.69; 95% CI [0.52, 0.91]; P = 0.008) and a 12% lower risk of term-SGA (RR: 0.88; 95% CI [0.81, 0.96]; P = 0.005). The protective effect of prenatal BEP supplementation on preterm-SGA was stronger among multiparous women and women without anemia. The protective effects on all three SVN types under the four-group categorization were stronger among women enrolled before 20 weeks of gestation. The main limitations of the study included the absence of some BEP trials and the small event numbers for some SVN types.
CONCLUSIONS: Prenatal BEP supplementation reduces the risk of SVNs to varying extents. Further research is needed to determine the optimal targeting approach for providing BEP supplements to vulnerable pregnant women who are most likely to benefit from the supplementation
The association between academic pressure and adolescent depressive symptoms and self-harm: a longitudinal, prospective study in England.
Get PDFBACKGROUND: Academic pressure could increase the risk of adolescent depression and self-harm. However, there are few longitudinal studies of this association, and those that exist have limitations. We aimed to investigate associations between perceived levels of academic pressure and subsequent depressive symptoms and self-harm from adolescence to early adulthood. Our hypothesis was that higher levels of academic pressure would be associated with higher levels of depressive symptoms and self-harm. METHODS: In this longitudinal study, we used data from the Avon Longitudinal Study of Parents and Children (Avon, UK) that includes adolescents born in 1991-92. Our primary exposure of interest was academic pressure measured at age 15 years, using items from a school experiences questionnaire (total scores 0-9). Outcomes were depressive symptoms assessed with the Short Mood and Feelings Questionnaire at five timepoints between age 16 years and 22 years (total scores 0-26), and a self-harm questionnaire at four timepoints between age 16 years and 24 years. Analyses were linear (depressive symptoms) and logistic (self-harm in the previous year) multilevel models in samples with multiply imputed data, before and after adjustments. FINDINGS: We included 4714 adolescents (2725 [57·8%] female, 1989 [42·2%] male). In fully adjusted models, a 1-point increase in academic pressure at age 15 years was associated with a 0·43 (95% CI 0·36-0·51) point increase in depressive symptoms. This association was largest when depressive symptoms were assessed at age 16 years (0·53, 0·42-0·64), but remained at age 22 years (0·35, 0·23-0·47). For self-harm, in fully adjusted models, each 1-point increase in academic pressure was associated with an 8% higher odds of self-harm (adjusted odds ratio 1·08, 1·01-1·16), with no differences over time. INTERPRETATION: Our findings support the hypothesis that academic pressure is a potential modifiable risk factor for adolescent depressive symptoms, and possibly self-harm. Interventions to reduce academic pressure could be developed and evaluated. FUNDING: Sir Henry Dale Fellowship, Wellcome Trust, and Royal Society
A Scoping Review of Preventive Interventions to Reduce Violence Against Women Across Southeast Asian Countries
Get PDFViolence against women (VAW) remains pervasive throughout Southeast Asia, with profound health, social, and economic consequences. To identify what peer-reviewed interventions are available to address violence against women in Southeast Asia, this scoping review aimed to identify and synthesize preventive interventions addressing VAW across the 11 countries of Southeast Asia. Guided by PRISMA-ScR and PICOS frameworks, nine academic databases were systematically searched for peer-reviewed literature published from 2000 to 2024. Inclusion and exclusion criteria focused on empirical interventions targeting VAW at individual, community, and system levels. Study characteristics and program outcomes were extracted and tabulated. Thirteen studies were identified, conducted in Thailand, Vietnam, the Philippines, Malaysia, Cambodia, Indonesia, and Timor-Leste. Most interventions targeted individuals–women at risk, couples, perpetrators, men, refugees, and students–while a smaller number that addressed community or health system levels. Designs included randomized controlled trials, mixed methods, and qualitative approaches. Positive outcomes were noted in knowledge, attitudes, empowerment, and help-seeking, but evidence for sustained behavioral change or reduction in violence was limited. Despite notable innovation and some success, prevention efforts remain fragmented and under-evaluated, with significant geographic and population gaps. Scaling up contextually grounded, multi-level, and participatory interventions, alongside rigorous evaluation and inclusion of marginalized groups, is urgently needed. Future research should prioritize longitudinal and participatory methods, incorporate local language, and address cultural factors to inform effective, equitable VAW prevention across Southeast Asia