Peronophythora litchii is an oomycete pathogen responsible for litchi downy blight, a significant threat to global litchi production. Autophagy, a conserved degradation pathway crucial for the growth, development, and pathogenicity of phytopathogenic organisms, remains an area of active investigation. In this study, we characterized the function of the Atg26 homolog PlAtg26b in P. litchii. Using the CRISPR/Cas9 genome editing system, we generated PlATG26b knockout mutants and determined that PlAtg26b localizes to mitochondria under stress conditions. Although deletion of PlATG26b did not impair selective autophagy, it markedly reduced Atg8-PE synthesis, vegetative hyphal growth, asexual and sexual reproduction, and zoospore release. Furthermore, PlATG26b-deficient mutants exhibited significantly reduced virulence on litchi fruits and leaves. Collectively, our findings demonstrate that PlAtg26b plays a pivotal role in the biological development and pathogenicity of P. litchii.
Guilherme Alves de Lima Henn, Karene Ferreira Cavalcante, Marina Farrel Côrtes
et al.
Introduction/Objective: Difficulty in etiologic diagnosis of infectious gastroenteritis delays appropriate treatment and impairs patient care. The lack of Brazilian studies on syndromic molecular tests limits the use of faster and more accurate diagnostics. In this context, we evaluated the potential clinical impact and cost-effectiveness of the BioFire FilmArray Gastrointestinal (FAGI) panel compared with standard diagnostic methods (control group) in gastroenteritis cases at an infectious disease’s referral hospital in a capital city in Northeast Brazil, a resource-limited region. Methods: Observational, retrospective study including 327 patients ‒ 161 in the FAGI group and 166 in the control group. Data were collected from medical records and analyzed to compare length of hospital stay, number of antimicrobials used per patient, total treatment days and treatment cost. Results: Patients in the FAGI group had a median of 5 fewer days of antimicrobial treatment (median days: 6 vs. 11, p<0.001), an 83% reduction in total antimicrobial costs (median total cost: BRL 4,697 vs. BRL 27,174, p<0.001) and a 77% increase in pathogen detection (median detections: 103 vs. 24, p<0.001) compared with the control group. No differences were observed in length of hospital stay between groups (median days: 12 vs. 13, p=0.44). Conclusion: The FAGI panel was associated with a significant reduction in the duration of antimicrobial treatment and total treatment costs, as well as increased pathogen detection rates. The results suggest that the BioFire panel can offer substantial benefits in terms of patient care and cost savings, highlighting its potential for broader implementation in clinical practice, especially in resource-limited settings, to improve outcomes in the management of infectious gastroenteritis.
This paper proposes a hypothetical model for the dual role of respiratory aerosols and inflammatory exudates in the dynamics and progression of SARS-CoV-2 lung infection. Starting from a new paradigm in infectious disease transmission, we reflect on the often-overlooked role of physical transmission media within the host individual. The hypothesis posits that tiny aerosols (including those inhaled externally and those self-generated and re-inhaled by the host) play a crucial role in the initial seeding and early expansion of the infection in the lungs, explaining the multifocal characteristics observed in early CT imaging. As the infection progresses, inflammatory exudates, formed due to lung inflammation, become a new efficient vehicle, driving the large-scale spread of the virus within the lungs and accounting for the development of diffuse lesions. This model reveals a "dynamic equilibrium point" where the dominant mechanism shifts from aerosol-mediated to exudate-mediated spread. Although direct validation of this hypothesis faces ethical and technical challenges, existing clinical imaging, viral kinetics, and epidemiological patterns provide indirect support. The paper also conceptualizes ideal experimental designs and retrospective analyses to validate the hypothesis. Finally, we discuss the implications of this hypothesis for public health practice, emphasizing the importance of improving ventilation in the microenvironment of infected individuals to achieve a "for all, by all" (literally "everyone for me, I for everyone") bidirectional protection. This research aims to provide a new framework for understanding the pathophysiology of respiratory infectious diseases and to offer theoretical basis for developing more cost-effective and broadly applicable intervention strategies.
This paper presents a hybrid modeling approach that couples an Agent-Based Model (ABM) with a partial differential equation (PDE) model in an epidemic setting to simulate the spatial spread of infectious diseases using a compartmental structure with seven health states. The goal is to reduce the computational complexity of a full-ABM by introducing a coupled ABM-PDE model that offers significantly faster simulations while maintaining comparable accuracy. Our results demonstrate that the hybrid model not only reduces the overall simulation runtime (defined as the number of runs required for stable results multiplied by the duration of a single run) but also achieves smaller errors across both 25% and 100% population samples. The coupling mechanism ensures consistency at the model interface: agents crossing from the ABM into the PDE domain are removed and represented as density contributions, while surplus density in the PDE domain is used to generate agents with plausible trajectories derived from mobile phone data. We evaluate the hybrid model using real-world mobility and infection data for the Berlin-Brandenburg region in Germany, showing that it captures the core epidemiological dynamics while enabling efficient large-scale simulations.
The Bayesian analysis of infectious disease surveillance data from multiple locations typically involves building and fitting a spatio-temporal model of how the disease spreads in the structured population. Here we present new generally applicable methodology to perform this task. We introduce a parsimonious representation of seasonality and a biologically informed specification of the outbreak component to avoid parameter identifiability issues. We develop a computationally efficient Bayesian inference methodology for the proposed models, including techniques to detect outbreaks by computing marginal posterior probabilities at each spatial location and time point. We show that it is possible to efficiently integrate out the discrete parameters associated with outbreak states, enabling the use of dynamic Hamiltonian Monte Carlo (HMC) as a complementary alternative to a hybrid Markov chain Monte Carlo (MCMC) algorithm. Furthermore, we introduce a robust Bayesian model comparison framework based on importance sampling to approximate model evidence in high-dimensional space. The performance of our methodology is validated through systematic simulation studies, where simulated outbreaks were successfully detected, and our model comparison strategy demonstrates strong reliability. We also apply our new methodology to monthly incidence data on invasive meningococcal disease from 28 European countries. The results highlight outbreaks across multiple countries and months, with model comparison analysis showing that the new specification outperforms previous approaches. The accompanying software is freely available as a R package at https://github.com/Matthewadeoye/DetectOutbreaks.
Akanksha Arya, Owen Renault, William Eissler
et al.
Background: There is a high prevalence of catheter associated urinary tract infections (CAUTIs) on a hospital cardiology unit, with a rate of 2.48 CAUTIs per 1,000 catheter days over the past two years compared to the national average of 0.96 CAUTIs for similar units. CAUTIs lead to increased lengths of stay, mortality, and hospital expenditures. Per NHSN, the presence of an indwelling urinary catheter (IUC) increases the risk for developing a CAUTI by 3-7% each day an IUC is in place. Method: A process improvement approach was utilized to study the problem of increased CAUTIs and implement a PDSA intervention.
Infectious and parasitic diseases, Public aspects of medicine
Irene A. Kretchy, Deborah Atobrah, David A. Adumbire
et al.
Abstract Background Malaria infection in pregnancy is a critical determinant of maternal and neonatal health outcomes in endemic regions. Intermittent preventive treatment of malaria in pregnancy (IPTp) using sulfadoxine-pyrimethamine has been recommended by the World Health Organization (WHO), but its uptake remains low because of factors such as gender norms and expectations. However, interventions to optimize IPTp uptake, especially in malaria-endemic regions, have resulted in a decline in malaria during pregnancy, maternal and neonatal mortality, low birth weight, and placental parasitaemia. This scoping review aimed to synthesize evidence on IPTp uptake, particularly emphasizing gender-related strategies. Methods The modified version of Arksey and O'Malley's framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) were adopted for this review. Documents were retrieved from the following electronic databases and search engines: scopus, Web of Science, CINAHL Complete (EBSCO), PubMed, WHO, Global Index Medicus, and Google Scholar. The titles and abstracts of the publications were independently screened via Rayyan review management software, and the data were organized using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework and gender analysis matrix. Results A total of 32 studies met the inclusion criteria. The most reported criterion was the effectiveness of the interventions, which demonstrated an increase in IPTp uptake after the intervention. The gender analysis framework revealed that involving both men and women in decision-making processes, empowering women, and promoting shared roles could improve the success of IPTp interventions. Conclusions Interventions to increase IPTp uptake should be targeted at empowering women through education, increasing financial independence, and making decisions about their health.
Arctic medicine. Tropical medicine, Infectious and parasitic diseases
Caleb Sullivan, Pubudu Senanayake, Michael J. Plank
Accounting for population age structure and age-specific contact patterns is crucial for accurate modelling of human infectious disease dynamics and impact. A common approach is to use contact matrices, which estimate the number of contacts between individuals of different ages. These contact matrices are frequently based on data collected from populations with very different demographic and socioeconomic characteristics from the population of interest. Here we use a comprehensive household composition dataset based on Aotearoa New Zealand census and administrative data to construct a household contact matrix and a synthetic population that can be used for modelling. We investigate the behaviour of a compartment-based and an agent-based epidemic model parameterised using this data, compared to a commonly used contact matrix that was constructed by projecting international data onto New Zealand's population. We find that using the New Zealand household data, either in a compartment-based model or in an agent-based model, leads to lower attack rates in older age groups compared to using the projected contact matrix. This difference becomes larger when household transmission is more dominant relative to non-household transmission. We provide electronic versions of the synthetic population and household contact matrix for other researchers to use in infectious disease models.
The existence and local stability of some non-negative equilibrium points of a class of SIRS infectious disease models with non-linear infection and treatment rates are investigated under the condition that the total population is a constant. The qualitative theory of differential equations was used to demonstrate that the endemic equilibrium point of the system is either a stable equilibrium, an unstable equilibrium or a degenerate equilibrium under different circumstances. Subsequently, the local stability of the non-negative equilibrium point of the system is analyzed. Finally, the bifurcation theory is used to prove that the system takes the natural recovery growth rate as the parameter of the saddle-node branching, and the conditions for the existence of the model saddle-node branching are given.
Luis Felipe Rivera, Carlos Lezcano-Coba, Josefrancisco Galué
et al.
Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, clinical and epidemiologic reports are limited, and outbreaks are occurring at an increasing frequency. We addressed the data gap by analyzing all available clinical and epidemiologic data of MADV and VEEV infections recorded since 1961 in Panama. A total of 168 human alphavirus encephalitis cases were detected in Panama during 1961‒2023. We described the clinical signs and symptoms and epidemiologic characteristics of those cases, and also explored signs and symptoms as potential predictors of encephalitic alphavirus infection compared with those of other arbovirus infections occurring in the region. Our results highlight the challenges for the clinical diagnosis of alphavirus disease in endemic regions with overlapping circulation of multiple arboviruses.
Yaqian Li,1 Xiaodan Jiao,2 Guozhu Sun,3 Fuxu Wang,4 Xikun Wu,1 Weichong Dong,1 Wenpeng Lu,3 Zhiyong Zhang,1 Yadong Yuan,2 Zhiqing Zhang1 1Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 3Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 4Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Zhiqing Zhang, Department of Pharmacy, The Second Hospital of Hebei Medical University, 215 hepingxi Road, Shijiazhuang, Hebei Province, 050000, People’s Republic of China, Email 26500007@hebmu.edu.cn Yadong Yuan, Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, 215 hepingxi Road, Shijiazhuang, Hebei Province, 050000, People’s Republic of China, Email yuanyd1108@163.comPurpose: Determining the optimal dosage of norvancomycin (NVCM) for Chinese patients with community-acquired pneumonia (CAP) caused by gram-positive cocci remains uncertain. This research aimed to identify influential factors affecting NVCM pharmacokinetics and explore optimal dosage regimens via population pharmacokinetic (PPK) analysis.Patients and Methods: A prospective analysis was conducted at the Second Hospital of Hebei Medical University (Shijiazhuang, China). CAP patients aged ≥ 18 years and receiving intravenous NVCM were enrolled. Each patient underwent the collection of 3– 8 blood samples for analysis during the treatment. Nonlinear mixed effect model (NONMEM) software was used to develop PPK models, while Monte Carlo simulations were employed to optimize dose regimens. Pharmacokinetic-pharmacodynamic (PK/PD) breakpoint was defined as daily area under the concentration on the second day of therapy to minimum inhibitory concentration ratio (AUC24-48h/MIC) ≥ 361, and a steady-state AUC to MIC radio (AUCss,24h/MIC) ≥ 361.Results: A prospective PPK analysis of 231 NVCM concentrations was performed in 34 patients. A two-compartment model with first-order elimination adequately described the pharmacokinetics. The population typical clearance (CL) of NVCM was 3.15 L/h, and the central volume of distribution was 12.3 L. Notably, CL exhibited significant correlations with age and serum creatinine (Scr) levels. For mild or moderate CAP patients, the recommended doses were 400– 800 mg every 12 h to achieve the target exposure with AUCss,24h/MIC ≥ 361. For community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia, the suggested dosage regimen was 600– 800 mg every 8 h, which could achieve the target exposure preferably within the initial 24 to 48 h.Conclusion: Age and Scr levels significantly influenced the pharmacokinetic parameters of NVCM in CAP patients. Our model-informed precision dosing approach may help for early optimization of NVCM exposure. Further prospective studies with larger samples will be needed.Keywords: norvancomycin, population pharmacokinetics, community-acquired pneumonia, dosing optimization
Linda Batsa Debrah, Charles Gyasi, Monica Ahiadorme
et al.
Abstract Background Onchocerciasis causes chronic systemic inflammation. Several studies have used markers such as haemato-biochemical indices to predict the occurrence of systemic inflammation. This study assessed the variability and predictability of haemato-biochemical indices and blood composite ratios (BCRs) in microfilariae positive (MF+) and microfilariae negative (MF-) subgroups of onchocercomata participants. Methods One hundred and five (105) MF + and 34 MF- participants were retrospectively recruited into the study. Screening for the presence of O. volvulus microfilariae was done from skin snips taken from the left and right iliac crests of participants using established and approved protocols. Haematological and biochemical indices were measured using standard laboratory automated analyzers. Blood composite ratios (BCRs) were calculated as ratios of the absolute parameters involved. Results A significantly increased total WBC, absolute eosinophil, eosinophil percent and absolute basophil were observed in the MF + participants compared to MF- participants. Reduced gamma-glutamyl transferase (GGT) with increased estimated glomerular filtration rate (eGFR) was significantly associated with MF + participants compared to MF- participants. BCRs were significantly higher for eosinophil-to-neutrophil ratio (ENR), eosinophil-to-monocyte ratio (EMR), eosinophil-to-basophil ratio (EBR) and eosinophil-to-lymphocyte ratio (ELR) in MF + participants compared to MF- participants. After multivariate adjustment, onchocercomata participants with increased eosinophil counts (aOR = 13.86, 95% CI [2.07–92.90], p = 0.007), ENR x10 (aOR = 1.42, 95% CI [1.05–1.93], p = 0.025), EMR (aOR = 2.64, 95% CI [1.25–5.60], p = 0.011), EBR (aOR = 1.07, 95% CI [1.01–1.10], p = 0.020) and ELR x10 (aOR = 1.69, 95% CI [1.14–2.51], p = 0.009) were more likely to have microfilaridermia. Conclusions Elevated eosinophil counts with higher ENR, EMR, EBR and ELR levels are significantly associated with microfilaridermia in onchocercomata participants. Combining BCRs with eosinophil count significantly led to an improvement in the conventional model for predicting microfilaridermia.
Abstract Background The proportional trends of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) according to various factors have not been analyzed in detail in previous studies. We aimed to evaluate the trends of HPV-associated OPSCC in the United States. Methods This retrospective cohort study included 13,081 patients with OPSCC from large population-based data using Surveillance, Epidemiology, and End Results (SEER) 2010–2017 database, 17 Registries. Patients were diagnosed with OPSCC primarily in the base of tongue (BOT), posterior pharyngeal wall (PPW), soft palate (SP), and tonsil and were tested for HPV infection status. We analyzed how the proportional trends of patients with OPSCC changed according to various demographic factors. Additionally, we forecasted and confirmed the trend of HPV (+) and (−) patients with OPSCC using the autoregressive integrated moving average (ARIMA) model. Results The proportion of patients who performed the HPV testing increased every year, and it has exceeded 50% since 2014 (21.95% and 51.37% at 2010 and 2014, respectively). The HPV-positive rates tended to increase over past 7 years (66.37% and 79.32% at 2010 and 2016, respectively). Positivity rates of HPV were significantly higher in OPSCC located in the tonsil or BOT than in those located in PPW or SP. The ARIMA (2,1,0) and (0,1,0) models were applied to forecast HPV (+) and (−) patients with OPSCC, respectively, and the predicted data generally matched the actual data well. Conclusion This large population-based study suggests that the proportional trends of HPV (+) patients with OPSCC has increased and will continue to increase. However, the trends of HPV (+) and (−) patients differed greatly according to various demographic factors. These results present a direction for establishing appropriate preventive measures to deal with HPV-related OPSCC in more detail.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Infectious and parasitic diseases
Elizabeth Amona, Indranil Sahoo, Edward Boone
et al.
Qatar has undergone distinct waves of COVID-19 infections, compounded by the emergence of variants, posing additional complexities. This research uniquely delves into the varied efficacy of existing vaccines and the pivotal role of vaccination timing in the context of COVID-19. Departing from conventional modeling, we introduce two models that account for the impact of vaccines on infections, reinfections, and deaths. Recognizing the intricacy of these models, we use the Bayesian framework and specifically utilize the Metropolis-Hastings Sampler for estimation of model parameters. The study conducts scenario analyses on two models, quantifying the duration during which the healthcare system in Qatar could have potentially been overwhelmed by an influx of new COVID-19 cases surpassing the available hospital beds. Additionally, the research explores similarities in predictive probability distributions of cumulative infections, reinfections, and deaths, employing the Hellinger distance metric. Comparative analysis, employing the Bayes factor, underscores the plausibility of a model assuming a different susceptibility rate to reinfection, as opposed to assuming the same susceptibility rate for both infections and reinfections. Results highlight the adverse outcomes associated with delayed vaccination, emphasizing the efficacy of early vaccination in reducing infections, reinfections, and deaths. Our research advocates prioritizing early vaccination as a key strategy in effectively combating future pandemics. This study contributes vital insights for evidence-based public health interventions, providing clarity on vaccination strategies and reinforcing preparedness for challenges posed by infectious diseases. The data set and implementation code for this project is made available at \url{https://github.com/elizabethamona/VaccinationTiming}.
Matthew D. Johnston, Bruce Pell, Jared Pemberton
et al.
We investigate how a population's natural and vaccine immunity affects the competitive balance between two strains of an infectious disease with different epidemiological characteristics. Specifically, we consider the case where one strain is more transmissible and the other strain is more immune-resistant. The competition of these strains is modeled by two SIR-type models which incorporate waning natural immunity and which have distinct mechanisms for vaccine immunity. Waning immunity is implemented as a gamma-distributed delay, which is analyzed using the linear chain trick to transform the delay differential equation systems into a system of ordinary differential equations. Our analysis shows that vaccination has a significant effect on the competitive balance between two strains, potentially leading to dramatic flips from one strain dominating in the population to the other. We also show that which strain gains an advantage as a population's immunity level increases depends upon the integration between the mechanisms of natural and vaccine immunity. The results of this paper are consequently relevant for public policy.
Shunta Takazawa, Tomohiro Kotaki, Satsuki Nakamura
et al.
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has necessitated the global development of countermeasures since its outbreak. However, current therapeutics and vaccines to stop the pandemic are insufficient and this is mainly because of the emergence of resistant variants, which requires the urgent development of new countermeasures, such as antiviral drugs. Replicons, self-replicating RNAs that do not produce virions, are a promising system for this purpose because they safely recreate viral replication, enabling antiviral screening in biosafety level (BSL)-2 facilities. We herein constructed three pCC2Fos-based RNA replicons lacking some open reading frames (ORF) of SARS-CoV-2: the Δorf2–8, Δorf2.4, and Δorf2 replicons, and validated their replication in Huh-7 cells. The functionalities of the Δorf2–8 and Δorf2.4 replicons for antiviral drug screening were also confirmed. We conducted puromycin selection following the construction of the Δorf2.4-puro replicon by inserting a puromycin-resistant gene into the Δorf2.4 replicon. We observed the more sustained replication of the Δorf2.4-puro replicon by puromycin pressure. The present results will contribute to the establishment of a safe and useful replicon system for analyzing SARS-CoV-2 replication mechanisms as well as the development of novel antiviral drugs in BSL-2 facilities.
Abstract Background Leptospirosis is an infectious disease caused by pathogenic Leptospira spp., which could result in severe illnesses. Indirect contact with these pathogens is more common. Individuals could contract this disease through contact with contaminated water or during floods. In this case, we present the details of a 40-year-old male pig farmer who suffered from severe pulmonary hemorrhagic leptospirosis and multiple organ failure. The diagnosis of leptospirosis was confirmed through metagenomics next-generation sequencing (mNGS) while the patient received extracorporeal membrane oxygenation (ECMO) support, and antibiotic treatment was adjusted accordingly. The patient underwent comprehensive treatment and rehabilitation in the intensive care unit. Conclusion This case illustrates the importance of early diagnosis and treatment of leptospirosis. While obtaining the epidemiological history, second-generation metagenomics sequencing was utilized to confirm the etiology. The prompt initiation of ECMO therapy provided a crucial window of opportunity for addressing the underlying cause. This case report offers valuable insights for diagnosing patients with similar symptoms.