Pathogens最新文献

Treatment of bacteremia has traditionally consisted of a 7-14-day course of intravenous (IV) antibiotics. Transitioning from IV to oral (PO) antibiotics in uncomplicated cases of Gram-negative and Gram-positive bacteremia is non-inferior to a complete course of IV antibiotics. High-dose oral amoxicillin has been used in practice for treating bacteremia but has limited safety and efficacy data. We conducted a retrospective chart review between June 2022 and June 2024 to characterize the use of high-dose amoxicillin and evaluate its efficacy and safety. A convenient sample size of 100 patients was used. Patients admitted to hospital who received at least one dose of high-dose amoxicillin (1 g PO TID) for the treatment of bacteremia were included. Patients undergoing hemodialysis and patients receiving amoxicillin for other infections were excluded. The average patient was a 60-year-old male (66% male) with a Gram-positive respiratory or skin source bacteremia. The median time to transition to oral amoxicillin was 5 days. The median duration of total treatment was 14 days. Respiratory sources were treated for a shorter duration, whereas skin sources were treated for longer. Readmission to hospital occurred in 28% of cases. The majority of readmissions were unrelated to the original infection, and 92% of patients were cured. There were no observed adverse events, bacteremia relapses, or deaths. In this observational study, transitioning to high-dose oral amoxicillin was primarily used for treatment of uncomplicated respiratory and skin infections with secondary bacteremia. A high rate of clinical success was observed with high-dose PO amoxicillin, with no adverse events reported.

Human cytomegalovirus (HCMV) infection is a significant complication in transplant recipients. Following HCMV reactivation, the recovery of T-cell responses serves as a key indicator of protection from HCMV disease. This study aimed to assess the HCMV-specific CD4⁺ and CD8⁺ T-cell responses and their cytokine production (IFNγ, TNFα, IL2) against various HCMV proteins (IE-1, pp65, gB, gH/gL/pUL128L) in solid organ transplant recipients (SOTRs) and hematopoietic stem cell transplant recipients (HSCTRs) with active HCMV infection. The cohort consisted of 16 SOTR and 16 HSCTR categorized into two groups: (i) Controllers, who spontaneously controlled the infection, and (ii) Non-Controllers, who required antiviral treatment. T-cell responses were analyzed following stimulation with peptide pools and intracellular cytokine staining. Prior to transplantation, all patients exhibited a significantly higher frequency of CD4⁺ T cells specific to pp65 compared to gH and gL/pUL128L. During the peak of infection, T-cell frequencies across all peptides were similar, but at infection resolution, the frequency of pp65 and gB-specific CD4⁺IFNγ⁺ T cells was significantly higher than gL/pUL128L. Additionally, pp65 and IE-1-specific CD8⁺IFNγ⁺ T-cell responses were significantly greater than those against gH and gL/pUL128L at the resolution of infection. Notably, Controllers exhibited significantly higher frequencies of monofunctional pp65-specific T cells, particularly in CD8⁺ T cells producing IFNγ and TNFα. The response to pp65, especially IFNγ production, may serve as a key marker for identifying patients capable of controlling HCMV infection.

Various microbial agents have been found in the feces of both humans and animals, especially in newborns. While some of these agents are recognized as causing diarrhea, the role of others, specifically bopiviruses of the family Picornaviridae, in diarrhea remains uncertain. In this study, we conducted an analysis of 214 fecal samples from cattle (n = 114), sheep (n = 82), and goats (n = 18) with diarrhea, collected from farms across 17 different provinces in Türkiye. All samples were tested using RT-PCR targeting the 3D^(RdRp) region of bopiviruses, and two samples from sheep (2.4%) tested positive. The 7303 nt-long complete coding sequence of Bopivirus/Sheep/KS-1M/2024/TUR and partial 3D^(RdRp), VP3, and 2A-2C sequences of Bopivirus/Sheep/ANK-K30/2017/TUR were determined by additional RT-PCR, 3'RACE-PCR reactions and Sanger sequencing. Both strains show close sequence and phylogenetic relationship to members of species "Bopivirus B" of genus Bopivirus. Bopivirus/Sheep/KS-1M/2024/TUR is most closely related to a sheep Bopivirus B strain (sheep/14-73/2018/ITA) from Italy, but the phylogenetic separation, the low sequence identities and high p-distance values in VP1 to existing genotypes of "B1" and "B2" suggest that both strains could belong to novel genotypes ("B3" and "B4") in species "Bopivirus B", although additional closely related sequences are necessary for proper typing.

Immune dysregulation is a hallmark of human immunodeficiency virus (HIV) infection, characterized by persistent immune activation and systemic inflammation that drive T cell exhaustion and senescence, contributing to disease progression and non-AIDS comorbidities, most notably tuberculosis (TB). With rising HIV prevalence, the incidence of HIV-TB co-infection continues to rise, highlighting the need to understand their immunopathological interplay. This narrative review aims to examine the association between immune dysregulation in HIV-TB co-infection, with a focus on cytokine profiles and immunological biomarkers. Relevant literature was retrieved from multiple databases, with evidence demonstrating differential expression of cytokines-IL-17A, IFN-γ, TNF, IL-10, IL-6, IL-4, and IL-2-and T cell activation markers, such as CD38 and HLA-DR on CD4⁺ T cells in latent and active TB among HIV-infected individuals. These immune mediators are consistently co-expressed at higher levels in active TB compared to latent TB, suggesting heightened immune activation of both innate and adaptive immune responses in HIV-TB co-infection. However, these findings are largely based on observational data, and the precise mechanism by which cytokine and T cell biomarker dysregulation contributes to HIV-TB pathogenesis remains incompletely understood, underscoring the need for larger, mechanistic studies to address these gaps in the pathogenic pathway.

Background: Numerous studies have reported on the epidemiology of hand, foot and mouth disease (HFMD) reinfection and its potential influencing factors; however, findings regarding reinfection rates as well as determinants such as gender, age, residence, and pathogens remain inconsistent. Due to this heterogeneity in reported outcomes, a comprehensive systematic review and meta-analysis are warranted to consolidate existing evidence. Methods: Effect estimates were expressed as reinfection rates, odds ratio (OR)/hazard ratio (HR) and 95% confidence intervals (CI). When necessary, data were converted to ensure consistency across comparison groups. Results: A thorough search was carried out using the predetermined literature retrieval approach across the PubMed, Web of Science, and Embase databases. Finally, 9 articles met the inclusion criteria and were included in this study. The results indicated that the overall reinfection rate for HFMD was 4.1% (95% CI: 2.0-6.2%). Males compared to females (overall effect = 1.256, 95% CI: 1.176-1.341), younger compared to older children (overall effect = 2.972, 95% CI: 1.512-5.843), scattered children compared to students (overall effect: 4.017, 95% CI: 1.560-10.344), and enterovirus 71 (EV71) compared to non-EV71 enteroviruses (overall effect = 0.71, 95% CI: 0.59-0.86) were associated with the HFMD reinfection. Conclusions: The overall HFMD reinfection rate was 4.1% (95% CI: 2.0-6.2%). Male, younger age, kindergarten children, and infection with non-EV71 enteroviruses (compared to EV71), were identified as significant risk factors for recurrent HFMD. Targeted intervention strategies should be developed for these high-risk populations to effectively reduce the incidence of reinfection.

L. monocytogenes is the causative agent of human listeriosis, a deadly disease with fatality rates up to 20%. L. monocytogenes has the ability to grow under harsh environmental conditions. It can form biofilms in food industries, making it capable of persisting in facilities. Given this scenario, it is of utmost importance to rapidly detect this bacterium not only in foods but also on food-contact surfaces. For the successful outcome of any given detection technology, it is imperative to properly process the samples. In the present work, PBS, LPT, and LPT-Pronase were compared to determine which one could provide better results in DNA-based detection. Additionally, the effect of a short TSB pre-enrichment was assessed. To better mimic a real scenario, L. monocytogenes monospecies and multispecies biofilms were analyzed. It was observed that supplementing LPT with pronase, a protein-degrading enzyme, could better detach the biofilm, which achieved a 0.5 cycle reduction compared to the other broths, and the pre-enrichment reduced the real-time PCR by ~2 cycles. The samples were analyzed by real-time PCR and colorimetric LAMP, and the same results were obtained with both techniques regardless of the concentration of L. monocytogenes present in the biofilm; the initial concentration was 1.8 log CFU/cm² 15 min after the pre-enrichment. The results were confirmed by real-time PCR, which demonstrated the applicability of the methodology to be applied in decentralized setups, such as food-processing facilities, with minimal laboratory infrastructure.

Trypanosoma cruzi is the causative agent of Chagas disease, which affects 6-7 million people worldwide. Although the possibility of oral transmission was first scientifically suggested in 1913, it was not until 1968 that the first confirmed cases of human infection via food consumption were reported. This long gap contributed to the widespread perception that oral transmission was a rare or incidental event. Over the past two decades, significant advances have been made in understanding the biological and clinical aspects of oral transmission, including the molecular mechanisms by which metacyclic trypomastigotes establish infection via the digestive route. Experimental studies in murine models have further deepened our knowledge of the biology and pathogenesis of oral infection. Concurrently, multiple outbreaks of T. cruzi infection through contaminated food and beverages have been reported across Latin America, providing valuable insights into the molecular epidemiology and clinical characteristics of this transmission route. Moreover, experimental evidence has shown that the consumption of meat from animals infected during the acute phase can also lead to T. cruzi infection, highlighting carnivory as a potential alternative transmission mechanism. This review aims to comprehensively analyze oral infection by T. cruzi, considering clinical and epidemiological data, parasite biology, and findings from murine experimental models. Strategies for controlling foodborne transmission of Chagas disease are also discussed.

Background: Enterovirus-D68 (EV-D68) was long underreported, with only sporadic cases of respiratory disease worldwide until 2014, when numerous countries experienced significant outbreaks of EV-D68. In Croatia, sporadic detections have primarily resulted from an absence of systematic surveillance. Following the increased incidence of EV-D68 across Europe in 2022, we started to characterize EV-positive respiratory samples in Zagreb to confirm the presence of EV-D68 and identify circulating lineages through phylogenetic analysis.

Methods: Respiratory samples from individuals with acute respiratory infection and additional clinical symptoms were tested at the Virology Laboratory of the Croatian Institute of Public Health, and EV-positive samples were further screened using the real-time RT-qPCR method for EV-D68. VP1 sequences were obtained by sequencing and subsequently genotyped.

Results: Between March 2022 and December 2024, EV was detected in 2048 respiratory samples. Annual distributions of EV detections were 656 (10.0%) in 2022, 785 (8.1%) in 2023, and 607 (7.4%) in 2024. EV-D68 was identified in 13.1% of EV-positive samples in 2022, 1.4% in 2023, and 19.6% in 2024. The peaks in EV-D68 circulation were observed in July (n = 24) and September (n = 24) in 2022 and in September 2024 (n = 62). Phylogenetic analysis of EV-D68 VP1 sequences revealed the presence of two major clades, A2 and B3. The sequences from 2022 clustered exclusively within clade B3, while in 2024 A2 clade was newly introduced.

Conclusions: We confirmed the presence of EV-D68 in Croatia with circulating lineages corresponding to those detected elsewhere in Europe. The absence of routine testing has likely led to an underestimation of EV-D68 prevalence. These findings underscore the urgent need for ongoing surveillance and genomic characterization to clarify EV-D68 epidemiology in Croatia.

Background: Non-typhoidal (NT) Salmonella spp. constitutes a major cause of foodborne illness. Culture is the gold standard, but it is time consuming, whereas multiplex nucleic acid amplification tests (NAATs)/Polymerase Chain Reaction (PCR) offer faster detection with variable reported performance.

Objectives: To compare the diagnostic accuracy of multiplex NAAT/PCR and culture for Salmonella spp. using various statistical models with or without a gold standard assumption.

Methods: A systematic search (PubMed, Web of Science, Scopus; up to April 2024) identified 44 studies (55 comparisons). Diagnostic performance was evaluated using the frequentists bivariate model (BM) and Split Component Synthesis (SCS) and the Bayesian bivariate models (BBMs) and hierarchical summary ROC (BHSROC).

Results: Across models, multiplex NAAT/PCR demonstrated high specificity (>98%) but model-dependent variability in sensitivity (85.5-94.8%), consistently substantial between study heterogeneity and threshold variation. The BM and BBM yielded a higher sensitivity estimate with narrower non-overlapping confidence intervals while SCS and BHSROC models, which are more robust to threshold differences, produced more conservative estimates with wider uncertainty. In Bayesian latent class analyses, culture remained highly accurate (Se: 97.17%, 95% CrI: 70.3-99.99; Sp: 96.06%, 95% CrI: 78.9-99.99), but with wide credible intervals indicating variation between studies, perhaps due to the different protocols used.

Conclusion: Model choice affects inferred diagnostic accuracy, particularly when high heterogeneity is present. Both multiplex NAAT/PCR and culture showed high accuracy; hence, a combination of the two tests could optimise rapid diagnosis and treatment. Future research should include cost effectiveness and decision analysis to update the diagnostic algorithms.

The epidemiological situation in Poland for IBV GII (formerly known as D1466) has seemed stable over the years, but an increase in such infections has been recently reported. In this study, genetic characterization of the representatives of this genotype was performed in order to determine whether the new epidemic wave of GII IBV was responsible for changes in this status quo. Genotyping based on the complete S1 coding region of eight Polish IBV field strains from 2011 to 2021 confirmed that they belonged to genotype II, with two of them clustered in the two previously identified GII-1 and GII-2 lineages. In turn, the S1 coding region sequences of the next six Polish strains are very different from the previous ones and form a separate group on the phylogenetic tree. However, comprehensive analysis of all complete S1 coding regions of GII strains did not fulfill all parameters needed to create the separate GII lineage, and they all seem to belong to the GII-1 lineage. Further analysis of the partial S1 sequence of 15 IBV GII strains showed their genetic distinctiveness and indicates the ongoing evolution of this virus genotype. Considering the results of our study and the recent outbreaks of GII-2 in Western Europe, it appears that infections with GII virus strains mainly affect egg-producing, long-lived chickens, commercial layers, and breeders. Furthermore, due to the high diversity of these viruses, their circulation in the poultry population may remain undetected, and for this reason, the observed production problems in laying flocks may be attributed to other, unrelated factors.