Streptococcus pneumoniae remains a global health concern, causing diseases from sinusitis, otitis media, to invasive pneumococcal diseases (IPD), such as bacteremia, bacteremic pneumonia, empyema, and meningitis. Key IPD risk factors include age under five or over 50 years, chronic medical conditions, and lifestyle factors. In Taiwan, IPD incidence has declined following national immunization program. However, morbidity and mortality remain substantial, particularly among older adults. There are two types of pneumococcal vaccines, polysaccharide conjugate vaccines (PCV) and pneumococcal polysaccharide vaccines (PPSV). These vaccines target specific IPD serotypes but may lead to serotype replacement. In Taiwan, the available/forthcoming vaccines include PCV13, PCV15, PCV20, PCV21, and PPSV23, with numbers indicating serotype coverage. This guidance, developed and endorsed by eight national academic societies, serves as an adjunct to the Taiwan Advisory Committee on Immunization Practices recommendations. Using the GRADE framework, it provides evidence-based recommendations for adult pneumococcal vaccination. It emphasizes health promotion to assist healthcare professionals in vaccine selection tailored to current local epidemiology and individual vaccination history. A shared decision-making approach is encouraged, considering individual vulnerabilities, exposure risks, and lifestyle factors. This guidance addresses optimal timing, dosing schedules, coadministration, and safety; grounded in immunological evidence on efficacy, effectiveness, and immunogenicity. In recognition of feasibility of implementation, single-dose PCV20 or PCV21 is proposed as a simplified alternative to complex sequential strategies. However, PCV21 is recommended only where PCV7 serotypes are well controlled or no longer prevalent. This guidance reflects evolving pneumococcal vaccination strategies in response to serotype dynamics and availability of higher-valency conjugate vaccines.
Community-associated methicillin-resistant Staphylococcus aureus ST8/SCCmecIVl occasionally causes invasive infections. Only severe cases harbored p32kb, with repA1, oriT-based recombination with conjugative pWtra, and a virulence gene cluster with varying citABC positivity associated with intramuscular and non-intramuscular infections. Our findings highlight the potentially critical role of citA (CitA superantigen), which may be applied as a potential severity marker.
BACKGROUND:Aspergillus-specific immunoglobulin G (IgG) positivity typically indicates exposure to Aspergillus species, but its clinical significance among chronic lung diseases remains uncertain. METHODS:This prospective study enrolled patients with bronchiectasis, chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung disease (ILD) in Taiwan between July 2019 and June 2023. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured at baseline and repeated 1 year later. Lung function rapid decline was defined as FEV1 decline ≥ 60 mL/year or FVC decline ≥ 10 % predicted/year based on previous literature. RESULTS:A total of 97 patients were enrolled, including 75 (77.3 %) with bronchiectasis, 42 (43.3 %) with COPD, 26 (26.8 %) with asthma, and 6 (6.2 %) with ILD. Higher Aspergillus-specific IgG levels were significantly associated with greater FEV1 decline (r = 0.34, P < 0.001) but not with greater FVC decline (r = 0.10, P = 0.327). Multivariable analysis demonstrated that higher Aspergillus-specific IgG levels were an independent risk factor for rapid FEV1 decline (odds ratio = 1.04; 95 % confidence interval [CI]: 1.01-1.08; P = 0.007). The area under the receiver operating characteristic curve of Aspergillus-specific IgG for predicting FEV1 rapid decline was 0.72 (95 % CI: 0.61-0.82). A cutoff of 30 mgA/L provided a sensitivity of 63.64 % and specificity of 71.43 % in predicting rapid FEV1 decline. CONCLUSIONS:Higher Aspergillus-specific IgG levels may be associated with rapid FEV1 decline in patients with chronic lung diseases, although this association requires further validation in larger, disease-specific cohorts.
OBJECTIVES:To explore factors significantly associated with plasma procalcitonin (PCT) concentration elevation among patients with monomicrobial Gram-negative bacteremia. METHODS:Sepsis patients hospitalized in intensive care units between 2020 and 2024 were eligible for this study. Their demographic characteristics, comorbidities, development of shock and disseminated intravascular coagulation, key laboratory data-including plasma C-reactive protein (CRP) and PCT concentrations-sonographic and radiographic findings, and septic workup results were collected. To determine the median PCT level, patients with monomicrobial Gram-negative bacteremia were stratified into two equal groups. RESULTS:Patients with bacteremia secondary to biliary tract infection (n = 24), urinary tract infection (UTI; n = 118), and primary source (n = 71), showed high proportions of Enterobacterales species as causative etiologies. A total of 358 patients with monomicrobial Gram-negative bacteremia were included in the final analysis. Patients with plasma PCT concentrations above the median value (20.2 ng/mL) did not exhibit higher mortality rates compared to those with concentrations below the median. Additionally, diabetes mellitus, UTI associated with hydronephrosis, and shock development were identified as independent predictors for markedly elevated plasma PCT concentrations among patients with monomicrobial Gram-negative bacteremia (odds ratio [OR], 1.66, 3.83, and 2.09; 95 % confidence interval [CI], 1.02-2.70, 1.64-8.93, and 1.25-3.50; P values, 0.043, 0.002, and 0.005, respectively). In contrast, the presence of Child-Pugh class C liver cirrhosis was a negative predictor of high plasma PCT concentrations (OR 0.35, 95 % CI 0.11-0.97, and P = 0.049). CONCLUSIONS:This study recognized factors with significant impact on plasma PCT concentrations among patients with monomicrobial Gram-negative bacteremia.
PURPOSE:To evaluate the effectiveness and safety of oral levofloxacin verse trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of macrolides-resistant pertussis in pediatric outpatients. METHODS:A prospective observational study was conducted at a pediatric pertussis outpatient clinic during the pertussis outbreak in 2024. For eligible children with PCR-confirmed pertussis, administration of either levofloxacin (8-10 mg/kg/dose, once or twice daily) or TMP-SMX (4-20 mg/kg/dose, twice daily) depended on parents' preference. Effectiveness and safety were evaluated for the 5-14 days duration of levofloxacin and TMP-SMX treatment in terms of alleviation of cough symptoms, bacteriologic clearance of Bordetella pertussis and adverse effects. RESULTS:Among 193 enrolled pertussis cases, eighty-four (43.53 %) received levofloxacin and 109 (56.48 %) received TMP-SMX. After completing treatment, paroxysmal cough resolved or improved in 96.43 % of levofloxacin group and 94.50 % (103/109) of TMP-SMX group (p = 0.554). Nocturnal cough resolved or improved in 98.81 % of levofloxacin group and in 98.17 % of TMP-SMX group (p = 0.057). There was no significant difference in bacteriologic clearance rate between levofloxacin group and TMP-SMX group determined by PCR (92.00 % vs 87.06 %, p = 0.378) and culture (100 % vs 100 %, p > 0.378). Symptom resolution rate did not differ significantly among patients treated for 5 or 7 days with either levofloxacin or TMP-SMX. Adverse events were reported in 9.2 % of TMP-SMX-treated patients and 2.4 % of levofloxacin-treated patients (p < 0.05). Drug rash was reported in nine (8.26 %) TMP-SMX-treated patients. CONCLUSIONS:Oral levofloxacin showed a comparable clinical effectiveness and a favorable safety profile to TMP-SMX for the treatment of non-severe pertussis with a 5-7 days course in children.
BACKGROUND:Hemodialysis (HD) patients with nasal Staphylococcus aureus carriage are at an increased risk of S. aureus infection. PURPOSE:This study investigated the incidence of S. aureus bacteremia and associated mortality in HD patients receiving active screening and decolonization (ASD) program for nasal S. aureus carrier in a teaching hospital HD unit. METHODS:The ASD program was divided into five stages: 1: preintervention, 2: preparation, 3: intervention, 4: interruption, and 5: reintervention. Nasal screening was conducted every 3 months in stages 3 and 5. Patients colonized with S. aureus received decolonization with mupirocin to the nares and 4 % chlorhexidine gluconate body wash. S. aureus bacteremia and mortality were assessed. Whole-genome sequencing was conducted on S. aureus isolate in stage 3. RESULTS:In preintervention stage, the bacteremia incidence and mortality rate were 7.8 and 3.1 cases per 100 patient-years(PY). In the intervention stage, the incidence rate decreased to 1 case per 100 PY without mortality. In the reintervention stage, the incidence and mortality rates were 2.1 and 0.6 cases per 100 PY. The rates in stages 3, 4, and 5 were significantly lower than those in preintervention stage (p < 0.05). Genomic analysis of S. aureus isolates from stage 3 revealed genetically diversity. High-level mupirocin-resistant S. aureus isolates carrying mupA-bearing plasmids were identified. CONCLUSIONS:ASD programs for S. aureus carrier may improve clinical outcomes in HD units. However, mupirocin resistance may emerge after decolonization, indicating a need for ongoing monitoring and alternative decolonization strategies.
Background Acinetobacter seifertii, a recently identified member of the Acinetobacter calcoaceticus–Acinetobacter baumannii (Acb) complex, has emerged as a cause of severe human infections. It is closely related to Acinetobacter nosocomialis, a major pathogen of the Acb complex. Here, we aimed to explore the clinical and molecular differences between these two species. Methods This retrospective study enrolled 83 adults with A. seifertii bacteremia and 402 adults with A. nosocomialis bacteremia from four medical centers over a 9-year period. Species identification was confirmed using matrix-assisted laser desorption ionization–time of flight mass spectrometry and rpoB sequencing. Clinical information, antimicrobial susceptibility, and carbapenem resistance determinants were analyzed. Results There were no significant differences in the underlying diseases or mortality between patients with A. seifertii and A. nosocomialis bacteremia. However, A. seifertii bacteremia was more frequently associated with intensive care unit (ICU) admission, recent ICU stay, central venous catheter use, ventilator use at bacteremia onset, and pneumonia as the primary infection source than A. nosocomialis bacteremia. A. seifertii exhibited significantly lower susceptibility to colistin, amikacin, gentamicin, ceftazidime, and cefepime than A. nosocomialis. Carbapenem resistance was primarily mediated by ISAba1-blaOXA-51-like in A. seifertii and IS1006-ΔISAba3-blaOXA-58-like in A. nosocomialis. Conclusion A. seifertii and A. nosocomialis exhibit distinct antimicrobial susceptibility profiles and carbapenem resistance mechanisms but share similar mortality rates. The ability of both species to act as reservoirs of carbapenem resistance highlights the importance of accurate identification, antimicrobial stewardship, and infection control strategies to mitigate the spread of resistant strains.
BACKGROUND:Respiratory syncytial virus (RSV) is a leading cause of respiratory infections in infants and young children. The COVID-19 pandemic significantly disrupted global RSV epidemiology. This study aimed to investigate the impact of the pandemic on RSV epidemiology in northern Taiwan from 2018 to 2023. METHODS:We retrospectively enrolled children aged <5 years with positive RSV antigen tests from 2018 to 2023, dividing into four study periods based on the COVID-19 pandemic timeline: 2018-2019, 2020-2021, 2022, 2023. RESULTS:The number of RSV positive cases was 1155 in 2018-2019, 780 in 2020-2021, 784 in 2022, and 1116 in 2023. The proportion of RSV-positive children aged 2-5 years increased progressively from 23.9 % (2018-2019) to 52.0 % (2023) (P < 0.001). The mean age of infected children increased over time (P < 0.001). Among children under 2 years old, hospitalization rates declined from 82.0 % (2018-2019) to 68.1 % (2023) in subsequent intervals (P < 0.001). Compared to 2018-2019, seasonal peaks delayed by 2 months in 2020, absent in 2021, and delayed by 3 and 2 months in 2022 and 2023, respectively. The RSV seasonal peaks varied with shortened peaks during the COVID pandemic. ICU admission rates declined from 2.9 % to 1.9 % while mortality declined from 0.2 % to 0 %. Independent risk factors for severe disease included age under 3 months, bronchopulmonary dysplasia, congenital heart disease, cerebral palsy, neurodevelopmental disorders, and co-infection with Streptococcus pneumoniae. CONCLUSIONS:The COVID-19 pandemic significantly altered the seasonality and clinical characteristics of RSV infections in northern Taiwan, likely due to the varying intensity of public health interventions.
OBJECTIVES:Vancomycin-resistant enterococcal bloodstream infections (VRE-BSIs) carry high mortality in patients with malignancy. While neutropenia is a known risk factor for mortality in patients with malignancy and BSI, its impact on the effectiveness of daptomycin and linezolid in VRE-BSI is not well defined. METHODS:We conducted a multicenter cohort study of hospitalized patients aged ≥18 years with malignancy and VRE-BSI between 2010 and 2021. Eligible patients received linezolid or high-dose daptomycin (≥8 mg/kg). Those with pneumonia or Enterococcus species other than E. faecium were excluded. Only the first VRE-BSI episode per patient was analyzed. The primary outcome was 14-day mortality, assessed using multivariable logistic regression. RESULTS:A total of 474 patients were included (linezolid, n = 90; daptomycin, n = 384); 128 (27.0 %) had neutropenia. The 14-day mortality was 32.9 % (156/474). Mortality was higher in neutropenic than non-neutropenic patients (45/128 [35.2 %] vs. 111/346 [32.1 %]; P = 0.005). Among neutropenic patients, mortality was 6/8 (75.0 %) with linezolid and 49/120 (40.8 %) with daptomycin; in non-neutropenic patients, mortality was 16/82 (19.5 %) and 85/264 (32.2 %), respectively. In multivariable analysis, linezolid use in neutropenic patients was associated with higher mortality (aOR 8.48; 95 % CI, 1.40-51.30; P = 0.02). CONCLUSIONS:Neutropenia was associated with worse outcomes in patients with VRE-BSI, and linezolid-treated neutropenic patients showed higher mortality in this cohort. These findings should be interpreted cautiously given the small sample size and residual confounding. High-dose daptomycin may be considered, particularly in neutropenic patients, but confirmatory studies are needed.
BACKGROUND:Third-generation cephalosporin-resistant Enterobacterales is a recognized global concern. This study investigated the molecular epidemiology of β-lactamase genes and antimicrobial susceptibility patterns among ceftriaxone-resistant Enterobacterales causing intra-abdominal and urinary tract infections in Taiwan between 2009 and 2019. METHODS:Data from the SMART surveillance program were analyzed, including Enterobacterales isolates with ceftriaxone minimum inhibitory concentrations ≥4 μg/mL. β-lactamase genes were detected using multiplex polymerase chain reaction assays. RESULTS:The overall ceftriaxone-resistant rate among Enterobacterales was 28.2 %, with a significant annual increase in ceftriaxone-resistant Klebsiella pneumoniae in both community- and hospital-acquired infections. Among the 2614 ceftriaxone-resistant isolates, the most common species were Escherichia coli (58.4 %), K. pneumoniae (16.3 %), and Enterobacter cloacae (9.9 %). Of all ceftriaxone-resistant isolates, 27.8 % carried only AmpC genes, 38.8 % carried only ESBL genes, and 16.2 % harbored both. High carriage rates of AmpC-encoding genes were observed in E. coli (38.9 %) and K. pneumoniae (48.9 %), with an overall prevalence of 44 %. The most common genotypes were blaCMY (41.2 %), blaDHA (31.8 %), and blaACT/blaMIR (27 %). Ceftolozane/tazobactam showed poor susceptibility against ceftriaxone-resistant isolates carrying only AmpC (20.1 %) and most ceftriaxone-resistant Enterobacterales (<55 %), except E. coli. Ertapenem demonstrated low susceptibility to K. pneumoniae, E. cloacae (both approximately 50 %), and isolates harboring only AmpC genes (57.9 %). CONCLUSIONS:A high prevalence and diversity of AmpC genes were observed in E. coli and K. pneumoniae. The limited activity of ertapenem and ceftolozane/tazobactam suggests that the molecular mechanisms underlying ceftriaxone-resistant Enterobacterales in Taiwan are complex and likely involve factors beyond AmpC and ESBL carriage.
BACKGROUND:Microbes and their metabolites are implicated in respiratory diseases, including allergic rhinitis (AR); however, the interaction between the gut and respiratory tract and the role of microbes remains unclear. We investigated the gut and nasal microbiota variations between AR and control mice and their role in the bidirectional regulation of the gut-nasal axis. METHODS:We validated the OVA-induced establishment of an AR mouse model based on nasal symptoms and histopathology. The microbiota and metabolites in the feces and nasal lavage fluid were analyzed, and a correlation analysis was performed. Structural changes in the colonic and nasal mucosa were examined using electron microscopy, and ZO-1 and Claudin 1 protein expression was assessed using immunofluorescence and western blotting. RNA-seq identified changes in gene expression in the nasal mucosa. Mendelian randomization analysis was applied to exploit the causal relationship between gut microbiota, gut microbiota-derived metabolites and AR. RESULTS:AR mice exhibited aggravated nasal symptoms, local histological disruption, and inflammatory cell infiltration in the nasal mucosa and gut tissues, with significant changes in the microbiota and metabolites at both sites. Correlation analysis revealed that gut microbes influenced fecal and nasal lavage fluid metabolite changes and vice versa. AR mice also have impaired nasal mucosal and colonic interepithelial junctions, reduced ZO-1 and Claudin 1 expression, and upregulated immune-inflammatory pathways in the nasal mucosa. CONCLUSION:The microbiota in the gut and nasal cavity interact bidirectionally, coordinating the gut-nasal axis and contributing to AR pathology. These findings provide insights for advancing AR research and management.
BACKGROUND:Dialysis patients are vulnerable to SARS-CoV-2 infection and subsequent complications. However, the vaccine-induced immunity, especially against new variants, following two AZD1222 and two booster doses in hemodialysis patients remain largely unknown. METHODS:In this observational cohort study, we monitored immune responses in 127 hemodialysis patients receiving the 3rd and 4th vaccinations until three months after the 4th immunization. Humoral and cellular immunity were assessed by anti-SARS-CoV-2 receptor-binding domain(RBD) antibody, neutralizing antibodies against the ancestral virus, delta, omicron BA.1 and BA.2 and SARS-CoV-2 specific IFN-γ releasing assay (Covi-FERON). RESULTS:The primary series and the fourth dose predominantly consisted of two-dose AZD1222 and mRNA-1273, respectively. The most common vaccines chosen for the third dose was mRNA-1273(n = 84), following by BNT 162b2(n = 38). Anti-RBD antibody increased to 13803.8 and 18197U/ml after the 3rd and 4th vaccination, respectively, but dropped to 8709.6U/ml three months after the fourth vaccination. One month after the fourth vaccination, 99 %,98 %,51.5 % and 93.9 % participants had neutralizing antibodies against the ancestral virus, delta, omicron BA.1 and BA.2, respectively. 87.9 % and 81.8 % patients reacted to the ancestral or alpha and beta or gamma spike antigens in Covi-FERON, respectively, after four vaccinations. Higher Covi-FERON reactions were associated with increased IL-2 and IL-4 secretion. In linear mixed effect models, mRNA-1273 as the third vaccination was associated higher anti-RBD antibody titers and higher neutralization against the ancestral virus and delta compared with BNT162b2 but with higher mild adverse events following vaccination. CONCLUSIONS:Two AZD1222 and two mRNA booster doses confer substantial humoral and cellular immunity against variants including omicron in hemodialysis patients.
BACKGROUND:Machine learning (ML) techniques are increasingly being used in health outcome research to develop predictive models. However, ML models are often referred to as "black box models" because they lack interpretability. Our goal was to develop an ML model to predict mortality risk in patients with community-onset bacteremia. METHODS:We conducted a retrospective cohort study on 715 patients with bacteremia at a medical center in 2019. Model-agnostic methods were employed to visually explain the relationships between the predictors and the 30-day mortality risk. The model's performance was evaluated using the area under the receiver operating characteristic curve, calibration plots with the Brier score, accuracy, recall, precision, and F1 score. RESULTS:The top ten important predictors that significantly influenced the 30-day mortality prediction were the Pitt bacteremia score, septic shock, Charlson comorbidity index, length of stay in the ICU, neutrophil segment (%), age, neutrophil band (%), glucose, lymphocytes (%), and hemoglobin. The top three overall interaction strengths were septic shock, Charlson comorbidity index and Pitt bacteremia score, all of which significantly interacted with other predictors. CONCLUSION:ML revealed risk factors for 30-day mortality, including the Pitt bacteremia score, septic shock, age, pneumonia, and comorbidity, which also had multiple synergistic effects on 30-day mortality.
Background Multidrug-resistant Klebsiella pneumoniae (MDR-KP) leads global health concerns as an infectious agent due to many virulence factors, including biofilm formation. The growing urgency for alternative treatment strategies beyond antibiotics has renewed interest in bacteriophages. Pathogen evolution is dynamic and can lead to phage resistance. Methods Bacteriophages were isolated from environmental sources and screened against a panel of 280 MDR- K. pneumoniae clinical isolates (74 from 2018 to 2020 and 167 from 2022-23 and 39 environmental KP isolates). Phages were grouped by host range and DNA fingerprinting. Five candidate phages with unique and broad host coverage were selected for further characterization and genome sequencing. Results Five candidate phages exhibited diverse host range patterns, strong bacteriolytic activity and significant antibiofilm activity even at low multiplicity of infection. Whole genome sequencing analysis revealed phage KPØ6 to be a novel Taipevirus species with low intergenomic similarity to known phages, and it showed the broadest host range on isolates from the 2018–2020 panel. A significant rise in phage resistance among MDR-KP isolate panels of 2018–2020 and 2022–2023 was observed. Conclusion Lytic bacteriophages offer a promising alternative for tackling MDR-KP infections, especially within healthcare environments. The phages characterized in this study demonstrate strong potential for both biocontrol and therapeutic use against MDR-KP, including infections involving biofilms. However, the dynamic nature of bacterial evolution over five years reiterates the need to update phage banks.
BACKGROUND:People living with HIV (PLWH) are at increased risk for metabolic disorders, including diabetes and prediabetes. While hemoglobin A1c (HbA1c) is widely used for glycemic assessment, its reliability in PLWH is questioned due to altered red blood cell turnover. Glycated albumin (GA) has been proposed as an alternative, but its diagnostic utility remains unclear in PLWH. This study aims to compare the correlations of HbA1c and GA with fasting plasma glucose (FPG), evaluate their diagnostic performance, and identify factors influencing discrepancies between them in PLWH. METHODS:This retrospective cross-sectional study included 236 PLWH with documented FPG, HbA1c, and GA levels. Correlations between glycemic markers were assessed using Pearson's correlation coefficients. Diagnostic performance for prediabetes and diabetes was evaluated using receiver operating characteristic (ROC) curves, and a GA cut-off was determined using the Youden index. Multivariable logistic regression was performed to identify predictors of HbA1c-GA mismatch. RESULTS:HbA1c showed a moderate correlation with FPG (r = 0.33, p value < 0.001), while GA had a weaker correlation (r = 0.18, p value = 0.005). The area under the ROC curve (AUC) for detecting glycemic abnormalities was 0.66 for HbA1c and 0.57 for GA. The optimal GA cut-off for prediabetes derived from ROC analysis was 12.42 %, improving sensitivity but reducing specificity. Multivariable analysis identified low mean corpuscular volume (MCV <80 fL) as an independent predictor of HbA1c-GA mismatch (odds ratio = 4.94, 95 % confidence interval: 1.95-12.50, pvalue < 0.001). CONCLUSION:HbA1c or GA alone do not reliably capture glycemic abnormalities in PLWH. A lower GA cut-off (12.42 %) for prediabetes improves sensitivity but remains suboptimal. A combined approach incorporating FPG is recommended to enhance prediabetes and diabetes screening accuracy in this population.
BACKGROUND:Adherence to antiretroviral therapy (ART) is critical for successful viral suppression in people living with HIV (PLHIV). The comparative effectiveness of two-drug regimens (2DRs) versus three-drug regimens (3DRs)-particularly in Asian populations-is an underexplored topic. METHODS:This retrospective cross-sectional study was conducted at two hospitals in Taiwan between November 2023 and January 2025. Adherence was measured in terms of the proportion of days covered (PDC) over 365 days. Logistic regression analyses were used to evaluate the effectiveness of viral suppression and factors associated with regimen selection. RESULTS:Of the 628 PLHIV included, most were men, aged between 30 and 50 years, identified as lesbian, gay, bisexual, or transgender, and had received their diagnosis of HIV >5 years prior to this study. Among the participants receiving 3DRs (81.37 %), 3.72 % had viral loads exceeding 200 copies/mL. Regarding those receiving 2DRs (18.63 %), 2.56 % exhibited similar viral loads (p = 0.781). Multivariable analysis indicated that PDC ≥75 % was strongly associated with viral suppression (adjusted odds ratio [aOR] = 45.80, p < 0.0001), with no significant difference in viral suppression rates between regimens. The participants receiving 3DRs were less likely to have >75 % adherence (aOR = 0.18, p = 0.018) and to have a long HIV history (>5 years; aOR = 0.22, p = 0.041). CONCLUSION:Adherence, not regimen type, is the key factor affecting viral suppression. Nevertheless, the findings should be cautiously interpreted because of potential bias and small subgroup sizes. Further prospective studies should evaluate the comparative efficacy of these regimens.
Sexually transmitted infections (STIs) continue to pose major public health challenges globally, with millions of new cases reported annually. The asymptomatic characteristic of many STIs makes accurate and cost-effective diagnostic methods essential for screening and diagnosis. This paper evaluates the utility of enzyme-linked immunosorbent assays (ELISAs) in diagnoses of HIV, HPV, HSV, HBV, HCV, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and Treponema pallidum. Compared to nucleic acid amplification tests (NAATs), ELISAs have advantages that include minimal training requirements, lower costs, and suitability for community screening programs. Despite their practical advantages, conventional ELISAs face key performance limitations, cross-reactivity, lower sensitivity, and delayed detection, that have restricted their broader adoption, reducing the potential for ELISAs to become a standard STI detection method. Currently, advancements in ultrasensitive and digital ELISA technologies have greatly improved their accuracy and may improve the dilemma. This review describes current ELISA methodologies, efficacies, and limitations as observed in and reported for clinical applications and offers a comprehensive perspective on essential STI diagnostic improvements, motivated by the belief that ELISA techniques can significantly contribute to the early detection, treatment, and containment of STIs.
BACKGROUND:To disclose Proteus mirabilis copper detoxification mechanisms, we performed Tn5-mutagenesis and an hha gene-disrupted mutant was isolated, exhibiting increased copper sensitivity. We investigated the role of Hha in P. mirabilis, focusing on the virulence aspects. METHODS:Assays of copper susceptibility, swarming/swimming, biofilm formation, persister cell formation, killing by macrophages, adhesion, invasion, urothelial cell cytokine expression, wax moth virulence, were performed. The invertible element assay, TEM, EMSA and SDM were used to examine MR/P fimbria expression, flagellar production, Hha-flhDC promoter binding and the importance of Hha 13th amino acid cysteine (Hha C13), respectively. RT-PCR was conducted to demonstrate the tomB-hha operon. Hha-related gene expression and regulation were elucidated by RT-qPCR and transcriptional reporter assay. RESULTS:We showed P. mirabilis hha and tomB form an operon and TomB antagonized Hha toxicity. The Hha was involved in copper susceptibility, swimming/swarming, biofilm formation and persister cell formation. The hha mutant had lower adhesion/invasion abilities, triggered higher cytokine expression of urothelial cells and was more sensitive to macrophage killing and attenuated in wax moth. P. mirabilis Hha C13 is crucial in toxicity and Hha-TomB interaction. Deletion of hha reduced relA/rpoS expression. CpxR controlled hha promoter activity. Finally, copper was the signal to induce cpxR/hha expression. CONCLUSION:We disclosed that P. mirabilis Hha of the toxin-antitoxin system (TA) participates in virulence and its regulation by copper-sensing CpxR. This work provides Hha as a potential drug target for combating P. mirabilis urinary tract infections and opens new perspectives for studying TA aiming at controlling bacterial virulence.
BACKGROUND:To compare diagnostic performances and accuracy of non-invasive specimens and bronchoalveolar lavage fluid (BALF) for diagnosing Pneumocystis pneumonia (PCP) in immunocompromised pneumonia patients. METHODS:A prospective study of 112 immunocompromised patients to evaluate P. jirovecii fungal loads in paired sputum and BALF from the same patients. Patients were classified as definite PCP, probable PCP, and non-PCP based on criteria blinded to qPCR results. Optimal diagnostic cut-offs were derived, and agreement between specimen types was analyzed. RESULTS:A BALF fungal load threshold of 2,613 DNA copies/μL demonstrated high sensitivity (82.6 %, 95 % CI: 62.9-93.0) and specificity (96.7 %, 95 % CI: 90.8-99.1) for PCP diagnosis. In sputum, a cut-off of 474 DNA copies/μL offered moderate sensitivity (65.2 %, 95 % CI: 44.9-81.2) and high specificity (89.0 %, 95 % CI: 80.9-93.9), enabling the exclusion of PCP in patients with low clinical suspicion. Fungal loads in sputum correlated well with BALF but showed greater variability in confirmed PCP cases, highlighting limitations for non-invasive diagnosis in high-risk patients. CONCLUSION:Non-invasive fungal load in sputum provides a valuable tool for excluding PCP in immunocompromised pneumonia patients, potentially reducing the need for bronchoscopy.
OBJECTIVES:Diagnosing paediatric Community-Acquired Pneumonia (CAP) is challenging due to the difficulty in obtaining lung specimens. Studies suggest that the upper-airway density of Streptococcus pneumoniae is related to the risk and severity of CAP. We studied the association between S. pneumoniae and its density in the upper airways with CAP and its severity. Additionally, we examined the relationship between respiratory viral load and severe CAP. METHODS:Seven hundred fifteen children with radiologically confirmed CAP and 673 controls were enrolled over 11 years. Nasopharyngeal aspirates (NPA) were tested for 20 viruses and bacteria using semi-quantitative polymerase chain reaction (PCR). NPAs positive for S. pneumoniae were further analysed by quantitative PCR. Adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) were calculated to assess the association between S. pneumoniae density and CAP and CAP severity. RESULTS:Fewer cases than controls were colonised with S. pneumoniae (culture: 37.6 % vs 51.9 %, p < .001; PCR: 55.3 % vs 69.1 %, p < .001), and the median density was lower (6.20 log10 copies/mL vs 6.62 log10 copies/mL, p < .001). No association was found between S. pneumoniae density and CAP severity. CAP severity was significantly associated with high Respiratory Syncytial Virus (RSV) load (aOR 2.26, 95 % CI 1.43-3.57, p < .001) or high Human Metapneumovirus (HMPV) load (aOR 4.32, 95 % CI 2.19-8.48, p < .001), adjusted by pneumococcal density, other pathogens, age, sex, comorbidities, prior antibiotics and season. CONCLUSIONS:Detection and density of S. pneumoniae in the upper airways do not correlate with CAP presence or severity. High RSV and HMPV loads were linked to severe CAP.
