Re-evaluating efficacy of vaccines against highly pathogenic avian influenza virus in poultry: A systematic review and meta-analysis.

The global spread of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b virus since 2021 necessitates a re-evaluation of the role of vaccination in controlling HPAI outbreaks among poultry, which has been controversial because of the concern of silent spread with viral mutation and spillover to human. We systematically reviewed and meta-analyzed all existing data from experimental challenge trials to assess the efficacy of HPAI vaccines against mortality in specific pathogen free (SPF) chickens, with evaluation of the certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Out of 223 screened publications, 46 trials met our eligibility criteria. Inactivated vaccines showed an efficacy of 95% (risk ratio [RR] = 5% [95% CI: 1% to 17%], I2 = 0%, CoE high) against homologous strains and an efficacy of 78% (RR = 22% [95% CI: 14% to 37%], I2 = 18%, CoE high) against heterologous strains (test for subgroup difference p = 0.02). Live recombinant vaccines exhibited the highest efficacy at 97% (RR = 3% [95% CI: 1% to 13%], I2 = 0%, CoE high). Inactivated recombinant vaccines had an overall efficacy of 90% (RR = 10% [95% CI: 6% to 16%], I2 = 47%, CoE high). Commercial vaccines showed an overall efficacy of 91% (RR = 9% [95% CI: 5% to 17%], I2 = 23%, CoE high), with 96% efficacy (RR = 4% [95% CI: 1% to 21%], I2 = 0%, CoE high) against homologous strains and 90% efficacy (RR = 10% [95% CI: 5% to 20%], I2 = 31%, CoE moderate) against heterologous strains. Our systematic review offers an updated and unbiased assessment of vaccine efficacy against HPAI-related mortality, providing timely and crucial information for re-evaluating the role of vaccination in poultry avian influenza control policy amist the global HPAI outbreak post-2021.

Changing epidemiology and antimicrobial resistance of bacteria causing bacteremia in Taiwan: 2002-2020.

Bacteremia is associated with significant morbidity and mortality. The emergence of bacteria with antimicrobial resistance (AMR) has further exacerbated the poor outcomes associated with bacteremia. The Taiwan Surveillance of Antimicrobial Resistance (TSAR) program was established in 1998 to monitor bacterial epidemiology and antimicrobial resistance trends across all patient types and age groups. Between 2002 and 2020, a total of 14,539 non-duplicate bacteremia isolates were collected biennially from 29 hospitals during the months of July-September as part of the TSAR program. The three most common bacteremia agents were Escherichia coli (31%), Staphylococcus aureus (13.6%), and Klebsiella pneumoniae (12.7%) overall. However, there was a steady increase in the proportions of E. coli and Enterococcus faecium isolated from bacteremia cases (both P < 0.001), while the proportions of Acinetobacter spp. decreased. Regarding antimicrobial resistance, there was a notable increase in rates of third-generation cephalosporin and fluoroquinolone non-susceptibility among E. coli and K. pneumoniae, while the rates of carbapenem non-susceptibility were elevated but remained milder in these two species, especially in E. coli. Of concern is the alarming increase in vancomycin resistance among E. faecium, rising from 10.0% in 2004 to 47.7% in 2020. In contrast, the prevalence of methicillin-resistant S. aureus has remained stable at 51.2% overall. In conclusion, E. coli, with increasing third-generation cephalosporin and fluoroquinolone resistance, is the predominant cause of bacteremia in Taiwan during the 18-year surveillance. The escalating proportion of E. faecium in bacteremia, coupled with a concurrent upsurge in vancomycin resistance, presents a therapeutic challenge in the recent decade. IMPORTANCE: AMR surveillance not only enables the identification of regional variations but also supports the development of coordinated efforts to combat AMR on a global scale. The TSAR has been a biennial, government-endorsed, multicenter study focusing on pathogens isolated from inpatients and outpatients in Taiwan hospitals since 1998. Our report presents an 18-year comprehensive analysis on blood isolates in the 2002-2020 TSAR program. The study highlights an alarming increase in the proportion of E. faecium causing bacteremia accompanied by elevated vancomycin resistance. It is worth noting that this trend differs from the observations in the United States and China. Understanding the composition of bacteria causing bacteremia, along with their prevalence of antimicrobial resistance, holds significant importance in establishing healthcare and research priorities. Additionally, this knowledge serves as a critical factor in evaluating the effectiveness of preventive interventions.

Impact of vaccination and high-risk group awareness on the mpox epidemic in the United States, 2022-2023: a modelling study.

Background: The unprecedented global outbreak of mpox in 2022 posed a public health challenge. In addition to the mpox vaccine campaign in the United States (US), community organisations and public health agencies initiated educational efforts to promote sexual risk reduction. This modelling study estimated the impact of the two-dose vaccination campaign and sexual behaviour changes coincident with high-risk group awareness on the mpox epidemic in the US. Methods: We fitted a deterministic, risk-structured SEIARV model to the epidemic curve of reported mpox cases in the US between May 22, 2022 and December 22, 2022. We evaluated the putative effects of the two preventive responses in the US -- vaccination and sexual risk reduction -- at the population-level, by calculating the prevention percentages of cumulative cases compared to the counterfactual scenario without interventions. We performed sensitivity analyses with four parameters: case reporting fidelity, vaccine effectiveness, proportion of asymptomatic cases, and assortative mixing. Findings: Model fitting revealed a basic reproduction number of 3.88 and 0.39 for the high-risk and low-risk populations, respectively, with 71.8% of mpox cases estimated from the high-risk population. A two-dose vaccination campaign, solely, could prevent 21.2% (10.2%-24.1%) of cases, while behaviour changes due to high-risk group awareness alone could prevent 15.4% (14.3%-20.6%). The combination of both measures were synergistic, with the model suggesting that 64.0% (43.8%-69.0%) of US cases were averted that would have otherwise occurred. Interpretation: Our models suggest that the 2022-2023 mpox epidemic in the US was controlled by a combination of two-dose mpox vaccination campaign and high-risk group awareness and sexual risk reduction. Funding: Taiwan Ministry of Education grant #NTU-112L9004, Taiwan National Science and Technology Council grant #MOST-109-2314-B-002-147-MY3 and grant #NSC-112-2314-B-002-216-MY3. SHV was supported, in part, by US National Institutes of Health grant #P30MH062294.

Revisiting the association between vitamin D deficiency and active tuberculosis: A prospective case-control study in Taiwan.

BACKGROUND: To revisit the association between vitamin D deficiency (VDD, defined as serum 25(OH)D < 20 ng/ml) and incident active tuberculosis (TB), after two potentially underpowered randomized trials showed statistically non-significant 13%-22% decrease in TB incidence in vitamin D supplementation groups. METHODS: We prospectively conducted an age/sex-matched case-control study that accounting for body-mass index (BMI), smoking, and other confounding factors to examine the association between VDD and active TB among non-HIV people in Taiwan (latitude 24°N), a high-income society which continues to have moderate TB burden. RESULTS: We enrolled 62 people with incident active TB and 248 people in control group. The TB case patients had a significantly higher proportion of VDD compared to the control group (51.6% vs 29.8%, p = 0.001). The 25(OH)D level was also significantly lower in TB patients compared to control group (21.25 ± 8.93 ng/ml vs 24.45 ± 8.36 ng/ml, p = 0.008). In multivariable analysis, VDD (adjusted odds ratio [aOR]: 3.03, p = 0.002), lower BMI (aOR: 0.81, p < 0.001), liver cirrhosis (aOR: 8.99, p = 0.042), and smoking (aOR: 4.52, p = 0.001) were independent risk factors for incident active TB. CONCLUSIONS: VDD is an independent risk factor for incident active TB. Future randomized trials examining the effect of vitamin D supplementation on TB incidence should focus on people with a low BMI or other risk factors to maximize the statistical power.

Quantifying the contribution of smear-negative, culture-positive pulmonary tuberculosis to nosocomial transmission.

BACKGROUND: Despite current guidelines for tuberculosis (TB) control in health care settings, which focused on smear-positive cases, prevention of nosocomial TB transmission continues to be a challenge. Here, we report the results of the first hospital-wide prospective study applying interferon-gamma release assay to investigate the role of smear-negative, culture-positive index cases in nosocomial TB transmission. METHODS: We prospectively identified cases of culture-confirmed smear-negative pulmonary TB receiving aerosol-generating procedures (AGPs) and cases of culture-confirmed smear-positive pulmonary TB admitted at a medical center. Nosocomial transmission was evaluated by screening their close contacts for latent TB infection (LTBI) using an interferon-gamma release assay. RESULTS: A total of 93 smear-negative index receiving AGP and 122 smear-positive index were enrolled. Among them, 13 (14.0%) and 43 (35.2%) index cases, respectively, had secondary cases of LTBI (P < .001). Sputum smear negativity (adjusted odds ratio: 0.20 [0.08-0.48]) and AGP (sputum suction; adjusted odds ratio: 3.48 [1.34-9.05]) are independent factors of transmission. A similar proportion in the close contacts of the 2 index groups had LTBI (17 [15.3%] and 63 [16.0%], respectively), and the former index group contributed to 21.3% of the nosocomial transmission. CONCLUSIONS: Smear-negative, culture-positive index cases receiving AGPs could be as infectious as smear-positive index cases. Hospital TB control policy should also focus on the former group.

Effect of early dexamethasone on outcomes of COVID-19: A quasi-experimental study using propensity score matching.

BACKGROUND: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain. METHODS: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians' decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days. RESULTS: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97-1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94-1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12-1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02-1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01-1.98). CONCLUSION: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19.