Tropical Medicine &International Health, EarlyView.

Abstract Background To address antibiotic overuse, the Japanese government implemented a novel financial incentive policy in 2018. The policy enables eligible healthcare facilities to claim 800 JPY (≈5.7 USD) per case wherein a rationale to not prescribe antibiotics is offered to children aged

Abstract Background Shigella sonnei has caused sexually transmitted enteric infections in men who have sex with men (MSM) in Vancouver. We recently observed a high rate of multidrug-resistant (MDR) S. sonnei bacteremia among persons experiencing homelessness (PEH). We aim to describe the wider epidemiology, clinical outcomes, and genomics of S. sonnei infections over time.Methods A retrospective review of 163 patients with S. sonnei infections was undertaken from 2015 –2022. We collected demographic, clinical, and microbiological data over two time periods: historical (2015-2020) and recent (2021-2022). Severe shigellosis definition included hospitalization, bacteremia, or death. Whole genome sequencing was performed to identify genotype, infer relatedness, and predict antimicrobial resistance.Results S. sonnei infections rose from 8.3 (historical-period) to 56.5 cases/year (recent-period). Over time, the primary population characteristics associated with shigellosis shifted from MSM (45, 98%) to PEH (86,77%). The population intersection between MSM and PEH historically and recently was similar and occurred in three (6%) and ten (9%) of patients, respectively. Severe shigellosis was significantly higher in the recent compared to historical period (69 [61%] versus 7 [14%], p

Abstract Background Most individuals on combination antiretroviral therapy (ART) have HIV plasma viral loads below the limit of detection. However, episodes of low-level viremia (LLV) are observed in subsets of individuals, risk factors and clinical significance of which remain debated.Methods We included participants enrolled in the Swiss HIV Cohort Study, starting ART between July 1999 and April 2023, with HIV RNA

Volume 13, Issue 1, December 2024 .

Volume 13, Issue 1, December 2024 .

Abstract Purpose Cytomegalovirus (CMV) is associated with significant morbidity and mortality among solid organ transplant (SOT) recipients. Strategies for CMV prevention include universal prophylaxis or preemptive approach. We aimed to evaluate the optimal approach. Methods We performed a systematic review and meta-analysis of randomized controlled trials comparing prophylaxis versus preemptive therapy for CMV in SOT. The primary outcome was CMV disease. Subgroup analysis of outcomes in D+ R− patients was performed. Results Nine trials have met inclusion criteria, five of them included kidney transplant recipients, all compared val/ganciclovir universal prophylaxis versus preemptive approach. Universal prophylaxis resulted in lower probability of CMV infection (relative risk [RR] 0.44, 95% confidence interval [CI] 0.33–0.58), yet the impact on CMV disease was insignificant (RR 0.54, 95% CI 0.24–1.23), in neither SOT recipients in general nor among D+R− subgroup (RR 0.93, 95% CI 0.37–2.32). Late-onset CMV disease rates were lower with preemptive approach. Sensitivity analysis according to allocation concealment and blinding showed similar results for CMV disease. No significant differences were demonstrated for the outcomes of mortality, bacterial or fungal infection or graft related outcomes. Acute kidney injury was significantly more common with prophylaxis (RR 1.79, 95% CI 1.12–2.89). Conclusion Preemptive approach is a reasonable approach for CMV prevention in SOT recipients, if feasible. Strategies for combining the preemptive with prophylaxis strategies, as well as immune monitoring, should be investigated. …

Abstract Purpose Early recognition of sepsis is critical to patient outcome, with mortality increasing with every hour of delay in treatment. The aim of this study was to investigate the use of a point-of-care molecular host response assay to differentiate sepsis from inflammation after surgery. Methods Three molecular host response assays (SeptiCyte® RAPID) were performed in 61 patients after major abdominal surgery with admission to the intensive care unit and drawn blood cultures. The first (T0) was taken ± 3 h around the time of obtaining blood cultures, the second 24 h later (T24) and the third at discharge from the intensive care unit (Tex). The primary endpoint was the agreement of SeptiCyte® RAPID results with the diagnosis of sepsis. SeptiScore® indicates sepsis probability (low risk 0 - high risk 15). Patients were retrospectively classified into sepsis and inflammation by three blinded experts. Results 25 (42.4%) patients were categorized as “inflammation” and 34 (57.6%) patients as “sepsis”. At T0 and T24 septic patients showed significantly higher mean SeptiScores® of 8.0 (± 2.2 SD) vs. 6.3 (± 2.1 SD) and 8.5 (± 2.1 SD) vs. 6.2 (± 1.8 SD), respectively. The Receiver Operating Curves (ROC) for the ability to discriminate between sepsis and inflammation had an Area Under the Curve (AUC) of 0.71 (T0) and 0.80 (T24). Conclusion Embedded in a comprehensive diagnostic algorithm molecular host response analysis could broaden the possibilities for infection diagnostics to differentiate between sepsis and inflammatory response after surgery. But validation in larger cohorts is needed. …

Introduction: The US state of Florida has the third highest rate of HIV as well as high rates of sexually transmitted infections (STIs) indicating critical HIV and STI prevention needs remain unmet. To address gaps in the STI care continuum in people with HIV (PWH), evidence-based interventions were implemented across three Ryan White HIV/AIDS Program (RWHAP) funded clinics in Florida between August 2020–August 2021. Interventions included comprehensive sexual health history (SHH) taking using audio computer-assisted self-interview (ACASI) software, self-collected extragenital gonorrhea and chlamydia testing, and the introduction of a lesbian, gay, bisexual, transgender, and queer (LGBTQ+) welcoming environment. Methods: We 1) assessed the acceptability of these interventions and examined if acceptability differed among youth and sexual, racial and ethnic minorities, 2) determined the proportion of appropriate STI testing completed based on the SHH assessment, 3) examined whether STI at-risk individuals underwent STI screening 3-6 months after initial evaluation, and 4) determined the proportion of positive STI test results among priority intervention groups in Florida. Results: Acceptability of all interventions was high. Youth, lesbian, gay, and bisexual, and Hispanic individuals were significantly more likely to notice and like LGTBQ+ welcoming measures. The proportion of recommended tests completed was high, although only a subset of at-risk individuals completed re-screening. 11.9% of rectal samples were positive for chlamydia and 6.5% of pharyngeal samples were positive for gonorrhea. Conclusions: Our study highlights the importance of incorporating comprehensive sexual health care protocols, including extragenital STI testing, into the overall care of PWH. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

Background: In the United States, young men who have sex with men (YMSM) and young transgender women (YTGW) are disproportionately affected by HIV infection. Adequate HIV knowledge is critical for protecting adolescents and young adults at risk for HIV. This study aimed to evaluate the effectiveness of the mLab App intervention in enhancing HIV knowledge among YMSM and YTGW. Methods: This study was a secondary analysis of data collected from a randomized controlled trial (RCT) evaluating the effect of the mLab App on HIV knowledge. We calculated interactions between groups (mLab App intervention, standard of care, at-home testing) over time (6 and 12 months) following the baseline observation, indicating a difference in the outcome scores from baseline to each time across groups. Results: While the mLab App group initially had lower HIV knowledge compared to those in other groups, access to the App demonstrated a progressive impact on HIV knowledge over time. Despite the absence of a statistically significant effect at the 6-month, the long-term evaluation suggests improvements in HIV knowledge during the 12-month intervention follow-up. Conclusion: Our study suggests the potential of the mLab App as a valuable tool for long-term HIV education and awareness for YMSM and YTGW. Further research is needed to understand the factors influencing the short-term effect on HIV knowledge. The mLab App may be a useful intervention for improving HIV knowledge. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Background This study aims to develop and examine the performance of machine learning (ML) algorithms in predicting viral suppression among statewide people living with HIV (PWH) in South Carolina (SC). Methods Extracted through the electronic reporting system in SC, the study population was adult PWH who were diagnosed between 2005-2021. Viral suppression was defined as viral load…

People with HIV (PWH) appear to be at an elevated risk for severe COVID-19 outcomes. Several studies have shown that PWH with pronounced immunodeficiency (e.g., lower CD4 count) have a higher risk for worse clinical outcomes, including COVID-19-related hospitalization and death.[1, 2] Severe COVID-19 outcomes among PWH might be partially due to the exacerbating syndemic effects of COVID-19, HIV, and other risk factors (e.g., low socio-economic status, more chronic comorbidities) on health inequalities.[3, 4] Yet, the evidence regarding the effectiveness of COVID-19 vaccines in this high-risk group remains sparse.[5, 6] Despite several large population-based studies that have evaluated COVID-19 vaccine effectiveness (VE) in this population, more evidence is warranted to confirm the robustness of previous findings and inform COVID-19 vaccine strategies for PWH.

Semi-automated surveillance systems save time compared to traditional manual methods, particularly for non-ventilator hospital-acquired pneumonia (nvHAP), a nosocomial infection which can affect all non-intubated patients. In semi-automated surveillance, a computerized algorithm selects patients with high probability (i.e. ‘at risk’) for subsequent manual confirmation. This study aimed to evaluate the performance of several single indicators and algorithms to preselect patients at risk for nvHAP.

Post-hoc analyses of the MERINO trial highlight the uncertainty associated with establishing piperacillin tazobactam (PTZ) susceptibility in extended-spectrum beta lactamase (ESBL) producing Enterobacterales. Herein, we compare the concordance of susceptibility for PTZ between the VITEK 2, disk diffusion, and Etest with broth microdilution (BMD) as the reference standard.

We read with interest the article by Webb and colleges suggesting that Nesisseria elongata should be considered as a “HACEK-bacterium” and that the “HACEK” mnemonic should be revised to “HANCEK” (1). The role of the HACEK mnemonic is to remind the clinician that a blood culture result with any of the HACEK-bacteria might represent infective endocarditis (IE). The expression HACEK-bacteria is very well known and is well established (2). We agree with several arguments about N. elongata put forward by the authors but we do not agree with the conclusion to add N.

A post hoc analysis used pooled STRIVE/ReSTORE trial data to determine outcomes with rezafungin versus caspofungin by Candida species and antifungal susceptibility.

Up from September 2024 (with the first notification of cases to WHO on September 28), an outbreak of Marburg virus disease (MVD) emerged in Rwanda, East Africa, and at the time of writing (14 November 2024), it is drawing to a close. This is due to a robust and well-coordinated public health response by Rwandan authorities, bolstered by strong South-South collaboration with partner countries across sub-Saharan Africa, and a central role played by female healthcare workers [1]. As of 14 November 2024, 66 confirmed cases of MVD have been reported, rendering it the third-largest MVD outbreak ever recorded.

Diagnosing infectious encephalitis can be challenging as it can be caused by a wide range of pathogens, with viruses being the most common cause. In a substantial number of patients, no pathogen is identified despite a clinical diagnosis of infectious encephalitis. Recent advancements in diagnostic testing have introduced new methods to address this diagnostic challenge and improve pathogen detection.

Streptococcus pneumoniae infection can lead to serious and potentially life-threatening illness, referred to as invasive pneumococcal disease (IPD). This includes bloodstream infection, bacteraemic pneumonia, empyema, and meningitis. The impact is greatest amongst young children, patients with immunosuppression and chronic diseases, and in older adults [1].

Human campylobacteriosis, is a leading bacterial foodborne infection, primarily caused by contaminated food, especially poultry. In Denmark, notified domestic Campylobacter cases have annually ranged from 3,740 to 5,389 over the past five years, with chicken often identified as the primary infection source. The Danish authorities and the food industry have been actively working together to control Campylobacter and to reduce the risk of human infection from chicken meat. Since 2019, Denmark has routinely used Whole Genome Sequencing (WGS) to detect clusters of Campylobacter jejuni and Campylobacter coli infections and link potential outbreaks to food sources, enhancing outbreak detection and targeted interventions [1].

To evaluate the effectiveness of ceftaroline vs. vancomycin or daptomycin in the treatment of methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSIs).

Abstract Our group previously demonstrated that NETs were involved in interstitial lung diseases (ILD) among patients with idiopathic inflammatory myopathies (IIM) and the experimental autoimmune myositis (EAM) mouse model, and that NETs activated lung fibroblasts through the TLR9-miR7-Smad2 axis. This study aimed to establish a novel mouse model of myositis-associated interstitial lung disease (MAILD) by using a TLR9 agonist (ODN2395). ODN2395 and muscle homogenate were used to induce MAILD in BALB/c mice. MAILD was evaluated using histopathology, immunohistochemistry, serum NETs determination, and myositis-specific antibody profile. Furthermore, TLR9 and IRF3 were examined in a lung biopsy tissue from a dermatomyositis patient with ILD. MAILD mice developed inflammatory myopathy with positive expression of myositis specific antibodies. ILD occurred in all mice of MAILD group. ODN2395 at doses of 5μg, 10μg or 20μg induced ILD, with increasing severity as the dose increased, but 20μg ODN2395 was not recommended due to non-specific damage to lungs. ILD could occur as early as one week after immunization and was most pronounced by the fourth/fifth week. MAILD process was accompanied by NETs infiltration and TLR9 activation. TLR9 activation was demonstrated in the patient with DM-ILD. Serum levels of Cit-H3 were elevated in the MAILD group. Skeletal muscle homogenate and ODN2395 induced neutrophils to form NETs in vitro. Combined with muscle homogenate, ODN2395 induced a novel MAILD mouse model with NETs infiltration and TLR9 activation, which are similar to pathogenesis of IIM-ILD, suggesting that MAILD model could replace EAM model in IIM-ILD research.

Abstract Vaccines are crucial for protecting health globally; however, their widespread use relies on rigorous clinical development programmes. This includes Phase 3 randomised controlled trials (RCTs) to confirm their safety, immunogenicity, and efficacy. Traditionally, such trials used fixed designs with predetermined assumptions, lacking the flexibility to change during the trial or stop early due to overwhelming evidence of either efficacy or futility. Modern vaccine trials benefit from innovative approaches like adaptive designs, allowing for planned trial adaptations based on accumulating data. Here, we provide an overview of the evolution of Phase 3 vaccine trial design and statistical analysis methods from traditional to more innovative contemporary methods. This includes adaptive trial designs, which offer ethical advantages and enable early termination if indicated; Bayesian methods, which combine prior knowledge and observed trial data to increase efficiency and enhance result interpretation; modern statistical analysis methods, which enable more accurate and precise inferences; the estimand framework, which ensures the primary question of interest is addressed in a trial; novel approaches using machine learning methods to assess heterogeneity of treatment effects; and statistical advances in safety analysis to evaluate reactogenicity and clinical adverse events. We conclude with insights into the future direction of vaccine trials, aiming to inform clinicians and researchers about conventional and novel RCT design and analysis approaches to facilitate the conduct of efficient, timely trials.