Therapeutic Advances in Infectious Disease最新文献

Background: South Africa has the third-highest adult prevalence rate globally, with women comprising 64% of cases. Despite the accessibility of pre-exposure prophylaxis (PrEP), its adoption among women, particularly young women, remains alarmingly low.

Objectives: The objective of this initial investigation is to explore factors influencing the intentions of South African women to use PrEP, focusing on sociodemographic factors, HIV sexual risk behaviours and involvement in transactional sex.

Design: The research utilised an exploratory design employing surveys.

Methods: Surveys were conducted in 2015 with 64 women aged 19-49 residing in the Eastern Cape Province of South Africa. The data were analysed using descriptive statistics and multiple logistic regression. Data analysis was performed using SPSS 28.0 and R.

Results: Younger women, compared to older women, were more inclined to intend to use PrEP (p = 0.056, χ² = 3.655, df = 1, OR 0.92, CI (0.89, 0.99)). Women who used a condom were less likely to intend to use PrEP (p = 0.082, χ² = 3.025, df = 1, OR 0.29, CI (0.09, 1.14)). Respondents who engaged in transactional sex were more inclined to intend to use PrEP (p = 0.007, χ² = 7.330, df = 1, OR 6.86, CI (1.82, 31.0)).

Conclusion: Addressing factors that impact South African women's intentions to use PrEP is crucial for enhancing the adoption of PrEP among this population.

Background: Despite prophylactic pharmacotherapy being ranked as the best intervention yet, poor treatment adherence tempers tuberculosis preventive therapy (TPT) efficacy.

Objectives: This study aimed to investigate TPT non-adherence among household contacts and its determinants following the rollout of the 3HP regimen in northwest Ethiopia.

Design: A facility-based multicenter retrospective study was conducted in selected hospitals of northwest Ethiopia from October 17 to February 21, 2024.

Methods: Target populations were TPT-eligible household contacts (⩽15 years old) based on the national tuberculosis treatment guideline. Univariate and multivariate binary logistic regression model was fitted to identify potential predictors. p-Value < 0.05 was employed to adjudicate the significance level.

Results: Among 494 household contacts (HHCs) enrolled in this study, 27.94% were non-adherent. Age (5-10 years: adjusted odds ratio (AOR) (95% CI): 1.92 (1.05-3.19); 10-15 years: AOR (95% CI): 2.04 (1.01-4.12)), parental status (AOR (95% CI): 1.87 (1.02-5.24)), comorbidity (AOR (95% CI): 2.92 (1.08-5.69)), poor nutritional status (AOR (95% CI): 1.30 (1.06-2.43)), adverse drug reactions (AOR (95% CI): 4.01 (1.03-8.20)), adherence support (AOR (95% CI): 1.56 (1.08-6.69)) and TPT regimen type (AOR (95% CI): 4.23 (1.85-6.53)) predicts non-adherence.

Conclusion: Altogether, this study revealed a high level of non-adherence among HHCs in northwest Ethiopia, falling short of the national 2025/26 TPT targets. TPT should be accompanied by firm counseling and routine supervision to improve adherence.

We report the case of a 38-year-old woman with human immunodeficiency virus (HIV) infection diagnosed in 2010 and on antiretroviral treatment since 2014, with an undetectable viral load and a CD4 lymphocyte count of 527 cells/µL. The patient presented with weight loss, fever, hyporexia, nausea, vomiting, progressive dyspnea, purpuric abdominal lesions, and lower extremity edema. During hospitalization, she developed hemoptysis and severe respiratory failure and died a few hours later. Parasitological studies of sputum and stool showed abundant Strongyloides stercoralis larvae, confirming disseminated strongyloidiasis. This case highlights that severe S. stercoralis infection can occur even in patients with clinically controlled HIV, underscoring the need for screening in endemic regions.

Invasive pulmonary aspergillosis (IPA) is a severe opportunistic fungal infection that predominantly affects immunocompromised individuals, including those with hematologic malignancies, organ transplants, and, more recently, patients with post-COVID-19 immune dysregulation. Despite advancements in medical mycology, IPA continues to pose significant diagnostic and therapeutic challenges, contributing to high global morbidity and mortality. Diagnostic accuracy remains limited due to nonspecific clinical manifestations and the suboptimal performance of conventional tools such as bronchoalveolar lavage culture and galactomannan testing. However, recent innovations including polymerase chain reaction-based molecular assays, lateral flow devices, and immuno-positron emission tomography/magnetic resonance imaging offer improved sensitivity, specificity, and speed. Therapeutically, triazoles remain the cornerstone of IPA management, complemented by echinocandins and liposomal amphotericin B in refractory cases. The role of combination therapy and antifungal susceptibility testing is growing in response to rising azole resistance. Additionally, novel antifungal agents and immunotherapeutic approaches are currently under clinical investigation. Effective management of IPA requires a timely, multidisciplinary approach that combines advanced diagnostics with personalized antifungal strategies. Continued research is essential to standardize molecular techniques, refine immunotherapy, and expand access to next-generation antifungals to reduce the global burden of this life-threatening infection. This review aims to synthesize current evidence on the diagnosis and treatment of IPA, critically evaluate the strengths and limitations of existing diagnostic and therapeutic approaches, and explore emerging strategies to enhance clinical outcomes in the context of rising antifungal resistance.

Background: Infectious diseases of the spine (IDS) cause structural destruction and abscess formation, requiring precise early diagnosis. While conventional culture methods show limited sensitivity and slow turnaround, metagenomic next-generation sequencing (mNGS) offers a promising alternative with its broader pathogen spectrum, rapid turnaround time, high detection rate, and sensitivity, showing significant advantages in the diagnosis of IDS.

Objectives: This systematic review aims to synthesize the current evidence on the advantages and clinical utility of mNGS in diagnosing and managing IDS, focusing on pyogenic and granulomatous spinal infections.

Design: The systematic review conducted in accordance with PRISMA guidelines.

Data sources and methods: A comprehensive literature search was performed across nine electronic databases (including PubMed, Web of Science, and Embase) from 2010 to April 2025. Studies reporting on mNGS for pathogen detection in patients with suspected or confirmed spinal infections were included. The quality of included observational studies was assessed using the STROBE checklist. Data on detection spectrum, rate, sensitivity, turnaround time, and clinical impact were extracted and synthesized narratively due to high heterogeneity.

Results: Twenty-nine studies (25 retrospective studies and 4 case reports) from China were included. mNGS demonstrated a significantly broader detection spectrum, identifying common pathogens (e.g., Staphylococcus aureus, Mycobacterium tuberculosis) as well as rare and fastidious organisms that were missed by conventional methods. The pooled detection rate of mNGS (36.8%-95.5%) was consistently and significantly higher than that of culture (5.9%-59.2%). mNGS also showed superior sensitivity (39%-94.7%) compared to culture. The average turnaround time for mNGS (29-53 h) was substantially faster than for culture (2-10 days). mNGS-guided therapy was associated with improved clinical outcomes, including significant reductions in inflammatory markers.

Conclusion: mNGS represents a powerful diagnostic tool for IDS, offering broader detection spectrum, higher detection rate, faster turnaround time, and greater sensitivity compared to conventional methods. This enables more targeted antimicrobial therapy and improves clinical management. Challenges including high costs and difficulty in distinguishing colonization from infection remain. Future efforts should focus on technical optimization, workflow automation, protocol standardization, and outcome validation in larger prospective studies.

Trial registration: CRD420251170912.

Peptide-based vaccines, utilizing defined B- and T-cell epitopes, have emerged over the past two decades as promising alternatives to conventional vaccine platforms. Their key advantages, including excellent safety profiles, precise immunological targeting, and ease of manufacture, position them as a versatile tool in modern immunology. However, the widespread clinical application of these vaccines is significantly challenged by inherent limitations, most notably their low inherent immunogenicity and susceptibility to enzymatic degradation in vivo, leading to structural instability and short half-lives. This review systematically examines the innovative strategies being developed to overcome these critical obstacles. It delves into advances in rational vaccine design, highlighting the pivotal role of bioinformatics and computational tools for precise epitope selection and the engineering of sophisticated multi-epitope constructs that elicit broader immune responses. Furthermore, we provide a comprehensive analysis of novel drug delivery systems, such as a diverse range of nanoparticle carriers (e.g., liposomes, polymer-based), and review the mechanism of action of next-generation adjuvants. These technologies are crucial for enhancing antigen presentation, protecting the peptide payload, and promoting robust, durable cellular and humoral immunity. By synthesizing current literature from databases like PubMed and Google Scholar, this review offers a detailed overview of recent progress in peptide vaccine development against viral pathogens, drawing on key findings from both preclinical and clinical studies. It highlights key findings from preclinical and clinical studies and provides insights into the mechanistic actions and future potential of these precision vaccines in combating evolving viral threats.

Babesiosis and Lyme disease are tick-borne infections endemic to the northeastern and upper Midwestern United States. Although both diseases can involve multiple organ systems, acute liver failure (ALF) is exceedingly uncommon. Co-infection with Babesia microti and Borrelia burgdorferi may exacerbate disease severity, create diagnostic uncertainty, and delay appropriate therapy. We describe a 77-year-old man with type II diabetes mellitus, stage IV chronic kidney disease, and heart failure with preserved ejection fraction who presented with dyspnea, cough, and peripheral edema. Initial evaluation suggested decompensated heart failure and acute kidney injury consistent with cardiorenal syndrome. Within 24 h, however, he developed ALF (total bilirubin 6.8 mg/dL; aspartate aminotransferase 2656 U/L; alanine aminotransferase 1421 U/L; INR 3.5), thrombocytopenia (95 × 10⁹/L), acute anemia (hemoglobin 7.7 g/dL), and encephalopathy. Initial infectious, autoimmune, and ischemic evaluations were unrevealing. Despite empiric antimicrobial therapy with intravenous ceftriaxone, vancomycin, and doxycycline, his condition rapidly deteriorated, and he died. Postmortem testing identified B. microti parasitemia of 2.4% and B. burgdorferi co-infection. This case highlights the importance of considering tick-borne coinfections in patients presenting with ALF and shock, even in the absence of classic features such as fever, rash, or overt hemolysis. Increased clinician awareness of atypical presentations of endemic tick-borne diseases may help reduce diagnostic delays and improve outcomes in severe or unusual clinical scenarios.

Trichoderma is a genus of rare filamentous fungi that can cause invasive fungal infections in immunocompromised patients. We report a case of necrotizing gingival and sinus infection due to T. longibrachiatum in an allogeneic stem cell transplant recipient. The patient received a combination of antifungal and aggressive surgical debridement, achieving clinical cure. The treatment included amphotericin B, voriconazole and caspofungin with the latter switch to rezafungin to consolidate therapy. Rezafungin might represent a useful alternative for fungal infections with limited therapeutic options, but further studies are needed to confirm its role in Trichoderma spp. infections.

Background: Empirical antibiotic therapy (EAT) in febrile neutropenia (FN) remains challenging due to multidrug-resistant (MDR) Gram-negative bacteria, often leading to inappropriate empirical antibiotic therapy (IEAT).

Objective: To demonstrate that risk stratification based on machine learning (ML) and prior colonisation with MDR bacteria may support the tailoring of EAT in patients with haematological malignancies.

Design: Retrospective proof-of-concept cohort study.

Methods: All consecutive FN episodes in patients with haematological malignancies were retrospectively included from January 2020 to March 2023 at a tertiary-level university hospital. We compared real-world, clinician-driven empirical antibiotic use with a simulated approach guided by an ML-based risk stratification model combined with prior colonisation data. The main outcomes were antibiotic selection and rates of IEAT.

Results: A total of 553 FN episodes in 398 haematological patients were analysed. Bloodstream infection (BSI) occurred in 141/553 episodes (25.5%). Anti-pseudomonal (PsA) beta-lactams were prescribed in 515/553 episodes (93.1%), with carbapenems in 406/553 (73.4%). The clinician-driven approach resulted in 16/70 (22.9%) GNB-BSI episodes receiving IEAT. The ML plus colonisation-guided approach would have reduced the use of meropenem by 29.7% (-2.08 days; 95% CI, -2.42 to -1.73; p < 0.001) and anti-PsA beta-lactams by 6.7% (-0.47 days; 95% CI, -0.76 to -0.19; p = 0.001), and would also have led to a reduction in the rate of IEAT from 16/70 (22.9%) to 6/70 (8.6%) (p = 0.035).

Conclusion: ML-based risk stratification combined with colonisation status would allow for personalised antibiotic therapy in FN, potentially reducing IEAT and improving antimicrobial use. These results support integrating these tools into clinical practice.