Therapeutic Advances in Infectious Disease最新文献

Cryptococcal meningitis (CM) is a severe opportunistic infection in people living with HIV (PLWH). We report a 54-year-old man with advanced HIV infection who presented with CM due to Cryptococcus neoformans. Induction therapy with liposomal amphotericin B (4 mg/kg/day) plus fluconazole (800 mg/day) was prolonged to 10 weeks because flucytosine was initially unavailable; intravenous flucytosine (25 mg/kg q6h) was introduced when accessible. Maintenance fluconazole (800 mg/day) was continued, and antiretroviral therapy (ART) with dolutegravir plus emtricitabine/tenofovir disoproxil was initiated after 8 weeks. One year later, despite virological suppression, he developed neurological deterioration compatible with recurrent CM in the absence of culture confirmation. He underwent re-induction with liposomal amphotericin B plus flucytosine, followed by off-label secondary prophylaxis with oral isavuconazole (200 mg/day). Over 6 months, he maintained HIV-RNA suppression, showed CD4+ T-cell recovery (from 94 to 165 cells/mm³), and experienced neurological stabilization without further CM episodes or drug-related toxicity. Isavuconazole's pharmacokinetic profile, oral availability, and limited antiretroviral drug-drug interactions supported its use as extended secondary prophylaxis in this setting, although limited access in low- and middle-income countries remains a concern. This case highlights isavuconazole as a potential alternative prophylactic strategy when fluconazole is ineffective or not tolerated.

Chronic pulmonary aspergillosis (CPA) often arises in the setting of structural lung damage and is associated with chronic inflammation, which increases the risk of venous thromboembolic disease (VTE), including pulmonary embolism (PE). However, the clinical context and pathophysiological mechanisms underlying CPA/VTE remain poorly defined. This study aims to highlight the clinical challenges through a case series and systematic review of existing literature regarding this rare co-occurrence. We present three complex cases from Kiruddu National Referral Hospital in Uganda: two males, one female, aged 44-80 years, with post-tuberculosis lung disease. All three were diagnosed with Aspergillus IgG-positive CPA and confirmed PE (two acute, one with chronic thromboembolic pulmonary hypertension (CTEPH)). One presented with concurrent active tuberculosis (TB) relapse and severe immunosuppression (CD4 T-cells < 200 cells/mm³), and two had HIV. All patients received itraconazole and anticoagulation with rivaroxaban. Two patients survived and are stable on therapy, while one patient died due to septic shock. A systematic search of PubMed, Embase, Scopus, and Web of Science yielded seven studies reporting nine patients with coexisting CPA and VTE/PE. Underlying conditions most frequently included prior TB (n = 3) and chronic obstructive pulmonary disease (n = 3). PE was chronic in three patients (including one with CTEPH), with CPA subtypes ranging from simple aspergilloma to subacute invasive aspergillosis and angioinvasive aspergillosis. Proposed mechanisms included endothelial damage due to Aspergillus angioinvasion and creation of post-PE lung cavities/infarcts suitable for Aspergillus colonization. Anticoagulation was used in six cases, but was complicated by hemoptysis in three. Two-thirds of patients improved with antifungal therapy, while three deaths were reported. CPA may coexist with PE/DVT due to fungal angioinvasion, chronic inflammation, or immobilization from advanced lung disease. Management requires individualized balancing of antifungal and anticoagulation therapy, with heightened vigilance for bleeding.

Background: Contingency management (CM) has been used to reinforce abstinence in the treatment of substance use disorders (SUD). Novel applications of CM in people who use drugs (PWUD) have been used to facilitate other desirable behaviors.

Objective: Describe and assess preliminary outcomes of a program intended to reduce risk for HIV and related infections in a population of PWUD through increased healthcare engagement.

Design: Patients receiving care for SUD at a collocated clinic receive shaping CM-based incentives for risk assessment, testing, and clinic attendance.

Methods: Baseline cohort characteristics are assessed, and engagement in clinical care during the early period of the program is described.

Results: Participants are majority African American, female, and meet criteria for experiencing financial resource strain. During the first year of the program, no significant changes in clinic appointment attendance were observed.

Conclusion: Patient-centered CM-based incentivization implemented in a low-barrier, harm-reduction setting may facilitate incremental health behavior changes to reduce infection-related comorbid risk. There is a need to expand approaches to those with high risk and barriers.

Background: Coronavirus disease 2019 (COVID-19) remains an epidemic worldwide, and long COVID is a major social concern. Therapeutic options for relieving symptoms of COVID-19 pneumonia are limited. Clarithromycin (CAM), a macrolide antimicrobial, also functions as an immunomodulator.

Objectives: To assess the efficacy of CAM in improving clinical symptoms and attenuating inflammation in patients with mild COVID-19, with the aim of preventing progression to severe disease.

Design: An exploratory, multicenter, randomized-controlled, open-label trial.

Methods: This trial enrolled patients with mild COVID-19 pneumonia without oxygen supplementation from May 2021 through February 2022 in eight hospitals in Japan. Patients were randomly assigned in a 1:1:1 ratio to groups A (CAM 800 mg/day, 7 days), B (CAM 400 mg/day, 7 days), or C (standard treatment). The primary endpoint was the number of days required for 50% improvement in seven symptoms (fatigue, headache, cough, shortness of breath, taste/smell disturbance, and general unwellness) based on severity scores. Secondary endpoints included inflammatory cytokines, viral load, immunoglobulins, and pneumonia infiltrations.

Results: A total of 56 patients were enrolled and randomized. The primary endpoint did not differ significantly between groups (A: 5.0 days, B: 4.0 days, C: 4.0 days), though the seven symptoms tended to disappear earlier in group A than group C (p = 0.08), and fatigue significantly decreased in group A (p = 0.005). Serum inflammatory cytokines, tumor necrosis factor (TNF)-α, granulocyte colony stimulating factor (G-CSF), interleukin (IL)-7, IL-15, and proliferation factors, transforming growth factor (TGF)-α, fibroblast growth factor (FGF)-2, and fms-like tyrosine kinase 3 ligand (Flt3-L), significantly decreased in group A. IL-8 and IFN-γ in nasal drip significantly decreased in both group A and B. Serious adverse events did not increase in CAM groups, though mild gastrointestinal and liver events occurred in group A.

Conclusion: CAM is safe and potentially useful for improving partial COVID-related symptoms and exerting immunomodulation during COVID-19 pneumonia.

Trial registration: Japan Registry of Clinical Trials (jRCT; registration number: jRCTs071210011; https://jrct.mhlw.go.jp/latest-detail/jRCTs071210011) on April 13, 2021.

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.