Therapeutic Advances in Infectious Disease最新文献

Background: Immunosuppressive treatment can attenuate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune responses. Moreover, SARS-CoV-2 has neuroinvasive potential and may induce a persistent pro-inflammatory milieu following infection.

Objectives: To investigate if diminished post-vaccine humoral responses can be overcome with additional vaccine doses and/or breakthrough COVID-19 infections, and if COVID-19 infection can lead to a pro-inflammatory state with neuroaxonal/neuroglial injury in the intermediate-term in patients with central nervous system (CNS) neuroimmunological diseases.

Design: A prospective observational study conducted at National Neuroscience Institute, Singapore.

Methods: Serum levels of SARS-CoV-2 neutralising antibodies (NAbs) were measured in patients with CNS neuroimmunological diseases following their fourth SARS-CoV-2 mRNA vaccine (V4), or after breakthrough COVID-19 infection following three prior SARS-CoV-2 mRNA vaccinations, or both. Serum levels of pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor (TNF) were evaluated post-COVID-19 infection and post-V4, compared to baseline within individuals. Serum neurofilament-light chain (NfL) and glial fibrillary acidic protein (GFAP), biomarkers of neuroaxonal and astroglial injury, respectively, were measured at baseline and post-COVID-19 infection within patients with relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD).

Results: Sixty-one patients with various CNS neuroimmunological diseases were recruited, including 34 with MS and 19 with NMOSD. All had received at least three doses of the SARS-CoV-2 mRNA vaccine. Patients on anti-CD20/sphingosine-1-phosphate-receptor modulators (S1PRM) showed significantly reduced NAbs levels in both post-V4 and post-COVID-19 infection scenarios, compared to patients on other immunotherapies. No significant differences between baseline and post-COVID-19 infection concentrations of IL-6 and TNF were observed. Within RRMS and NMOSD patients, NfL and GFAP levels remained similar between baseline and post-COVID-19 infection.

Conclusion: Anti-CD20/S1PRM treatments are associated with persistently diminished humoral responses post-V4/infection. Patients with CNS neuroimmunological diseases do not show biomarker evidence of intermediate-term pro-inflammatory states and neural injury after COVID-19 infection.

Background: Fascioliasis, caused by Fasciola hepatica and F. gigantica, is a neglected tropical disease that has significant medical and veterinary importance. This foodborne zoonotic trematodiases primarily affects poor rural populations in tropical and subtropical areas, where prevalence can be as high as 21%.

Objective: This study aims to characterize the clinical features, laboratory findings, and outcomes of fascioliasis in a real-world cohort.

Design: Retrospective study.

Methods: Patients ⩾ 18 years old diagnosed with fascioliasis were identified from TriNetX, a global federated research network, on October 26, 2024. We used the International Classification of Diseases results to define fascioliasis (ICD-10 code B66.3) for the period 2021-2024. These data include demographics, diagnoses, comorbidities, procedures, clinical laboratory results, and medications. All variables except outcomes were not time-bound to the diagnosis date.

Results: In a cohort of 174 predominantly middle-aged, female, and Caucasian patients, we found high rates of essential hypertension, neoplasms, heart disease, liver disease, and sleep disorders. Key symptoms included upper abdominal pain, skin complaints, dyspnea, and malaise/fatigue. Some outcomes were hepatomegaly, cholelithiasis, and cholangitis in 10% of patients, with hepatic cirrhosis being rare. Among hospitalized patients within 3 months of diagnosis, 63% experienced abdominal pain. Of the 13 patients who developed cholangitis or cholelithiasis, most were men, had abdominal pain, nausea/vomiting, dysphagia, and ascites with a history of liver or intrahepatic bile neoplasia. A total of 90-day mortality was low (less than 6%). Triclabendazole was reported in only 6% of these patients.

Conclusion: In a large real-world case series of fascioliasis, we found a high frequency of comorbidities and typical gastrointestinal symptoms. The low use of triclabendazole may be due to limited access to the product in certain countries or its omission from the database if prescribed in the outpatient setting. Mortality was very low, but biliary and liver complications warrant characterization through additional prospective clinical studies.

Background: Tumor necrosis factor-alpha (TNF-α) is implicated in the pathogenesis of autoimmune conditions and sepsis. Although anti-TNF-α therapies have demonstrated clinical efficacy in rheumatoid arthritis (RA), there is no established evidence for benefit in patients with sepsis.

Objectives: We sought to quantify circulating TNF-α in patients with RA and compare results to TNF-α levels in sepsis.

Design: We performed a systematic review and meta-analysis of circulating TNF-α in patients with RA. We searched Cochrane Library, Google Scholar, Ovid Embase, Ovid MEDLINE, Scopus, and Web of Science Core Collection databases from inception until May 30, 2023. We included randomized controlled studies and observational reports containing more than ten subjects that reported mean serum or plasma TNF-α levels. We used the Newcastle-Ottawa Scale to assess methodological quality of studies.

Data sources and methods: Summary data were extracted and analyzed using a random-effects model to estimate the pooled mean circulating TNF-α. Circulating TNF-α in RA was compared to TNF-α levels reported in our systematic review and meta-analysis characterizing cytokine levels in sepsis.

Results: We identified and screened 8764 studies, and 104 studies satisfied the inclusion criteria (5399 total participants, including 4419 females). Pooled estimated mean RA TNF-α was 23.1 pg/mL (95% CI 17.8-30.1) in the random-effects model. There was significantly lower TNF-α in RA patients using disease-modifying antirheumatic drugs (DMARDs, p = 0.04) and patients using corticosteroids (p = 0.01). After adjustment for age and sex, there was no significant difference between TNF-α in RA compared to sepsis.

Conclusion: No significant difference between adjusted TNF-α levels in patients with RA versus sepsis was determined. Since TNF-α antagonists show benefit in RA but not sepsis despite comparable circulating concentrations, we conclude TNF-α does not contribute to sepsis pathogenesis. TNF-α concentration may be slightly higher due to study heterogeneity.

Trial registration: This investigation was registered in PROSPERO (CRD42023425361).

A 79-year-old female diagnosed with myelodysplastic syndrome (MDS) and germline GATA2 mutation, on compassionate cobimetinib, was admitted with subacute cough and dyspnea. Chest imaging demonstrated a new, large, left hilar mass and consolidation with scattered diffuse mediastinal, supraclavicular, and hilar lymphadenopathy. A core biopsy of the right supraclavicular lymph node was performed. Acid-fast bacilli (AFB) cultures from both the lymph node and blood were positive, while all fungal cultures were negative. Two distinct AFB colonies were observed on solid media and identified as Mycobacterium avium complex and Mycobacterium kansasii. Disseminated non-tuberculous mycobacterial infections involving two distinct species are rare, pose treatment challenges, and may correlate with cobimetinib administration for MDS, as well as GATA2 germline mutations.

Chikungunya virus (CHIKV) has emerged as a serious candidate for "Disease X"-the name for an unknown agent that could cause a global pandemic. This paper searches for the unique traits of CHIKV that match that designation. Critical mutations like E1-A226V and E2 L210Q have driven CHIKV's rapid adaptability and its transmission from Aedes mosquitoes to over 110 countries around the world. Public health impact is amped because the virus can cause debilitating diseases including chronic arthritis and severe neonatal complications. Populations remain vulnerable despite a recently approved vaccine, as there is little distribution of it and no treatments for the virus. By underscoring urbanization, climate change, and global travel as ecologic and genetic factors that enable the emergence and persistence of CHIKV, this paper emphasizes that these critical enablers of CHIKV need to be addressed both in the context of host range and transmission potential. However, phylogenetic studies and surveillance data for its capacity to sustain transmission cycles show how important it is to be included in improved global health strategies. Improved early detection, improved vector control, equitable vaccine distribution, and greater international collaboration are critical to reduce the pandemic potential of CHIKV. This paper aims to explore the genetic adaptations of CHIKV that have driven its increased transmission and expanded geographic spread. It examines how key mutations enable the virus to adapt to different mosquito vectors, contributing to its pandemic potential. The paper also assesses the epidemiological and environmental factors influencing CHIKV's emergence and persistence, alongside the public health challenges posed by limited vaccine availability and treatment options. Finally, it highlights prevention strategies and the importance of global preparedness to reduce the risk of widespread outbreaks.

Background: Group B Streptococcus (GBS) infection among pregnant women is a major risk factor for a significant proportion of early-onset disease and late-onset disease in infants worldwide; however, data on the epidemiological features of GBS in Vietnam are very limited.

Objectives: To determine the prevalence, potential risk factors, and serotype distribution of GBS isolates isolated from rectovaginal specimens of Vietnamese pregnant women.

Design: Cross-sectional study.

Methods: A cross-sectional study was conducted at three hospitals in Hanoi City, Vietnam, from October 2021 to May 2022. Combined rectovaginal swabs were collected from pregnant women at 35-37 weeks of gestation. GBS was isolated from swabs using selective enrichment in Todd-Hewitt broth and cultured on Columbia agar plates with 5% sheep blood, and Chromogenic Strepto B. All isolates were confirmed through the Gram staining, the CAMP test, and specific Polymerase Chain Reaction (PCR). GBS serotyping was performed by using the multiplex PCR assays. Risk factors for GBS carriage were analyzed using univariate and multivariate logistic regression tools.

Results: The prevalence of rectovaginal GBS carriage was 19.52% of 876 participants. Multivariate analysis identified two independent risk factors associated with GBS colonization: a high level of education and yellow vaginal discharge. Among these isolates, serotype III (n = 40, 23.39%) was the most frequently found, followed by serotypes V (n = 37, 21.64%), VI (n = 21, 12.28%), Ia (n = 18, 10.53%), Ib (n = 17, 9.95%), II (n = 8, 8.77%), and VII (n = 1, 0.58%), respectively. Capsular types IV, VIII, and IX were not detected. No statistically significant correlation was found between GBS infection and the distribution of the identified serotypes.

Conclusion: The GBS colonization rate in pregnant women was consistent with findings from other studies worldwide. Higher educational attainment and the presence of yellow vaginal discharge were independently associated with an increased risk of GBS colonization. The predominance of GBS serotypes III, V, and VI was a notable feature among the strains isolated from pregnant women in Vietnam.

Background: Bloodstream infections (BSI) caused by carbapenemase-producing Enterobacterales (CPE) represent a significant threat to patients with acute leukemia due to their high mortality. Ceftazidime-avibactam (CAZ-AVI) has emerged as a therapeutic alternative against these infections; however, its efficacy in immunocompromised patients remains unclear.

Objective: To determine the impact of ceftazidime-avibactam on mortality due to BSI caused by CPE in patients with acute leukemia.

Design: A retrospective cohort study was conducted at the Hospital Nacional Edgardo Rebagliati Martins in Lima, Peru.

Methods: We included patients diagnosed with acute leukemia who developed BSI due to CPE during their hospital stays. Mortality was assessed for up to 30 days after BSI onset.

Results: We evaluated 41 patients with a median age of 51 years; 56.1% had acute myeloid leukemia and 43.9% had acute lymphoblastic leukemia. Mortality at 30 days occurred in 60.9% of patients. The most frequent type of chemotherapy administered was induction (51.2%). Empiric antibiotic therapy with meropenem was administered to 97.6% of the patients, and ceftazidime-avibactam was prescribed as a targeted therapy to 48.8%. In the multivariate Cox regression model, the prescription of ceftazidime-avibactam reduced the risk of death (adjusted hazard ratio, 0.29; 95% CI: 0.09-0.92; p = 0.012) compared with those who received other antibiotic therapies, such as colistin.

Conclusion: In patients with acute leukemia who developed bloodstream infections due to CPE during hospitalization, the prescription of ceftazidime-avibactam reduced 30-day mortality risk.

Here we describe a composite vignette of a patient who developed necrotic wounds and systemic infection after reported exposure to xylazine, a veterinary anesthetic found as an adulterant in the unregulated drug supply. While exposure to xylazine-containing compounds via the use of fentanyl is not a new phenomenon, xylazine's prevalence in overdose deaths has escalated, and its geographic distribution has expanded to include rural areas such as Maine. We use this composite vignette to highlight: (1) the growing number of overdoses in Maine where xylazine was found in combination with fentanyl, (2) the potential severe, infection-related complications of xylazine exposure, and (3) describe novel harm reduction strategies that utilize community- and laboratory-based drug checking technology.

Background: Echinocandins are recommended as an initial treatment for invasive candidiasis. Although safety and efficacy profiles of both anidulafungin and caspofungin are well established, direct head-to-head comparisons have not been reported before.

Objective: Compare efficacy and safety of anidulafungin versus caspofungin among patients with invasive candidiasis.

Design: Retrospective observational study.

Methods: Adult patients with invasive candidiasis who were treated with either anidulafungin or caspofungin for ⩾5 days were retrospectively reviewed over a period of 6 years. The primary endpoint was global response, defined as clinical and microbiological success at the end of treatment duration.

Results: A total of 223 patients who received either anidulafungin (n = 176) or caspofungin (n = 47) were initially included. Propensity score matching (based on age, malignancy, level of care, presence of candidemia, and other factors) was performed to improve comparability of the two groups. As a result, 32 patients in the caspofungin arm and 79 patients in the anidulafungin arm were included in the final analysis. Around three-quarters of the cohort had candidemia, and the most common isolated Candida species were C. albicans and C. glabrata. Response rates were comparable between both groups, with the primary outcome of global response showing no significant difference (56.3% for the caspofungin group vs 63.3% for anidulafungin, p = 0.490). Similarly, no differences between the two groups were observed in terms of 90-day all-cause mortality (p = 0.672) or any other secondary endpoints.

Conclusion: Our data suggest that anidulafungin and caspofungin have comparable global response among patients with invasive candidiasis. Additionally, both studied echinocandins showed no significant difference in 90-day all-cause mortality. However, due to the limited sample size, larger studies are needed to confirm these results.