International Journal of Infectious Diseases最新文献

Background: Ticks transmit multiple pathogens, including B. burgdorferi, the agent of Lyme disease, and tick-borne encephalitis virus (TBEV), which can cause severe neurological disease and death despite frequent pauci- or asymptomatic infections. The Limousin region is considered at risk for TBEV because of dense tick (Ixodes) populations, although no clinical TBE cases have yet been reported there.

Methods: This study assessed TBEV seroprevalence in 880 patients tested for Lyme disease at Limoges University Hospital between January 2020 and January 2023. Presence of neutralizing antibodies was confirmed with a microneutralization assay. Seropositive TBEV cases were asked about epidemiological data.

Results: Anti-TBEV IgG antibodies were detected in 2.61% (23/880) of sera. Three cases had high titers of neutralizing antibodies. For two of them, travel history or missing epidemiological data limited interpretation, but one case from Corrèze department, exhibited an exposure history and lab testing data that strongly support TBEV infection.

Conclusion: For the first time, this study enabled the identification of several factors supporting the hypothesis of the circulation of TBEV in the Limousin region, France, confirming the spread of TBEV from the east to the west of the country and the need for increasing TBEV surveillance.

Objectives: Oxazolidinones are antibiotics of remarkable clinical importance, and resistance to these drugs is a matter of concern. This study investigated the presence of optrA, poxtA and cfr transferable oxazolidinone resistance determinants among enterococci and other non-obligate anaerobic fecal Gram-positives from healthy children living in a rural area of Bolivia.

Methods: Fecal samples were collected in transport medium and screened for isolates growing on Colistin-Nalidixic Acid blood agar containing florfenicol 16 mg/L. Isolates were identified by MALDI-ToF mass spectrometry and subjected to Real-time PCR to detect the presence of optrA, poxtA and cfr genes. Antimicrobial susceptibility to florfenicol, vancomycin and linezolid was tested by reference broth microdilution.

Results: Overall, 184/420 (43.8%) faecal samples yielded growth on the selective medium and 241 isolates of 13 different species of Lactobacillales (mostly Enterococcus spp. but also lactococci and Vagococcus teuberi) were obtained for further investigation. Most of them carried either optrA (182/241) or poxtA (43/241) or a combination thereof (7/241). cfr was detected in 5/241 isolates, always in combination with the other genes.

Conclusions: Present findings report the highest prevalence of faecal carriage of optrA- and poxtA-positive commensals so far observed in healthy subjects, raising concerns about the potential clinical and epidemiological implications.

Objectives: This prospective study aimed to (i) determine the intrarenal prevalence of hepatitis B virus (HBV) DNA in HBV surface antigen (HBsAg) negative patients with renal cell carcinoma (RCC), and (ii) characterize its molecular forms, including cccDNA and integrated sequences.

Methods: Renal tissues from 83 consecutive HBsAg-negative patients who underwent nephrectomy for RCC (n=54) or for non-malignant disease (control group, CG, n=29) were tested by highly sensitive PCR for total HBV DNA, cccDNA, and viral RNA, and subjected to high-throughput HBV DNA integration sequencing. Among RCC cases, 36/54 had clear cell renal cell carcinoma (ccRCC), and 18/54 had papillary or chromophobe RCC.

Results: HBV DNA was detected in 35.2% (19/54) of RCC cases versus 3.4% (1/29) of controls (P=0.001). Among RCC subtypes, HBV DNA prevalence was 25% (9/36) in ccRCC versus 55.6% (10/18) in non-ccRCC (papillary or chromophobe) (P=0.03). Both cccDNA and integrated HBV sequences were present in RCC tissues harboring viral DNA.

Conclusions: ntrarenal presence of HBV DNA is a frequently occurring event strongly associated with RCC, suggesting a potential direct role of HBV in renal carcinogenesis.

Background: Anti-interferon-γ autoantibody syndrome (AIGAs) is a primary immunodeficiency disorder characterized by neutralizing autoantibodies blocking IFN-γ signaling, predisposing patients to severe opportunistic infections. No definitive treatment protocol exists, and conventional therapies carry infection risks. Hemoadsorption (HA) is effective for autoimmune diseases but has not been specifically investigated for AIGAs.

Case presentation: A 65-year-old Chinese female was admitted with 10-month painless disseminated lymphadenopathy. 18F-FDG PET/CT showed multiple hypermetabolic lymph nodes, and ultrasound-guided biopsy revealed necrotizing granulomatous inflammation. Metagenomic next-generation sequencing (mNGS) identified Mycobacterium abscessus, and ELISA confirmed high AIGA levels (88.05% at 1:3200 dilution). She received anti-nontuberculous mycobacteria (NTM) therapy (clarithromycin, minocycline, contezolid) combined with one HA session using a cytokine adsorption column. Post-treatment, AIGA levels normalized to 0% at 24 weeks and remained stable. 72-week follow-up showed resolved lymphadenopathy and reduced lymph node size/metabolic activity on PET/CT.

Conclusion: This is the first report of single-session HA for AIGAs complicated by disseminated Mycobacterium abscessus infection. HA effectively reduced AIGA levels, controlled infection, and avoided global immunosuppression, providing a promising adjunctive therapy for AIGAs patients with severe disseminated infections.

Objectives: Post-acute sequelae of COVID-19 (PASC) are more common in unvaccinated or immunocompromised individuals. In Singapore, neutralising monoclonal antibodies (mAbs) were offered early in the disease course to such high-risk patients. We evaluated the impact of early mAb use on the risk of post-acute multi-system complications and symptoms.

Methods: Using national COVID-19 registries and healthcare claims data, we conducted a retrospective cohort study including all Singaporeans who were unvaccinated, partially vaccinated, or immunocompromised at the time of SARS-CoV-2 infection between July 2021 and December 2022. Individuals were stratified by receipt of mAbs. Overlap weighting was applied to balance baseline characteristics. Competing risks regression was used to compare outcomes from 31 to 300 days post-infection, adjusted for demographics, vaccination status, and comorbidities.

Results: Of 19,689 eligible hospitalised individuals, 6.9% received early mAb therapy. While mAb treatment had no significant impact on overall post-acute sequelae (aHR for any sequelae:1.26[0.98-1.63]), we observed an increased risk of autoimmune diseases (aHR=2.20[1.22-3.97]), particularly systemic lupus erythematosus and rheumatoid arthritis). There was also elevated risk of deep venous thrombosis (aHR=1.83[1.03-3.22]), but this was no longer significant after adjusting for prior healthcare utilisation.

Conclusions: Early mAb therapy did not significantly alter overall PASC risk but was associated with increased autoimmune complications. These findings may highlight the need for long-term safety monitoring in future mAb trials for SARS-CoV-2.

Introduction: To identify plasma cytokine biomarkers predictive of immunologic non-response in people living with HIV (PLHIV) undergoing long-term antiretroviral therapy (ART).

Methods: PLHIV on ART with sustained HIV RNA <50 copies/mL were enrolled at Guangzhou Eighth People's Hospital and followed for 4 years. Participants were classified as immunological responders (IR) or immunological non-responders (INR) after 4 years of ART, and stratified by baseline CD4+ T cell count (≤200 vs. >200 cells/μL). Plasma concentrations of 14 cytokines were measured at baseline and 2 years using a multiplex bead-based immunoassay. ROC analyses were used to assess predictive value.

Results: Among 136 participants, 71 were IR and 65 were INR. Lower baseline CD4+ T cell counts correlated with elevated cytokine levels, which declined over time irrespective of immune outcome. Baseline IP-10, MCP-2, and Granzyme B levels correlated positively with 4-year CD4+ T cell recovery. IP-10 was significantly higher in IR than INR among PLHIV with baseline CD4+ T cell count ≤ 200 cells/μL, whereas MCP-1 was elevated in INR in the >200 cells/μL subgroup. Combining IP-10 or MCP-1 with baseline CD4+ T cell counts improved INR prediction compared to CD4+ T cell count alone.

Conclusion: IP-10 and MCP-1 demonstrated strong predictive value for INR in PLHIV with low and high baseline CD4+ T cell counts, respectively. These cytokines may serve as valuable biomarkers for guiding individualized immune monitoring in ART-treated PLHIV.

Objectives: Acute sore throat is a common reason for antibiotic prescribing. Physicians often experience uncertainty in managing these and guideline adherence remains suboptimal. There is a need for antibiotic stewardship programmes (ASPs) for this setting. The objective was to evaluate if a multifaceted ASP could improve long-term guideline adherence.

Methods: This was a randomised controlled trial in primary care centres in Sweden. Centres were randomly assigned to intervention or control group. The six months intervention comprised of multiple meetings with practitioners to reflect on the current sore throat guideline, didactic patient case discussions, local quality improvement initiatives, and repeated individual audits and feedback using laboratory and prescribing data for their patients. The primary outcome was the change in the proportion of antibiotic-prescribed cases with a positive rapid antigen detection test for Streptococcus pyogenes.

Results: At baseline, approximately two thirds of pharyngotonsillitis cases were managed in accordance with the Swedish national guideline. No significant change in guideline adherence was observed in either group at 6, 12, or 18 months from baseline.

Conclusion: The addition of a six-month multifaceted ASP did not improve long-term guideline adherence for these patients. Alternative approaches need to be explored to support sustainable changes in prescribing behaviour.

Background: Pulmonary infections in tuberculosis (TB)-endemic settings are heterogeneous and commonly polymicrobial. Nanopore-targeted sequencing (NTS) enables detection of mycobacteria, bacteria, and fungi in a single targeted assay. However, performance across pathogen classes in TB-endemic cohorts remains limited.

Methods: We conducted a prospective study at a specialized TB hospital, enrolling adults with suspected pulmonary infections across five predefined diagnostic categories: pulmonary TB, nontuberculous mycobacterial pulmonary disease, bacterial, fungal, and polymicrobial infection. Respiratory specimens (n=312) from 305 patients were tested in parallel by conventional microbiological testing (CMT) and NTS. Blinded clinical diagnoses served as the reference standard.

Results: Among 283 paired cases, NTS identified the adjudicated pathogens in 263 cases, whereas culture identified them in 185 cases. NTS showed a sensitivity/specificity of 83.0%/99.4% for Mycobacterium tuberculosis, 89.8%/98.2% for nontuberculous mycobacteria, 92.9%/91.1% for fungi, and 97.4%/57.8% for bacteria. In 72 polymicrobial infections, NTS detected all adjudicated pathogens in 77.8% versus 62.5% for CMT, a non-significant difference (P=0.06). Overall, NTS provided a 12.2% incremental diagnostic yield.

Conclusions: NTS offers sensitive, single-assay detection of diverse pulmonary pathogens in TB-endemic settings. By streamlining workflows and improving detection of fastidious or co-infecting organisms, it may complement conventional methods. However, bacterial NTS findings in non-sterile respiratory specimens require clinical correlation.

Background: Using a prospective, community-recruited cohort with data on background symptom prevalence and repeated longitudinal symptom assessments, we estimated post-infection risks of long COVID symptoms compared with contemporaneous uninfected controls.

Methods: We analyzed the CHASING COVID Cohort, a U.S. longitudinal study with surveys and serology (March 2020-December 2023). Infection status (January 2021-December 2022) was determined from self-reported PCR/antigen results, serology, or CSTE probable criteria. We emulated 24 monthly target trials comparing individuals newly infected at time zero with those remaining uninfected. Outcomes were new-onset long-COVID symptoms not reported pre-infection, assessed overall and within three clusters (neurological, autonomic, exercise intolerance) at 4-8 and 9-12 months post-infection. Inverse probability of treatment and censoring weights adjusted for confounding and informative loss to follow-up.

Results: The analysis included 1,055 infected and 52,310 uninfected person-trials. At 4-8 months, the adjusted risk of any long-COVID symptom was 22.6% (95% CI, 20.5-24.8) among infected versus 11.3% (11.1-11.5) among uninfected (adjusted risk difference [aRD], 11.3% [9.2-13.5]; adjusted risk ratio [aRR], 2.01 [1.81-2.20]). At 9-12 months, risks were 19.2% (17.0-21.3) vs 12.4% (12.2-12.7) (aRD, 6.7% [4.6-8.9]; aRR, 1.54 [1.37-1.72]). Across all three clusters, infected participants had consistently higher risks at both intervals.

Conclusions: SARS-CoV-2 infection was associated with elevated risk of new-onset long-COVID symptoms persisting up to 12 months. Using a national community-recruited cohort, contemporaneous uninfected controls, and target-trial emulation clarifies the burden attributable to infection and supports ongoing surveillance and targeted prevention and care.

We report two cases of HIV-positive individuals virologically suppressed on antiretroviral treatment who developed nephrotic-range glomerular disease with massive proteinuria. Both were treated with tacrolimus to control proteinuria, achieving complete and sustained remission for over five years. Subsequently, they developed Kaposi sarcoma, raising concerns about prolonged use of calcineurin inhibitors in people living with HIV with glomerular diseases. This may impair oncogenic immune surveillance and promote reactivation of latent viruses such as human herpesvirus-8. These cases underscore the need for caution when using long-term immunosuppression in PLWH with glomerular disease, as treatment options remain limited. This clinical course has not been previously reported.