International Journal of Infectious Diseases最新文献

We describe five cases of neurological scrub typhus that highlight two critical, underrecognized aspects of this disease. First, cerebrospinal fluid metagenomic next-generation sequencing (CSF mNGS) accurately identified Orientia tsutsugamushi in all three patients tested, while the conventional Weil-Felix test was negative in every case, establishing mNGS as a pivotal diagnostic tool. Second, we uncovered a high prevalence of thyroid dysfunction, with nonthyroidal illness syndrome (NTIS) present in three of four patients tested, a novel systemic complication linked to severe inflammatory stress. Additional notable findings included frequent hypokalemia, at times severe enough to mimic periodic paralysis, and urban acquisition in two cases, suggesting an expanding epidemiological footprint. All patients improved on doxycycline-based regimens. This series underscores the diagnostic superiority of CSF mNGS and reveals NTIS as a key endocrine manifestation in neurological scrub typhus, urging greater clinical vigilance.

Delayed hemolytic anemia (DHA) is a rare, severe complication of artemisinin-based therapies. We report a case of DHA following an extended course of oral artemether-lumefantrine (AL) in a 50-year-old male with follicular lymphoma treated with rituximab 10 months ago and severe Plasmodium falciparum malaria (parasitemia >10%). The patient developed significant hemolysis eight days post-treatment. Laboratory findings were consistent with DHA, including reticulocytosis and, notably, a positive direct Coombs test. The patient's underlying immunosuppression, pre-existing hepatosplenomegaly, and the prolonged AL regimen likely contributed to the severity. The positive Coombs test suggests a possible immune-mediated component, differentiating it from the typical non-immune mechanism. This case highlights that DHA can occur after oral AL, not just intravenous artesunate, and underscores the critical need for vigilant post-treatment monitoring (2-4 weeks) of hemoglobin in high-risk patients with comorbidities or high parasite burdens.

Objective: This study aimed to present the first documented case of fatal granulomatous amoebic encephalitis (GAE) caused by Balamuthia mandrillaris and Epstein-Barr virus (EBV) co-infection, to evaluate the diagnostic performance of MetaCAP targeted sequencing against mNGS, and to provide a national epidemiological profile of this disease in China.

Methods: A 55-year-old male presenting with fever and altered consciousness was comprehensively evaluated. Parallel testing of blood, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid (BALF) was conducted using both MetaCAP and mNGS technologies. The diagnostic sensitivity of both platforms was directly compared. Additionally, a retrospective analysis of 41 confirmed cases in China was performed to delineate the epidemiological and clinical characteristics.

Results: MetaCAP sequencing confirmed the presence of B. mandrillaris and EBV in CSF and blood, with the amoeba also detected in BALF. It demonstrated superior sensitivity, identifying B. mandrillaris at significantly higher levels in blood (1,064 vs. 7 RPM) and in BALF (7 RPM vs. undetected by mNGS). The epidemiological analysis revealed a unique adult-predominant pattern and geographic clustering among Chinese cases.

Conclusion: This study reports a novel viral-amoebic co-infective GAE and validates MetaCAP as a highly sensitive diagnostic tool, outperforming mNGS for detecting fastidious pathogens. The integrated national cohort data provide critical insights into the disease's profile in China, suggesting that MetaCAP can significantly improve diagnostic yield and guide earlier intervention.

Background: The H9N2 subtype of avian influenza virus (AIV) is widely distributed in poultry and occasionally infects humans, posing a potential public health risk. While most infections are mild, severe disease can occur in vulnerable individuals.

Methods: We describe a case of H9N2 infection in a lung transplant recipient who developed severe pneumonia and respiratory failure. Viral isolation and full-genome sequencing were conducted, followed by phylogenetic, evolutionary, and structural analyses to characterize the virus. The isolate was also compared with environmental samples monitored in our surveillance program.

Results: Genomic sequencing identified an H9N2 strain carrying two hemagglutinin (HA) substitutions, Y264H and T195S, a combination not commonly reported in circulating avian strains but recently detected in our environmental surveillance samples. Phylogenetic analysis indicated that the PB1 and PB2 genes of the H9N2 virus were closely related to those of avian H3N8 viruses. Structural modeling suggested that the HA substitutions may influence receptor-binding stability, though their impact on viral adaptation requires further investigation.

Conclusions: This case illustrates that H9N2 infection can cause severe disease in immunocompromised patients and provides genomic and structural insights into a reassortant H9N2 strain detected in humans. The close similarity of the HA gene sequence between this strain and environmental isolates highlights the importance of continued surveillance of avian influenza viruses.

Objectives: This study aimed to characterise the real-world use of cefiderocol in treating Gram-negative bacterial infections (GNBIs) across Italian hospitals.

Methods: We conducted a multicentre retrospective study enrolling patients with GNBI treated with cefiderocol from January 2021 to February 2023. Statistical analyses included Kaplan-Meier survival estimates and multivariable Cox regression. A propensity score analysis with inverse probability of treatment weighting (IPTW) was also performed to compare the treatment effect of combination therapy versus monotherapy adjusting for imbalances between treatment groups.

Results: A total of 239 patients were included. Bloodstream infections were the most common (49.8%), followed by ventilator-associated and hospital-acquired pneumonia. Acinetobacter baumannii was the most common isolate (64.8%), followed by Klebsiella spp. (23%), Pseudomonas aeruginosa (17.6%), and Stenotrophomonas maltophilia (8.8%). Overall 30-day survival was 71% (95% CI: 65-76), with no significant differences between monotherapy and combination therapy. Independent predictors of higher 30-day mortality were: having received 2 or 3 previous lines of antibiotic therapy (aHR: 4.26, 95% CI: 1.00-18.20; aHR: 7.33, 95% CI: 1.53-35.05), SARS-CoV-2 coinfection (aHR: 4.19, 95% CI: 2.04-8.59), and isolation of NDM-producing Klebsiella spp. (aHR: 6.22, 95% CI: 2.09-18.50).

Conclusions: Real-world experience supports the role of cefiderocol as a valuable option for GNBIs, with no clinical advantage of combination therapy over monotherapy. Notably, NDM-producing infections and use of cefiderocol as salvage therapy are associated with poor outcomes, highlighting the need for optimised treatment strategies.

Objectives: Human papillomavirus (HPV) is the main cause of anal carcinoma, whose incidence is rising globally, especially among men who have sex with men (MSM). This study estimated anal HPV prevalence, investigated genotype distribution, and identified associated factors among MSM in Brazil.

Methods: The SMESH study, a multicenter cross-sectional survey (2019-2023), analyzed 1,375 MSM (≥18 years) from nine Brazilian capitals using respondent-driven sampling. Participants completed questionnaires and provided self-collected anal samples for HPV detection. Weighted analyses were applied.

Results: Anal HPV prevalence was 72.4% (95%CI: 67.6-77.3), with 62.3% (95%CI: 56.9-67.8) harboring high-risk HPV and 36.4% (95%CI: 30.9-41.8) infected with quadrivalent vaccine types. MSM living with HIV (18.1%), compared to HIV-negative MSM, had higher overall (87.7% vs. 69.6%, p<0.001) and high-risk HPV prevalence (78.9 vs. 58.9%, p<0.001). Vaccinated MSM presented lower rates of quadrivalent vaccine types, particularly HPV 16. Younger age (25-34 years), frequent group sex, and regular drug use during sex were associated with HPV infection.

Conclusion: The high prevalence of anal HPV among Brazilian MSM highlights the importance of expanding HPV vaccination coverage, particularly for HIV-positive MSM, and reinforces the need for gender-neutral vaccination of all girls and boys before sexual debut.

Purpose: Persistent inflammation in people with HIV (PWH) on antiretroviral therapy (ART) may drive comorbidities and disease progression. Since CCR5 signalling regulates viral entry and immune activation, maraviroc (MVC) may contribute to attenuate inflammation, though previous findings have been inconsistent. This study evaluated a broad panel of markers to assess the long-term immunomodulatory effects of MVC when added at ART initiation.

Methods: We conducted a longitudinal observational study including PWH starting ART with MVC (MVC group, n=14) or without MVC (Non-MVC group, n=28), matched by sex, age and ART regimen. Plasma markers were quantified by Proximity Extension Assay (PEA) and ELISA methods. Mixed multivariate models analyzed marker dynamics, and functional analyses identified enriched biological pathways.

Results: PEA showed significant variation in up to fifteen inflammatory markers (e.g., CXCL9, CXCL10, IFN-γ, CCL19) among both groups over ART initiation. Moreover, IL-18 declined significantly only in the MVC group (17.6% per year by PEA, and 35.5% by ELISA, p-value<0.05). Functional Enrichment analyses showed a stronger downregulation of inflammation-related pathways, particularly the chemokine signalling, in the MVC group (q-value<0.05).

Conclusion: Our results suggest that MVC intensification at ART initiation might contribute to reducing IL-18 levels and inflammation-driven immune pathways, providing insights for strategies to mitigate persistent inflammation in PWH.

Background: To assess the clinical utility of neutrophil extracellular trap (NET)-related biomarkers as potential diagnostic and prognostic indicators for sepsis in older patients.

Methods: 39 sepsis older patients (age > 60 years) diagnosed and 28 older patients suffering from infections between August 2024 and April 2025 were enrolled in this study. Peripheral blood plasma was collected to measure NET-related biomarkers, including double-stranded DNA (dsDNA), citrullinated histone H3 (citH3), myeloperoxidase-DNA (MPO-DNA) complex, and nucleosomes. Clinical and laboratory data were extracted from electronic medical records.

Results: Patients with sepsis exhibited significantly higher levels of dsDNA, citH3, MPO-DNA, and nucleosomes compared to controls. Non-surviving patients with sepsis had notably elevated dsDNA levels compared to survivors. Correlation analysis revealed a strong positive association between NET-related biomarkers, neutrophil counts, and Sequential Organ Failure Assessment scores. Receiver operating characteristic (ROC) curve analysis indicated that dsDNA was a reliable diagnostic marker for sepsis (area under the curve [AUC] = 0.81, 95% confidence interval [CI], 0.71 - 0.92, P < 0.001) and mortality prediction (AUC = 0.86, 95% CI, 0.75 - 0.97, P < 0.001).

Conclusion: NET-related biomarkers, particularly dsDNA and MPO-DNA, are significantly elevated in sepsis older patients and are independently associated with an increased risk of sepsis.

Objective: In a national program of integration of rapid HIV diagnosis with linkage to antiretroviral therapy (ART), this multicenter, single-arm trial evaluated the efficacy and feasibility of same-day initiation of coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in a high-income setting.

Methods: Adults aged ≥20 years and without prior ART exposure were enrolled and started BIC/FTC/TAF within 24 hours of confirmed HIV diagnosis. Primary endpoints included engagement in care and plasma HIV RNA load (PVL)<50 copies/mL at Week 48. Secondary endpoints included PVL<200 copies/mL at Weeks 1, 4, and 48, and drug-related adverse events.

Results: Among 225 enrolled participants (94.2% being gay, bisexual, and other men who have sex with men), 34.9% had CD4<200 cells/μL and 63.2% PVL>100,000 copies/mL. At Week 48, 96.0% of the participants retained in care and 76.0% and 81.0% achieved PVL<50 copies/mL in intention-to-treat and per-protocol analysis, respectively; and 96.5% achieved PVL<200 copies/mL in per-protocol analysis. A high baseline PVL and low CD4 count were associated with lower odds of achieving PVL <50 copies/mL. No serious adverse events were attributable to BIC/FTC/TAF.

Conclusion: Initiation of BIC/FTC/TAF on the same day of HIV diagnosis is feasible, safe, and efficacious in achieving virologic suppression and engagement in care.

Clinical trial registration: NCT04712058.