Journal of Infection最新文献

Immune checkpoint inhibitors designed to reinvigorate immune responses suppressed by cancer cells have revolutionized cancer therapy. Similarities in immune dysregulation between cancer and infectious diseases has prompted investigations into the role of immune checkpoints in infectious diseases, including the therapeutic potential of immune checkpoint blockade and drug repurposing. While most research has centered around viral infections, data for bacterial infections are emerging. This systematic review reports on the in vivo effect of immune checkpoint blockade on bacterial burden and selected immune responses in preclinical studies of bacterial infection, aiming to assess if there could be a rationale for using immunotherapy for bacterial infections. Of the 42 analyzed studies, immune checkpoint blockade reduced the bacterial burden in 60% of studies, had no effect in 28% and increased the bacterial burden in 12%. Findings suggest that the effect of immune checkpoint blockade on bacterial burden is context-dependent and in part relates to the pathogen. Further preclinical research is required to understand how the therapeutic effect of immune checkpoint blockade is mediated in different bacterial infections, and if immune checkpoint blockade can be used as an adjuvant to conventional infection management strategies.

Background: Half the global tuberculosis health burden is due to post-tuberculosis lung disease. Host-directed therapies have been proposed to reduce this burden. N-acetylcysteine (NAC) provides the conditionally essential amino acid cysteine required for synthesis of glutathione, an antioxidant thiol. We recently reported clinical outcomes of a trial of adjunctive NAC in patients with pulmonary tuberculosis, finding that NAC improved the secondary endpoint of recovery of lung function. Here we report the effects of NAC on biomarkers of oxidation, inflammation, and infection in that trial.

Methods: 140 adults with moderate or far-advanced pulmonary tuberculosis were randomly assigned to standard tuberculosis treatment with or without NAC 1200mg twice daily for months 1-4. Sputum and blood samples were obtained at specified intervals to measure total glutathione, MTB-induced cytokines, haemoglobin, whole blood mycobactericidal activity (WBA), and sputum MTB burden.

Results: NAC treatment rapidly increased total glutathione (P<.0001), but levels did not reach those of healthy volunteers (P<.001). NAC reduced MTB-induced TNF-α (P =.011) without affecting IL-10, and accelerated the recovery of hemoglobin in participants with low values on entry. NAC did not affect killing in ex vivo whole blood culture but did slow the clearance of MTB from sputum (P=0.003).

Conclusion: Adjunctive NAC showed antioxidant and anti-inflammatory effects consistent with the amelioration of immunopathology seen in preclinical models. Two biomarkers of antimicrobial activity showed discordant results; neither demonstrated the enhanced antimicrobial effects seen preclinically. The reduction of oxidative stress and inflammation by NAC may explain its effects on the recovery of lung function post-TB.

In solid organ transplant recipients (SOTRs), the oncogenic virus human herpesvirus-8 (HHV-8) also named Kaposi sarcoma herpesvirus (KSHV) causes four clinical diseases: Kaposi Sarcoma, Primary Effusion Lymphoma, Multicentric Castleman Disease (MCD), and KSHV inflammatory cytokine syndrome (KICS). This review outlines these clinical scenarios and discusses their management. Although HHV8-related disease in SOTR was first described more than three decades ago, there is a lack of data on treatment so much of the guidance is based on evidence in other immunodeficient patients, particularly people living with HIV. Whilst reduction of immunosuppression and switch from calcineurin inhibitors to mTOR inhibitors may be sufficient in early-stage post-transplant KS, systemic chemotherapy is necessary for advanced-stage KS and in KSHV-related lymphomas. For MCD and KICS, which usually follow primary HHV-8 infection, rituximab-based immunochemotherapy regimens are the cornerstone of treatment for these potentially lethal diseases. Although HHV-8 infection in SOTR is well recognized, it remains under-reported and greater awareness of the different clinical presentations of HHV-8 in this context is fundamental to improve outcomes.

Objective: To evaluate the long-term humoral immune response to Nipah virus (NiV) in a cohort of 25 survivors after 25 years of post-infection.

Methods: A total of 25 survivors of NiV infection from the 1998 outbreak were recruited for sample collection. The serum IgG antibody response to NiV antigens, specifically nucleocapsid (N), fusion glycoprotein (F) and attachment glycoprotein (G) was evaluated using ELISA. Additionally, the samples were tested for neutralizing antibodies and memory B cell responses.

Results: Detection rates of anti-NiV-F and anti-NiV-G were 56% and 60%, respectively, among the survivors at a 1:100 dilution, whereas only 20% were specifically reactive to rNiV-N. Notably, all samples that tested positive for NiV-F and NiV-G at this dilution also exhibited neutralizing antibodies, highlighting the specificity of these assays. Live virus neutralization assay showed that 72% of survivors had detectable neutralizing antibodies, with varying titers, indicating long-lasting immune memory. Furthermore, memory B cell responses specific to NiV-F and NiV-G were observed in six randomly selected survivors, suggesting the presence of enduring immunological memory.

Conclusions: These findings highlight the potential of NiV-F and NiV-G as reliable markers for NiV exposure and underscore the need for continuous surveillance and research. Such efforts are crucial for advancing vaccine development and improving preparedness for future NiV outbreaks.

Objectives: Pediatric tuberculosis (TB) diagnosis is complicated by challenges in obtaining invasive respiratory specimens that frequently contain few Mycobacterium tuberculosis (Mtb) bacilli. We report the diagnostic performance of an Mtb antigen-derived peptide (MAP-TB) assay and its ability to monitor TB treatment response.

Methods: Study cohorts enrolled children who presented with presumptive TB at two hospitals in South Africa from 2012 to 2017 (157 children aged <13 years) and at community-based clinics in the Dominican Republic from 2019 to 2023 (101 children aged <18 years). Children were evaluated for TB at enrollment and six months post-enrollment and assigned confirmed, unconfirmed, or unlikely TB diagnoses using the 2015 NIH diagnostic criteria for pediatric TB. MAP-TB assay performance was evaluated using serum collected at baseline and at regular intervals post-enrollment following STARD guidelines.

Results: MAP-TB sensitivity for confirmed and unconfirmed TB was comparable to culture and Xpert sensitivity for confirmed TB, but MAP-TB specificity revealed age-dependence, decreasing from 98·1% to 78·4%, when including children aged <1 year. MAP-TB values decreased by six months post-treatment initiation in children with symptom improvement.

Conclusions: Serum MAP-TB results can effectively diagnose pediatric TB, including unconfirmed and extrapulmonary TB missed by current methods, and correspond to effective treatment.