Journal of Infection最新文献

Objectives: We aimed to evaluate the effectiveness of TYPHIBEV®, which was introduced through a catch-up campaign and routine immunization in Nepal, in preventing blood culture-confirmed typhoid fever among children.

Methods: We conducted a test-negative, case-control study where typhoid test-positive cases were defined as vaccine-eligible pediatric patients who tested positive for Salmonella Typhi by blood culture at participating health facilities and test-negative controls were vaccine-eligible patients who tested negative for S. Typhi on blood cultures. We matched by age, location, date of blood culture, and surveillance site. We used conditional logistic regression to calculate odds ratios(OR), and vaccine effectiveness was calculated as 1-OR.

Results: Between October 1, 2022 and December 31, 2024, 40 typhoid cases and 113 matched, test-negative controls were enrolled. Both cases and controls were similar in sociodemographic characteristics and water, sanitation and hygiene-related living conditions. Among 39 cases and 108 controls with known vaccine status, 20 cases (51%) and 91 controls (84%) had received TCV. Vaccine effectiveness was 89% (95% CI: 65-97%) and was lower among children <5 years (72%, 95% CI: -203-97%) compared with those 5-15 years (98%, 95% CI: 80-100%). Vaccine effectiveness estimates did not significantly differ when restricted to participants with documented vaccination status.

Conclusions: The findings indicate that TYPHIBEV® was highly effective in preventing typhoid fever over a 30-month follow-up period following national introduction, with effectiveness estimates comparable to those observed for Typbar-TCV®.

Objective: This scoping review aims to evaluate the application of environmental DNA/RNA (eNA) technology in real-world studies on neglected tropical diseases (NTDs), assessing its methodology and detection effectiveness, and providing an evidence-based roadmap for optimizing eNA used to support progress toward the 2030 targets.

Background: As the NTDs roadmap reaches its midpoint, eNA technology has seen increasing adoption. This non-invasive approach enables qualitative/quantitative assessment of environmental transmission risks, complementing conventional detection methods.

Methods: We synthesized real-world field applications of eNA technology across NTDs through systematic searches in four English, and one Chinese database (2002-2024). A total of 71 studies met our inclusion criteria after screening.

Results: Despite heterogeneous transmission mechanisms among NTDs, we identified 6 standardized field applications for eNA studies, along with practical optimization strategies. A total of 3 pathways were concluded of how eNA technology can accelerate the NTDs elimination. For the performance, comparative analyses showed moderate concordance with conventional methods, while eNA demonstrated superior sensitivity in detection of pathogens and hosts. With the gap analysis, we demonstrated the advances of eNA applications in all NTDs.

Conclusions: This scoping review supports eNA technology as a promising tool for NTDs detection and surveillance. Through experience sharing and summarization, the eNA technology needs further optimization and standardization to enhance its disease surveillance capacity, thereby accelerating the achievement of NTDs roadmap targets.

Objectives: We report immunogenicity, safety, and efficacy over 12 months following a fourth COVID-19 mRNA or protein vaccine dose.

Methods: Adults aged ≥18 years were randomised 1:1 to receive a bivalent mRNA vaccine (mRNA-1273.214/mRNA-1273.222, Moderna; n=177) or a protein vaccine (NVX-CoV-2373, Novavax; n=176). A self-selected control group (no fourth dose) was also recruited (n=143). Follow-up occurred at six- and 12-months post-vaccination. Geometric mean concentrations (GMCs) of anti-Spike binding IgG and surrogate neutralising antibodies to Ancestral and Omicron variants (BA.1, BA.4/5 and JN.1), and IFN-γ concentrations (IGRA) as a proxy for T cell immunity were compared between the study groups.

Results: The IgG levels against Ancestral strain were higher in the Moderna group than the Novavax group at six- [Geometric mean ratio (GMR): 1.59, 95% CI: 1.38 to 1.82] and 12-months post-vaccination (GMR: 1.34, 95% CI:1.16 to 1.55), and similarly for Omicron BA.1, BA.4/5 and JN.1 variants (six months: ranged from GMR: 1.62 to 1.66, 95% CI: 1.41 to 1.91; 12 months: ranged from GMR: 1.33 to 1.43, 95% CI: 1.15 to 1.67). Similar results for neutralising antibodies were also observed. However, no differences in IGRA were observed between Moderna and Novavax. The IgG GMCs against Ancestral strain and Omicron variants in both vaccine groups were higher than the control group at both timepoints (six months: ranged from GMR: 1.24 to 2.40; 12 months: ranged from GMR: 1.04 to 1.62). As a post-hoc analysis, 68.1% (94/138) in the control group, had a SARS-CoV-2 infection over the 12-month period, compared with 43.0% (74/172) and 47.0% (77/164) in the Moderna and Novavax group, respectively.

Conclusions: While the bivalent Moderna vaccine induced higher immune responses than the Ancestral Novavax vaccine as a fourth dose, both vaccines appeared to provide comparable protection against SARS-CoV-2 Omicron variants over 12-months.

Background: People with HIV (PWH) using antiretroviral therapy are at increased risk to develop cardiovascular diseases (CVD). We hypothesized that residual viremia (RV; unquantifiable low, but detectable viral load) increases CVD risk.

Methods: We enrolled 1,895 virally suppressed PWH and compared CVD incidence in participants with and without RV. Extensive multi-omics characterization was performed. Incident CVD was registered after 2-year follow-up and adjusted odds ratios (aOR) calculated accounting for classical CVD risk factors. The numbers of expected and actual CVD events were compared using CVD risk scores.

Findings: RV, detected in one-third of participants, strongly increased the risk of developing a first cardiovascular event (3·1% vs. 1·2%, aOR 2·8, p=0·004). Participants with RV experienced twice the number of events predicted by the SCORE2 risk model. The association between RV and CVD was not driven by inflammation, immune activation, gut barrier dysfunction, or lipometabolic perturbations.

Interpretation: Residual viremia independently associated with CVD development, highlighting the need for tailored prevention and examination of novel intervention strategies.

Funding: Supported by an unrestricted grant from ViiV Healthcare with no involvement in study design, analysis, interpretation, or manuscript writing.

Objectives: HIV reservoirs in myeloid cells, including tissue-resident macrophages, persist despite antiretroviral therapy, hindering viral eradication. We have tested an approach for HIV clearance through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and anti-apoptotic molecules during viral reactivation. Whether the SECH approach can effectively target reservoirs of the myeloid lineage is investigated.

Methods: We examined whether SECH treatments could deplete HIV-infected macrophages from HIV⁺ donors ex vivo, and in humanized mice in vivo. We also performed spatial transcriptome analyses of myeloid HIV reservoirs in the brains of humanized mice that escaped SECH treatments.

Results: SECH treatments can eliminate HIV-infected macrophages from HIV⁺ donors ex vivo, and in a portion of humanized mice in vivo. Spatial transcriptome analyses showed increases in epigenetic repressors for HIV transcription, as well as elevated autophagy and glycolysis genes in brain myeloid cells resistant to SECH treatments, while counteracting these molecular mechanisms sensitized the myeloid reservoirs to cell death.

Conclusions: Our data suggest that myeloid HIV reservoirs resistant to depletion display limited HIV gene expression by epigenetic repressors, and express more pro-survival genes, while targeting these mechanisms helps to promote the clearance of myeloid HIV reservoirs.