Journal of Infection最新文献

Objectives: Early detection of treatment failure is essential to improve the management of drug-resistant tuberculosis (DR-TB). We evaluated the molecular bacterial load assay (MBLA) in comparison to standard diagnostic tests for monitoring therapy of patients affected by drug-resistant TB.

Methods: The performance of MBLA in tracking treatment response in a prospective cohort of patients with pulmonary MDR/RR- and pre-XDR/XDR-TB was compared with mycobacterial culture, mycobacterial DNA detection using GeneXpert (Xpert) and microscopy detection of sputum acid-fast-bacilli.

Results: Mycobacterium tuberculosis culture conversion was used as the read-out for treatment responses. The MBLA was most concordant during the early phase of treatment, detecting changes in bacterial load with similar accuracy to microscopy and outperforming Xpert. When considering all timepoints, concordance with MGIT results was 72.1% for MBLA, 57.4% for Xpert and 76.7% for microscopy. The AUC for culture conversion was higher for MBLA (0.88, CI 0.84-0.95) than for Xpert (0.78, CI 0.72-0.85) and microscopy (0.77, CI 0.71-0.83).

Conclusions: MBLA was superior in the early identification of successful culture conversion compared to microscopy and Xpert and could be a useful biomarker to evaluate novel entities in Phase IIA early-bactericidal-activity drug trials regardless of the degree of M. tuberculosis drug resistance.

Background: Ureaplasma parvum (U. parvum) is generally regarded as innocuous, and studies focusing on variations in pathogenicity among U. parvum serovars are inadequate. We elucidated the variations in the pathogenicity of U. parvum serovars in promoting human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN).

Methods: This cross-sectional study used baseline data from a Chinese multicenter prospective cohort of women of childbearing age undergoing routine cervical cancer screening. We employed multivariate logistic regression analysis to estimate the pathogenic effects of specific U. parvum serovars on HPV infection and CIN. Causal mediation analysis was performed to ascertain the direct effects of specific U. parvum serovars on CIN and their indirect implications via HPV infection.

Findings: The final data analysis encompassed 7,058 participants. Upon adjusting for confounding factors, a positive association was observed between U. parvum serovars 1, 3, and 6 and HPV infection (OR 1.53, 95%CI 1.15-2.03; OR 1.31, 95%CI 1.06-1.64; OR 2.34, 95%CI 1.90-2.87); however, only participants with U. parvum serovar 6 showed an increased risk of CIN (OR 1.90, 95%CI 1.19-3.02). No substantial correlation was observed between U. parvum serovar 14 and HPV or CIN incidence. HPV infection potentially mediates the influence of U. parvum serovar 6 on CIN, with a mediation proportion of 76.66%.

Interpretations: Our findings suggest that different U. parvum serovars vary in pathogenicity regarding HPV and CIN. Early detection of specific U. parvum serovars, such as U. parvum serovar 6, in HPV-infected individuals may enable early intervention therapies, and reduce the risk of CIN development.

Background: Despite vaccination, SARS-CoV-2 evolution leads to breakthrough infections and reinfections worldwide. Knowledge of hybrid immunization is crucial for future broad-spectrum SARS-CoV-2 vaccines.

Methods: In this study, we investigated neutralizing antibodies (nAbs) against the SARS-CoV-2 ancestral virus (wild-type [WT]), pre-Omicron VOCs, Omicron subvariants, and SARS-CoV-1 using plasma collected from four distinct cohorts: individuals who received three doses of BBIBP-CorV/CoronaVac vaccines, those who experienced BA.5 breakthrough infections, those with XBB breakthrough infections, and those with BA.5-XBB consecutive infections following three-dose vaccination.

Findings: Following Omicron breakthrough infections, the levels of nAbs against WT and pre-Omicron VOCs were higher due to immune imprinting established by WT-based vaccination, in comparison to nAbs against Omicron variants. Interestingly, the XBB breakthrough infections elicited a broader neutralization spectrum against SARS-CoV-2 variants compared to the BA.5 breakthrough infections. This observation suggests that the XBB variant demonstrates superior immunogenicity relative to BA.5. Notably, hybrid immunization of BA.5 breakthrough infections after WT vaccination led to additional immune imprinting, resulting in a broadened neutralization profile against both WT and BA.5 variants in BA.5-XBB consecutive infections. However, the duration of nAbs was shorter in these reinfections compared to the breakthrough infections. Additionally, the expanded immune imprinting from previous WT vaccination and BA.5 breakthrough infections account for the enhanced plasma neutralization immunodominance observed in the antigenic cartography for BA.5-XBB consecutive infections.

Interpretation: Overall, we demonstrated a persistent and expanded effect of immune imprinting from prior SARS-CoV-2 exposures. Thus, future vaccines should specifically address the latest variants, and booster shots should be given at a longer interval after the previous infection or vaccination.