Clinical Infectious Diseases最新文献

Background: Approximately 95% of people infected with Mycobacterium tuberculosis do not progress to tuberculosis (TB) disease. Identifying key determinants of TB progression could focus prevention efforts.

Methods: Contacts of pulmonary TB patients were enrolled in a prospective multi-center cohort study (Regional Prospective Observational Research in Tuberculosis [RePORT]-Brazil) from 2015 to 2019 and followed for 24 months. Empirical review and least absolute shrinkage and selection operator (LASSO) regression, using baseline clinical and laboratory information, were used as dimension reduction techniques to determine factors for inclusion in prediction models. Models were created for: (1) all contacts, (2) contacts interferon-gamma release assay (IGRA)-positive at baseline, and (3) IGRA-positive contacts who did not receive TB preventive therapy (TPT; <30 days isoniazid). Internal validation was performed using bootstrapping.

Results: Among 1846 contacts of 619 TB index patients, 25 (1.4%) progressed to TB. No TPT was a risk factor for progression to TB among all contacts (mixed-effects adjusted hazard ratio [aHR] = 16.55, 95% confidence interval [CI]: 2.22-124.45). Internal validation with all contacts yielded an area under the receiver operating characteristic curve of 0.80 (95% CI: .72-.86]. Body mass index (BMI) was inversely associated with increased risk of progressing to active TB among IGRA-positive contacts who did not receive TPT (aHR = 0.89, 95% CI: .80-.99). Interferon-gamma release assay-positive contacts with BMI <25 kg/m2 had a 4.14-fold (95% CI: 1.17-14.67) higher risk of progression to TB than IGRA-positive contacts with BMI ≥25 kg/m2: 8.4% versus 2.1%, respectively.

Conclusions: Body mass index <25 kg/m2, a readily available biomarker, identified IGRA-positive close TB contacts at high risk of progressing to TB disease. Prioritizing this high-risk group for TB preventive therapy could improve TB prevention efforts. BMI <25 kg/m², a readily available biomarker, identified IGRA-positive close contacts at high risk for progression to TB in a large observational Brazilian cohort. Prioritizing this high-risk group for TB preventive therapy could significantly improve TB prevention efforts.

Background: Dolutegravir (DTG)/lamivudine dual therapy (DT) has demonstrated noninferiority to triple therapy (TT) in the GEMINI trials. Although the population with ≤200 CD4 cells/mm3 had a lower response rate, this was unrelated to virological failure. This trial evaluated the antiviral activity of dolutegravir/lamivudine among antiretroviral therapy (ART)-naive patients with human immunodeficiency virus (HIV) with a CD4 count ≤200 cells/mm3.

Methods: DOLCE is a randomized, hypothesis-based, open-label, multicenter study l, assessing the antiviral efficacy of DTG/3TC at week 48 in treatment-naive people with HIV (PWH) with CD4 counts ≤200 cells/mm3. Participants were randomly assigned in a 2:1 ratio to receive DTG/3TC as a single tablet regimen or DTG plus Tenofovir disoproxil fumarate (TDF)/XTC: Emtricitabine or lamivudine (FTC or 3TC). The primary endpoint was the proportion of participants with pVL <50 copies/mL at week 48 (Food and Drug Administration snapshot analysis intent-to-treat exposed population). This report presents results at week 48.

Results: Baseline characteristics were similar in both arms. In the DT arm, median CD4 cell count was 109 cells/mm (interquartile range [IQR]: 49-177) and median pVL was 180,000 copies/mL (IQR: 53 309-468 691); 45.4% had CD4 <100 cells/mm3, and 61.4% had pVL >100 000 copies/mL. CDC (Centers for Disease Control and Prevention) stage C: 31.4%. At week 48, virological suppression (pVL <50 copies/mL) was achieved 82.2% in the DT (125/152), and the CD4 count increased by +200 cells/mm3. Per-protocol analysis showed a response rate of 91.9%. Severe adverse events (n = 17) were reported in 15 of 152 participants (11.1%).

Conclusions: Dolutegravir/3TC demonstrated high efficacy in a population with low CD4 counts and high viral load. This study adds information regarding the efficacy and safety of DTG/3TC, regardless of baseline CD4 counts and viral load.

Clinical trials registration: NCT04880395.

Background: Modern assays for the detection of Chlamydia trachomatis (CT) rely on nucleic acid amplification testing (NAAT) of DNA or ribosomal RNA. However, it is also known that both viable ("living") and non-viable ("dead") CT can be detected by NAAT. Multiple laboratory techniques to measure CT viability have emerged.

Methods: We searched PubMed, EMBASE, Scopus, and Dimensions as well as conference abstracts for entries between January 2000 and May 2023. We included any studies that measured CT viability among NAAT-positive samples. Viability assays include enhanced cell culture, direct fluorescent antibody (DFA), messenger RNA (mRNA) detection via digital droplet polymerase chain reaction (PCR, ddPCR), viability PCR (V-PCR), and real-time PCR measuring RNA-to-DNA ratio (RDR) (eg, InSignia®). A meta-analysis was performed on the proportions of non-viable CT by anatomical site.

Results: We screened 31 342 records and included 16 studies in the analysis. The pooled proportions of non-viable CT by site were: 33% (95% confidence interval [CI]: 19%-47%) in rectal swabs (8 studies), 17% (95% CI: 7%-27%) in cervical swabs (6 studies), 15% (95% CI: 6%-25%) in vaginal swabs (6 studies), and 11% (95% CI: 9%-17%) in urine/urethral swabs (2 studies).

Conclusions: All included studies found that a proportion of NAAT-detected CT is non-viable. The findings have far-reaching implications for screening programs and studies evaluating new STI tests and antimicrobial regimens.

Objectives: Neisseria meningitidis is primarily associated with severe systemic infections but can infect the eye and periocular tissues. Most meningococcal eye infections have a mild prognosis, but there is a significant increase in the risk of invasive disease. UK public health guidelines recommend chemoprophylaxis for meningococcal eye infection cases and contacts. This study involved a clinical and microbiological analysis of meningococcal eye infections in England over a 13-year period.

Methods: The analysis included all English cases of eye infection with confirmed isolation of N. meningitidis from ocular samples between 2010 and 2022. Microbiological data were integrated with clinical information collected by public health professionals, including age, clinical presentation, and treatment.

Results: Among 263 meningococcal eye infection cases, nearly half were observed in infants, with the highest risk in neonates. Conjunctivitis was the most common presentation, and most cases resolved without complications following treatment. Young children were more likely to receive intravenous antibiotics compared to older age groups. Around 3% of cases progressed to invasive disease (groups B, Y, or W); however, all patients survived. Most eye-derived isolates were non-groupable and reflected the profile of carriage strains in the UK, indicating an incidental infection not requiring encapsulation.

Conclusions: Meningococcal eye infections typically reflect strains circulating within the population suggesting they arise from exposure to respiratory secretions. Although cases often present with mild symptoms, the risk of invasive disease shortly after onset highlights the need for prompt recognition, systemic treatment, and a swift public health response.

Background: Longer-term outcome data following second-line antiretroviral therapy initiation in resource-limited settings is limited, especially in regions where genotypic resistance is inaccessible. This analysis evaluated extended efficacy and tolerability data from the D2EFT study.

Methods: D2EFT is a completed, multicenter, phase IIIB/IV, randomized, open-label trial in 14 low- and middle-income countries. People with human immunodeficiency virus (HIV) who had failed first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens were switched to 1 of ritonavir-boosted darunavir plus 2 nucleoside reverse transcriptase inhibitors (DRV/r + 2NRTIs), ritonavir-boosted darunavir plus dolutegravir (DTG + DRV/r), or dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine (DTG + TDF/XTC), with or without pre-switch genotyping. Here we report virological suppression at 96 weeks, defined as HIV RNA <50 copies/mL in a modified intention-to-treat population.

Results: Between November 2017 and January 2022, 1190 participants were screened, 828 were randomized, and 826 were included in the analysis. At week 96, the proportions of participants with HIV RNA <50 copies/mL were 191/251 (76.1%) in DRV/r + 2NRTIs, 215/251 (85.7%) in DTG + DRV/r, and 231/283 (81.6%) in DTG + TDF/XTC. The treatment differences (95% confidence intervals [CIs]) in proportions achieving virological suppression were 9.6% (2.7, 16.4) in DTG + DRV/r and 9.0% (1.4, 16.6) in DTG + TDF/XTC, compared to DRV/r + 2NRTIs. Intermediate or high-level dolutegravir resistance was identified in 3/27 (13%) of virological failures in individuals taking DTG + TDF/XTC but in no one taking DTG + DRV/r. No darunavir resistance was observed.

Conclusions: After 96 weeks of follow-up, DTG + DRV/r and DTG + TDF/XTC demonstrated virological superiority over DRV/r + 2NRTIs after first-line NNRTI-failure. However, emerging dolutegravir resistance, which was observed only in individuals taking DTG + TDF/XTC, requires ongoing global surveillance.