Open Forum Infectious Diseases最新文献

Background: This study was conducted to evaluate screening procedures for anal high-grade squamous intraepithelial lesions (HSILs) with anal liquid-based cytology (aLBC) and biomarkers to identify candidates for high-resolution anoscopy (HRA).

Methods: This cross-sectional study included men who have sex with men with HIV. Participants underwent HRA, aLBC, and biomarker testing. Three screening procedures were compared with aLBC: biomarker alone, cytology and biomarker in all, and cytology and reflex biomarkers (biomarkers applied if aLBC results were atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion). Biomarkers included Linear Array (LA), LA for 14 high-risk human papillomavirus (LA 14 HR-HPV) genotypes, LA HPV-16, Hybrid Capture 2 (HC2), E6/E7 mRNA, and E6/E7 mRNA HPV-16.

Results: Of 354 participants, 179 (50.6%) had atypical squamous cells of undetermined significance or worse, requiring HRA (sensitivity, 80%; specificity, 57.3%; area under the curve, 0.687; reference, biopsy-proven HSIL). Cytology and reflex biomarkers per E6/E7 mRNA, LA 14 HR-HPV, and HC2 and the biomarker-alone procedure with HC2 showed comparable accuracy (sensitivities: 71.6%, 78.8%, 73.1%, 75.7%; specificities: 73.5%, 67.9%, 76.1%, 65.5%; areas under the curve: 0.726, 0.734, 0.746, 0.706) with fewer HRA referrals (number needed to diagnose: 2.2, 2.1, 2, 2.4).

Conclusions: Our findings suggest that E6/E7 mRNA, LA 14 HR-HPV, and HC2 in the cytology and reflex biomarkers procedure, as well as HC2 in the biomarker-alone procedure, can improve anal HSIL screening effectiveness.

Background: We investigated hospitalized carbapenem-resistant Enterobacterales (CRE) and extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) cases with and without COVID-19, as identified through Emerging Infections Program surveillance in 10 sites from 2020 to 2022.

Methods: We defined a CRE case as the first isolation of Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes, K oxytoca, K pneumoniae, or K variicola resistant to any carbapenem. We defined an ESBL-E case as the first isolation of E coli, K pneumoniae, or K oxytoca resistant to any third-generation cephalosporin and nonresistant to all carbapenems tested. Specimens were drawn from a normally sterile site or urine among hospitalized residents of the surveillance area in a 30-day period. We defined COVID-19 as a positive SARS-CoV-2 test result (SC2⁺) within 14 days before CRE or ESBL-E specimen collection and performed multivariable logistic regression analyses.

Results: Of 1595 CRE and 1866 ESBL-E hospitalized cases, 38 (2.4%) and 60 (3.2%), respectively, had a SC2⁺. Among these cases, a SC2⁺ was associated with intensive care unit admission (adjusted odds ratio [aOR], 1.69 [95% CI, 1.14-2.50]; aOR, 1.48 [95% CI, 1.03-2.12]) and 30-day mortality (aOR, 1.79 [95% CI, 1.22-2.64]; aOR, 1.94 [95% CI, 1.39-2.70]).

Conclusions: CRE and ESBL-E infections among hospitalized patients with preceding COVID-19 were uncommon but had worse outcomes when compared with cases without COVID-19. COVID-19 prevention in patients at risk of CRE and ESBL-E infections is needed, as well as continued infection control measures and antibiotic stewardship for patients with COVID-19.

Background: Identifying risk factors for mortality in patients with Staphylococcus aureus bacteremia (SAB) is crucial due to its high fatality. However, data on risk factors for infection-attributable deaths considering competing risk events such as non-infection-attributable deaths remain limited. We performed a competing risk analysis to elucidate risk factors associated with 30-day infection-attributable mortality in a large cohort of patients with SAB.

Methods: This retrospective cohort study included adult patients diagnosed with SAB at a tertiary hospital from August 2008 to December 2019. Competing risk analysis was performed using Fine and Gray models to estimate subdistribution hazard ratios (sHRs) for 30-day infection-attributable death.

Results: Among 1936 patients, 444 (22.9%) died within 30 days. Of these, 338 (76.1%) were infection-attributable and 106 (23.9%) were non-infection-attributable deaths. The multivariable Fine and Gray model identified significant risk factors for 30-day infection-attributable death (sHRs with 95% confidence intervals): an increase in age by 10 years (1.14 [1.02-1.26]), presence of malignancy (1.54 [1.17-2.02]), liver cirrhosis (2.15 [1.56-2.97]), corticosteroid use (1.61 [1.19-2.17]), septic shock (3.28 [1.98-5.42]), elevated C-reactive protein (1.60 [1.19-2.14]), pneumonia (1.81 [1.21-2.72]), persistent bacteremia (1.73 [1.31-2.30]), and failure to remove the eradicable focus (2.40 [1.38-4.19]) or absence of an eradicable focus (1.49 [1.08-2.04]). Except for age and malignancy, these factors were not significantly associated with non-infection-related death.

Conclusions: Specific risk factors for infection-attributable death in patients with SAB were identified, distinct from those for nonattributable death. These findings can aid in the early identification of patients at risk for SAB-attributable mortality.

Disparities in coronavirus disease 2019 mortality are driven by inequalities in group-specific incidence rates (IRs), case fatality rates (CFRs), and their interaction. For emerging infections, such as severe acute respiratory syndrome coronavirus 2, group-specific IRs and CFRs change on different time scales, and inequities in these measures may reflect different social and medical mechanisms. To be useful tools for public health surveillance and policy, analyses of changing mortality rate disparities must independently address changes in IRs and CFRs. However, this is rarely done. In this analysis, we examine the separate contributions of disparities in the timing of infection-reflecting differential infection risk factors such as residential segregation, housing, and participation in essential work-and declining CFRs over time on mortality disparities by race/ethnicity in the US state of Michigan. We used detailed case data to decompose race/ethnicity-specific mortality rates into their age-specific IR and CFR components during each of 3 periods from March to December 2020. We used these estimates in a counterfactual simulation model to estimate that that 35% (95% credible interval, 30%-40%) of deaths in black Michigan residents could have been prevented if these residents were infected along the timeline experienced by white residents, resulting in a 67% (61%-72%) reduction in the mortality rate gap between black and white Michigan residents during 2020. These results clearly illustrate why differential power to "wait out" infection during an infectious disease emergency-a function of structural racism-is a key, underappreciated, driver of inequality in disease and death from emerging infections.

Background: Arboviruses, including Dengue (DENV), Zika, and chikungunya, cause recurrent outbreaks of varying intensity in tropical countries. This study aimed to investigate other arboviruses, including Zika and chikungunya, in patients clinically suspected of Dengue and to characterize the circulating Dengue serotypes and genotypes in Northern Vietnam from 2020 to 2022. To date, information on this topic in the region has been limited.

Methods: Multiplex real-time polymerase chain reaction (PCR) was used to detect Dengue, Zika, and chikungunya RNA, and DENV serotypes were identified via real-time reverse transcriptase PCR from 426 clinically Dengue suspected patients. Patients were screened for NS1 antigen and anti-DENV immunoglobulin (Ig) G/IgM antibodies. Phylogenetic analysis of DENV Capsid-premembrane gene sequences was performed to investigate genotype distribution.

Results: Dengue was confirmed in 95% of cases, with no Zika or chikungunya RNA detected. DENV-2 was the predominant serotype (61%), followed by DENV-1 (31%) and DENV-4 (7%). Coinfections were observed, with DENV-1 and DENV-2 being the most common. In 2022, a high incidence of Dengue cases with warning signs and severe Dengue was observed, accompanied by elevated liver enzyme levels and reduced platelet counts. Phylogenetic analysis revealed that the DENV-1 and DENV-4 serotypes clustered with previously reported regional virus, while DENV-2 showed a shift from genotype Asian I to Cosmopolitan over the study period.

Conclusions: This study underscores a significant rise in Dengue severity and shifts in DENV genotypes in recent years in Northern Vietnam, emphasizing the importance of understanding genotype dynamics and clinical dynamics for improving outbreak preparedness and response strategies.

Background: To better understand factors associated with virologic response, we retrospectively characterized the HIV proviruses of 7 people with HIV who received long-acting cabotegravir/rilpivirine (CAB/RPV-LA) and were selected according to the following criteria: virologic control achieved despite a history of viral replication on 1 or both corresponding antiretroviral classes (n = 6) and virologic failure (VF) after CAB/RPV-LA initiation (n = 1).

Methods: Last available blood samples before the initiation of CAB/RPV-LA were analyzed retrospectively. Near full-length HIV DNA genome haplotypes were inferred from Nanopore sequencing by the in vivo Genome Diversity Analyzer to search for archived drug resistance mutations (DRMs) and evaluate the frequency and intactness of proviruses harboring DRMs.

Results: Archived DRMs including G-to-A mutations were found in samples from 3 patients who maintained virologic control. Genomes harboring DRMs were majorly in minority variants (<20%) and were defective in all cases except for 1 participant. In this participant, intact genomes with the H221Y mutation on reverse transcriptase were detected representing 11 copies per 10⁶ peripheral blood mononuclear cells. The other mutations observed in the participants of the study resulted most likely from hypermutations. The patient with VF presented archived mutations, all associated with defects. Other factors could explain this VF.

Conclusions: Our findings highlight the difficulty in interpreting the clinical significance of DRMs when detected in proviral DNA and the need to filter out hypermutated sequences. Detected DRMs could be harbored by defective archived genomes unlikely to contribute to treatment failure.

Pancreatic tuberculosis (TB) is an uncommon extrapulmonary presentation of TB. Identification of coinfection with HIV may unmask not only disseminated TB but also immune reconstitution inflammatory syndrome (IRIS). We present the case of a 70-year-old Indian woman newly diagnosed with AIDS and pancreatic tuberculosis with miliary disseminated disease. Her clinical course was complicated by IRIS related to HIV-TB coinfection despite sequential and targeted anti-infective therapies. We review the presentation, pathophysiology, and risk factors for developing IRIS with HIV and pancreatic TB.

Background: The BASE study (NCT03998176), a phase 4, 48-week (W), single-arm, prospective trial, revealed that the use of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV and substance use disorders (PWH/SUD) was safe and effective without emergent antiretroviral resistance despite incomplete adherence. Here, we present the W96 results.

Methods: A retrospective analysis of all participants enrolled in the BASE study was completed from W48 to W96. End points of interest at W96 included the proportion of participants with viral suppression (VS; HIV RNA <50 copies/mL [c/mL]), incidence of protocol-defined virologic failure (PDVF; 2 consecutive ≥400 c/mL), safety, adherence (percentage of days covered [PDC]), retention in care, and prevalence of ongoing substance use.

Results: All enrolled BASE participants (n = 43) were included in the W96 analysis. At W48, 21 participants (49%) had achieved VS (intent-to-treat [ITT]). Thirty-six (84%) participants completed W96, with 19 achieving an HIV RNA <50 copies/mL (ITT, 44%; per-protocol, 54%). Seven participants (19%) met PDVF; genotyping was performed on 2, with no evidence of treatment-emergent antiretroviral resistance noted. No safety signals were identified or attributed to B/F/TAF. Adherence to B/F/TAF decreased 18% after W48 (mean PDC: W0-W48, 72%; W48-W96, 54%; P < .01). Participants exhibiting adherence rates of ≥4 doses/wk (PDC ≥57%) were more likely to achieve VS (PDC ≥57%, 84.2%, vs PDC <57%, 15.8%; P < .01). Retention in care remained stable, and participants continued to use substances through W96.

Conclusions: At W96, the proportion of PWH/SUD achieving VS with B/F/TAF decreased to 44%, along with an adherence decrease of 18%, with no evidence of treatment-emergent HIV drug resistance occurring.

Candida auris is a rapidly emerging fungal pathogen associated with high resistance rates, particularly in healthcare settings. It most commonly affects patients with severe underlying medical conditions and requiring complex medical care. Patients with invasive medical devices tend to be at increased risk for getting C auris and developing infection. This article presents a case of C auris ventriculitis successfully treated with intravenous liposomal amphotericin B and oral flucytosine. A 41-year-old man with multiple comorbidities, including recent placement of a ventriculoperitoneal shunt, presented with suspected sepsis. Candida auris was isolated from cerebrospinal fluid cultures. Antifungal therapy along with removal of the shunt led to resolution of infection without complications. This case highlights the challenges posed by C auris infections and underscores the importance of appropriate treatment strategies.