Open Forum Infectious Diseases最新文献

Background: Understanding the risk of hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can guide effective public health interventions and severity assessments. This study calculated infection-hospitalization ratios (IHRs) and infection-case ratios (ICRs) to understand the relationship between SARS-CoV-2 infections, cases, and hospitalizations among different age groups during periods of Delta and Omicron variant predominance.

Methods: After calculating antinucleocapsid SARS-CoV-2 antibody seroprevalence using residual commercial laboratory serum specimens, 2 ratios were computed: (1) IHRs using coronavirus disease 2019 hospitalization data and (2) ICRs using Centers for Disease Control and Prevention surveillance data. Ratios were calculated across age groups (0-17, 18-49, 50-69, and ≥70 years) for 2 time periods (September-December 2021 [Delta] and December 2021-February 2022 [Omicron]).

Results: Pediatric IHRs increased from 76.7 during Delta to 258.4 during Omicron. Adult IHRs ranged from 3.0 (≥70 years) to 21.6 (18-49 years) during Delta and from 10.0 (≥70 years) to 119.1 (18-49 years) during Omicron. The pediatric ICR was lower during the Delta period (2.7) compared with the Omicron period (3.7). Adult ICRs (Delta: 1.1 [18-49 years] to 2.1 [70+ years]; Omicron: 2.2 [>70+ years] to 2.9 [50-69 years]) were lower than pediatric ICRs during both time periods.

Conclusions: All age groups exhibited a lower proportion of infections associated with hospitalization in the Omicron period than the Delta period; the proportion of infections associated with hospitalization increased with each older age group. A lower proportion of SARS-CoV-2 infections were associated with reported cases in the Omicron period than in the Delta period among all age groups.

Background: Healthcare workers are at increased risk of exposure to respiratory pathogens including Streptococcus pneumoniae (pneumococcus). While little asymptomatic carriage has been reported in young-to-middle-aged adults, this may be due to nonsensitive diagnostic methods. The aim of the current study was to investigate the rates of pneumococcal carriage in a large cohort of healthcare workers, using saliva as a respiratory specimen.

Methods: We evaluated pneumococcal carriage in convenience samples of saliva, self-collected from asymptomatic healthcare workers (Connecticut, USA) who were testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 30 March to 11 June 2020. DNA extracted from the culture-enriched saliva was later tested using quantitative polymerase chain reaction for piaB, lytA, and serotype. Saliva samples were considered positive for pneumococcus when the piaB cycle threshold value was <40.

Results: Study participants were 22-74 years old (mean age, 38.5 years), 75% female, 75% white, and with occupations including registered nurses (48%), medical doctors (23%), and patient care assistants (5%). Overall, 138 of 1241 samples (11%) from 86 of 392 individuals (21%) tested piaB positive at some point during the 4-month study period, with 28 (33%) colonized individuals positive at multiple time points. Carriers reflected the overall study population. No significant demographic characteristics were associated with detection of pneumococcus. Colonized individuals primarily carried serotypes 19F (25.6%) and 3 (12.8%).

Conclusions: During a period of mandatory masking, we identified a cumulative pneumococcal carriage prevalence of 21% among healthcare workers. This study highlights that healthcare workers may act as unrecognized reservoirs of pneumococcus in the population. Despite long-standing pediatric immunization programs, vaccine-targeted serotypes continue to be prevalent among the adult population.

Background: Limited data have described the testing patterns and outcomes of adults (≥18 years) with acute respiratory illness (ARI) in the emergency department setting.

Methods: This prospective cohort study includes patients with ARI from a program sponsored by the Centers for Disease Control and Prevention entitled Respiratory Virus Laboratory Emergency Department Network Surveillance (RESP-LENS) from August 2021 until March 2024 (91 hospitals). Patients with ARIs were identified weekly by electronic surveillance for 1 or more of 130 ICD-10 codes that defined ARI. Patients were followed for 30 days for the primary outcomes of hospitalization and mortality. Testing for RSV with nasopharyngeal swabbing followed by reverse transcription polymerase chain reaction was done as part of usual care. Risk of 30-day mortality and RSV positivity was tested in a generalized estimating equation.

Results: From 1 210 394 patients with ARI, 345 185 (28.5%) adults underwent RSV testing, which was positive in 2.4%. In adults who were RSV+, the overall mortality rate was 1.9% as compared with 2.9% in adults who were RSV-. Mortality with RSV+ status increased with age ≥65 years to 3.8% (95% CI, 3.1%-4.5%). However, in the generalized estimating equation, RSV+ status was not associated with a higher rate of hospitalization (adjusted odds, 0.79; 95% CI, .75-.84) or 30-day mortality (odds, 0.62; 95% CI, .53-.74) relative to those who were RSV-. Age ≥65 years, incremental worsening of vital signs, male sex, and heart failure were independently associated with death.

Conclusions: Among adults with ARI presenting to an emergency department who were tested for RSV as part of their usual care, laboratory-confirmed RSV positivity was not associated with increased risk, including hospitalization, intensive care unit requirement, or death.

Background: Xpert MTB/XDR (Cepheid) is recommended by the World Health Organization for drug susceptibility testing in patients with tuberculosis, with potential for rapid detection of isoniazid and fluoroquinolone resistance. However, diagnostic accuracy and clinical utility in a programmatic setting are unknown.

Methods: We evaluated the accuracy and clinical utility of Xpert MTB/XDR in patients with rifampicin-resistant pulmonary tuberculosis during programmatic implementation in Georgia between July 2022 and August 2024, using phenotypic drug susceptibility testing (DST) as a reference standard.

Results: An overall 140 patients were tested with Xpert MTB/XDR and phenotypic DST, and 94.9% and 33.8% had isoniazid and fluoroquinolone resistance by phenotypic DST, respectively. Xpert MTB/XDR showed 99.2% sensitivity (95% CI, 95.5%-100%) and 100% specificity (95% CI, 54.1%-100%) for isoniazid resistance. Sensitivity and specificity for fluoroquinolone resistance were 88.4% (95% CI, 74.9%-96.1%) and 100% (95% CI, 95.6%-100%). When indeterminate/invalid Xpert MTB/XDR results were included, 17.4% (8/46) and 6.2% (8/129) of patients with phenotypic fluoroquinolone and isoniazid resistance were missed. Median turnaround time for Xpert MTB/XDR was 1 day (IQR, 1-3) and median time to treatment was 4 days (IQR, 1-7). Phenotypic DST results took a median 43 days (IQR, 29-63) longer than Xpert MTB/XDR results. Finally, 95% (115/121; 95% CI, 89.5%-98.2%) of patients had fluoroquinolones appropriately prescribed based on Xpert MTB/XDR results.

Conclusions: Programmatic data confirm the high accuracy of Xpert MTB/XDR, despite being below the World Health Organization target product profile targets for fluoroquinolones, with significantly faster time to results than phenotypic DST.

Background: Hepatitis C virus (HCV) has emerged as a sexually transmitted infection in gay, bisexual, and other men who have sex with men (GBM). We estimated the seroprevalence and incidence of HCV infection and examined patterns of HCV testing among GBM using human immunodeficiency virus preexposure prophylaxis (PrEP) in Ontario, Canada.

Methods: We analyzed data from the Ontario PrEP Cohort Study (ON-PrEP), a prospective cohort of PrEP users from 10 Ontario clinics. Participants completed an online questionnaire and study staff collected clinical information into a study database biannually for 2 years. We estimated the baseline seroprevalence and incidence of HCV infection and examined patterns of HCV testing during follow-up. We further explored differences in sociodemographic/clinical variables between those with and without prevalent/incident HCV infection through bivariate analysis.

Results: Among 557 eligible PrEP users, 382 (68.6%) underwent baseline HCV antibody testing, of whom 5 tested HCV seropositive, giving a seroprevalence of 1.3% (95% confidence interval [CI], .43%-3.03%). Only 245 (43.9%) participants underwent HCV antibody testing after baseline, and median time to participants' first follow-up test was 245 days. During follow-up, 2 participants tested newly HCV seropositive, giving an incidence of 0.47/100 person-years (95% CI, .06-1.69) over 428.9 years of follow-up. Participants with prevalent/incident HCV infection during the study appeared more likely to report giving money, drugs, gifts, or services for sex in the 3 months preceding enrollment compared to those who never tested HCV seropositive (P = .02).

Conclusions: HCV seroprevalence and incidence were low but not negligible among Ontario PrEP users. HCV antibody and RNA testing were suboptimal.

Background: Excluding pregnant women with human immunodeficiency virus (HIV) from clinical trials results in inadequate pregnancy safety data for new antiretroviral therapies (ART). More rapid accumulation of ART pregnancy safety data is required. The Antiretroviral Pregnancy Registry (APR) collects teratogenicity data on ART exposures during conception and pregnancy, yet reporting to the registry is suboptimal, impacting ART choices for women with HIV globally. This research assesses awareness of the APR and barriers to reporting among HIV providers in the United States (US) and Australia.

Methods: Anonymous, online surveys were conceived independently by researchers in the US and Australia. The surveys were distributed through national email distribution lists to healthcare providers for pregnant women with HIV and their newborns or women of reproductive potential with HIV, to assess their awareness of the APR and barriers to reporting.

Results: In total, 146 healthcare providers (66 US, 80 Australia) completed the survey. Respondents from the US had greater awareness of the registry and more reporting experience, describing the process as complex and laborious. Providers from Australia were largely unaware that the APR accepts reports from outside the US. Key barriers to reporting were uncertainty about how to report and incomplete access to all relevant maternal and pediatric data.

Conclusions: Barriers to reporting to the APR are context specific. There is scope to raise the global profile of the APR to expedite data collection, reducing time between antiretroviral licensure and accumulation of sufficient pregnancy safety data.

Background: HIV viremia has been considered a cardiovascular disease (CVD) risk factor, but many studies have had insufficient data on potential confounders. We explored the association between viremia and CVD after adjusting for established risk factors and analyzed whether consideration of viremia would improve CVD prediction.

Methods: Adults from RESPOND were followed from the first date with available data until the first of rigorously defined CVD, loss to follow-up, death, or administrative censoring. We first analyzed the associations between 6 measures of viremia (time-updated, before antiretroviral therapy [ART], viremia category, and measures of cumulative viremia) and CVD after adjusting for the variables in the D:A:D CVD score (age, sex/gender, smoking, family history, diabetes, recent abacavir, CD4 count, blood pressure, cholesterol, high-density lipoprotein, cumulative use of stavudine, didanosine, indinavir, lopinavir, and darunavir). We subsequently compared predictive performance with and without viremia in 5-fold internal cross-validation.

Results: A total of 547 events were observed in 17 497 persons (median follow-up, 6.8 years). Although some viremia variables were associated with CVD in univariable analyses, there were no statistically significant associations after adjusting for potential confounders, neither for measures of current viral load, pre-ART viral load, highest viremia category during ART, nor cumulative viremia (modeled both as total cumulative viremia, cumulative viremia during ART, and recent cumulative viremia). Consistently, none of the viremia variables improved prediction capacity.

Conclusions: In this large international cohort, HIV viremia was not associated with CVD when adjusting for established risk factors. Our results did not show viremia to be predictive of CVD among people with HIV.

In this multicenter study of 387 patients who were immunocompromised, 4.5% with invasive pulmonary aspergillosis also had Pneumocystis jirovecii pneumonia. Predictors of coinfection included elevated β-D-glucan and prolonged corticosteroid use. Coinfection correlated with reduced 30-day survival (22% vs 57%), suggesting that early identification and prophylaxis may improve outcomes.

The skip phenomenon (SP) is a pattern where blood cultures are intermittently positive before final clearance. We report that one-third of patients with Staphylococcus lugdunensis infective endocarditis experienced the SP. Patients with the SP experienced both a longer duration of bacteremia and hospital stay, with a higher 1-year mortality rate.

Background: The burden of hepatitis C virus (HCV)-related hospitalizations is substantial, particularly among people with HIV and HCV. In Ontario, Canada, use of direct-acting antivirals (DAAs) increased following policies removing fibrosis-stage restrictions and approving of pangenotypic agents in 2017 and 2018, respectively. We examined the impact of expanded DAA access on HCV-related hospitalizations in people with HIV.

Methods: We conducted a population-based study using administrative databases between April 2003 and December 2022. We used segmented negative binomial regression to examine changes in level and trend of quarterly HCV-related hospitalization rates in people with HIV following the policy changes and compared predicted rates in the absence of expanded DAA access with observed rates during this period.

Results: We identified 2943 HCV-related hospitalizations among people with HIV during our study period. Rates of HCV-related hospitalizations were substantially higher among people with HIV than individuals without HIV. In the postintervention period, there was an immediate level increase in the rate of HCV-related hospitalizations (rate ratio, 1.23; 95% CI, 1.18-1.29), followed by a decrease in trend (rate ratio, 0.94 per quarter; 95% CI, .93-.94). We estimated that expanding DAA access was associated with 192 fewer hospitalizations in people with HIV between 2019 and 2022.

Conclusions: Policies expanding DAA access have reduced HCV-related hospitalizations in people with HIV. However, rates were higher relative to those in people without HIV. Further research is needed to identify and address disparities in clinical outcomes among people with HIV and HCV.