Open Forum Infectious Diseases最新文献

Background: Our previous study suggested that mixed infection with R5 and X4/dual human immunodeficiency virus type 1 (HIV-1) may contribute to coreceptor switch from R5 to X4 HIV-1. To confirm this hypothesis, we investigated mixed HIV-1 infections in people who inject drugs (PWID) infected with the CRF01_AE subtype.

Methods: Viral plasma RNA from PWID were extracted, the V3 region of the HIV-1 gp120 gene was amplified, and deep sequencing was performed. Coreceptor usage was determined using phenotypic assay by cloning each V3 region. Coreceptor usage of minor HIV-1 variants detected by deep sequencing was predicted based on the amino acid sequences of the V3 region.

Results: Deep sequencing of plasma from 36 PWID revealed that mixed HIV-1 infection involving different coreceptor usage occurred in 13 cases (36.1%). Phylogenetic analysis revealed that R5 variants were dominant, whereas X4/dual variants were detected as minor populations in most cases. In 1 case, however, R5 variants emerged as a distinct minor population mixed with X4/dual variants as the major population. Notably, plasma viral RNA load (pVL) was higher in cases of mixed infection with R5 and X4/dual HIV-1 than in those infected solely with R5 HIV-1.

Conclusions: Our observations suggest a possible association between mixed HIV-1 coreceptor usage and coreceptor switch in CRF01_AE-infected PWID, and that mixed infection may be associated with pVL.

Background: Most studies of human metapneumovirus (HMPV) epidemiology have been among inpatients. This study examined the epidemiology of HMPV compared with other common viruses among outpatients seeking care for an acute respiratory illness (ARI) during 5 influenza seasons (2016-2017 to 2019-2020, before the coronavirus disease 2019 pandemic, and in 2021-2022, during the pandemic).

Methods: Outpatients ≥6 months old seeking care for ARI and presenting with cough of ≤7 days' duration provided nasal and pharyngeal swab samples, demographic data, and access to electronic medical record data. Samples were tested with reverse-transcription polymerase chain reaction assays for HMPV, influenza, parainfluenza virus (PIV) 1-4, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Student's t and χ² tests were used to compare HMPV cases with other ARIs.

Results: After exclusion of 68 coinfections, 7143 patients remained; 2017 had influenza, 762 had RSV, 423 had HMPV, 83 had PIV, 352 had SARS-CoV-2, and 3506 tested polymerase chain reaction negative for all of these viruses. Of all patients with ARI each influenza season, 30.2%-37.1% tested positive for influenza, 11.3%-13.6% for RSV, 4.7%-7.3% for HMPV, and 0.1%-1.9% for PIV. Compared with patients with RSV, those with HMPV less often had congestion, dyspnea, and sore throat. Compared with patients with influenza, those with HMPV were less likely to have fever but more often had congestion or dyspnea and felt worse at 7-14-day follow-up. Children recovered from HMPV faster than adults.

Conclusions: HMPV is an important cause of outpatient ARI during influenza season. Patients with HMPV had slightly different demographic characteristics and symptoms from those with other ARIs.

Background: The clinical and microbiological features of infection due to non-tuberculous mycobacteria (NTM) after hematopoietic stem-cell transplantation (HSCT) remain poorly understood.

Methods: We performed a retrospective, multinational case-control study that included HSCT recipients (≥12 years) diagnosed with NTM disease between January 2008 and December 2018. Controls were HSCT recipients with no evidence of NTM disease, matched (1:2 ratio) by participating center and post-transplant survival. Logistic regression on matched pairs was used to investigate risk factors for NTM disease.

Results: We included 25 cases of NTM disease. The most common HSCT type was allogeneic from unrelated donor (72.0%) after myeloablative conditioning (76.0%). Predominant hematological conditions were acute myelogenous leukemia (28.0%) and myelodysplastic syndrome (24.0%). Most patients (88.0%) had previously received immunosuppressive therapy. The most common species identified were Mycobacterium avium complex (64.0%) and rapidly growing mycobacteria (20.0%). Most patients (68.0%) had pulmonary disease. All but one received antimycobacterial therapy for a median of 267.5 days. Macrolides (83.3%), rifamycins (58.3%) and ethambutol (62.5%) were the most commonly used drugs. Four patients (16.7%) developed adverse events requiring therapy discontinuation. All-cause and attributable mortality rates were 28.0% and 4.0%, respectively. One patient experienced relapse after 464 days. Diagnosis of a non-NTM infection (adjusted odds ratio [aOR]: 3.11; 95% confidence interval [95% CI]: 1.25-7.78) and corticosteroid therapy (aOR: 2.88; 95% CI: 1.16-7.17), both within the previous 90 days, were associated with NTM disease.

Conclusions: NTM disease is a serious complication among heavily immunocompromised HSCT recipients associated with prior non-NTM infection and corticosteroid therapy.

Background: Tuberculosis (TB) recurrence remains a significant public health concern, even in regions with low incidence. Recurrent TB may result from endogenous reactivation of a previous infection or from exogenous reinfection with a new strain. Distinguishing between these mechanisms is crucial for understanding TB dynamics and optimizing control strategies. This study aims to determine the frequency of TB recurrence in Aragón, Spain, a region with low TB incidence, and to identify factors associated with reactivation and reinfection over a 30-year period.

Methods: A retrospective, descriptive study including all genotyped Mycobacterium tuberculosis isolates from 1993 to 2022 was conducted in Aragón. IS6110-RFLP was the method used to genotype strains. Recurrences were classified as reactivation or reinfection based on molecular profiles. Clinical and epidemiological data were retrieved from medical records. Appropriate statistical tests were applied to compare groups.

Results: Among 3510 genotyped TB cases, 81 (2.30%) were recurrent: 68 reactivations (1.93%) and 15 reinfections (0.42%). Reinfection was significantly associated with change of residence, HIV infection, cancer diagnosis in the second episode, and multimorbidity. Time to recurrence was significantly longer in reinfections (median 7.0 years) compared to reactivations (2.0 years). Most isolates belonged to Lineage 4 , and reinfection strains were more often linked to clustered strains circulating in the community.

Conclusions: In this low-incidence setting, TB recurrence is rare and mainly the result of reactivation. Reinfections, though less frequent, are linked to mobility, HIV co-infection, neoplasm, and compromised health status. These findings underscore the importance of long-term molecular surveillance and targeted follow-up for high-risk patients.

Background: SARS-CoV-2 is a major cause of outpatient-attended acute respiratory infections (ARIs). Data from Africa are limited on SARS-CoV-2 infection, variants, symptom profile, and longitudinal trends for outpatient presentation.

Methods: Starting December 2020, we established ARI surveillance at 5 outpatient clinics in coastal Kenya, recruiting ∼15 participants (any age) per week per clinic for SARS-CoV-2 testing and genome analysis. Participants provided respiratory samples, demographic details, and vaccination and symptom data. We compared SARS-CoV-2 clinical and molecular epidemiology before and during Omicron waves using multivariate logistic regression.

Results: By February 2025, we had recruited 14 562 ARI cases, with 1053 (7.2%) testing positive for SARS-CoV-2. The median age of cases was 25 years (IQR, 15-41) and 65.0% were female. Nine infection waves were recorded, with positivity ranging 8.2% to 25.6%. Interwave intervals increased from ≤3 months in 2021 to ≥6 months in 2024. Sixty-eight PANGO lineages were identified from 782 (74.2%) sequenced cases, with 4 predominating local waves (AY.116, BQ.1.8, FY.4.1, LF.7.3.2), which were rare globally (<0.5%) during their detection period. Overall, common symptoms among positive cases were cough (91.5%), nasal discharge (76.7%), and fever (53.1%). Loss of sense of smell was strongly predictive of COVID-19 in the pre-Omicron era, but body malaise, sore throat, joint pain, and nasal discharge were predictive during the Omicron period.

Conclusions: SARS-CoV-2 increasingly shows seasonal annual patterns in coastal Kenya, with its clinical features resembling established endemic respiratory viruses. Its case burden is most pronounced in young adults. Locally dominant genetic variants may differ from those globally.

[This corrects the article DOI: 10.1093/ofid/ofaf368.].

Background: Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) is standard therapy for high-risk nonmuscle-invasive bladder cancer. However, M bovis infections can occur and are not well understood. We aimed to characterize clinical phenotypes, diagnosis, management, and outcomes of culture-confirmed M bovis BCG infections following intravesical therapy for urothelial carcinoma.

Methods: A retrospective single-center review of adults with culture-confirmed M bovis infection after intravesical BCG (May 2009-July 2024) was conducted, abstracting clinical, microbiologic, treatment, and outcome data.

Results: Twenty-two White male patients (median age, 77 years) were included; 8 (36.4%) had localized genitourinary infection, 6 (27.3%) had dissemination limited to blood, and 8 (36.4%) had dissemination to other organs. Patients with bloodstream-only infection presented acutely (median 1.5 days after last BCG), whereas those with localized or organ-disseminated disease presented months to years after BCG, with the longest diagnostic delays in organ-disseminated infection. Despite all cases had culture-proven M bovis BCG infection, acid-fast smear, Mycobacterium tuberculosis complex polymerase chain reaction, and histopathology had limited sensitivity. All isolates were susceptible to rifampin, isoniazid, and ethambutol; all were resistant to pyrazinamide. Median treatment duration exceeded 9 months, 94.7% achieved cure, and attributable mortality was 5.0% (1 vascular graft infection).

Conclusions: M bovis BCG infections following intravesical therapy have favorable outcomes but are often associated with diagnostic delays and prolonged treatment. Early suspicion, comprehensive diagnostic evaluation, and timely surgical source control when indicated are critical. Management strategies should be tailored based on the extent of disease dissemination and individual host factors.

Background: Staphylococcus aureus is the most common cause of skin and soft tissue infection (SSTI). Nasal S. aureus colonization may precede SSTI, and decolonization may decrease SSTI risk. However, many S. aureus-colonized persons are oropharyngeally colonized, sometimes without concomitant nasopharyngeal colonization. However, there are few data on oropharyngeal S. aureus decolonization, especially in children.

Methods: We performed a prospective, double-blind, randomized controlled clinical trial of twice-daily 0.12% chlorhexidine gluconate (CHG) gargle vs a placebo for 7 days in healthy children oropharyngeally colonized with S. aureus. At each study visit (days 1, 8, 29), throat and nares cultures were performed. All S. aureus isolates underwent spa typing.

Results: We screened 189 children, 120 (63%) of whom had S. aureus oropharyngeal colonization; of these, 67 (56%) were randomized. The median participant age was 11 years (mean, 11.7), and 27 (40%) were female. In the intention-to-treat population, oropharyngeal colonization at day 8 was 45% (15/33) and 79% (27/34) in the CHG and placebo groups, respectively (P = .004), and 61% (20/33) vs 85% (29/34) at day 29 (P = .03). Among children who were oropharyngeally decolonized at day 8 but positive for S. aureus at day 29, 8/12 (66%) exhibited a new spa type compared with baseline.

Conclusions: We found that a 7-day 0.12% chlorhexidine gluconate mouthwash regimen significantly reduced S. aureus oropharyngeal colonization compared with placebo. This difference persisted at day 29, suggesting that CHG mouthwash may be a promising adjunctive decolonization agent that may decrease the high SSTI recurrence risk in children.

Background: We assessed the diagnostic agreement of BioFire FilmArray multiplex polymerase chain reaction (PCR) with Seegene Allplex PCR for testing fecal samples collected during a diarrhea outbreak in resource-limited settings.

Methods: Fecal samples from consented British military personnel training in Kenya were collected without preservative and tested onsite with the FilmArray PCR platform. Anonymized corresponding samples frozen near the point of care were tested 16-18 months later in the United Kingdom using Seegene PCR (reference standard). We compared test sensitivity and specificity and assessed agreement using Cohen κ coefficients.

Results: Samples were analyzed from 60 individuals (80% male; median age [interquartile range], 24 [22-28] years). The overall pathogen detection rates did not differ significantly between FilmArray and Seegene PCR (55 of 60 [91.7%] vs 53 of 59 [89.8%], respectively [P > .9]). Campylobacter spp detection was significantly higher with Seegene (17 of 59 [28.8%] vs 6 of 60 [10%] for FilmArray PCR P = .03). The sensitivity of FilmArray PCR was moderate for Cryptosporidium spp (65% [95% confidence interval, 45.37%-80.77%]), and low for Campylobacter spp (35.3% [14.21%-61.67%%) and norovirus (7.14% [.18%-33.87%]). Its specificity was good to excellent for detection of Campylobacter spp, Cryptosporidium spp, enteroaggregative Escherichia coli, and sapovirus.

Conclusions: The study shows moderate concordance of FilmArray with Seegene PCR in the detection of 5 enteropathogens and poor to fair concordance for 7 others, but high-quality case-control studies are needed to assess agreement between these platforms. However, based on performance characteristics, including platform versatility and ease of use, and in the absence of a gold (reference) standard test, the FilmArray platform remains a suitable near-patient field-expedient platform for diarrhea diagnostics in resource-limited settings.

Background: Omadacycline, an aminomethylcycline tetracycline available orally and intravenously, is approved for the treatment of patients with acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia, some of whom have difficulty swallowing tablets. The objective of this study was to assess the stability and recovery of crushed omadacycline 150-mg tablets.

Methods: The recovery and stability of crushed omadacycline 150-mg tablets was assessed using 3 crushing methods (pill crusher, mortar/pestle, and sandwich bag method) and 3 dispersal products (water, vanilla syrup, or applesauce) over 24 hours at room temperature and administered via nasogastric tube. Omadacycline and its epimer (OMC-4-epimer) concentrations were assessed via liquid chromatography tandem mass spectrometry.

Results: There was no significant difference in recovery of omadacycline or OMC-4-epimer proportion based on crushing technique. There were significantly higher proportions of OMC-4-epimer in applesauce experiments than in water or vanilla syrup experiments, regardless of crushing methods. All experiments had significantly less recovery of omadacycline and increased proportions of OMC-4-epimer at 24 hours compared with earlier time points. There was no significant difference in recovery of omadacycline or OMC-4-epimer proportion using either type of nasogastric tube with omadacycline recovery above 91%.

Conclusions: The optimal method for recovery and stability of crushed omadacycline was to rinse the crushing device thoroughly into the collection container and disperse it into water, with consumption immediately or after no more than 4 hours. Vanilla syrup may be used as an alternative dispersal vehicle to be consumed immediately if used.