Open Forum Infectious Diseases最新文献

Background: We evaluated 1-year engagement in pre-exposure prophylaxis (PrEP) care and associated factors among gay, bisexual, and other men who have sex with men (GBMSM) in a large cohort of oral PrEP users in the Paris region, France.

Methods: We included in this analysis cisgender GBMSM enrolled in the ANRS PREVENIR cohort study from 3 May 2017 to 28 February 2019. We categorized 1-year PrEP engagement into 4 categories: high (consistent visits, attendance, and prescription refills at months 3, 6, 9, and 12), low (missed visits or no prescription refills), disengagement (PrEP discontinuation), and lost to follow-up. We used a logistic regression model to identify sociodemographic and behavioral factors associated with high engagement in PrEP care.

Results: Of 3211 participants, 2685 GBMSM were included in the analysis. At enrollment, participants had a median age of 36 years, with 88% born in Europe and 52.4% already undergoing PrEP. At month 12, 1612 (60.0%) participants met the high engagement definition, 438 (16.3%) exhibited low engagement, 459 (17.1%) disengaged from PrEP care, and 176 (6.6%) were lost to follow-up. In multivariable analysis, high engagement in PrEP care at 1 year was associated with older age (P < .001), being born in Europe (P = .01), having a higher education level (P = .05), already undergoing PrEP at enrollment (P < .001), having a bacterial sexually transmitted infection in the prior year (P = .01), earlier enrollment in the study (P = .04), and using PrEP daily or switching between PrEP regimens within the first year (P < .001).

Conclusions: Younger GBMSM, those born outside Europe, and those who were PrEP naive had lower engagement rates in the cohort, requiring tailored support.

Background: Risk of herpes zoster (HZ) infection increases with age and immunosuppression. We estimated the impact of HZ and post-herpetic neuralgia (PHN) on direct costs and health care resource utilization (HCRU) in patients ≥50 years, including those with comorbidities, as limited information exists in Italy.

Methods: This retrospective analysis used reimbursement data from local health authorities in Italy (January 2009-June 2022). Cases of HZ and PHN identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes and drug prescriptions were characterized and followed up for 1 year before and after the index date. The direct HCRU costs for patients with HZ/PHN were compared with those for patients without HZ/PHN.

Results: Of the total 193 259 patients with HZ/PHN identified (mean age, 61.6 years), 145 923 were ≥50 years old (immunocompromised: 29.9%; ≥1 chronic condition: 76.1%). During follow-up, 18.8% of patients ≥50 years of age with HZ progressed to PHN complications, and 3618 hospital admissions were reported (median length of stay, 9 days). Drug prescriptions and all-cause hospitalizations were the main contributors to total annual direct health care costs, estimated at M€272 for patients with HZ/PHN, whose burden increased with age. Higher health care costs were observed in patients with HZ/PHN vs patients without HZ/PHN. Moreover, average health care costs were up to 4× higher for patients with HZ and PHN compared with those without PHN.

Conclusions: HZ causes a significant economic impact on the health care system, driven mainly by high costs of medications and hospitalizations among older adults and those with comorbidities, particularly when complicated by PHN.

Background: Early antifungal initiation in invasive aspergillosis (IA) is recommended. Changing antifungals occurs for a myriad of reasons but associated costs are unclear.

Methods: US claims data for adults admitted for IA were identified from 10/1/2015 to 11/30/2022. Patients were stratified by those who did and did not change antifungal therapy. Adjusted all-cause healthcare utilization and costs/patient during index hospitalization and at 1, 6, and 12-months after the index date between the cohorts that did and did not change antifungal therapy were compared.

Results: Among 1,192 IA patients, 707 (59.3%) changed their initial antifungal therapy over follow-up. The index hospital length of stay was longer (Δ = 6 days, P < .001) and costs were higher (Δ = $65,149, P < .001) in the change vs. no change cohort. Median 1, 6, and 12-months all-cause costs were higher in patients changing antifungal therapy vs. not (Δ = $90,938-$192,953).

Conclusions: Changing antifungals was associated with longer hospital stays and costs and higher all-cause costs over 12-months.

Background: India has the highest global burden of human tuberculosis (TB) and the largest cattle herd with endemic bovine TB (bTB). However, the extent of cross-species transmission and the zoonotic spillover risk, including drug-resistant Mycobacterium tuberculosis complex (MTBC) strains circulating in cattle, remain uncharacterized.

Methods: To address this major knowledge gap, we investigated tissue samples from 500 apparently healthy cattle at a slaughterhouse in Chennai, India. Whole genome sequencing was performed to characterize the isolates.

Results: Sixteen animals (32 per 1000 [95% confidence interval, 16-47]) were MTBC-positive, a rate that is nearly an order of magnitude greater than the reported human TB incidence in the region. Thirteen isolates were identified as Mycobacterium orygis and 3 were M tuberculosis: 1 was a mixed infection of M tuberculosis lineage 1 and M orygis, and the other 2 had pure growth of M tuberculosis lineage 2, in both cases pre-extensively drug-resistant (pre-XDR) with identical resistance patterns and separated by 7 single-nucleotide polymorphisms. The results confirm that bTB in this region is primarily due to M orygis and M tuberculosis, and not Mycobacterium bovis.

Conclusions: The detection of pre-XDR M tuberculosis in cattle highlights a potential public health concern, since controlling human TB alone may be insufficient without addressing bovine TB. Overall, our findings underscore an urgent need for targeted interventions to mitigate zoonotic tuberculosis transmission in regions where bTB is endemic.

Background: Data on mRNA-1273 (Moderna) vaccine effectiveness (VE) in children aged 6 months to 5 years are limited. The objectives of this study were to assess mRNA-1273 vaccine effectiveness against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19)-related hospitalization among children aged 6 months to 5 years during the initial 5 months of the vaccination campaign rollout, as well as to determine whether VE varied by age group (6 months to <2 years vs 2 to 5 years).

Methods: We used a test-negative study with linked health administrative data in Ontario, Canada, to evaluate vaccine effectiveness of mRNA-1273 against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization from July 28 to December 31, 2022. Participants included symptomatic children aged 6 months to 5 years who were tested by real-time polymerase chain reaction. The primary outcome was symptomatic infection, and the secondary outcome was COVID-19-related hospitalization.

Results: We included 572 test-positive cases and 3467 test-negative controls. Receipt of mRNA-1273 was associated with reduced symptomatic SARS-CoV-2 infection (VE, 90%; 95% CI, 53%-99%) and COVID-19-related hospitalization (VE, 82%; 95% CI, 4%-99%) ≥7 days after the second dose. We were unable to detect heterogeneity in VE across age groups.

Conclusions: Our findings suggest that mRNA-1273 vaccine effectiveness was initially strong against symptomatic SARS-CoV-2 infection and hospitalization in children aged 6 months to 5 years. Further research is needed to understand long-term effectiveness.

Among 3127 episodes of suspected infective endocarditis, the 2023 Duke-International Society for Cardiovascular Infectious Diseases clinical criteria showed an accuracy of 90% for infective endocarditis diagnosis. A new heart murmur was present in 690 (22%) episodes. Excluding imaging and surgical findings decreased the accuracy to 73%, while using the physical examination criterion slightly improved the accuracy to 78%.

Background: The global resurgence of disseminated tuberculosis (TB) after the coronavirus disease 2019 pandemic highlights the necessity of understanding host risk factors, especially in adults without human immunodeficiency virus.

Methods: We reviewed TB cases admitted to Shanghai Public Health Clinical Center from 2017 to 2022. We analyzed baseline characteristics and outcomes. To identify risk factors for disseminated TB, as well as its subsite distribution and mortality, we employed logistic regression and Cox proportional hazards models.

Results: Among 1062 patients, including 283 with disseminated TB, 558 with pulmonary TB (PTB), and 221 with extrapulmonary TB, those with disseminated TB had the highest mortality rate. The following factors were associated with disseminated TB: age ≥45 years, body mass index (BMI) <18.5 kg/m², immunosuppressive therapy, and end-stage renal disease (ESRD). A BMI <18.5 kg/m² was found to correlate with all subsites of disseminated TB, while aged ≥45 years specifically increased incidence of bone and joint TB. Female patients showed a higher risk for lymphatic, peritoneal, and intestinal TB. Additionally, immunosuppressive therapy and ESRD were linked to various TB subsites. During a 12-month follow-up period, 19.8% of patients with disseminated TB died. Factors contributing to reduced survival included BMI <18.5 kg/m², immunosuppressive therapy, ESRD, pulmonary cavities, and meningeal involvement.

Conclusions: Age, low BMI, immunosuppressive therapy, and ESRD are significant risk factors for disseminated TB and also significantly impact patient survival rates. These findings are of great importance for the development of clinical management and preventive measures.

Background: Melioidosis is a multisystem infectious disease caused by the environmental bacterium Burkholderia pseudomallei. Osteomyelitis (OM) and septic arthritis (SA) are uncommon primary presentations for melioidosis but important secondary foci, often requiring prolonged therapy and multiple surgeries. We characterized the epidemiology, presentation, treatment, and outcomes of patients from 24 years of the Darwin Prospective Melioidosis Study (DPMS).

Methods: DPMS patients from October 1, 1999, until September 30, 2023, were included if they had a primary or secondary diagnosis of OM or SA. Epidemiological, risk factor, clinical, and outcome data were retrieved from the DPMS database. Antibiotic and surgical data were collated from patient records.

Results: From 1129 consecutive patients with culture-confirmed melioidosis, 122 (10.8%) had OM and/or SA, with 115 evaluable. Ninety-four of 1129 (8.3%) had OM, and 62/1129 (5.5%) had SA, with 41/115 (35.7%) of these having both OM and SA. Many combined infections involved contiguous bone and joints or soft tissue. Fifty-nine (51.3%) were male, and only 4.3% were ≤16 years old. Diabetes mellitus was present in 69.6%, and only 12.2% had no identifiable clinical risk factor. There were 8 deaths (7.0%) and 20 (17.4%) recurrent infections. Seventy-one (61.7%) had operative management, with combined infection associated with more procedures and longer length of stay.

Conclusions: The current paradigm of care for osteoarticular melioidosis involves prolonged intravenous antibiotics in conjunction with timely and complete operative management, and in our setting where these are available, outcomes are good. In many melioidosis-endemic regions these resources are limited, and mortality remains high.

Background: Human norovirus (HuNoV) is a major cause of enteric infectious gastroenteritis and is classified into several genotypes based on its capsid protein amino acid sequence and nucleotide sequence of the polymerase gene. Among these, GII.4 is the major genotype worldwide. Epidemiological studies have highlighted the prevalence of GII.2. Although recent advances using human tissue- and induced pluripotent stem cell (iPSC)-derived intestinal epithelial cells (IECs) have enabled in vitro replication of multiple HuNoV genotypes, GII.2 HuNoV could replicate only in tissue-derived IECs and not in iPSC-derived IECs.

Methods: We investigated the factors influencing GII.2 HuNoV replication in IECs, focusing on histo-blood group antigens. We also assessed the immunogenicity of GII.2 virus-like particles (VLPs) and their ability to induce neutralizing antibodies. Antibody cross-reactivity was tested to determine whether GII.2 VLPs could neutralize other HuNoV genotypes, including GII.4, GII.3, GII.6, and GII.17.

Results: Our findings indicated that GII.2 HuNoV replication in vitro requires the presence of both H and B antigens. Moreover, GII.2 VLPs generated neutralizing antibodies effective against both GII.2 and GII.4 but not against GII.3, GII.6, or GII.17. Comparatively, GII.2 and GII.17 VLPs induced broader neutralizing responses than GII.4 VLPs.

Conclusions: The findings of this study suggests that GII.2 and GII.17 VLPs may be advantageous as HuNoV vaccine candidates because they elicit neutralizing antibodies against the predominant GII.4 genotype, which could be particularly beneficial for infants without prior HuNoV exposure. These insights will contribute to the development of effective HuNoV vaccines.

[This retracts the article DOI: 10.1093/ofid/ofae647.].