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Abstract Background After months of few mpox cases, an increased number of cases were reported in Chicago during May 2023; predominantly among fully vaccinated patients. We investigated the outbreak scope, differences between vaccinated and unvaccinated patients, and hypotheses for monkeypox virus (MPXV) infection after vaccination.Methods We interviewed patients and reviewed medical records to assess demographic, behavioral, and clinical characteristics, mpox vaccine status, and vaccine administration routes. We evaluated serum antibody levels after infection and compared patient viral genomes with MPXV sequences in available databases. We discussed potential vaccine compromise with partners who manufactured, handled, and administered vaccine associated with breakthrough infections.Results During March 18–June 27, 2023, we identified 49 mpox cases; 57% of these mpox patients were fully vaccinated (FV). FV patients received both JYNNEOS doses subcutaneously (57%), intradermally (7%), or via heterologous administration (36%). FV patients had more median sex partners (3, IQR=1-4) versus not fully vaccinated (NFV) patients (1, IQR=1-2). Thirty-six of 37 sequenced specimens belonged to lineage B.1.20 of clade IIb MPXV, which did not demonstrate any amino acid changes relative to B.1, the predominant lineage from May 2022. Vaccinated patients demonstrated expected humoral antibody responses; none were hospitalized. No vaccine storage excursions were identified. Approximately 63% of people at risk for mpox in Chicago were FV during this period.Conclusions Our investigation indicated cases were likely due to frequent behaviors associated with mpox transmission, even with relatively high vaccine effectiveness and vaccine coverage. Cases after vaccination might occur in similar populations.

Abstract Background Research on influenza burden in adults has focused on crude subgroups with cut-points at 65-years, limiting insight into how burden varies with increasing age. This study describes the incidence of influenza-related outpatient visits, emergency room (ER) visits, and hospitalizations, along with healthcare resource use and complications in the aging adult population.Methods Individuals ≥18 years of age in the United States were evaluated retrospectively in five seasonal cohorts (2015–2020 seasons) in strata of age with 5-year increments. Person-level electronic medical records linked to pharmacy and medical claims were used to ascertain patient characteristics and outcomes. Influenza-related medical encounters were identified based on diagnostic codes (ICD-10 codes J09*–J11*).Results Incidence of influenza-related outpatient visits was highest among people aged 18–34 years and declined with increasing age. For ER visits, incidence tended to be elevated for people aged 18–34 years, relatively stable from 35 through 60, and increased rapidly after 60. Hospitalization incidence remained relatively stable until about 50 years of age and then increased with age. One in three patients was diagnosed with pneumonia after hospitalization, regardless of age. Across seasons, age groups, and clinical settings, on average, 40.8% of individuals were prescribed antivirals and 17.2% antibiotics.Conclusions Incidence of influenza-related hospitalizations begins to increase around age 50 rather than the more common cut-point of 65, whereas incidence of outpatient visits was highest among younger adults. Influenza infections frequently led to antiviral and antibiotic prescriptions, underscoring the role influenza vaccination can play in combating antimicrobial resistance.

Abstract Background Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months’ treatment in patients with NTM-PD.Methods The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life–Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months’ treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains.Results Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7–86.7) and 81.5 (70.4–92.6), respectively. Among 228 patients who completed the QOL-B after 6 months’ treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91–0.96) and respiratory symptoms (0.92; 0.89–0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28–1.39) or respiratory symptoms (1.30; 0.62–2.74).Conclusions After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion.Clinical Trials Registration ClinicalTrials.gov identifier: NCT03934034.

Abstract Prior infection with SARS-CoV-2 is typically measured by nucleocapsid serology assays. In this study, we show that the Simoa serology assays and T cell intracellular cytokine staining assays are more sensitive than the clinical Elecsys assay for detection of nucleocapsid-specific immune responses. These data suggest that the prevalence of prior SARS-CoV-2 infection in the population may be higher than currently appreciated.

Abstract We studied the association of mitochondrial DNA (mtDNA) haplogroups with weight and body mass index (BMI) gain at 96 weeks in 1,019 treatment-naïve persons with HIV (PWH) who initiated first-line antiretroviral therapy (ART) since 2014. The mean increase in weight and BMI over the study period was 2.90 Kg and 0.98 Kg/m2, respectively. We found a significant adjusted association between the major UK mtDNA haplogroup and lower weight and BMI increase at 96 weeks after ART initiation. Our findings reveal a potential role for mitochondrial genetics in the complex phenomenon of weight gain after initial ART in PWH.

Abstract Diabetes is more common among people living with HIV (PLWH), as compared with healthy individuals. In a prospective multicenter study (N = 248), we identified normoglycemic (48.7%), prediabetic (44.4%) and diabetic (6.9%) PLWH. HbA1c and fasting blood glucose (FBG) sensitivity in defining dysglycemia was 96.8%, while addition of oral glucose tolerance test led to reclassification of only 4 patients. Inclusion of 93 additional PLWH with known DM enabled identification of multiple independent predictors of dysglycemia or diabetes: older age, higher BMI, Ethiopian origin, HIV duration, lower integrase inhibitor exposure and advanced disease at diagnosis. Shotgun metagenomic microbiome analysis revealed 4 species that were significantly expanded with hyperglycemia/hyperinsulinemia, and 2 species that were differentially more prevalent in prediabetic/diabetic PLWH. Collectively, we uncover multiple potential host and microbiome predictors of altered glycemic status in PLWH, while demonstrating that FBG and HbA1C likely suffice for diabetes screening. These potential diabetic predictors merit future prospective validation.

ObjectivesDelivery of virtual care increased throughout the COVID-19 pandemic and persisted after physical distancing measures ended. However, little is known about how to measure the quality of virtual care, as current measures focus on in-person care and may not apply to a virtual context. This scoping review aims to understand the connections between virtual care modalities used with ambulatory patient populations and quality measures across the Quintuple Aim (provider experience, patient experience, per capita cost, population health and health equity). DesignVirtual care was considered any interaction between patients and/or their circle of care occurring remotely using any form of information technology. Five databases (MEDLINE, Embase, PsycInfo, Cochrane Library, JBI) and grey literature sources (11 websites, 3 search engines) were searched from 2015 to June 2021 and again in August 2022 for publications that analysed virtual care in ambulatory settings. Indicators were extracted, double-coded into the Quintuple Aim framework; patient and provider experience indicators were further categorised based on the National Academy of Medicine quality framework (safety, effectiveness, patient-centredness, timeliness, efficiency and equity). Sustainability was added to capture the potential for continued use of virtual care. Results13 504 citations were double-screened resulting in 631 full-text articles, 66 of which were included. Common modalities included video or audio visits (n=43), remote monitoring (n=11) and mobile applications (n=11). The most common quality indicators were related to patient experience (n=58 articles), followed by provider experience (n=25 articles), population health outcomes (n=23 articles) and health system costs (n=19 articles). ConclusionsThe connections between virtual care modalities and quality domains identified here can inform clinicians, administrators and other decision-makers how to monitor the quality of virtual care and provide insights into gaps in current quality measures. The next steps include the development of a balanced scorecard of virtual care quality indicators for ambulatory settings to inform quality improvement. …

IntroductionChronic inflammation plays a key role in knee osteoarthritis pathophysiology and increases risk of comorbidities, yet most interventions do not typically target inflammation. Our study will investigate if an anti-inflammatory dietary programme is superior to a standard care low-fat dietary programme for improving knee pain, function and quality-of-life in people with knee osteoarthritis. Methods and analysisThe eFEct of an Anti-inflammatory diet for knee oSTeoarthritis study is a parallel-group, assessor-blinded, superiority randomised controlled trial. Following baseline assessment, 144 participants aged 45–85 years with symptomatic knee osteoarthritis will be randomly allocated to one of two treatment groups (1:1 ratio). Participants randomised to the anti-inflammatory dietary programme will receive six dietary consultations over 12 weeks (two in-person and four phone/videoconference) and additional educational and behaviour change resources. The consultations and resources emphasise nutrient-dense minimally processed anti-inflammatory foods and discourage proinflammatory processed foods. Participants randomised to the standard care low-fat dietary programme will receive three dietary consultations over 12 weeks (two in-person and one phone/videoconference) consisting of healthy eating advice and education based on the Australian Dietary Guidelines, reflecting usual care in Australia. Adherence will be assessed with 3-day food diaries. Outcomes are assessed at 12 weeks and 6 months. The primary outcome will be change from baseline to 12 weeks in the mean score on four Knee injury and Osteoarthritis Outcome Score (KOOS4) subscales: knee pain, symptoms, function in daily activities and knee-related quality of life. Secondary outcomes include change in individual KOOS subscale scores, patient-perceived improvement, health-related quality of life, body mass and composition using dual-energy X-ray absorptiometry, inflammatory (high-sensitivity C reactive protein, interleukins, tumour necrosis factor-α) and metabolic blood biomarkers (glucose, glycated haemoglobin (HbA1c), insulin, liver function, lipids), lower-limb function and physical activity. Ethics and disseminationThe study has received ethics approval from La Trobe University Human Ethics Committee. Results will be presented in peer-reviewed journals and at international conferences. Trial registration numberACTRN12622000440729. …

ObjectivesThe impact of the COVID-19 pandemic on adolescent’s mental health and relationships has received growing attention, yet the challenges and support needs of adolescents living in existing deprivation are not well understood. The current qualitative study, part of a broader project cocreating mental health and life-skill workshops with young people, documents adolescents’ lived experience and support needs 4 years on from the COVID-19 pandemic. Design20 semi-structured interviews and 6 focus groups were transcribed and thematically analysed in NVivo V.12 to inform codesigned workshops to support adolescents’ needs. SettingIslington borough in North London, United Kingdom. Participants20 adolescents aged 14–25 years (mean=18.3; 60% female, 60% white) from Islington with a history of difficulties (eg, mental health, deprivation, court order) were referred by Islington local authority teams to our study. ResultsThematic analyses revealed eight themes on adolescents’ COVID-19 experiences and five associated suggestions on ‘support needs’: health challenges and support; relationships and support; routines and support; educational challenges and learning support; inequality and support; distrust; loss of opportunities and grief. ConclusionsIn our qualitative study, adolescents spoke of positive reflections, challenges, and need for support 4 years on from the COVID-19 pandemic. Many adolescents shared their lived experiences for the first time with someone else and wished they would have the space and time to acknowledge this period of loss. Adolescents living with existing inequality and deprivation before the pandemic have reported sustained and exacerbated impacts during the pandemic, hence coproduced support for adolescents should be a priority. …

Abstract Background Human papillomavirus (HPV) is a common sexually transmitted infection and the leading cause of cervical cancer. The HPV vaccine is a safe and effective way to prevent HPV infection. In Zambia, the vaccine is given during Child Health Week to girls aged 14 years who are in and out of school in two doses over two years. The focus of this evaluation was to establish the cost to administer a single dose of the vaccine as well as for full immunisation of two doses. Methods This work was part of a broader study on assessing HPV programme implementation in Zambia. For HPV costing aspect of the study, with a healthcare provider perspective and reference year of 2020, both top-down and micro-costing approaches were used for financial costing, depending on the cost data source, and economic costs were gathered as secondary data from Expanded Programme for Immunisation Costing and Financing Project (EPIC), except human resource costs which were gathered as primary data using existing Ministry of Health salary scales and reported time spent by different health cadres on activities related to HPV vaccination. Data was collected from eight districts in four provinces, mainly using a structured questionnaire, document reviews and key informant interviews with staff at national, provincial, district and health facility levels. Administrative coverage rates were obtained for each district. Results Findings show that schools made up 53.3% of vaccination sites, community outreach sites 30.9% and finally health facilities 15.8%. In terms of coverage for 2020, for the eight districts sampled, schools had the highest coverage at 96.0%. Community outreach sites were at 6.0% of the coverage and health facilities accounted for only 1.0% of the coverage. School based delivery had the lowest economic cost at USD13.2 per dose and USD 28.1 per fully immunised child (FIC). Overall financial costs for school based delivery were US$6.0 per dose and US$12.4 per FIC. Overall economic costs taking all delivery models into account were US$23.0 per dose and US$47.6 per FIC. The main financial cost drivers were microplanning, supplies, service delivery/outreach and vaccine co-financing; while the main economic cost drivers were human resources, building overhead and vehicles. Nurses, environmental health technicians and community-based volunteers spent the most time on HPV related vaccination activities compared to other cadres and represented the greatest human resource costs. Conclusions The financial cost of HPV vaccination in Zambia aligns favourably with similar studies conducted in other countries. However, the economic costs appear significantly higher than those observed in most international studies. This discrepancy underscores the substantial strain placed on healthcare resources by the program, a burden that often remains obscured. While the vaccine costs are currently subsidized through the generous support of Gavi, the Vaccine Alliance, it’s crucial to recognize that these expenses pose a considerable threat to long-term sustainability. Consequently, countries such as Zambia must proactively devise strategies to address this challenge. …

Abstract Background Blood transfusion is associated with exposure to blood Transfusion Transmissible Infection (TTIs). The threat posed by the blood-borne pathogens is disproportionately distributed in different healthcare facilities in Cameroon. Thus, there is a need for continuous surveillance of TTIs in the country. This study aimed to assess the screening procedure for blood transfusion and determine the trend in immunological markers of TTIs among blood donors at the Mamfe District Hospital. Methods A prospective descriptive, cross-sectional and analytical study was conducted at Mamfe District Hospital from March to May 2022. A total of 165 blood donors were recruited by the consecutive sampling method. Donors were screened using both Rapid diagnostic tests,T. pallidum haemagglutination test and indirect enzyme-linked immunosorbent assay (ELISA) for the detection of TTIs. Data generated was entered into an Excel spreadsheet and analysed using the statistical software R, version 4.2.0. Statistical analysis included descriptive statistics of percentages, means ± standard deviation, and student t-test was used to compare both diagnostic techniques, and was considered significant when p 

Abstract Background There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory. Methods BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student’s t-test. Results The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation. Conclusions Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells. …

Abstract Background Non-sputum-based tests are needed to predict or diagnose tuberculosis (TB) disease in people living with HIV (PWH). The enzyme indoleamine 2, 3-dioxygenase-1 (IDO1) is expressed in tuberculoid granuloma and catabolizes tryptophan (Trp) to kynurenine (Kyn). IDO1 activity compromises innate and adaptive immune responses, promoting mycobacterial survival. The plasma Kyn-to-Trp (K/T) ratio is a potential TB diagnostic and/or predictive biomarker in PWH on long-term antiretroviral therapy (ART). Methods We compared plasma K/T ratios in samples from PWH, who were followed up prospectively and developed TB disease after ART initiation. Controls were matched for age and duration of ART. Kyn and Trp were measured at 3 timepoints; at TB diagnosis, 6 months before TB diagnosis and 6 months after TB diagnosis, using ultra performance liquid chromatography combined with mass spectrometry. Results The K/T ratios were higher for patients with TB disease at time of diagnosis (median, 0.086; IQR, 0.069–0.123) compared to controls (0.055; IQR 0.045–0.064; p = 0.006), but not before or after TB diagnosis. K/T ratios significantly declined after successful TB treatment, but increased upon treatment failure. The K/T ratios showed a parabolic correlation with CD4 cell counts in participants with TB (p = 0.005), but there was no correlation in controls. Conclusions The plasma K/T ratio helped identify TB disease and may serve as an adjunctive biomarker for for monitoring TB treatment in PWH. Validation studies to ascertain these findings and evaluate the optimum cut-off for diagnosis of TB disease in PWH should be undertaken in well-designed prospective cohorts. Trial registration ClinicalTrials.gov Identifier: NCT00411983. …

Abstract Objective Healthcare-associated Gram-negative bacterial meningitis is a substantial clinical issue with poor outcomes, especially for neurosurgical patients. Here, we aimed to study the characteristics and treatment options of patients with healthcare-associated carbapenem-non-susceptible (Carba-NS) Gram-negative bacterial meningitis. Methods This observational cohort study was conducted at a teaching hospital from 2004 to 2019. The clinical characteristics of patients with meningitis with Carba-NS and carbapenem-susceptible (Carba-S) bacilli were compared, and the antimicrobial chemotherapy regimens and outcomes for Carba-NS Gram-negative bacterial meningitis were analyzed. Results A total of 505 patients were included, of whom 83.8% were post-neurosurgical patients. The most common isolates were Acinetobacter spp. and Klebsiella spp., which had meropenem-resistance rates of 50.6% and 42.5%, respectively, and showed a markedly growing carbapenem-resistance trend. Kaplan–Meier curve analysis revealed that Carba-NS Gram-negative bacilli were associated with a significantly higher in-hospital mortality rate (18.8%, 35/186) compared to the Carba-S group (7.4%, 9/122; P = 0.001). For Carba-NS Enterobacterales meningitis, aminoglycoside-based and trimethoprim-sulfamethoxazole-based regimens yielded significantly higher clinical efficacy rates than non-aminoglycoside-based and non-trimethoprim-sulfamethoxazole-based regimens (69.0% vs. 38.7%, P = 0.019 and 81.8% vs. 46.9%, P = 0.036, respectively). For Carba-NS A. baumannii complex meningitis, tetracycline-based (including doxycycline, minocycline, or tigecycline) therapy achieved a significantly higher clinical efficacy rate (62.9%, 22/35) than the non-tetracycline-based therapy group (40.4%, 19/47; P = 0.044). Conclusions Our findings revealed that Carba-NS Gram-negative bacilli are associated with higher in-hospital mortality in patients with healthcare-associated meningitis. The combination therapies involving particular old antibiotics may improve patients’ outcome. Trial registration This study was registered on the Chinese Clinical Trial Register under ChiCTR2000036572 (08/2020). …

Abstract Background Street foods are any foods or drinks prepared or sold by street vendors in an open space. The purpose of this study was to determine the Bacteriological safety and antibiotic resistance patterns of Staphylococcus aureus and Enterobacteriaceae isolated from street foods. Method A laboratory-based cross-sectional study was used from December 2022 to February 2023 on street foods of Addis Ababa, Hawassa, Dire Dawa, and Jimma towns of Ethiopia. 525 street foods and 175 water samples were taken from 175 street food vending stalls. Proportional allocation to the total town population and stratified sampling techniques were used to select vending stalls. Samples were analyzed for the presence of bacteria following the standard microbiological methods used for the isolation, enumeration, and identification of bacteria. Pour plate technique was used to transfer the suspension to MacConkey agar, Mannitol Salt Agar, and Salmonella Shigella Agar. The antibiotic susceptibility test was performed using the Kirby-Bauer disk diffusion method. SPSS software was used to analyze the data. Result Out of 525 food samples, 279 (53%) were contaminated by bacteria. From 175 water samples, 95 (54.3%) were contaminated with Escherichia coli. From both samples in total, eleven bacterial species were isolated. Staphylococcus aureus was the most frequently isolated species. Shigella, Klebsiella, and Salmonella group A have statistically significant with the type of food. Erythromycin (54%), Streptomycin (17%), and Amoxicillin (14%) were the most resistant antibiotics. Least resistance was observed to Ciprofloxacin (5%). Conclusion Street foods of the selected towns were highly contaminated with various antibiotic-resistant organisms. Hence, the relevant authorities ought to ensure the proper handling of street food by enforcing safety measures. Additionally, they should initiate a widespread awareness campaign promoting the prudent use of antibiotics among both street food vendors and the broader population. …

Abstract Background HIV self-testing (HIVST) can use either oral-fluid or blood-based tests. Studies have shown strong preferences for self-testing compared to facility-based services. Despite availability of low-cost blood-based HIVST options, to date, HIVST implementation in sub-Saharan Africa has largely been oral-fluid-based. We investigated whether users preferred blood-based (i.e. using blood sample derived from a finger prick) or oral fluid-based HIVST in rural and urban Malawi. Methods At clinics providing HIV testing services (n = 2 urban; n = 2 rural), participants completed a semi-structured questionnaire capturing sociodemographic data before choosing to test using oral-fluid-based HVST, blood-based HIVST or provider-delivered testing. They also completed a self-administered questionnaire afterwards, followed by a confirmatory test using the national algorithm then appropriate referral. We used simple and multivariable logistic regression to identify factors associated with preference for oral-fluid or blood-based HIVST. Results July to October 2018, N = 691 participants enrolled in this study. Given the choice, 98.4% (680/691) selected HIVST over provider-delivered testing. Of 680 opting for HIVST, 416 (61.2%) chose oral-fluid-based HIVST, 264 (38.8%) chose blood-based HIVST and 99.1% (674/680) reported their results appropriately. Self-testers who opted for blood-based HIVST were more likely to be male (50.3% men vs. 29.6% women, p 

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