69832 research outputs found
Sort by
Parental involvement in infection prevention and control in low- and middle-income country neonatal units: a scoping review.
Get PDFOBJECTIVE: To review the literature on caregiver involvement in infection prevention and control in low- and middle-income country (LMIC) neonatal units (NNUs).
INTRODUCTION: There is a high burden and mortality of neonatal infections globally, with most of the burden falling on LMIC. Healthcare-associated infections (HCAIs) are a particular challenge, with neonatal sepsis being one of the most common HCAIs. It is urgent to prevent infections, as both identification and treatment of neonatal sepsis are increasingly difficult in these contexts. Parents are consistently present on NNUs but their involvement in infection prevention and control (IPC) has been underexplored.
INCLUSION CRITERIA: Included studies were carried out in LMIC NNUs and reported on caregivers' involvement in design, implementation or experience of IPC interventions. METHODS: Five databases were searched in four languages and were screened by two authors. Reference searching was carried out of included papers. Data were analysed by each sub-question; caregiver involvement in intervention design (descriptive analysis), caregiver involvement in IPC delivery (quantitative analysis) and caregiver experience of hygiene and care (thematic analysis).
RESULTS: 38 studies were included. Caregiver involvement in IPC design was limited, with examples from four papers. 30 papers contained information about caregiver delivery of IPC interventions. Most activities were related to being educated on IPC, carrying out core IPC activities or providing a specific aspect of an intervention (most frequently Kangaroo Mother Care). 10 papers discussed caregiver experience of NNU hygiene including ethnographic accounts from Ghana, Malawi, Mexico, India and Brazil. Across all contexts hierarchical social structures and challenging communication between healthcare professionals and families was a barrier to effective IPC within NNUs. Families showed a good understanding of core IPC practices and an awareness of contextual challenges of IPC.
CONCLUSION: Caregiver involvement in IPC is limited to date. However, interventions such as Kangaroo Mother Care indicate the benefits that can be achieved. Hierarchical structures and communication challenges between healthcare professionals and families are a barrier to inclusion at present and must be addressed in any designed intervention
Genomic insights into pyrazinamide and fluoroquinolone resistance in multidrug-resistant tuberculosis in Khyber Pakhtunkhwa, Pakistan.
Get PDFBACKGROUND: Tuberculosis (TB), caused by bacteria of the Mycobacterium tuberculosis complex (MTBC), remains a global health challenge, exacerbated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains.
OBJECTIVES: This study employs whole-genome sequencing (WGS) to characterise genetic mutations associated with pyrazinamide (PZA) and fluoroquinolone (FQ) resistance in MDR-TB isolates from KPK.
METHODOLOGY: MDR and pre-XDR TB samples were collected and processed at the Provincial Tuberculosis Reference Laboratory under Biosafety Level III conditions. Samples underwent microscopy, GeneXpert MTB/RIF assay, culture, and drug susceptibility testing. DNA was extracted from positive cultures and subjected to WGS. Bioinformatics tools were used to analyse sequencing data, identify resistance-associated mutations, and assess genetic diversity among isolates.
RESULTS: Out of the 78 MTBC isolates analysed, 67 (85.9 %) were identified as MDR-TB, with 48 categorized as pre-XDR, while 11 were drug-susceptible. The isolates predominantly came from young patients (mean age: 29.5 years, SD ±12.64), with a higher proportion of female patients (61.53 %). Mutations in the pncA gene, associated with PZA resistance, were identified in 51 isolates. Resistance to fluoroquinolones was linked to mutations in the gyrA and gyrB genes in 48 isolates. WGS confirmed PZA resistance in 51 isolates, 39 (76.47 %) of which also exhibited FQ resistance.
CONCLUSION: Phylogenetic analysis revealed that Lineage 3 (L3) was predominant (58.97 %), followed by L4, L2, and L1 strains. The clustering of drug-resistant strains within L3 suggests ongoing localized transmission. These findings underscore the urgent need for targeted interventions, including enhanced molecular surveillance and tailored treatment strategies, to combat MDR-TB in KPK
Association between critical care occupancy and code status decisions during resource scarcity: a retrospective cohort study.
Get PDFBACKGROUND: Code status determination typically relies on the expected benefits and harms of treatment intensification and patient values and preferences. Resource availability may also influence code status decisions. During the COVID-19 pandemic, the demand for critical care often exceeded the available resources. This study investigated the association between critical care occupancy and code status decisions during the COVID-19 pandemic.
METHODS: We conducted a retrospective cohort study of adult patients hospitalized at Geneva University Hospital for acute COVID-19-related illness during two successive pandemic waves, in spring and autumn 2020. Multivariable logistic regression was used to analyze the association between critical care occupancy at admission and code status attribution while accounting for clinical and demographic characteristics, including age, sex, ROX index (pulse oximetry/fraction of inspired oxygen/respiratory rate), comorbidities, malignancy, nationality, insurance, and socioeconomic status.
RESULTS: A total of 2,122 patients were included in the analysis. Higher critical care occupancy was associated with an increased likelihood of being assigned an intensive care unit (ICU)-ineligible code status. The odds ratios (ORs) were 1.61 (95% CI 1.11-2.32), 1.59 (1.11-2.28) and 1.71 (1.06-2.76) for critical care occupancy levels of 100-119%, 120-139% and ≥ 140%, respectively, compared with the prepandemic baseline capacity. Other factors significantly associated with the assignment of an ICU-ineligible code status included age 70-79 years (OR 8.56; 95% CI 4.12-17.77), 80-89 years (OR 32.78; 95% CI 16.16-66.50) and ≥90 years (OR 49.04; 95% CI 23.05-104.31) and a higher comorbidity index (OR 1.22; 95% CI 1.07-1.39). Conversely, complementary hospitalization insurance was associated with lower odds of being assigned an ICU-ineligible code status (OR 0.52; 95% CI 0.29-0.92).
CONCLUSIONS: Our study revealed a positive association between critical care occupancy and ICU-ineligible code status, suggesting the presence of implicit triaging during periods of high resource strain. This raises several ethical concerns, including the use of non-consensual triage criteria, lack of transparency and the risk of moral distress for healthcare professionals
Pneumococcal carriage prevalence, serotype distribution, and vaccine coverage in Ethiopia 12 years after pneumococcal vaccine introduction.
Get PDFINTRODUCTION: Ethiopia introduced the 10-valent pneumococcal conjugate vaccine (PCV10, GlaxoSmithKline plc.) in 2011 and switched to 13-valent vaccine (PCV13, Pfizer Inc.) in 2020. In 2023, we conducted a study in four settings in Ethiopia to determine the vaccine coverage, residual vaccine-type carriage prevalence, serotype distribution, and factors associated with carriage across all age groups.
METHODS: A cross-sectional survey was conducted in urban and rural areas of eastern and southwest Ethiopia in 2023. In total, 50 participants in each of 10 age groups (<1, 1-2, 3-4, 5-9, 10-14, 15-19, 20-39, 40-49, 50-59, and ≥ 60 years) were randomly selected using population registers in Harar, Kersa and Gilgel Gibe demographic surveillance systems, and using random GPS points for Jimma city. After informed consent, data on socioeconomic characteristics and vaccine coverage were collected. A single nasopharyngeal swab was collected and cultured for pneumococci. Pneumococci were serotyped using latex agglutination and confirmatory Quellung reaction.
RESULTS: A total of 2006 participants were enrolled. The age-standardized population prevalence of pneumococcal carriage (all serotypes) in rural settings was 56 % (95 %CI 48-64 %) in the east and 26 % (95 %CI 20-31 %) in the southwest, and in urban settings, 15 % (95 %CI 11-20 %) in the east and 16 % (95 %CI 12-19 %) in the southwest. PCV13 serotype carriage prevalence among children aged <5 years ranged from 7.4 to 9.3 % in the urban areas, to 16-22 % in the rural areas. Coverage of the third dose of PCV, recorded in vaccination cards of participants aged <5 years, was 49 %-87 % in the urban areas; it was much lower at 13-22 % in the rural areas.
CONCLUSIONS: There is considerable residual circulation of vaccine serotypes in Ethiopia, particularly in rural areas and the east, and low vaccine coverage. Pneumococcal epidemiology varies by geographical region and urban/rural setting, implying an unequal burden of pneumococcal disease across the country 12 years post-PCV introduction
Postpartum hemorrhage after SARS-CoV-2 infection in pregnancy: A Scandinavian register-based cohort study.
Get PDFINTRODUCTION: The aim was to evaluate whether SARS-CoV-2 infection during pregnancy was associated with severe postpartum hemorrhage (PPH), as SARS-CoV-2 infection has been shown to affect the coagulation system. MATERIAL AND METHODS: In this national register-based cohort study in Sweden, Denmark, and Norway, we studied the association between severe PPH according to a registered positive test for SARS-CoV-2 during pregnancy between March 1, 2020 and March 31, 2023 using logistic regression analyses to estimate odds ratios (ORs) with 95% confidence intervals (CI). Country-specific estimates of association were combined in random effects meta-analyses. The primary outcome was severe PPH, defined as a blood loss >1500 mL and/or receiving a blood transfusion. RESULTS: We included 542 394 singleton deliveries (264 804 in Sweden, 143 775 in Denmark, and 133 815 in Norway), of which 62 606 women (11%) had a positive SARS-CoV-2 test during pregnancy, and 20 786 (3.8%) deliveries were registered with a severe PPH. Overall, we observed no association between testing positive for SARS-CoV-2 during pregnancy and severe PPH (combined adjusted OR 1.04; 95% CI: 0.96-1.12). The results were similar for different calendar periods corresponding to dominant SARS-CoV-2 variants. We did, however, observe an association between severe PPH and women testing positive within 7 days before delivery (combined adjusted OR 1.30; 95% CI: 1.10-1.53). CONCLUSIONS: There was no association identified between SARS-CoV-2 test positivity and PPH of >1500 mL and/or blood transfusion in pregnant women from three Scandinavian countries. However, we observed a 30% higher odds of severe PPH among pregnant women who tested positive within one week before delivery
serojump: A Bayesian tool for inferring infection timing and antibody kinetics from longitudinal serological data.
Get PDFUnderstanding acute infectious disease dynamics at individual and population levels is critical for informing public health preparedness and response. Serological assays, which measure a range of biomarkers relating to humoral immunity, can provide a valuable window into immune responses generated by past infections and vaccinations. However, traditional methods for interpreting serological data, such as binary seropositivity and seroconversion thresholds, often rely on heuristics that fail to account for individual variability in antibody kinetics and timing of infection, potentially leading to biased estimates of infection rates and post-exposure immune responses. To address these limitations, we developed serojump, a novel probabilistic framework and software package that uses individual-level serological data to infer infection status, timing, and subsequent antibody kinetics. We validated serojump using simulated serological data and real-world SARS-CoV-2 datasets from The Gambia. In simulation studies, the model accurately recovered individual infection status, population-level antibody kinetics, and the relationship between biomarkers and immunity against infection, demonstrating robustness under observational noise. Benchmarking against standard serological heuristics in real-world data revealed that serojump achieves higher sensitivity in identifying infections, outperforming static threshold-based methods and precision in inferred infection timing. Application of serojump to longitudinal SARS-CoV-2 serological data taken during the Delta wave provided additional insights into i) missed infections based on sub-threshold rises in antibody level and ii) antibody responses to multiple biomarkers post-vaccination and infection. Our findings highlight the utility of serojump as a pathogen-agnostic, flexible tool for serological inference, enabling deeper insights into infection dynamics, immune responses, and correlates of protection. The open-source framework offers researchers a platform for extracting information from serological datasets, with potential applications across various infectious diseases and study designs
Driving innovation from discovery to access: Meeting report of the 7 th Global Forum on TB Vaccines (8-10 October 2024, Rio de Janeiro, Brazil).
Get PDFWe urgently need novel, effective, and accessible vaccines to end tuberculosis (TB) as a public health crisis. The 7th Global Forum on TB Vaccines was convened from 8-10 October 2024 in Rio de Janeiro, Brazil. Under the theme of "Driving innovation from discovery to access," the program covered the breadth of TB vaccine research and development (R&D) through implementation, while underscoring the need for greater innovation and investments to advance development and ensure rapid, affordable, and equitable access. Participants shared the latest research on: approaches to diversify the TB vaccine pipeline, candidates advancing through late-stage trials toward licensure, and efforts to ensure new TB vaccines reach the populations that most need them. The forum provided a platform to learn from diverse experts across the field, including researchers, industry, funders, civil society, and affected communities. Participants examined cross-cutting enablers throughout, including opportunities to establish novel partnership and financing models, enhance open science, optimize R&D practices, and strengthen leadership and engagement with community members and high burden countries alike. In this report, we synthesize key themes and findings from the meeting, highlighting progress and priorities in the TB vaccine field
Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity: A population-based cohort study.
Get PDFBACKGROUND: Long-term health consequences of COVID-19, particularly among individuals with pre-existing chronic diseases, are not fully understood. This study investigates whether SARS-CoV-2 infection increases the risk of developing multimorbidity (≥2 chronic conditions) and evaluates protective effects of vaccination.
METHODS: We analyzed territory-wide electronic health records from Hong Kong, linking Hospital Authority data with COVID-19 infection and vaccination records from the Department of Health. A retrospective matched-cohort study was conducted among patients with one pre-existing chronic condition. Participants were stratified into three groups: (1) no documented COVID-19 infection, (2) COVID-19 infection with incomplete vaccination (<3 doses), and (3) COVID-19 infection with full vaccination (≥3 doses). The primary outcome was the incidence of a second chronic condition from a pre-specified list.
RESULTS: Among 1,038,175 eligible individuals, 68,975 (6.64%) developed multimorbidity over a median follow-up of 192 days (IQR: 96-313). The non-COVID-19 group (51,288 cases) had an incidence rate of 68.88 per 1000 person-years (95% CI: 68.18-69.37). In contrast, the COVID-19/unvaccinated group (9455 cases) exhibited a significantly higher rate (86.58; 95% CI: 84.85-88.35). The COVID-19/vaccinated group (8232 cases) showed a moderated rate (72.84; 95% CI: 71.27-74.43). Adjusted incidence rate ratios were 1.26 (95% CI: 1.23-1.29) for unvaccinated and 1.08 (95% CI: 1.05-1.11) for vaccinated individuals compared to the non-COVID-19 group. Results remained consistent across age, sex, and comorbidity subgroups.
INTERPRETATION: COVID-19 infection is associated with an increased risk of multimorbidity in patients with pre-existing conditions. Full vaccination attenuates this risk substantially, highlighting its critical role in mitigating post-infection complications
Modular Combinatorial DNA Assembly of Group B Streptococcus Capsular Polysaccharide Biosynthesis Pathways to Expediate the Production of Novel Glycoconjugate Vaccines.
Get PDFBACKGROUND/OBJECTIVES: Streptococcus agalactiae (or Group B Streptococcus, GBS) is a major cause of neonatal meningitis globally. There are 10 serotypes of GBS, which are distinguished by their capsular polysaccharide (CPS) structure, with serotypes Ia, Ib, II, III, IV and V responsible for up to 99% of infections. Currently, there are no licensed vaccines against GBS. The most developed candidates are glycoconjugate vaccines, which can be highly effective but are also expensive to produce by existing approaches and unaffordable for many parts of the world. Biosynthesis of recombinant glycans and glycoconjugates in tractable strains of bacteria offers a low-cost alternative approach to current chemical conjugation methods. METHODS: In this study, we apply combinatorial hierarchical DNA assembly to the heterologous biosynthesis of GBS III, IV and V CPSs in E. coli. Each gene was removed from its native regulation, paired with synthetic regulatory elements and rebuilt from the bottom up to generate libraries of reconstituted pathways. These pathways were screened for glycan biosynthesis using serotype-specific antisera. RESULTS: We identified several configurations that successfully biosynthesised the GBS CPSs. Furthermore, we exploited the conserved nature of the GBS CPS biosynthesis loci and the flexibility of modular DNA assembly by constructing hybrid pathways from a minimal pool of glycosyltransferase genes. We show that transferase genes with homologous function can be used interchangeably between pathways, obviating the need to clone a complete locus for each new CPS assembly. CONCLUSIONS: In conclusion, we report the first demonstration of heterologous GBS CPS IV and V biosynthesis in E. coli, a key milestone towards the development of low-cost recombinant multivalent GBS glycoconjugate vaccines
Pattern Mixture Sensitivity Analyses via Multiple Imputations for Non-Ignorable Dropout in Joint Modeling of Cognition and Risk of Dementia.
Get PDFMotivated by the Swedish Betula study, we consider the joint modeling of longitudinal memory assessments and the hazard of dementia. In the Betula data, the time-to-dementia onset or its absence is available for all participants, while some memory measurements are missing. In longitudinal studies of aging, one cannot rule out the possibility of dropout due to health issues resulting in missing not at random longitudinal measurements. We, therefore, propose a pattern-mixture sensitivity analysis for missing not-at-random data in the joint modeling framework. The sensitivity analysis is implemented via multiple imputation as follows: (i) multiply impute missing not at random longitudinal measurements under a set of plausible pattern-mixture imputation models that allow for acceleration of memory decline after dropout, (ii) fit the joint model to each imputed longitudinal memory and time-to-dementia dataset, and (iii) combine the results of step (ii). Our work illustrates that sensitivity analyses via multiple imputations are an accessible, pragmatic method to evaluate the consequences of missing not at-random data on inference and prediction. This flexible approach can accommodate a range of models for the longitudinal and event-time processes. In particular, the pattern-mixture modeling approach provides an accessible way to frame plausible missing not at random assumptions for different missing data patterns. Applying our approach to the Betula study shows that worse memory levels and steeper memory decline were associated with a higher risk of dementia for all considered scenarios