Infectious Units Research Articles

Emergent cesarean section during active labor-does cervical dilatation matter?

To compare the immediate and late complications associated with emergent cesarean sections (CS) performed during the first and second stages of active labor. We conducted a retrospective analysis of electronic medical records from a single academic center, including data from 577 patients who underwent emergent cesarean sections at 4cm or more of cervical dilatation. Patients were divided into two groups: those who had CS during the first stage of labor (4-9cm dilatation) and those who had CS at complete dilatation (10cm). Maternal and neonatal outcomes were compared, including rates of complications such as uterine atony, post-partum hemorrhage, infection, and neonatal intensive care unit (NICU) admission. Of the 577 patients, 352 underwent CS during active labor and 255 at complete dilatation. The complete dilatation group exhibited significantly higher rates of uterine atony (19.6% vs. 11.6%, p = 0.009) and uterine incision extension (34.2% vs. 16.5%, p = 0.0001). In addition, they had longer hospital stays (4.8 vs. 4.25days, p = 0.003) and higher outpatient clinic visit rates (21.3% vs. 9.9%, p = 0.0001). Infection-related complications on readmission were more common in the complete dilatation group (20% vs. 9.7%, p = 0.001). Neonatal outcomes, including APGAR scores and NICU admissions, did not differ significantly between the groups. Emergent cesarean sections performed at complete cervical dilatation are associated with increased intra-operative and post-operative complications compared to those performed during active labor. These findings highlight the importance of considering the stage of labor when planning cesarean delivery to minimize risks and optimize outcomes for both mother and neonate.

A measles virus collective infectious unit that caused lethal human brain disease includes many locally restricted and few widespread copy-back defective genomes.

During virus replication in cultured cells, copy-back defective viral genomes (cbDVGs) can arise. CbDVGs are powerful inducers of innate immune responses in vitro, but their occurrence and impact on natural infections of human hosts remain poorly defined. We asked whether cbDVGs were generated in the brain of a patient who succumbed to subacute sclerosing panencephalitis (SSPE) about 20 years after acute measles virus (MeV) infection. Previous analyses of 13 brain specimens of this patient indicated that a collective infectious unit (CIU) drove lethal MeV spread. In this study, we identified 276 replication-competent cbDVG species, each present in over 100 copies in the brain. Six species were detected in multiple forebrain locations, implying that they travelled long-distance with the CIU. The cbDVG to full-length genomes ratio was often close to 1 (0.6-1.74). Most cbDVGs were 324-2,000 bases in length, corresponding to 2%-12% of the full-length genome; all are predicted to have complementary terminal sequences. If improperly encapsidated, these sequences have the potential to form double-stranded structures that can induce innate immune responses. To assess this, we examined the transcriptome of all brain specimens. Several interferon and inflammatory response genes were upregulated, but upregulation levels did not correlate with cbDVG levels in the specimens. Thus, the CIU that drove MeV pathogenesis in this brain includes, in addition to two complementary full-length genome populations, many locally restricted and few widespread cbDVG species. The widespread cbDVG species may have been positively selected but how they impacted pathogenesis remains to be determined.IMPORTANCECopy-back defective viral genomes (cbDVGs) can drive virus-host interactions. They can suppress virus replication directly, by competing with full-length genomes, or indirectly by stimulating antiviral immunity. In vitro, cbDVG can slow down infections and promote persistence, but there is limited documentation of their presence in human hosts or of their impact on disease. We had the unique opportunity to analyze the brain of a patient who succumbed to subacute sclerosing panencephalitis, a rare but lethal consequence of measles. We detected more than 270 distinct cbDVG species; most were restricted to one specimen, but several reached all lobes of the forebrain, suggesting positive selection. Our analyses provide the missing knowledge of the diversity of cbDVG in a natural infection of a human host. They also reveal that a collective infectious unit that caused lethal human brain disease includes few widespread cbDVG, in addition to two ubiquitous complementary full-length genome populations.

Organellar genome dynamics of exogenous stages of Eimeria tenella

BackgroundCoccidia are a group of intracellular protozoal parasites within the phylum Apicomplexa. Eimeria tenella, one of the species that cause intestinal coccidiosis in poultry, can cause significant mortality and morbidity. Diploid oocysts of Eimeria species are shed in the feces of an infected host and must sporulate to achieve infectivity. This process results in eight haploid infectious units, called sporozoites, held within a single oocyst. Each Eimeria spp. parasite possesses a single apicoplast and a single mitochondrion, both of which carry multiple copies of their respective organellar genomes. Reports of copy numbers of organellar genomes have varied widely.MethodsWe report the application of quantitative polymerase chain reaction (qPCR), supported by next-generation sequencing, for the quantification of the extranuclear genomes relative to the nuclear genome over the course of sporulation and following its completion.ResultsAt 64 elapsed hours, 93.0% of oocysts were fully sporulated; no increase in percent sporulation was observed after this time. Apicoplast relative genome copy number showed several significant shifts up to 72 elapsed hours, after which no significant shifts were observed. Oocysts were shed with approximately 60% the amount of apicoplast DNA present at 72 h, after which point no significant shifts in apicoplast genome relative abundance occurred. Mitogenome relative copy number showed only two significant shifts, from 16 to 24 elapsed hours and from 24 to 32 elapsed hours. Oocysts were shed with approximately 28% the amount of mitochondrial DNA that was present at the time sporulation was deemed morphologically complete, at 64 elapsed hours.ConclusionsThe characterization of the dynamics of genome abundance in exogenous stages sheds new light on the basic biology of Eimeria spp. and supports the use of extranuclear targets for molecular modes of parasite quantification and identification with improved sensitivity and accuracy.Graphical

Application of hot water and cold air to reduce bacterial contamination on broiler carcasses.

Two physical treatments (heat via water bath and cold air) with various temperatures (20/70/75/80°C and - 80/-90°C) and exposure times (20, 30, 40 s) were carried out to identify a decontaminating effect on zoonotic pathogens on broiler carcasses. Subsequently, carcasses were analyzed for thermotolerant Campylobacter (C.), Salmonella, Escherichia (E.). coli and total colony count (TCC). Moreover, for the hot water treatment, qPCR with viable/dead differentiation (v-qPCR) was applied to detect viable but non-culturable cells (VBNC) of Campylobacter, referred to as intact but putatively infectious units (IPIU). Hot water immersion was tested on carcasses inoculated with C. jejuni and Salmonella, while cold air treatment was evaluated for naturally contaminated carcasses of broiler flocks colonized with Campylobacter. For hot water treatment, the statistically significant reducing effect was about 1 log10 CFU/ml for both Salmonella and Campylobacter for 70-80°C and 20/30 s treatments. The effect of heat treatment for Campylobacter was smaller when samples were analyzed with v-qPCR with reductions of 0.5-0.8 log10 IPIU/ml in mean. Cold air treatments at -90°C were effective in reducing the mean contamination level of Campylobacter by 0.4-0.5 log10 CFU/ml at all exposure times (p < 0.05). Hot water treatments showed a decreasing trend on TCC by 0.6-0.9 log10 CFU/ml (p < 0.05). TCC counts were not significantly affected by cold air treatment. For E. coli no statistically significant reductions were observed by hot water treatment. The cold air treatment at -90°C for 20 and 40 s led to a reduction of E. coli by 0.4 and 0.8 log10 CFU/ml (p < 0.05), respectively. Treatment of carcasses with higher bacterial levels tended to show higher reduction. The research demonstrated that the efficacy of physical treatments for decontamination of broiler carcasses was more pronounced for hot water immersion than for cold air exposure. In conclusion, the results shed light on the potential application of these physical treatments in practice to reduce the quantitative load of contaminating pathogens to enhance food safety in the broiler meat production.

Ex Vivo Machine Perfusion as a Platform for Lentiviral Gene Delivery in Rat Livers.

Developing new strategies for local monitoring and delivery of immunosuppression is critical to making allografts safer and more accessible. Ex vivo genetic modification of grafts using machine perfusion presents a promising approach to improve graft function and modulate immune responses while minimizing risks of off-target effects and systemic immunogenicity in vivo. This proof-of-concept study demonstrates the feasibility of using normothermic machine perfusion (NMP) to mimic in vitro conditions for effective gene delivery. In this study, lentiviral vectors carrying biosensor constructs with Gaussia Luciferase (GLuc) were introduced to rodent livers during a 72-hour perfusion period, with a targeted delivery of 3 × 107 infection units (IU). Following the initial 24-hour exposure required for viral transduction, an additional 48 hours was necessary to observe gene expression, analogous to in vitro benchmarks. The perfused livers displayed significantly increased luminescence compared to controls, illustrating successful genetic modification. These findings validate the ex vivo use of lentiviral particles in a rodent liver model and lay the groundwork for a broad range of applications through genetic manipulation of organ systems. Future studies will focus on refining this technology to enhance precision in gene expression and explore its implications for clinical transplantation.

Robot-Assisted Minimally Invasive Coronary Artery Bypass Grafting: Total Arterial Revascularization Using the Double-Docking Technique.

The right internal mammary artery is considered to be the second choice for arterial conduits for coronary artery bypass grafting (CABG). However, the widespread use of bilateral internal mammary artery (BIMA) grafting is limited owing to increased technical demands, lengthy procedure, and high incidence of sternal wound complications. We compared the early clinical outcomes of a novel robot-assisted double-docking technique (DDT) with an open sternotomy technique for total arterial revascularization using BIMA. Between June 2019 and June 2023, 445 patients with multivessel coronary artery disease underwent open sternotomy CABG using BIMA grafting and 145 patients underwent robot-assisted BIMA grafting using DDT. Comparative analysis of 104 pairs of matched patients obtained using propensity score matching was performed. Procedural characteristics, postoperative 30-day mortality, and composite outcome (major adverse cardiac and cerebrovascular events) at a median follow-up of 1.5 years were evaluated. Preprocedural characteristics were well balanced between the groups after propensity matching. The number of distal anastomoses performed in the conventional group was statistically higher than that performed using DDT (P < 0.001). The durations of postsurgical ventilation, intensive care unit stay, and in-hospital stay were significantly lower with the DDT than with conventional CABG (P < 0.001). There was no significant difference in all-cause mortality or major adverse cardiac events between the DDT and conventional CABG groups at a median follow-up of 1.5 years. The DDT is feasible and efficacious for revascularization of multiple coronary targets in select individuals. It is equivalent to open sternotomy in terms of early clinical outcomes and superior to open sternotomy with regard to rates of sternal infection and intensive care unit and in-hospital stay.

Prognostic Factors That Affect Mortality Patients with Acinetobacter baumannii Bloodstream Infection.

To evaluate the clinical features of patients with Acinetobacter baumannii bloodstream infection (BSI). Totally 200 inpatients with Acinetobacter baumannii BSI were included, clinical features of Acinetobacter baumannii BSI inpatients between 90-day survival and 90-day mortality groups, between 30-day survival and 30-day mortality groups, between patients infected with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) were analyzed. The prognostic factors of 90-day mortality were analyzed by univariate logistic regression and multivariate logistic regression. The survival curve in bloodstream infectious patients with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) was analyzed by Kaplan-Meier analysis. The 90-day mortality patients had significantly higher carbapenem-resistant bacterial infection and critical care unit (ICU) admission. The 90-day and 30-day mortality groups showed higher C-reactive protein (CRP) and serum creatinine (Scr) levels and lower red blood cells (RBC) and albumin (ALB) levels than their survival counterparts, respectively. Critical surgery, ICU admission and delayed antibiotic treatment were independently prognostic risk predictors for 90-day mortality in Acinetobacter baumannii BSI patients, while critical surgery and diabetes were independently prognostic risk predictors for 90-day mortality in carbapenem-resistant Acinetobacter baumannii BSI patients. Compared with sensitive group, MDR group showed significantly longer ICU and whole hospital stay, lower levels of lymphocytes, RBC, hemoglobin, lactate dehydrogenase and ALB, higher frequency of infection originating from the skin and skin structure. Moreover, patients in the MDR group had a significantly worse overall survival than the sensitive group. We identified the prognostic factors of Acinetobacter baumannii BSI and carbapenem-resistant Acinetobacter baumannii BSI patients. Critical surgery, ICU admission, delayed antibiotic treatment or diabetes were significantly associated with the mortality of those patients. Moreover, aggressive measures to control MDR Acinetobacter baumannii could lead to improved outcomes.

Patterns of Transmitted Drug Resistance Mutations and HIV-1 Subtype Dynamics in ART-Naïve Individuals in Veneto, Italy, from 2017 to 2024.

This study investigates the prevalence and patterns of transmitted drug resistance mutations (TDRMs) and HIV-1 subtypes among antiretroviral therapy (ART) naïve individuals in Veneto, Italy, from 2017 to 2024. This research aims to understand the dynamic landscape of TDRMs and HIV-1 genetic diversity to inform treatment strategies effectively. We included all adult ART-naïve people with HIV (PWH) from seven infectious disease units in Veneto, Italy. We collected the genotypic resistance testing conducted to predict drug susceptibility and subtype distribution using the Stanford HIVdb algorithm. We included 762 PWH, showing a slight but statistically significant decline in the B subtype among Italian PWH (p = 0.045) and an increase in non-B subtypes among foreigners, though it was not statistically significant (p = 0.333). The most frequent mutations were in Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), especially in non-B subtypes, with a notable rise from 10.7% in 2017-2019 to 15.5% in 2020-2024. Notably, TDRMs were consistently detected, highlighting an ongoing challenge despite the stable prevalence observed over the years. In addition, the data revealed a concerning rise in mutations against newer drug classes, such as integrase inhibitors. Conclusively, the study underscores the necessity of continuous surveillance of HIV subtypes and resistance patterns to adapt ART regimens optimally. Despite the stable levels of drug resistance, the emergence of resistance against newer drugs necessitates ongoing vigilance and possible adjustment in treatment protocols to enhance clinical outcomes and manage HIV drug resistance effectively.

Immunological insights: assessing immune parameters in medical professionals exposed to SARS-CoV-2

BackgroundThe immunological background responsible for the severe course of COVID-19 and the immune factors that protect against SARS-CoV-2 infection are still unclear. The aim of this study was to investigate immune system status in persons with high exposure to SARS-CoV-2 infection.MethodsSeventy-one persons employed in the observation and infectious diseases unit were qualified for the study between November 2020 and October 2021. Symptomatic COVID-19 was diagnosed in 35 persons. Anti-SARS-CoV-2 antibodies were also found in 8 persons. Peripheral blood mononuclear cells subpopulations were analyzed by flow cytometry, and the concentrations of cytokines and anti-SARS-CoV-2 antibodies were determined by ELISA.ResultsThe percentages of cytotoxic T lymphocytes (CTLs), CD28+ and T helper (Th) cells with invariant T-cell receptors were significantly higher in persons with symptomatic COVID-19 than in those who did not develop COVID-19’ symptoms. Conversely, symptomatic COVID-19 persons had significantly lower percentages of: a) CTLs in the late stage of activation (CD8+/CD95+), b) NK cells, c) regulatory-like Th cells (CD4+/CTLA-4+), and d) Th17-like cells (CD4+/CD161+) compared to asymptomatic COVID-19’ persons. Additionally, persons with anti-SARS-CoV-2 antibodies had a significantly higher lymphocyte count and IL-6 concentration than persons without these antibodies.ConclusionNumerous lymphocyte populations are permanently altered by SARS-CoV-2 infection. High percentages of both populations: NK cells—as a part of the non-specific response, and T helper cells’ as those regulating the immune response, could protect against the acute COVID-19 symptoms development. Understanding the immune background of COVID-19 may improve the prevention of this disease by identifying people at risk of a severe course of infection.Trial registrationThis is a retrospective observational study without a trial registration number.

Impact of rapid-antiretroviral therapy in a cohort of treatment-naïve migrants living with HIV in a high income setting.

We evaluated the effect of rapid ART (RA) compared to delayed ART (DA) on viral load suppression (viral load <50 cp/mL) and loss to follow-up (LTFU) in a cohort of migrants living with HIV (MLWHs) in Italy. Data were retrospectively gathered from MLWHs who began care at the Infectious and Tropical Diseases Unit of the Careggi University Hospital from January 2014 to December 2022. RA was defined as antiretrovirals prescribed within 7 days of HIV diagnosis. The study ended on April 30, 2023, or upon patient LTFU. Chi-square and non-parametric tests assessed differences in categorical and continuous variables, respectively. Kaplan-Meyer survival analysis was performed to estimate the probability of loss to follow-up. Cox regression analysis was performed to evaluate factors associated with a loss to follow-up. 87 MLWHs were enrolled: 20 (23%) on RA and 67 (77%) on DA. In the RA group there were more PLWH with a previous AIDS event (p < .001) however, there was no significant difference in the LTFU rates between the groups (aHR 0.6, 95%CI 0.1-3.1; p = .560; Logrank = 0.2823). Being an out-of-status MLWH was the only predictor of LTFU. By 6months, virological suppression was achieved in 61.2% (n = 41) in DA and 70.0% in the RA group (n = 14) (Logrank p = .6747). RA did not significantly affect LTFU rates or the achievement of viral load suppression. The study suggests that further research is needed to assess the impact of RA in high income settings.

Long non-coding RNAs — regulators of rubella virus infection and antiviral response

Introduction. Rubella virus is an RNA-containing virus capable of infecting human cells and causing infectious disease. Infection of pregnant women with rubella virus can lead to abortion or congenital rubella syndrome (CRS), a set of long-term birth defects including incomplete fetal organ development and mental retardation. There is no specific treatment for rubella and CRS. The regulation of antiviral immune response and viral reproduction by long non-coding RNAs is currently under active investigation. In this study, we evaluated the changes in the expression profile of long non-coding RNAs in rubella virus-infected A549 epithelial by RNA sequencing. Materials and Methods. A549 cells were infected with a wild-type variant of laboratory strain C-77 of rubella virus with a multiplicity of infection of 1.0 infectious units per cell and incubated for 72 hours. Virus titres were determined by the CCID method in the sensitive RK-13 cell culture. 48 h after infection, the cell monolayer was lysed, RNA was isolated, and libraries were prepared for sequencing. Sequencing was performed on the NextSeq500 platform (Illumina, USA) in paired-end reading mode. Validation of the obtained RNA sequencing data was performed using quantitative real-time PCR. Results. Rubella virus replication affects the production of some long non-coding RNAs by altering their expression profile. Thus, upon infection of A549 epithelial cells with rubella virus, there was a significant increase in the expression of such long non-coding RNAs as GAS5, NEAT1, LUCAT1, MIR210HG, MEG3, EPB41L4A-AS1, ZFAS1, and SNHG 1, 7, 12, 29, 32. DANCR, IGFL2-AS1, IGFL2-AS1, MIR1915HG, and SNHG14 were most significantly decreased in expression. Gene ontology (GO)-analysis revealed that long non-coding RNAs are involved at different levels in the mechanisms of immune response, in particular, RNA processing and nucleic acid metabolism; therefore, up- and down-regulation of these molecules leads to modulation of human antiviral immune response in response to rubella virus infection. Conclusion. Thus, the regulation of long non-coding RNA production by rubella virus has been shown for the first time. Differentially expressed long non-coding RNAs can be used as prognostic and diagnostic biomarkers of viral diseases.

Preoperative Malnutrition Increases Risk of In-Hospital Mortality, Major Infection, and Longer Intensive Care Unit Stay After Ventricular Septal Defect Closure.

High energy requirements and poor feeding can lead to growth failure in patients with ventricular septal defect (VSD), but effects of preoperative malnutrition on surgical outcomes are poorly understood, especially in low-resource settings. We analyzed a cohort of children <5 years of age undergoing VSD closure at 60 global centers participating in the International Quality Improvement Collaborative for Congenital Heart Disease, 2015 to 2020. We calculated adjusted odds ratios (ORs) for in-hospital death and major infection and adjusted coefficients for duration of intensive care unit stay for 4 measures of malnutrition: severe wasting (weight-for-height Z score, <-3), moderate wasting (-3<weight-for-height Z score≤-2), underweight (weight-for-age Z score, ≤-2), and stunting (height-for-age Z score, ≤-2) according to World Health Organization Child Growth Standards. Among 10 966 children undergoing VSD closure in the analyzed cohort, 8136 (74%) were membranous VSDs. Median age was 9.6 months (interquartile range, 3.6-12.0), and 4088 (37.3%) had wasting/severe wasting, 5029 (45.9%) had underweight, and 3515 (32.1%) had stunting. There were 4749 (43.3%) children who met the criteria for ≥2 malnutrition categories. Overall, 84 patients (0.8%) died in-hospital, and 199 (1.8%) had major infection. Severe wasting (OR, 3.38 [95% CI, 1.55-7.35]; P=0.002), underweight (OR, 6.46 [95% CI, 2.81-14.8]; P<0.001), and stunting (OR, 2.73 [95% CI, 1.40-5.34]; P=0.003) were independent predictors of mortality. Similar results were observed for infection and duration of intensive care unit stay. Underweight was the strongest predictor of adverse outcomes. Children meeting criteria for all 3 (stunting, wasting, and underweight) had 17.2 times higher odds of mortality (P<0.001) than nonmalnourished children. Malnutrition was associated with mortality, infection, and longer intensive care unit stay in a global cohort of children undergoing VSD closure.

Viral Hepatitis and HIV Screening in Seasonal Mountain Workers: Feasibility and Results of a First French Experiment

Introduction: The Mobile Hepatitis Team (MHT) was set up in 2013, with main objective was to increase outreach screening care treatment access and cure of our target population. Target population was drugs users, prisoners, homeless, precarious people, migrants, and psychiatric patients. Seasonal workers working in mid-mountain ski resorts in the Eastern Pyrenees constitute a population at risk of viral hepatitis and HIV. This young population presents sexual risk behaviors and consumption of addictive products without regular access to care because of their mobility, moving from one workplace to another according to the seasons. They do not have a regular general practitioner, do not perform screening tests and there is no access to care other than the mandatory occupational medicine visit at the beginning of the season. In previous actions on the health aera of the high cantons of the department of Pyrénées-Orientales. We met with invested partners who referred us to this specific population of seasonal workers and their lack of access to screening and care, except for the occupational medicine hiring visit, organized before the beginning of the winter season, late November in early December. Objective: To detect viral hepatitis and HIV in a population at viral risk and far from care and offer them immediate treatment of the type of linkage to care “TEST TO CURE”. Methodology: 2-weeks HCV HBV and HIV finger sticks by trained nurses and orientation to the hepatology or the infectious units. Results: only 28 HCV finger sticks were completed. We also met 4 patients with known HCV serology. Three patients received DAA treatment and one patient spontaneous cured with negative RNA. One new patient had RNA C positive on balance sheet without social rights. We oriented him towards sour social worker to treat him later. Two patients had 2 real time HCV viral load not detected (including one post treatment follow-up) and one RNA negative without antiviral treatment, in case of HCV spontaneous clearance. For HBV, 16 finger sticks were completed, all negative. We did not meet as many seasonal workers as originally planned. This is why we conducted a second session over 2 days only targeted on these temporary accommodations. We realized 26 HCV and HIV finger sticks. One patient was HIV positive. HIV serology was unknow until our screening session. Nobody was HCV positive but 62% of screened people were drugs users or former drugs users. Discussion: our study was a success even the low number of people screened in the first 2-week session. The second 2-day session was more efficient. It was the first experience of hepatitis and HIV screening in this population of seasonal mountain workers. Conclusion: despite all limits, hepatitis and HIV screening among seasonal mountain workers was an innovative and efficient action. This action could be easily replicated in all populations of seasonal workers, whether in the mountains or by the sea.

Tixagevimab/cilgavimab prophylaxis against COVID-19 in solid organ transplant recipients: a systematic review and meta-analysis.

Tixagevimab/cilgavimab (Tix/Cil) shows promise as a prophylactic treatment against coronavirus disease 2019 (COVID-19) in solid organ transplant recipients (SOTRs). This study was performed to assess the effectiveness of Tix/Cil for preexposure prophylaxis against COVID-19 in this population. We systematically searched the Cochrane Library, Web of Science, PubMed, and Embase databases to identify articles relevant to our study up to December 15, 2023. Comprehensive Meta-Analysis (ver. 3.0) was used for data analysis. The meta-analysis included seven eligible retrospective studies, encompassing a total of 4,026 SOTRs. The analysis revealed significant differences in SOTRs who received Tix/Cil preexposure prophylaxis relative to those who did not. Specifically, these differences were observed in the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.15-0.60), hospitalization (OR, 0.24; 95% CI, 0.08-0.70), and intensive care unit admission (OR, 0.07; 95% CI, 0.02-0.22). However, mortality rate did not differ significantly between the two groups (P=0.06). The evidence supporting the effectiveness of Tix/Cil as preexposure prophylaxis against SARS-CoV-2 in SOTRs is of a low to moderate level. Further high-quality research is necessary to understand its effects on this population.

Vaccination against COVID-19 among healthcare workers as a cocoon strategy for people living with HIV

IntroductionHealthcare professionals working in infectious disease units are often engaged in the care of patients with HIV infection. A cocoon vaccination strategy may protect those who are immunocompromised from a severe course of COVID-19. MethodsThe research was conducted between January 2021 and June 2022. The study participants were 450 healthcare workers (HCWs) from the Hospital for Infectious Diseases in Warsaw who were vaccinated against COVID-19 with the BNT162b2 mRNA vaccine (Pfizer-BioNTech) –, thefirst available type of vaccine in Poland. Sera were collected according to the schedule of the study. Statistical analyses were performed with non-parametric tests: Wilcoxon's test was used to compare dependent numerical variables, and Fisher's exact test and the Chi-squared test to compare categorical variables. A p value of <0.05 was considered statistically significant. ResultsAmong the 450 HCWs working in the Hospital for Infectious Diseases in Warsaw 412 (91,5 %) were vaccinated against COVID-19. In total 170 (41,3 %) vaccinated HCWs were included in the final analysis. Their median age was 51 years [interquartile range (IQR): 41–60 years] and median body mass index (BMI) was 25.10 [IQR: 22.68–29.03]. Most of the cohort consisted of women (n = 137, 80.59 %), with the majority working directly with patients (n = 137, 73.21 %). It was found that as early as 14 days after the second dose of the vaccine, 100 % of the study participants achieved a positive result for SARS CoV-2 S-RBD antibodies. There were 168 subjects who had had a COVID-19 diagnosis before entering study and after vaccination 65 HCWs was diagnosed with COVID-19. ConclusionsDue to the fact that people living with HIV with severe immunodeficiency may have an incomplete immune response to COVID vaccination and be at risk of a severe course of the disease, the cocoon strategy of vaccinating medical personnel may be beneficial for these patients.

Poor in vivo transduction of myocardium by lentiviral vectors is likely caused by a post-entry block of transduction

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Stichting LSH-TKI Introduction In cardiac gene therapy, two prototypic viral vectors are typically considered for long-term transgene expression, i.e. lentivirus (LV) and adeno-associated virus (AAV) vectors. Compared to AAV vectors, LV vectors have the advantages of a larger insert capacity and the ability to confer permanent transgene expression due to integration of the vector genome in the host cell’s chromosomal DNA . However, standard VSV G protein-pseudotyped LV vectors (VSV G-LV vectors) has shown suboptimal transduction of cardiac myocytes in vivo. Purpose In this study, we aimed to improve LV-mediated transduction of cardiomyocytes in vivo by evaluating LV vectors carrying various different envelopes and compared the most potent variants with AAV1 capsid-pseudotyped AAV2 vectors (AAV2/1 vectors). Methods We made a panel of LV vectors pseudotyped with envelope proteins from 76 different viruses carrying an expression cassette for enhanced green fluorescent protein (eGFP). Transduction efficiencies in neonatal rat ventricular myocytes (NRVMs), human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cardiomyocyte progenitor cells (CMPCs) were determined by fluorescence-activated cell sorting (FACS) as percentage eGFP-positive cells. Male NOD -SCID mice aged 3-6 months were injected directly into the left ventricular myocardium with eGFP-encoding VSV G-LV and AAV2/1 vectors at doses of 1.4 x 10^7 infectious units and 2.0 x 10^10 genome copies, respectively, or PBS as a control. Mice were sacrificed one and four weeks after surgery. Per heart, left ventricular and eGFP-positive area was determined from 40 – 50 slides and the ratio was used as a measure of transduction efficiency. Results Of the panel of pseudotyped LVs none was able to consistently outperform VSV G-LV vectors, which reached transduction efficiencies in vitro of 58% in NRVMs to 96% in hiPSC-CMs and 100% in CMPCs . In AAV2/1 vector-injected hearts, the eGFP expressing area in the left ventricle increased from 1.07% in week 1 to 5.42% in week 4. In contrast, eGFP expression in LV-injected hearts was 0.31% and 0.16% after 1 week and 4 weeks, respectively (figure 1). Conclusion In vitro screening of a panel of pseudotyped LV vectors showed standard VSV G-LV vectors as top performer. Despite encouraging in vitro results and previously reported findings, VSV G-LV vectors was unable to provide for robust in vivo transduction. The observation that none of the 76 different envelopes yielded a meaningful improvement of lentiviral transduction rates together with the discrepancy between in vitro and in vivo transduction efficiencies, suggest that a post-entry block of transduction likely represents an important component of the poor in vivo performance.Figure 1in vivo transduction

Examining pancreatic stone protein response in ICU-acquired bloodstream infections: a matched event analysis.

Pancreatic stone protein (PSP) exhibits potential as a plasma biomarker for infection diagnosis and risk stratification in critically ill patients, but its significance in nosocomial infection and intensive care unit (ICU)-acquired bloodstream infection (BSI) remains unclear. This study explores the temporal responses of PSP in ICU-acquired BSI caused by different pathogens. From a large cohort of ICU patients, we selected episodes of ICU-acquired BSI caused by Gram-negative rods (GNRs), enterococci, or Candida species. Events were matched on length of ICU stay at infection onset, Severe Organ Failure Assessment (SOFA) score, presence of immune deficiency, and use of renal replacement therapy. PSP concentrations were measured at infection onset (T0) and at 24, 48 and 72h prior to infection onset as defined by the first occurrence of a positive blood culture. Absolute and trend differences in PSP levels between pathogen groups were analysed using one-way analysis of variance. Sensitivity analyses were performed in events with a new or worsening systematic inflammatory response based on C-reactive protein, white cell count and fever. We analysed 30 BSI cases per pathogen group. Median (IQR) BSI onset was on day 9 (6-12). Overall, PSP levels were high (381 (237-539) ng/ml), with 18% of values exceeding the assay's measurement range. Across all 90 BSI cases, there was no clear trend over time (median change 34 (- 75-189) ng/ml from T-72 to T0). PSP concentrations at infection onset were 406 (229-497), 350 (223-608), and 480 (327-965) ng/ml, for GNR, enterococci, and Candida species, respectively (p = 0.32). At every time point, absolute PSP levels and trends did not differ significantly between pathogens. PSP values at T0 correlated with SOFA scores. Eighteen (20%) of 90 BSI events did not exhibit a systemic inflammatory response, primarily in Candida species. No clear change in PSP concentration before BSI onset or between-group differences were found in sensitivity analyses of 72 cases. Against a background of overall (very) high plasma PSP levels in critically ill patients, we did not find clear temporal patterns or any pathogen-specific differences in PSP response in the days preceding onset of ICU-acquired BSI.

Anthropology and ethnobotany in health mediation: an illustration of a clinical, personalized approach for Haitian migrants in a French Guianese hospital.

In French Guiana, a European territory in Guiana shield in the Amazon area, close to 40% of the current population was born abroad. In this context, it is important to listen to the experiences of migrants to better understand the difficulties encountered within the healthcare pathways. This is the aim of ANRS Parcours d'Haïti project, an epidemiological, biographical and socio-anthropological study conducted on a representative sample of the Haitian community in French Guiana and focusing on the social determinants of health. Within the framework of this study, the Infectious and Tropical Diseases clinical team of Cayenne Hospital has established close collaboration with health mediators and the ethnobotanist anthropologist of the study. To illustrate the contribution of a personalized approach to health mediation, we report the case of a migrant woman of Haitian origin admitted to the Infectious and Tropical Diseases Unit. We highlight the different socio-cultural aspects addressed and their place in the care process through a thematic discussion and socio-anthropological analysis of the care relationship, based on participatory ethnography and inductive analysis of an in-depth interview with the patient. This example illustrates the need for a multidisciplinary approach to ensure culturally adapted care for patients. Personal interviews are important because they allow to better take into account the cultural specificities of patients' experiences and the socio-cultural environment in which they live (and especially, in the case of Haitian patients, their religious affiliation). By allowing them to speak and express themselves freely, they integrate not only their own cultural baggage, but also their own expectations and representations of the disease they suffer from and how it should be treated. Ultimately, this tripartite collaboration between patient, caregiver, and anthropologist or health mediator leads to a better therapeutic alliance. The analysis of this health care relationship is emblematic of the issue of cultural competence and pre-conceptualizes what intercultural mediation in health care could be, as close as possible to the caregiver and the individual.

Natural History and Management of Hepatitis C in Children: 25 Years Experience of a Reference Center in Northern Italy.

Hepatitis C virus (HCV) infection natural history and management in the pediatric population are still debated. We retrospectively evaluated the outcome of a HCV pediatric population managed at the Pediatric Infectious Disease Unit of Luigi Sacco Hospital (Milan, Italy) from January 1997 to January 2022 (median follow-up 10 years) and we focused on the role of new drugs and transient elastography. Fifty-seven patients were enrolled: 8 (14%) had a spontaneous clearance, 33 were treated (58%), 7 (12%) were not treated because they were under 12 years old and 9 were lost at follow-up. HCV RNA was undetectable in all treated patients at the end of therapy, after 12 weeks (SVR12) and for the rest of their follow-up. All patients treated underwent elastography before and 1 year after therapy. Median stiffness pretherapy was 5.6 kPa, and 9 patients (16%) had abnormal transient elastography (>7 kPa, median 8.7 kPa). Median stiffness after treatment in the abnormal group was 6.8 kPa. Direct-acting antiviral agents are a safe and effective therapy for HCV chronic infection in the pediatric population. Liver elastography is normal in many vertically infected children before 12 years, but, when abnormal, it shows a significant improvement after direct-acting antiviral agent treatment. Further studies are needed to evaluate the role of elastography at diagnosis and follow-up in children.

Pharmacogenetics of tenofovir drug transporters in the context of HBV: Is there an impact?

BackgroundCurrent treatments for chronic hepatitis B management include orally administered nucleos(t)ide analogues, such as tenofovir (TDF), which is an acyclic adenine nucleotide analogue used both in HBV and human immune deficiency virus (HIV). The course of HBV infection is mainly dependent on viral factors, such as HBV genotypes, immunological features and host genetic variables, but a few data are available in the context of HBV, in particular for polymorphisms of genes encoding proteins involved in drug metabolism and elimination.Consequently, the aim of this study was to evaluate the potential impact of genetic variants on TDF plasma and urine concentrations in patients with HBV, considering the role of HBV genotypes. MethodsA retrospective cohort study at the Infectious Disease Unit of Amedeo di Savoia Hospital, Torino, Italy, was performed. Pharmacokinetic analyses were performed through liquidi chromatography, whereas pharmacogenetic analyses through real-time PCR. FindingsSixty - eight patients were analyzed: ABCC4 4976 C>T genetic variant showed an impact on urine TDF drug concentrations (p = 0.014). In addition, SLC22A6 453 AA was retained in the final regression multivariate model considering factors predicting plasma concentrations, while ABCC4 4976 TC/CC was the only predictor of urine concentrations in the univariate model. InterpretationIn conclusion, this is the first study showing a potential impact of genetic variants on TDF plasma and urine concentrations in the HBV context, but further studies in different and larger cohorts of patients are required.