Infection and Immunity, Ahead of Print.

Abstract Background Several studies suggested pancreatic stone protein (PSP) as a promising biomarker to predict mortality among patients with severe infection. The objective of the study was to evaluate the performance of PSP in predicting intensive care unit (ICU) mortality and infection severity among critically ill adults admitted to the hospital for infection. Methods A systematic search across Cochrane Central Register of Controlled Trials and MEDLINE databases (1966 to February 2022) for studies on PSP published in English using ‘pancreatic stone protein’, ‘PSP’, ‘regenerative protein’, ‘lithostatin’ combined with ‘infection’ and ‘sepsis’ found 46 records. The search was restricted to the five trials that measured PSP using the enzyme-linked immunosorbent assay technique (ELISA). We used Bayesian hierarchical regression models for pooled estimates and to predict mortality or disease severity using PSP, C-Reactive Protein (CRP) and procalcitonin (PCT) as main predictor. We used statistical discriminative measures, such as the area under the receiver operating characteristic curve (AUC) and classification plots. Results Among the 678 patients included, the pooled ICU mortality was 17.8% (95% prediction interval 4.1% to 54.6%) with a between-study heterogeneity (I-squared 87%). PSP was strongly associated with ICU mortality (OR = 2.7, 95% credible interval (CrI) [1.3–6.0] per one standard deviation increase; age, gender and sepsis severity adjusted OR = 1.5, 95% CrI [0.98–2.8]). The AUC was 0.69 for PSP 95% confidence interval (CI) [0.64–0.74], 0.61 [0.56–0.66] for PCT and 0.52 [0.47–0.57] for CRP. The sensitivity was 0.96, 0.52, 0.30 for risk thresholds 0.1, 0.2 and 0.3; respective false positive rate values were 0.84, 0.25, 0.10. Conclusions We found that PSP showed a very good discriminative ability for both investigated study endpoints ICU mortality and infection severity; better in comparison to CRP, similar to PCT. Combinations of biomarkers did not improve their predictive ability. …

Abstract Introduction The aim of this study was to investigate how long hospitalized patients stayed positive to the nasopharyngeal swab, and what demographic and clinical factors influence the time-to-negative swab. Methods We enrolled in a multicenter, observational, retrospective study involving 17 COVID-19 units in eight cities of the Campania, southern Italy all patients hospitalized from March 2020 to May 2021 diagnosed with Severe Acute Respiratory Distress Syndrome-Coronavirus-2 (SARS-CoV-2) infection for whom time-to-negative swab was available. Results 963 patients were enrolled. We defined three groups considering time-to-negative swab: the first including patients with time-to-negative swab before the 26th day, the second including patients with time-to-negative swab from day 26 to day 39, and the third including patients with time-to-negative swab > 39 days. 721 (74.9%) patients belonged to the first group, 194 (20.1%) to the second, and 52 (5.4%) belonged to the third group. Belonging to group 2 and 3 seemed to be influenced by age (p value 

Abstract Introduction Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections commonly cause hospital-acquired infections. The study aimed to compare the outcomes of CRKP infections between patients receiving ceftazidime avibactam +/− aztreonam and polymyxins in a hospital setting with a high prevalence of New Delhi Metallo Beta Lactamase production. Methods We conducted a retrospective cohort study from January 2020 to September 2022 in critically ill adult patients admitted to a non-COVID-19 medical intensive care unit with CRKP infection. The patients were followed up for a total of 30 days or death, whichever was later. Results Of a total of 106 patients included in the study, 65 patients received polymyxins and 41 patients received ceftazidime–avibactam +/− aztreonam. Higher 30-day mortality was noted in the polymyxin group (56.9% vs. 29.2%, P = 0.005). The mean time to event (mortality) in ceftazidime–avibactam +/− aztreonam was 23.9 + 1.5 days which was significantly higher compared to polymyxins (17.9 + 1.2 days, p = 0.006). On Cox regression analysis, after adjusting for the covariates, the hazard ratio for time to event with the use of polymyxin was 2.02 (95% CI: 1.03–3.9). Conclusion Ceftazidime–avibactam + aztreonam is possibly associated with better clinical outcomes in patients infected with CRKP. …

Abstract Purpose Timely and accurate data on the epidemiology of sepsis are essential to inform policy decisions and research priorities. We aimed to investigate the validity of inpatient administrative health data (IAHD) for surveillance and quality assurance of sepsis care. Methods We conducted a retrospective validation study in a disproportional stratified random sample of 10,334 inpatient cases of age ≥ 15 years treated in 2015–2017 in ten German hospitals. The accuracy of coding of sepsis and risk factors for mortality in IAHD was assessed compared to reference standard diagnoses obtained by a chart review. Hospital-level risk-adjusted mortality of sepsis as calculated from IAHD information was compared to mortality calculated from chart review information. Results ICD-coding of sepsis in IAHD showed high positive predictive value (76.9–85.7% depending on sepsis definition), but low sensitivity (26.8–38%), which led to an underestimation of sepsis incidence (1.4% vs. 3.3% for severe sepsis-1). Not naming sepsis in the chart was strongly associated with under-coding of sepsis. The frequency of correctly naming sepsis and ICD-coding of sepsis varied strongly between hospitals (range of sensitivity of naming: 29–71.7%, of ICD-diagnosis: 10.7–58.5%). Risk-adjusted mortality of sepsis per hospital calculated from coding in IAHD showed no substantial correlation to reference standard risk-adjusted mortality (r = 0.09). Conclusion Due to the under-coding of sepsis in IAHD, previous epidemiological studies underestimated the burden of sepsis in Germany. There is a large variability between hospitals in accuracy of diagnosing and coding of sepsis. Therefore, IAHD alone is not suited to assess quality of sepsis care. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background Despite the fact that prison inmates are a population at higher risk than other groups of suffering from intestinal parasite infections in relation to their living conditions, information about these diseases in prison environments is still scarce. Herein, we analyze the status of intestinal parasite infections in a Spanish prison. Methods A cross-sectional study involving 528 inmates was conducted from April to June 2022 among inmates at Centro Penitenciario Picassent (Valencia, Spain). Stool specimens were examined using the direct wet mount technique, the formol-ether concentration technique, and the Ziehl-Neelsen staining method. We used STATA 16.1 for data analysis. We consider a p-value less than 0.05 significant at a 95% confidence level. Results Of the 528 inmates (471 men and 57 women; a mean age of 41.94 years) enrolled in the study, 83 (15.7%) were infected. Only six species of protozoa were detected. The gut potential microeukaryotic pathobiont Blastocystis sp. was the predominant parasite, accounting for 37 (44.6%) of the infections. Gut parasite amebas (6.6%) and pathobionts (5.3%) were more prevalent than flagellates (2.3%). The prevalence of infection with pathogenic species (8.9%) was similar to that of non-pathogenic species (8.7%). Infection among men (15.2%) was higher than in women (0.6%) (p 

Abstract Background Dialister pneumosintes is an anaerobic, Gram negative bacillus, found in the human oral cavity and associated with periodontitis. It has also been isolated from gastric mucosa and stool samples. Recent case reports implicate D. pneumosintes in local infection such as dental root canals, sinusitis, Lemierres syndrome and brain abscesses, as well as distal infections of the liver and lung through haematogenous spread. Case presentation We present a novel case of aortic graft infection and aortoenteric fistula (AEF) in a 75 year old Caucasian male, associated with D. pneumosintes bacteraemia. Microbiological evaluation of septic emboli in the lower limbs revealed other gastrointestinal flora. This suggests either AEF leading to graft infection and subsequent distal emboli and bacteraemia, or a dental origin of infection which seeded to the graft, resulting in AEF and systemic infection. To our knowledge this is the first report of D. pneumosintes associated aortic graft infection. The patient underwent surgical explantation, oversew of the aorta and placement of extra-anatomical bypass graft in conjunction with antimicrobial therapy, making a good recovery with discharge home after a 35-day hospital admission. Conclusion We report a case of Dialister pneumosintes bacteraemia associated with aortic graft infection. To our knowledge, vascular graft-associated infection with D. pneumosintes has not been reported before. …

Abstract The objective of the study was to analyze the spatial distribution of vaccination coverage of bacterial meningitis vaccine: A, C, W and Y (menacwy) and identify the association between socioeconomic and social environment factors with menacwy vaccine coverage among adolescents in the state of Minas Gerais (MG), Brazil. This is an ecological, mixed study, conducted with secondary data from the 853 municipalities of the State of MG, Brazil, from 2020 to 2022, provided by the information system of the National Immunization Program. For spatial statistical analysis, spatial dependence and the presence of spatial clusters formed by municipalities with high and low vaccination coverage of Menacwy were evaluated. In the year 2021, MG presented the largest vaccination coverage (60.58%) since the introduction of the Menacwy vaccine by the PNI. Regarding the analysis of global regressions, it is observed that for the year 2020, as the MG Index of Social Responsibility-Health increased and MG Index of Social Responsibility—Public Security increased, increased the vaccination coverage of the municipalities of the Menacwy vaccine. Finally, compared to 2021, similar association was observed in relation to the proportion of the population served by the Family Health Strategy of the municipalities of the state of MG and per capita spending on education activities: as this indicator increased, with increased coverage of the Vaccine of the Menacwy vaccine of the state municipalities. They reinforce the importance of assessing the quality-of-care management and health surveillance system, professional training, and damage reduction to populations, especially adolescents. …

Abstract Background The gastrointestinal tract contains a massive microbiota, and targeting the gut could be a potential intervention for sepsis. However, the interaction between sepsis and the intestinal microbiota is defined as an “incompletely understood bidirectional relationship”. Methods This retrospective observational cohort study investigated the fecal microbiota of sepsis patients admitted to the Department of Critical Care Medicine of the Central Hospital of Wuhan, China, from May 2019 to January 2020. 14 septic patients were divided into the non-severe group and the severe group according to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Herein, fecal samples were serially collected on admission, the third, fourth, and fifth days, and ICU discharge. The fecal microbiota was analyzed by 16S rRNA gene sequencing and its correlation with clinical parameters was evaluated. Results Bacteroidetes, Firmicutes, and Proteobacteria were dominant phyla at ICU admission, and fecal biodiversity was not significantly different between the non-severe group (APACHE II  15). However, the diversity of the gut microbiota was significantly lower at ICU discharge than that at ICU admission with the extension of treatment time. Further significant difference flora analysis (LEfSe) showed that the genera Veillonella and Ruminococcus were the most discriminant biomarkers at ICU admission in non-severe and severe patients, respectively, while Enterococcus was the most discriminant biomarker at ICU discharge in all septic patients. Of note, liver function tests, including ALT, AST, TBIL, and DBIL correlated with the prevalence of various bacterial genera. Conclusions The diversity of the gut microbiota in patients with sepsis decreases dramatically during ICU stay, and there are distinct dynamic changes in gut microbiota among patients with different severity in sepsis. …

Abstract Background Tuberculosis, along with HIV, is the leading cause of mortality and morbidity globally. Despite the fact that several primary studies have been conducted on the incidence rate of tuberculosis in HIV-infected people in Sub-Saharan Africa, the regional-level tuberculosis incidence rate remains unknown. The objective of this study is to determine the tuberculosis incidence rate and its associated factors in HIV-infected people in Sub-Saharan Africa. Methods A systematic review and meta-analysis were conducted by searching four databases for studies published in English between January 1, 2000, and November 25, 2022. The study was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. To assess the quality of the studies, the Joanna Briggs Institute critical appraisal checklist was used. A random-effects model meta-analysis was used to determine the pooled incidence of tuberculosis using STATA version 15. The I2 heterogeneity test was used to assess heterogeneity. Subgroup and sensitivity analyses were performed. Funnel plots and Egger’s regression tests were used to investigate publication bias. The pooled estimate predictors of tuberculosis incidence rate with a 95% confidence interval were also determined using the hazard ratio of each factor (HR). Results Out of a total of 3339 studies, 43 were included in the analysis. The overall pooled incidence rate of tuberculosis in HIV-infected people was 3.49 per 100 person-years (95% CI: 2.88–4.17). In the subgroup analysis, the pooled incidence rate of tuberculosis in HIV-infected children was 3.42 per 100 person-years (95% CI: 1.78, 5.57), and it was 3.79 per 100 person-years (95% CI: 2.63, 5.15) in adults. A meta-analysis revealed that underweight (AHR = 1.79, 95% CI: 1.61–1.96), low CD4 count (AHR = 1.23, 95% CI: 1.13–1.35), male gender (AHR = 1.43, 95% CI: 1.22–1.64), advanced WHO clinical stages (AHR = 2.29, 95% CI: 1.34–3.23), anemia (AHR = 1.73, 95% CI: 1.34–2.13), bedridden or ambulatory (AHR = 1.87, 95%), lack of isoniazid preventive therapy (AHR = 3.32, 95% CI: 1.08–2.28), and lack of cotrimoxazole (AHR = 1.68, 95% CI: 1.08–2.28) were risk factors for tuberculosis incidence. HIV patients who received antiretroviral therapy had a 0.53 times higher risk of acquiring tuberculosis than HIV patients who did not receive antiretroviral therapy (AHR = 0.53; 95% CI: 0.3–0.77). Conclusion In this systematic review and meta-analysis study, the incidence rate of tuberculosis among HIV-positive people was higher than the WHO 2022 Africa regional estimated report. To reduce the incidence of tuberculosis among HIV patients, HIV patients should take isoniazid prevention therapy (IPT), cotrimoxazole prophylaxis, and antiretroviral therapy (ART) without interruption, as well as increase the frequency and diversity of their nutritional intake. Active tuberculosis screening should be increased among HIV-infected people. …

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

Journal of Medical Virology, Volume 95, Issue 9, September 2023.

AbstractEbola virus disease is marked by the rapid virus replication and spread. Ebola virus (EBOV) enters the cell by macropinocytosis, replicates in the cytoplasm, and nascent virions egress from the cell surface to infect neighboring cells. Here, we show that EBOV uses an alternate route to disseminate: tunneling nanotubes (TNTs). TNTs, an actin-based long-range intercellular communication system, allows for direct exchange of cytosolic constituents between cells. Using live, scanning electron and high-resolution quantitative 3D-microscopy, we show that EBOV infection of primary human cells results in the enhanced formation of TNTs, containing viral nucleocapsids. TNTs promoted the intercellular transfer of nucleocapsids in the absence of live virus, and virus could replicate in cells devoid of entry factors after initial stall. Our studies suggest an alternate model of EBOV dissemination within its host, laying the groundwork for further investigations into the pathogenesis of filoviruses and, importantly, stimulating new areas of antiviral design.

AbstractTo gain insight into interactions among respiratory viruses, we modeled influenza A virus (IAV) - SARS-CoV-2 coinfections using differentiated human airway epithelial cultures. Replicating IAV induced a more robust interferon response than SARS-CoV-2 and suppressed SARS-CoV-2 replication in both sequential and simultaneous infections, whereas SARS-CoV-2 did not enhance host cell defense during influenza infection or suppress IAV replication. Oseltamivir, an antiviral targeting influenza, reduced IAV replication during coinfection but also reduced the host antiviral response and restored SARS-CoV-2 replication. These results demonstrate how perturbations in one viral infection can impact its effect on a coinfecting virus.

AbstractBacterial vaginosis (BV) is a dysbiotic condition of the vaginal microbiome associated with higher risk of infection by Neisseria gonorrhoeae - the cause of gonorrhea. Here we test if one known facet of BV - the presence of bacterial cytolysins – leads to mobilization of intracellular contents that enhance gonococcal virulence. We cloned and expressed recombinant vaginolysin (VLY), a cytolysin produced by the BV-associated bacterium Gardnerella, verifying that it liberates contents of cervical epithelial (HeLa) cells, while vector control preparations did not. We tested if VLY mediates a well-known gonococcal virulence mechanism – the molecular mimicry of host glycans. To evade host immunity, N. gonorrhoeae caps its lipooligosaccharide (LOS) with α2-3-linked sialic acid. For this, gonococci must scavenge a metabolite made inside host cells. Flow-cytometry based lectin-binding assays showed that gonococci exposed to vaginolysin-liberated contents of HeLa cells displayed greater sialic acid capping of their LOS. This higher level of bacterial sialylation was accompanied by increased binding of the complement regulatory protein Factor H, and greater resistance to complement attack. Together these results suggest that cytolytic activities present during BV may enhance the ability of N. gonorrhoeae to capture intracellular metabolites and evade host immunity via glycan molecular mimicry.

IntroductionOlder surgical candidates are at increased risk of a phenomenon known as postoperative cognitive dysfunction (POCD). Several studies have looked at the incidence of POCD at different time points following surgery, using different study methods. Fewer have assessed whether changes in cognition after surgery are attributable to surgery and how they impact patient function and quality of life. The aim of this systematic review is to summarise and appraise studies addressing any of the following research questions (RQs): (RQ1) what is the frequency of POCD after non-cardiac surgery?; (RQ2) is non-cardiac surgery associated with an increased risk of cognitive decline?; (RQ3) is POCD after non-cardiac surgery associated with patient-important outcomes? Methods and analysisThis protocol adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Three electronic databases (MEDLINE, PsycINFO and EMBASE) will be systematically searched from their inception date. Identified studies will be screened by two reviewers for eligibility using Covidence, and data will be extracted into a standardised electronic form. We will evaluate methodological quality of included studies using the Quality In Prognosis Studies and its adaptation to the overall prognosis question, and the CLARITY risk of bias for cohort and case–control studies. For RQ1, we will estimate an average POCD frequency at different time points by performing a meta-analysis of included studies when appropriate. For RQ2 and RQ3, we will extract and meta-analyse the effect measures for the association of surgery with cognitive decline when compared with the non-surgical comparator, and association of cognitive changes with functional changes, quality of life and other patient-important outcomes based on available evidence. We will narratively summarise and discuss the different methods implemented in the existing studies to answer the three RQs, and when meta-analysis is deemed infeasible, we will qualitatively report the results of the included studies. Ethics and disseminationThis project involves the collection and analysis of data from previously published studies and therefore does not require ethics approval. We plan to present the findings of this research project at peer-reviewed conferences and publish the results in peer-reviewed journals. PROSPERO registration numberCRD42022370674. …

ObjectiveThis survey investigated the relationship between social isolation, depression, nutritional status and quality of life among community-dwelling older adults during COVID-19. DesignThis was a cross-sectional survey study. SettingCommunities in Pudong New Area, Shanghai, China that have contracted with Renji Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. ParticipantsFrom May to July 2022, 406 community-dwelling older adults were selected by convenience sampling in Shanghai, China. Primary and secondary outcome measuresThe Lubben Social Network Scale, Geriatric Depression Scale, 36-item Short Form Health Survey Scale and risk assessment of malnutrition were used in older adults. Mediation models were constructed to determine the mediating role of depression and nutritional status on social isolation and quality of life among older adults. ResultsThe prevalence of social isolation among older adults in the community was 44.3%. The total social isolation score in community-dwelling older adults was positively associated with the total malnutrition risk and quality of life scores, and negatively associated with depression (p

ObjectivesTargeted testing policy for HIV/syphilis at Dutch sexual health centres (SHCs) was evaluated for its efficiency in younger heterosexuals but not for heterosexuals ≥25 years. Currently, all older heterosexuals are tested for HIV/syphilis at SHCs. To explore possibilities for increased efficiency of testing in heterosexuals aged >25 years, this study aimed to identify determinants of HIV and syphilis diagnoses that could be used in targeted testing strategies. DesignAn observational study using surveillance data from all Dutch SHC. ParticipantsWomen and heterosexual men aged >25 years visiting SHC between 2015 and 2021. Primary and secondary outcome measuresThe primary outcome was HIV/syphilis diagnosis, determinants of a diagnosis were analysed. Based on these determinants and their applicability in SHC practice, different targeted testing scenarios were evaluated. For each scenario, the percentage of consultations involving HIV and syphilis testing and the total amount of missed HIV and syphilis diagnoses were calculated. Results109 122 consultations were included among 75 718 individuals. The strongest determinants of HIV/syphilis diagnosis were HIV/syphilis-specific symptoms (adjusted OR (aOR) 34.9 (24.1–50.2)) and receiving partner notification (aOR 18.3 (13.2–25.2)), followed by low/middle education level (aOR 2.8 (2.0–4.0)), male sex (aOR 2.2 (1.6–3.0)) and age ≥30 years (aOR 1.8 (1.3–2.5)). When applying feasible determinants to targeted testing scenarios, HIV/syphilis testing would have been conducted in 54.5% of all consultations, missing 2 HIV and 3 syphilis diagnoses annually (13.4% and 11.4% of all diagnoses, respectively). In the scenario with the lowest number of missed HIV/syphilis diagnoses (0.3 HIV and 2 syphilis diagnoses annually), HIV/syphilis testing would have been conducted in 74.2% of all consultations. ConclusionsIn any targeted testing scenario studied, HIV and/or syphilis diagnoses would have been missed. This raises the question whether it is acceptable to put any of these scenarios into practice. This study contributes to a discussion about the impact of targeted testing policy. …

IntroductionCoronary heart disease (CHD) is one of the common cardiovascular diseases that seriously jeopardise human health, and endothelial inflammation and dyslipidaemia are the initiating links leading to its occurrence. Percutaneous coronary intervention (PCI) is one of the most effective surgical treatments for CHD with narrowed or blocked blood vessels, which can quickly unblock the blocked vessels and restore coronary blood supply. However, most patients may experience coronary microcirculation disorders (CMDs) and decreased cardiac function after PCI treatment, which directly affects the efficacy of PCI and the prognosis of patients. Preprotein converting enzyme subtilisin/Kexin 9 (PCSK9) inhibitors are novel pleiotropy lipid-lowering drug with dual anti-inflammation and lipid-lowering effects, and represent a new clinical pathway for rapid correction of dyslipidaemia. Therefore, we designed this protocol to systematically evaluate the effects of PCSK9 inhibitors on coronary microcirculation and cardiac function in patients with CHD after PCI, and to provide high-quality evidence-based evidence for the clinical application of PCSK9 inhibitors. Methods and analysisThis protocol is reported strictly in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols Guidelines. We will search PubMed, EMBASE, Web of Science and three Chinese databases (CNKI, Wanfang and VIP database) according to preset search strategies, without language and publication data restrictions. We will work with manual retrieval to screen references that have been included in the literature. Google Scholar will be used to search for grey literature. The final included literature must meet the established inclusion criteria. Titles, abstracts and full text will be extracted independently by two reviewers, and disagreements will be resolved through discussion or the involvement of a third reviewer. Extracted data will be analysed using Review Manager V.5.3. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias. Publication bias will be assessed by funnel plots. Heterogeneity will be assessed by I2 test and subgroup analyses will be used to further investigate potential sources of heterogeneity. The quality of the literature will be assessed by GRADE score. This protocol will start in January 2026 and end in December 2030. Ethics and disseminationThis study is a systematic review of published literature data and no special ethical approval was required. PROSPERO registration numberCRD42022346189. …

IntroductionPrompt detection of hepatocellular carcinoma (HCC) in patients with chronic liver diseases is critical for enhancing prognosis. Existing imaging techniques and serum markers fall short of clinical needs. This study aims to establish a non-invasive diagnostic model for early HCC detection in the Chinese population. Methods and analysisThis prospective, multicentre, observational study will enrol 2000 participants, including HCC patients, those with chronic liver diseases (hepatitis, cirrhosis and benign liver space-occupying lesions), and healthy individuals. The study will collect demographic data and blood samples, which will be used to test α-fetoprotein (AFP), des--carboxy-prothrombin (DCP) and circulating tumour DNA (ctDNA) methylation. The GAMAD (Gender+Age+Methylation+AFP+DCP) model involving gender, age, ctDNA methylation signature, AFP and DCP will be developed and blindly validated in training and validation sets (1400 and 600 cases, respectively). Primary endpoints include sensitivity, specificity and accuracy (receiver operating characteristic curves; area under the curve value) of GAMAD for HCC and/or high-risk HCC groups. Secondary endpoints involve comparing GAMAD with the established GALAD (Gender+Age+AFP-L3+AFP+DCP) model and each blood index (AFP, DCP and methylation signature) to evaluate: (1) GAMAD’s clinical utility for HCC patients in all stages according to different staging systems; (2) GAMAD’s discrimination ability for patients in various subgroups, including liver cirrhosis (LC) related HCC and LC, hepatitis B virus (HBV) related HCC and HBV, hepatitis C virus (HCV) related HCC and HCV, and non-alcoholic fatty liver disease (NAFLD) related HCC and NAFLD. Ethics and disseminationThis trial has been approved by the Medical Ethics Committees of the First Hospital of Jilin University (#22K073-001), the Eastern Hepatobiliary Surgery Hospital, Naval Medical University (#EHBHKY2023-H0003-P001) and Tianjin Third Central Hospital (#IRB2023-007-01). All participants in the trial will provide written informed consent. Results of this study will be disseminated in peer-reviewed scientific journals and at conferences nationally and internationally. Trial registration numberNCT05626985. …

Strategic use of Plasmodium falciparum genetic variation has great potential to inform public health actions for malaria control and elimination. Malaria molecular surveillance (MMS) begins with a strategy to identify and collect parasite samples, guided by public-health priorities. In this review we discuss sampling design practices for MMS and point out epidemiological, biological, and statistical factors that need to be considered. We present examples for different use cases, including detecting emergence and spread of rare variants, establishing transmission sources and inferring in malaria transmission intensity. This review will potentially guide the collection of samples and data, serve as a starting point for further methodological innovation, and enhance utilization of MMS to support malaria elimination.

Tuberculosis (TB) is the leading infectious killer of adults worldwide and responsible for almost 2 million deaths each year. The fact that the disease is entirely preventable and curable makes these statistics especially bleak, and they speak to the gross inequalities that drive TB morbidity and mortality today. While in wealthier countries and populations, TB is considered a “disease of the past”, it was only in the mid-1950s that modern chemotherapeutic approaches to TB were developed. Prior to this time, “rest cures”, isolation in sanitoria, and painful surgeries were the norm, virtually guaranteeing death for most.

by Zanetta Gant, André Dailey, Xiaohong Hu, Wei Song, Linda Beer, Shacara Johnson Lyons, Damian J. Denson, Anna Satcher Johnson Objective(s) To examine associations between Index of Concentration at the Extremes (ICE) measures for economic and racial segregation and HIV outcomes in the United States (U.S.) and Puerto Rico. Methods County-level HIV testing data from CDC’s National HIV Prevention Program Monitoring and Evaluation and census tract-level HIV diagnoses, linkage to HIV medical care, and viral suppression data from the National HIV Surveillance System were used. Three ICE measures of spatial polarization were obtained from the U.S. Census Bureau’s American Community Survey: ICEincome (income segregation), ICErace (Black-White racial segregation), and ICEincome+race (Black-White racialized economic segregation). Rate ratios (RRs) for HIV diagnoses and prevalence ratios (PRs) for HIV testing, linkage to care within 1 month of diagnosis, and viral suppression within 6 months of diagnosis were estimated with 95% confidence intervals (CIs) to examine changes across ICE quintiles using the most privileged communities (Quintile 5, Q5) as the reference group. Results PRs and RRs showed a higher likelihood of testing and adverse HIV outcomes among persons residing in Q1 (least privileged) communities compared with Q5 (most privileged) across ICE measures. For HIV testing percentages and diagnosis rates, across quintiles, PRs and RRs were consistently greatest for ICErace. For linkage to care and viral suppression, PRs were consistently lower for ICEincome+race. Conclusions We found that poor HIV outcomes and disparities were associated with income, racial, and economic segregation as measured by ICE. These ICE measures contribute to poor HIV outcomes and disparities by unfairly concentrating certain groups (i.e., Black persons) in highly segregated and deprived communities that experience a lack of access to quality, affordable health care. Expanded efforts are needed to address the social/economic barriers that impede access to HIV care among Black persons. Increased partnerships between government agencies and the private sector are needed to change policies that promote and sustain racial and income segregation. …

The SARS-CoV-2 (“Covid-19”) pandemic altered human life throughout the world and led to devastating illness and many deaths [1]. This infection has been associated with a wide array of complications. Risk factors for adverse Covid-19 outcomes include older age and metabolic syndrome associated factors (diabetes, hypertension, obesity), which are also risk factors for one Covid-19 complication that merits attention: rhabdomyolysis [1, 2].

Abstract Background While anaemia following liver transplant is common, anaemia in the context of BK viraemia is not a commonly recognised phenomenon. Case presentation We present the case of 59-year old gentleman with severe anaemia in the context of BK viraemia and nephropathy following ABO incompatible liver transplant. Severity of anaemia appeared to correlate with high titres of BK virus in the serum. Bone marrow biopsy revealed hypocellular marrow with normal cytogenetics. Anaemia improved with treatment with cidofovir, intravenous immunoglobulin, reduction in immunosuppression and erythropoietin stimulating agent. Conclusion To our knowledge, this is the first case of anaemia post liver transplant contributed to by BK viraemia. …

Abstract Background The course of monkeypox can be severe. Our aim was to retrospectively compare the risk of hospital admission, the need for ventilation, sepsis, pneumonitis and death between the recent outbreak and historical outbreaks. Materials and Methods Cases of monkeypox were retrieved from the TriNetX database and assigned to either cohort I (recent outbreak between May 1st and September 16th, 2022) and cohort II (historical outbreaks before May 1st, 2022). After matching for age distribution, statistical analysis was performed. Results Of 640 patients with monkeypox 81 subjects per cohort remained after matching (mean age±standard deviation = 36.1±18.3 years). Within 56 days after diagnosis 10 patients per cohort were hospitalized (12.4%) and/or developed sepsis (12.4%). The risk of ventilation and pneumonitis were significantly lower among cohort I compared with cohort II (0 vs. 10 cases; risk difference = 12.4%; p = 0.001; Log-Rank test). No cases of death were recorded. Conclusion Even though monkeypox provides a risk of severe courses, the infection is self-limiting in most cases. Unlike past outbreaks, the risk of ventilation and pneumonitis may be relatively low among recent outbreaks. …

Abstract Background Severe community-acquired pneumonia (SCAP) is commonly treated with an empiric combination therapy, including a macrolide, or a quinolone and a β-lactam. However, the risk of Legionella pneumonia may lead to a prolonged combination therapy even after negative urinary antigen tests (UAT). Methods We conducted a retrospective cohort study in a French intensive care unit (ICU) over 6 years and included all the patients admitted with documented SCAP. All patients received an empirical combination therapy with a β-lactam plus a macrolide or quinolone, and a Legionella UAT was performed. Macrolide or quinolone were discontinued when the UAT was confirmed negative. We examined the clinical and epidemiological features of SCAP and analysed the independent factors associated with ICU mortality. Results Among the 856 patients with documented SCAP, 26 patients had atypical pneumonia: 18 Legionella pneumophila (LP) serogroup 1, 3 Mycoplasma pneumonia (MP), and 5 Chlamydia psittaci (CP). UAT diagnosed 16 (89%) Legionella pneumonia and PCR confirmed the diagnosis for the other atypical pneumonia. No atypical pneumonia was found by culture only. Type of pathogen was not associated with a higher ICU mortality in the multivariate analysis. Conclusion Legionella pneumophila UAT proved to be highly effective in detecting the majority of cases, with only a negligible percentage of patients being missed, but is not sufficient to diagnose atypical pneumonia, and culture did not provide any supplementary information. These results suggest that the discontinuation of macrolides or quinolones may be a safe option when Legionella UAT is negative in countries with a low incidence of Legionella pneumonia. …

Abstract Background Malaria cases in non-endemic zero-indigenous case areas are most likely to have been imported whatever of the route of importation. In countries recently declared malaria-free and now without local transmission, imported cases remain a threat to re-introduction of the disease and a burden on the health system. Case presentation Three days after returning from a long trip to malaria- endemic countries; Abyei-Sudan, Chad and Uganda, a 41-year-old male resident from Jericho, Palestine, suffered paroxysms of fever, general fatigue, myalgia, arthralgia, headache, and a strong desire to vomit. Thin and thick Giemsa-stained blood smears were prepared and examined microscopically using oil immersion. Immature trophozoites (ring forms) were seen to parasitize approximately 10% of the erythrocytes revealing hyperparasitemia equivalent to > 100,000 parasites/ µl indicating severe malaria [1, 2]. The double chromatin configuration (headphones) and accolé (applique) position are both indicative of Plasmodium falciparum infection. The 18S rRNA- PCR targeting the rPLU6-rPLU5 region was used to confirm the diagnosis. The next-generation sequencing (NGS) method was carried out according to the manufacturer’s instructions (Illumina® DNA Prep, (M) Tagmentation kit (20060060), Illumina) to identify Plasmodium spp. Furthermore, NGS produced a whole-genome sequence of 22.8Mbp of the 14 chromosomes and 25Kbp of the apicoplast. A BLAST search of the apicoplast DNA and selected chromosomal DNA revealed that P. falciparum was the causative agent. The merozoite surface protein-1 (msp-1) was used to construct a phylogenetic tree of 26 P. falciparum, including the one isolated from the patient from Jericho, which clustered with the Sudanese isolate indicating genetic relatedness between the two. Conclusion The travel history together with signs and symptoms of malaria, followed by prompt diagnosis using conventional microscopic inspection of Giemsa-stained films together with molecular DNA tracking tools like msp-1 were key means in tracking the place of origin of infection in the case of travel to multiple destination. …

Abstract Introduction Acute uncomplicated urinary tract infections are common in outpatient settings but are not treated optimally. Few studies of the outpatient use of antibiotics for specific diagnoses have been done in sub-Saharan Africa, so little is known about the prescribing patterns of medical officers in the region. Methods Aga Khan University has 16 outpatient clinics throughout the Nairobi metro area with a medical officer specifically assigned to that clinic. A baseline assessment of evaluation and treatment of suspected UTI was performed from medical records in these clinics. Then the medical officer from each of the 16 clinics was recruited from each clinic was recruited with eight each randomized to control vs. feedback groups. Both groups were given a multimodal educational session including locally adapted UTI guidelines and emphasis on problems identified in the baseline assessment Each record was scored using a scoring system that was developed for the study according to adequacy of history, physical examination, clinical diagnosis matching recorded data, diagnostic workup and treatment. Three audits were done for both groups; baseline (audit 1), post-CME (audit 2), and a final audit, which was after feedback for the feedback group (audit 3). The primary analysis assessed overall guideline adherence in the feedback group versus the CME only group. Results The overall scores in both groups showed significant improvement after the CME in comparison to baseline and for each group, the scores in most domains also improved. However, audit 3 showed persistence of the gains attained after the CME but no additional benefit from the feedback. Some deficiencies that persisted throughout the study included lack of workup of possible STI and excess use of non-UTI laboratory tests such as CBC, stool culture and H. pylori Ag. After the CME, the use of nitrofurantoin rose from only 4% to 8% and cephalosporin use increased from 49 to 67%, accompanied by a drop in quinolone use. Conclusion The CME led to modest improvements in patient care in the categories of history taking, treatment and investigations, but feedback had no additional effect. Future studies should consider an enforcement element or a more intensive feedback approach. …

Abstract Background Public health depends largely on people’s knowledge, beliefs, or behaviors regarding their health and medical treatments. Although works based on the health belief model have shown that public beliefs about medical treatments affect willingness to take the treatments, little is known about the effects of changes in beliefs on attitudes toward treatment. How one’s past experiences relate to one’s beliefs about a given medical treatment is worth considering. Methods We implemented an online panel survey in February 2021 and March 2022 in Japan before and after COVID-19 vaccines were administered to the public within the country. We exploited delayed localized hypersensitivity reactions to COVID-19 vaccines, namely, “COVID arm”, as an exogenous shock to investigate the relationship between past negative experiences and current beliefs about medical treatments or science. “COVID arm” was an unexpected side effect and thus likely caused updated beliefs about the vaccine. Out of the nonprobability sample of 15,000 respondents in the first wave in February 2021, 9,668 respondents also responded to the second wave conducted in March 2022. Outcome variables were whether experiencing “COVID arm” affected the respondents’ 1) confidence in vaccine safety, 2) willingness to take the next dose of COVID-19 vaccines, 3) acknowledgment of the importance of vaccination, and 4) confidence in science. We measured the impact of experience with “COVID arm” on changes in the probability that survey respondents would respond affirmatively to questions posed about the issues listed above. Results Experiencing “COVID arm” significantly lowered confidence in the safety of vaccination by 4.3 percentage points, which was approximately 6% of the sample mean for the first wave, and lowered the probability of taking a second dose of the COVID-19 vaccine by 1.5 percentage points. These adverse impacts were observed after conditioning background characteristics and prior confidence in vaccination. Experiencing “COVID arm” affected neither the acknowledged importance of vaccination nor confidence in science in a statistically significant way. Conclusions An unexpected and uncomfortable shock regarding beliefs about a treatment decreases willingness to take the treatment. An appropriate public health policy should account for this effect. Trial registration The survey was preregistered with the American Economic Association’s RCT Registry (Fukai et al., 2022). …

AbstractBackgroundNative vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO.MethodsWe searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin containing regimens. A random-effects model meta-analysis estimated relative risks (RR) and risk difference (RD) with 95% confidence intervals (CI).ResultsThirteen studies (two RCTs and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (RD -14%; 95% CI: -19%, -8%; P 

AbstractBackgroundCurrent Tuberculosis treatment regimens could be improved by adjunct host-directed-therapies (HDT) targeting host responses. We investigated the anti-mycobacterial capacity of macrophages from tuberculosis patients in a phase 1/2 randomized clinical trial (TBCOX2) of the Cyclooxygenase-2 inhibitor etoricoxib.MethodsPBMC from 15 tuberculosis patients treated with adjunctive COX-2i and 18 controls (standard therapy) were collected on day 56 after treatment initiation. The ex vivo capacity of macrophages to control mycobacterial infection was assessed by challenge with Mycobacterium avium, using an in vitro culture model. Macrophage inflammatory responses were analyzed by gene expression signatures, and concentrations of cytokines were analyzed in supernatants by multiplex.ResultsMacrophages from patients receiving adjunctive COX-2i treatment had higher Mav loads than controls after 6 days, suggesting an impaired capacity to control mycobacterial infection compared to macrophages from the control group. Macrophages from the COX-2i group had lower gene expression of TNF, IL-1B, CCL4, CXCL9, and CXCL10 and lowered production of cytokines IFN-β and S100A8/A9 than controls.ConclusionsOur data suggest potential unfavorable effects with impaired macrophage capacity to control mycobacterial growth in tuberculosis patients receiving COX-2i treatment. Larger clinical trials are required to analyze the safety of COX-2i as HDT in patients with tuberculosis.

AbstractBackgroundPeople with suspected malaria may harbor Plasmodium falciparum undetected by rapid diagnostic test (RDT). The impact is not fully understood of these sub-patent infections on the risk of developing clinical malaria.MethodsWe analyzed sub-patent P. falciparum infections using a longitudinal cohort in a high transmission site in Kenya. Weighted Kaplan-Meier models estimated the risk difference (RD) for clinical malaria during the 60 days following a symptomatic sub-patent infection. Stratum-specific estimates by age and transmission season assessed modification.ResultsOver 54 months, we observed 1,128 symptomatic RDT-negative suspected malaria episodes, of which 400 (35.5%) harbored sub-patent P. falciparum. Overall 60-day risk of developing clinical malaria was low following all episodes (8.6%,95% Confidence Interval: 6.7%, 10.4%). In the low transmission season, the risk of clinical malaria was slightly higher in those with sub-patent infection, whereas the opposite was true in the high transmission season (RD low season: 2.3%, CI: 0.4%, 4.2%; RD high season: -4.8%, CI: -9.5%, -0.05%).ConclusionsThe risk of developing clinical malaria among people with undetected sub-patent infections is low. A slightly elevated risk in the low season may merit alternate management, but RDTs diagnose clinically-relevant infections in the high transmission season.

Acute HIV infection (AHI) refers to the period immediately after acquiring HIV, when the virus spreads first through the mucosa and the local lymphoid tissue at the exposure site, and then disseminates systemically [1,2]. This initial phase of HIV infection can be divided into stages based on the sequential appearance of viral markers and antibodies in the blood [3]. It is during AHI when the latent HIV reservoir is established [4], although reseeding of the reservoir will continue in untreated chronic infection [5].

Journal of Medical Virology, Volume 95, Issue 9, September 2023.