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Background: Group B Streptococcus (GBS) infection remains a leading cause of newborn morbidity and mortality. The study aimed to determine the adherence rate to the universal screening policy a decade after its introduction. Secondly, whether the timing of antibiotics given in GBS carriers reduces the incidence of neonatal sepsis., Methods: Delivery records at Hong Kong Baptist Hospital in 2022 were examined to retrieve antenatal and intrapartum details regarding maternal GBS carrier status, previous maternal GBS carrier status, antibiotic treatment, timing of treatment, neonatal condition at birth and whether the neonate had sepsis. Univariate statistics was used to assess the relationship between maternal GBS carrier and neonatal sepsis overall. Incidence of neonatal sepsis was stratified according to mode of delivery and timing of antibiotic., Results: The adherence rate to the universal GBS screening policy was 97%. The risk of neonatal sepsis was 5.45 (95% CI 3.05 to 9.75) times higher in women who were GBS screened positive when compared to non-GBS carriers (p < 0.001). Amongst term neonates from GBS carriers delivered by Caesarean section, the risk of neonatal sepsis significantly decreased by 70% after antenatal antibiotic treatment (p = 0.041) whereas in term neonates delivered vaginally, the risk of neonatal sepsis decreased by 71% (p = 0.022) if intrapartum antibiotic prophylaxis was given 4 or more hours., Conclusion: Giving antenatal antibiotic treatment before Caesarean section or intrapartum antibiotic prophylaxis for 4 or more hours before vaginal delivery may decrease the risk of neonatal sepsis in term neonates delivered from GBS carriers., (© 2024. The Author(s).)

Molecular methods have improved the sensitivity of the detection of pneumococcal carriage in saliva. However, they typically require sample culture enrichment and nucleic acid extraction prior to performing the detection assay and may limit scalability for extensive surveillance of pneumococcus, particularly in low-resource settings. We evaluated the performance of a DNA-extraction-free method for the detection of pneumococcus in saliva. We developed a streamlined qPCR-based protocol for the detection of pneumococcus, omitting culture enrichment and DNA extraction. Using saliva samples collected from children attending childcare centers (New Haven, CT, USA), we evaluated the detection of pneumococcus using saliva lysates as compared to purified DNA extracted from culture-enriched aliquots of the paired samples using qPCR targeting the pneumococcal piaB gene. Of the 759 saliva samples tested from 92 children [median age 3.65 years; IQR (2.46-4.78)], pneumococcus was detected in 358 (47.2%) saliva lysates prepared using the extraction-free protocol and in 369 (48.6%) DNA extracted from culture-enriched samples. We observed near-perfect agreement between the two protocols (Cohen's kappa: 0.92; 95% CI: 0.90-0.95). Despite a high correlation between C T values generated by the two methods ( r = 0.93, P < 0.0001), the C T values generated from saliva lysates were higher (lower concentration) than those from culture-enriched samples (Δ C T = 6.69, P < 0.00001). The cost of detecting pneumococcus using saliva lysates was at least fivefold lower (US$2.53) compared to the cost of the culture-enriched method (range: US$13.60-US$19.46). For pneumococcal carriage surveillance in children, our findings suggest that a DNA extraction-free approach may offer a cost-effective alternative to the resource-intensive culture-enrichment method.IMPORTANCESurveillance for carriage of pneumococcus is a key component of evaluating the performance of pneumococcal vaccines and informing new vaccination strategies. To improve the scalability of pneumococcal carriage surveillance, we show that molecular detection of pneumococcus in saliva from children can be performed without culture enrichment and DNA extraction. Our findings show that using the extraction-free method can improve surveillance efforts for pneumococcal carriage in children, overcoming the resource-intensive hurdle that comes with the use of molecular methods, particularly in low-resource settings., Competing Interests: D.M.W. has received consulting fees from Pfizer, Merck, and GSK and is a PI on research grants from Pfizer and Merck. A.L.W. has received consulting and/or advisory board fees from Pfizer, Merck, Diasorin, PPS Health, Co-Diagnostics, and Global Diagnostic Systems for work unrelated to this project and is a principal investigator on research grants from Pfizer, Merck, NIH RADx UP, and SalivaDirect, Inc. to Yale University and on research grants from NIH RADx, Balvi.io, and Shield T3 to SalivaDirect, Inc. All other co-authors declare no conflict of interest.

Viral hepatitis during pregnancy is common globally. In this review, we focus on the antenatal screen for hepatitis A, B, C and E, the prevention of mother-to-child transmission (MTCT) of hepatitis B and C, and the management of hepatitis A, B, C and E during pregnancy. Neonatal timely administration of hepatitis B immunoglobulin and hepatitis B vaccine is the cornerstone for preventing MTCT of hepatitis B virus (HBV), and perinatal antiviral prophylaxis with tenofovir disoproxil fumarate in mothers with positive HBeAg or HBV DNA >2 × 10 5 IU/ml also plays important roles in further reducing MTCT. Avoidance of risk practices in managing labor and delivery process of women with HCV infection may be useful to reduce MTCT of HCV. Early recognition of severe hepatic injury or liver failure associated with hepatitis viruses by regular liver function tests is critical to prevent maternal mortality associated with hepatitis., Competing Interests: Declaration of competing interest The author has no conflicts of interest to report., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Detection of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) in humans is important to prevent transmission. However, the most optimal culture method to detect CR-PA is unknown. This systematic review aims to determine which culture method is most sensitive and which culture methods are used to detect CR-PA in humans. Second, to establish the most feasible culture method taking into account the turnaround time (TAT), and third, to provide an overview of the sampling sites used to detect carriage., Methods: We systematically searched the electronic databases Embase, Medline Ovid, Cochrane, Scopus, CINAHL, and Web of Science until January 27, 2023. All diagnostic accuracy studies comparing two or more culture methods to detect CR-PA and recent outbreak or surveillance reports on CR-PA carriage or infection in humans, which describe culture methods and their results, were eligible for inclusion. We used QUADAS-2 guideline for diagnostic accuracy studies and the STROBE or ORION guideline for outbreak-surveillance studies to assess the risk of bias., Results: Six diagnostic accuracy studies were included. An enrichment broth was found to increase the detection of CR-PA. Using an enrichment broth extended the TAT by 18-24 h, yet selective media could reduce the TAT by 24 h compared to routine media. In total, 124 outbreak-surveillance studies were included, of which 17 studies with surveillance samples and 116 studies with clinical samples. In outbreak-surveillance studies with surveillance samples, perianal, rectal swabs or stools were the most common sampling site/specimen (13/17, 76%). A large variety was observed in whether and which kind of enrichment broth and selective media were used., Conclusions: We found a benefit of using an enrichment step prior to inoculation of the material onto selective media for the detection of CR-PA. More research is needed to determine the most sensitive sampling site and culture method., Trail Registration: This study was registered in the PROSPERO International prospective register of systematic reviews (registration number: CRD42020207390, http://www.crd.york.ac.uk/PROSPERO/display&#95;record.asp?ID=CRD42020207390 )., (© 2024. The Author(s).)

Background and Objective: The prevalence of Hepatitis Delta Virus (HDV) is underestimated and the assessment of fibrosis is recommended for this infection. We tested the diagnostic impact of an annual screening for HDV serology in Hepatitis B Surface Antigen (HBs Ag) chronic carriers and followed the progression of fibrosis in these patients., Methods: Between January 2014 and October 2021, we annually tested all chronic HBs Ag-positive patients for HDV antibody (HDV Ab). Each HDV Ab positive patient underwent annually repeated elastometry. Patients with detectable HDV RNA levels (group 1) were compared to those with undetectable HDV RNA (group 2)., Results: We identified 610 chronic HBs Ag-positive patients, and repeated screening for HDV Ab was performed in 534 patients. Sixty (11%) patients were HDV Ab positive at baseline and were considered as "coinfected". Seven cases of HDV superinfection were diagnosed through repeated screening. In co-infected patients, cirrhosis was initially diagnosed in 12/60 patients and developed in six patients during follow-up. HDV RNA PCR was performed in 57/67 patients and 27 had detectable levels (group 1). Cumulative incidence of cirrhosis at 7 years was 13.8% (95% CI 0-30) in group 1 and 0 (95% CI 0-0) in group 2 (p = 0.026)., Conclusion: A systematic screening for HDV in chronic HB Ag carriers revealed a high prevalence of HDV Ab. Repeated serological screening enables the diagnosis of superinfections in asymptomatic patients. Regular assessment of fibrosis using elastometry leads to the identification of incidental cirrhosis in patients with detectable HDV RNA., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Objectives: Universal screening for methicillin-resistant Staphylococcus aureus (MRSA) entails additional costs, and there is no consensus for targeted screening for high-risk units. The aims of this study were to determine the prevalence of MRSA in geriatric care units, and to identify the factors associated with MRSA colonization on admission., Methods: This retrospective case-control study (1:1) in the geriatric care unit of six Belgian hospitals covered the period from 1 st January 2021 to 31 st December 2022. Cases were patients with a positive MRSA screening result within 48 h of admission to the geriatric care unit, and controls were patients with a negative screening result., Results: In total, 556 patients were included in this study (278 in each group). Prevalence per 100 admissions for the total sample was 2.3 [95% confidence interval (CI) 2.2-2.6]. Significant multi-variate factors associated with MRSA carriage on admission were: history of MRSA, nursing home origin, and chronic skin lesions. Applying these three factors would give an area under the receiver operating characteristic (ROC) curve of 0.73 (95% CI 0.71-0.77), and would allow screening to be carried out in only 55.4% of cases (95% CI 51.2-59.6%)., Conclusions: Using these factors as screening criteria in geriatric care units could significantly reduce the number of patients screened for MRSA, while maintaining satisfactory sensitivity and specificity., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Tonsillar Fusobacterium necrophorum PCR Ct-values were higher in participants with asymptomatic tonsillar carriage than patients with pharyngeal infections. However, Ct-values were not associated with severity of disease or predictive of development of complications and hence lacked clinical usefulness. The reporting of F. necrophorum Ct-values in clinical samples is not recommended., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Roommates of unrecognized nosocomial methicillin-resistant Staphylococcus aureus (MRSA) cases are at a higher acquisition risk; however, optimal surveillance strategies are unknown., Methods: Using simulation, we analyzed surveillance testing and isolation strategies for MRSA among exposed hospital roommates. We compared isolating exposed roommates until conventional culture testing on day 6 and a nasal polymerase chain reaction test on day 3 (PCR3) with/without day 0 culture testing (Cult0). The model represents MRSA transmission in medium-sized hospitals using data and recommends best practices from the literature and Ontario community hospitals., Results: Cult0 + PCR3 incurred a slightly lower number of MRSA colonizations and 38.9% lower annual cost in the base case compared to Cult0 + culture testing on day 6 because the reduced isolation cost compensated for the increased testing cost. The reduction in MRSA colonizations was due to a 54.5% drop in MRSA transmissions during isolation as PCR3 reduced the exposure of MRSA-free roommates to new MRSA carriers. Removing the day 0 culture test from Cult0 + PCR3 increased total cost, the number of MRSA colonization, and missed cases by $1,631, 4.3%, and 50.9%, respectively. Improvements were higher under aggressive MRSA transmission scenarios., Discussion and Conclusions: Adopting direct nasal polymerase chain reaction testing for determining post-exposure MRSA status reduces transmission risk and costs. Day 0 culture would still be beneficial., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Equine piroplasmosis (EP) is caused by Theileria equi and Babesia caballi, transmitted by tick vectors. Horses can suffer an acute, subacute, and chronic forms of the disease, with clinical signs such as poor performance, fever, pale mucosal membranes, and jaundice. The diagnosis of EP subclinical cases is complex due to the sensitivity of real-time PCR and the limited parasite load in some carriers, making it challenging to differentiate them from seropositive, PCR negative (S+PCR-) individuals. This study aimed to describe haematological and biochemical changes in asymptomatic EP carriers, EP S+PCR- horses and control horses (EP seronegative and PCR negative). It also investigated potential haemato-biochemical markers to aid in distinguishing true EP carriers alongside molecular and serological tests. A comprehensive haematology and biochemistry profile was conducted on 410 sera and EDTA blood samples, comprising 130 EP positives by real-time PCR and competitive ELISA (cELISA) (carriers), 130 EP negatives by real-time PCR but positive to cELISA (S+PCR-) and 150 EP negative horses to real-time PCR and c-ELISA (controls). Our study confirmed that a haematological and biochemistry profile could help to differentiate between EP carriers/S+PCR- from healthy horses. Carriers and S+PCR- horses showed significant increases in the white blood cell count (WBC), high total proteins (TP) and total globulins (GLOB) concentration, and liver function markers compared to controls. Additionally, the evaluation of uric acid (UA) suggested oxidative stress in carrier horses. However, no useful haemato-biochemical diagnostic markers were identified to aid the challenging differentiation of EP carriers and S+PCR- horses, highlighting the need for improvement in molecular/serological diagnosis for these horses., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Eliazar Camino reports financial support was provided by Complutense University of Madrid. Eliazar Camino reports a relationship with Complutense University of Madrid that includes: funding grants., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

For children, the gold standard for the detection of pneumococcal carriage is conventional culture of a nasopharyngeal swab. Saliva, however, has a history as one of the most sensitive methods for surveillance of pneumococcal colonization and has recently been shown to improve carriage detection in older age groups. Here, we compared the sensitivity of paired nasopharyngeal and saliva samples from PCV7-vaccinated 24-month-old children for pneumococcal carriage detection using conventional and molecular detection methods. Nasopharyngeal and saliva samples were collected from 288 24-month-old children during the autumn/winter, 2012/2013. All samples were first processed by conventional diagnostic culture. Next, DNA extracted from all plate growth was tested by qPCR for the presence of the pneumococcal genes piaB and lytA and a subset of serotypes. By culture, 161/288 (60 %) nasopharyngeal swabs tested positive for pneumococcus, but detection was not possible from saliva due to abundant polymicrobial growth on culture plates. By qPCR, 155/288 (54 %) culture-enriched saliva samples and 187/288 (65 %) nasopharyngeal swabs tested positive. Altogether, 219/288 (76 %) infants tested positive for pneumococcus, with qPCR-based carriage detection of culture-enriched nasopharyngeal swabs detecting significantly more carriers compared to either conventional culture ( P <0.001) or qPCR detection of saliva ( P =0.002). However, 32/219 (15 %) carriers were only positive in saliva, contributing significantly to the overall number of carriers detected ( P =0.002). While testing nasopharyngeal swabs by qPCR proved most sensitive for pneumococcal detection in infants, saliva sampling could be considered as complementary to provide additional information on carriage and serotypes that may not be detected in the nasopharynx and may be particularly useful in longitudinal studies, requiring repeated sampling of study participants.

Background: Disease control relies on pathogen identification and understanding reservoirs. Staphylococcus aureus infection prevention is based upon decades of research on colonization and infection, but diminishing returns from mitigation efforts suggest significant knowledge gaps. Existing knowledge and mitigation protocols are founded upon culture-based detection, with almost no information about pathogen quantities., Methods: We used culture and a quantitative polymerase chain reaction assay on samples from 3 body sites to characterize colonization more comprehensively than previous studies by describing both prevalence and pathogen quantity., Results: We show a much higher overall prevalence (65.9%) than previously documented, with higher quantities and prevalence associated with the nares, non-Hispanic males (86.9%), and correlating with colonization in other body sites. These results suggest that research and clinical practices likely misclassify over half of colonized persons, limiting mitigation measures and their impact., Conclusions: This work begins the process of rebuilding foundational knowledge of S aureus carriage with more accurate and wholistic approaches., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Carriage studies are fundamental to assessing the effects of pneumococcal vaccines. Because a large proportion of oral streptococci carry homologues of pneumococcal genes, non-culture-based detection and serotyping of upper respiratory tract (URT) samples can be problematic. In the current study, we investigated whether culture-free molecular methods could differentiate pneumococci from oral streptococci carried by adults in the URT., Methods: Paired nasopharyngeal (NP) and oropharyngeal (OP) samples were collected from 100 older adults twice a month for 1 year. Extracts from the combined NP + OP samples (n = 2400) were subjected to lytA real-time polymerase chain reaction (PCR). Positive samples were subjected to pure culture isolation, followed by species confirmation using multiple approaches. Multibead assays and whole-genome sequencing were used for serotyping., Results: In 20 of 301 combined NP + OP extracts with positive lytA PCR results, probable pneumococcus-like colonies grew, based on colony morphology and biochemical tests. Multiple approaches confirmed that 4 isolates were Streptococcus pneumoniae, 3 were Streptococcus pseudopneumoniae, 12 were Streptococcus mitis, and 1 were Streptococcus oralis. Eight nonpneumococcal strains carried pneumococcus-like cps loci (approximate size, 18-25 kb) that showed >70% nucleotide identity with their pneumococcal counterparts. While investigating the antigenic profile, we found that some S. mitis strains (P066 and P107) reacted with both serotype-specific polyclonal (type 39 and FS17b) and monoclonal (Hyp10AG1 and Hyp17FM1) antisera, whereas some strains (P063 and P074) reacted only with polyclonal antisera (type 5 and FS35a)., Conclusion: The extensive capsular overlap suggests that pneumococcal vaccines could reduce carriage of oral streptococci expressing cross-reactive capsules. Furthermore, direct use of culture-free PCR-based methods in URT samples has limited usefulness for carriage studies., Competing Interests: Potential conflicts of interest. F. G. and M. H. N. are University of Alabama at Birmingham (UAB) employees, and M. H. N. reports that UAB has intellectual property rights on some reagents used in this study. A. R. B. serves as an advisor for Merck and GlaxoSmithKline and received research funding from Janssen, Pfizer, and Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Knowledge about the duration of digestive carriage of ESBL- and carbapenemase-producing Enterobacteriaceae is an essential information, impacting clinical decisions (empiric treatment for known carriers) and infection control measures (preemptive precautions, sequential screening). Ten to 50% carriers are still colonized after one year, but these numbers might be overestimated. Use of genomic typing is required to distinguish endogenous long-term carriage from exogenous recolonization events. Median length of colonization appears to range between 0,5 and 13 months for E-ESBL and 0,7 to 10 months for CPE. We performed a narrative review of the literature on this topic. We finally suggest a few future perspectives., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: In a previous study of men attending Melbourne Sexual Health Centre who had Neisseria gonorrhoeae detected by urine Aptima Combo 2 (AC2) testing, 11% were asymptomatic. This study aimed to determine whether N. gonorrhoeae can be cultured from asymptomatic men screening positive for N. gonorrhoeae by nucleic acid amplification testing (NAAT) of urine., Methods: Between 1 July 2017 and 31 March 2019, all men attending Melbourne Sexual Health Centre were tested for N. gonorrhoeae by AC2 testing of urine whether urethral symptoms were reported or not. NAAT-positive men were recalled and a urethral swab performed for gonococcal culture using modified Thayer-Martin media with determination of minimum inhibitory concentrations (MICs) by agar dilution., Results: There were 1001 cases (860 individuals) positive for N. gonorrhoeae by urine AC2: 892 (89%) reported urethral symptoms; 109 (11%) did not. Twenty-five asymptomatic cases were excluded because of antibiotic use at or following screening. Of the remaining 84 asymptomatic men, 41 (49%) had a urethral swab performed a median of 5 days after screening. Twenty-one men had urethral discharge at the return visit, 11 of whom reported the discharge at the return visit. Of the 41 men who were swabbed, 31 (76%; 95% CI 60% to 88%) were culture positive for N. gonorrhoeae . Among the 21 men who subsequently developed discharge, 19 (90%; 95% CI 70% to 99%) were culture positive. Among the 20 men who remained asymptomatic, 12 (60%; 95% CI 36% to 81%) were culture positive. MIC profiles were obtained from all isolates., Conclusions: Gonorrhoea was isolated in most but not all asymptomatic men screening positive for N. gonorrhoeae by urine NAAT. Clinicians should consider performing urethral culture in such men to ensure optimal surveillance for antimicrobial resistance. Isolation of N. gonorrhoeae by culture in men without discharge indicates these are true infections with viable organisms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the most common neurological manifestation associated with human T-cell lymphotropic virus type-1 (HTLV-1) infection. Although cognitive impairment has been highlighted in the spectrum of HTLV-1 neurological manifestations, it may go unnoticed in those who do not spontaneously report it. We aimed at evaluating the applicability of a self-perceived memory score (SMS) and the cognitive event-related potential (P300) for early detection of cognitive impairment in HTLV-1-infected people. The SMS was measured by a 0-10 point numeric scale combined with a sad-happy face rating scale. The higher the number, the better was the SMS. The P300 was obtained through an oddball paradigm with a mental counting task. The participants were 15 (21.4%) individuals with HAM/TSP, 20 (28.6%) HTLV-1 asymptomatic carriers, and 35 (50%) seronegative controls. We found that SMS (p < 0.001) and P300 latency (p < 0.001) got progressively worse from the seronegative controls to the asymptomatic carriers and then to the HAM/TSP. The results that indicated cognitive impairment were SMS < 7.2 points and P300 latency > 369.0 ms. The HAM/TSP group showed the highest prevalence of altered P300 (80%) and SMS (87%). Interestingly, the asymptomatic group also presented significantly higher prevalence of altered SMS (60%) and P300 (35%) when compared to controls (< 10%). The frequency of cognitive impairment was 16 times higher in the HTLV-1 asymptomatic group and 69 times higher in the HAM/TSP group when compared to controls. The use of SMS in the medical consultation was a useful and easy-to-apply method to screen HTLV-1-infected subjects for everyday memory complaints., (© 2022. Journal of NeuroVirology, Inc.)

Hepatitis B and hepatitis C (HBV/HCV) are important global public health concerns. We aimed to evaluate the association between maternal HBV/HCV carrier status and long-term offspring neurological hospitalisations. A population-based cohort analysis compared the risk for long-term childhood neurological hospitalisations in offspring born to HBV/HCV carrier vs. non-carrier mothers in a large tertiary medical centre between 1991 and 2014. Childhood neurological diseases, such as cerebral palsy, movement disorders or developmental disorders, were pre-defined based on ICD-9 codes as recorded in hospital medical files. Offspring with congenital malformations and multiple gestations were excluded from the study. A Kaplan-Meier survival curve was constructed to compare cumulative neurological hospitalisations over time, and a Cox proportional hazards model was used to control for confounders. During the study period (1991-2014), 243,682 newborns met the inclusion criteria, and 777 (0.3%) newborns were born to HBV/HCV mothers. The median follow-up was 10.51 years (0-18 years). The offspring from HBV/HCV mothers had higher incidence of neurological hospitalisations (4.5 vs. 3.1%, hazard ratio (HR) = 1.91, 95% CI 1.37-2.67). Similarly, the cumulative incidence of neurological hospitalisations was higher in children born to HBV/HCV carrier mothers (Kaplan-Meier survival curve log-rank test p < 0.001). The increased risk remained significant in a Cox proportional hazards model, which adjusted for gestational age, mode of delivery and pregnancy complications (adjusted HR = 1.40, 1.01-1.95, p = 0.049). We conclude that maternal HBV or HCV carrier status is an independent risk factor for the long-term neurological hospitalisation of offspring regardless of gestational age and other adverse perinatal outcomes.

Leptospirosis is a global zoonotic disease caused by pathogenic bacteria of the genus Leptospira. We sought to determine if rodents in U.S. Virgin Islands (USVI) are carriers of Leptospira. In total, 140 rodents were sampled, including 112 Mus musculus and 28 Rattus rattus. A positive carrier status was identified for 64/140 (45.7%); 49 (35.0%) were positive by dark-field microscopy, 60 (42.9%) by culture, 63 (45.0%) by fluorescent antibody testing, and 61 (43.6%) by real-time polymerase chain reaction (rtPCR). Molecular typing indicated that 48 isolates were L. borgpetersenii and 3 were L. kirschneri; the remaining nine comprised mixed species. In the single culture-negative sample that was rtPCR positive, genotyping directly from the kidney identified L. interrogans. Serotyping of L. borgpetersenii isolates identified serogroup Ballum and L. kirschneri isolates as serogroup Icterohaemorrhagiae. These results demonstrate that rodents are significant Leptospira carriers and adds to understanding the ecoepidemiology of leptospirosis in USVI., (© 2022. The Author(s).)

Intensive care unit-acquired infection (ICU-AI) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) carriage are a major concern worldwide. Our objective was to investigate the impact of ESBL-PE carriage on ICU-AI. Our study was prospective, observational, and noninterventional. It was conducted over a 5-year period (Jan 2013-Dec 2017) in the medical-surgical intensive care unit of the Cayenne General Hospital (French Amazonia). During the study period, 1,340 patients were included, 271 (20.2%) developed ICU-AI, and 16.2% of these were caused by ESBL-PE. The main sites of ICU-AI were ventilator-associated pneumonia (35.8%) and primary bloodstream infection (29.8%). The main responsible microorganisms were Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae (ESBL-P in 35.8% of isolates), and Enterobacter cloacae (ESBL-P in 29.8% of isolates). Prior ESBL-PE carriage was diagnosed in 27.6% of patients with ICU-AI. In multivariable analysis, the sole factor associated with ESBL-PE as the responsible organism of ICU-AI was ESBL-PE carriage before ICU-AI (P < 0.001; odds ratio: 7.9 95% CI: 3.4-18.9). ESBL-PE carriers (74 patients) developed ICU-AI which was caused by ESBL-PE in 32 cases (43.2%). This proportion of patients carrying ESBL-PE who developed ICU-AI to the same microorganism was 51.2% in ESBL-P K. pneumoniae, 5.6% in ESBL-P Escherichia coli, and 40% in ESBL-P Enterobacter spp. NPV of ESBL-PE carriage to predict ICU-AI caused by ESBL-PE was above 94% and PPV was above 43%. Carriage of ESBL-P K pneumoniae and Enterobacter spp. is a strong predictor of ICU-AI caused by these two microorganisms.

Early detection of infectious diseases is crucial for reducing transmission and facilitating early intervention. In this study, we built a real-time smartwatch-based alerting system that detects aberrant physiological and activity signals (heart rates and steps) associated with the onset of early infection and implemented this system in a prospective study. In a cohort of 3,318 participants, of whom 84 were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this system generated alerts for pre-symptomatic and asymptomatic SARS-CoV-2 infection in 67 (80%) of the infected individuals. Pre-symptomatic signals were observed at a median of 3 days before symptom onset. Examination of detailed survey responses provided by the participants revealed that other respiratory infections as well as events not associated with infection, such as stress, alcohol consumption and travel, could also trigger alerts, albeit at a much lower mean frequency (1.15 alert days per person compared to 3.42 alert days per person for coronavirus disease 2019 cases). Thus, analysis of smartwatch signals by an online detection algorithm provides advance warning of SARS-CoV-2 infection in a high percentage of cases. This study shows that a real-time alerting system can be used for early detection of infection and other stressors and employed on an open-source platform that is scalable to millions of users., (© 2021. The Author(s).)

A direct, real-time reverse transcriptase PCR test on pooled saliva was validated in 2,786 participants against oropharyngeal swabs. Among asymptomatic/pre-symptomatic participants, the test was found to be in 99.21% agreement and 45% more sensitive than contemporaneous oropharyngeal swabs. The test was then used for surveillance testing on 44,242 saliva samples from asymptomatic participants. Those whose saliva showed evidence of SARS-CoV-2 within 50 cycles of amplification were referred for confirmatory testing, with 87% of those tested by nasal swab within 72 hours receiving a positive diagnostic result on Abbott ID NOW or real-time PCR platforms. Median Ct values on the saliva PCR for those with a positive and negative confirmatory tests was 30.67 and 35.92 respectively, however, binary logistic regression analysis of the saliva Ct values indicates that Ct thresholds as high as 47 may be useful in a surveillance setting. Overall, data indicate that direct RT-PCR testing of pooled saliva samples is an effective method of SARS-CoV-2 surveillance., Competing Interests: The authors have declared that no competing interests exist.

Background: Multi-drug resistant organisms, especially Vancomycin-Resistant Enterococcus (VRE) and Carbapenam Resistant Klebsiella pneumoniae (KPC), are serious health threat. Early detection of resistant bacteria colonization among patients in intensive care units (ICUs) not only enables effective treatment but more importantly prevents disease and limits transmission. Therefore, we aimed to to assess the frequency of VRE and KPC colonization via rectal swab sampling., Methods: The study was carried out in ICUs of a tertiary hospital. Two rectal swab samples were collected within the first 24 hours of admission and another one was taken every subsequent 15 days to test for for VRE and KPC carriage., Results: A total 316 rectal swab samples taken from 230 patients. Forty-seven patients were screened at least 2 times. 183 patients were not further screened due to discharge, exitus or transfer to other wards. Thirty-six patients (16%) were determined to be VRE (+). The most frequently isolated strain was E. faecium (80.5%) and its most common genotype was VanA (87.5%). Seven patients (3%) were identified as KPC (+). OXA-48 type crbapenamase was confirmed in all KPC isolates., Conclusion: This study shows that VRE and KPC colonization continues to be a serious threat in ICUs., (© 2021 Karaşin G et al.)

Listeria genus comprises two pathogenic species, L. monocytogenes (Lm) and L. ivanovii, and non-pathogenic species. All can thrive as saprophytes, whereas only pathogenic species cause systemic infections. Identifying Listeria species' respective biotopes is critical to understand the ecological contribution of Listeria virulence. In order to investigate the prevalence and abundance of Listeria species in various sources, we retrieved and analyzed 16S rRNA datasets from MG-RAST metagenomic database. 26% of datasets contain Listeria sensu stricto sequences, and Lm is the most prevalent species, most abundant in soil and host-associated environments, including 5% of human stools. Lm is also detected in 10% of human stool samples from an independent cohort of 900 healthy asymptomatic donors. A specific microbiota signature is associated with Lm faecal carriage, both in humans and experimentally inoculated mice, in which it precedes Lm faecal carriage. These results indicate that Lm faecal carriage is common and depends on the gut microbiota, and suggest that Lm faecal carriage is a crucial yet overlooked consequence of its virulence., (© 2021. The Author(s).)

Throughout the coronavirus disease 2019 (COVID-19) pandemic, countries have relied on a variety of ad hoc border control protocols to allow for non-essential travel while safeguarding public health, from quarantining all travellers to restricting entry from select nations on the basis of population-level epidemiological metrics such as cases, deaths or testing positivity rates 1,2 . Here we report the design and performance of a reinforcement learning system, nicknamed Eva. In the summer of 2020, Eva was deployed across all Greek borders to limit the influx of asymptomatic travellers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and to inform border policies through real-time estimates of COVID-19 prevalence. In contrast to country-wide protocols, Eva allocated Greece's limited testing resources on the basis of incoming travellers' demographic information and testing results from previous travellers. By comparing Eva's performance against modelled counterfactual scenarios, we show that Eva identified 1.85 times as many asymptomatic, infected travellers as random surveillance testing, with up to 2-4 times as many during peak travel, and 1.25-1.45 times as many asymptomatic, infected travellers as testing policies that utilize only epidemiological metrics. We demonstrate that this latter benefit arises, at least partially, because population-level epidemiological metrics had limited predictive value for the actual prevalence of SARS-CoV-2 among asymptomatic travellers and exhibited strong country-specific idiosyncrasies in the summer of 2020. Our results raise serious concerns on the effectiveness of country-agnostic internationally proposed border control policies 3 that are based on population-level epidemiological metrics. Instead, our work represents a successful example of the potential of reinforcement learning and real-time data for safeguarding public health., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Antimicrobial-resistant organisms (AMROs) can colonize people without symptoms for long periods of time, during which these agents can spread unnoticed to other patients in healthcare systems. The accurate identification of asymptomatic spreaders of AMRO in hospital settings is essential for supporting the design of interventions against healthcare-associated infections (HAIs). However, this task remains challenging because of limited observations of colonization and the complicated transmission dynamics occurring within hospitals and the broader community. Here, we study the transmission of methicillin-resistant Staphylococcus aureus (MRSA), a prevalent AMRO, in 66 Swedish hospitals and healthcare facilities with inpatients using a data-driven, agent-based model informed by deidentified real-world hospitalization records. Combining the transmission model, patient-to-patient contact networks, and sparse observations of colonization, we develop and validate an individual-level inference approach that estimates the colonization probability of individual hospitalized patients. For both model-simulated and historical outbreaks, the proposed method supports the more accurate identification of asymptomatic MRSA carriers than other traditional approaches. In addition, in silica control experiments indicate that interventions targeted to inpatients with a high-colonization probability outperform heuristic strategies informed by hospitalization history and contact tracing.

Malaria elimination and eradication efforts have stalled globally. Further, asymptomatic infections as silent transmission reservoirs are considered a major challenge to malaria elimination efforts. There is increased interest in a mass screen-and-treat (MSAT) strategy as an alternative to mass drug administration to reduce malaria burden and transmission in endemic settings. This study systematically synthesized the existing evidence on MSAT, from both epidemiological and economic perspectives. Searches were conducted on six databases (PubMed, EMBASE, CINALH, Web of Science, Global Health, and Google Scholar) between October and December 2020. Only experimental and quasi-experimental studies assessing the effectiveness and/or cost-effectiveness of MSAT in reducing malaria prevalence or incidence were included. Of the 2,424 citation hits, 14 studies based on 11 intervention trials were eligible. Eight trials were conducted in sub-Saharan Africa and three trials in Asia. While five trials targeted the community as a whole, pregnant women were targeted in five trials, and school children in one trial. Transmission setting, frequency, and timing of MSAT rounds, and measured outcomes varied across studies. The pooled effect size of MSAT in reducing malaria incidence and prevalence was marginal and statistically nonsignificant. Only one study conducted an economic evaluation of the intervention and found it to be cost-effective when compared with the standard of care of no MSAT. We concluded that the evidence for implementing MSAT as part of a routine malaria control program is growing but limited. More research is necessary on its short- and longer-term impacts on clinical malaria and malaria transmission and its economic value.

Objectives: Previous studies have been unable to identify patient or staff reservoirs for the majority of the nosocomial S. aureus acquisitions which occur in the presence of good infection control practice. We set out to establish the extent to which undetected pre-existing carriage explains apparent nosocomial S. aureus acquisition., Methods: Over two years elective cardiothoracic admissions were screened for S. aureus carriage before and during hospital admission. Routine screening (nose/groin/wound sampling), was supplemented by sampling additional body sites (axilla/throat/rectum) and culture-based methods optimised to detect fastidious phenotypes (small colony variants, cell wall deficient variants) and molecular identification by PCR., Results: 35% of participants (53/151) were S. aureus carriers according to routine pre-healthcare screening; increasing to 42% (63/151) when additional body sites and enhanced cultures were employed. 71% (5/7) of apparent acquisitions were explained by pre-existing carriage using augmented measures. Enhanced culture identified a minority of colonised individuals (3/151 including 1 MRSA carrier) who were undetected by routine and additional screening cultures. 4/14 (29%) participants who became culture-negative during admission had S. aureus genomic material detected at discharge., Conclusions: Conventional sampling under-estimates carriage of S. aureus and this explains the majority of apparent S. aureus acquisitions among elective cardiothoracic patients., Competing Interests: Declaration of Competing Interest All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: no support from any organization for the submitted work; no authors received personal fees in the past three years outside the submitted work; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2021. Published by Elsevier Ltd.)

Background: SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs., Methods and Findings: We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers' instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies' heterogeneity in design and reporting., Conclusions: In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CMD is a member of the Editorial Board of PLOS Medicine.

We aimed to detect typhoid carriers by performing duodenal fluid culture in patients in a tertiary care hospital in Pakistan. A cross-sectional study was conducted during 2017 at the Aga Khan University Hospital, Karachi. Patients who underwent upper gastrointestinal endoscopy were included. Participants were interviewed, and duodenal fluid samples were taken for culture to detect Salmonella typhi (S. typhi) and paratyphi. A polymerase chain reaction on 100 randomly selected sub-samples was also conducted. A total of 477 participants were enrolled. The mean age was 42.4±15.5 years. History of typhoid fever was present in 73 (15.3%) participants. Out of the 477 duodenal fluid cultures tested for various micro-organisms, 250 (52.4%) were positive. Neither S. typhi nor paratyphi were isolated. S. typhi was also not detected by PCR. To better detect S. typhi carriage in general population, future studies should target people with gall bladder diseases and screen them using culture and PCR based methods.

Background/aims: During the natural course of Chronic Hepatitis B (CHB) infection, differentiation between inactive carrier (IC) and HBeAg negative CHB is a subject of ongoing debate. We studied the role of hepatitis B surface antigen (HBsAg) level as a means of differentiating between CHB and IC in a group of untreated chronic HBeAg-negative HBV-infected patients., Study: A total of 115 HBeAg negative carriers were enrolled and followed up for>12 months; 78 as inactive carriers (IC), and 37 as active carriers (AC). Among ACs, patients were categorized according to the highest rate of viral load: AC1 (n=23), active carriers with persistent HBV-DNA<20,000 IU/mL; AC2 (n=14), active carriers with HBV-DNA>20,000 IU/mL., Results: HBsAg levels were higher in AC compared to IC patients (1607 IU/ml vs. 225 IU/ml respectively, P=0.001). Among the AC group, the 23 AC1 cases had HBsAg levels significantly lower than the 14 AC2 patients (1756 IU/mL vs. 3327 IU/mL respectively; P<10 -3 ). HBsAg showed weak correlation with HBV-DNA in the whole cohort (r=0.44, P<0.01). The suggested cutoff value of HBsAg titer to differentiate between the two groups was 938 IU/mL. Combined single-point quantification of HBsAg (938 IU/mL) and HBV DNA (2000 IU/mL) identified IC with 87.2% specificity and 91.7% positive predictive value., Conclusion: This study confirms the predictability of a one-time combined HBsAg and HBV DNA measurement for true inactive carriers requiring neither strict follow-up nor antiviral treatment., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in attenuating coronavirus disease 2019 (Covid-19) when administered in real-world conditions., Methods: We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. From December 14, 2020, to April 10, 2021, the participants completed weekly SARS-CoV-2 testing by providing mid-turbinate nasal swabs for qualitative and quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis. The formula for calculating vaccine effectiveness was 100% × (1 - hazard ratio for SARS-CoV-2 infection in vaccinated vs. unvaccinated participants), with adjustments for the propensity to be vaccinated, study site, occupation, and local viral circulation., Results: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥14 days after dose 2), 11 partially vaccinated (≥14 days after dose 1 and <14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (<14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7)., Conclusions: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.)., (Copyright © 2021 Massachusetts Medical Society.)

COVID-19 pandemic exerts a health care emergency around the world. The illness severity is heterogeneous. It is mostly unknown why some individuals who are positive for SARS-CoV-2 antibodies stay asymptomatic while others show moderate to severe disease symptoms. Reliable biomarkers for early detection of the disease are urgently needed to attenuate the virus's spread and help make early treatment decisions. Bioactive sphingolipids play a crucial role in the regulation of viral infections and pro-inflammatory responses involved in the severity of COVID-19. However, any roles of sphingolipids in COVID-19 development or detection remain unknown. In this study, lipidomics measurement of serum sphingolipids demonstrated that reduced sphingosine levels are highly associated with the development of symptomatic COVID-19 in the majority (99.24%) SARS-CoV-2-infected patients compared to asymptomatic counterparts. The majority of asymptomatic individuals (73%) exhibited increased acid ceramidase (AC) in their serum, measured by Western blotting, consistent with elevated sphingosine levels compared to SARS-CoV-2 antibody negative controls. AC protein was also reduced in almost all of the symptomatic patients' serum, linked to reduced sphingosine levels, measured in longitudinal acute or convalescent COVID-19 samples. Thus, reduced sphingosine levels provide a sensitive and selective serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients., (© 2021. The Author(s).)

Reports of P. vivax infections among Duffy-negative hosts have accumulated throughout sub-Saharan Africa. Despite this growing body of evidence, no nationally representative epidemiological surveys of P. vivax in sub-Saharan Africa have been performed. To overcome this gap in knowledge, we screened over 17,000 adults in the Democratic Republic of the Congo (DRC) for P. vivax using samples from the 2013-2014 Demographic Health Survey. Overall, we found a 2.97% (95% CI: 2.28%, 3.65%) prevalence of P. vivax infections across the DRC. Infections were associated with few risk-factors and demonstrated a relatively flat distribution of prevalence across space with focal regions of relatively higher prevalence in the north and northeast. Mitochondrial genomes suggested that DRC P. vivax were distinct from circulating non-human ape strains and an ancestral European P. vivax strain, and instead may be part of a separate contemporary clade. Our findings suggest P. vivax is diffusely spread across the DRC at a low prevalence, which may be associated with long-term carriage of low parasitemia, frequent relapses, or a general pool of infections with limited forward propagation.

Background: Routine viral testing strategies for SARS-CoV-2 infection might facilitate safe airline travel during the COVID-19 pandemic and mitigate global spread of the virus. However, the effectiveness of these test-and-travel strategies to reduce passenger risk of SARS-CoV-2 infection and population-level transmission remains unknown., Methods: In this simulation study, we developed a microsimulation of SARS-CoV-2 transmission in a cohort of 100 000 US domestic airline travellers using publicly available data on COVID-19 clinical cases and published natural history parameters to assign individuals one of five health states of susceptible to infection, latent period, early infection, late infection, or recovered. We estimated a per-day risk of infection with SARS-CoV-2 corresponding to a daily incidence of 150 infections per 100 000 people. We assessed five testing strategies: (1) anterior nasal PCR test within 3 days of departure, (2) PCR within 3 days of departure and 5 days after arrival, (3) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection), (4) rapid antigen test on the day of travel and PCR test 5 days after arrival, and (5) PCR test 5 days after arrival. Strategies 2 and 4 included a 5-day quarantine after arrival. The travel period was defined as 3 days before travel to 2 weeks after travel. Under each scenario, individuals who tested positive before travel were not permitted to travel. The primary study outcome was cumulative number of infectious days in the cohort over the travel period without isolation or quarantine (population-level transmission risk), and the key secondary outcome was the number of infectious people detected on the day of travel (passenger risk of infection)., Findings: We estimated that in a cohort of 100 000 airline travellers, in a scenario with no testing or screening, there would be 8357 (95% uncertainty interval 6144-12831) infectious days with 649 (505-950) actively infectious passengers on the day of travel. The pre-travel PCR test reduced the number of infectious days from 8357 to 5401 (3917-8677), a reduction of 36% (29-41) compared with the base case, and identified 569 (88% [76-92]) of 649 actively infectious travellers on the day of flight; the addition of post-travel quarantine and PCR reduced the number of infectious days to 2520 days (1849-4158), a reduction of 70% (64-75) compared with the base case. The rapid antigen test on the day of travel reduced the number of infectious days to 5674 (4126-9081), a reduction of 32% (26-38) compared with the base case, and identified 560 (86% [83-89]) actively infectious travellers; the addition of post-travel quarantine and PCR reduced the number of infectious days to 3124 (2356-495), a reduction of 63% (58-66) compared with the base case. The post-travel PCR alone reduced the number of infectious days to 4851 (3714-7679), a reduction of 42% (35-49) compared with the base case., Interpretation: Routine asymptomatic testing for SARS-CoV-2 before travel can be an effective strategy to reduce passenger risk of infection during travel, although abbreviated quarantine with post-travel testing is probably needed to reduce population-level transmission due to importation of infection when travelling from a high to low incidence setting., Funding: University of California, San Francisco., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We aimed to compare respiratory pathogen carriage by PCR during three different time periods in 2020 in sheltered homeless people in Marseille, France. The overall prevalence of respiratory pathogen carriage in late March-early April (69.9%) was significantly higher than in late April (42.3%) and mid-July (45.1%). Bacterial carriage significantly decreased between late March-early April and late April. SARS-CoV-2 was detected only in late March-early April samples (20.6%). Measures aiming at mitigating SARS-CoV-2 transmission were effective and also impacted bacterial carriage. Seasonal variations of bacterial carriage between winter and summer in this population were not marked.

Methicillin-resistant Staphylococcus aureus (MRSA) has long been known as a major cause of hospital-acquired (HA-MRSA) infections worldwide. For the past twenty years, an increasing number of studies have described its emergence in the community as well. In Portugal, a country with a high-prevalence of HA-MRSA, there are only limited data available on the epidemiology of MRSA in the community. We studied the prevalence of S. aureus and MRSA colonization among healthy adults in Portugal. Between February 2015 and December 2016, a longitudinal study was conducted in which 87 adults aged 25-50 years old were followed for six months. For each participant nasopharyngeal, oropharyngeal and saliva samples were obtained monthly and, in some cases, weekly. A total of 1,578 samples (n = 526 for each sampling site) were examined for the presence of S. aureus and MRSA by classical culture-based methods. Fifty-seven adults (65.5%) carried S. aureus at least once during the six months period of the study: 19.5% were persistent S. aureus carriers and 46.0% were intermittent carriers. Carriage rates per sampling site were 20.5% in nasopharynx, 18.3% in oropharynx, and 13.5% in saliva. Simultaneous screening of the three sampling sites increased detection of S. aureus, which overall occurred in 34.4% of the 526 sampling time-points. No MRSA were isolated. In conclusion, this study adds novel information about the MRSA scenario in the Portuguese community. Our results indicate that, in Portugal, MRSA does not seem to circulate among healthy adults without risk factors and therefore this age group does not constitute, at the current time, a reservoir of MRSA in the community., Competing Interests: This work was partially supported by an Investigator-Initiated Research Grant from Pfizer to RSL. Other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Streptococcus equi subsp. equi (SEE) is a host-restricted bacterium that causes the common infectious upper respiratory disease known as strangles in horses. Perpetuation of SEE infection appears attributable to inapparent carrier horses because it neither persists long-term in the environment nor infects other host mammals or vectors, and infection results in short-lived immunity. Whether pathogen factors enable SEE to remain in horses without causing clinical signs remains poorly understood. Thus, our objective was to use next-generation sequencing technologies to characterize the genome, methylome, and transcriptome of isolates of SEE from horses with acute clinical strangles and inapparent carrier horses-including isolates recovered from individual horses sampled repeatedly-to assess pathogen-associated changes that might reflect specific adaptions of SEE to the host that contribute to inapparent carriage. The accessory genome elements and methylome of SEE isolates from Sweden and Pennsylvania revealed no significant or consistent differences between acute clinical and inapparent carrier isolates of SEE. RNA sequencing of SEE isolates from Pennsylvania demonstrated no genes that were differentially expressed between acute clinical and inapparent carrier isolates of SEE. The absence of specific, consistent changes in the accessory genomes, methylomes, and transcriptomes of acute clinical and inapparent carrier isolates of SEE indicates that adaptations of SEE to the host are unlikely to explain the carrier state of SEE. Efforts to understand the carrier state of SEE should instead focus on host factors., Competing Interests: No authors have competing interests.

Background & Aims: Although the role of gut microbiota in Clostridioides difficile infection (CDI) has been well established, little is known about the role of mycobiota in CDI. Here, we performed mycobiome data analysis in a well-characterized human cohort to evaluate the potential of using gut mycobiota features for CDI diagnosis., Methods: Stool samples were collected from 118 hospital patients, divided into 3 groups: CDI (n = 58), asymptomatic carriers (Carrier, n = 28), and Control (n = 32). The nuclear ribosomal DNA internal transcribed spacer 2 was sequenced using the Illumina HiSeq platform to assess the fungal composition. Downstream statistical analyses (including Alpha diversity analysis, ordination analysis, differential abundance analysis, fungal correlation network analysis, and classification analysis) were then performed., Results: Significant differences were observed in alpha and beta diversity between patients with CDI and Carrier (P < .05). Differential abundance analysis identified 2 genera (Cladosporium and Aspergillus) enriched in Carrier. The ratio of Ascomycota to Basidiomycota was dramatically higher in patients with CDI than in Carrier and Control (P < .05). Correlations between host immune factors and mycobiota features were weaker in patients with CDI than in Carrier. Using 4 fungal operational taxonomic units combined with 6 host immune markers in the random forest classifier can achieve very high performance (area under the curve ∼92.38%) in distinguishing patients with CDI from Carrier., Conclusions: Our study provides specific markers of stool fungi combined with host immune factors to distinguish patients with CDI from Carrier. It highlights the importance of gut mycobiome in CDI, which may have been underestimated. Further studies on the diagnostic applications and therapeutic potentials of these findings are warranted., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

We analyze data from the fall 2020 pandemic response efforts at the University of Colorado Boulder, where more than 72,500 saliva samples were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using qRT-PCR. All samples were collected from individuals who reported no symptoms associated with COVID-19 on the day of collection. From these, 1,405 positive cases were identified. The distribution of viral loads within these asymptomatic individuals was indistinguishable from what has been previously observed in symptomatic individuals. Regardless of symptomatic status, ∼50% of individuals who test positive for SARS-CoV-2 seem to be in noninfectious phases of the disease, based on having low viral loads in a range from which live virus has rarely been isolated. We find that, at any given time, just 2% of individuals carry 90% of the virions circulating within communities, serving as viral "supercarriers" and possibly also superspreaders., Competing Interests: Competing interest statement: Some of the authors of this study have financial ties to companies that offer commercial SARS-CoV-2 testing (Q.Y., N.R.M., C.L.P., and S.L.S. are cofounders of Darwin Biosciences; T.K.S., P.K.G., and E.L. are cofounders of TUMI Genomics). R.P. is a cofounder of Faze Medicines, and R.D.D. is a cofounder of Arpeggio Biosciences., (Copyright © 2021 the Author(s). Published by PNAS.)

Background: There is a lack of population level data on risk factors, incidence and impact of SARS-CoV-2 infection in pregnant women and their babies. The primary aim of this study was to describe the incidence, characteristics and outcomes of hospitalized pregnant women with symptomatic and asymptomatic SARS-CoV-2 in the UK compared to pregnant women without SARS-CoV-2., Methods and Findings: We conducted a national, prospective cohort study of all hospitalized pregnant women with confirmed SARS-CoV-2 from 01/03/2020 to 31/08/2020 using the UK Obstetric Surveillance System. Incidence rates were estimated using national maternity data. Overall, 1148 hospitalized women had confirmed SARS-CoV-2 in pregnancy, 63% of which were symptomatic. The estimated incidence of hospitalization with symptomatic SARS-CoV-2 was 2.0 per 1000 maternities (95% CI 1.9-2.2) and for asymptomatic SARS-CoV-2 was 1.2 per 1000 maternities (95% CI 1.1-1.4). Compared to pregnant women without SARS-CoV-2, women hospitalized with symptomatic SARS-CoV-2 were more likely to be overweight or obese (adjusted OR 1.86, (95% CI 1.39-2.48) and aOR 2.07 (1.53-2.29)), to be of Black, Asian or Other minority ethnic group (aOR 6.24, (3.93-9.90), aOR 4.36, (3.19-5.95) and aOR 12.95, (4.93-34.01)), and to have a relevant medical comorbidity (aOR 1.83 (1.32-2.54)). Hospitalized pregnant women with symptomatic SARS-CoV-2 were more likely to be admitted to intensive care (aOR 57.67, (7.80-426.70)) but the absolute risk of poor outcomes was low. Cesarean births and neonatal unit admission were increased regardless of symptom status (symptomatic aOR 2.60, (1.97-3.42) and aOR 3.08, (1.99-4.77); asymptomatic aOR 2.02, (1.52-2.70) and aOR 1.84, (1.12-3.03)). The risks of stillbirth or neonatal death were not significantly increased, regardless of symptom status., Conclusions: We have identified factors that increase the risk of symptomatic and asymptomatic SARS-CoV-2 in pregnancy. Clinicians can be reassured that the majority of women do not experience severe complications of SARS-CoV-2 in pregnancy., Competing Interests: MK, MQ, PB, PO’B, JJK received grants from the NIHR in relation to the submitted work. KB, NV, NS, CG have no conflicts of interest to declare. EM is Trustee of RCOG, British Menopause Society and Newly Chair of the Board of Trustees Group B Strep Support. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Pulmonary specimen pairs from five patients who presented with pulmonary colonization and later developed Pneumocystis Pneumonia (PcP) were retrospectively examined for P. jirovecii genotyping. A match of genotypes in pulmonary specimen pairs of three patients was observed, whereas a partial match and a mismatch were observed in the fourth and fifth patients, respectively. The genotyping results suggest that the colonization state can differ from PcP but can also represent the incubation period of PcP. Clinicians should not systematically rule out the treatment of putative colonized patients and should at least discuss the initiation of prophylaxis on a case-by-case basis., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Serotype-specific diagnosis of pneumococcal community-acquired pneumonia in children under age 5 years would mark a major advancement for understanding pneumococcal epidemiology and supporting vaccine decision-making., Methods: A Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and subsequently validated in adults, but its applicability to children is unknown. This study aimed to set appropriate cutoffs for use of the UAD in a healthy pediatric population and apply these cutoffs in children with pneumonia in sub-Saharan Africa. The cutoffs were determined by assessing 379 urines obtained from healthy children under age 5 years from the Bobo-Dioulasso area for serotypes included in 13-valent pneumococcal conjugate vaccine (UAD-1) and the 11 other serotypes unique to 23-valent pneumococcal polysaccharide vaccine (UAD-2)., Results: Based on the assigned cutoff values, among 108 children who met the World Health Organization consolidation endpoint criteria, UAD-1 and UAD-2 were positive in 23.3% and 8.3%, respectively; among 364 children with clinically suspected pneumonia who did not meet the World Health Organization criteria, UAD-1 and UAD-2 were positive for 6.6% and 3.6%, respectively. Pneumococcal carriage prevalence was similar among pneumonia cases (30%) versus controls (35%) as was semiquantitative carriage density., Conclusions: UAD-1 and UAD-2 were able to distinguish community controls from children with pneumonia, particularly pneumonia with consolidation. Future studies are needed to confirm these results and more fully assess the contribution of pneumococcal carriage and concurrent viral infection., Competing Interests: J.M. and B.D.G. were employees of Agence de Medicine Preventive during the implementation of the study and currently work for Pfizer Inc. M.W.P. and Q.J. currently work for Pfizer Inc. E.B. worked for Pfizer Inc. during the previous 3 years but is not currently an employee. The other authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: COVID-19 care home outbreaks represent a significant proportion of COVID-19 morbidity and mortality in the UK. National testing initially focused on symptomatic care home residents, before extending to asymptomatic cohorts., Aim: The aim was to describe the epidemiology and transmission of COVID-19 in outbreak free care homes., Methods: A two-point prevalence survey of COVID-19, in 34 Liverpool care homes, was performed in April and May 2020. Changes in prevalence were analysed. Associations between care home characteristics, reported infection, prevention and control interventions, and COVID-19 status were described and analysed., Findings: No resident developed COVID-19 symptoms during the study. There was no significant difference between: the number of care homes containing at least one test positive resident between the first (17.6%, 95% confidence interval (CI) 6.8-34.5) and second round (14.7%, 95% CI 5.0-31.1) of testing (p>0.99); and the number of residents testing positive between the first (2.1%, 95% CI 1.2-3.4) and second round (1.0%, 95% CI 0.5-2.1) of testing (P=0.11). Care homes providing nursing care (risk ratio (RR) 7.99, 95% CI 1.1-57.3) and employing agency staff (RR 8.4, 95% CI 1.2-60.8) were more likely to contain test positive residents. Closing residents shared space was not associated with residents testing positive (RR 2.63, 95% CI 0.4-18.5)., Conclusions: Asymptomatic COVID-19 care homes showed no evidence of disease transmission or development of outbreaks; suggesting that current infection prevention and control measures are effective in preventing transmission. Repeat testing at two to three weeks had limited or no public health benefits over regular daily monitoring of staff and residents for symptoms. These results should inform policies calling for regular testing of asymptomatic residents., (Copyright © 2021. Published by Elsevier Ltd.)

It is unclear whether universal PCR screening for SARS-CoV-2 in asymptomatic individuals prior to admission is useful. From April to December 2020, the positive rate of universal pre-admission screening was 0.005% (4/76,521) in a tertiary care hospital in Korea. The positive rates were not different between the periods (period 1 (daily new patients of <1 per million inhabitants) vs. period 2 (1-8.3 per million inhabitants) vs. period 3 (10.3 to 20 per million inhabitants); P = 0.45). Universal pre-admission screening for SARS-CoV-2 had a lower positive rate than that of symptom-based screening (0.005% vs. 0.049% (53/109,257), p < 0.001). In addition, seven patients with negative pre-admission test results had subsequent positive PCR during hospitalization, and four patients had secondary transmission. Universal pre-admission PCR screening may not be practical in settings of low prevalence of COVID-19, and negative PCR results at admission should not serve as a basis for underestimating the risk of nosocomial spread from asymptomatic patients.

Lateral flow devices (LFDs) are quickly being implemented for use in large-scale population surveillance programs for SARS-CoV-2 infection in the United Kingdom. These programs have been piloted in city-wide screening in the city of Liverpool and are now being rolled out to support care home visits and the return home of University students for the Christmas break. Here, we present data on the performance of LFDs to test almost 8,000 students at the University of Birmingham between December 2 and December 9, 2020. The performance is validated against almost 800 samples using PCR performed in the University Pillar 2 testing lab and theoretically validated on thousands of Pillar 2 PCR testing results performed on low-prevalence care home testing samples. Our data show that LFDs do not detect infections presenting with PCR Ct values over 29 to 30 as determined using the Thermo Fisher TaqPath asssay. This may be of particular importance in detecting individuals that are either at the early, or late stages of infection, and reinforces the need for frequent, recurrent testing., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Competing interests statement: We have read and understood the BMJ policy on declaration of interests and declare the following interests: KW, JP, JG, JT, JD are grant holders for ISRCTN49639731 and JP, JG, and JD are grant holders for ISRCTN74746075, both funded by the UK National Institute for Health Research. JP is chief executive officer and trustee of Group B Strep Support and a trustee of the Confederation of Meningitis Organisations. AA has no interests to declare. Further details of The BMJ policy on financial interests are here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests

An outbreak of SARS-CoV2 infection in a Barcelona prison was studied. One hundred and forty-eight inmates and 36 prison staff were evaluated by rt-PCR, and 24.1% (40 prisoners, two health workers and four non-health workers) tested positive. In all, 94.8% of cases were asymptomatic. The inmates were isolated in prison module 4, which was converted into an emergency COVID unit. There were no deaths. Generalised screening and the isolation and evaluation of the people infected were key measures. Symptom-based surveillance must be supplemented by rapid contact-based monitoring in order to avoid asymptomatic spread among prisoners and the community at large.