The immunology of Epstein-Barr virus-induced disease.

Epstein-Barr virus (EBV) is usually acquired silently early in life and carried thereafter as an asymptomatic infection of the B lymphoid system. However, many circumstances disturb the delicate EBV-host balance and cause the virus to display its pathogenic potential. Thus, primary infection in adolescence can manifest as infectious mononucleosis (IM), as a fatal illness that magnifies the immunopathology of IM in boys with the X-linked lymphoproliferative disease trait, and as a chronic active disease leading to life-threatening hemophagocytosis in rare cases of T or natural killer (NK) cell infection. Patients with primary immunodeficiencies affecting the NK and/or T cell systems, as well as immunosuppressed transplant recipients, handle EBV infections poorly, and many are at increased risk of virus-driven B-lymphoproliferative disease. By contrast, a range of other EBV-positive malignancies of lymphoid or epithelial origin arise in individuals with seemingly intact immune systems through mechanisms that remain to be understood.

Efficient and targeted COVID-19 border testing via reinforcement learning.

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 rates1,2. 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 policies3 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.

Underdetection of cases of COVID-19 in France threatens epidemic control.

As countries in Europe gradually relaxed lockdown restrictions after the first wave, test-trace-isolate strategies became critical to maintain the incidence of coronavirus disease 2019 (COVID-19) at low levels1,2. Reviewing their shortcomings can provide elements to consider in light of the second wave that is currently underway in Europe. Here we estimate the rate of detection of symptomatic cases of COVID-19 in France after lockdown through the use of virological3 and participatory syndromic4 surveillance data coupled with mathematical transmission models calibrated to regional hospitalizations2. Our findings indicate that around 90,000 symptomatic infections, corresponding to 9 out 10 cases, were not ascertained by the surveillance system in the first 7 weeks after lockdown from 11 May to 28 June 2020, although the test positivity rate did not exceed the 5% recommendation of the World Health Organization (WHO)5. The median detection rate increased from 7% (95% confidence interval, 6-8%) to 38% (35-44%) over time, with large regional variations, owing to a strengthening of the system as well as a decrease in epidemic activity. According to participatory surveillance data, only 31% of individuals with COVID-19-like symptoms consulted a doctor in the study period. This suggests that large numbers of symptomatic cases of COVID-19 did not seek medical advice despite recommendations, as confirmed by serological studies6,7. Encouraging awareness and same-day healthcare-seeking behaviour of suspected cases of COVID-19 is critical to improve detection. However, the capacity of the system remained insufficient even at the low epidemic activity achieved after lockdown, and was predicted to deteriorate rapidly with increasing incidence of COVID-19 cases. Substantially more aggressive, targeted and efficient testing with easier access is required to act as a tool to control the COVID-19 pandemic. The testing strategy will be critical to enable partial lifting of the current restrictive measures in Europe and to avoid a third wave.

Temperature-dependent carrier state mediated by H-NS promotes the long-term coexistence of Y. pestis and a phage in soil.

The study of carrier state phages challenged the canonical lytic-lysogenic binary, and carrier state appears to be ubiquitous and ecologically important. However, the mechanisms of the carrier state are not well elucidated due to the limited phage models. Herein, we reported phage HQ103, similar to Escherichia coli phage P2. In contrast to the temperate P2 phage, the HQ103 phage does not insert its genome into the bacterial chromosome and displays a dual behavior depending on the temperature. At 37°C, HQ103 lyses the host and forms clear plaques due to the truncation of repressor CI and mutation of promoter Pc. In contrast, HQ103 maintains a carrier state lifestyle with Y. pestis at an environmental temperature (21°C). Mechanistically, we found that the host-encoded histone-like nucleoid-structuring protein H-NS, which is highly expressed at 21°C to silence the Cox promoter Pe and inhibits the phage lytic cycle. Subsequently, the HQ103 carrier state Y. pestis could grow and co-exist with the phage in the soil at 21°C for one month. Thus, this study reveals a novel carrier state lifestyle of phage HQ103 due to the H-NS mediated xenogeneic silencing and demonstrates that the carrier state lifestyle could promote long-term phage-host coexist in nature.

A quantitative approach for measuring the reservoir of latent HIV-1 proviruses.

A stable latent reservoir for HIV-1 in resting CD4+ T cells is the principal barrier to a cure1-3. Curative strategies that target the reservoir are being tested4,5 and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation1. However, these quantitative outgrowth assays and newer assays for cells that produce viral RNA after activation6 may underestimate the reservoir size because one round of activation does not induce all proviruses7. Many studies rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of these assays is unclear, as the vast majority of proviruses are defective7-9. Here we describe a more accurate method of measuring the HIV-1 reservoir that separately quantifies intact and defective proviruses. We show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. These findings have implications for targeting the intact proviruses that are a barrier to curing HIV infection.

Asymptomatic Low-Density Plasmodium falciparum Infections: Parasites Under the Host's Immune Radar?

A large body of evidence suggests that low parasite carriage in Plasmodium falciparum asymptomatic infection is required for the maintenance of malaria immunity. However, the fact that treating such infections has little to no impact on subsequent clinical malaria is rarely noted. In this paper, we review data and argue that low-density parasite carriage in asymptomatic infection may not support host immune processes and that parasites are virtually under the host's immunological radar. We also discuss factors that may be constraining parasitemia in asymptomatic infections from reaching the threshold required to cause clinical symptoms. A thorough understanding of this infectious reservoir is essential for malaria control and eradication because asymptomatic infections contribute significantly to Plasmodium transmission.

Persistent asymptomatic Plasmodium falciparum parasite carriage has been recognized as one of the major contributors to malaria transmission that impedes worldwide elimination efforts. Asymptomatic infection is required for maintaining clinical immunity, hence the controversy regarding its treatment. Evidence from transcriptional and cellular profiling indicates asymptomatic low parasite carriage may not support host immune processes. Interventions targeted at persistent asymptomatic infections may be crucial for malaria control.

Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines.

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.).

Carriage of methicillin-resistant Staphylococcus aureus in children <6 years old: a retrospective follow-up study of the natural course and effectiveness of decolonization treatment.

BACKGROUND: Decolonization treatment of MRSA carriers is recommended in Denmark, except in households with MRSA-positive children <2 years old (wait-and-see approach). OBJECTIVES: To investigate a wait-and-see approach in children 2-5 years old, and the effect of decolonization treatment of MRSA carriage in all children <6 years old. PATIENTS AND METHODS: In this retrospective follow-up study, we included MRSA carriers <6 years old in the Capital Region of Denmark from 2007 to 2021. Data were collected from laboratory information systems and electronic patient records. We divided children into age groups of <2 years or 2-5 years and decolonization treatment versus no treatment. Treatment was chlorhexidine body washes and nasal mupirocin, sometimes supplemented with systemic antibiotics. Children were followed until becoming MRSA free, or censoring. The probability of becoming MRSA free was investigated with Cox regression (higher HRs indicate faster decolonization). RESULTS: Of 348 included children, 226 were <2 years old [56/226 (25%) received treatment] and 122 were 2-5 years old [90/122 (74%) received treatment]. Multivariable analyses did not show a larger effect of decolonization treatment versus no treatment in <2-year-olds (HR 0.92, 95% CI 0.52-1.65) or 2-5-year-olds (HR 0.54, 95% CI 0.26-1.12). Without treatment, 2-5-year-olds tended to clear MRSA faster than <2-year-olds (HR 1.81, 95% CI 0.98-3.37). CONCLUSIONS: We did not find a larger effect of decolonization treatment versus no treatment in children <6 years old, and 2-5-year-olds tended to become MRSA free faster than <2-year-olds. These results support a wait-and-see approach for all children <6 years old, but further studies are needed.

Neisseria genes required for persistence identified via in vivo screening of a transposon mutant library.

The mechanisms used by human adapted commensal Neisseria to shape and maintain a niche in their host are poorly defined. These organisms are common members of the mucosal microbiota and share many putative host interaction factors with Neisseria meningitidis and Neisseria gonorrhoeae. Evaluating the role of these shared factors during host carriage may provide insight into bacterial mechanisms driving both commensalism and asymptomatic infection across the genus. We identified host interaction factors required for niche development and maintenance through in vivo screening of a transposon mutant library of Neisseria musculi, a commensal of wild-caught mice which persistently and asymptomatically colonizes the oral cavity and gut of CAST/EiJ and A/J mice. Approximately 500 candidate genes involved in long-term host interaction were identified. These included homologs of putative N. meningitidis and N. gonorrhoeae virulence factors which have been shown to modulate host interactions in vitro. Importantly, many candidate genes have no assigned function, illustrating how much remains to be learned about Neisseria persistence. Many genes of unknown function are conserved in human adapted Neisseria species; they are likely to provide a gateway for understanding the mechanisms allowing pathogenic and commensal Neisseria to establish and maintain a niche in their natural hosts. Validation of a subset of candidate genes confirmed a role for a polysaccharide capsule in N. musculi persistence but not colonization. Our findings highlight the potential utility of the Neisseria musculi-mouse model as a tool for studying the pathogenic Neisseria; our work represents a first step towards the identification of novel host interaction factors conserved across the genus.

Period prevalence of uveitis in human T-lymphotropic virus 1 carriers versus noncarriers in a highly endemic area: The Nagasaki Islands Study.

The magnitude of the effect of human T-lymphotropic virus 1 (HTLV-1) infection on uveitis remains unclear. We conducted a cross-sectional study in a highly endemic area of HTLV-1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle-aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV-1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age- and sex-adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV-1 infection status. Thirty-two (0.8%) participants had uveitis. For HTLV-1 carriers, the age- and sex-adjusted OR (95% CI) of uveitis was 3.27 (1.57-6.72) compared with noncarriers. In conclusion, HTLV-1 infection was associated with a higher risk of uveitis among mostly middle-aged and older Japanese residents in a highly endemic HTLV-1 area. Our findings suggest that physicians who treat HTLV-1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV-1 infection.

Carrier state of enterotoxigenic Escherichia coli virulence markers in pigs: Effects on gut microbiota modulation and immune markers transcription.

Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in pigs at early age, leading to high mortality rates and significant economic losses in the swine industry. ETEC effect on gut microbiota and immune system is mostly studied in diarrheic model under controlled laboratory conditions, however its impact on asymptomatic carriers remains unknown. Thus, we investigated whether ETEC can modulate gut microbiota or regulate the transcription of immune markers in asymptomatic pigs in farm environment. Stool samples from newborn piglets, nursery and growing pigs, and sows were screened for ETEC markers, then submitted to 16S-rDNA sequencing to explore gut microbiota composition in carriers (ETEC+) and non-carriers (ETEC-) animals. We observed a reduced α-diversity in ETEC+ animals (p < 0.05), while bacterial compositions were mostly driven by ageing (p > 0.05). Prevotella marked ETEC-carrier group, while Rikenellaceae RC9 gut group was a marker for a healthy gut microbiota, suggesting that they might be biomarker candidates for surveillance and supplementation purposes. Furthermore, we observed transcription regulation of il6 and tff2 genes in ETEC+ in newborn and nursery stages, respectively. Our findings indicate that ETEC presence modulate gut microbiota and the immune response in asymptomatic pigs; nevertheless, further studies using a probabilistic design must be performed to assess the effect of ETEC presence on gut imbalance in pigs despite the age bias.

Validation testing to determine the sensitivity of lateral flow testing for asymptomatic SARS-CoV-2 detection in low prevalence settings: Testing frequency and public health messaging is key.

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.

Bayesian modeling of the impact of antibiotic resistance on the efficiency of MRSA decolonization.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity and mortality. Colonization by MRSA increases the risk of infection and transmission, underscoring the importance of decolonization efforts. However, success of these decolonization protocols varies, raising the possibility that some MRSA strains may be more persistent than others. Here, we studied how the persistence of MRSA colonization correlates with genomic presence of antibiotic resistance genes. Our analysis using a Bayesian mixed effects survival model found that genetic determinants of high-level resistance to mupirocin was strongly associated with failure of the decolonization protocol. However, we did not see a similar effect with genetic resistance to chlorhexidine or other antibiotics. Including strain-specific random effects improved the predictive performance, indicating that some strain characteristics other than resistance also contributed to persistence. Study subject-specific random effects did not improve the model. Our results highlight the need to consider the properties of the colonizing MRSA strain when deciding which treatments to include in the decolonization protocol.

Geographical distribution of invasive meningococcal disease and carriage: A spatial analysis.

Little information exists concerning the spatial relationship between invasive meningococcal disease (IMD) cases and Neisseria meningitidis (N. meningitidis) carriage. The aim of this study was to examine whether there is a relationship between IMD and asymptomatic oropharyngeal carriage of meningococci by spatial analysis to identify the distribution and patterns of cases and carriage in South Australia (SA). Carriage data geocoded to participants' residential addresses and meningococcal case notifications using Postal Area (POA) centroids were used to analyse spatial distribution by disease- and non-disease-associated genogroups, as well as overall from 2017 to 2020. The majority of IMD cases were genogroup B with the overall highest incidence of cases reported in infants, young children, and adolescents. We found no clear spatial association between N. meningitidis carriage and IMD cases. However, analyses using carriage and case genogroups showed differences in the spatial distribution between metropolitan and regional areas. Regional areas had a higher rate of IMD cases and carriage prevalence. While no clear relationship between cases and carriage was evident in the spatial analysis, the higher rates of both carriage and disease in regional areas highlight the need to maintain high vaccine coverage outside of the well-resourced metropolitan area.

Nasal carriage of virulent and multidrug resistant Staphylococcus aureus: a possible comorbidity of COVID-19.

BACKGROUND: Staphylococcus aureus (S. aureus) associated with COVID-19 has not been well documented. This cross-sectional study evaluated the association between nasal S. aureus carriage and COVID-19. METHODS AND RESULTS: Nasopharyngeal samples were collected from 391 participants presenting for COVID-19 test in Lagos, Nigeria, and S. aureus was isolated from the samples. Antimicrobial susceptibility test was done by disc diffusion method. All S. aureus isolates were screened for the presence of mecA, panton-valentine leucocidin (PVL) and toxic shock syndrome toxin (TSST) virulence genes by polymerase chain reaction. Staphylococcal protein A (spa) typing was conducted for all the isolates. Participants with COVID-19 had double the prevalence of S. aureus (42.86%) compared to those who tested negative (20.54%). A significant association was seen between S. aureus nasal carriage and COVID-19 (p = 0.004). Antimicrobial sensitivity results showed resistance to oxacillin (100%), cefoxitin (53%), and vancomycin (98.7%). However, only 41% of the isolates harbored the mecA gene, with SCCmecV being the most common SCCmec type. There was no association between the carriage of virulence genes and COVID-19. A total of 23 Spa types were detected, with t13249 and t095 being the two most common spa types. CONCLUSION: This study examined the association between nasal S. aureus carriage and SARS-COV-2 infection. Further research is required to fully explore the implications of S. aureus co-infection with COVID-19.

Combination therapy with anti-HIV-1 antibodies maintains viral suppression.

Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg-1 of each antibody at 0, 3 and 6 weeks. Infusions of the two antibodies were generally well-tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for between 15 and more than 30 weeks (median of 21 weeks), and none developed viruses that were resistant to both antibodies. We conclude that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.

In search of the best method to detect carriage of carbapenem-resistant Pseudomonas aeruginosa in humans: a systematic review.

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_record.asp?ID=CRD42020207390 ).

Nasal carriage of Staphylococcus aureus in healthy dairy cows in Algeria: antibiotic resistance, enterotoxin genes and biofilm formation.

BACKGROUND: Staphylococcus aureus can colonize and infect a variety of animal species. In dairy herds, it is one of the leading causes of mastitis cases. The objective of this study was to characterize the S. aureus isolates recovered from nasal swabs of 249 healthy cows and 21 breeders of 21 dairy farms located in two provinces of Algeria (Tizi Ouzou and Bouira). METHODS: The detection of enterotoxin genes was investigated by multiplex PCRs. Resistance of recovered isolates to 8 antimicrobial agents was determined by disc-diffusion method. The slime production and biofilm formation of S. aureus isolates were assessed using congo-red agar (CRA) and microtiter-plate assay. Molecular characterization of selected isolates was carried out by spa-typing and Multi-Locus-Sequence-Typing (MLST). RESULTS: S. aureus was detected in 30/249 (12%) and 6/13 (28.6%) of nasal swabs in cows and breeders, respectively, and a total of 72 isolates were recovered from positive samples (59 isolates from cows and 13 from breeders). Twenty-six of these isolates (36.1%) harbored genes encoding for staphylococcal enterotoxins, including 17/59 (28.8%) isolates from cows and 9/13 (69.2%) from breeders. Moreover, 49.1% and 92.3% of isolates from cows and breeders, respectively, showed penicillin resistance. All isolates were considered as methicillin-susceptible (MSSA). Forty-five (76.3%) of the isolates from cows were slime producers and 52 (88.1%) of them had the ability to form biofilm in microtiter plates. Evidence of a possible zoonotic transmission was observed in two farms, since S. aureus isolates recovered in these farms from cows and breeders belonged to the same clonal lineage (CC15-ST15-t084 or CC30-ST34-t2228). CONCLUSIONS: Although healthy cows in this study did not harbor methicillin-resistant S. aureus isolates, the nares of healthy cows could be a reservoir of enterotoxigenic and biofilm producing isolates which could have implications in human and animal health.

Genetic Determinants in MRSA Carriage and Their Association with Decolonization Outcome.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases the risk of infection. Response to decolonization treatment is highly variable and determinants for successful decolonization or failure of eradication treatment are largely unknown. Insight into genetic predictors of eradication failure is potentially useful in clinical practice. The aim of this study was to explore genetic characteristics that are associated with MRSA decolonization failure. This cohort study was performed in a tertiary care hospital in the Netherlands. Patients with ≥ 1 positive MRSA culture from any site and with available whole -genome sequencing data of the MRSA isolate between 2017 and 2022 were included. Lineages, resistance, and virulence factors were stratified by MRSA decolonization outcome. In total, 56 patients were included: 12/56 (21%) with treatment failure and 44/56 (79%) with successful decolonization (with or without preceding treatment). A significant association was found between ciprofloxacin-resistant lineages and failure of eradication (OR 4.20, 95%CI 1.11-15.96, P = 0.04). Furthermore, livestock-associated MRSA and the major community-associated MRSA lineages ST6-t304 and ST8-t008 were associated with successful eradication treatment or spontaneous clearance. In conclusion, this explorative study showed a higher eradication failure rate in complicated MRSA carriers with ciprofloxacin-resistant MRSA lineages, which are predominantly healthcare-associated. Further studies are warranted to confirm the higher eradication failure risk of ciprofloxacin-resistant lineages, and identify the underlying mechanisms.

Identifying asymptomatic spreaders of antimicrobial-resistant pathogens in hospital settings.

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.