Involuntary admissions for non-affective psychotic disorders in young refugees and peers in Denmark: A population cohort study.

INTRODUCTION: People with psychotic disorders are at increased risk of experiencing involuntary hospital admissions relative to other psychiatric patients. Within this group, refugees and other minority groups may be at even greater risk. However, little is known about the role of migration background in the risk of involuntary admissions around the time of first psychosis-related treatment. METHOD: We utilized nationwide administrative data from Denmark covering the period 2006-2018. We included all persons aged 18-35 years in first treatment for psychotic disorders [inpatient and hospital-based outpatient settings (N = 11,871)]. We estimated odds ratios (OR) of any involuntary inpatient admission within three months of first treatment using logistic regression, and rate ratios (RR) of further involuntary admissions, total number of involuntary admissions, and days of involuntary care among patients initially admitted involuntarily using Poisson regression. We compared refugees with majority peers (native-born with native-born parent), other migrants, and descendants of non-refugee migrants. RESULTS: Compared with the majority group, refugees, non-refugee migrants and descendants were at increased risk of involuntarily admissions (ORrange = 2.12-2.69). Differences in sex, age, education, household income and family situation did not explain these disparities. In contrast, the risk of subsequent involuntary care did not differ between groups (RRrange = 0.77-1.31). CONCLUSIONS: The findings highlight the need to review if and why processes of needs detection and voluntary treatment enrolment are less effective for minorities in Denmark. Further studies should investigate the pathways to care across population groups to inform interventions that address disparities.

α-Hemolysin-mediated endothelial injury contributes to the development of Staphylococcus aureus-induced dermonecrosis.

Staphylococcus aureus α-hemolysin (Hla) is a pore-forming toxin critical for the pathogenesis of skin and soft tissue infections, which causes the pathognomonic lesion of cutaneous necrosis (dermonecrosis) in mouse models. To determine the mechanism by which dermonecrosis develops during S. aureus skin infection, mice were given control serum, Hla-neutralizing antiserum, or an inhibitor of Hla receptor [A-disintegrin and metalloprotease 10 (ADAM10) inhibitor] followed by subcutaneous infection by S. aureus, and the lesions were evaluated using immunohistochemistry and immunofluorescence. Hla induced apoptosis in the vascular endothelium at 6 hours post-infection (hpi), followed by apoptosis in keratinocytes at 24 hpi. The loss of vascular endothelial (VE)-cadherin expression preceded the loss of epithelial-cadherin expression. Hla also induced hypoxia in the keratinocytes at 24 hpi following vascular injury. Treatment with Hla-neutralizing antibody or ADAM10 inhibitor attenuated early cleavage of VE-cadherin, cutaneous hypoxia, and dermonecrosis. These findings suggest that Hla-mediated vascular injury with cutaneous hypoxia underlies the pathogenesis of S. aureus-induced dermonecrosis.

Risk Factors for Persistent Staphylococcus aureus Bacteremia in Children.

BACKGROUND: Staphylococcus aureus is a leading cause of pediatric bacteremia. Persistent S. aureus bacteremia (SAB) is associated with increased morbidity and mortality in adults and children. Risk factors for S. aureus bacteremia have been well established, but there is a limited understanding of the factors that contribute to the development of persistent SAB in children. METHODS: This is a single-center retrospective secondary analysis of a prospective observational study of pediatric patients hospitalized with S. aureus infection over a 3.5-year period at a large, quaternary, children's hospital. RESULTS: Two hundred fifty-nine children with confirmed S. aureus infection were enrolled in the study. Sixty-five of these were found to have bacteremia, with 28 (43%) developing persistent bacteremia. Patients with persistent SAB were culture-positive for a median of 3.5 days compared with 1 day for those without (P ≤ 0.001). Children with persistent SAB were more likely to have an identified osteoarticular source of infection (93%, n = 26 vs. 62%, n = 23; P = 0.008) and had a shorter median duration to culture positivity than those without persistent SAB (16 hours vs. 20 hours; P ≤ 0.001). In addition, children with persistent SAB had higher median values of presenting erythrocyte sedimentation rate, peak erythrocyte sedimentation rate, presenting C-reactive protein and peak C-reactive protein. Not surprisingly, hospital length of stay was longer in children with persistent SAB compared with those without. CONCLUSIONS: These findings suggest that a shorter time to culture positivity, osteoarticular infection, and higher presenting and peak values for select inflammatory markers are potential risk factors for persistent SAB in children.

Neighborhood social composition and refugee mental health - quasi-experimental evidence of associations from a Danish population register study.

BACKGROUND: Refugees are at an elevated risk of some mental disorders with studies highlighting the contributing role of post-migration factors. Studies of migrant groups show neighborhood social composition, such as ethnic density, to be important. This is the first longitudinal study to examine this question for refugees and uses a novel quasi-experimental design. METHODS: We followed a cohort of 44 033 refugees from being first assigned housing under the Danish dispersal policy, operating from 1986 to 1998, until 2019. This comprised, in effect, a natural experiment whereby the influence of assigned neighborhood could be determined independently of endogenous factors. We examined three aspects of neighborhood social composition: proportion of co-nationals, refugees, and first-generation migrants; and subsequent incidence of different mental disorders. RESULTS: Refugees assigned to neighborhoods with fewer co-nationals (lowest v. highest quartile) were more likely to receive a subsequent diagnosis of non-affective psychosis, incident rate ratio (IRR) 1.25 (95% confidence interval (CI) 1.06-1.48), and post-traumatic stress disorder (PTSD), IRR 1.21 (95% CI I.05-1.39). A comparable but smaller effect was observed for mood disorders but none observed for stress disorders overall. Neighborhood proportion of refugees was less clearly associated with subsequent mental disorders other than non-affective psychosis, IRR 1.24 (95% CI 1.03-1.50). We found no statistically significant associations with proportion of migrants. CONCLUSIONS: For refugees, living in a neighborhood with a lower proportion of co-nationals is related to subsequent increased risk of diagnosed mental disorders particularly non-affective psychosis and PTSD.

Toxin-neutralizing Abs are associated with improved T cell function following recovery from Staphylococcus aureus infection.

BACKGROUNDT cell responses are impaired in Staphylococcus aureus-infected children, highlighting a potential mechanism of immune evasion. This study tested the hypotheses that toxin-specific antibodies protect immune cells from bacterial killing and are associated with improved T cell function following infection.METHODSS. aureus-infected and healthy children (N = 33 each) were prospectively enrolled. During acute infection and convalescence, we quantified toxin-specific IgG levels by ELISA, antibody function using a cell killing assay, and functional T cell responses by ELISPOT.RESULTSThere were no differences in toxin-specific IgG levels or ability to neutralize toxin-mediated immune cell killing between healthy and acutely infected children, but antibody levels and function increased following infection. Similarly, T cell function, which was impaired during acute infection, improved following infection. However, the response to infection was highly variable; up to half of children did not have improved antibody or T cell function. Serum from children with higher α-hemolysin-specific IgG levels more strongly protected immune cells against toxin-mediated killing. Importantly, children whose serum more strongly protected against toxin-mediated killing also had stronger immune responses to infection, characterized by more elicited antibodies and greater improvement in T cell function following infection.CONCLUSIONThis study demonstrates that, despite T cell impairment during acute infection, S. aureus elicits toxin-neutralizing antibodies. Individual antibody responses and T cell recovery are variable. These findings also suggest that toxin-neutralizing antibodies protect antigen-presenting cells and T cells, thereby promoting immune recovery. Finally, failure to elicit toxin-neutralizing antibodies may identify children at risk for prolonged T cell suppression.FUNDINGNIH National Institute of Allergy and Infectious Diseases R01AI125489 and Nationwide Children's Hospital.

Risk of unemployment and work disability among refugee and non-refugee migrants with incident psychotic disorders in Sweden and Denmark.

BACKGROUND: Unemployment and work disability are common among individuals with non-affective psychotic disorders (NAPDs) but it is unknown whether rates differ among migrants and native-born individuals. The present study aimed to compare the risk of these outcomes during the first 5 years of illness in non-refugee migrants, refugees and native-born individuals with NAPDs in Sweden and Denmark-two countries with different immigration policies and models of early psychosis care. METHODS: Using national registers, we identified all individuals aged 18-35 years in Sweden and Denmark who received an incident NAPD diagnosis between 2006 and 2013 (N = 6750 and 8320, respectively). Cohorts were followed for 5 years to determine the days of unemployment and sickness absence (analyzed using zero-inflated negative binomial models) and the time to receipt of disability pension (analyzed using complementary log-log models). RESULTS: Relative to their native-born peers, refugees and non-refugee migrants in Sweden and non-refugee migrants in Denmark were significantly less likely to have zero unemployment days (OR range: 0.54-0.72) and all migrant groups experienced more unemployment days (IRR range: 1.26-1.37). Results were largely unchanged after adjustment for sociodemographic and clinical factors. In the adjusted model, both Swedish migrant groups and refugees in Denmark were more likely to experience zero sickness absence days than native-born individuals (OR range: 1.48-1.56). Only refugees in Denmark were at greater risk of disability pension. CONCLUSIONS: Non-refugee migrants and refugees with NAPDs in both Sweden and Denmark are particularly vulnerable to experiencing unemployment. Targeted interventions may help to reduce these disparities and promote long-term work ability among migrant groups.

Incidence of non-affective psychotic disorders in refugees and peers growing up in Denmark and Sweden: a registry linkage study.

PURPOSE: Higher rates of non-affective psychotic disorders (NAPD) in minority groups have been reported in many countries. However, few studies have explored how rates differ between refugees and other minority groups and none with an international comparative angle. A comparative perspective makes it possible to relate group differences to aspects national context that underpin the social determinants of disease. METHODS: We compared the incidence of treated NAPD among youth born in or who immigrated to Denmark/Sweden before turning 18. Youth aged 18-35 during 2006-2018 were included (NDenmark/NSweden = 1,606,423/2,614,721) and were followed until first NAPD treatment (cases [Denmark/Sweden] = 12,193/9,641), 36th birthday, emigration or death. Incidence rates (IR) and ratios (IRR) comparing refugees, non-refugee migrants, descendants of non-refugee migrants and majority youth were obtained through Poisson regression on data aggregated by country, sex and age, contrasted by sex and country. Complementary analyses on individual-level data adjusting for further socio-demographic factors were conducted in each country separately. RESULTS: Incidence rates were higher in all groups compared with the majority group (IRRrange = 1.4-2.9, 95% CI[min, max] = 1.2-3.1). Relative differences between the three minority groups were smaller (IRRrange = 0.7-1.0, 95% CI[min, max] = 0.5-1.2). Although incidence rates were higher in Denmark than Sweden, relative group differences were similar. CONCLUSION: Exposures shared between young refugees and other minority groups growing up in Denmark and Sweden may be especially important for their excess risk of NAPD. Further studies should investigate the mechanisms behind the elevated rates in minority groups with special paid attention to factors such as discrimination, social exclusion and acculturation stress.

Comparison of Hospitalization for Nonaffective Psychotic Disorders Among Refugee, Migrant, and Native-Born Adults in Sweden and Denmark.

Importance: Determining whether migrants with nonaffective psychotic disorders (NAPDs) experience poorer outcomes after illness onset is essential to ensure adequate health care provision to these disadvantaged populations. Objective: To compare cumulative hospital days for NAPDs during the first 5 years of illness among refugee, nonrefugee, and second-generation migrants and their Swedish and Danish peers. Design, Setting, and Participants: This was a prospective cohort study of individuals treated for incident NAPDs in inpatient or outpatient settings between January 1, 2006, and December 31, 2013, and followed up for 5 years. This population-based study used Swedish and Danish national registries. Included participants were individuals in Sweden and Denmark, aged 18 to 35 years, treated for incident NAPDs. Data analyses were conducted from November 2022 to August 2023. Exposures: Population group (determined according to residency in either country, not both countries), categorized as refugee (migrants whose residence in Sweden or Denmark was registered as refugee status or family reunification with a refugee), nonrefugee (all other individuals born outside Sweden and Denmark), second generation (individuals born in Sweden or Denmark with at least 1 parent born abroad), or native born (individuals born in Sweden or Denmark with both parents born in these countries). Main Outcome and Measures: Total hospital days for NAPDs during the first 5 years of illness, analyzed using a hurdle model. Among those ever admitted, total number of admissions and mean admission length were examined. Results: In total, 7733 individuals in Sweden (mean [SD] age, 26.0 [5.1] years; 4919 male [63.6%]) and 8747 in Denmark (mean [SD] age 24.8 [5.0] years; 5324 male [60.9%]) were followed up for 5 years or until death or emigration. After adjusting for a range of sociodemographic and clinical factors, the odds of experiencing any hospital days for NAPD were significantly higher among migrant groups compared with their native-born peers (Sweden: second generation, odds ratio [OR], 1.17; 95% CI, 1.03-1.33; P = .01; nonrefugee migrant, OR, 1.45; 95% CI, 1.21-1.73; P < .001; refugee, OR, 1.25; 95% CI, 1.06-1.47; P = .009; Denmark: second generation, OR, 1.21; 95% CI, 1.05-1.40; P = .01; nonrefugee migrant, OR, 1.33; 95% CI, 1.14-1.55; P < .001). These odds were highest among nonrefugee (Sweden: OR, 2.53; 95% CI, 1.59-4.03; P < .001; Denmark: OR, 2.61; 95% CI, 1.70-4.01; P < .001) and refugee (Sweden: OR, 1.96; 95% CI, 1.43-2.69; P < .001; Denmark: OR, 2.14; 95% CI, 1.42-3.21; P < .001) migrants from Africa and those who had arrived within 3 to 5 years (Sweden: nonrefugee migrants, OR, 1.93; 95% CI, 1.26-2.95; P = .002; refugees, OR, 2.38; 95% CI, 1.46-3.88; P < .001; Denmark: nonrefugee migrants, OR, 1.66; 95% CI, 0.96-2.85; P = .07; refugees, OR, 3.40; 95% CI, 1.13-10.17; P = .03). Among those ever hospitalized, refugees in both countries (Sweden, incidence rate ratio [IRR], 1.30; 95% CI, 1.12-1.51; P < .001; Denmark, IRR, 1.47; 95% CI, 1.24-1.75; P < .001) and second-generation migrants in Denmark (IRR, 1.22; 95% CI, 1.07-1.39; P = .003) experienced more days hospitalized for NAPDs than native-born individuals. Conclusions and Relevance: In this prospective cohort study of individuals with NAPDs, results suggest that refugee, nonrefugee, and second-generation migrants experience more days hospitalized for these disorders than their native-born peers. Patterns were consistent across 2 countries with different models of psychosis care and immigration and integration policies.

Differences in postpartum mental healthcare among women with identified needs: The role of migration status.

AIMS: The aim of this study was to examine the association between women's migrant status (majority, immigrant, descendant) and use of postpartum mental healthcare and investigate whether migration characteristics are associated with mental healthcare use. METHODS: Retrospective cohort study. We included all mothers of children born between 2002 and 2018 in 34 municipalities of Denmark who had an identified mental health need as clinically assessed by a child health visitor (CHV) or by a score of 11 or more on the Edinburgh Postpartum Depression Scale (EPDS). Women were followed until the first mental healthcare received 2 years' postpartum, death or emigration. Using Cox regression models, we estimated the time to mental healthcare by migrant status and explored the role of migration characteristics. RESULTS: A total of 29% of women (n = 45,573) had a mental health need identified by the CHV, and 7% (n = 4968) had an EPDS ⩾ 11. Immigrants accounted for 19.5%, and descendants for 4.7% of the sample. Immigrants were at lower risk of using mental healthcare than the majority group (CHV: hazard ratio adjusted (HRa) 0.75 (0.70-0.79), EPDS: HRa 0.67 (0.58-0.78)), as were descendants (CHV: HRa 0.77 (0.70-0.86), EPDS: HRa 0.69 (0.55-0.88)). Among migrants, those not refugees, newly arrived, whose partners were immigrants or descendants, and those originally from Africa showed a lower risk of using postpartum mental healthcare. CONCLUSIONS: Our findings emphasize the need to strengthen access to mental healthcare for immigrants and descendants experiencing postpartum mental health concerns and consider migration characteristics as indicators of potential inequalities in access to maternal mental healthcare.

Antipsychotic treatment patterns in refugees and their Swedish-born peers with first-episode non-affective psychosis: findings from the REMAIN study.

BACKGROUND: Previous studies suggest that migrants tend to utilise antipsychotics less often than their native-born peers. However, studies examining antipsychotic use among refugees with psychosis are lacking. AIMS: To compare the prevalence of antipsychotic drug use during the first 5 years of illness among refugees and Swedish-born individuals with a newly diagnosed non-affective psychotic disorder, and to identify sociodemographic and clinical factors associated with antipsychotic use. METHOD: The study population included refugees (n = 1656) and Swedish-born persons (n = 8908) aged 18-35 years during 2007-2018, with incident diagnosis of non-affective psychotic disorder recorded in the Swedish in-patient or specialised out-patient care register. Two-week point prevalence of antipsychotics use was assessed every 6 months in the 5 years following first diagnosis. Factors associated with antipsychotic use (versus non-use) at 1 year after diagnosis were examined with modified Poisson regression. RESULTS: Refugees were somewhat less likely to use antipsychotics at 1 year after first diagnosis compared with Swedish-born persons (37.1% v. 42.2%, age- and gender-adjusted risk ratio 0.88, 95% CI 0.82-0.95). However, at the 5-year follow-up, refugees and Swedish-born individuals showed similar patterns of antipsychotic use (41.1% v. 40.4%). Among refugees, higher educational level (>12 years), previous antidepressant use and being diagnosed with schizophrenia/schizoaffective disorder at baseline were associated with an increased risk of antipsychotics use, whereas being born in Afghanistan or Iraq (compared with former Yugoslavia) was associated with decreased risk. CONCLUSIONS: Our findings suggest that refugees with non-affective psychotic disorders may need targeted interventions to ensure antipsychotic use during the early phase of illness.

Toxin expression during Staphylococcus aureus infection imprints host immunity to inhibit vaccine efficacy.

Staphylococcus aureus infections are a major public health issue, and a vaccine is urgently needed. Despite a considerable promise in preclinical models, all vaccines tested thus far have failed to protect humans against S. aureus. Unlike laboratory mice, humans are exposed to S. aureus throughout life. In the current study, we hypothesized that prior exposure to S. aureus "imprints" the immune response to inhibit vaccine-mediated protection. We established a mouse model in which S. aureus skin and soft tissue infection (SSTI) is followed by vaccination and secondary SSTI. Unlike naïve mice, S. aureus-sensitized mice were incompletely protected against secondary SSTI by vaccination with the inactivated α-hemolysin (Hla) mutant HlaH35L. Inhibition of protection was specific for the HlaH35L vaccine and required hla expression during primary SSTI. Surprisingly, inhibition occurred at the level of vaccine-elicited effector T cells; hla expression during primary infection limited the expansion of T cells and dendritic cells and impaired vaccine-specific T cell responses. Importantly, the T cell-stimulating adjuvant CAF01 rescued inhibition and restored vaccine-mediated protection. Together, these findings identify a potential mechanism for the failure of translation of promising S. aureus vaccines from mouse models to clinical practice and suggest a path forward to prevent these devastating infections.

Health outcomes in young adulthood among former child refugees in Denmark, Norway and Sweden: A cross-country comparative study.

AIMS: This study aimed at comparing several health outcomes in young adulthood among child refugees who settled in the different immigration and integration policy contexts of Denmark, Norway and Sweden. METHODS: The study population included refugees born between 1972 and 1997 who immigrated before the age of 18 and settled in the three Nordic countries during 1986-2005. This population was followed up in national registers during 2006-2015 at ages 18-43 years and was compared with native-born majority populations in the same birth cohorts using sex-stratified and age-adjusted regression analyses. RESULTS: Refugee men in Denmark stood out with a consistent pattern of higher risks for mortality, disability/illness pension, psychiatric care and substance misuse relative to native-born majority Danish men, with risk estimates being higher than comparable estimates observed among refugee men in Norway and Sweden. Refugee men in Sweden and Norway also demonstrated increased risks relative to native-born majority population men for inpatient psychiatric care, and in Sweden also for disability/illness pension. With the exception of increased risk for psychotic disorders, outcomes among refugee women were largely similar to or better than those of native-born majority women in all countries. CONCLUSIONS: The observed cross-country differences in health indicators among refugees, and the poorer health outcomes of refugee men in Denmark in particular, may be understood in terms of marked differences in Nordic integration policies. However, female refugees in all three countries had better relative health outcomes than refugee men did, suggesting possible sex differentials that warrant further investigation.

Regulation of the Sae Two-Component System by Branched-Chain Fatty Acids in Staphylococcus aureus.

Staphylococcus aureus is a ubiquitous Gram-positive bacterium and an opportunistic human pathogen. S. aureus pathogenesis relies on a complex network of regulatory factors that adjust gene expression. Two important factors in this network are CodY, a repressor protein responsive to nutrient availability, and the SaeRS two-component system (TCS), which responds to neutrophil-produced factors. Our previous work revealed that CodY regulates the secretion of many toxins indirectly via Sae through an unknown mechanism. We report that disruption of codY results in increased levels of phosphorylated SaeR (SaeR~P) and that codY mutant cell membranes contain a higher percentage of branched-chain fatty acids (BCFAs) than do wild-type membranes, prompting us to hypothesize that changes to membrane composition modulate the activity of the SaeS sensor kinase. Disrupting the lpdA gene encoding dihydrolipoyl dehydrogenase, which is critical for BCFA synthesis, significantly reduced the abundance of SaeR, phosphorylated SaeR, and BCFAs in the membrane, resulting in reduced toxin production and attenuated virulence. Lower SaeR levels could be explained in part by reduced stability. Sae activity in the lpdA mutant could be complemented genetically and chemically with exogenous short- or full-length BCFAs. Intriguingly, lack of lpdA also alters the activity of other TCSs, suggesting a specific BCFA requirement managing the basal activity of multiple TCSs. These results reveal a novel method of posttranscriptional virulence regulation via BCFA synthesis, potentially linking CodY activity to multiple virulence regulators in S. aureus. IMPORTANCE Two-component systems (TCSs) are an essential way that bacteria sense and respond to their environment. These systems are usually composed of a membrane-bound histidine kinase that phosphorylates a cytoplasmic response regulator. Because most of the histidine kinases are embedded in the membrane, lipids can allosterically regulate the activity of these sensors. In this study, we reveal that branched-chain fatty acids (BCFAs) are required for the activation of multiple TCSs in Staphylococcus aureus. Using both genetic and biochemical data, we show that the activity of the virulence activator SaeS and the phosphorylation of its response regulator SaeR are reduced in a branched-chain keto-acid dehydrogenase complex mutant and that defects in BCFA synthesis have far-reaching consequences for exotoxin secretion and virulence. Finally, we show that mutation of the global nutritional regulator CodY alters BCFA content in the membrane, revealing a potential mechanism of posttranscriptional regulation of the Sae system by CodY.

Tissue specificity drives protective immunity against Staphylococcus aureus infection.

Infections caused by Staphylococcus aureus range from mild to severe and frequently recur. Emerging evidence suggests that the site and severity of infection drive the potency of elicited immune responses and susceptibility to recurrent infection. In this study, we used tractable mouse models of S. aureus skin infection (SSTI) and pneumonia to determine the relative magnitude of elicited protective immunity. Surprisingly, despite both SSTI and pneumonia eliciting antibody and local effector T cell responses, only SSTI elicited protective antibody and memory T cell responses and subsequent protection against secondary SSTI and pneumonia. The failure of pneumonia to elicit protective immunity was attributed to an inability of S. aureus pneumonia to elicit toxin-specific antibodies that confer protection during secondary infection and was associated with a failure to expand antigen-specific memory T cells. Taken together, these findings emphasize the importance of understanding protective immunity in the context of the tissue-specificity.

Antibiotic Treatment of Staphylococcus aureus Infection Inhibits the Development of Protective Immunity.

Recurrent Staphylococcus aureus infections are common, suggesting a failure to elicit protective immunity. Given the emergence of antibiotic resistance, a vaccine is urgently needed, but there is no approved vaccine for S. aureus. While antibiotics are routinely used to treat S. aureus infections, their impact on the development of protective immunity is not understood. Using an established mouse model of S. aureus skin and soft tissue infection (SSTI), we observed that antibiotic therapy effectively resolved infection but failed to elicit protection against secondary (2°) SSTI. Key contributors to protective immunity, toxin-specific antibodies and interleukin-17A (IL-17A)-producing T cells, were not strongly elicited in antibiotic-treated mice. Delaying antibiotic treatment failed to resolve skin lesions but resulted in higher antibody levels after infection and strong protection against 2° SSTI, suggesting that the development of protective immunity requires a longer period of antigen exposure. We next investigated if combining α-hemolysin (Hla) vaccination with antibiotics during primary infection would both treat infection and generate durable protective immunity. This "therapeutic vaccination" approach resulted in rapid resolution of primary infection and protection against recurrent infection, demonstrating that concurrent vaccination could circumvent the deleterious effects of antibiotic therapy on elicited immune responses. Collectively, these findings suggest that protective immunity is thwarted by the rapid elimination of antigen during antibiotic treatment. However, vaccination in conjunction with antibiotic treatment can retain the benefits of antibiotic treatment while also establishing protective immunity.

Labour market marginalisation in young refugees and their majority peers in Denmark and Sweden: The role of common mental disorders and secondary school completion.

BACKGROUND: Due to the circumstances of their early lives, young refugees are at risk of experiencing adverse labour market and health outcomes. The post-settlement environment is thought to play a decisive role in determining how this vulnerability plays out. This study compared trends in labour market marginalisation in young refugees and their majority peers during early adulthood in two national contexts, Denmark and Sweden, and explored the mediating role of common mental disorders and secondary school completions. METHODS: Using registry data, 13,390/45,687 refugees were included in Denmark/Sweden and 1:5 matched to majority peers. Inequalities in labour market marginalisation were investigated during 2012-2015 in each country using linear probability models and mediation analysis. Country trends were standardised to account for differences in observed population characteristics. RESULTS: The risk of marginalisation was 2.1-2.3 times higher among young refugees compared with their majority peers, but the risk decreased with age in Sweden and increased in Denmark for refugees. Birth-cohort differences drove the increase in Denmark, while trends were consistent across birth-cohorts in Sweden. Differences in population characteristics did not contribute to country differences. Common mental disorders did not mediate the inequality in either country, but secondary school completions did (77-85% of associations eliminated). CONCLUSIONS: The findings document both the vulnerability of young refugees to labour market marginalisation and the variability in this vulnerability across post-settlement contexts. While the contrast in policy climates in Denmark and Sweden sharpened over time, the risk of marginalisation appeared more similar in younger cohorts, pointing to the importance of factors other than national immigration and integration policies. Institutional efforts to assist young refugees through secondary education are likely to have long-lasting consequences for their socio-economic trajectories.

Differences in psychiatric care utilization between refugees, non-refugee migrants and Swedish-born youth.

BACKGROUND: The study aimed to examine differences in, and characteristics of psychiatric care utilization in young refugees who came to Sweden as unaccompanied or accompanied minors, compared with that of their non-refugee immigrant and Swedish-born peers. METHODS: This register-linkage cohort study included 746 688 individuals between 19 and 25 years of age in 2009, whereof 32 481 were refugees (2896 unaccompanied and 29 585 accompanied) and 32 151 non-refugee immigrants. Crude and multivariate Cox regression models yielding hazard ratios (HR) and 95% confidence intervals (CI) were conducted to investigate subsequent psychiatric care utilization for specific disorders, duration of residence and age at migration. RESULTS: The adjusted HRs for psychiatric care utilization due to any mental disorder was significantly lower in both non-refugee and refugee immigrants when compared to Swedish-born [aHR: 0.78 (95% CI 0.76-0.81) and 0.75 (95% CI 0.72-0.77, respectively)]. Within the refugee group, unaccompanied had slightly lower adjusted risk estimates than accompanied. This pattern was similar for all specific mental disorders except for higher rates in schizophrenia, reaction to severe stress/adjustment disorders and post-traumatic stress disorder. Psychiatric health care utilization was also higher in immigrants with more than 10 years of residency in Sweden entering the country being younger than 6 years of age. CONCLUSIONS: For most mental disorders, psychiatric health care utilization in young refugees and non-refugee immigrants was lower than in their Swedish-born peers; exceptions are schizophrenia and stress-related disorders. Arrival in Sweden before the age of 6 years was associated with higher rates of overall psychiatric care utilization.

Impaired T-Lymphocyte Responses During Childhood Staphylococcus aureus Infection.

BACKGROUND: Staphylococcus aureus infections are common throughout the lifespan, with recurrent infections occurring in nearly half of infected children. There is no licensed vaccine, underscoring the need to better understand how S. aureus evades protective immunity. Despite much study, the relative contributions of antibodies and T cells to protection against S. aureus infections in humans are not fully understood. METHODS: We prospectively quantified S. aureus-specific antibody levels by ELISA and T-cell responses by ELISpot in S. aureus-infected and healthy children. RESULTS: S. aureus-specific antibody levels and T-cell responses increased with age in healthy children, suggesting a coordinated development of anti-staphylococcal immunity. Antibody levels against leukotoxin E (LukE) and Panton-Valentine leukocidin (LukS-PV), but not α-hemolysin (Hla), were higher in younger infected children, compared with healthy children; these differences disappeared in older children. We observed a striking impairment of global and S. aureus-specific T-cell function in children with invasive and noninvasive infection, suggesting that S. aureus-specific immune responses are dysregulated during childhood infection regardless of the infection phenotype. CONCLUSIONS: These findings identify a potential mechanism by which S. aureus infection actively evades adaptive immune responses, thereby preventing the development of protective immunity and maintaining susceptibility to recurrent infection.