Associations between adjustment disorder and hospital-based infections in the Danish population.

OBJECTIVE:There is some evidence that posttraumatic stress disorder (PTSD) is associated with increased risk of infections, and it is unknown whether adjustment disorder is as well. We assessed the association between adjustment disorder and subsequent infections, and assessed additive interaction with sex. METHODS:The study population included a nationwide cohort of all Danish-born residents of Denmark diagnosed with adjustment disorder between 1995 and 2011, and an age- and sex-matched general population comparison cohort. We compared rates of infections requiring inpatient or outpatient hospitalization in the two cohorts. We fit Cox proportional hazards models to compute adjusted hazard ratios (aHR) for the associations between adjustment disorder and 32 types of infections, and calculated interaction contrasts to assess interaction between adjustment disorder and sex. RESULTS:Adjustment disorder was associated with increased rates of infections overall (n = 19,838 infections, aHR = 1.8, 95% confidence interval = 1.8. 1.9), and increased rates of each individual infection type (aHRs for 30 infections ranged from 1.5 to 2.3), adjusting for baseline psychiatric and somatic comorbidities and marital status. For many infection types (e.g., skin infections, pneumonia), interaction contrasts indicated rate differences were greater among men than women, while for two (urinary tract infections and sexually transmitted infections), rate differences were greater for women. CONCLUSIONS:These findings are consistent with studies examining the relationship between psychological stress and infections, and between PTSD and infections. They may be explained by a combination of the triggering of unhealthy behaviors as well as immune responses to stress

A large population-based investigation into the genetics of susceptibility to gastrointestinal infections and the link between gastrointestinal infections and mental illness.

Gastrointestinal infections can be life threatening, but not much is known about the host's genetic contribution to susceptibility to gastrointestinal infections or the latter's association with psychiatric disorders. We utilized iPSYCH, a genotyped population-based sample of individuals born between 1981 and 2005 comprising 65,534 unrelated Danish individuals (45,889 diagnosed with mental disorders and 19,645 controls from a random population sample) in which all individuals were linked utilizing nationwide population-based registers to estimate the genetic contribution to susceptibility to gastrointestinal infections, identify genetic variants associated with gastrointestinal infections, and examine the link between gastrointestinal infections and psychiatric and neurodevelopmental disorders. The SNP heritability of susceptibility to gastrointestinal infections ranged from 3.7% to 6.4% on the liability scale. Significant correlations were found between gastrointestinal infections and the combined group of mental disorders (OR = 2.09; 95% CI: 1.82-2.4, P = 1.87 × 10-25). Correlations with autism spectrum disorder, attention deficit hyperactivity disorder, and depression were also significant. We identified a genome-wide significant locus associated with susceptibility to gastrointestinal infections (OR = 1.13; 95% CI: 1.08-1.18, P = 2.9 × 10-8), where the top SNP was an eQTL for the ABO gene. The risk allele was associated with reduced ABO expression, providing, for the first time, genetic evidence to support previous studies linking the O blood group to gastrointestinal infections. This study also highlights the importance of integrative work in genetics, psychiatry, infection, and epidemiology on the road to translational medicine

Prosthetic joint infections

Objectives: To review the available literature on prosthetic joint infections and provide recommendations on management particularly the importance of identifying the causative organism and starting the most appropriate antimicrobial therapy. Methods: The medical literature was searched using PubMed, employing the key words prosthetic joint infections. There appears to be no UK consensus guidelines on the management of prosthetic joint infections or the use of prophylactic antibiotics to prevent them. There is however a number of key documents and trust policies which deal with the subject extensively. We also made use of ‘The Sanford Guide to Antimicrobial therapy 2012’ for the latest recommendations on the correct antimicrobial therapy. Conclusion: Although diagnosis is often difficult, there are a number of investigations which can help us identify the organism. We recommend that the local prevalence of such infections is studied together with identification of the commonest organisms. Work is already underway between the infectious disease team and orthopaedic surgeons to devise locally adapted protocols for the identification and management of such infections. They should work in close liaison to implement the correct treatment which often involves a combination of both surgical and antimicrobial therapy.peer-reviewe

Drug resistance mediating Plasmodium falciparum polymorphisms and clinical presentations of parasitaemic children in Uganda.

BackgroundPlasmodium falciparum genetic polymorphisms that mediate altered drug sensitivity may impact upon virulence. In a cross-sectional study, Ugandan children with infections mutant at pfcrt K76T, pfmdr1 N86Y, or pfmdr1 D1246Y had about one-fourth the odds of symptomatic malaria compared to those with infections with wild type (WT) sequences. However, results may have been confounded by greater likelihood in those with symptomatic disease of higher density mixed infections and/or recent prior treatment that selected for WT alleles.MethodsPolymorphisms in samples from paired episodes of asymptomatic and symptomatic parasitaemia in 114 subjects aged 4-11 years were followed longitudinally in Tororo District, Uganda. Paired episodes occurred within 3-12 months of each other and had no treatment for malaria in the prior 60 days. The prevalence of WT, mixed, and mutant alleles was determined using multiplex ligase detection reaction-fluorescent microsphere assays.ResultsConsidering paired episodes in the same subject, the odds of symptomatic malaria were lower for infections with mutant compared to WT or mixed sequence at N86Y (OR 0.26, 95% CI 0.09-0.79, p = 0.018), but not K76T or D1246Y. However, symptomatic episodes (which had higher densities) were more likely than asymptomatic to be mixed (for N86Y OR 2.0, 95% CI 1.04-4.0, p = 0.036). Excluding mixed infections, the odds of symptomatic malaria were lower for infections with mutant compared to WT sequence at N86Y (OR 0.33, 95% CI 0.11-0.98, p = 0.046), but not the other alleles. However, if mixed genotypes were grouped with mutants in this analysis or assuming that mixed infections consisted of 50% WT and 50% mutant genotypes, the odds of symptomatic infection did not differ between infections that were mutant or WT at the studied alleles.ConclusionsAlthough infections with only the mutant pfmdr1 86Y genotype were associated with symptomatic infection, this association could primarily be explained by greater parasite densities and therefore greater prevalence of mixed infections in symptomatic children. These results indicate limited association between the tested polymorphisms and risk of symptomatic disease and highlight the value of longitudinal studies for assessing associations between parasite factors and clinical outcomes

Development of reverse-transcription PCR techniques to analyse the density and sex ratio of gametocytes in genetically diverse Plasmodium chabaudi infections

We have developed cross-genotype and genotype-specific quantitative reverse-transcription PCR (qRT-PCR) assays to detect and quantify the number of parasites, transmission stages (gametocytes) and male gametocytes in blood stage Plasmodium chabaudi infections. Our cross-genotype assays are reliable, repeatable and generate counts that correlate strongly (R(2)s > 90%) with counts expected from blood smears. Our genotype-specific assays can distinguish and quantify different stages of genetically distinct parasite clones (genotypes) in mixed infections and are as sensitive as our cross-genotype assays. Using these assays we show that gametocyte density and gametocyte sex ratios vary during infections for two genetically distinct parasite lines (genotypes) and present the first data to reveal how sex ratio is affected when each genotype experiences competition in mixed-genotype infections. Successful infection of mosquito vectors depends on both gametocyte density and their sex ratio and we discuss the implications of competition in genetically diverse infections for transmission success

Host and bacterial proteases influence biofilm formation and virulence in a murine model of enterococcal catheter-associated urinary tract infection

Urinary tract infections: targeting enzymes might help Identifying bacterial and host enzymes that support biofilm formation may help prevent urinary tract infections caused by catheters. Enterococcus faecalis bacteria is a leading cause of catheter-associated urinary tract infections, the most common type of hospital-acquired infections. Michael Caparon and colleagues at Washington University School of Medicine in Missouri, USA, studied these infections in mice. They examined the effects of two protein-degrading enzymes, both from the bacterium and one can be activated by urine trypsin-like protease from the animals. Mutations that impaired either one of the enzymes had no effect on the infection, but when both the bacterial enzymes were impaired by mutation the formation of biofilms was significantly reduced. Treating the mice with chemicals that inhibited both bacterial and host enzymes dramatically reduced catheter-induced inflammation and related problems. This suggests drugs targeting these enzymes could be useful in clinical care

The spread of multi drug resistant infections is leading to an increase in the empirical antibiotic treatment failure in cirrhosis: a prospective survey

Background The spread of multi-resistant infections represents a continuously growing problem in cirrhosis,particularly in patients in contact with the healthcare environment. Aim Our prospective study aimed to analyze epidemiology, prevalence and risk factors of multiresistant infections, as well as the rate of failure of empirical antibiotic therapy in cirrhotic patients. Methods All consecutive cirrhotic patients hospitalized between 2008 and 2013 with a microbiologically-documented infection (MDI) were enrolled. Infections were classified as Community- Acquired (CA), Hospital-Acquired (HA) and Healthcare-Associated (HCA). Bacteria were classified as Multidrug-Resistant (MDR) if resistant to at least three antimicrobial classes, Extensively-Drug-Resistant (XDR) if only sensitive to one/two classes and Pandrug-Resistant (PDR) if resistant to all classes. Results One-hundred-twenty-four infections (15% CA, 52% HA, 33% HCA) were observed in 111 patients. Urinary tract infections, pneumonia and spontaneous bacterial peritonitis were the more frequent. Forty-seven percent of infections were caused by Gram-negative bacteria. Fifty-one percent of the isolates were multi-resistant to antibiotic therapy (76% MDR, 21% XDR, 3% PDR): the use of antibiotic prophylaxis (OR = 8.4; 95%CI = 1.03-76; P = 0,05) and current/recent contact with the healthcare-system (OR = 3.7; 95%CI = 1.05-13; P = 0.04) were selected as independent predictors. The failure of the empirical antibiotic therapy was progressively more frequent according to the degree of resistance. The therapy was inappropriate in the majority of HA and HCA infections. Conclusions Multi-resistant infections are increasing in hospitalized cirrhotic patients. A better knowledge of the epidemiological characteristics is important to improve the efficacy of empirical antibiotic therapy. The use of preventive measures aimed at reducing the spread of multi-resistant bacteria is also essential

Exercise for acute respiratory infections

No abstract available