Assessment of a novel BLOOMY score for predicting mortality in hospitalised adults with bloodstream infection.

PURPOSE: A German multicentre study BLOOMY was the first to use machine learning approach to develop mortality prediction scores for bloodstream infection (BSI) patients, but the scores have not been assessed in other cohorts. Our aim was to assess how the BLOOMY 14-day and 6-month scores estimate mortality in our cohort of 497 cases with BSI. METHODS: Clinical data, laboratory data, and patient outcome were gathered retrospectively from patient records. The scores were calculated as presented in the BLOOMY study with the exception in the day of the evaluation. RESULTS: In our cohort, BLOOMY 14-day score estimated death by day 14 with an area under curve (AUC) of 0.87 (95% Confidence Interval 0.80-0.94). Using ≥ 6 points as a cutoff, sensitivity was 68.8%, specificity 88.1%, positive predictive value (PPV) 39.3%, and negative predictive value (NPV) 96.2%. These results were similar in the original BLOOMY cohort and outweighed both quick Sepsis-Related Organ Failure Assessment (AUC 0.76) and Pitt Bacteraemia Score (AUC 0.79) in our cohort. BLOOMY 6-month score to estimate 6-month mortality had an AUC of 0.79 (0.73-0.85). Using ≥ 6 points as a cutoff, sensitivity was 98.3%, specificity 10.7%, PPV 25.7%, and NPV 95.2%. AUCs of 6-month score to estimate 1-year and 5-year mortality were 0.80 (0.74-0.85) and 0.77 (0.73-0.82), respectively. CONCLUSION: The BLOOMY 14-day and 6-month scores performed well in the estimations of mortality in our cohort and exceeded some established scores, but their adoption in clinical work remains to be seen.

Epidemiology and emm types among group A streptococcal pharyngitis in Finland: a prospective laboratory-based study.

PURPOSE: Streptococcus pyogenes (mostly termed group A Streptococcus - GAS) is the most important bacterial causative of pharyngitis. However, epidemiology of GAS pharyngitis is not widely established. This study describes GAS pharyngitis cases and emm-type distribution in a prospective study covering over 2 years in two Hospital Districts in Finland. METHODS: A prospective, systematic collection of GAS pharyngitis isolates was conducted between March 2018 and December 2020 in two large Hospital Districts in Finland. Patient characteristics (age, gender) were included if available. All GAS isolates collected were emm typed. RESULTS: Altogether 1320 GAS pharyngitis strains were collected, 904 in the Hospital District 1 (HD1) and 416 in Hospital District 2 (HD2). In HD1, age and gender data were available. Females were overrepresented (58% of all cases). In addition, the age and gender distributions were noted to be significantly different (p < 0.0001) with females having a more uniform distribution until age of 40. emm28 was common among the age group of 20-29-year-olds and emm89 in children under 10 years of age, respectively. In HD1, most of the isolates were collected during winter and autumn months. Significant differences by season in the frequency of emm12, emm89, emm75 and group of "others" were observed. CONCLUSION: Age distribution among GAS pharyngitis cases was significantly different between genders (p < 0.0001). In addition, age group specific and seasonal variations in emm GAS types causing the disease were observed. These findings warrant further investigation, especially for understanding population-based spread of GAS even in more detail.

Presence of Streptococcus pyogenes in the throat in invasive Group A Streptococcal disease: a prospective two-year study in two health districts, Finland.

PURPOSE: Streptococcus pyogenes (Group A Streptococcus, GAS) is an important human pathogen that can cause severe invasive (iGAS) infections. Throat carriage has been assumed to possibly lead to hematogenous seeding. Retrospective studies may estimate the incidence of throat carriage in iGAS patients inaccurately. In this study we aimed to gather data on the presence of GAS in the throat among iGAS patients in a prospective setting. METHODS: We conducted a prospective clinical study covering iGAS infections in adult patients in two university hospitals in Finland from June 2018 to July 2020. Recruited patients' throats were swabbed for culture and isothermal amplification tests (IAT) to search for GAS. The study was registered at ClinicalTrials.gov as ID NCT03507101. RESULTS: We enrolled 45 patients. Throat swabs were obtained from 39/45 (87%) patients. Ten patients (22%) had a positive IAT for GAS. They were statistically significantly more likely to be male (9/10 [90%] vs 13/29 [45%], p = .024). Several different emm types caused the iGAS infections. CONCLUSIONS: GAS was frequently observed in throat swabs of patients with iGAS infection. This may suggest that hematogenous seeding from the nasopharynx is a possible portal of entry.

Evaluation of the Roche-SD Biosensor rapid antigen test: Antigen is not reliable in detecting SARS-CoV-2 at the early stage of infection with respiratory symptoms.

We evaluated a rapid antigen test against SARS-CoV-2 virus (Roche-SD Biosensor; RSDB-RAT) in children and adults with respiratory symptoms compared to those with nonrespiratory symptoms or asymptomatic. Also the performance of RSDB-RAT with respect to the duration of respiratory symptoms was assessed. A viral cross-reactivity panel was included. RSDB-RAT was reliable in detecting SARS-CoV-2 in children and adults if the respiratory symptoms had endured 1 to 7 days. If the respiratory symptoms had lasted less than 1 day, the sensitivity was significantly lower. No cross-reactivity with other respiratory viruses was observed.

Comparison of 2 fully automated tests detecting antibodies against nucleocapsid N and spike S1/S2 proteins in COVID-19.

Automated assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in coronavirus disease 2019 (COVID-19) diagnostics have recently come available. We compared the performance of the Elecsys® Anti-SARS-CoV-2 and LIAISON® SARS-CoV-2 S1/S2 IgG tests. The seroconversion panel comprised of 120 samples from 13 hospitalized COVID-19 patients. For the sensitivity and specificity testing, samples from COVID-19 outpatients >15 days after positive nucleic acid amplification test (NAAT) result (n = 35) and serum control samples collected before the COVID-19 era (n = 161) were included in the material. Samples for the detection of possible cross-reactions were also tested. Based on our results, the SARS-CoV-2 antibodies can be quite reliably detected 2 weeks after NAAT positivity and 3 weeks after the symptom onset with both tests. However, since some COVID-19 patients were positive only with Elecsys®, the antibodies should be screened against N-antigen (Elecsys®) and reactive samples confirmed with S antigen (LIAISON®), but both results should be reported. In some COVID-19 patients, the serology can remain negative.

Enterovirus infection during pregnancy is inversely associated with atopic disease in the offspring.

BACKGROUND: Prenatal environment has been shown to influence child's risk of atopic diseases. Laboratory-confirmed data about the role of maternal infections during pregnancy is scarce. OBJECTIVE: The aim of this study was to determine the associations between serologically confirmed maternal infections during pregnancy and atopic disease in the offspring. METHODS: This was a nested case-control study within a prospective birth cohort study. Altogether 202 atopic case children and 333 matched non-atopic control children were included. Atopic outcome was defined as having an atopic disease and IgE sensitization by the age of 5 years. We analysed serologically acute enterovirus (EV), influenza virus A (IAV) and Mycoplasma pneumoniae (M. pneumoniae) infections during pregnancy, and mother's seropositivity against human cytomegalovirus (CMV) and Helicobacter pylori. RESULTS: Maternal EV infection during pregnancy was inversely associated with atopic outcome in the offspring (odds ratio 0.43; 95% confidence interval: 0.23-0.80, P = 0.008). Acute IAV or M. pneumoniae infections or seropositivity against CMV or Helicobacter pylori were not associated with the atopic outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Our results suggest that maternal EV infections during pregnancy are inversely associated with atopic disease in the offspring. Our finding provides further support to the previous studies suggesting an important role of the in utero environment in the development of atopic diseases.

Sepsis-related mortality in 497 cases with blood culture-positive sepsis in an emergency department.

OBJECTIVE: Few studies have sought to establish how often death after sepsis is related to the sepsis and how often underlying diseases have a major role in case fatality. METHODS: In this retrospective cohort study, data were collected on 497 cases with blood culture-positive sepsis in an emergency department (ED). RESULTS: Sepsis was categorized as severe in 31% of cases; 7% had septic shock. The quick Sepsis-related Organ Failure Assessment score was positive in 136 out of 473 cases (29%). Ninety-eight patients died by day 90; in 16 of these cases (16%) the death was sepsis-related in a patient without a rapidly fatal underlying disease, in 45 cases (46%) the death was sepsis-related in a patient with a rapidly fatal underlying disease, and in 37 cases (38%) the death was unrelated to sepsis. Sepsis-related death occurred in 58 out of 61 cases (95%) by day 28. CONCLUSIONS: Underlying diseases were found to have a considerable role in the death of patients suffering from blood culture-positive sepsis in an ED of a developed country, as only 16% of the deaths by day 90 occurred where death was sepsis-related and the patient had a life-expectancy of more than 6 months. Improving the outcome of sepsis with new treatments is thus challenging. It is possible that day 7+day 28 mortality is a more appropriate endpoint than day 90 mortality when studying the outcome of sepsis, as this time-span includes most of the patients whose death was related to sepsis.

Use of an automated PCR assay, the GenomEra S. pneumoniae, for rapid detection of Streptococcus pneumoniae in blood cultures.

BACKGROUND: Streptococcus pneumoniae is recognized as a major cause of pneumonia, meningitis, and bacteremia. Since the mortality rate for pneumococcal bacteremia remains high, the reliable detection of the bacterium in blood samples is important. In this study, the performance of a new automated PCR assay, the GenomEra(™) S. pneumoniae, for direct detection of S. pneumoniae in blood cultures was investigated. METHODS: In total, 200 samples were analyzed, including 90 previously identified culture collection isolates and 110 blood culture specimens. The species identification was confirmed with routine diagnostic methods including MALDI-TOF or 16S rDNA sequencing. RESULTS: From culture collection, the GenomEra S. pneumoniae assay correctly identified all 37 S. pneumoniae isolates consisting of 18 different serotypes, while all 53 non-S. pneumoniae isolates yielded negative test results. Of 110 blood culture specimens, 46 grew S. pneumoniae and all were positive by the GenomEra assay direct from bottle. The detection sensitivity and specificity of the GenomEra assay for direct analysis of S. pneumoniae in signal positive blood culture bottles was 100%, respectively. With a straightforward sample preparation protocol of blood cultures the results were available within 55 min, thus being significantly quicker than by the routinely used identification methods (18-48 h). The two-step, time-resolved fluorometric measurement mode employed by the GenomEra CDX(™) instrument showed no interference from blood or charcoal. CONCLUSION: The GenomEra S. pneumoniae assay is a tool that performs well for the rapid and reliable detection of S. pneumoniae in blood cultures.

The 'Hygiene hypothesis' and the sharp gradient in the incidence of autoimmune and allergic diseases between Russian Karelia and Finland.

Autoimmune and allergic diseases have become a major health problem in the Western world during past decades. The hygiene hypothesis suggests that decreased microbial exposure in childhood leads to increasing prevalence of these diseases. This review summarizes epidemiological evidence and current immunological knowledge concerning the hygiene hypothesis. Recent results from Russian Karelia and Finland imply that environmental factors have greatly contributed to the increasing prevalence of immune-mediated disorders. Infections, or lack of them, may indeed be strongly involved in the development of both autoimmune and allergic diseases.

Role of enterovirus infections in IgE sensitization.

Among other infectious agents, enteroviruses have been associated with protection against allergic diseases. The aim of the present study was to confirm these findings using a highly sensitive and specific neutralization antibody assay and to investigate whether the protective effect is related to certain enterovirus serotypes. Antibodies against 12 enterovirus serotypes were measured in 60 children who were positive for allergen-specific IgE and in 190 control children. Echoviruses seemed to be more protective than coxsackie-B-viruses and echovirus 11 had the strongest independent protective effect (P = 0.001; OR = 0.35, 95% CI: 0.18-0.67). The results support previous observations suggesting that infections by certain enterovirus types are associated with protection against IgE sensitization.

Co-occurrence of allergic sensitization and type 1 diabetes.

BACKGROUND: The mechanisms leading to abnormal immune regulation in type 1 diabetes and allergic diseases may be partly overlapping. If so, these diseases should co-occur more often than expected. We investigated this phenomenon in two contrasting socio-economic environments, Finland and Russian Karelia. METHODS: We screened 413 Finnish children (of whom 147 had type 1 diabetes) and 244 Russian Karelian children (132 had type 1 diabetes) for total immunoglobulin E (IgE) levels and specific IgE against birch, cat, and egg albumen. In addition we analysed diabetes-related human leukocyte antigen (HLA) haplotypes and antibodies against hepatitis A virus (HAV) and recorded allergic diseases by a questionnaire in Russian Karelia. RESULTS: In Russian Karelia 15% of the patients with type 1 diabetes, but only 4% of the control subjects had allergen-specific IgE (P = 0.012). A similar difference was observed in the frequency of allergic symptoms. Co-occurrence of allergic sensitization and type 1 diabetes was associated with lack of HAV antibodies and was not seen in Finland where infections are less frequent than in Karelia. CONCLUSION: Our findings support the idea of common mechanisms in the pathogenesis of allergic diseases and type 1 diabetes, which may be particularly important in an environment with low penetrance of these diseases.

Time trends in allergic sensitisation and Helicobacter pylori prevalence in Finnish pregnant women.

BACKGROUND: An increase in the prevalence of allergic conditions has been documented in Finland, correlating with the diminishing prevalence of Helicobacter pylori infections. We investigated whether the increase of allergic sensitisation still continues and correlates with the prevalence of H. pylori infections. METHODS: The sera from 958 pregnant women in 1983, 1989, 1995 and 2001 were analysed for the presence of antibodies against H. pylori. In addition, allergen-specific IgE antibodies and total levels of IgE antibodies were measured. RESULTS: A clear birth cohort effect was found in the prevalence of allergic sensitization: allergen-specific IgE was more frequent among recent birth cohorts than earlier ones (p = 0.001). The frequency of H. pylori antibodies followed the opposite trend (p < 0.001) and the increase in allergic sensitisation was only seen among H. pylori-negative women. A modest increase was also seen in allergic sensitisation between the 4 time series among the H. pylori-negative subjects (p = 0.04). Total IgE levels did not differ between birth cohorts or time series. CONCLUSION: The results suggest that hygiene-related environmental factors have played a role in the increase of allergic sensitisation during the last decades.

Serological evidence of thyroid autoimmunity among schoolchildren in two different socioeconomic environments.

CONTEXT: The mechanisms leading to thyroid autoimmunity are largely unknown. OBJECTIVE: Our objective was to assess the role of environment in the development of thyroid autoimmunity. DESIGN: Prevalence of thyroid autoantibodies in two neighboring populations living in completely different socioeconomic circumstances (Russian Karelia and Finland) was studied. SETTING: We studied two population-based cohorts partly sharing the same ancestry. PATIENTS OR OTHER PARTICIPANTS: A total of 532 schoolchildren from Russian Karelia and 532 schoolchildren in Finland matched for age, gender, and season of the blood sampling were included. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: The prevalence of thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb) and HLA-DQ alleles was measured. RESULTS: The prevalence of TPOAb was significantly lower in Russian Karelian than in Finnish children (0.4 vs. 2.6%, P=0.006). A similar difference was observed for TGAb (0.6 vs. 3.4%, P=0.002). Finnish girls tested positive for both TPOAb (4.3 vs. 0.4%, P=0.01) and TGAb (5.3 vs. 0.9%, P=0.01) more frequently than Finnish boys. Seven of the 23 tested subjects with signs of thyroid autoimmunity (30%) had increased serum TSH concentrations as a sign of subclinical hypothyroidism. The frequency of HLA genotypes did not differ between the two countries or between autoantibody-positive and -negative subjects. CONCLUSIONS: The prevalence of thyroid autoimmunity is lower in Russian Karelia than in Finland. This difference was not related to ethnic background or HLA-DQ alleles. The results support the idea that the Russian Karelian environment, which is characterized by inferior prosperity and standard of hygiene, may provide protection against thyroid autoimmunity.