Exploring the dynamics of Borrelia burgdorferi sensu lato antibodies—a registry-based study on laboratory data from Sweden and Denmark

Objectives: Lyme borreliosis (LB) is the most common tick-transmitted infection in the northern hemisphere and is caused by bacteria in the Borrelia burgdorferi sensu lato (Bbsl)-complex. The diagnosis is partially based on serology, and clinicians often take follow-up serum samples to look for seroconversion or an increase in IgG-antibody levels. In this registry-based study, we proposed a method for determining actual changes in IgG and examined antibody reactivity and decay. Methods: Serological data from the departments of clinical microbiology at Karlstad Hospital, Sweden, and Slagelse Hospital, Denmark, were used to calculate a seroreactivity cut-off (SCOFF), above which changes between two samples from the patient cannot be explained by random variation. Increases in IgG reactivity as well as IgG and IgM decay were illustrated using time-to-event analysis and the SCOFF. Results: A total of 44,861 serum samples from 34,157 patients were tested for Bbsl-antibodies. Of the 4301 patients with follow-up samples taken within 100 days, 201 (4.67%) were above the SCOFF of 1.42 with a median time to follow-up sample of 36 days (interquartile range: 21). IgG demonstrated longer median time for all antibody levels (indeterminate: 4.6 years, low: 7.0 years, moderate-high: 8.8 years) than IgM antibodies (indeterminate: 2.1 years, low: 3.9 years, moderate-high: 6.8 years) and higher initial antibody levels persisted significantly longer for both IgG and IgM antibodies (p &lt; 0.001). Of the 7868 patients with follow-up samples, isolated IgM reactivity preceded an increase in IgG reactivity in 18 patients (0.23%). Discussion: The SCOFF indicated little biological and random variation for Bbsl-specific IgG antibodies on the platforms used during the study. In most follow-up samples, both IgG and IgM antibodies persisted for years, with longer seropositivity associated with high initial antibody levels and IgG-type antibodies. The diagnostic value of isolated IgM reactivity was limited.</p

Longitudinal trajectory patterns of plasma albumin and C-reactive protein levels around diagnosis, relapse, bacteraemia, and death of acute myeloid leukaemia patients

BACKGROUND: No study has evaluated C-reactive protein (CRP) and plasma albumin (PA) levels longitudinally in patients with acute myeloid leukaemia (AML). METHODS: We studied defined events in 818 adult patients with AML in relation to 60,209 CRP and PA measures. We investigated correlations between CRP and PA levels and daily CRP and PA levels in relation to AML diagnosis, AML relapse, or bacteraemia (all ±30 days), and death (─30-0 days). RESULTS: On the AML diagnosis date (D0), CRP levels increased with higher WHO performance score (PS), e.g. patients with PS 3/4 had 68.1 mg/L higher CRP compared to patients with PS 0, adjusted for relevant covariates. On D0, the PA level declined with increasing PS, e.g. PS 3/4 had 7.54 g/L lower adjusted PA compared to PS 0. CRP and PA levels were inversely correlated for the PA interval 25-55 g/L (R = - 0.51, p < 10-5), but not for ≤24 g/L (R = 0.01, p = 0.57). CRP increases and PA decreases were seen prior to bacteraemia and death, whereas no changes occurred up to AML diagnosis or relapse. CRP increases and PA decreases were also found frequently in individuals, unrelated to a pre-specified event. CONCLUSIONS: PA decrease is an important biomarker for imminent bacteraemia in adult patients with AML.publishersversionpublishe

Impact of C-reactive protein and albumin levels on short, medium, and long term mortality in patients with diffuse large B-cell lymphoma

Objectives and study design: In this population-based study of 602 patients, we amended C-reactive protein (CRP) and plasma albumin (PA) levels around the diagnosis of diffuse large B-cell lymphoma (DLBCL) to the International Prognostic Index (IPI) and assessed 0-90, 91-365, and +365-day survival.Results: The CRP did not contribute to the IPI's prognostic or discriminatory ability, regardless of time period, particularly not in models with PA. In contrast, the PA was an important contributor, especially in the 0-90 day period, but also up to one year after the diagnosis. For day 0-90, the model with the IPI only had an Area Under the Receiver Operating Characteristics (AUROC) of 0.742, whereas the IPI with PA as a continuous variable rendered an AUROC of 0.841. Especially the lower PA quartile (18-32 g/L) contributed to the worse prognosis.Conclusions: The amendment of PA to the IPI may significantly improve the short-term prognostic and discriminative ability.Key messagesThe amendment of the plasma albumin (PA) level to the International Prognostic Index significantly improved the prediction of mortality up to one year after the diagnosis of diffuse large B-cell lymphoma.It was especially the lower quartile of the PA level (18-32 g/L) that contributed to the worse prognosis.publishersversionpublishe

Evidence of rickettsiae in Danish patients tested for Lyme neuroborreliosis: a retrospective study of archival samples

Abstract Background With a prevalence of 4.7–13% in Danish Ixodes ricinus ticks, Rickettsia helvetica is one of the most frequently detected tick-borne organisms in Denmark. Most reports of human exposure have described asymptomatic seroconversion or a mild, self-limiting flu-like illness but it has also been implicated as a cause of subacute lymphocytic meningitis. Because Borrelia burgdorferi sensu lato (Bbsl) and R. helvetica are both found in the same tick species, potential co-transmission is a possibility. We examined 1) the seroprevalence of anti-rickettsia antibodies in patients investigated for Lyme neuroborreliosis (LNB), and 2) the cerebrospinal fluid (CSF) and sera of same patients for the presence of Rickettsia DNA. Methods Ninety-nine sera and 87 CSF samples from patients with intrathecal synthesis of anti-Borrelia antibodies and 101 sera and 103 CSF samples from patients with no detectable intrathecal synthesis were retrospectively examined for this study. Sera were analyzed for antibodies against spotted fever group (SFG) rickettsiae and both the CSF and sera were tested for Rickettsia DNA using a genus-specific real-time PCR. Results Of the patients tested for LNB, 32% (64/200) had IgG antibodies against SFG rickettsiae. Among patients with confirmed intrathecal synthesis of Borrelia-specific antibodies, 38% (38/99) exhibited IgG antibodies. None of these values were statistically significant when compared with sera from healthy blood donors (p = 0.7 and 0.19). Rickettsia DNA was found in the CSF of 4% (8/190) of patients. Conclusion No statistically significant difference was found in the seroprevalence of anti-rickettsia antibodies in patients tested for LNB and healthy blood donors, indicative of a low rate of exposure in this group of patients. Eight patients showed evidence of Rickettsia DNA in the CSF, five of whom had LNB. However, cycle threshold (Ct) values were high, indicating low concentrations of DNA, and no apparent alteration in the clinical manifestations of LNB were noted in the medical records of these patients

Pleural infection: a retrospective study of clinical outcome and the correlation to known etiology, co-morbidity and treatment factors

Abstract Background We explored the hypothesized importance of early knowledge of microbiological etiology in patients with pleural infection, including comorbidity and treatment factors in the outcome analyses. Methods Data from the medical records of a large cohort of 437 consecutive patients in 9 hospitals in East-Denmark were included retrospectively. Results Microbiology, co-morbidity, therapy and outcome are described in detail. Patient groups with microbiology negative and known bacterial etiology had a similar 30-day and 90-day mortality. There were no differences in initial antibiotic treatment regimens, antibiotic treatment duration, rate of intra-pleural fibrinolysis treatment, surgical referral rate, and ICU admittance rate. Patients with microbiology negative etiology were younger (60.8 vs 64.3 years) and fewer had predisposing risk factors (59% vs 71%), but pleural drainage was more often delayed (49% vs 36%). Mortality was similar in patients treated with either of the two nationally recommended initial antibiotic regimens. However, higher 90-day mortality (22.5% vs 9.7%), disease severity (31.5% vs 6.2%), and ICU admittance rate (21.3% vs 2.9%) was observed in a sub-group with initial broad-spectrum treatment compared to patients receiving the nationally recommended initial treatments, irrespective of knowledge of etiology. Several factors correlated independently to 90-day mortality, including age, predisposing risk factors, surgical referral (Odds-Ratios > 1), drainage delay and intra-pleural fibrinolysis (ORs < 1). Conclusions No difference was found between patients with microbiology negative and known bacterial etiology regarding outcome or treatment parameters. Treatment factors and predisposing factors independently relating to mortality were found in the cohort. Broad-spectrum antibiotics were initially used for treatment of patients with more severe illness and poorer outcome