Spotted fever group rickettsiae and Anaplasma phagocytophilum in Borrelia burgdorferi sensu lato seropositive individuals with or without Lyme disease: A retrospective analysis.

Background: The Ixodes ricinus tick is the main vector of Borrelia burgdorferi and tick-borne encephalitis virus in Switzerland. Spotted fever group Rickettsiae (SFG) and Anaplasma phagocytophilum have been detected in Swiss ticks, however, information about the extent and clinical presentation of these infections in humans is scant. Methods: Indirect fluorescent antibody tests for SFG rickettsiae and Anaplasma phagocytophilum were performed on serum samples of 121 Borrelia burgdorferi seropositive patients with and without Lyme disease and 43 negative controls. Results: Out of 121 Borrelia burgdorferi seropositive individuals, 65 (53.7%) were seropositive for IgG and 15 (12.4%) for IgM antibodies to SFG rickettsiae. IgM antibodies were detected more frequently in early-than in late-stage of Lyme disease (12 out of 51 and 2 out of 49; respectively; p â€‹= â€‹0.0078). Significantly higher IgG antibody titers against SFG rickettsiae were found in patients with late-stage compared to patients with early-stage Lyme disease (mean titer 1:261 and 1:129, respectively; p â€‹= â€‹0.038). This difference was even more pronounced in patients with acrodermatitis chronica atrophicans compared to patients with early stage of Lyme disease (mean titer 1:337 and 1:129, respectively; p â€‹= â€‹0.009).In patients presenting with fatigue, headache and myalgia, the prevalence of IgG antibodies against SFG rickettsiae was significantly higher (7 out of 11; 63.6%) than in Borrelia burgdorferi seropositive individuals without clinical illness (1 out of 10; 10%; p â€‹= â€‹0.024). IgG antibodies to Anaplasma phagocytophilum were detected in 12 out of 121 individuals (9.9%), no IgM antibodies were found. Conclusion: Infections with SFG rickettsiae and Anaplasma phagocytophilum are underdiagnosed and should be ruled out after a tick bite. Further studies are needed to elucidate the possible causative role of SFG rickettsiae for myalgia, headache and long-lasting fatigue after a tick bite and to determine the necessity for an antibiotic treatment.

External quality assessment providers' services appear to more impact the immunohaematology performance of laboratories than national regulatory and economic conditions.

OBJECTIVES: Medical laboratories may, at their own discretion, exceed but not undercut regulatory quality requirements. Available economic resources, however, may drive or hinder eagerness to exceed minimum requirements. Depending on the respective scopes of regulatory and economic framework conditions, differing levels of quality efforts to safeguard laboratory performance can be anticipated. However, this has not yet been investigated. METHODS: Immunohaematology external quality assessment (EQA) results collected by 26 EQA providers from their participant laboratories in 73 countries from 2004 to 2019 were evaluated. Error rates were aggregated in groups according to the respective national regulatory and economic framework conditions, to whether or not expert advice was provided in case of incorrect results, and the frequency of EQA samples. RESULTS: These representative data indicate no association between national regulatory (mandatory participation in EQA, monitoring of performance of individual laboratories by authorities, financial consequences of incorrect results) and economic (level of national income, share of national health expenditure) conditions to the quality performance of medical laboratories in immunohaematology. However, EQA providers' support for laboratories in the event of incorrect results appear to be associated with lower error rates, but a high EQA sample frequency with higher error rates. CONCLUSIONS: Further research into the impact of introducing or changing services of EQA providers is needed to confirm the results found in this first of its kind study.

Nationwide Implementation of Pathogen Inactivation for All Platelet Concentrates in Switzerland.

INTRODUCTION: Bacterial contamination of platelet concentrates (PCs) has been identified as the most prevalent transfusion-associated infectious risk. To prevent PC-related septic transfusion reactions, the Intercept® pathogen inactivation procedure was introduced for all PCs in Switzerland in 2011. METHODS: Based on numbers of transfused units and mandatorily reported adverse events with high imputability, we compare the risks associated with transfusion of conventional PCs (cPCs) and pathogen-inactivated PCs (PI-PCs). RESULTS: From 2005 to 2011, a total of 158,502 cPCs have been issued in Switzerland, and 16 transfusion-transmitted bacterial infections (including 3 fatalities) were reported. This corresponds to a morbidity and mortality rate of ca. 1:9,900 and 1:52,800, respectively. From 2011 to 2016, a total of 205,574 PI-PCs have been issued, and no transfusion-transmitted bacterial infection was reported. Despite continuously increasing transfusion reaction rates per 1,000 RBC and plasma issued between 2008 and 2016, we observed reductions of 66% for life-threatening and fatal reactions and of 26% for all high-imputability transfusion reactions related to PI-PCs as compared to cPCs. No increased rates of bleeding or clinical observations of ineffectiveness of PI-PCs have been reported. After implementation of PI-PCs, the annual increase in platelet usage per 1,000 inhabitants decelerated. DISCUSSION: Swiss hemovigilance data confirm a favorable safety profile of the nationwide introduced Intercept pathogen inactivation procedure and its reliable prevention of septic transfusion reactions and fatalities due to bacterially contaminated PCs.

Platelet Transfusion Induces Alloimmunization to D and Non-D Rhesus Antigens.

BACKGROUND: Platelet concentrates (PC) contain residual contaminating red blood cells (RBC), being higher in pooled buffy coat PC (BC-PC) than in apheresis units (AP-PC). Data about PC-induced alloimmunization against non-D Rhesus (Rh) antigens are limited. METHODS: For all newly detected RhD and non-D alloantibodies between August 2015 and September /2017 we prospectively evaluated if they were triggered through PC by analyzing for incompatible RBC and/or PC transfusions. RESULTS: We found 5,799 positive results in 89,190 antibody screening tests. We identified 13 newly detectable Rh antibodies through incompatible PCs in 11 patients: 6× anti-D, 4× anti-E, 2× anti-c, 1× anti-f. They received a total of 156 PC (83 BC-PC; 73 AP-PC): 5 patients received incompatible BC-PC only, 1 patient received incompatible AP-PC only, 5 patients received incompatible BC-PC and AP-PC. Quality control showed a mean (range) of 0.304 (0.152-1.662) and 0.014 (0.003-0.080) × 109 RBC/l for BC-PC and AP-PC, respectively. Ten of the 11 patients received RBC transfusions, all of them being antigen-negative for the alloantibodies identified. CONCLUSIONS: PC transfusions may not only induce RhD alloimmunization, but also immunization against further Rh antigens such as c, E, and f. The risk seems higher for BC-PC than for AP-PC. The results may have impact on future recommendations of PC transfusion with respect to Rh compatibility and upper limits of RBC contamination.

A Case of Possible Chagas Transmission by Blood Transfusion in Switzerland.

BACKGROUND: Transfusion-transmitted Chagas disease has been reported from endemic countries in Latin America. Switzerland is a non-endemic country but high prevalence of antibodies against Trypanosoma cruzi was found among immigrants. Immigrants may participate in blood donation; therefore, risk-adapted anti-T. cruzi screening for blood donors was implemented in Switzerland in 2013. METHODS: Between January 2013 and July 2015, 1 out of 1,183 at-risk donors, tested at Blood Transfusion Service Zurich, was found anti-T. cruzi IgG-positive. RESULTS AND CONCLUSION: Out of 54 donations given by the index donor (ID), we identified 77 blood products which were delivered to hospitals. Archived serum samples from the donations given during the prior 5 years were available for retrospective testing. All samples from ID revealed positive findings for anti-T. cruzi IgG. Donor-triggered look-back procedure identified a 70-year-old male recipient of a platelet concentrate (PC) donated by ID. The recipient succumbed of acute T. cruzi infection 2 years after transfusion of the PC.

The role of isoagglutinins in intravenous immunoglobulin-related hemolysis.

BACKGROUND: Increased reporting of intravenous immunoglobulin (IVIG)-related hemolytic reactions (HRs) triggered an investigation by the German and Swiss health authorities to identify potential risk factors. STUDY DESIGN AND METHODS: From the EudraVigilance database HRs reported between 2008 and 2013 were retrieved for seven IVIG preparations. HRs were classified as mild to moderate (hemoglobin [Hb] decline < 2 g/dL)] or severe (Hb decline > 2 g/dL) and separately analyzed for IVIG doses of less than 2 g/kg body weight and 2 g/kg body weight or more. It was assessed whether HR reporting rates correlate with the isoagglutinin content of the different preparations. RESULTS: Of 569 HR cases retrieved, 103 cases were excluded due to insufficient data, leaving 466 for analysis. Ninety-three cases were classified as mild to moderate and 373 as severe. Approximately 80% of the severe HRs concerned patients with blood group A and only three patients with blood group O. Testing of isoagglutinin titers revealed substantial differences between the seven preparations. IVIG products with high anti-A/anti-B titers (≥32) had elevated HR reporting rates, particularly when cumulative doses at least 2 g/kg were administered. CONCLUSION: The isoagglutinin content of IVIGs correlates with the risk for HRs. Exclusion of high-titer donations and manufacturing steps that deplete isoagglutinins should be considered for risk mitigation. In patients with blood groups A or AB receiving doses of at least 2 g/kg, the use of IVIG batches with low isoagglutinin titers should be considered to prevent HRs.

Swiss Haemovigilance Data and Implementation of Measures for the Prevention of Transfusion Associated Acute Lung Injury (TRALI).

SUMMARY: In Switzerland, blood donations are collected exclusively from healthy non-remunerated voluntary blood donors mainly by 13 regional Blood Transfusion Services throughout the country. Thereby, self-sufficient blood supply for a population of about 7.5 million is achieved, and approximately 300,000 units of red cells, 75,000 therapeutic units of fresh plasma, and 20,000 therapeutic units of platelets are transfused annually. Reporting to Swissmedic (the Swiss agency for therapeutic products) of all suspected adverse transfusion events on a standardised form is mandatory. Data are then analysed to estimate the risks of the most serious transfusion events. Together with transfusion of an incorrect blood component and bacterial contamination of platelet concentrates, TRALI is a significant risk of transfusion in Switzerland and occurs in approximately every 8,000-20,000 FFP transfusions according to current haemovigilance data. Among 25 reported cases between 2002 and November 2007, 4 are proven immune TRALI, 2 are highly likely immune TRALI, 10 are possibly immune TRALI, 8 are non-immune TRALI, and 1 is a suspected case which could not be confirmed as TRALI. Based on the hypothesis of an immunological trigger of TRALI, an exclusion of the transfusion of plasma from female donors can be considered as a precautionary measure which might have prevented 4 cases of proven immune TRALI, 2 cases of highly likely immune TRALI, and an unknown number of the 10 cases of possibly immune TRALI. Based on these data and encouraging preliminary reports of the effects of comparable measures in other countries, the decision was made that starting with January 1st 2007 the production of quarantined FFP is restricted to donations from men or from women confirming that they have never been pregnant (to their knowledge) or with negative tests for antibodies against HLA class I and II. The analysis of further vigilance data is needed to elucidate the efficacy of this preventive measure.

Rapid, accurate and non-invasive detection of cerebrospinal fluid leakage using combined determination of beta-trace protein in secretion and serum.

BACKGROUND: beta-Trace protein (Btp) has been proposed as a valuable marker of cerebrospinal fluid (CSF) leakage overcoming the drawbacks of beta-2-transferrin (B-2Tr) determination. However, there is still controversy about the appropriate cut-offs to be used (range 0.35-6 mg/L). The aim of the study was to evaluate cut-offs of Btp determination for detection CSF leakage. Further, we assessed whether the Btp secretion to serum ratio (Btp-sec/ser-ratio) would add diagnostic value. METHODS: Prospective study in patients with suspected CSF leakage. Quantitative determination of Btp in secretion and serum (Dade-Behring) and qualitative measurement of B-2-Tr in secretion and serum. Results were assessed in view of clinical data. Cut-offs and diagnostic characteristics were determined by ROC analysis. RESULTS: A total of 176 samples were assessed originating from 105 patients. In 43 samples CSF leakage could be confirmed. Sensitivity of B-2-Tr was 84%, specificity amounted to 100%. The area under the curve (AUC) for Btp-measurement in secretion was 0.98. At a cut-off of 0.68 mg/L, sensitivity was 100% and specificity 91%. At a cut-off of 1.11 mg/L, the specificity was 100% with a sensitivity of 93%. The Btp-sec/ser-ratio has an AUC of 0.99. Combining a 0.68 mg/L cut-off in secretion with a Btp-sec/ser-ratio cut-off of 4.9 reveals a sensitivity of 99% and a specificity of 100%. CONCLUSIONS: Btp is a rapid and accurate marker for the presence of CSF leakage. Combining measurement of Btp in secretion together with determination of the Btp-sec/ser-ratio enhances the diagnostic characteristics of the Btp assay. Determination of Btp in both serum and secretion is thus recommended.