C6 peptide enzyme immunoassay in Lyme borreliosis serology

The cut-off values used in C6 peptide-based enzyme immunoassay (EIA), a widely used test in Lyme borreliosis (LB) serology, have not been thoroughly analysed. The objective of the study was to examine the performance of the C6 EIA, and to determine optimal cut-off values for the test. The analysed data contained results of 1368 serum samples. C6 EIA index values were compared statistically with the immunoblot (IB) test results. The identified cut-off values were further tested in a well-defined LB patient cohort. Cut-off value 1.6 appeared to be optimal when C6 EIA was used as a stand-alone test. When using C6 EIA as the first-tier test, the optimal cut-off values were 0.9 and 2.4 for negative and positive results. When C6 EIA was used as a second-tier test, samples yielding C6 index values >= 3.0 could be considered positive. The identified cut-off values had also a high sensitivity to identify seropositivity among definite LB patients. The identified cut-off values refine the role of C6 EIA in LB serology. Importantly, the use of C6 EIA leads to a reduction in the number of samples that need to be analysed using an IB, thus also reducing the costs. Two alternative workflows for LB serology including the C6 EIA are suggested.Peer reviewe

Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland

Reports on real-world experience on efficacy of bezlotoxumab (BEZ) has been lacking thus far. We retrospectively studied the efficacy and safety of BEZ in preventing the recurrence of Clostridium difficile infection (CDI) in five university hospitals in Finland. Seventy-three percent of our 46 patients remained free of recurrence in the following 3 months and the performance remained as 71% effective also among immunocompromised patients. In severe CDI, BEZ prevented recurrence in 63% of cases. From our study patients, 78% had three or more known risk factors for recurrence of CDI. Eight of our patients were waiting for fecal microbiota transplantation but after stopping the antibiotics that were continued to prevent recurrence of CDI and after receiving BEZ, all remained free of recurrence and did not need the procedure. Success with BEZ as an adjunctive treatment in preventing recurrence of CDI in high-risk patients may be rated as high. Among a subgroup of our patients, those already evaluated to be in need of fecal microbiota transplantation, BEZ seems to be an alternative option.</p

Scedosporium apiospermum as a rare cause of central skull base osteomyelitis.

We report a case of Scedosporium apiospermum mold causing ear infection, central skull base osteomyelitis and finally, occlusion of carotid artery in a 48-year-old diabetic man. The exact diagnosis was established and the severity of the disease understood several months after the onset of symptoms. Despite of appropriate antifungal therapy, and repeated surgical and otological procedures, the infection progressed to fatal cerebral infarction

C6 peptide enzyme immunoassay in Lyme borreliosis serology

The cut-off values used in C6 peptide-based enzyme immunoassay (EIA), a widely used test in Lyme borreliosis (LB) serology, have not been thoroughly analysed. The objective of the study was to examine the performance of the C6 EIA, and to determine optimal cut-off values for the test. The analysed data contained results of 1368 serum samples. C6 EIA index values were compared statistically with the immunoblot (IB) test results. The identified cut-off values were further tested in a well-defined LB patient cohort. Cut-off value 1.6 appeared to be optimal when C6 EIA was used as a stand-alone test. When using C6 EIA as the first-tier test, the optimal cut-off values were 0.9 and 2.4 for negative and positive results. When C6 EIA was used as a second-tier test, samples yielding C6 index values ≥3.0 could be considered positive. The identified cut-off values had also a high sensitivity to identify seropositivity among definite LB patients. The identified cut-off values refine the role of C6 EIA in LB serology. Importantly, the use of C6 EIA leads to a reduction in the number of samples that need to be analysed using an IB, thus also reducing the costs. Two alternative workflows for LB serology including the C6 EIA are suggested.</p

Consumption of healthcare services and antibiotics in patients with presumed disseminated Lyme borreliosis before and after evaluation of an infectious disease specialist

Our objective was to study the consumption of healthcare services and antibiotics in patients with suspicion of disseminated Lyme borreliosis (LB) before and after consultation of an infectious disease specialist. We evaluated retrospectively all presumed disseminated LB patients (n = 256) with a referral to the Department of Infectious Diseases (DID) in Helsinki University Hospital in 2013. Medical records from all healthcare providers in the area were reviewed and the number of physician contacts because of symptoms leading to LB suspicion and antimicrobial purchases were calculated 1 year before and after consultation or treatment at the DID. Patients were divided into three groups according to certainty of LB: unlikely, possible or probable/definite LB. The number of healthcare contacts 1 year before referral was higher among 121 patients with unlikely LB (6; interquartile range [IQR] 3-10), than 65 possible (4; IQR 2.5-7; p = 0.018) or 66 probable/definite LB patients (4; IQR 2.8-7; p = 0.010). The median number of contacts to healthcare during one year after consultation or treatment was 3 (IQR 0.5-7), 1 (IQR 0-3) and 0.5 (IQR 0-2.3), respectively, with a statistically significant difference between the groups (p<0.001). Antibiotics were purchased by 151 (60%) patients one year before referral and by 127 (50%) patients year after consultation or treatment at DID without statistically significant difference between groups with different LB certainty. These antibiotic purchases do not include the treatments prescribed by infectious disease specialists. In the case of 27 patients, an antimicrobial treatment was recommended in the consultation reply. In conclusion, patients with unlikely LB used more healthcare services than patients with possible or probable/definite LB. Antimicrobial consumption was similar between groups of different LB certainty

Clinical characteristics and evaluation of the incidence of cryptococcosis in Finland 2004-2018

Background Cryptococcosis is one of the major causes of mortality among HIV patients worldwide. Though most often associated with late stage HIV infection/AIDS, a significant number of cases occur in other immunocompromised patients such as solid organ transplant recipients and patients with hematological malignancies. Immunocompromised patients are a heterogeneous group and their number increases constantly. Since little is known about the incidence and the clinical features of cryptococcosis in Northern Europe, our aim was to investigate the clinical characteristics of cryptococcosis patients in Finland. Methods We retrospectively reviewed the laboratory confirmed cryptococcosis cases in Finland during 2004-2018. Only those who were treated for cryptococcosis were included in the study. Initial laboratory findings and medical records were also collected. Results A total of 22 patients with cryptococcosis were included in our study. The annual incidence of cryptococcosis was 0.03 cases per 100,000 population. Ten patients were HIV-positive and 12 out of 22 were HIV-negative. Hematological malignancy was the most common underlying condition among HIV-negative patients. Conclusions To our knowledge, this is the first study of the clinical presentation and incidence of cryptococcosis in Finland. We demonstrate that invasive cryptococcal infection occurs not only in HIV/AIDS patients or otherwise immunocompromised patients but also in immunocompetent individuals. Even though cryptococcosis is extremely rare in Finland, its recognition is important since the prognosis depends on rapid diagnostics and early antifungal therapy.Peer reviewe

The Borrelia afzelii outer membrane protein BAPKO_0422 binds human Factor-H and is predicted to form a membrane-spanning beta-barrel

The deep evolutionary history of the Spirochetes places their branch point early in the evolution of the diderms, before the divergence of the present day Proteobacteria. As a Spirochete, the morphology of the Borrelia cell envelope shares characteristics of both Gram-positive and Gram-negative bacteria. A thin layer of peptidoglycan, tightly associated with the cytoplasmic membrane is surrounded by a more labile outer membrane (OM). This OM is rich in lipoproteins but with few known integral membrane proteins. The OmpA domain is an eight-stranded membrane-spanning β-barrel, highly conserved among the Proteobacteria but so far unknown in the Spirochetes. In the present work we describe the identification of four novel OmpA-like β-barrels from Borrelia afzelii, the most common cause of erythema migrans rash in Europe. Structural characterisation of one these proteins (BAPKO_0422) by small angle X-ray scattering (SAXS) and circular dichroism indicate a compact globular structure rich in β-strand consistent with a monomeric β-barrel. Ab initio molecular envelopes calculated from the scattering profile are consistent with homology models and demonstrate that BAPKO_0422 adopts a peanut shape with dimensions 25 x 45 Å. Deviations from the standard C-terminal signature sequence are apparent; in particular the C-terminal Phe residue commonly found in Proteobacterial OM proteins is replaced by Ile/Leu or Asn. BAPKO_0422 is demonstrated to bind human factor-H and therefore may contribute to immune evasion by inhibition of the complement response. Encoded by chromosomal genes, these proteins are highly conserved between Borrelia subspecies and may be of diagnostic or therapeutic value

IL-6 and other biomarkers as predictors of severity in COVID-19

ObjectiveCytokine release syndrome is suggested to be the most important mechanism triggering acute respiratory distress syndrome and end organ damage in COVID-19. The severity of disease may be measured by different biomarkers.MethodsWe studied markers of inflammation and coagulation as recorded in 29 patients on admission to the hospital in order to identify markers of severe COVID-19 and need of ICU.ResultsPatients who were eventually admitted to ICU displayed significantly higher serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. No statistical differences were found between the groups in median levels of lymphocytes, D-dimer or ferritin.ConclusionsIL-6 and CRP were the strongest predictors of severity in hospitalized patients with COVID-19.</p