Serum neurofilament light chain associates with symptom burden in Lyme neuroborreliosis patients: a longitudinal cohort study from Norway.

OBJECTIVES: Serum neurofilament light chain (sNfL), an indicator of neuronal damage, is increasingly recognized as a potential biomarker for disease activity in neurodegenerative disorders. In this study, we wanted to investigate sNfL as a prognostic marker in a large, well-defined population of 90 patients with Lyme neuroborreliosis (LNB). In addition, we sought to explore associations between symptoms and sNfL levels during the acute phase of LNB. MATERIALS AND METHODS: Patients diagnosed with definite or possible LNB were recruited from a double-blinded, placebo-controlled, multi-center trial, in which the participants were randomly assigned to 2 or 6 weeks of oral doxycycline treatment. The sNfL levels were measured using a single molecule array assay at both diagnosis and 6-month follow-up, and analysed against clinical parameters, variations in symptom burden and long-term complaints as assessed by a composite clinical score. RESULTS: At the time of diagnosis, approximately 60% of the patients had elevated sNfL levels adjusted for age. Notably, mean sNfL levels were significantly higher at diagnosis (52 pg/ml) compared to 6 months after treatment (12 pg/ml, p < 0.001), when sNfL levels had normalized in the majority of patients. Patients with objective signs of spinal radiculitis had significantly higher baseline sNfL levels compared to patients without spinal radiculitis (p = 0.033). CONCLUSION: Our findings suggest that sNfL can serve as a biomarker for peripheral nerve tissue involvement in the acute phase of LNB. As found in an earlier study, we confirm normalization of sNfL levels in blood after treatment. We found no prognostic value of acute-phase sNfL levels on patient outcome.

Escherichia marmotae-a Human Pathogen Easily Misidentified as Escherichia coli.

We hereby present the first descriptions of human-invasive infections caused by Escherichia marmotae, a recently described species that encompasses the former "Escherichia cryptic clade V." We describe four cases, one acute sepsis of unknown origin, one postoperative sepsis after cholecystectomy, one spondylodiscitis, and one upper urinary tract infection. Cases were identified through unsystematic queries in a single clinical lab over 6 months. Through genome sequencing of the causative strains combined with available genomes from elsewhere, we demonstrate Es. marmotae to be a likely ubiquitous species containing genotypic virulence traits associated with Escherichia pathogenicity. The invasive isolates were scattered among isolates from a range of nonhuman sources in the phylogenetic analyses, thus indicating inherent virulence in multiple lineages. Pan genome analyses indicate that Es. marmotae has a large accessory genome and is likely to obtain ecologically advantageous traits, such as genes encoding antimicrobial resistance. Reliable identification might be possible by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), but relevant spectra are missing in commercial databases. It can be identified through 16S rRNA gene sequencing. Escherichia marmotae could represent a relatively common human pathogen, and improved diagnostics will provide a better understanding of its clinical importance. IMPORTANCE Escherichia coli is the most common pathogen found in blood cultures and urine and among the most important pathogenic species in the realm of human health. The notion that some of these isolates are not Es. coli but rather another species within the same genus may have implications for what Es. coli constitutes. We only recently have obtained methods to separate the two species, which means that possible differences in important clinical aspects, such as antimicrobial resistance rates, virulence, and phylogenetic structure, may exist. We believe that Es. marmotae as a common pathogen is new merely because we have not looked or bothered to distinguish between the thousands of invasive Escherichia passing through microbiological laboratories each day.

An immunocompromised woman in her twenties with abdominal pain and vaginal discharge. / Immunsupprimert kvinne i 20-årene med magesmerter og utflod.

BACKGROUND: Women of reproductive age who present with abdominal pain and purulent vaginal discharge are commonly seen in primary health care and gynaecological outpatient clinics. Their symptoms are often caused by sexually transmitted infections and efficiently treated with empiric antibiotics. However, in some cases diagnostics are more challenging. CASE PRESENTATION: We present the case history of a woman in her twenties with multiple sclerosis under rituximab treatment. She presented with a wide range of symptoms over twelve months, including upper and lower respiratory tract infections, urinary bladder urgency, chronic abdominal pain, diarrhoea, bloody stools, weight loss and fatigue. She underwent urological and gastroenterological examinations which yielded normal findings. After the onset of genital discomfort and copious amounts of vaginal discharge, gynaecological examination and routine microbiological testing of discharge were negative. Finally, she presented with septicaemia and progressive abdominal pain. Laparoscopy was performed due to absence of recovery after initial transvaginal ultrasound-guided aspiration of ovarian cysts. The microbe Ureaplasma urealyticum was detected in ovarian pus. Treatment with doxycycline resulted in full recovery. INTERPRETATION: It is important to consider opportunistic microbes in immunocompromised patients, as they might pose a major diagnostic challenge and require the involvement of several specialties.

Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high-income low-tuberculosis prevalence setting.

The diagnosis of extrapulmonary tuberculosis (EPTB) is often challenging due to paucibacillary nature of the disease. Xpert MTB/RIF Ultra (Ultra) has been developed to improve detection of Mycobacterium tuberculosis complex (MTC) in paucibacillary specimens. The objective of the study was to assess the performance of Ultra for the diagnosis of EPTB in a high-income low TB prevalence country. Extrapulmonary samples received for TB diagnostics at two hospitals in Norway between January 2015 and January 2016 were prospectively and consecutively included. Defrosted samples were subjected to Ultra. Culture and routine PCR tests were used as reference standard. A total of 82 samples, 10 culture and/or routine PCR positive (confirmed TB) samples and 72 culture and routine PCR negative samples were included in analysis. The overall sensitivity and specificity of Ultra were 90% (9/10, 95% CI 56-100) and 99% (71/72, 95% CI 93-100), respectively. Ultra was positive in 6/7 smear negative confirmed TB samples. To conclude, Ultra showed a high sensitivity and specificity in extrapulmonary specimens and may contribute to a rapid diagnosis of EPTB in a low TB prevalence setting.

Diagnosis of extrapulmonary tuberculosis using the MPT64 antigen detection test in a high-income low tuberculosis prevalence setting.

BACKGROUND: Extrapulmonary tuberculosis (EPTB) poses diagnostic challenges due to the paucibacillary nature of the disease. The immunochemistry-based MPT64 antigen detection test (MPT64 test) has shown promising results for diagnosing EPTB in previous studies performed in low-resource settings, with higher sensitivity than microscopy and culture. The aim of this study was to investigate the performance of the MPT64 test in a routine clinical setting in a high-income low TB prevalence country. METHODS: Extrapulmonary samples sent for TB diagnostics to microbiology and pathology laboratories at three regional tertiary care hospitals in Norway in a one-year period were included and subjected to the MPT64 test in parallel to the routine TB diagnostic tests. RESULTS: Samples from 288 patients were included and categorised as confirmed TB cases (n = 26), clinically diagnosed TB cases (n = 5), non-TB cases (n = 243) and uncategorised (n = 14), using a composite reference standard (CRS). In formalin-fixed biopsies, the sensitivity (95% CI) of the MPT64 test, microscopy, PCR-based tests pooled, and culture was 37% (16-62), 20% (4-48), 37% (16-62) and 50% (23-77), respectively, against the CRS. The MPT64 test showed a good positive predictive value (88%) and an excellent specificity (99, 95% CI 92-100) in formalin-fixed biopsies. In fine-needle aspirates, pus and fluid samples, the test performance was lower. CONCLUSIONS: The MPT64 test was implementable in pathology laboratories as part of routine diagnostics, and although the sensitivity of the MPT64 test was not better than culture in this setting, the test supplements other rapid diagnostic methods, including microscopy and PCR-based tests, and can contribute to strengthen the diagnosis of EPTB in formalin-fixed biopsies in the absence of culture confirmation.

Serological diagnostics of Lyme borreliosis: comparison of assays in twelve clinical laboratories in Northern Europe.

Lyme borreliosis (LB), caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex, is the most common tick-borne infection in Europe. Laboratory diagnosis of LB is mainly based on the patients' medical history, clinical signs and symptoms in combination with detection of Borrelia-specific antibodies where indirect enzyme-linked-immunosorbent assay (ELISA) is the most widely used technique. The objective of the study was to evaluate and compare the diagnostic accuracy (sensitivities and specificities) of serological tests that are currently in use for diagnosis of LB in clinical laboratories in Northern Europe, by use of a large serum panel. The panel consisted of 195 serum samples from well-characterized and classified patients under investigation for clinically suspected LB (n = 59) including patients with Lyme neuroborreliosis, Lyme arthritis, acrodermatitis chronica atrophicans, erythema migrans or other diseases (n = 112). A total of 201 serum samples from healthy blood donors were also included. The panel (396 serum samples altogether) was sent to 12 clinical laboratories (using five different ELISA methods) as blinded for group affiliation and the laboratories were asked to perform serological analysis according to their routine procedure. The results from the study demonstrated high diagnostic concordance between the laboratories using the same diagnostic assay and lower diagnostic concordance between laboratories using different diagnostic assays. For IgG, the results were in general rather homogenous and showed an average sensitivity of 88% (range 85-91%) compared to IgM which showed lower average sensitivity of 59% (range 50-67%) and more heterogeneous results between assays and laboratories.