The distribution limit of the common tick, Ixodes ricinus, and some associated pathogens in north-western Europe.

In north-western Europe, the common tick, Ixodes ricinus, is widely established, its distribution appears to be increasing and the spread of tick-borne diseases is of increasing concern. The project 'Flått i Nord' (Ticks in northern Norway) commenced in spring 2009 with the intention of studying the tick's distribution and that of its pathogens in northern Norway. Several methods were used: cloth-dragging, collecting from trapped small mammals, and collecting from pets. Since 2010, the occurrence of ticks in the region of northern Norway was determined directly by cloth-dragging 167 times in 109 separate locations between the latitudes of 64 °N and 70 °N (included seven locations in the northern part of Trøndelag County). The northernmost location of a permanent I. ricinus population was found to be Nordøyvågen (66.2204 °N, 12.59 °E) on the Island of Dønna. In a sample of 518 nymphal and adult ticks, the Borrelia prevalence collected close to this distribution limit varied but was low (1-15 %) compared with the locations in Trøndelag, south of the study area (15-27 %). Five specimens (1 %) were positive for Rickettsia helvetica. The length of the vegetation growing season (GSL) can be used as an approximate index for the presence of established populations of I. ricinus. The present study suggests that the threshold GSL for tick establishment is about 170 days, because the median GSL from 1991 to 2015 was 174-184 days at sites with permanent tick populations, showing a clear increase compared with the period 1961-1990. This apparent manifestation of climate change could explain the northward extension of the range of I. ricinus.

Serodiagnosis of Borrelia miyamotoi disease by measuring antibodies against GlpQ and variable major proteins.

OBJECTIVES: Borrelia miyamotoi disease (BMD) is an emerging tick-borne disease in the Northern hemisphere. Serodiagnosis by measuring antibodies against glycerophosphodiester-phosphodiesterase (GlpQ) has been performed experimentally but has not been extensively clinically validated. Because we had previously shown the differential expression of antigenic variable major proteins (Vmps) in B. miyamotoi, our aim was to study antibody responses against GlpQ and Vmps in PCR-proven BMD patients and controls. METHODS: We assessed seroreactivity against GlpQ and four Vmps in a well-described, longitudinal cohort of sera from BMD patients (n=182), healthy blood donors (n=136) and controls (n=68). All samples were tested by ELISA and positive sera were tested by western blot, and antibody dynamics and diagnostic value were assessed. RESULTS: IgM antibodies against GlpQ and Vmps peaked between 11 and 20 days, and IgG between 21 and 50 days, after disease onset. Various combinations of GlpQ and Vmps increased sensitivity and/or specificity compared to single antigens. Notably, the GlpQ or variable large protein (Vlp)-15/16 combination yielded a sensitivity of 94.7% (95% CI: 75.4-99.7) 11-20 days after disease onset and a specificity of 96.6% (92.7-98.4) for IgM. A specificity of 100% (97.8-100) for IgM, and 98.3% for IgG (95.2-100), was found when positivity was defined as reactivity to GlpQ and any Vmp, with maximum sensitivities of 79% (56.7-91.5) for IgM and 86.7% (62.1-97.6) for IgG. CONCLUSIONS: We clearly demonstrate here the diagnostic potential of these seromarkers. Our findings will facilitate future epidemiological and clinical studies on BMD and lead to the development of a serologic test to be used in clinical practice.

Chlamydophila pneumoniae diagnostics: importance of methodology in relation to timing of sampling.

The diagnostic impact of PCR-based detection was compared to single-serum IgM antibody measurement and IgG antibody seroconversion during an outbreak of Chlamydophila pneumoniae in a military community. Nasopharyngeal swabs for PCR-based detection, and serum, were obtained from 127 conscripts during the outbreak. Serum, drawn many months before the outbreak, provided the baseline antibody status. C. pneumoniae IgM and IgG antibodies were assayed using microimmunofluorescence (MIF), enzyme immunoassay (EIA) and recombinant ELISA (rELISA). Two reference standard tests were applied: (i) C. pneumoniae PCR; and (ii) assay of C. pneumoniae IgM antibodies, defined as positive if >or=2 IgM antibody assays (i.e. rELISA with MIF and/or EIA) were positive. In 33 subjects, of whom two tested negative according to IgM antibody assays and IgG seroconversion, C. pneumoniae DNA was detected by PCR. The sensitivities were 79%, 85%, 88% and 68%, respectively, and the specificities were 86%, 84%, 78% and 93%, respectively, for MIF IgM, EIA IgM, rELISA IgM and PCR. In two subjects, acute infection was diagnosed on the basis of IgG antibody seroconversion alone. The sensitivity of PCR detection was lower than that of any IgM antibody assay. This may be explained by the late sampling, or clearance of the organism following antibiotic treatment. The results of assay evaluation studies are affected not only by the choice of reference standard tests, but also by the timing of sampling for the different test principles used. On the basis of these findings, a combination of nasopharyngeal swabbing for PCR detection and specific single-serum IgM measurement is recommended in cases of acute respiratory C. pneumoniae infection.

Immunoglobulin E in the feces of children and adolescents from some tropical and subtropical countries.

Eighteen of 27 individuals, aged from 6 months to 19 years (mean 5 years, 7 months), from countries in the tropics or the subtropics had either intestinal parasitic infestations or intestinal enteropathogenic bacterial infections or both. Fourteen of those with intestinal pathogens had detectable concentrations of IgE in their fecal extracts, ranging from less than 0.5 to 420 IU/ml extract (mean 33 IU/ml). This rate of occurrence was significantly higher than the number of IgE-positive fecal extracts in a group of 54 healthy nonallergic Norwegian children (p less than 0.001), but did not differ from that of a group of 40 allergic children (p greater than 0.20). The individuals with intestinal helminthic infection had the highest fecal IgE concentrations. Of the 9 individuals who did not have any demonstrable intestinal pathogen, low concentrations of IgE could be detected in feces from only 2, which did not differ from the rate in the healthy Norwegian controls. The concentrations of IgE in the feces of the subjects from tropical/subtropical regions correlated linearly with the corresponding serum concentrations of IgE (r = 0.69; p less than 0.001). The results indicate that the combined load of intestinal pathogens, including helminths, protozoa, and enteropathogenic bacteria, may stimulate IgE production in the gut.

Clearance of vasoactive intestinal polypeptide (VIP) in the porcine pulmonary circulation.

The clearance of vasoactive intestinal polypeptide (VIP) in the lung was determined in pigs. To measure the first pass uptake, a bolus of VIP (0.9 pmol.kg-1 and 9 pmol.kg-1) with an inert intravascular marker, indocyanine green (ICG), was injected into the right atrium. The percent uptake of VIP after the higher bolus, as estimated by comparing the levels of VIP and ICG in the pulmonary artery and the aorta, was 36 +/- 6% during control infusion and 36 +/- 13% during continuous infusion of VIP (3 pmol.kg-1.min-1). The VIP concentrations in the pulmonary artery and the aorta were not different under baseline conditions, but during continuous VIP infusion the levels of plasma VIP in the pulmonary artery were higher than those in the aorta (24.3 +/- 1.6 pmol.l-1 and 20.4 +/- 1.3 pmol.l-1, resp. P less than 0.0001). These results indicate that the lung is not a source of plasma VIP, but the pulmonary circulation is a substantial contributor to the removal of VIP from plasma.

[Bronchial asthma. Treatment in relation to physiopathology and bronchial hyperreactivity]. / Asthma bronchiale. Behandling i relasjon til patofysiologi og bronkial hyperreaktivitet.

Inflammation is a characteristic feature of the pathophysiology of bronchial asthma. Therefore, long-term treatment with anti-inflammatory medication such as inhaled steroids and cromoglycate is now favoured in asthma. Short-acting adrenergic beta 2-agonists inhibiting early response after inhaled allergen provocation do not influence late reaction or inflammation. Bronchial hyperreactivity, which is a consistent characteristic of asthma, is related to late reaction. This review deals with current knowledge on bronchial hyperreactivity, and on the pathophysiology and the treatment of asthma.

Characterization of secretin-like immunoreactivity in pregnancy.

The plasma secretin-like immunoreactivity (SLI) in 23 healthy females was elevated in late pregnancy (34 +/- 3 pmol/l) as compared with 23 non-pregnant female controls (12 +/- 2 pmol/l; p less than 0.01). The plasma SLI in pregnancy eluted close to albumin on a Sephadex G-200 column, whereas 50-75% of the recovered SLI was displaced to the elution volume of free secretin when plasma was exposed to 6 mol/l urea. When 125I-labelled secretin was incubated with plasma in the absence of secretin antibodies, 40% of the intact label eluted in the void volume of a Sephadex G-50 Fine column in pregnancy, compared with only 18% in the nonpregnant state. The present study supports the notion that secretin circulates bound to plasma proteins and suggests that the protein binding of secretin is enhanced in late pregnancy, a feature common to several classical hormones.

Benign meningococcemia with IgG and IgM antimeningococcal antibodies measured by ELISA.

Six patients with benign meningococcemia are presented. The clinical picture was typically intermittent fever with chills, skin eruptions, maculopapules (often hemorrhagic) and arthritis/arthralgia in a person in good general condition. Meningococci of serogroup B were isolated from the blood of 3 patients, from the cerebrospinal fluid of 1 patient and from the nasopharynx of the remaining 2 patients. In 4 patients we assayed the levels of IgG and IgM antibodies against meningococcus serogroup B in an enzyme-linked immunosorbent test (ELISA), using whole bacteria as the antigen. All of them had higher antibody levels than the geometric means for healthy controls of both IgG and IgM, except for 1 patient who did not develop IgG antibodies.

Antibody response in patients infected with one common strain of Campylobacter jejuni. Evidence for production of antibodies against thermostable soluble antigens.

Antibody production was investigated for ten patients from a group of 20 who had contracted infections with a strain of Campylobacter jejuni of serotype PEN 6,7. Production of antibody was determined by titrating ten sets of paired sera for agglutination of formalin-treated and heat-treated cell suspensions and by passive hemagglutination using both sheep and human O Rh-red blood cells sensitized with extracted soluble thermostable antigens. All patients had demonstrable antibodies against the formalin-treated cells, six had a four-fold or greater increase in antibody levels. Nine patients showed antibodies against the heat-inactivated cells of whom five showed a fourfold or greater rise in antibody levels. Three patients developed antibodies against the extracted thermostable antigens. Sera from 100 blood donors served as controls. Six paired sera from patients that had antibodies against the heated suspension were analyzed by an immunofluorescence technique for determining IgM, IgA and IgG antibodies against live and heat-inactivated bacteria. Each of the six sera displayed antibody response primarily of the IgM and IgA class with highest levels against live cell suspensions.

Plasma gastrointestinal regulatory peptides in exercise-induced asthma.

To determine the role of gastrointestinal regulatory peptides in exercise-induced asthma (EIA), we studied plasma levels of various gastrointestinal regulatory peptides before and after a 6-min exercise test in seven subjects with EIA and five normal and three asthmatic subjects without EIA. In the EIA group, plasma vasoactive intestinal polypeptide (VIP) rose significantly 5 min and plasma cholecystokinin (CCK) 0 and 20 min after the test compared with the controls. The changes in plasma somatostatin, secretin, pancreatic polypeptide (PP), motilin and insulin showed no significant differences between the two groups. VIP may play an ameliorating role in bronchial asthma, but the relation of CCK to the lung is speculative and awaits further studies.