An Epidemic of Sylvatic Rabies in Finland

When rabies reappeared in Finland in April 1988, the country had been rabies free since 1959. Soon a picture of sylvatic rabies become evident, its main vector and victim being the raccoon dog (Nyctereutes procyonoides). Between 8 April 1988 and 16 February 1989, 66 virologically verified cases were recorded (48 raccoon dogs, 12 red foxes, 2 badgers, 2 cats, l dog and 1 dairy bull) in an area estimated at 1700 km2 in south-eastern Finland. The greatest distance between recorded cases was 67 km. A positive reaction with monoclonal antibody p-41 indicated that the virus was an arctic-type strain. A field trial on oral immunization of small predators was initiated in September 1988 using Tübingen fox baits according to the Bavarian model of bait distribution. Each bait contained 5*107 TCID50/ml modified live rabies virus (SAD-B19). The 6 months’ surveillance indicate a seroconversion rate of 72% (N=126) in the raccoon dog population, 67% (N=56) in the red foxes and 13% (N=16) in the badgers, when titers ≥1.0 IU/ml are considered seropositive. In the whole follow-up period, no statistically significant difference could be detected between the raccoon dogs and red foxes in the rate of seroconversion or in the uptake of tetracycline from the baits. Notably high antibody levels were recorded in both raccoon dogs and red foxes within 4–5 months after vaccination. Of the seropositive animals, the proportion of animals with titers 3.0 IU/ml or greater was higher in raccoon dogs (73%) than in red foxes (51%) (x2= 5.29, p< 0.05). The trial shows that raccoon dogs can be immunized against rabies in the field with vaccine baits originally developed for controlling sylvatic rabies in foxes.     

Large Outbreak Caused by Methicillin Resistant Staphylococcus pseudintermedius ST71 in a Finnish Veterinary Teaching Hospital – From Outbreak Control to Outbreak Prevention

Introduction

The purpose of this study was to describe a nosocomial outbreak caused by methicillin resistant Staphylococcus pseudintermedius (MRSP) ST71 SCCmec II-III in dogs and cats at the Veterinary Teaching Hospital of the University of Helsinki in November 2010 – January 2012, and to determine the risk factors for acquiring MRSP. In addition, measures to control the outbreak and current policy for MRSP prevention are presented.

Methods

Data of patients were collected from the hospital patient record software. MRSP surveillance data were acquired from the laboratory information system. Risk factors for MRSP acquisition were analyzed from 55 cases and 213 controls using multivariable logistic regression in a case-control study design. Forty-seven MRSP isolates were analyzed by pulsed field gel electrophoresis and three were further analyzed with multi-locus sequence and SCCmec typing.

Results

Sixty-three MRSP cases were identified, including 27 infections. MRSPs from the cases shared a specific multi-drug resistant antibiogram and PFGE-pattern indicated clonal spread. Four risk factors were identified; skin lesion (OR = 6.2; CI_95% 2.3–17.0, P = 0.0003), antimicrobial treatment (OR = 3.8, CI_95% 1.0–13.9, P = 0.0442), cumulative number of days in the intensive care unit (OR = 1.3, CI_95% 1.1–1.6, P = 0.0007) or in the surgery ward (OR = 1.1, CI_95% 1.0–1.3, P = 0.0401). Tracing and screening of contact patients, enhanced hand hygiene, cohorting and barrier nursing, as well as cleaning and disinfection were used to control the outbreak. To avoid future outbreaks and spread of MRSP a search-and-isolate policy was implemented. Currently nearly all new MRSP findings are detected in screening targeted to risk patients on admission.

Conclusion

Multidrug resistant MRSP is capable of causing a large outbreak difficult to control. Skin lesions, antimicrobial treatment and prolonged hospital stay increase the probability of acquiring MRSP. Rigorous control measures were needed to control the outbreak. We recommend the implementation of a search-and-isolate policy to reduce the burden of MRSP.     

Immune cell phenotype and functional defects in Netherton syndrome

Background

Netherton syndrome (NS) is a rare life-threatening syndrome caused by SPINK5 mutations leading to a skin barrier defect and a severe atopic diathesis. NS patients are prone to bacterial infections, but the understanding of the underlying immune deficiency is incomplete.

Results

We analyzed blood lymphocyte phenotypes and function in relation to clinical infections in 11 Finnish NS patients, aged 3 to 17?years, and healthy age-matched controls. The proportion of B cells (CD19⁺) and naïve B cells (CD27^?, IgD⁺) were high while memory B cells (CD27⁺) and switched memory B cells (CD27⁺IgM^?IgD^?), crucial for the secondary response to pathogens, was below or in the lowest quartile of the reference values in 8/11 (73%) and 9/11 (82%) patients, respectively. The proportion of activated non-differentiated B cells (CD21^low, CD38l^ow) was below or in the lowest quartile of the reference values in 10/11 (91%) patients. Despite normal T cell counts, the proportion of naïve CD4⁺ T cells was reduced significantly and the proportion of CD8⁺ T central memory significantly elevated. An increased proportion of CD57⁺ CD8⁺ T cells indicated increased differentiation potential of the T cells. The proportion of cytotoxic NK cells was elevated in NS patients in phenotypic analysis based on CD56DIM, CD16⁺ and CD27^? NK cells but in functional analysis, decreased expression of CD107a/b indicated impaired cytotoxicity.The T and NK cell phenotype seen in NS patients also significantly differed from that of age-matched atopic dermatitis (AD) patients, indicating a distinctive profile in NS. The frequency of skin infections correlated with the proportion of CD62L⁺ T cells, naïve CD4⁺ and CD27⁺ CD8⁺ T cells and with activated B cells. Clinically beneficial intravenous immunoglobulin therapy (IVIG) increased naïve T cells and terminal differentiated effector memory CD8⁺ cells and decreased the proportion of activated B cells and plasmablasts in three patients studied.

Conclusions

This study shows novel quantitative and functional aberrations in several lymphocyte subpopulations, which correlate with the frequency of infections in patients with Netherton syndrome. IVIG therapy normalized some dysbalancies and was clinically beneficial.

     

Within‐population genetic effects of mtDNA on metabolic rate in Drosophila subobscura

A growing body of research supports the view that within‐species sequence variation in the mitochondrial genome (mtDNA) is functional, in the sense that it has important phenotypic effects. However, most of this empirical foundation is based on comparisons across populations, and few studies have addressed the functional significance of mtDNA polymorphism within populations. Here, using mitonuclear introgression lines, we assess differences in whole‐organism metabolic rate of adult Drosophila subobscura fruit flies carrying either of three different sympatric mtDNA haplotypes. We document sizeable, up to 20%, differences in metabolic rate across these mtDNA haplotypes. Further, these mtDNA effects are to some extent sex specific. We found no significant nuclear or mitonuclear genetic effects on metabolic rate, consistent with a low degree of linkage disequilibrium between mitochondrial and nuclear genes within populations. The fact that mtDNA haplotype variation within a natural population affects metabolic rate, which is a key physiological trait with important effects on life‐history traits, adds weight to the emergent view that mtDNA haplotype variation is under natural selection and it revitalizes the question as to what processes act to maintain functional mtDNA polymorphism within populations.     

Differentially methylated regions in maternal and paternal uniparental disomy for chromosome 7

DNA methylation is a hallmark of genomic imprinting and differentially methylated regions (DMRs) are found near and in imprinted genes. Imprinted genes are expressed only from the maternal or paternal allele and their normal balance can be disrupted by uniparental disomy (UPD), the inheritance of both chromosomes of a chromosome pair exclusively from only either the mother or the father. Maternal UPD for chromosome 7 (matUPD7) results in Silver-Russell syndrome (SRS) with typical features and growth retardation, but no gene has been conclusively implicated in SRS. In order to identify novel DMRs and putative imprinted genes on chromosome 7, we analyzed eight matUPD7 patients, a segmental matUPD7q31-qter, a rare patUPD7 case and ten controls on the Infinium HumanMethylation450K BeadChip with 30 017 CpG methylation probes for chromosome 7. Genome-scale analysis showed highly significant clustering of DMRs only on chromosome 7, including the known imprinted loci GRB10, SGCE/PEG10, and PEG/MEST. We found ten novel DMRs on chromosome 7, two DMRs for the predicted imprinted genes HOXA4 and GLI3 and one for the disputed imprinted gene PON1. Quantitative RT-PCR on blood RNA samples comparing matUPD7, patUPD7, and controls showed differential expression for three genes with novel DMRs, HOXA4, GLI3, and SVOPL. Allele specific expression analysis confirmed maternal only expression of SVOPL and imprinting of HOXA4 was supported by monoallelic expression. These results present the first comprehensive map of parent-of-origin specific DMRs on human chromosome 7, suggesting many new imprinted sites.     

The Association of Episiotomy with Obstetric Anal Sphincter Injury–A Population Based Matched Cohort Study

Objectives

To estimate the independent association of episiotomy with obstetric anal sphincter injuries (OASIS) using first a cross-sectional and then a matched pair analysis.

Design

A matched cohort.

Setting

Data was gathered from the Finnish Medical Birth Register from 2004–2011.

Population

All singleton vaginal births (n = 303,758).

Methods

Women resulting matched pairs (n = 63,925) were matched based on baseline risk of OASIS defined based on parity (first or second/subsequent vaginal births), age, birth weight, mode of delivery, prior caesarean section, and length of active second stage of birth.

Results

In cross-sectional analysis episiotomy was associated with a 12% lower incidence of OASIS (adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.80 to 0.98) in first vaginal births and with a 132% increased incidence of OASIS in second or subsequent vaginal births (aOR 2.32, 95% CI 1.77 to 3.03). In matched pair analysis episiotomy was associated with a 23% (aOR 0.77, 95% CI 0.69 to 0.86) lower incidence of OASIS in first vaginal births and a 61% (aOR 1.61, 95% CI 1.14 to 2.29) increased incidence of OASIS in second or subsequent vaginal births compared to women who gave birth without an episiotomy. The matched pair analysis showed a 12.5% and a 31.6% reduction in aORs of OASIS associated with episiotomy, respectively.

Conclusions

A matched pair analysis showed a substantial reduction in the aORs of OASIS with episiotomy, due to confounding by indication. This indicates that results of observational studies evaluating an association between episiotomy and OASIS should be interpreted with caution.     

Performance of blue- and green-sensitive photoreceptors of the cricket Gryllus bimaculatus

The compound eye of the cricket Gryllus bimaculatus contains a specialized dorsal rim area (DRA) populated by distinct blue-sensitive photoreceptors responsible for perception of polarized light. The rest of the eye is dominated by green-sensitive photoreceptors. Using patch clamp we studied dissociated ommatidia of nocturnal adults and diurnal eight-instar nymphs with the goals (1) of characterizing the biophysical properties of cricket photoreceptors in general and (2) describing the functionally dissimilar blue- and green-sensitive photoreceptors in terms of voltage-gated channel composition and signal coding. Despite different lifestyles, adult and nymph photoreceptors were indistinguishable. No significant circadian changes were observed in K⁺ currents. In contrast, prominent differences were seen between blue- and green-sensitive photoreceptors. The former were characterized by relatively low absolute sensitivity, high input resistance, slow quantum bumps with long latencies, small light-induced and K⁺ currents and low steady-state depolarization. Information rate, a measure of photoreceptor performance calculated from voltage responses to bandwidth-limited white noise-modulated light contrast, was 87 ± 8 bits s^?1 in green-sensitive photoreceptors vs. 59 ± 14 bits s^?1 in blue-sensitive photoreceptors, implying a limited role of DRA in the perception of visual contrasts. In addition, evidence of electrical coupling between photoreceptors is presented.     

Growth and genotype × environment interactions in Betula pendula: can tree genetic variation be maintained by small-scale forest ground heterogeneity?

Forest ground heterogeneity can affect interactions among tree species and control the assembly of local forest communities. Less is known of the effects of spatial heterogeneity on the maintenance of tree genetic variation through small-scale genotype × environment (G × E) interactions. We measured growth variation within and among 17 Betula pendula genotypes, planted in a clear-cut forest site through the summers 2009–2011. We assessed the spatial heterogeneity at two scales: among forest stands having history of the same or different tree species combinations (treated as replicate blocks), and along a gradient of within-block forest density, revealed by the stump density. To add a temporal perspective, we distinguished between old (cut 50 years earlier) and new stumps (cut one year earlier). The broad-sense heritabilities for growth were 0.093–0.055 and the coefficients of genotypic variation 0.37–0.21 in 2009–2011. The growth difference among the genotypes was 3.5–5.5 fold, significant in all years, and the rank of genotype means correlated positively between the years. The most favourable block had 106 % higher growth than the least favourable block and the amount of total variation explained by block increased from 0.4 % in 2009 to 6.9 % in 2011. Genotype × block interaction was marginally significant in 2009, but not later. Similarly, the response of growth to old stump density in sapling vicinity varied among the genotypes in 2009, but not later. In 2010 and 2011, the mean growth increased by 50–91 % along the old stump density gradient. Our results suggest that despite creating significant variation in sapling growth the small-scale forest ground heterogeneity, which reflects the recent forest history, may not significantly contribute to the maintenance of genetic variation in B. pendula populations.