Sindbis-virus ja pogostantauti Suomessa

Sindbis virus (SINV) (genus Alphavirus, family Togaviridae) is an enveloped virus with a genome of single-stranded, positive-polarity RNA of 11.7 kilobases. SINV is widespread in Eurasia, Africa, and Australia, but clinical infection only occurs in a few geographically restricted areas, mainly in Northern Europe. In Europe, antibodies to SINV were detected from patients with fever, rash, and arthritis for the first time in the early 1980s in Finland. It became evident that the causative agent of this syndrome, named Pogosta disease, was closely related to SINV. The disease is also found in Sweden (Ockelbo disease) and in Russia (Karelian fever). Since 1974, for unknown reason, the disease has occurred as large outbreaks every seven years in Finland. This study is to a large degree based on the material collected during the 2002 Pogosta disease outbreak in Finland. We first developed SINV IgM and IgG enzyme immunoassays (EIA), based on highly purified SINV, to be used in serodiagnostics. The EIAs correlated well with the hemagglutination inhibition (HI) test, and all individuals showed neutralizing antibodies. The sensitivities of the IgM and IgG EIAs were 97.6% and 100%, and specificities 95.2% and 97.6%, respectively. E1 and E2 envelope glycoproteins of SINV were shown to be recognized by IgM and IgG in the immunoblot early in infection. We isolated SINV from five patients with acute Pogosta disease; one virus strain was recovered from whole blood, and four other strains from skin lesions. The etiology of Pogosta disease was confirmed by these first Finnish SINV strains, also representing the first human SINV isolates from Europe. Phylogenetic analysis indicated that the Finnish SINV strains clustered with the strains previously isolated from mosquitoes in Sweden and Russia, and seemed to have a common ancestor with South-African strains. Northern European SINV strains could be maintained locally in disease-endemic regions, but the phylogenetic analysis also suggests that redistribution of SINV tends to occur in a longitudinal direction, possibly with migratory birds. We searched for SINV antibodies in resident grouse (N=621), whose population crashes have previously coincided with human SINV outbreaks, and in migratory birds (N=836). SINV HI antibodies were found for the first time in birds during their spring migration to Northern Europe, from three individuals: red-backed shrike, robin, and song thrush. Of the grouse, 27.4% were seropositive in 2003, one year after a human outbreak, but only 1.4% of the grouse were seropositive in 2004. Thus, grouse might contribute to the human epidemiology of SINV. A total of 86 patients with verified SINV infection were recruited to the study in 2002. SINV RNA detection or virus isolation from blood and/or skin lesions was successful in eight patients. IgM antibodies became detectable within the first eight days of illness, and IgG within 11 days. The acute phase of Pogosta disease was characterized by arthritis, itching rash, fatigue, mild fever, headache, and muscle pain. Half of the patients reported in self-administered questionnaires joint symptoms to last > 12 months. Physical examination in 49 of these patients three years after infection revealed persistent joint manifestations. Arthritis (swelling and tenderness in physical examination) was diagnosed in 4.1% (2/49) of the patients. Tenderness in palpation or in movement of a joint was found in 14.3% of the patients in the rheumatologic examination, and additional 10.2% complained persisting arthralgia at the interview. Thus, 24.5% of the patients had joint manifestations attributable to the infection three years earlier. A positive IgM antibody response persisted in 3/49 of the patients; both two patients with arthritis were in this group. Persistent symptoms of SINV infection might have considerable public health implications in areas with high seroprevalence. The age-standardized seroprevalence of SINV (1999-2003, N=2529) in the human population in Finland was 5.2%. The seroprevalence was high in North Karelia, Kainuu, and Central Ostrobothnia. The incidence was highest in North Karelia. Seroprevalence in men (6.0%) was significantly higher than in women (4.1%), however, the average annualized incidence in the non-epidemic years was higher in women than in men, possibly indicating that infected men are more frequently asymptomatic. The seroprevalence increased with age, reaching 15.4% in persons aged 60-69 years. The incidence was highest in persons aged 50-59 years.Pogostantauti on virusinfektio, joka ilmenee ihmisellä nivel- ja ihottumaoirein. Noin 5 % suomalaisista on sairastanut infektion. Pogostantautia esiintyy syyskesällä, sillä ilmeisesti loppukesän hyttyslajit siirtävät viruksen ihmiseen. Spesifiä hoitoa tai rokotetta tautiin ei ole. Tauti löydettiin vuonna 1974 Ilomantsissa ja potilaiden vasta-ainetutkimukset osoittivat, että taudinaiheuttaja on läheistä sukua Sindbis-virukselle. Sindbis-virusta esiintyy Euraasiassa, Afrikassa ja Oseaniassa, mutta ihmisten tautitapauksia lähinnä vain Pohjois-Euroopassa, etenkin Suomessa. Pogostantauti on puhjennut satojen tai tuhansien potilaiden epidemiaksi täsmälleen seitsemän vuoden välein. Viimeisin epidemia oli syyskesällä 2002, jolloin diagnosoitiin 600 tapausta. Tämä väitöskirjatutkimus pohjautuu suurelta osin vuoden 2002 pogostantautiepidemian aikana koottuun näyte- ja potilasaineistoon. Potilaita seurattiin akuutin vaiheen jälkeen kolmen vuoden ajan. Väitöstutkimuksessa kuvattiin akuutin pogostantaudin tyyppioireiksi nivelkivut/-turvotus, kutiava ihottuma, väsymys, kuume, lihaskivut ja päänsärky. Nämä oireet alkavat usein samanaikaisesti. Tyypillisesti oireilevia niveliä ovat nilkat, polvet, sormet ja ranteet. Tutkimuksessa osoitettiin, että pogostantauti aiheuttaa osalle potilaista vuosikausia kestäviä niveloireita. Kolmen vuoden kuluttua infektiosta 4 %:lla potilaista todettiin krooninen niveltulehdus, ja kaikkiaan 14 %:lla todettiin objektiivisesti havaittavia pitkittyneitä niveloireita. Tutkimuksen mukaan Pohjois-Karjalassa noin 10 % väestöstä on sairastanut pogostantaudin, joten voidaan arvioida, että maakunnan alueella on satoja potilaita, joiden krooninen niveltulehdus johtuu aiemmin saadusta Sindbis-virusinfektiosta. Pogostantaudin mahdollisuus tulisi siis huomioida epäselvien niveltulehdusten erotusdiagnostiikassa. Tutkimuksessa kehitettiin potilasdiagnostiikkaan sopivia vasta-ainetestejä sekä kuvattiin infektion jälkeistä vasta-aineiden kinetiikkaa. Lisäksi työssä eristettiin viisi uutta Sindbis-viruskantaa suoraan akuuttien potilaiden iho- ja verinäytteistä. Kyseessä ovat ensimmäiset ihmisestä eristetyt Sindbis-viruskannat Euroopassa. Viruskantojen sukupuuanalyysi osoitti niiden olevan läheistä sukua Etelä-Afrikan kannoille. Virus saattaakin levitä maailmanlaajuisesti pohjois-eteläsuunnassa muuttolintujen välityksellä. Tutkimuksessa osoitettiin, että pienessä osassa Suomeen palaavista muuttolinnuista on Sindbis-virusvasta-aineita. Lisäksi suomalaisten metsäkanalintujen Sindbis-virusvasta-aineiden esiintyvyydessä havaittiin mahdollinen yhteys pogostantaudin vuosittaiseen esiintyvyyteen. Sekä muuttolinnuilla että vuoden ympäri Suomessa olevilla metsäkanalinnuilla saattaa siis olla rooli pogostantaudin erikoisessa seitsemän vuoden epidemiasyklissä, jonka syytä ei edelleenkään tunneta

Saliva-based testing for diagnosis of SARS-CoV-2 infection : A meta-analysis

Non peer reviewe

Suspicion of Lyme borreliosis in patients referred to an infectious diseases clinic : what did the patients really have?

Objective: To evaluate the conditions behind the symptoms in patients with suspected Lyme borreliosis (LB) who were referred to an infectious diseases clinic. Methods: In this retrospective, population-based study, we collected data from the medical records of all patients referred for infectious disease consultations in 2013 due to presumed LB from a population of 1.58 million. The patients were classified according to the certainty of LB on the basis of their symptoms, signs and laboratory results. Data on the outcomes and subsequent alternative diagnoses during the 4-year follow-up period were reviewed from all of the available patient records from public, private and occupational healthcare providers. Results: A total of 256 patients (16/100 000) were referred as a result of suspicion of LB; 30 (12%) of 256 were classified with definite, 36 (14%) with probable and 65 (25%) with possible LB. LB was unlikely in 121 (47%) patients. A novel diagnosis was discovered in the background symptoms in 73 (29%) of pa-tients. Previously diagnosed comorbidities caused at least some of the symptoms in 48 (19%) patients. Other explanations for symptoms were found in 81 (67%) of 121 of unlikely and 22 (34%) of 65 of possible LB patients. The spectrum of conditions behind the symptoms was quite broad and most often were musculoskeletal, neurological, psychological or functional disorders. Conclusions: LB was unlikely in half of the patients with presumed LB. In most cases the patients had other conditions that explained their symptoms. Elisa Kortela, Clin Microbiol Infect 2021;27:1022 (c) 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Rapid increase in SARS-CoV-2 seroprevalence during the emergence of Omicron variant, Finland

Non peer reviewe

Inactivation of group 2 sigma factors upregulates production of transcription and translation machineries in the cyanobacterium Synechocystis sp PCC 6803

We show that the formation of the RNAP holoenzyme with the primary sigma factor SigA increases in the Delta sigBCDE strain of the cyanobacterium Synechocystis sp. PCC 6803 lacking all group 2 s factors. The high RNAP-SigA holoenzyme content directly induces transcription of a particular set of housekeeping genes, including ones encoding transcription and translation machineries. In accordance with upregulated transcripts, Delta sigBCDE contain more RNAPs and ribosomal subunits than the control strain. Extra RNAPs are fully active, and the RNA content of Delta sigBCDE cells is almost tripled compared to that in the control strain. Although Delta sigBCDE cells produce extra rRNAs and ribosomal proteins, functional extra ribosomes are not formed, and translation activity and protein content remained similar in Delta sigBCDE as in the control strain. The arrangement of the RNA polymerase core genes together with the ribosomal protein genes might play a role in the co-regulation of transcription and translation machineries. Sequence logos were constructed to compare promoters of those housekeeping genes that directly react to the RNAP-SigA holoenzyme content and those ones that do not. Cyanobacterial strains with engineered transcription and translation machineries might provide solutions for construction of highly efficient production platforms for biotechnical applications in the future

Parachlamydia acanthamoebae Detected during a Pneumonia Outbreak in Southeastern Finland, in 2017–2018

Community-acquired pneumonia (CAP) is a common disease responsible for significant morbidity and mortality. However, the definite etiology of CAP often remains unresolved, suggesting that unknown agents of pneumonia remain to be identified. The recently discovered members of the order Chlamydiales, Chlamydia-related bacteria (CRB), are considered as possible emerging agents of CAP. Parachlamydia acanthamoebae is the most studied candidate. It survives and replicates inside free-living amoeba, which it might potentially use as a vehicle to infect animals and humans. A Mycoplasma pneumoniae outbreak was observed in Kymenlaakso region in Southeastern Finland during August 2017–January 2018. We determined the occurrence of Chlamydiales bacteria and their natural host, free-living amoeba in respiratory specimens collected during this outbreak with molecular methods. Altogether, 22/278 (7.9%) of the samples contained Chlamydiales DNA. By sequence analysis, majority of the CRBs detected were members of the Parachlamydiaceae family. Amoebal DNA was not detected within the sample material. Our study further proposes that Parachlamydiaceae could be a potential agent causing atypical CAP in children and adolescents

Evaluation of commercial and automated SARS-CoV-2 IgG and IgA ELISAs using coronavirus disease (COVID-19) patient samples

Antibody-screening methods to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) need to be validated. We evaluated SARS-CoV-2 IgG and IgA ELISAs in conjunction with the EUROLabworkstation (Euroimmun, Lubeck, Germany). Overall specificities were 91.9% and 73.0% for IgG and IgA ELISAs, respectively. Of 39 coronavirus disease patients, 13 were IgG and IgA positive and 11 IgA alone at sampling. IgGs and IgAs were respectively detected at a median of 12 and 11 days after symptom onset.Peer reviewe

Roles of Close Homologues SigB and SigD in Heat and High Light Acclimation of the Cyanobacterium Synechocystis sp. PCC 6803

Acclimation of cyanobacterium Synechocystis sp. PCC6803 to suboptimal conditions is largely dependent on adjustments of gene expression, which is highly controlled by the sigma factor subunits of RNA polymerase (RNAP). The SigB and SigD sigma factors are close homologues. Here we show that the sigB and sigD genes are both induced in high light and heat stresses. Comparison of transcriptomes of the control strain (CS), Delta sigB, Delta sigD, Delta sigBCE (containing SigD as the only functional group 2 sigma factor), and Delta sigCDE (SigB as the only functional group 2 sigma factor) strains in standard, high light, and high temperature conditions revealed that the SigB and SigD factors regulate different sets of genes and SigB and SigD regulons are highly dependent on stress conditions. The SigB regulon is bigger than the SigD regulon at high temperature, whereas, in high light, the SigD regulon is bigger than the SigB regulon. Furthermore, our results show that favoring the SigB or SigD factor by deleting other group 2 sigma factors does not lead to superior acclimation to high light or high temperature, indicating that all group 2 sigma factors play roles in the acclimation processes

The Finnish New Variant of Chlamydia trachomatis with a Single Nucleotide Polymorphism in the 23S rRNA Target Escapes Detection by the Aptima Combo 2 Test

In 2019, more than 200 cases of Chlamydia trachomatis negative/equivocal by the Aptima Combo 2 assay (AC2, target: 23S rRNA) with slightly elevated relative light units (RLUs), but positive by the Aptima Chlamydia trachomatis assay (ACT, target: 16S rRNA) have been detected in Finland To identify the cause of the AC2 CT false-negative specimens, we sequenced parts of the CT 23S rRNA gene in 40 specimens that were AC2 negative/equivocal but ACT positive. A single nucleotide polymorphism (SNP; C1515T in the C. trachomatis 23S rRNA gene) was revealed in 39 AC2/ACT discordant specimens. No decrease in the number of mandatorily notified C. trachomatis cases was observed nationally in Finland in 2010–2019. When RLUs obtained for AC2 negative specimens were retrospectively evaluated in 2011–2019, a continuous increase in the proportion of samples with RLUs 10–19 was observed since 2014, and a slight increase in the proportion of samples with RLUs 20–84 in 2017–2019, indicating that the Finnish new variant of C. trachomatis might have been spreading nationally for several years. This emphasizes that careful surveillance of epidemiology, positivity rate and test performance are mandatory to detect any changes affecting detection of infections