Epidemiology of tularemia in Finland

Tularemia is a zoonotic disease caused by the facultative intracellular bacterium Francisella tularensis. Recurrent outbreaks with hundreds of cases are reported in Finland and Sweden every few years. In other European countries the disease is quite rare, but sporadic outbreaks have been reported from various countries. Specific risk factors associated with ulceroglandular and pneumonic tularemia were investigated in a population-based case-control study presented in this thesis (study I). In addition, the public health impact of tularemia in Finland was analyzed and information on clinical features of the disease and patient characteristics was collected. Reported mosquito bites and farming activities were independently associated with ulceroglandular tularemia, whereas exposure to hay dust was associated with pneumonic tularemia. Spatial and temporal epidemiology of tularemia in Finland was investigated based on notifications to the National Infectious Disease Register (study IV). The prevalence of F. tularensis antibodies in the adult general population was studied using serum samples from a nationwide population-based health survey (study IV). A serologic response to F. tularensis was found in 2% of the population. Occurrence of F. tularensis in wild rodents was studied by screening a total of 547 wild small mammals from 14 locations around Finland for the presence of F. tularensis DNA by PCR analysis (study II). High copy numbers of F. tularensis-specific DNA were detected in tissue samples of only 5 field voles originating from one location. The pathogenesis of F. tularensis infection in wild voles was studied in an experimental infection (study III). A rapid lethal clinical course, bacteremia and tissue necrosis were observed in the infected field voles and bank voles. The correlation between vole population cycles and human tularemia outbreaks was assessed using surveillance data from 1995-2013 (study IV). Vole population peaks clearly preceded subsequent tularemia outbreaks one year later. In conclusion, this thesis describes risk factors for tularemia as well as the clinical characteristics and epidemiology of the disease in Finland. Moreover, the kinetics of F. tularensis infection in voles and the occurrence of F. tularensis in wildlife in Finland are represented. Since 1995, more than 5000 cases of tularemia have been reported. About 2% of the adult population has antibodies against F. tularensis. Incidence and seroprevalence are highest in Northern Ostrobothnia. Ulceroglandular and pneumonic tularemia have different risk factors. In rodents, F. tularensis infection is rare and mostly fatal. Rodents act as amplification hosts of F. tularensis, and high rodent densities predict tularemia outbreaks in humans in the following year.Jänisrutto (tularemia) on zoonoottinen, eli eläimestä ihmiseen tarttuva infektio, jonka aiheuttaja on Francisella tularensis bakteeri. Jänisruttoa esiintyy lähinnä pohjoisella pallonpuoliskolla, ja taudin ilmaantuvuus on erityisen suuri Suomessa ja Ruotsissa. Muissa Euroopan maissa tauti on melko harvinainen, mutta yksittäisiä taudinpurkauksia on raportoitu useista maista. Jänisruton eri tautimuotojen riskitekijöitä kartoitettiin laajassa tapaus-verrokki tutkimuksessa. Lisäksi arvioitiin taudin kansanterveydellistä vaikutusta ja kerättiin tietoa taudin kliinisestä kuvasta. Tutkimuksen perusteella jänisruton haavaumina ja imusolmuksetulehduksina ilmenevä (ulseroglandulaarinen) muoto leviää pääasiallisesti hyönteispistojen välityksellä ja liittyy maanviljelytyöhön. Jänisruton keuhkomuodon todettiin olevan voimakkaasti yhteydessä heinäpölylle altistumiseen. Jänisruton ilmaantuvuutta eri vuosina eri puolilla Suomea selvitettiin tartuntatautirekisteriin tehtyjen ilmoitusten perusteella. Lisäksi tutkittiin jänisrutto-vasta-aineiden esiintyvyyttä aikuisväestössä. Taudin ilmaantuvuus on selvästi suurinta Pohjois- ja Etelä-Pohjanmaalla sekä Keski-Suomessa, mutta eri vuosina epidemiat esiintyvät eri paikkakunnilla. Epidemioita esiintyi elo-syyskuussa vuosina 1995, 1996, 2000, 2003, 2006, 2007, 2009, 2012. Jänisrutto-vasta-aineita todettiin 2 %:lla aikuisväestöstä, osuus oli korkein Pohjois-Pohjanmaalla, vastaten tartuntatautirekisterin ilmoituksia. Bakteerin esiintymistä jyrsijöissä kartoitettiin tutkimalla satojen luonnosta pyydettyjen pikkunisäkkäiden kudosnäytteitä geeninmonistusmenetelmällä, jolla osoitettiin suuria bakteerimääriä viiden peltomyyrän kudoksissa. Kokeellisessa infektiossa F. tularensis bakteerin ossoitettiin leviävän laajalle metsä- ja peltomyyrien elimistössä aiheuttaen oireellisen infektion ja kuoleman. Myyrien osoitettiin erittävän bakteeria virtsaan ja ulosteeseen. Myyrien jäännökset voivat näin ollen kontaminoida ympäristöä ja aiheuttaa tartuntavaaraa ihmisille. Myös jyrsijöiden kannanvaihteluiden merkitystä ihmisten jänisruttotartunnoille tutkittiin. Myyräkannat vaihtelevat tyypillisesti 3 vuoden sykleissä. Tutkimuksessa osoitettiin, että jänisruttoepidemiat esiintyvät tyypillisesti runsasta myyrävuotta seuraavana vuonna.. Todennäköisesti F. tularensis lisääntyy tehokkaasti runsaassa myyräpopulaatiossa, leviää ympäristöön ja päätyy veteen ja siinä kehittyviin hyttysiin, jotka tartuttavat bakteerin ihmisiin. Tutkimuksen perusteella voidaan päätellä jänisruton esiintymisen olevan paitsi paikallista, myös syklistä ja syklien liittyvän jyrsijäkantojen vaihteluun

Genomic characterization of ESBL/AmpC-producing and high-risk clonal lineages of Escherichia coli and Klebsiella pneumoniae in imported dogs with shelter and stray background

Objectives: Extended spectrum ,B-lactamase (ESBL)-and ampicillinase C (AmpC)-carrying Enterobacteriaceae have been widely reported among companion animals. According to previous studies, dogs with a shelter or stray background might be at risk of carrying such bacteria. The aim of this study was to ex-plore, with whole-genome sequencing (WGS), the genomic characteristics of ESBL-producing Escherichia coli and Klebsiella pneumoniae isolated from imported dogs with a stray or shelter background. Methods: E. coli (n = 58) and K. pneumoniae (n = 2) isolates from imported dogs originating from seven countries were included. Phenotypic resistance was investigated by selective isolation and antibiotic sus-ceptibility testing. Whole-genome sequencing was used to study the genomic characteristics and the pres-ence of antimicrobial resistance genes (ARGs) and virulence determinants of the ESBL/AmpC-producing E. coli and K. pneumoniae isolates. Results: A high diversity of different ARGs (n = 56) and sequence types (STs) (n = 32), including high -risk clonal lineages ST410 (n = 3) and ST307 (n = 1), was identified in E. coli and K. pneumoniae isolates, respectively. Genes encoding resistance to ,beta-lactams accounted for the majority, with the most frequent being blaCTX-M-15. Moreover, 17 (29%) E. coli isolates qualified as presumptive extraintestinal pathogenic and/or uropathogenic E. coli. Conclusions: Our results highlight the multiplicity of genetic backgrounds disseminating ESBL/AmpC-genes in the studied dogs, calling for further investigation of possible drivers responsible for the dissem-ination of ARGs in animal shelters and amongst stray dogs. From a public health perspective, enhanced genomic surveillance of ESBL/AmpC-producing Enterobacteriaceae in dogs is needed in Finland. (C) 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.Peer reviewe

Mortality and alcohol-related morbidity in patients with delirium tremens, alcohol withdrawal state or alcohol dependence in Norway: A register-based prospective cohort study

Background and Aims: Little is known about long-term consequences of delirium tremens (DT). This study aimed to compare all-cause and cause-specific mortality and alcohol-related morbidity between patients with: (i) DT, (ii) alcohol withdrawal state (AWS) and (iii) alcohol dependence (AD). Design: A national longitudinal health registry study with linked data from the Norwegian Patient Registry and the Norwegian Cause of Death Registry. Setting: Norway. Participants: All patients registered in the Norwegian Patient Registry between 2009 and 2015 with a diagnosis of AD (ICD-10 code F10.2), AWS (F10.3) or DT (F10.4) and aged 20–79 years were included (n = 36 287). Measurements: Patients were categorized into three mutually exclusive groups; those with DT diagnosis were categorized as DT patients regardless of whether or not they had received another alcohol use disorder diagnosis during the observation period or not. Outcome measures were: annual mortality rate, standardized mortality ratios (SMR) for all-cause and cause-specific mortality and proportion of alcohol-related morbidities which were registered in the period from 2 years before to 1 year after the index diagnosis. Findings: DT patients had higher annual mortality rate (8.0%) than AWS (5.0%) and AD (3.6%) patients, respectively. DT patients had higher mortality [SMR = 9.8, 95% confidence interval (CI) = 8.9–10.7] than AD patients (SMR = 7.0, 95% CI = 6.8–7.2) and AWS patients (SMR = 7.8, 95% CI = 7.2–8.4). SMR was particularly elevated for unnatural causes of death, and more so for DT patients (SMR = 26.9, 95% CI = 21.7–33.4) than for AD patients (SMR = 15.2, 95% CI = 14.2–16.3) or AWS patients (SMR = 20.1, 95% CI = 16.9–23.9). For all comorbidities, we observed a higher proportion among DT patients than among AWS or AD patients (P < 0.001). Conclusions: People treated for delirium tremens appear to have higher rates of mortality and comorbidity than people with other alcohol use disorders

14C-Cobalamin Absorption from Endogenously Labeled Chicken Eggs Assessed in Humans Using Accelerator Mass Spectrometry.

Traditionally, the bioavailability of vitamin B-12 (B12) from in vivo labeled foods was determined by labeling the vitamin with radiocobalt (57Co, 58Co or 60Co). This required use of penetrating radioactivity and sometimes used higher doses of B12 than the physiological limit of B12 absorption. The aim of this study was to determine the bioavailability and absorbed B12 from chicken eggs endogenously labeled with 14C-B12 using accelerator mass spectrometry (AMS). 14C-B12 was injected intramuscularly into hens to produce eggs enriched in vivo with the 14C labeled vitamin. The eggs, which provided 1.4 to 2.6 μg of B12 (~1.1 kBq) per serving, were scrambled, cooked and fed to 10 human volunteers. Baseline and post-ingestion blood, urine and stool samples were collected over a one-week period and assessed for 14C-B12 content using AMS. Bioavailability ranged from 13.2 to 57.7% (mean 30.2 ± 16.4%). Difference among subjects was explained by dose of B12, with percent bioavailability from 2.6 μg only half that from 1.4 μg. The total amount of B12 absorbed was limited to 0.5-0.8 μg (mean 0.55 ± 0.19 μg B12) and was relatively unaffected by the amount consumed. The use of 14C-B12 offers the only currently available method for quantifying B12 absorption in humans, including food cobalamin absorption. An egg is confirmed as a good source of B12, supplying approximately 20% of the average adult daily requirement (RDA for adults = 2.4 μg/day)

Genotyping and phylogenetic placement of Bacillus anthracis isolates from Finland, a country with rare anthrax cases

Anthrax, the zoonotic disease caused by the gram-positive bacterium Bacillus anthracis, is nowadays rare in northern parts of Europe including Finland and Scandinavia. Only two minor outbreaks of anthrax in 1988 and in 2004 and one sporadic infection in 2008 have been detected in animals in Finland since the 1970’s. Here, we report on two Finnish B. anthracis strains that were isolated from spleen and liver of a diseased calf related to the outbreak in 1988 (strain HKI4363/88) and from a local scrotum and testicle infection of a bull in 2008 (strain BA2968). These infections occurred in two rural Finnish regions, i.e., Ostrobothnia in western Finland and Päijänne Tavastia in southern Finland, respectively

Experimental Infection of Voles with Francisella tularensis Indicates Their Amplification Role in Tularemia Outbreaks

Peer reviewe

Small mammals as carriers of zoonotic bacteria on pig and cattle farms – Prevalence and risk of exposure in an integrative approach

To prevent foodborne infections from pigs and cattle, the whole food chain must act to minimize the contamination of products, including biosecurity measures which prevent infections via feed and the environment in production farms. Rodents and other small mammals can be reservoirs of and key vectors for transmitting zoonotic bacteria and viruses to farm animals, through direct contact but more often through environmental contamination. In line with One Health concept, we integrated results from a sampling study of small mammals in farm environments and data from a capture-recapture experiment into a probabilistic model which quantifies the degree of environmental exposure of zoonotic bacteria by small mammals to farm premises. We investigated more than 1200 small mammals trapped in and around 38 swine and cattle farm premises in Finland in 2017/2018. Regardless of the farm type, the most common species caught were the yellow-necked mouse (Apodemus flavicollis), bank vole (Clethrionomys glareolus), and house mouse (Mus musculus). Of 554 intestine samples (each pooled from 1 to 10 individuals), 33% were positive for Campylobacter jejuni. Yersinia enterocolitica was detected in 8% of the pooled samples, on 21/38 farm premises. Findings of Salmonella and the Shiga-toxin producing Escherichia coli (STEC) were rare: the pathogens were detected in only single samples from four and six farm premises, respectively. The prevalence of Campylobacter, Salmonella, Yersinia and STEC in small mammal populations was estimated as 26%/13%, 1%/0%, 2%/3%, 1%/1%, respectively, in 2017/2018. The exposure probability within the experimental period of four weeks on farms was 17–60% for Campylobacter and 0–3% for Salmonella. The quantitative model is readily applicable to similar integrative studies. Our results indicate that small mammals increase the risk of exposure to zoonotic bacteria in animal production farms, thus increasing risks also for livestock and human health

Siipikarjan lintuinfluenssariski Suomessa – riskiprofiili

Korkeapatogeenisen lintuinfluenssan aiheuttama paine suomalaisiin siipikarjoihin on kohonnut. Tautia on todettu vuoden 2016 jälkeen luonnonvaraisilla linnuilla yhä useammin ja yhä laajemmalla alueella. Kartoitimme riskitekijöitä, jotka voisivat johtaa lintuinfluenssan leviämiseen siipikarjaan Suomessa. Samalla arvioimme siipikarjan alueellista ja ajallista lintuinfluenssatartuntariskiä sekä siipikarjan ulkonapitokiellon tarkoituksenmukaista laajuutta ja ajankohtaa. Aineistona käytimme BirdLifen lintuseuranta-aineistoja, siipikarjan salmonellavalvontaohjelmaan kuuluvien tilojen tarkastuskäyntipöytäkirjoja, Ruokaviraston eläintenpitäjärekisteriä ja lintuinfluenssaseurannan tuloksia, kirjallisuutta sekä asiantuntijahaastatteluista saatua tietoa. Lintuinfluenssalle vähiten alttiit alueet ovat Pohjois- ja Koillis-Suomessa. Altistumisriski on vähäisin talvisin. Ulkonapitokielto vähentää altistumisriskiä, mutta Suomessa on alueita ja ajankohtia, jolloin siipikarjan ulkonapitokiellon laajutta tai ajankohtaa voisi muuttaa. Euroopan kulloisenkin kevään lintuinfluenssatilanne voitaisiin huomioida ulkonapitokiellon ajanjaksoa määriteltäessä. Tehokkain tapa suojata siipikarja lintuinfluenssalta on pitopaikan hyvä tautisuojaus

Salmonellan leviäminen suomalaisille sika- ja nautatiloille

Hankkeen tavoitteina oli tunnistaa nauta- ja sikatilojen salmonellatartuntojen lähteitä sekä toimintatapoja, joilla saneeraus ja tartuntojen ehkäisy tiloilla parhaiten onnistuu. Lukuisista tartuntalähteistä tärkeimmiksi arvioimme yhdyskuntalinnut ja muut haittaeläimet sekä turkistuotanto mahdollisena alkulähteenä haittaeläinten välittämille tartunnoille. Viime vuosina nauta- ja sikatiloille tehtyjen saneerausten aineistosta arvioimme seikkoja, jotka johtivat saneerauksen onnistumiseen tai pitkittymiseen tai tartunnan uusimiseen. Saneeraus pitkittyi, jos tartunta oli alkutilanteessa levinnyt laajalle, tartuntalähdettä ei saatu heti selville, salmonellapositiivisia eläimiä ei poistettu ajoissa, puhdistus-, pesu- ja desinfiointitoimet eivät olleet riittäviä tai käytettävissä oleva työpanos ei riittänyt. Saneerauksen onnistumista edistivät hyvä työnjohto, systemaattisuus, saneeraussuunnitelma sekä suunnitelman ja muiden ohjeiden noudattaminen. Tarkastelimme tilan salmonellatartunnan ja sen saneerauksen vaatimuksia myös työturvallisuuden suhteen. Salmonellatartunnan ehkäisy edellyttää tilatason tautisuojausta, jonka on oltava jokapäiväistä ja kohdistuttava tilan koko toimintaan ottaen huomioon haittaeläimistä aiheutuva tartuntavaara. Hankkeessa syntyi tietopääomaa salmonellan epidemiologiseen seurantaan, saneerausneuvontaan ja suosituksia tukemaan salmonellatorjuntaa.Tämä julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa. (tietokayttoon.fi) Julkaisun sisällöstä vastaavat tiedon tuottajat, eikä tekstisisältö välttämättä edusta valtioneuvoston näkemystä