Genomic Characterization of Invasive Meningococcal Serogroup B Isolates and Estimation of 4CMenB Vaccine Coverage in Finland.

Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a significant cause of morbidity and mortality worldwide. In Finland, the incidence rate of IMD is low, with meningococcal serogroup B (MenB) accounting for around one-third of IMD cases annually. The aim of this study was to investigate the genetic variability of invasive MenB isolates collected in Finland between 2010 and 2017 (n = 81), including the genes encoding the 4-component MenB vaccine (4CMenB; Bexsero; GSK) antigens and their promoters, and to evaluate the 4CMenB potential coverage. Whole-genome sequencing was performed. The meningococcal antigen typing system (MATS) was used to characterize MenB isolates and predict the potential coverage of 4CMenB. MATS was complemented by genetic MATS (gMATS) through association of antigen genotyping and phenotypic MATS results. Multilocus sequence typing revealed predominance of the ST-41/44 clonal complex among which sequence type (ST)-303 was the most common and was predicted to be covered by 4CMenB. Of the 4 major vaccine antigens, the factor H-binding protein variant 1, neisserial heparin binding antigen peptide 2, and the PorA P1.4 antigen were predominant, whereas Neisseria adhesin A was present in only 4% of the 81 isolates. MATS and gMATS 4CMenB strain coverage predictions were 78% and 86%, respectively, in a subpanel of 60 isolates collected during 2010 to 2014, with a gMATS prediction of 84% for all 81 isolates. The results suggest that 4CMenB could reduce the burden of IMD in Finland and that gMATS could be applied to monitor vaccine strain coverage and predict vaccine effectiveness.IMPORTANCE 4CMenB is a 4-component vaccine used against invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B (MenB). We investigated the genetic variability of MenB in Finland and evaluated 4CMenB strain coverage by 2 different methods: MATS (meningococcal antigen typing system) and gMATS (genetic MATS). In a set of MenB isolates, 78% (MATS) and 86% (gMATS) were predicted as covered by 4CMenB, suggesting that use of 4CMenB would help reduce IMD incidence in Finland. MATS has been used in 13 countries worldwide, generating information on phenotypic characteristics that could infer protection by 4CMenB. Based on these data and genetic information, gMATS coverage predictions can be made. gMATS predicts coverage consistent with MATS for about 94% of tested strains. Unlike MATS, gMATS does not require live isolates, thus allowing the analysis also of noncultivable strains, making the coverage predictions more accurate. Therefore, gMATS can replace MATS to assess 4CMenB coverage, including in regions with no prior MATS data.

Summary of available surveillance data on hepatitis C virus infection from eight Arctic countries, 2012 to 2014.

We summarised available hepatitis C virus (HCV) surveillance data for 2012-14 from Arctic/sub-Arctic countries/regions. We sent a HCV data collection template by email to public health authorities in all jurisdictions. Population statistics obtained from census sources for each country were used to estimate rates of reported acute and chronic/undifferentiated HCV cases. Seven countries with Arctic regions (Canada, Denmark, Finland, Greenland, Norway, Sweden and the United States, represented by the state of Alaska), including three Canadian territories and one province, as well as 11 Russian subnational Arctic regions, completed the data collection template. Data on acute HCV infection during 2014 was available from three Arctic countries and all Russian Arctic regions (rate range 0/100,000 population in Greenland, as well as Nenets and Chukotka Automous Okrugs (Russian subnational Arctic regions) to 3.7/100,000 in the Russian Republic of Komi). The rate of people with chronic/undifferentiated HCV infection in 2014 ranged from 0/100,000 in Greenland to 171.2/100,000 in Alaska. In most countries/regions, the majority of HCV-infected people were male and aged 19-64 years. Differences in surveillance methods preclude direct comparisons of HCV surveillance data between Arctic countries/regions. Our data can inform future efforts to develop standardised approaches to HCV surveillance in the Arctic countries/regions by identifying similarities/differences between the surveillance data collected.

Lyme Borreliosis in Finland, 1995-2014.

We investigated the epidemiology of Lyme borreliosis (LB) in Finland for the period 1995-2014 by using data from 3 different healthcare registers. We reviewed data on disseminated LB cases from the National Infectious Diseases Register (21,051 cases) and the National Hospital Discharge Register (10,402 cases) and data on primary LB (erythema migrans) cases from the Register for Primary Health Care Visits (11,793 cases). Incidence of microbiologically confirmed disseminated LB cases increased from 7/100,000 population in 1995 to 31/100,000 in 2014. Incidence of primary LB cases increased from 44/100,000 in 2011 to 61/100,000 in 2014. Overall, cases occurred predominantly in women, and we observed a bimodal age distribution in all 3 registers. Our results clearly demonstrate that the geographic distribution of LB has expanded in Finland and underscore the importance of LB as an increasing public health concern in Finland and in northern Europe in general.

A controlled survey of less typical long-term consequences after an extensive waterborne epidemic.

BACKGROUND: Extensive backflow of treated wastewater caused household water contamination in a Finnish town in 2007. The drinking water of 9 500 residents became heavily polluted with faecal microbes, resulting in a large gastroenteritis epidemic. Cases of reactive arthritis, milder joint symptoms and prolonged gastrointestinal symptoms were observed after the outbreak. A follow-up survey was performed to study less familiar long-term health consequences within a year from the outbreak. METHODS: The contaminated group comprised a sample of residents of the area with polluted water supply (N = 323) and the control group a sample of residents in a nearby municipality (N = 186). The presence of 20 general symptoms or complaints was inquired by a mail survey. Quarterly prevalence of each symptom or complaint was measured. Twelve of these proceeded to further analysis. RESULTS: The response rate was 53% (323/615) in the contaminated group and 54% (186/343) in the control group. Rash, eye irritation, heartburn and weight loss were more prevalent in the contaminated group during the first year quarter. In the last year quarter, only eye irritation was significantly more common in the contaminated group. CONCLUSION: The excess prevalence of four complaints at the first year quarter can be explained by acute gastroenteritis or intensive water chlorination. The excess prevalence of eye irritation at the fourth year quarter cannot be explained by chlorination anymore but might be a sign of co-existing reactive joint disease. In general, long-term consequences of the outbreak can be considered minor in terms of the surveyed symptoms or complaints.

Epidemiology of hepatitis B infection in Finland: Implications for immunisation policy.

OBJECTIVES: We describe the current epidemiology of acute and chronic hepatitis B infections in Finland. We estimate the total incidence of chronic hepatitis B following from the current incidence of acute infections and the influx of chronic carriers of hepatitis B associated with net immigration. We evaluate the incidence of hepatitis B infections preventable by a universal vaccination programme among infants. METHODS: We analysed hepatitis B cases reported to the National Infectious Disease Register during 2004-2012 and used pre-developed methods to adjust for acute asymptomatic infections. We estimated the projected incidence of chronic infection by applying age-specific risks of chronic infection to the estimated incidence of acute infection. We estimated the influx of chronic carriers associated with immigration by utilising data on immigration during 2004-2012 and the WHO regional estimates of carriage prevalence. RESULTS: The estimated incidence of acute hepatitis B infection in Finland, adjusted for asymptomatic infections, was 1.67 per 100,000 per year (95% Crl 1.43-1.94) which is 4.2-fold to the register-based incidence. The estimated lifetime risks of acute and chronic hepatitis B infections were 0.13% and 0.01%, respectively. We estimated that annually seven new chronic infections would result from infections acquired in Finland. These new chronic infections accounted for 1.2% of the total incidence of chronic infections. We estimated that eventually three chronic infections per year would be potentially preventable by a universal infant vaccination programme. CONCLUSIONS: Partly due to the fact that hepatitis B infections in neonates and in children are rare, a very limited number of chronic hepatitis B infections resulted from infection acquired within the country. A vast majority of chronic hepatitis B infections occurred among foreign-born persons and were therefore not preventable by a universal infant immunisation programme in Finland. Even with a targeted immunisation programme, the incidence of hepatitis B infection has remained low.

Association between heavy precipitation events and waterborne outbreaks in four Nordic countries, 1992-2012.

We conducted a matched case-control study to examine the association between heavy precipitation events and waterborne outbreaks (WBOs) by linking epidemiological registries and meteorological data between 1992 and 2012 in four Nordic countries. Heavy precipitation events were defined by above average (exceedance) daily rainfall during the preceding weeks using local references. We performed conditional logistic regression using the four previous years as the controls. Among WBOs with known onset date (n = 89), exceedance rainfall on two or more days was associated with occurrence of outbreak, OR = 3.06 (95% CI 1.38-6.78), compared to zero exceedance days. Stratified analyses revealed a significant association with single household water supplies, ground water as source and for outbreaks occurring during spring and summer. These findings were reproduced in analyses including all WBOs with known outbreak month (n = 186). The vulnerability of single households to WBOs associated with heavy precipitation events should be communicated to homeowners and implemented into future policy planning to reduce the risk of waterborne illness.

Respiratory diphtheria in an asylum seeker from Afghanistan arriving to Finland via Sweden, December 2015.

In December 2015, an asylum seeker originating from Afghanistan was diagnosed with respiratory diphtheria in Finland. He arrived in Finland from Sweden where he had already been clinically suspected and tested for diphtheria. Corynebacterium diphtheriae was confirmed in Sweden and shown to be genotypically and phenotypically toxigenic. The event highlights the importance of early case detection, rapid communication within the country and internationally as well as preparedness plans of diphtheria antitoxin availability.

Siberian subtype tick-borne encephalitis virus in Ixodes ricinus in a newly emerged focus, Finland.

The first tick-borne encephalitis (TBE) cases in Kotka, Finland appeared in 2010. Altogether ten human cases have been diagnosed by 2014. Four had long-lasting sequelae. We collected 195 Ixodes ricinus ticks, nine rodents, and eleven shrews from the archipelago of Kotka in 2011. Three Siberian subtype TBE virus (TBEV) strains were isolated from the ticks and three mammals were positive for TBEV antibodies. The archipelago of Kotka is a newly emerged TBE focus of Siberian subtype TBEV circulating notably in I. ricinus. The patients had on average longer hospitalization than reported for the European subtype infection.

Surveillance of endemic foci of tick-borne encephalitis in Finland 1995-2013: evidence of emergence of new foci.

The geographical risk areas for tick-borne encephalitis (TBE) in Finland remained the same until the beginning of the 21st century, but a considerable geographical expansion has been observed in the past 10 years. In order to support public health measures, the present study describes the number of laboratory-confirmed TBE cases and laboratory tests conducted and the associated trends by hospital district, with a particular emphasis on the suspected geographical risk areas. An additional investigation was conducted on 1,957 clinical serum samples throughout the country taken from patients with neurological symptoms to screen for undiagnosed TBE cases. This study identified new TBE foci in Finland, reflecting the spread of the disease into new areas. Even in the most endemic municipalities, transmission of TBE to humans occurred in very specific and often small foci. The number of antibody tests for TBE virus more than doubled (an increase by 105%) between 2007 and 2013. Analysis of the number of tests also revealed areas in which the awareness of clinicians may be suboptimal at present. However, it appears that underdiagnosis of neuroinvasive TBE is not common.

[Tick-borne encephalitis in Finland from 2010 to 2012]. / Puutiaisaivokuume Suomessa 2010-2012.

The frequency of occurrence of tick-borne encephalitis has increased significantly in Europe and Finland during the past twenty years. There has been a suspicion that the Finnish cases have at least over the last few years been more severe than described in the literature. We analyzed the approximately one hundred cases of tick-borne encephalitis diagnosed in Finland over a three-year period. In two thirds of the patients general physical condition deteriorated clearly, the disease caused permanent disability or the patients required supportive measures in the hospital, such as ventilator therapy. Assessment of the course and severity of the disease would seem to be impossible on the basis of individual symptoms, such as duration of fever.

Meningococcal serogroup Y disease in Europe: Continuation of high importance in some European regions in 2013.

Neisseria meningitidis or meningococcus is divided into 12 distinct serogroups of which A, B, C, W, X, and Y are medically most important and cause health problems in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Globally, serogroup A has been prevalent in the African "meningitis belt" whereas serogroup B and C have predominated in Europe. In a paper published earlier in this journal (1) , an increase in serogroup Y invasive meningococcal disease (IMD) in some European countries was reported based on the epidemiological data for 2010, 2011 and 2012. Here, we report additional data from 30 European countries indicating that high or increased serogroup Y disease levels have continued in 2013 in certain regions of Europe. In the Western and Central Europe, there were no major changes in the proportion of serogroup Y IMD cases in 2013 compared to 2012. In the Scandinavian countries, proportion of serogroup Y disease remained high, ranging from 26% to 51% in 2013. This was in contrast to Baltic, Eastern and most Southern European countries, where the proportion of serogroup Y IMD was low similarly to previous years. For the last 2 decades, the mean age of patients affected by serogroup Y was 41 y for 7 countries from which data was available and 50% of cases were in patients aged 45 to 88 y. The age distribution of serogroup Y was bimodal and did not change significantly despite the increase of the total number and the proportion of serogroup Y IMD in some European regions.

Genome analysis of Campylobacter jejuni strains isolated from a waterborne outbreak.

BACKGROUND: Waterborne Campylobacter jejuni outbreaks are common in the Nordic countries, and PFGE (pulsed field gel electrophoresis) remains the genotyping method of choice in outbreak investigations. However, PFGE cannot assess the clonal relationship between isolates, leading to difficulties in molecular epidemiological investigations. Here, we explored the applicability of whole genome sequencing to outbreak investigation by re-analysing three C. jejuni strains (one isolated from water and two from patients) from an earlier resolved Finnish waterborne outbreak from the year 2000. RESULTS: One of the patient strains had the same PFGE profile, as well as an identical overall gene synteny and three polymorphisms in comparison with the water strain. However, the other patient isolate, which showed only minor differences in the PFGE pattern relative to the water strain, harboured several polymorphisms as well as rearrangements in the integrated element CJIE2. We reconstructed the genealogy of these strains with ClonalFrame including in the analysis four C. jejuni isolated from chicken in 2012 having the same PFGE profile and sequence type as the outbreak strains. The three outbreak strains exhibited a paraphyletic relationship, implying that the drinking water from 2000 was probably contaminated with at least two different, but related, C. jejuni strains. CONCLUSIONS: Our results emphasize the capability of whole genome sequencing to unambiguously resolve the clonal relationship between isolates of C. jejuni in an outbreak situation and evaluate the diversity of the C. jejuni population.

Novel microbiological and spatial statistical methods to improve strength of epidemiological evidence in a community-wide waterborne outbreak.

Failures in the drinking water distribution system cause gastrointestinal outbreaks with multiple pathogens. A water distribution pipe breakage caused a community-wide waterborne outbreak in Vuorela, Finland, July 2012. We investigated this outbreak with advanced epidemiological and microbiological methods. A total of 473/2931 inhabitants (16%) responded to a web-based questionnaire. Water and patient samples were subjected to analysis of multiple microbial targets, molecular typing and microbial community analysis. Spatial analysis on the water distribution network was done and we applied a spatial logistic regression model. The course of the illness was mild. Drinking untreated tap water from the defined outbreak area was significantly associated with illness (RR 5.6, 95% CI 1.9-16.4) increasing in a dose response manner. The closer a person lived to the water distribution breakage point, the higher the risk of becoming ill. Sapovirus, enterovirus, single Campylobacter jejuni and EHEC O157:H7 findings as well as virulence genes for EPEC, EAEC and EHEC pathogroups were detected by molecular or culture methods from the faecal samples of the patients. EPEC, EAEC and EHEC virulence genes and faecal indicator bacteria were also detected in water samples. Microbial community sequencing of contaminated tap water revealed abundance of Arcobacter species. The polyphasic approach improved the understanding of the source of the infections, and aided to define the extent and magnitude of this outbreak.

Detection of Francisella tularensis in voles in Finland.

Francisella tularensis is a highly virulent intracellular bacterium causing the zoonotic disease tularemia. It recurrently causes human and animal outbreaks in northern Europe, including Finland. Although F. tularensis infects several mammal species, only rodents and lagomorphs seem to have importance in its ecology. Peak densities of rodent populations may trigger tularemia outbreaks in humans; however, it is still unclear to which extent rodents or other small mammals maintain F. tularensis in nature. The main objective of this study was to obtain information about the occurrence of F. tularensis in small mammals in Finland. We snap-trapped 547 wild small mammals representing 11 species at 14 locations around Finland during 6 years and screened them for the presence of F. tularensis DNA using PCR analysis. High copy number of F. tularensis-specific DNA was detected in tissue samples of five field voles (Microtus agrestis) originating from one location and 2 years. According to DNA sequences of the bacterial 23S ribosomal RNA gene amplified from F. tularensis-infected voles, the infecting agent belongs to the subspecies holarctica. To find out the optimal tissue for tularemia screening in voles, we compared the amounts of F. tularensis DNA in lungs, liver, spleen, and kidney of the infected animals. F. tularensis DNA was detectable in high levels in all four organs except for one animal, whose kidney was F. tularensis DNA-negative. Thus, at least liver, lung, and spleen seem suitable for F. tularensis screening in voles. Thus, liver, lung, and spleen all seem suitable for F. tularensis screening in voles. In conclusion, field voles can be heavily infected with F. tularensis subsp. holarctica and thus potentially serve as the source of infection in humans and other mammals.

Meningococcal serogroup Y emergence in Europe: high importance in some European regions in 2012.

Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 and 2011 from various European countries previously published in this journal. (1)(,) (2) Here, data from 33 European countries is reported indicating that the emergence of serogroup Y continued in 2012 in various regions of Europe, especially in Scandinavia, while in Eastern and South-Eastern Europe the importance of serogroup Y remained low.

The duration of gastrointestinal and joint symptoms after a large waterborne outbreak of gastroenteritis in Finland in 2007--a questionnaire-based 15-month follow-up study.

An extensive drinking water-associated gastroenteritis outbreak took place in the town of Nokia in Southern Finland in 2007. 53% of the exposed came down with gastroenteritis and 7% had arthritis-like symptoms (joint swelling, redness, warmth or pain in movement) according to a population-based questionnaire study at 8 weeks after the incident. Campylobacter and norovirus were the main pathogens. A follow-up questionnaire study was carried out 15 months after the outbreak to evaluate the duration of gastrointestinal and joint symptoms. 323 residents of the original contaminated area were included. The response rate was 53%. Participants were inquired about having gastroenteritis during the outbreak and the duration of symptoms. Of those with gastroenteritis, 43% reported loose stools and abdominal pain or distension after the acute disease. The prevalence of symptoms declined promptly during the first 3 months but at 15 months, 11% reported continuing symptoms. 32% of the respondents with gastroenteritis reported subsequent arthritis-like symptoms. The disappearance of arthritis-like symptoms was more gradual and they levelled off only after 5 months. 19% showed symptoms at 15 months. Prolonged gastrointestinal symptoms correlated to prolonged arthritis-like symptoms. High proportion of respondents continued to have arthritis-like symptoms at 15 months after the epidemic. The gastrointestinal symptoms, instead, had declined to a low level.

[A domestic human case of hepatitis E in Finland]. / Suomalaismiehen kotoperäinen E-hepatiittitartunta.

We describe the first verified domestic HEV case in a previously healthy 53-year-old man who presented a three-day history of upper stomach pain, nausea, fever, arthralgia and fatigue. At the first phase laboratory tests revealed high levels of AST and ALT and at the second phase high levels of bilirubin. Serum was positive for anti-HEV IgM and for HEV RNA confirming the diagnosis of acute hepatitis E. The HEV was genotype 3. Jaundice resolved in three months. In nonendemic areas autochthonous hepatitis E is more common than previously recognized and is possible in patients with acute hepatitis.

Excess healthcare costs of a large waterborne outbreak in Finland.

BACKGROUND: The economic effects of waterborne outbreaks have rarely been reported. A large waterborne outbreak occurred in the town of Nokia in Finland in 2007 with half of the population in the contaminated area suffering from gastroenteritis. We studied the healthcare costs of this outbreak. METHODS: Healthcare costs were studied using register data from the Nokia Health Care Centre, data collected in the regional university hospital, and data from laboratory register on stool samples. RESULTS: Total excess healthcare costs were EUR 354,496, which is approximately EUR 10 per resident of Nokia. There were 2052 excess visits because of gastroenteritis in Nokia Health Care Centre, 403 excess episodes in the university hospital, and altogether over 2000 excess stool samples due to the outbreak. Care in the Nokia Health Care Centre accounted for 44% and care in the university hospital for 42% of the excess healthcare costs while stool samples accounted for only 10%. CONCLUSIONS: Despite the high morbidity, the total cost was low because most patients had a relatively mild illness. The situation would have been worse if the microbes involved had been more hazardous or if the financial situation of the community had been worse. Prevention of waterborne outbreaks is important, as there is a risk of severe short- and long-term health effects and substantial health-economic costs.

Clostridium difficile contamination of public tap water distribution system during a waterborne outbreak in Finland.

AIMS: In November through December 2007, the drinking water distribution system in the town of Nokia, Finland, was contaminated with treated sewage effluent that resulted in a large gastroenteritis outbreak in the community. The aim of the present study was to investigate if the contaminated water in this outbreak was also a potential source of Clostridium difficile infections. METHODS: Samples from the contaminated tap water and treated sewage effluent were collected. Stool samples from a portion of patients that fell ill during the outbreak were examined for C. difficile. PCR ribotyping was performed on toxin positive C. difficile isolates and the genetic profiles of the water and patient isolates were compared. RESULTS: Twelve toxin-positive C. difficile isolates were found in water samples: five from contaminated tap water and seven from treated sewage effluent. Among these, four and five distinct PCR ribotype profiles were identified, respectively. Four PCR ribotype profiles were found among nine human faecal C. difficile isolates. Two isolates, one from tap water and one from a patient, had an indistinguishable PCR ribotype profile. CONCLUSIONS: Our findings demonstrate for the first time C. difficile contamination of a tap water distribution system and waterborne transmission of toxigenic C. difficile seems possible.