Whole genome analysis of Mycobacterium tuberculosis isolates from recurrent episodes of tuberculosis, Finland, 1995-2013.

Recurrent tuberculosis (TB) is caused by an endogenous re-activation of the same strain of Mycobacterium tuberculosis (relapse) or exogenous infection with a new strain (re-infection). Recurrence of TB in Finland was analysed in a population-based, 19-year study, and genotyping was used to define relapse and re-infection. The M. tuberculosis isolates from patients with suspected relapse were further analysed by whole genome sequencing (WGS) to determine the number and type of mutations occurring in the bacterial genome between the first and second disease episodes. In addition, publicly available tools (PhyResSE and SpolPred) were used to predict drug resistance and spoligotype profile from the WGS data. Of the 8299 notified TB cases, 48 (0.6%) patients had episodes classified as recurrent. Forty-two patients had more than one culture-confirmed TB episode, and isolates from two episodes in 21 patients were available for genotyping. In 18 patients, the M. tuberculosis isolates obtained from the first and second TB episodes had identical spoligotypes. The WGS analysis of the 36 M. tuberculosis isolates from the 18 suspected relapse patients (average time between isolates 2.8 years) revealed 0 to 38 single nucleotide polymorphisms (median 1, mean 3.78) between the first and second isolate. There seemed to be no direct relation between the number of years between the two isolates, or treatment outcome, and the number of single nucleotide polymorphisms. The results suggest that the mutation rate may depend on multiple host-, strain- and treatment-related factors.

Tuberculosis in immigrants in Finland, 1995-2013.

Increasing immigration from high tuberculosis (TB) incidence countries is a challenge for surveillance and control in Finland. Here, we describe the epidemiology of TB in immigrants by using national surveillance data. During 1995-2013, 7030 (84·7%) native and 1199 (14·4%) immigrant cases were identified. The proportion of immigrant cases increased from 5·8% in 1995 to 32·1% in 2013, consistent with increasing immigrant population (2·1-5·6%) and decreasing incidence of TB in the native population (from 12·1 to 3·5/100 000). TB cases in immigrants were significantly younger, more often female, and had extrapulmonary TB more often than native cases (P < 0·01 for all comparisons); multidrug resistance was also more common in immigrants than natives (P < 0·01). Immigrant cases were born in 82 different countries; most commonly in Somalia and the former Soviet Union/Russia. During 2008-2013, 433 Mycobacterium tuberculosis isolates from immigrants were submitted for spoligotyping; 10 different clades were identified. Clades were similar to those found in the case's country of birth. Screening immigrants from high-incidence countries and raising awareness of common characteristics and symptoms of TB is important to ensure early diagnosis and to prevent transmission.

Genotypic characterization and historical perspective of Mycobacterium tuberculosis among older and younger Finns, 2008-2011.

The Mycobacterium tuberculosis genotypes obtained from elderly Finns were assessed and compared with those obtained from younger Finns to comprehend the epidemiology of tuberculosis (TB) in Finland. From 2008 to 2011, a total of 1021 M. tuberculosis isolates were characterized by spoligotyping and 15-locus mycobacterial interspersed repetitive units-variable number tandem repeat typing. In total, 733 Finnish-born cases were included in the study, of which 466 (64%) were born before 1945 (older Finns). Of these, 63 (14%) shared an M. tuberculosis genotype with foreign-born or younger Finnish cases (born after 1945), and 59 (13%) shared a genotype with older Finnish cases. Eighty-five per cent had a unique genotypic profile while 70% belonged to T or Haarlem families, suggesting that ongoing transmission is infrequent among young and elderly Finns. Simultaneous reactivation of TB among older Finns was the most likely cause for clustering. As most isolates belonged to Haarlem or T, Finland was most likely affected by a similar TB epidemic at the beginning of the twentieth century as that seen in Sweden and Norway. Younger Finns were significantly more likely to be clustered (56% versus 27%, p<0.001), have pulmonary TB (87% versus 71%, p<0.001) and to be sputum smear positive (57% versus 48%, p<0.05) indicating that the risk of TB transmission from younger Finns is likely to be larger than from older Finns. The M. tuberculosis isolates from elderly Finns were associated with dominant lineages of the early twentieth century and differed from the heterogeneous lineages found among younger TB patients. Additionally, younger TB patients were more likely to transmit TB than elderly Finns.

Population-based burden of bloodstream infections in Finland.

Bloodstream infections (BSI) are a major cause of mortality, morbidity and medical cost, but few population-based studies have concomitantly evaluated BSI incidence and mortality. Data on BSI episodes reported to national, population-based surveillance by all clinical microbiology laboratories in Finland during 2004-07 were linked to vital statistics. Age-, sex and microbe-specific incidence and mortality rates were calculated. During 2004-07, 33 473 BSI episodes were identified; BSI incidence increased from 147 to 168 per 100 000 population (average annual increase, 4.4%; p <0.001). Rates were highest among persons ≥65 years and <1 year, and higher among male patients than female patients (166 versus 152 per 100 000). The most common aetiologies were Escherichia coli (27%) and Staphylococcus aureus (13%). Among male patients, 52% of BSI were caused by gram-positive bacteria compared with 42% among female patients (p <0.001). The overall 30-day case-fatality was 13%. Of the deaths, 32% occurred within 2 days, 70% were among people aged 65 years or more and 33% were caused by E. coli or S. aureus infections. The BSI mortality rate increased from 19 to 22 per 100 000 (average annual increase: 4.0%, p 0.01). Among people aged 25 years or more, the mortality rate was 1.4-fold higher in men than women (34 versus 25 per 100 000 population). Overall excess annual mortality from BSI in the population was 18 per 100 000. The substantial BSI burden among the elderly and among adult men highlights the need for developing and implementing effective interventions, particularly for BSI caused by E. coli and S. aureus. One-third of BSI deaths occurred early, emphasizing the importance of early identification and treatment.

Two cases of food-borne botulism in Finland caused by conserved olives, October 2011.

In October 2011 in Finland, two persons fell ill with symptoms compatible with botulism after having eaten conserved olives stuffed with almonds. One of these two died. Clostridium botulinum type B and its neurotoxin were detected in the implicated olives by PCR and mouse bioassay, respectively. The olives were traced back to an Italian manufacturer and withdrawn from the market. The public and other European countries were informed through media and Europe-wide notifications.

An extensive gastroenteritis outbreak after drinking-water contamination by sewage effluent, Finland.

An inappropriate cross-connection between sewage- and drinking-water pipelines contaminated tap water in a Finnish town, resulting in an extensive waterborne gastroenteritis outbreak in this developed country. According to a database and a line-list, altogether 1222 subjects sought medical care as a result of this exposure. Seven pathogens were found in patient samples of those who sought treatment. To establish the true disease burden from this exposure, we undertook a population-based questionnaire investigation with a control population, infrequently used to study waterborne outbreaks. The study covered three areas, contaminated and uncontaminated parts of the town and a control town. An estimated 8453 residents fell ill during the outbreak, the excess number of illnesses being 6501. Attack rates were 53% [95% confidence interval (CI) 49.5-56.4] in the contaminated area, 15.6% (95% CI 13.1-18.5) in the uncontaminated area and 6.5% (95% CI 4.8-8.8) in the control population. Using a control population allowed us to differentiate baseline morbidity from the observed morbidity caused by the water contamination, thus enabling a more accurate estimate of the disease burden of this outbreak.

Healthcare-associated infections in Finnish acute care hospitals: a national prevalence survey, 2005.

The objectives of the first national prevalence survey on healthcare-associated infections (HAIs) in Finland were to assess the extent of HAI, distribution of HAI types, causative organisms, prevalence of predisposing factors and use of antimicrobial agents. The voluntary survey was performed during February-March 2005 in 30 hospitals, including tertiary and secondary care hospitals and 10 (25%) other acute care hospitals in the country. The overall prevalence of HAI was 8.5% (703/8234). Surgical site infection was the most common HAI (29%), followed by urinary tract infection (19%) and primary bloodstream infection or clinical sepsis (17%). HAI prevalence was higher in males, among intensive care and surgical patients, and increased with age and severity of underlying illness. The most common causative organisms, identified in 56% (398/703) of patients with HAIs, were Escherichia coli (13%), Staphylococcus aureus (10%) and Enterococcus faecalis (9%). HAIs caused by multi-resistant microbes were rare (N = 6). A total of 122 patients were treated in contact isolation due to the carriage of multi-resistant microbes. At the time of the survey, 19% of patients had a urinary catheter, 6% central venous line and 1% were ventilated. Antimicrobial treatment was given to 39% of patients. These results can be used for prioritising infection control measures and planning more detailed incidence surveillance of HAI. The survey was a useful tool to increase the awareness of HAI in participating hospitals and to train infection control staff in diagnosing HAIs.

Molecular genetics of drug-resistant Mycobacterium tuberculosis isolates in Finland, 1995-2004.

SETTING: Modern molecular methods help us to understand the transmission and epidemiology of Mycobacterium tuberculosis. OBJECTIVE: To analyse the molecular epidemiology of drug-resistant tuberculosis (TB), and to characterise isoniazid (INH) and rifampicin (RMP) resistance conferring mutations in Finland during 1995-2004. DESIGN: A total of 3959 new M. tuberculosis isolates underwent drug susceptibility testing; all phenotypically resistant isolates were genotyped by IS6110 restriction fragment length polymorphism and spoligotyping if necessary. INH- and/or RMP-resistant isolates were sequenced for their resistance associated genes, katG locus 315 and rpoB, respectively. RESULT: Of the 3959 isolates tested (92.4% of culture-positive cases), 183 (4.6%) were resistant to at least one first-line anti-tuberculosis drug; 14 (0.4%) isolates were multidrug-resistant. Thirty-seven (20.4%) resistant isolates belonged to 17 clusters, and the largest cluster included four isolates. The Beijing family genotype accounted for 8.8% (16 isolates) of all drug-resistant isolates. A Ser315Thr mutation in katG was found in 46.7% (56 isolates) of the INH-resistant isolates and rpoB was mutated in 85.7% (18 isolates) of the isolates resistant to RMP. CONCLUSION: Transmission of drug-resistant TB is rare in Finland, especially between indigenous and immigrant populations. Screening of mutations that confer INH and RMP resistance seems to be feasible if risk factors for multidrug resistance exist.

Increase in bloodstream infections in Finland, 1995-2002.

A national, population-based laboratory surveillance of bloodstream infections (BSI) in Finland was performed. Blood-culturing rates were determined from data from clinical microbiology laboratories and trends in rates were evaluated using Poisson regression. During 1995-2002, 51,510 cases of BSI were notified; the annual incidence increased from 104 to 145 cases/100,000 (40%). Rates increased in all age groups but persons aged >or= 75 years accounted for 28% of cases and showed the largest rate increase. Escherichia coli, coagulase-negative staphylococci, Staphylococcus aureus and Streptococcus pneumoniae accounted for 58% of isolates and their relative proportions were unchanged over time. The annual blood-culturing rate increased by one-third during the study period but the number of BSI detected per blood cultures remained unchanged. Regional BSI incidence was significantly associated with blood-culturing rates. We conclude that the increase in BSI rates may have been due to more frequent blood culturing but was not associated with changes in the reporting system or aetiology of BSI.

Predictors of death from severe pneumonia among children 2-59 months old hospitalized in Bohol, Philippines: implications for referral criteria at a first-level health facility.

OBJECTIVE: To determine predictors of death among children 2-59 months old admitted to hospital with severe pneumonia. METHODS: Prospective observational study from April 1994 to May 2000 to investigate serious infections in children less than 5 years old admitted to a tertiary care government hospital in a rural province in central Philippines. The quality of clinical and laboratory work was monitored. The WHO classification for severe pneumonia was used for patient enrolment. RESULTS: There were 1249 children with severe pneumonia and no CNS infection. Thirty children died. Using univariate analysis, the following factors were significantly associated with death: age 2-5 months, dense infiltrates on chest radiography and presence of definite bacterial pathogens in the blood. Stepwise logistic regression analysis revealed the following independent predictors of death: age 2-5 months, weight for age z-score less than -2 SD, dense infiltrates on chest radiography and definite pathogens isolated in the blood. When the results of chest radiographs and blood cultures were not included to mimic facilities available at first-level facilities, age 2-5 months and weight for age z-score less than -2 SD remained independent predictors of death. CONCLUSION: When resources are limited, children with lower chest wall indrawing (severe pneumonia) who are 2-5 months old or moderately to severely malnourished should be referred for immediate higher-level care.

A randomized study on donor immunization with tetanus-diphtheria, Haemophilus influenzae type b and inactivated poliovirus vaccines to improve the recipient responses to the same vaccines after allogeneic bone marrow transplantation.

The HLA-identical sibling donors of 111 bone marrow transplantation (BMT) recipients were randomised to receive or not to receive tetanus-diphtheria (T-d), Haemophilus influenzae type b (Hib), and inactivated poliovirus (IPV) vaccines 2-10 weeks before BM harvest. Fifty-three (DV+ group) recipients received the graft from a vaccinated donor and 58 (DV- group) from an unvaccinated donor. All recipients were vaccinated with the T-d, Hib and IPV vaccines at 3, 6 and 12 months after BMT. Diphtheria and Hib antibody concentrations were consistently higher in the DV+ than in the DV- group from 6 months post transplantation onwards. The differences were significant at 6 and 13 months for diphtheria and at 12 months for Hib antibody concentrations. Tetanus, PV1, PV2 and PV3 antibody levels were similar in both groups. Patients transplanted from donors with high tetanus, diphtheria and Hib antibody concentrations had higher respective antibody concentrations after BMT than those transplanted from donors with low antibody concentrations. Especially patients whose donors have low-specific antibody concentrations may benefit from donor vaccination with protein and conjugate vaccines.

Serious community-acquired neonatal infections in rural Southeast Asia (Bohol Island, Philippines).

OBJECTIVE: To determine the bacterial etiology, clinical presentation and risk factors for outcome of serious community-acquired infections in young infants. STUDY DESIGN: Infants younger than 60 days, admitted for severe pneumonia or suspected sepsis/meningitis were prospectively evaluated using complete blood count, blood culture, chest radiograph, cerebrospinal fluid (CSF) culture in suspected meningitis. chi2 or Fisher's exact test and stepwise logistic regression were used for analysis. RESULTS: Thirty-four of 767 enrolled infants had a positive blood or CSF culture. Gram-negative bacteria were more frequent than Gram positive: overall (P=0.004), in those below 7 days of age (P=0.002) and among home deliveries (P=0.012). Case fatality rates were higher among infants below 1 week old (OR 4.14, P<0.001), those with dense (OR 2.92, P<0.001) or diffuse radiographic infiltrates (OR 2.79, P=0.003). CONCLUSIONS: Gram-negative enteric bacteria are the predominant causes of community-acquired infections in Filipino infants below 2 months old. Age below 7 days and radiographic pneumonia predicted death.

Pneumococcal disease surveillance in Europe.

Pneumococcal disease (Pnc) is responsible for invasive pneumococcal disease (IPD)--mainly meningitis and septicaemia--and is an infection of public health importance in Europe. Following the licensure of an effective conjugate vaccine (PCV) in Europe, several European countries, including France, Germany, the Netherlands, Norway, Spain and the United Kingdom, are introducing universal Pnc childhood immunisation programmes. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed in late 2003 to each of the current 25 European Union member states as well as Norway and Switzerland to get a clearer picture of national surveillance for invasive pneumococcal disease (IPD) in Europe. All respondents were contacted in 2006 and asked to provide an update to the questionnaire. Twenty two of the 27 countries targeted completed and returned the questionnaire. Four of the 22 responding countries have no reporting requirement for IPD. Eighteen countries reported a total of 27 national surveillance systems. Case definitions employed in these systems differed. Fourteen of the 18 countries reported collection of IPD strains to a single reference lab for serotyping and in 12 countries to a single laboratory for susceptibility testing. Thirteen countries undertook laboratory quality assurance. Information on age and sex were widely collected, but only 11/27 systems collected information on pneumococcal polysaccharide vaccine status, while 5/27 systems collected information on pneumococcal conjugate vaccine status. The incidence of IPD reported in each of the 18 countries ranged from 0.4 to 20/100,000 in the general population, with a total of 23,470 IPD cases reported over a 12 month period. Surveillance for IPD in Europe is very heterogeneous. Several countries lack surveillance systems. Large differences in reported disease incidence may reflect both true differences, and also variations in patient and healthcare factors, including surveillance. If IPD surveillance in Europe can be strengthened, countries will be able to make informed decisions regarding the introduction of new pneumococcal vaccines and also to monitor and compare the impact and effectiveness of new programmes.

Pneumococcal disease surveillance in Europe.

Pneumococcal disease (Pnc) is responsible for invasive pneumococcal disease (IPD) - mainly meningitis and septicaemia - and is an infection of public health importance in Europe. Following the licensure of an effective conjugate vaccine (PCV) in Europe, several European countries, including France, Germany, the Netherlands, Norway, Spain and the United Kingdom, are introducing universal Pnc childhood immunisation programmes. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed in late 2003 to each of the current 25 European Union member states as well as Norway and Switzerland to get a clearer picture of national surveillance for invasive pneumococcal disease (IPD) in Europe. All respondents were contacted in 2006 and asked to provide an update to the questionnaire. Twenty two of the 27 countries targeted completed and returned the questionnaire. Four of the 22 responding countries have no reporting requirement for IPD. Eighteen countries reported a total of 27 national surveillance systems. Case definitions employed in these systems differed. Fourteen of the 18 countries reported collection of IPD strains to a single reference lab for serotyping and in 12 countries to a single laboratory for susceptibility testing. Thirteen countries undertook laboratory quality assurance. Information on age and sex were widely collected, but only 11/27 systems collected information on pneumococcal polysaccharide vaccine status, while 5/27 systems collected information on pneumococcal conjugate vaccine status. The incidence of IPD reported in each of the 18 countries ranged from 0.4 to 20/100 000 in the general population, with a total of 23 470 IPD cases reported over a 12 month period. Surveillance for IPD in Europe is very heterogeneous. Several countries lack surveillance systems. Large differences in reported disease incidence may reflect both true differences, and also variations in patient and healthcare factors, including surveillance. If IPD surveillance in Europe can be strengthened, countries will be able to make informed decisions regarding the introduction of new pneumococcal vaccines and also to monitor and compare the impact and effectiveness of new programmes.

Pneumococcal vaccination policy in Europe.

Infection due to Streptococcus pneumoniae (Pneumococcus) (Pnc) is an important cause of invasive clinical manifestations such as meningitis, septicaemia and pneumonia, particularly in young children and the elderly. A 23-valent polysaccharide Pnc vaccine (PPV) has been available for many years and a 7-valent conjugate Pnc vaccine (PCV) has been licensed since 2001 in Europe. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed to all 15 EU member states, Switzerland, Norway and the 10 accession countries in 2003 to ascertain current pneumococcal vaccination policy. Twenty three of the 27 target countries, constituting the current European Union (plus Norway and Switzerland), completed the questionnaire. PPV was licensed in 22 of the 23 responding countries and was in the official recommendations of 21. In all the 20/21 countries for which information was available, risk groups at higher risk of infection were targeted. The number of risk groups targeted ranged from one to 12. At least 17 countries recommend that PPV be administered to all those >65 years of age (in three countries, to those over 60 years of age). Thirteen countries had developed national recommendations for PCV in 2003. No country recommended mass infant immunisation at that time, but rather targeted specific risk groups (between 1 and 11), particularly children with asplenia (n=13) and HIV infection (n=12). PCV use was restricted to children under two years of age in seven countries, and in four countries to children under five years of age. Future decisions on use of pneumococcal vaccines in Europe will be decided on the basis of several factors including: local disease burden; the predicted impact of any universal programme, particularly the importance of serotype replacement and herd immunity (indirect protection to the unvaccinated population); the effectiveness of reduced dose schedules, and vaccine cost. Indeed, at least one country, Luxembourg, has since implemented a universal infant PCV immunisation policy.

Shigatoxigenic Escherichia coli (STEC) infections in Finland during 1998-2002: a population-based surveillance study.

During 1998-2002, 124 microbiologically confirmed infections caused by shigatoxigenic Escherichia coli (STEC) were reported in Finland. Of these, 25 (20%) were associated with recent foreign travel. Temporal, geographical and type distribution of the domestically acquired infections (n=99) caused by strains of serogroup O157 (n=52) and non-O157 (n=47) were analysed further. The median age of the patients was 6.8 years (range 0.2-73.1 years). Of the index cases within 26 families, 71% were <5 years old. Family-related infections accounted for 49%, sporadic infections 39%, and 11% were associated with three clusters. Only strains of serogroup O157 carrying eae and stx 2 or its variants caused separate clusters. The incidence of STEC infections was at its highest (0.64/100000) in 1998. Since 1999 it has declined considerably (0.17/100000 in 2002). STEC infections occurred in 14 hospital districts, mostly (28%) in the Helsinki region. However, the incidence was highest (10.3) in northwest Finland.

High sensitivity for tuberculosis in a national integrated surveillance system in Finland.

Little is known about the sensitivity of surveillance for tuberculosis after integration of formerly dedicated tuberculosis surveillance and control into the general health care system, an integration which took place in Finland in 1987. We compared routine laboratory notifications to the National Infectious Disease Register (NIDR) for Mycobacterium tuberculosis from January 1, 1995, to December 31, 1996, with data collected independently from all laboratories offering M. tuberculosis culture, and with data from patient records. 1059 culture-positive cases were found. The overall sensitivity of the NIDR was 93 % (984/1059). The positive predictive value of a culture-positive case in the NIDR to be a true culture-confirmed case was 99%. For the culture-confirmed cases in the NIDR, one or more physician notification forms had been submitted for 89%. A highly sensitive notification system for culture-positive tuberculosis can be achieved in an integrated national infectious disease surveillance system based on laboratory notification.

A large outbreak of campylobacteriosis associated with a municipal water supply in Finland.

In August 1998, an outbreak of campylobacteriosis occurred in one municipality in northern Finland. A 10% random sample of residents (population 15 000) was selected through the National Population Registry for a survey conducted by using postal questionnaires. Cases were defined as residents of the municipality with onset of acute gastroenteritis from 1 to 20 August 1998. Of 1167 respondents (response rate 78%), 218 (18.7%) met the case definition. Drinking non-chlorinated municipal tap water was strongly associated with illness (OR 34.4). The estimated total number of ill persons was 2700. Campylobacter jejuni was isolated from stool samples of 45 (61%) out of 74 patients tested. All five isolates tested had indistinguishable PFGE patterns. Water samples were negative for campylobacter and coliforms. Epidemiological and environmental evidence suggested mains repair as the source of contamination. Non-chlorinated ground-water systems may be susceptible to contamination and can cause large outbreaks.

Trends and outcome of nosocomial and community-acquired bloodstream infections due to Staphylococcus aureus in Finland, 1995-2001.

In Finland, Staphylococcus aureus bloodstream infections are caused predominantly (>99%) by methicillin-sensitive strains. In this study, laboratory-based surveillance data on Staphylococcus aureus bloodstream infections occurring in Finland from 1995 to 2001 were analyzed. Preceding hospitalizations for all persons with Staphylococcus aureus bloodstream infections were obtained from the national hospital discharge registry, and data on outcome was obtained from the national population registry. An infection was defined as nosocomial when a positive blood culture was obtained more than 2 days after hospital admission or within 2 days of admission if there was a preceding hospital discharge within 7 days. A total of 5,045 cases were identified. The annual incidence of Staphylococcus aureus bloodstream infection rose by 55%, from 11 per 100,000 population in 1995 to 17 in 2001. The increase was detected in all adult age groups, though it was most distinct in patients >74 years of age. Nosocomial infections accounted for 51% of cases, a proportion that remained unchanged. The 28-day death-to-case ratio ranged from 1% in the age group 1-14 years to 33% in patients >74 years of age. The 28-day death-to-case ratios for nosocomial and community-acquired infections were 22% and 13%, respectively, and did not change over time. The increase in incidence among elderly persons resulted in an increase in the annual rate of mortality associated with Staphylococcus aureus bloodstream infections, from 2.6 to 4.2 deaths per 100,000 population per year. Staphylococcus aureus bloodstream infections are increasing in Finland, a country with a very low prevalence of methicillin resistance. While the increase may be due in part to increased reporting, it also reflects a growing population at risk, affected by such factors as high age and/or severe comorbidity.