Point-of-care testing of group A streptococcal antigen: performance evaluated by external quality assessment.

The purpose of this study was to evaluate the overall performance of rapid antigen detection (RAD) in group A streptococcus (GAS) in Finland by using the results of external quality assurance (EQA) samples. We also compared the performance of laboratory professionals to that of nursing professionals. Around 22,800 EQA results among a total of 383 laboratories and physician's offices were analysed. Vocational data on the personnel who carried out the tests were available for 10,088 EQA samples, 7,428 of which were tested by laboratory technicians and 2,531 by nursing staff. The best overall performance was found with GAS-negative samples: 99% of the reports were correct. In contrast, the overall performance was only 76% when the samples were weakly positive for GAS antigen. The laboratory technicians performed statistically significantly better than the nursing staff, with both strongly positive (correct results 98.9% vs. 95.1%, respectively; p<0.001) and weakly positive (79.3% vs. 65.3%, respectively; p<0.001) samples. With negative samples, no difference in performance between the laboratory and nursing staff was found (99.5% vs. 99.0%, respectively). The professional skills of the person performing the RAD test for GAS have a major impact on the sensitivity of the test. Based on the results of this study, we suggest that EQA-like artificial specimens could be used as a tool to improve and validate the quality of RAD testing in individual testing sites.

Acute infections, infection pressure, and atopy.

BACKGROUND: During the recent years, a new theory postulating that lack of early childhood infections would increase the prevalence rate of allergies has rapidly gained momentum. This hygiene hypothesis has been widely disseminated to the general public and it has been suggested that vaccinations would accordingly indirectly increase rates of atopy. We thus investigated associations between acute infections, infection pressure (i.e. number of daily child contacts) and atopy in one of the largest population-based medical surveys ever published in the medical literature. METHODS: Almost all Finns born between 1976 and 1984 and a sample of older teenagers aged up to 19 years (n=5 47 190) were vaccinated and questioned to establish clinical history of mumps and rubella and manifestations of atopy (rhinoconjunctivitis, eczema, and asthma) in 1982-1986. A subsample (n=37 733) including all those subjects who were vaccinated during the first 2 months of the measles, mumps, and rubella (MMR) programme were also queried information about upper respiratory infections (URIs) and infection pressure. Crude and adjusted prevalence ratios of atopy among those with infectious disease history compared with those without it were calculated. RESULTS: The risk of URI and a history of mumps and rubella increased with the number of daily contacts. This association was apparent especially among the youngest subjects with regard to URIs whereas the proportion with histories of mumps and rubella increased with increasing infection pressure more clearly among the 6-year-olds. Atopy was not associated with daily child contacts among pre-schoolers. Children with histories of repeated URIs and MMR diseases had substantially more atopy than those with lower URI or MMR disease rates. CONCLUSIONS: Atopic subjects seem to be especially prone to clinically apparent acute respiratory tract infections, and might be in particular need of protection by immunizations. This study does not support the idea that the prevalence of atopy in affluent countries would be affected from disappearing respiratory tract infections.

Epidemiology of rubella in Finland.

Before rubella vaccination programmes began, rubella infection was prevalent in Finnish children. The disease occurred as epidemics at intervals of a few years. Rubella infection was most often contracted between the ages of 2 and 12 years. Vaccinations specifically aimed at eradicating rubella were begun with monocomponent vaccine in the mid-1970s, and the measles, mumps and rubella (MMR) vaccination programme with two injections got underway in 1982. A clear reduction in rubella cases was evident a few years after the launch of the MMR programme. Owing to a sufficiently high vaccination coverage (>95% since 1987), circulation of the indigenous rubella virus in the Finnish population ceased in the late 1990s. Some rubella cases have been imported to Finland since elimination, but they have not caused any secondary cases. This shows unambiguously that protection against rubella continues to be effective, although our cohort studies imply that the vaccine induced antibody levels do decrease with time. The MMR programme has also eliminated congenital rubella syndrome (CRS) from the country. The last CRS case was recorded in 1986. As a result of the high coverage two dose MMR vaccination programme, rubella was successfully eliminated from Finland. How long the acquired protection will last remains to be seen.

Prevalence of tick-borne-encephalitis virus antibodies in Lithuania.

BACKGROUND: Clinical infections caused by tick-borne encephalitis virus (TBEV) are quite common in Lithuania and cause significant disease burden not only as acute cases but as chronic sequealeae as well. In order to evaluate the spread of the disease and risk factors, a population based seroprevalence study was done. MATERIAL AND METHODS: about 1488 serum samples collected from healthy people from different parts of the country during the year 2000 were studied by hemagglutination inhibition (HI) method. For risk factor analysis detailed information was collected by a questionnaire. RESULTS: 44 samples (2.96%) were positive. This indicates that at least 1500 infections occur in the country annually. Seropositivity did not increase with increasing age. In certain areas, seropositivity was clearly higher than the average. Other living conditions or outdoor habits correlated poorly with seropositivity. Certain groups of people such as farmers, cattle breeders, or those having a summer cottage or spending time in the nature daily had increased risk. Seropositivity was significantly linked with meningoencephalitis without laboratory confirmation for TBE in the anamnesis, and drinking of goat milk. CONCLUSION: The study suggests that TBEV is prevalent in Lithuania. The data also supports the view that an increase in the incidence has occurred in the 1990s. The correlation between seropositivity and presumed risk factors do not seem strong enough to warrant a selective vaccination policy based on risk factors.

Roles and functions of a European Union Public Health Centre for Communicable Diseases and other threats to health.

An international consensus has been reached that a European Union (EU) Technical Coordination Structure (TCS) for communicable diseases is needed to improve Europe s future response to international communicable disease threats within and beyond its boundaries. After the American events of September 11 2001 and the deliberate releases of anthrax, the EU created a Health Security Committee, adopted a civil protection decision, and established for 18 months a team to develop responses for deliberate releases of biological and chemical agents. These two initiatives, the network s approach and health security work, must converge into a single stream addressing health protection for the people of Europe. They could be combined into a European Centre for Communicable Diseases that is planned to become active by 2005.

Mumps and rubella eliminated from Finland.

Many countries use trivalent measles-mumps-rubella (MMR) vaccine for their mumps and rubella immunization programs. In Finland, a national 2-dose MMR vaccination program for children, free of charge and on a voluntary basis, was launched in 1982. Serological confirmation of all suspected cases of mumps and rubella has been required since 1987. Despite intensive surveillance, no persistent sequelae or deaths attributable to vaccination have been detected. Indigenous mumps and rubella were eliminated in 1996, but 4 imported cases of mumps and 2 of rubella occurred from 1997 to 1999. Lack of secondary cases indicates sufficient immunity in the community. Compared with an epidemic year, up to thousands of cases of mumps meningoencephalitis and orchitis and around 50 cases of congenital rubella syndrome are now avoided annually. A 2-dose vaccine regimen in children during the last 17 years (1983-1999) has interrupted circulation of the target viruses entirely. Finland is the first country documented to be free of indigenous mumps and rubella (measles was eliminated in 1996). Despite the ongoing possibility of imported disease, major outbreaks probably can be avoided by maintaining high vaccination coverage and the 2-dose policy. JAMA. 2000;284:2643-2647.

Analysis of HIV-1 genetic subtypes in Finland reveals good correlation between molecular and epidemiological data.

The molecular epidemiology of HIV-1 genetic subtypes was studied in a cross-sectional sample collected from HIV-infected individuals living in Finland between 1988 and 1994 and compared with independently collected epidemiological data. Subtypes were determined by sequencing and phylogenetic analysis of the gag NCp7 and the env coding regions of PBMC provirus. Finnish viruses belonging to 7 subtypes were found. Two thirds (n = 70) of the sequences could be classified as subtype B, while others belonged to subtypes A, C, D, F and G and the circulating recombinant form AE(CM240) (n = 25). There were significant differences in gender distribution and mode-of-transmission between B-type infections and infections with the other subtypes. Most subtype B strains in Finland were associated with homosexual transmission and about half of these were acquired in Finland, while most individuals harbouring non-B infections indicated heterosexual transmission and direct or indirect contact with Africa or Southeast Asia. The heterogeneity of genetic subtypes in the country was in good agreement with the epidemiological data suggesting that a significant proportion of infections were imported. HIV-1 subtype determination may prove to be a valuable tool for providing objective epidemiological data.

Seropositivity to multiple sexually transmitted infections is not common.

BACKGROUND: Seropositivity for several sexually transmitted infections (STIs) is often used as a surrogate measure of sexual behavior. The authors assessed the concomitant seropositivity for STIs in women. GOAL: To estimate the excess of concomitant seropositivity for four STIs among fertile-aged women assuming no coinfections above what would be expected at random. STUDY DESIGN: Antibodies to herpes simplex virus type 2, human papillomavirus type 16, HIV, Chlamydia trachomatis, and Treponema pallidum were determined from a random sample of 1110 pregnant women in Tallinn, Estonia. RESULTS: A total of 310 combinations of the concomitant seropositivity were observed, whereas only 193 were expected by chance. Among persons seropositive for two STIs, 78 extra combinations were observed, whereas for three STIs, 35 extra combinations were observed. For four STIs, 3.8 extra combinations were found. CONCLUSIONS: Seropositivity to multiple STIs is not common. This fits the concept of different transmission probabilities and the spread of the STIs, and suggests that seropositivity alone should be used with caution as a surrogate to sexual behavior in women.

An AB recombinant and its parental HIV type 1 strains in the area of the former Soviet Union: low requirements for sequence identity in recombination. UNAIDS Virus Isolation Network.

In the former Soviet Union (SU) increasing numbers of HIV-1 infections among injecting drug users (IDU) have been reported, especially in the Ukraine. The main subtype transmitted among the IDUs seems to be subtype A, but limited numbers of subtype B cases have also been reported. In Kaliningrad, Russia, an AB recombinant strain was earlier shown to be responsible for the local outbreak. Here we describe the genetic relationship of HIV-1 strains circulating among IDUs in the former SU. For subtype A and the AB recombinant strains nearly full-length genomes were sequenced, and for one subtype B strain the entire envelope gene was cloned. The relationship between the AB recombinant strain and the subtype A and subtype B strains and the mosaic structure of the recombinant was studied by phylogenetic analysis. Ukrainian A and B strains were shown to be the probable parental viruses of the Kaliningrad AB recombinant strain. In the envelope gene the recombination breakpoint could also be precisely mapped to a region of similarity of only 14 base pairs. This suggests that only short stretches of absolute sequence identity may be needed for efficient RNA recombination between HIV-1 subtypes.

Duration of rubella immunity induced by two-dose measles, mumps and rubella (MMR) vaccination. A 15-year follow-up in Finland.

A national two-dose vaccination program with a combined measles, mumps and rubella (MMR-II) vaccine was introduced in Finland, in 1982, immunizing children at the ages of 14-18 months and 6 years. Antibody levels were determined from serial samples from a group of originally 350 children during 15 years. The latest samples were taken 15.5 years after the first vaccination and 70% of the children could still be reached. The aim of this study was to determine the kinetics of rubella antibodies induced by the MMR-II vaccine in these individuals. Rubella antibodies were analyzed from three different cohorts: Group I seronegative children (n=166) vaccinated at 14-18 months and 6 years, Group II seronegative children (n=139) and Group III seropositive children (n=16) vaccinated at 6 and 11-13 years. Samples collected 0-9 years after vaccination were analyzed by hemolysis-in-gel (HIG) and later samples by enzyme immunoassay (EIA) techniques. The primary vaccination induced 100% seropositivity in vaccinees with a mean zone diameter of 10 (+/-1.3), 10.2 (+/-1.1) and 11.5 (+/-0.9) mm, in Groups I, II and III, respectively. The seropositivity rate was still high at 15 years, 99%, 100% and 100% with the geometric mean titer 23, 46 and 105 IU/ml, respectively. At 15 years, antibody levels <15 IU/ml which is the suggested protective level, were found in 31, 9 and 0% of children in Groups I, II and III, respectively. Because almost a third of the individuals in Group I now, at the age of 17 years, had low levels of rubella antibodies, it is possible that rubella infections may re-emerge during pregnancy. A careful surveillance including serological follow-up is therefore very important.

Secondary measles vaccine failures identified by measurement of IgG avidity: high occurrence among teenagers vaccinated at a young age.

Failure to seroconvert (primary vaccine failure) is believed to be the principal reason (approx. > 95%) why some vaccinees remain susceptible to measles and is often attributed to the persistence of maternal antibodies in children vaccinated at a young age. Avidity testing is able to separate primary from secondary vaccine failures (waning and/or incomplete immunity), but has not been utilized in measles epidemiology. Low-avidity (LA) and high-avidity (HA) virus-specific IgG antibodies indicate primary and secondary failure, respectively. Measles vaccine failures (n = 142; mean age 10.1 years, range 2-22 years) from an outbreak in 1988-9 in Finland were tested for measles-virus IgG avidity using a protein denaturating EIA. Severity of measles was recorded in 89 failures and 169 non-vaccinees (mean age 16.2 years, range 2-22 years). The patients with HA antibodies (n = 28) tended to have clinically mild measles and rapid IgG response. Among failures vaccinated at < 12, 12-15 and > 15 months of age with single doses of Schwarz-strain vaccine in the 1970s, 50 (95% CI 1-99), 36 (CI 16-56) and 25% (CI 8-42) had HA antibodies, respectively. When a single measles, mumps and rubella (MMR) vaccine had been given after 1982 at 15 months of age, only 7% (CI 0-14) showed HA antibodies. Omitting re-vaccinees and those vaccinated at < 15 months, Schwarz-strain recipients had 3.6 (CI 1.1-11.5) higher occurrence of HA responses compared to MMR recipients. Apart from one municipality, where even re-vaccinees had high risk of primary infection, 89% (CI 69 to approximately 100) of the infected re-vaccinees had an HA response. Secondary measles-vaccine failures are more common than was more previously thought, particularly among individuals vaccinated in early life, long ago, and among re-vaccinees. Waning immunity even among individuals vaccinated after 15 months of age, without the boosting effect of natural infections should be considered a relevant possibility in future planning of vaccination against measles.

Enterovirus RNA in serum is a risk factor for beta-cell autoimmunity and clinical type 1 diabetes: a prospective study. Childhood Diabetes in Finland (DiMe) Study Group.

Recent prospective studies have documented serologically an increased frequency of enterovirus infections in prediabetic children, indicating that these infections may initiate and accelerate the beta-cell damaging process several years before the clinical manifestation of type 1 diabetes. The aim of the present study was to establish whether these serological findings would be supported by the detection of enterovirus RNA in a unique prospective series of sera collected from prediabetic children 0-10 years before the manifestation of clinical type 1 diabetes. Reverse transcription followed by polymerase chain reaction employing highly conserved primers among enteroviruses were used to amplify enteroviral sequences. Viral RNA was found in 22% (11/49) of follow-up samples from prediabetic children but in only 2% (2/105) of those from controls (OR 14.9, P < 0.001). Persisting RNA positivity was not observed in any of these children. The presence of enterovirus RNA was associated with concomitant increases in the levels of autoantibodies against islet cells (OR 21.7, P < 0.01) and glutamic acid decarboxylase (OR 15.4, P < 0.05), but not in the levels of antibodies against insulin or the tyrosine phosphatase-like IA-2 protein. In contrast to the prediabetic children, those with newly diagnosed type 1 diabetes were negative for enterovirus RNA. The results thus complement previous serological data, suggesting that enterovirus infections are an important risk factor underlying type 1 diabetes and associated with the induction of beta-cell autoimmunity even years before symptoms appear.

Measles history and atopic diseases: a population-based cross-sectional study.

CONTEXT: Many recent cross-sectional studies have suggested that lack of early exposure to communicable diseases, including measles, in affluent countries may have increased rates of atopic disease. OBJECTIVE: To study the association between natural measles infection and atopy. DESIGN AND SETTING: Cross-sectional nationwide study in Finland using data gathered between November 1, 1982, and June 30, 1986. SUBJECTS: A total of 547910 individuals aged 14 months to 19 years who at the time of measles-mumps-rubella (MMR) vaccination had relevant information collected on the occurrence of measles and allergic rhinitis, eczema, and asthma. MAIN OUTCOME MEASURES: Lifetime occurrence of atopic manifestations in subjects who had had measles compared with those who had not, expressed as age-specific and age-adjusted prevalence ratios. RESULTS: The age-adjusted prevalence ratio of atopic manifestations among those who had had measles (n = 20 690) compared with those who had not (n = 527 220) was 1.32 (95% confidence interval [CI], 1.27-1.36) for eczema, 1.41 (95% CI, 1.33-1.49) for rhinitis, and 1.67 (95% CI, 1.54-1.79) for asthma. The positive association between measles and atopy was evident at all ages, in both urban and rural dwellers, and among subjects with many or few contacts at home or in day care. CONCLUSIONS: Based on our data, measles and atopy occur more frequently together than expected, which does not support the hypothesis that experiencing natural measles infection offers protection against atopic disease.

An international outbreak of Vero cytotoxin-producing Escherichia coli O157 infection amongst tourists; a challenge for the European infectious disease surveillance network.

In March 1997, an outbreak of Vero cytotoxin-producing Escherichia coli O157 (VTEC) infection occurred amongst holidaymakers returning from Fuerteventura, Canary Islands. For the investigation, a confirmed case was an individual staying in Fuerteventura during March 1997, with either E. coli O157 VTEC isolated in stool, HUS or serological evidence of recent infection; a probable case was an individual with bloody diarrhoea without laboratory confirmation. Local and Europe-wide active case finding was undertaken through national centres, Salm-Net and the European Programme of Intervention Epidemiology, followed by a case-control study. Fourteen confirmed and one probable case were identified from England (7), Finland (5), Wales (1), Sweden (1) and Denmark (1) staying in four hotels. Three of the four hotels were supplied with water from a private well which appeared to be the probable vehicle of transmission. The case-control study showed illness was associated with consumption of raw vegetables (OR 8.4, 95% CI 1-5-48.2) which may have been washed in well water. This investigation shows the importance of international collaboration in the detection and investigation of clusters of enteric infection.

Changing epidemiology of hepatitis B infection in Finland.

Finland has, until recently, had a very low incidence of hepatitis B infection, reflected in transmission mainly amongst adolescent and adult age-groups with high-risk behaviour. Several recent local outbreaks of acute hepatitis B in Finland may indicate a change in the epidemiology of this infection. We examine time trends of hepatitis B notifications to the new national infectious disease registry. We also analyse all hepatitis B cases notified over the 2-y period from 1 January 1995 to 31 December 1997 by age, sex, place of residence, country of birth and reported route of transmission. The reported incidence of acute hepatitis B increased 3-fold over this period. The main reported route of transmission was related to injecting drug use, although a significant proportion of adolescent female cases was reportedly infected through heterosexual intercourse. A critical evaluation of the current targeted vaccination approach and other prevention policies is required.

[A recombinant HIV-1 strain causing an epidemic among injection drug addicts in Kaliningrad]. / Rekombinantnyi shtamm VICh-1, vyzvavshii épidemiiu sredi in''ektsionnykh narkomanov v Kaliningrade.

The analysis of the genetic structure of HIV causing the epidemic in Kaliningrad Province. A new recombinant virus of subtype A/B was detected with the use of the polymerase chain reaction, the cloning of amplified fragments, sequencing and the phylogenetic analysis of the obtained data. The results thus obtained indicate that the epidemic in Kaliningrad was caused by a recombinant strain, and not due to co-infection caused by two HIV strains of different subtypes. The study of HIV-1 DNA revealed the divergence between the samples was extremely low, which was characteristic of epidemics connected with the transmission of the virus in the process of the intravenous use of narcotic drugs.