Missed hepatitis b/c or syphilis diagnosis among Kurdish, Russian, and Somali origin migrants in Finland: linking a population-based survey to the national infectious disease register.

BACKGROUND: Migrants are considered a key population at risk for sexually transmitted and blood-borne diseases in Europe. Prevalence data to support the design of infectious diseases screening protocols are scarce. We aimed to estimate the prevalence of hepatitis B and C, human immunodefiency virus (HIV) infection and syphilis in specific migrant groups in Finland and to assess risk factors for missed diagnosis. METHODS: A random sample of 3000 Kurdish, Russian, or Somali origin migrants in Finland was invited to a migrant population-based health interview and examination survey during 2010-2012. Participants in the health examination were offered screening for hepatitis B and C, HIV and syphilis. Notification prevalence in the National Infectious Diseases Register (NIDR) was compared between participants and non-participants to assess non-participation. Missed diagnosis was defined as test-positive case in the survey without previous notification in NIDR. Inverse probability weighting was used to correct for non-participation. RESULTS: Altogether 1000 migrants were screened for infectious diseases. No difference in the notification prevalence among participants and non-participants was observed. Seroprevalence of hepatitis B surface antigen (HBsAg) was 2.3%, hepatitis C antibodies 1.7%, and Treponema pallidum antibodies 1.3%. No cases of HIV were identified. Of all test-positive cases, 61% (34/56) had no previous notification in NIDR. 48% of HBsAg, 62.5% of anti-HCV and 84.6% of anti-Trpa positive cases had been missed. Among the Somali population (n = 261), prevalence of missed hepatitis B diagnosis was 3.0%. Of the 324 Russian migrants, 3.0% had not been previously diagnosed with hepatitis C and 2.4% had a missed syphilis diagnosis. In multivariable regression model missed diagnosis was associated with migrant origin, living alone, poor self-perceived health, daily smoking, and previous diagnosis of another blood-borne infection. CONCLUSIONS: More than half of chronic hepatitis and syphilis diagnoses had been missed among migrants in Finland. Undiagnosed hepatitis B among Somali migrants implies post-migration transmission that could be prevented by enhanced screening and vaccinations. Rate of missed diagnoses among Russian migrants supports implementation of targeted hepatitis and syphilis screening upon arrival and also in later health care contacts. Coverage and up-take of current screening among migrants should be evaluated.

Similar Antibody Levels in 3-Year-Old Children Vaccinated Against Measles, Mumps, and Rubella at the Age of 12 Months or 18 Months.

BACKGROUND: Measles-mumps-rubella (MMR) vaccinations have been offered to Finnish children at 14-18 months and 6 years of age. In May 2011, the recommended age for the first vaccine dose was lowered to 12 months because of the European measles epidemic. METHODS: Fingertip capillary blood samples were collected from 3-year-old Finnish children vaccinated once with MMR vaccine at 11-19 months of age. The immunoglobulin G (IgG) antibodies to all 3 MMR antigens were measured with enzyme-linked immunosorbent assay. Neutralizing antibodies and the avidity of antibodies were measured for measles virus. RESULTS: From April through October 2013, 187 children were enrolled. Equally high proportions of the samples were seropositive for measles virus, mumps virus, or rubella virus antibodies, and there were no significant differences in the IgG antibody concentrations in children vaccinated at 11-13 months of age, compared with those vaccinated at 17-19 months of age. However, among children vaccinated at 11-13 months of age, boys had lower antibody concentrations than girls. Neutralizing measles virus antibody titers were above the threshold for protective immunity in all 78 samples analyzed. The measles virus antibody avidity indexes were high for all children. CONCLUSIONS: MMR induces similar antibody responses in 12-month-old children as compared to 18-month-old children, but in boys increasing age appears to improve the antibody responses.

The clinical picture of juvenile parotitis in a prospective setup.

AIM: To characterize the features of juvenile parotitis in a prospective setup and epidemiology. METHODS: All children with parotitis admitted to Helsinki University Central Hospital 2005-2010 were recruited. Clinical characteristics, given treatment, outcome, blood leukocyte count, C-reactive protein, serum amylase and trypsinogen, SPINK-1 genotype and mumps antibodies were recorded. To map the epidemiology, a questionnaire was sent to 1000 randomly selected 13-year-old children. RESULTS: The prospective study included 41 children (aged ≤ 17) with acute parotitis, all in good general condition. Serum amylase, but not trypsinogen, was elevated in majority of the cases (79%) and C-reactive protein in 68%. Eleven (27%) children had an elevated blood leukocyte count. None had acute mumps. Most children recovered well, 51% being treated symptomatically only. Seven children were treated on ward. Seventeen (46%) children had recurrent symptoms. One child (2.4%) had SPINK P55S mutation. According to the epidemiological questionnaire, 1.1% of the respondents (8/728, response rate 73%) reported a verified episode(s) of parotitis. CONCLUSION: Juvenile parotitis has a frequency close to 1%. In the majority, the general condition is good during the episode. Serum amylase serves as an additional marker for the disease. Parotitis has a tendency to recur in almost half of the cases.

Fever with rash in patients returning from popular tourist resort Phuket, Thailand: dengue--or measles?

We report three recent cases of measles in travelers to a popular vacation resort, Phuket, Thailand, two initially diagnosed clinically as dengue, one as drug reaction. In countries with no indigenous measles, clinicians may no longer recognize the disease. When left misdiagnosed, the patients continue to be potential transmitters.

Waning antibody levels and avidity: implications for MMR vaccine-induced protection.

BACKGROUND: The measles-mumps-rubella (MMR) vaccine is effective in eliciting a good antibody response. In addition to the amount of antibodies, the avidity of these antibodies might be important in protecting against disease. METHODS: The amount of circulating antibodies for measles, mumps, and rubella was measured with enzyme immunoassays, and the avidity of these antibodies was determined by urea dissociation. Three groups of twice-MMR-vaccinated individuals and 1 group of naturally infected individuals were studied. One vaccinated group (n = 71) was studied 6 months and 20 years after a second MMR vaccination. RESULTS: The antibody avidity indexes were high for measles and rubella but low for mumps. Twenty years after a second MMR vaccination, antibody levels for all 3 viruses waned. Also, the mean avidity index decreased by 8% for measles, 24% for mumps, and remained unchanged for rubella. Antibody avidity correlated with antibody concentration for measles. There was partial correlation for rubella and no correlation for mumps. CONCLUSIONS: Measles and rubella induced high-avidity antibodies and mumps induced low-avidity antibodies after both vaccination and natural infection. Waning of both the concentration as well as the avidity of antibodies might contribute to measles and mumps infections in twice-MMR-vaccinated individuals.

Increased circulation of hepatitis A virus genotype IIIA over the last decade in St Petersburg, Russia.

The current study, covering the period 2004-2009, is a part of long-term monitoring for hepatitis A virus (HAV) strains circulating in St Petersburg, Russia. The HAV RNA was isolated directly from the sera of hepatitis A patients and RT-PCR was carried out using primer pairs for VP1/2A and VP1 genomic regions. PCR products were sequenced and 324 nucleotides from VP1/2A and 332 from the VP1 region were used for phylogenetic analysis. The results show that the IA subtype was the most common circulating subtype during the follow-up period, as found in the previous study: almost 90% of the isolated HAV strains belonged to the IA subtype. The large hepatitis A food-borne outbreak in St Petersburg in 2005 was caused by HAV IA. However, the proportion of HAV isolates belonging to subtype IIIA significantly increased in the period 2001-2009 (7.9%) compared to the period 1997-2000 (none found). The subtype IIIA was first found in St Petersburg in 2001 among a group of intravenous drug users. The increase in its circulation during the decade suggests that this previously unusual genotype has been permanently introduced into the general population of St Petersburg. These results indicate the usefulness of molecular epidemiological methods for studying changes in the circulation of HAV strains.

Immunity after (re)vaccination of paediatric patients following haematopoietic stem cell transplantation.

AIMS: Loss of specific immunity follows allogeneic haematopoietic stem cell transplantation (HSCT) in the majority of cases. Responses to (re)vaccinations can be used as indicators of a functional immunological recovery. METHODS: Twenty-three paediatric recipients of HSCT were enrolled in a single centre setting and responses to scheduled immunizations analysed. RESULTS: Immunity to vaccine-preventable diseases was impaired post HSCT, but (re)vaccinations induced protective responses in 59-100%, depending on the vaccine, regardless of prior graft-versus-host disease (GVHD) history. CONCLUSION: Despite the marked impact of moderate to severe chronic prior GVHD on both the qualitative and quantitative T-cell recovery post allogenic HSCT, most paediatric recipients of allogeneic stem cell grafts appear to attain protective antibody levels after immunization.

MMR vaccination and disease elimination: the Finnish experience.

Measles, mumps and rubella (MMR) vaccinations have been included in Finland's national vaccination program as a two-dose schedule since 1982. Owing to the high (>95%) coverage of vaccinations, indigenous MMR diseases were eliminated from Finland by the mid-1990s. In 1982, the incidence of measles, mumps and rubella was 105, 43 and 64 per 100,000 population, respectively, but declined to 0.1 per 100,000 population for all MMR diseases in 1995. Since then, the few cases of measles, mumps and rubella imported annually have not caused any outbreaks. Several research projects that started along with the vaccination campaign have provided important support throughout the program. The vaccine was proven to be safe, immunogenic and effective. Antibody follow-up has revealed that MMR vaccine-induced antibodies wane over time, and concerns have arisen about the continuation of this good situation. High vaccination coverage, enhanced surveillance and preparedness to administer additional doses when needed are key factors for future success. Here we present an overview of MMR vaccinations and the Finnish experience of the MMR disease elimination process, and we describe surveillance activities in the era following elimination in Finland.

Epidemiology of hepatitis A in Finland in 1990-2007.

The seroepidemiology of hepatitis A virus (HAV) for the period 1990-2007 and the molecular epidemiology for the period 1994-2007 in Finland were studied. The incidence of hepatitis A has been very low since 1990, at 0.3-3.6/100,000 inhabitants, excluding two outbreaks in 1994-1995 and 2002-2003, both of which were connected to intravenous drug use. Serum samples (3,217) collected in the period 1997-1998 were tested for hepatitis A antibodies to assess the percentage of seropositive Finns. More than 50% of Finns aged over 55 were seropositive for hepatitis A, while less than 5% of those aged under 40 were seropositive. In addition, patient samples (52,012) from the period 1990 to 2007 were assessed for antibodies against HAV. In these samples the proportion of acute HAV infections stayed at around 2% per year (excluding outbreaks), whereas the overall seropositivity for hepatitis A increased from some 30% to 45%, which was most likely due to increased vaccinations. For molecular epidemiology, samples from 1994 to 2007 were analyzed by RT-PCR and sequencing. The results showed that most of the strains (82%) of HAV were of genotype IA but with an increasing number of genotypes IB and IIIA appearing during the last years of the study. All the cases seemed to be travel related and there was no endemic strain circulating in Finland. The low seroprevalence, especially in younger age groups, makes the population vulnerable to infection, which can be compensated for by increasing the number of vaccinations.

Measles, mumps, and rubella in Finland: 25 years of a nationwide elimination programme.

A nationwide programme to eliminate indigenous measles, mumps, and rubella, mainly by vaccinating children twice, was launched in Finland in 1982. Strong scientific methods to examine the immunological, clinical, and epidemiological variables have accompanied the programme. Measles was eliminated in 1996, and mumps and rubella in 1997. Now, 25 years from the start of this programme, Finland is facing new challenges. Since elimination, eight, 32, and six cases of measles, mumps, and rubella, respectively, have been reported. Of those, seven cases were failures of mumps vaccinations and one case was a rubella vaccination failure. Although outbreaks have been averted, the risks are increasing because the unvaccinated population is growing, epidemics occur in nearby countries, breakthrough cases arise, and declining antibodies suggest waning immunity. The chances for natural boosters are now at a minimum, and individuals are increasingly protected solely by vaccination. To maintain the absence of these diseases, the adopted policy should continue, but the country should also be prepared for prompt supplementary vaccinations in the case of epidemic outbreaks.

Persistence of measles, mumps, and rubella antibodies in an MMR-vaccinated cohort: a 20-year follow-up.

BACKGROUND: The persistence of antibodies against measles, mumps, and rubella induced by the measles-mumps-rubella (MMR) vaccine and the kinetics of antibody decline after the second MMR vaccine dose were studied in the same cohort for 20 years. METHODS: Measles, mumps, and rubella antibodies were measured by enzyme immunoassay in 20-year follow-up serum samples (n= 183) of twice-vaccinated individuals, and measles antibodies were also measured in oral fluids (n = 177). Antibody decay was determined in a group (n = 58) with subsequent samples collected 1, 8, and 15 years after the second MMR dose. RESULTS: In total, 95%, 74%, and 100% of 183 vaccinees were still seropositive for measles, mumps, and rubella, respectively, and 85% of 177 vaccinees had measurable measles antibodies in their oral fluids. The antibody levels declined significantly after the second dose, but subsequently the rate of decline was slower. CONCLUSIONS: A high rate of seropositivity was found 20 years after the first MMR dose, particularly for rubella and measles. Our results show that MMR vaccine-induced antibodies wane significantly after the second dose. According to epidemiological data, the protection induced by MMR vaccination in Finland seems to persist at least until early adulthood. However, the situation requires constant vigilance.

Cellular immunity to mumps virus in young adults 21 years after measles-mumps-rubella vaccination.

BACKGROUND: Measles-mumps-rubella (MMR) vaccination has decreased the incidence of measles, mumps, and rubella virus infections in several countries. However, the persistence of MMR vaccine-induced immunity in the absence of endemic infection has remained unknown. METHODS: The persistence of cellular and humoral immunity to mumps virus was studied in 50 individuals (group A) who had been vaccinated twice with MMR vaccine during early childhood and were followed up for 21 years after their first vaccination. Eleven individuals (group B) with naturally acquired immunity to mumps virus were studied for comparison. RESULTS: Anti-mumps virus IgG antibodies were detectable (titer > or = 230) in 72% of the vaccinees. A mumps antigen-specific lymphoproliferative response (defined as a stimulatory index [SI] > or = 3) was observed in 98% of group A subjects (mean+/-SD SI, 26+/-30 [range, 0.5-252]) and in 100% of group B subjects (mean+/-SD SI, 22+/-27 [range, 5-123]). Significant mumps antigen-specific interferon- gamma production was detected in 73% of subjects in both groups A and B, and interleukin-10 production was detected in 40% and 36% of group A and B subjects, respectively. CONCLUSIONS: All presently seronegative vaccinees (n=14) had mumps antigen-specific lymphoproliferative responses, and only 1 of the seropositive vaccinees (n=36) was devoid of detectable cellular immunity. The results suggest a very long persistence of vaccine-induced anti-mumps virus cellular immunity.

Molecular epidemiology of hepatitis A in St. Petersburg, Russia, 1997-2003.

The molecular epidemiology of hepatitis A virus (HAV) strains circulating in the St. Petersburg and Karelia regions was studied during 1997-2003. Hepatitis A virus RNA was isolated from both clinical samples (stools or sera) and environmental samples (sewage water). RT-PCR was carried out using different primer pairs from the VP1/2A and VP1 genomic regions, the variable parts of the HAV genome. PCR products were sequenced and 306 nucleotides from the VP1/2A and 332 nucleotides from the VP1 region were used for phylogenetic analysis. The results show that the IA subtype was the most common during the follow-up period: >90% of the isolated HAV strains belonged to that subtype. The HAV strains found in intravenous drug users belonged to subtypes IA and IIIA. Only one out of a total of 88 sequenced strains was of the IB subtype. The subtypes IB and IIIA were found only in 2001-2003, which suggests that new strains were introduced into the endemic situation. The results indicate the usefulness of molecular epidemiological methods in studying changes in the circulating HAV strains and in tracing transmission routes.

Bioportfolio: lifelong persistence of variant and prototypic erythrovirus DNA genomes in human tissue.

Human erythrovirus is a minute, single-stranded DNA virus causing many diseases, including erythema infectiosum, arthropathy, and fetal death. After primary infection, the viral genomes persist in solid tissues. Besides the prototype, virus type 1, two major variants (virus types 2 and 3) have been identified recently, the clinical significance and epidemiology of which are mostly unknown. We examined 523 samples of skin, synovium, tonsil, or liver (birth year range, 1913-2000), and 1,640 sera, by qualitative and quantitative molecular assays for the DNA of human erythroviruses. Virus types 1 and 2 were found in 132 (25%) and 58 (11%) tissues, respectively. DNA of virus type 1 was found in all age groups, whereas that of type 2 was strictly confined to those subjects born before 1973 (P < 0.001). Correspondingly, the sera from the past two decades contained DNA of type 1 but not type 2 or 3. Our data suggest strongly that the newly identified human erythrovirus type 2 as well as the prototype 1 circulated in Northern and Central Europe in equal frequency, more than half a century ago, whereafter type 2 disappeared from circulation. Type 3 never attained wide occurrence in this area during the past > or =70 years. The erythrovirus DNA persistence in human tissues is lifelong and represents a source of information about our past, the Bioportfolio, which, at the individual level, provides a registry of one's infectious encounters, and at the population level, a database for epidemiological and phylogenetic analyses.

European seroepidemiology network 2: Standardisation of assays for seroepidemiology of varicella zoster virus.

BACKGROUND: The aim of the European Sero-Epidemiology Network (ESEN2) is to harmonise the serological surveillance of vaccine-preventable diseases in Europe. OBJECTIVE: To allow comparison of antibody prevalence in different countries by standardising results into common units. STUDY DESIGN: For varicella zoster virus (VZV), a reference laboratory established a panel of 148 samples, characterised by indirect enzyme-immunoassay (ELISA), indirect immunofluorescence, and complement fixation test. Fifty-seven samples were also studied by the fluorescence antibody to membrane antigen test. The geometric mean of the antibody activity (GMAA) obtained from four ELISA determinations was used to characterise each sample of the panel as positive (GMAA: >100 mIU/ml), equivocal (GMAA: 50-100 mIU/ml) or negative (GMAA: <50 mIU/ml) for antibody to VZV (anti-VZV). Thirteen laboratories, using five different ELISA tests, tested the panel. RESULTS: Agreement with the reference laboratory was above 85% in all cases, and the R(2) values obtained from regression analysis of the quantitative results were always higher than 0.87. Finally, the regression equations could be used to convert national values into a common unitage. CONCLUSION: This study confirmed that results for anti-VZV obtained by different ELISA methods can be converted into common units, enabling the comparison of the seroprevalence profiles obtained in the participant countries.

Etiology of mumps-like illnesses in children and adolescents vaccinated for measles, mumps, and rubella.

The possible viral etiology of mumps-like illnesses in patients vaccinated for measles, mumps, and rubella (MMR) was studied by use of serum samples prospectively collected, during 1983-1998, from 601 acutely ill Finnish children and adolescents with mumps-like symptoms. Mumps virus was excluded by testing serum samples for mumps antibodies, and the serum samples were further tested for antibodies to adenovirus, enterovirus, Epstein-Barr virus, parainfluenza virus types 1-3, and parvovirus B19. The serum samples of 114 children <4 years old were also tested for antibodies to human herpesvirus 6 (HHV-6). A viral etiology was verified in 84 cases (14%), most commonly Epstein-Barr virus (7%), followed by parainfluenza virus types 1, 2, or 3 (4%) and adenovirus (3%). HHV-6 infection was found in 5 children <4 years old (4%). This study confirms that mumps-like symptoms in MMR-vaccinated children and adolescents are often not caused by mumps virus infection. Careful laboratory-based diagnostic testing of MMR-vaccinated children and adolescents who develop clinical symptoms compatible with those of mumps is important in the treatment of individual patients, in the comprehension of the true epidemiology of these illnesses, and in the evaluation of the impact of MMR vaccination programs.

IgG avidity to distinguish secondary from primary measles vaccination failures: prospects for a more effective global measles elimination strategy.

The nearly 40-year long debate on the relevance of secondary measles vaccination failure has been inconclusive because a feasible method for the assessment of the duration of immunity has been lacking. Even if a two-dose measles vaccination policy is now universally endorsed, WHO still officially adheres to the view that a single successful measles vaccination, without natural boosters, induces a lifelong immunity and deems secondary failures epidemiologically irrelevant - in the belief that the latter are rare and do not participate in the transmission chain. A recently published study on measles-IgG avidity, which allows for separation of secondary from primary vaccination failures, tentatively showed that the official view does not necessarily hold true. The results may have wide implications on global measles eradication efforts. The potential of IgG avidity measurement in complex postvaccination measles epidemiology is discussed.