Pauli Leinikki

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.

Enterovirus RNA in serum is a risk factor for beta‐cell autoimmunity and clinical type 1 diabetes: A prospective study

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. J. Med. Virol. 61:214–220, 2000.

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.

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

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.

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.

Hepatitis A outbreak amongst intravenous amphetamine abusers in Finland

This article describes a widespread outbreak of hepatitis A virus (HAV) infection amongst drug abusers in Finland. Although attempts to demonstrate the virus in amphetamines failed, the infection was assumed to be linked to intravenous use of the drug. The unusual mode of transmission prompted us to analyse possible atypical clinical features as well as the spread of the virus to the general population, nowadays practically without protective immunity. Serologically verified cases that occurred in Helsinki were interviewed, their hospital records were analysed and their contacts were serology tested. Amphetamine lots, as well as faecal samples from patients, were examined with RT-PCR. Detailed information was obtained from 238 subjects, among whom 131 admitted drug abuse and 67 cases were classified as secondary cases. Phylogenetic analysis of virus strains from HAV-infected cases suggested a common origin, and epidemiological observations linked it with particular lots of amphetamine. Three cases died, and 3 presented with severe clinical disease. Icterus was more common among i.v. drug abusers than others. Infection with hepatitis A virus was probably related to the faecal contamination of amphetamine associated with the transportation of the drugs in the gastrointestinal tract.

Increased risk of malignant lymphoma indicated by elevated Epstein-Barr virus antibodies—a prospective study

We estimated Epstein-Barr virus (EBV) antibody-associated relative risks (RR) of malignant lymphoma/leukemia within a cohort of 39,000 healthy Finnish adults followed up for 12 years. Antibody analyses to EBV capsid antigen (VCA), early antigen (EA), and nuclear antigens (EBNA, EBNA1, and EBNA2) were based on concomitantly evaluated ELISA techniques. No increased risk was associated with mere EBV seropositivity. However, elevated EBV EA and EBNA antibody levels were associated with a statistically significant excess risk of malignant lymphoma/leukemia (RREA=3.4, 95 percent confidence interval [CI]=1.0–11.0; RREBNA=4.5, CI=1.2–16.9). These elevated antibody responses may be due either to destruction of neoplastic EBV positive B-cells and/or to activation of latent EBV infection early in the lymphomagenesis.

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 AECM240 (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.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.

Herpes simplex virus type 2 infection and cervical cancer: a prospective study of 12 years of follow-up in Finland.

This study was initiated to investigate the role of past herpes simplex virus type 2 (HSV-2) infection, as determined by serum antibody analysis, in the etiology of cervical neoplasia. Two Finnish registers, the registry of the Social Insurance Institutions Mobile Clinic Survey and the Finnish Cancer Registry, were linked. About 40,000 blood samples were drawn in 1968–72 and stored by the Social Insurance Institution. According to the Cancer Registry, 32 cases of cervical carcinoma or carcinoma in situ for which serum samples were available were diagnosed in this cohort during a follow-up of 12 years (1968–81). The serum samples of these individuals and age matched controls (2:1) from the cohort were analyzed for HSV-2 antibodies. HSV-2 infection as determined by the best available HSV-2 type-specific antibody assay, glycoprotein gG2-ELISA, was not related to cervical neoplasia, i.e., the risk of cervical neoplasia among the HSV-2 positive women was not higher than that among the negative ones (smoking-adjusted relative risk = 0.5, 95 percent confidence interval = 0.2–1.6). The results do not support the hypothesis that HSV-2 is an etiologic agent for cervical neoplasia.