Martti Virtanen

The Elimination of Indigenous Measles, Mumps, and Rubella from Finland by a 12-Year, Two-Dose Vaccination Program

BACKGROUND In the 1970s measles, mumps, and rubella were rampant in Finland, and rates of immunization were inadequate. In 1982 a comprehensive national vaccination program began in which two doses of a combined live-virus vaccine were used. METHODS Public health nurses at 1036 child health centers administered the vaccine to children at 14 to 18 months of age and again at 6 years, and also to selected groups of older children and young adults. Vaccination was voluntary and free of charge. In follow-up studies, we focused on rates of vaccination, reasons for noncompliance, adverse reactions, immunogenicity, persistence of antibody, and incidence of the three diseases. Since 1987, paired serum samples have been collected from all patients with suspected cases of measles, mumps, or rubella. RESULTS Over a period of 12 years, 1.5 million of the 5 million people in Finland were vaccinated. Coverage now exceeds 95 percent. The vaccine was efficient and safe, even in those with a history of severe allergy. No deaths or persistent sequelae were attributable to vaccination. The most frequent complication requiring hospitalization was acute thrombocytopenic purpura, which occurred at a rate of 3.3 per 100,000 vaccinated persons. The 99 percent decrease in the incidence of the three diseases was accompanied by an increasing rate of false positive clinical diagnoses. In 655 vaccinated patients with clinically diagnosed disease, serologic studies confirmed the presence of measles in only 0.8 percent, mumps in 2.0 percent, and rubella in 1.2 percent. The few localized outbreaks were confined to patients in the partially vaccinated age groups. There are now fewer than 30 sporadic cases of each of the three diseases per year, and those are probably imported. CONCLUSIONS Over a 12-year period, an immunization program using two doses of combined live-virus vaccine has eliminated indigenous measles, mumps, and rubella from Finland. Serologic studies show that most reported sporadic cases are now due to other causes, but a continued high rate of vaccination coverage is essential to prevent outbreaks resulting from exposure to imported disease.

Randomized, placebo-controlled double blind study on the efficacy of influenza immunization on absenteeism of health care workers.

BACKGROUND In healthy adults influenza immunization reduces absenteeism caused by respiratory infections, but data on its efficacy among health care workers are scarce. OBJECTIVE To determine the effect of the conventional inactivated influenza A vaccine on reducing absenteeism related to respiratory infections among pediatric health care providers. STUDY DESIGN A randomized, placebo-controlled, double blind study on vaccine efficacy was conducted in two pediatric hospitals during the winter season 1996 to 1997. The primary endpoint was days of work lost from the hospital because of respiratory infections. The documentation of absenteeism was based on personal sickness logs. RESULTS Of the 547 randomized vaccinees 427 (78%) persons completed the 4-month follow-up and returned the sickness logs. Immunization failed to reduce episodes of respiratory infections (1.8 episodes/study period among vaccinees vs. 2.0 among controls). Similarly the vaccine failed to affect the total number of days the vaccinees suffered from respiratory infections (13.5 days vs. 14.6 days, respectively). However, days of work lost because of respiratory infections (1.0 days vs. 1.4 days, respectively, P = 0.02) and especially total numbers of days the study persons felt themselves unable to work when either on or off duty (2.5 days vs. 3.5 days, P 0.02) were significantly decreased. CONCLUSION Influenza vaccination reduced absenteeism related to respiratory infections by 28%. We therefore believe that routine annual influenza immunizations should be recommended to health care providers working in pediatric settings.

No improvement in outcome of nationwide extremely low birth weight infant populations between 1996-1997 and 1999-2000

OBJECTIVE. Our goal was to investigate whether outcome in extremely low birth weight infants changes over time in Finland. PATIENTS AND METHODS. All infants with a birth weight <1000 g born in Finland in 1996–1997 and 1999–2000 were included in the study. Perinatal and follow-up data were collected in a national extremely low birth weight infant research register. Data concerning cerebral palsy and visual impairment were obtained from hospitals, the national discharge, and visual impairment registers. RESULTS. A total of 529 and 511 extremely low birth weight infants were born during 1996–1997 and 1999–2000. No changes were detected in prenatal, perinatal, neonatal, and postneonatal mortality rates between the periods. The survival rates including stillborn infants were 40% and 44%. The incidence of respiratory distress syndrome and septicemia increased from 1996–1997 to 1999–2000 (75% vs 83% and 23% vs 31%). The overall incidence of intraventricular hemorrhage increased (29% vs 37%), but the incidence of intraventricular hemorrhage grades 3 through 4 did not (16% vs 17%). The rates of oxygen dependency at the age corresponding with 36 gestational weeks, retinopathy of prematurity stages 3 to 5, cerebral palsy, and severe visual impairment did not change. Mortality remained higher in 1 university hospital area during both periods compared with the other 4 areas, but no regional differences in morbidity were detected during the later period. CONCLUSIONS. No significant changes were detected in birth or mortality rate in extremely low birth weight infants born in Finland during the late 1990s, but some neonatal morbidities seemed to increase. Regional differences in mortality were detected in both cohorts. Repeated long-term follow-up studies on geographically defined very preterm infant cohorts are needed for establishing reliable outcome data of current perinatal care. Regional differences warrant thorough audits to assess causalities.

Neonatal Candida parapsilosis outbreak with a high case fatality rate

A Candida parapsilosis outbreak of 58 cases in a neonatal intensive care unit lasted for 55 months. Patients infected by or colonized with C. parapsilosis were mainly very low birth weight infants (birth weight < 1500 g). Their mean birth weight was 817 g and their mean gestational age was 28 weeks. Statistical analysis including logistic regression confirmed that prematurity was the main risk factor. The analysis also suggested that C. parapsilosis infection (or colonization) was associated with a poor prognosis. In infants with gestational age < 29 weeks the risk for death in C. parapsilosis-infected patients was 16-fold greater than in those with no C. parapsilosis infection. The case fatality rate of C. parapsilosis patients was higher than that of the controls (9 of 23 vs. 1 of 40; P < 0.0001). The outbreak was most likely a result of cross-infection because C. parapsilosis could be isolated only from the patients and from the hands of four nurses immediately after they had cared for a colonized patient. Cessation of the outbreak was temporally associated with long term parenteral fluconazole (6 mg/kg/day) prophylaxis.

RAPID EFFECT ON ENDEMIC MEASLES, MUMPS, AND RUBELLA OF NATIONWIDE VACCINATION PROGRAMME IN FINLAND

An immunisation programme to eliminate measles, mumps, and rubella from Finland within 10 years was started in November, 1982. A combined live vaccine is being given twice, at the ages of 14-18 months and 6 years, but at the beginning of the project children between these age limits are also being immunised. Because vaccinations are traditionally done by the public health nurses, special attention was paid to their motivation. 2.5 years after the launch of the project, 80.9% of the target children had been vaccinated. The incidence of measles has fallen by 93% and that of mumps by 87% compared with a normal prevaccination year (1982). A similar fall in incidence was seen for rubella, but only in the vaccinated age groups. Although elimination of measles, mumps, and rubella is not likely to be achieved with the present vaccination coverage, a drastic fall in the incidence of all three target diseases has occurred already. Every effort is being made to improve the coverage and thus to achieve the ultimate goal of the project.

A national two year follow up study of extremely low birthweight infants born in 1996–1997

Objective: To study neurodevelopmental outcome in a two year cohort of extremely low birthweight (ELBW) infants at 18 months corrected age, to compare the development of the ELBW infant subcohort with that of control children, and to find risk factors associated with unfavourable outcome. Study design: All 211 surviving ELBW infants (birth weight < 1000 g) born in Finland in 1996–1997 were included in a national survey. The ELBW infants (n = 78) who were born and followed in Helsinki University Hospital belonged to a regional subcohort and were compared with a control group of 75 full term infants. A national follow up programme included neurological, speech, vision, and hearing assessments at 18 months of corrected age. Bayley infant scale assessment was performed on the subcohort and their controls at 24 months of age. Risk factors for unfavourable outcome were estimated using logistic and linear regression models. Results: The prevalence of cerebral palsy was 11%, of all motor impairments 24%, of ophthalmic abnormalities 23%, and of speech delay 42%. No impairment was found in 42% of children, and 18% were classified as severely impaired. The prevalence of ophthalmic abnormalities decreased with increasing birth weight and gestational age, but the prevalence of other impairments did not. In the subcohort, a positive correlation was found between the date of birth and Bayley scores. Conclusion: Ophthalmic abnormalities decreased with increasing birth weight and gestational age, but no other outcome differences were found between birthweight groups or in surviving ELBW infants born at 22–26 weeks gestation. The prognosis in the regional subcohort seemed to improve during the short study period, but this needs to be confirmed.

Day-to-Day Reactogenicity and the Healthy Vaccinee Effect of Measles-Mumps-Rubella Vaccination

Objective. Revaccination policies adopted in many countries to control measles have raised various safety issues including those concerning the second vaccine dose. We performed a prospective, double-blind, crossover trial among twins receiving a measles-mumps-rubella (MMR) vaccine. Study Design. The study comprised 1162 monozygous and heterozygous twins, each of whom randomly received placebo and then vaccine, or vice versa, 3 weeks apart, at 14 to 83 months of age. Most of the oldest children had previously been vaccinated against measles, and one half of the remainder of children had had the disease. Symptoms and signs were recorded daily on structured forms. Statistical methods included a complex analysis of the vaccine attributability of the symptoms and conditional logistic regression. Results. Vaccination-attributable events occurred in 6% overall. At 14 to 18 months of age, reactions developed between days 6 and 14, peaking at day 10. The clearest vaccine-attributable effect was fever exceeding 101.3 °F (38.5°C; odds ratio: 3.28; 95% confidence interval: 2.23–4.82; P < .001), but the same trend was found for rash, arthralgia, conjunctivitis, staying in bed, drowsiness, and irritability. At 6 years of age, systemic reactions occurred 5 to 15 times less frequently, only arthralgia being associated with vaccination. Zygocity, gender, history of allergy, or infections did not modify reactions. Instead, respiratory symptoms developed within days postinjection to a level of 15% to 20% without subsequent decline and with no difference between vaccinees and placebo recipients. Conclusion. Vaccination was avoided during infections, but many small children became mildly ill within a week or so with no relation to vaccination (the healthy vaccinee effect). MMR vaccine was virtually nonreactogenic when given at 6 years of age. vaccine, measles, mumps, rubella, reactogenicity, adverse events, zygocity, healthy vaccinee effect.

Twice vaccinated recipients are better protected against epidemic measles than are single dose recipients of measles containing vaccine

OBJECTIVE: To study measles risk after revaccination. DESIGN: A population-based case-control study during an epidemic season. MAIN OUTCOME MEASURE: Relative serologically confirmed measles risk. PARTICIPANTS AND METHODS: 153 vaccinated cases, mostly from rural areas, were serologically confirmed as measles at the central laboratory in 1988-89. A randomly selected group of 453 controls from either municipalities of vaccinated cases or from areas where measles attack rate was > 600/10(5), was identified via the population registry. Vaccination and measles histories of cases and controls were determined from official vaccination cards. RESULTS: Once and twice vaccinated had crude relative risk 15.6 and 2.3 compared with thrice vaccinated. When cases who had received their first vaccination at less than 14 months of age were omitted from analysis, once vaccinated had 4.0 (95% CI 1.2, 16.6) times higher age adjusted measles risk compared with twice vaccinated. When, omission was extended to cases from one particular municipality where even revaccinees had high measles risk during an explosive outbreak the corresponding risk ratio was 17.8 (2.8, 67.8). CONCLUSIONS: Twice vaccinated have better protection against epidemic measles compared with single dose recipients.

Gonadotropin-releasing hormone test and human chorionic gonadotropin test in the diagnosis of gonadotropin deficiency in prepubertal boys

The discriminatory power of a gonadotropin-releasing hormone test and a human chorionic gonadotropin test in diagnosing gonadotropin deficiency was studied in 23 prepubertal boys with hypogonadotropic hypogonadism (HH). The boys were originally referred because of genital hypoplasia, delayed sexual maturation, or suspicion of HH. The diagnosis of HH was established clinically, in most cases after follow-up of several years. The results were compared with those of a reference group consisting of 44 prepubertal boys with incomplete testicular descent. Post-hCG serum testosterone level was the most sensitive discriminating variable, and was subnormal in 11 of 12 boys with HH (in one of 16 in the reference group). Post-GnRH serum LH concentration was the second most sensitive, and was subnormal in 15 of 23 boys with HH (two of the reference group). Our data indicate that post-hCG testosterone levels are of greater value than post-GnRH gonadotropin levels in the diagnosis of HH in prepubertal boys.

The Outcome of Extremely Low Birthweight Infants

During the years 1978-89, all surviving extremely low birthweight infants (BW less than 1000 g, ELBWI) in the region of Southern Finland were admitted to the Childrens Hospital, University of Helsinki and followed up to six years. The number of liveborn ELBWI increased from 30 to 50/year during the first and last third of the follow-up. During the same twelve year period, the number of the surviving infants increased from 8 to 25/year, with the number and proportion of infants with birthweights of less than 800 g and with gestational ages of less than 27 weeks increasing from 3 to 15/year. Despite of the greater proportion of smaller infants the proportion of infants without intraventricular hemorrhage increased from 50 to 85%. The proportion of children with normal neurodevelopment at two years increased from 40-70% during the first five years of the study, to 63-84% during the last three years of the study. The proportion of children with major disabilities decreased from 28 to 8%. The factors associated with poor neurodevelopment were sepsis, year of birth, intraventricular hemorrhage, and birthweight. The neurological status at one year was a valid predictor of the outcome: at four years 94% of the infants were assessed and normal remained normal as neurologically abnormal remained abnormal or slightly abnormal. The neurologically normal ELBWI were tested at six years: visuomotor coordination was immature in 50%, emotional immaturity was found in 25% and delay of language development in 13%. In our unit increased survival of ELBWI infants has not been associated with an increase in the number of ELBWI infants with handicaps.(ABSTRACT TRUNCATED AT 250 WORDS)