Evidence of protective effect of BCG vaccination in persons at low risk of tuberculosis in Nordic countries.

SETTING: Norway, Sweden, Denmark and Finland have low incidence rates (IRs) of tuberculosis (TB) but the use of bacille Calmette-Guérin (BCG) vaccination has varied. OBJECTIVE: To assess if different IRs among persons at low risk in the four countries could be related to the different use of BCG vaccination, and to estimate the number of adolescent BCG vaccinations needed to prevent one case of TB in Norway. DESIGN: The study period was 1996-2005. In part A, IRs for cases classified as 'born in country/national' in the EuroTB database in all four countries were calculated. In part B, the IRs among persons born in Norway and Sweden with two parents from low-incidence countries were calculated for cases registered in the respective national TB registers. In both parts, IRs and IR ratios among 0-14-year-olds and 15-29-year-olds were compared and related to different BCG vaccination policies. RESULTS AND CONCLUSIONS: Our results are consistent with a protective effect of newborn BCG vaccination in native-born 0-14-year-olds in Finland, and of adolescent BCG vaccination in 15-29-year-olds in Norway. The Norwegian BCG vaccination programme conferred 61-64% protection to 15-29-year-olds; however, 21699-25125 vaccinations were needed to prevent one case.

Extensive transmission of an isoniazid-resistant strain of Mycobacterium tuberculosis in Sweden.

SETTING: City of Stockholm, Sweden. BACKGROUND: The incidence of tuberculosis (TB) in Sweden increased by 40% between 2003 and 2005. The spread of a unique TB strain resistant to isoniazid (INH) contributed to this increase. OBJECTIVE: To describe outbreaks of TB caused by this single strain, elucidate possible causes for its extensive spread and identify shortcomings of the TB control programme in Sweden. RESULTS: We identified a cluster consisting of 102 culture-confirmed TB cases with identical DNA fingerprints and 26 epidemiologically related cases, not confirmed by culture, all diagnosed between 1996 and 2005. Five partly separate outbreaks of this strain were discovered. Epidemiological links were established for 56% of the culture-confirmed cases and for all cases not confirmed by culture. Three patients died while receiving treatment, four became failures and eight defaulted or were lost to follow-up. Only eight patients received directly observed treatment (DOT) up to a period of 3 months, although 40% had poor adherence. CONCLUSIONS: Shortcomings of the national TB programme were revealed. Improved contact tracing and case holding, including DOT, is crucial to reduce TB transmission in Sweden.

Selective BCG vaccination in a country with low incidence of tuberculosis.

In 1975 the BCG vaccination policy in Sweden changed from routine vaccination of all newborn infants to selective vaccination of groups at higher risk. This report aims to evaluate the present BCG policy, with focus on the tuberculosis situation in Sweden during the period from 1989 to 2005. The population structure in Sweden has changed, with increasing numbers and proportions of people who were born outside Sweden, especially in countries with high prevalence of tuberculosis. BCG vaccination coverage fell from more than 95% before 1975 to less than 2% in 1976 to 1980, and then again increased to around 16% (corresponding to about 88% of the risk group recommended for vaccination). The increasing proportion of foreign born tuberculosis patients among all tuberculosis cases of illness in Sweden, and the high age-specific incidence of tuberculosis in the childbearing age groups in the foreign-born population, indicate the need to continue selective vaccination of children in families originating from countries with high tuberculosis incidence. The cumulative incidence of tuberculosis in the 30 cohorts born in Sweden after 1974 and observed to the end of 2004 was estimated at 0.5 cases per 100 000 person-years. Sweden still has one of the lowest incidences of tuberculosis in the world, which means a minimal average risk of infection for the majority of children born to Swedish parents. The observed increase of tuberculosis in 2005, partly attributed to an outbreak at a day nursery, is a reminder of the serious consequences of delayed diagnosis. Intensified active case finding is the most important action to prevent childhood tuberculosis, by means of eliminating the sources of infection to prevent transmission to the child population. Early detection and treatment of infected children is necessary to prevent development of serious disseminated tuberculosis.

Tuberculosis in Bacillus Calmette-Guérin-immunized and unimmunized children in Sweden: a ten-year evaluation following the cessation of general Bacillus Calmette-Guérin immunization of the newborn in 1975.

An analysis was made of childhood tuberculosis in Sweden between 1969 and 1984 which included the 6.25 years before and the 9.75 years after the cessation of general Bacillus Calmette-Guérin (BCG) immunization of the new-born on April 1, 1975. The annual incidence of tuberculosis per 100,000 children ages 0 to 4 years increased from an average of 1.1 cases in the period 1970 to 1974 to 1.3 cases in the period 1975 to 1979 and to 2.1 cases in the period 1980 to 1984, including both children born in Sweden and those born abroad. Among children born in Sweden after April 1, 1975, tuberculosis occurred in 58 (57 unimmunized and one BCG-immunized), or 1.3 cases per 100,000 person years up to and including 1984. Eighteen of the 58 children were asymptomatic. Minor symptoms were reported in 13 and clinical illness in 27 children, 2 of whom developed meningitis and 1 of whom died of miliary infection. The relative increase of tuberculosis in the mainly unimmunized cohorts born in Sweden after April 1, 1975, compared with the mainly BCG-immunized cohorts born in Sweden in the period 1969 to 1974 was, by the end of 1984, estimated at 6.0 (95% confidence interval, 2.3, 16.1). Tuberculosis was about 10 times more common in non-BCG-immunized children born in Sweden of foreign parents than in those born of Swedish parents.(ABSTRACT TRUNCATED AT 250 WORDS)

Pertussis in Sweden after the cessation of general immunization in 1979.

Immunization against pertussis was introduced in Sweden in the 1950s and discontinued in 1979. This was followed by a low endemic level of pertussis for 3 years. Thereafter the incidence gradually increased and there were two outbreaks in 1983 and in 1985. In the period 1980 to 1985 pertussis was confirmed by culture or serology in 36,729 patients of which 11% were younger than 12 months of age and 69% were ages 1 to 6 years. An estimate of the total frequency of pertussis in preschool children was made from reports from a sample of the child health centers. The annual incidence rate per 100,000 population ages 0 to 6 years increased from the 700 cases in 1981 to 3200 in 1985. The ratio of total cases to those reported from the laboratories was 3:1 in 1981 and 2:1 in 1985. The cumulative incidence rate by the average age of 4 years was estimated at 16% of the unimmunized cohort born in 1980 compared with 5% of the immunized cohort born in 1978. The seriousness of pertussis was evaluated by studying the 2282 pertussis patients hospitalized from 1981 to the end of 1983. Forty-eight percent were infants younger than 12 months of age. Neurologic complications were noted in 4% and pneumonia in 14% of the hospitalized patients. Eleven children received assisted ventilation. Fatal outcomes were reported in 3 children (0.1%), 2 of whom had severe congenital disabilities.

Mortality and morbidity from invasive bacterial infections during a clinical trial of acellular pertussis vaccines in Sweden.

A double blind placebo-controlled efficacy trial of two acellular pertussis vaccines was conducted in 3801 6- to 11-month-old children. Four vaccinated children died during 7 to 9 months follow-up as a result of Haemophilus influenzae type b meningitis, heroin intoxication with concomitant pneumonia, suspected septicemia, and Neisseria meningitidis Group B septicemia. From the actual death rate in children belonging to the same birth cohort in Sweden that could have been eligible for the trial, one death was expected among vaccinated children. Several investigations were carried out to examine the possibility that the deaths could be causally related to the vaccination. The relative risk for hospitalization due to systemic or respiratory infections was 1.07 (95% confidence interval, 0.95 to 1.20) and 0.83 (95% confidence interval, 0.64 to 1.08) in the vaccine groups as compared with the placebo group. Subsets of the population were studied for signs of immunosuppression. There was no indication of immunoglobulin deficiency or any sign of clinically significant leukopenia or lymphocytosis in vaccine recipients. The results of this analysis provide no evidence for a causal relation between vaccination with the studied acellular pertussis vaccines and altered resistance to invasive disease caused by encapsulated bacteria. The hypothesis that the two variables are related, however, cannot be refuted from these data.

Invasive bacterial infections during an efficacy trial of acellular pertussis vaccines--implications for future surveillance in pertussis vaccine programmes.

During a placebo controlled trial of acellular pertussis vaccines a cluster of invasive bacterial infections with fatal outcome occurred among vaccinated children as compared with unvaccinated Swedish children of the same birth cohort (4). Clinical and immunological studies did not support the hypothesis of an immunosuppressive effect of the vaccines, which would explain the deaths, but the hypothesis could not be refuted by the data. To evaluate the safety of acellular pertussis vaccines regarding rare severe events--in particular invasive infectious diseases--prospective studies seem to be needed, comparing very large groups. A coordinated and controlled vaccine programme during 1-2 years in most of Sweden combined with national reports of invasive infections may serve as a basis for such a study. A possible study design is given below.

[Shortages in Swedish tuberculosis care. Good results only in 71 percent of cases after 12-month treatment as shown in a current study]. / Det finns brister inom den svenska tuberkulosvården. Fullgott resultat efter tolv månader hos endast 71 procent visar aktuell studie.

During the period August 1994-December 1995 783 cases of active tuberculos (TB) were notified to the health authorities in Sweden. By means of questionnaires sent to the consulting physicians (92 per cent response rate) the treatment outcome was studied twelve months after the diagnosis. Out of 676 patients only 71 per cent were reported to have completed the treatment and be cured of TB. This indicates that there is room for improvement as regards monitoring patients, if necessary by Directly Observed Therapy (DOT), in order to make sure that prescribed treatment is adhered to.

[Policy program to minimize spread of infection. Prolonged cough may be a sign of tuberculosis]. / Policyprogram för minskad smittspridning. Långdragen hosta kan vara tuberkulos.

In a worldwide epidemiological perspective, Sweden is well favoured with an annual tuberculosis incidence of approximately six cases per 100,000 of the population. Neither the impact of the HIV pandemic nor the occurrence of multiresistant strains of Mycobacterium tuberculosis has yet become a major problem in the care of tuberculosis patients in Sweden. Only a few per cent of HIV patients have developed tuberculosis, and during the period, 1991-94, only one per cent of M. tuberculosis isolates in Sweden were resistant to such antimycobacterials as isoniazid and rifampicin. However, the epidemiological situation in the neighbouring Baltic states is a matter for concern. Bovine tuberculosis has been eradicated in Sweden, the last case having been diagnosed in 1978. Although the reported efficacy of BCG (bacillus Calmette-Guérin) tuberculosis vaccine varies according to the population studied, protective rates of 70-85 per cent have been reported for Sweden and other west European countries. Re-vaccination of tuberculin-negative individuals has not been shown to yield added protection. The aim of a national programme for protection against tuberculosis is to preserve our favourable epidemiological situation by early detection of new cases, effective contact tracing, and BCG vaccination of children in population groups at risk. The primary means of achieving this is the education of health care personnel to retain tuberculosis as a differential diagnosis. Moreover, national guidelines for contact tracing must be duly observed, and immigrants from high prevalence areas need to be screened for tuberculosis. Registration of all cases of tuberculosis should be maintained at regional and national levels, and follow-up must be meticulous until a successful outcome of treatment is accomplished. Recommendations for dealing with tuberculosis should be made available and duly implemented at all hospitals caring for tuberculosis patients, in order to avoid nosocomial transmission. Although BCG vaccination at birth was formerly general in Sweden, since 1975 only children considered to be at risk have been vaccinated. Thus, non-vaccinated young adults are now entering the health care sector as students or employees, and should be offered BCG vaccination. Moreover, the epidemiological situation both in Sweden and in neighbouring countries needs to be monitored carefully in order that recommendations concerning BCG vaccination and other preventive measures can be modified if necessary.