Adverse reactions to BCG.

In the post-war period the following BCG vaccines were successively in use for preventive vaccination in the Czech territory: (a) Copenhagen BCG, 1947-1950, (b) Prague BCG 725, 1951-1980, (c) Moscow BCG, 1981-1993, and (d) Behring BCG, from 1994 onwards. These BCG substrains can be now identified by modern methods of molecular genetics. Introducing the Moscow BCG brought about an elevated incidence of iatrogenic local and regional lymph node adverse reactions compared with the previous Prague BCG product and, as a new phenomenon, bone and joint involvements in children vaccinated at birth. The aim of this study was to analyze the incidence of postvaccination adverse reactions reported in the period from 1981 to 1993 as related to the Moscow BCG vaccine and, to demonstrate the effect of lower vaccination dosage on their frequency. The concentration of the Moscow BCG varied from 11 to 22.6 x 10(6) (average 16.2) CFU per 1 mg. In the period when full dose of BCG (0.05 mg per 0.1 ml) was applied to newborns 437 local and 195 regional lymph node complications were recorded, i.e. 0.08% of vaccinated were affected, demanding antituberculosis chemotherapy in 6.5% and surgical interventions in 24%. When the lowered vaccination dose (0.025 mg per 0.1 ml) was inoculated to newborns the local adverse reactions rose paradoxically affecting 0.1% of vaccinated but the regional lymph node reactions fell considerably to reach 0.01%; the demand for chemotherapy and surgery also fell down to 3.1 and 4.8% respectively. Bone and joint adverse involvements were recorded in 28 cases, i.e. in 3.7 per 10(5) of those vaccinated with the full dose.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of reduced doses of BCG vaccine on the occurrence of osseous complications after vaccination]. / Vliv snízené dávky BCG vakcíny na výskyt kostních komplikací po kalmetizaci.

The authors present a review on the incidence of osseous complications after calmettization with the Soviet BCG vaccine during the period from February 1, 1980 and June 30, 1985 when the total dose of the vaccine was used, as compared with the period from July 1, 1985 to December 31, 1989 when the dose of the vaccine was reduced to half. During the first period 28 cases of the disease were recorded (on average 5 cases in every year of birth) which was an incidence of 3.71/100,000 vaccinated children. After reduction of the vaccine dose to half another 11 cases of the disease were recorded, i.e. a reduction of the incidence to 2.30/100,000 vaccinated children. During the last two years of this period only one case in each vaccinated birth year was notified. A major part of the children with bone complications after calmettization was vaccinated with a batch of vaccine which contained a higher number of germs, close to the upper range of normal values. In the development of these complications thus, no doubt, among other factors also the dose of vaccine participates. As bone complications occur after calmettization even after reduction of the dose of vaccine to half, though the incidence was lower, is should be considered whether the hitherto used dose used for vaccination of neonates is not too high.

Osteitis caused by BCG vaccination.

A survey of 26 Czechoslovakian children diagnosed with BCG osteitis during 1981-1986 is presented. Mycobacterial culture was attempted in 19 cases with confirmation of bacillus Calmette-Guerin (BCG) Mycobacterium bovis strain in nine cases. Symptoms appeared approximately 17 months after vaccination; the proximal tibial end, distal femur, and proximal humerus were most affected. Although vaccination has been obligatory since 1953, a different vaccine was introduced in 1980, which led to the diagnosis of BCG osteitis in 1981. The vaccination doses, symptomatology, and methods of treatment are described. The risk of complications and a project for vaccination at later age are discussed.

The lipid substances and cytopathic effects in man of BCG strain "Copenhagen" and attenuated vole bacillus strain "Prague".

Both virulent and attenuated acid-fast micro-organisms (including BCG) may provoke in the infected or vaccinated host cytopathic effects characterized by the formation of specific granulation tissue or caseous necrosis. The mycobacterial antigens responsible for these reactions are localized in the lipid substances which are not essential for eliciting immunity to tuberculosis.The lipid contents of 3 mycobacterial strains (BCG-Prague, BCG-Copenhagen, and MP-Prague-the latter an attenuated strain of Myco. microti) were repeatedly analysed during the period 1964-66. The latter 2 strains-of high and low lipid content respectively-were injected intradermally into 2 tuberculin-positive human volunteers and their cytopathic effects studied. The local reaction to MP-Prague was minimal and healed completely after 1 month; severe ulcerous reactions requiring 4 months to heal were observed with BCG-Copenhagen.Electron-microscopic investigation of ultrathin sections showed marked differences in the surface structure of these strains, indicating that they had different ways of disintegrating in vivo.The authors suggest that mycobacterial strains with a low lipid content and established immunogenicity may be more valuable for tuberculosis prophylaxis than BCG or other attenuated mycobacteria.

Epidemiological and clinical study of tuberculosis in the district of Kolin, Czechoslovakia. Report for the first 4 years of the study (1961-64).

Many developed countries are faced with the problem of reorganizing their tuberculosis-control programme to bring it into line with modern conditions. The study reported was undertaken to provide guidelines for this reorganization. It was begun in the district of Kolín, Czechoslovakia, with a population of some 100 000, in 1961 and is still in progress. The paper covers the first 4 years of the study.In 1961 a thorough check-up was made on all persons registered as having active or inactive tuberculosis, or fibrotic lung lesions. In 1961 and 1963 a mass X-ray and tuberculin-testing campaign, with 95% coverage, was carried out for all persons over 14 years of age. All persons with active tuberculosis received adequate treatment. Persons registered as having tuberculosis or suspected tuberculosis were subjected to regular photofluorographic and bacteriological investigations. Newborn infants were given BCG vaccination, and persons aged 14 years and 19 years with negative tuberculin reactions were vaccinated.The prevalence of bacillary tuberculosis fell from 150 cases in 1960 to 91 in 1964, mainly owing to a decrease in the number of chronic cases. The incidence of bacillary tuberculosis detectable by direct smear microscopy, however, remained at about 25 cases throughout the period 1961-64. The risk of developing tuberculosis was found to be highest in persons with fibrotic lung lesions or inactive tuberculosis, and in men above 45 years of age and women above 65 with previously normal photofluorograms.It is concluded from the study that in developed countries priority should be given to adequate treatment of all persons with active tuberculosis, and to early diagnosis in persons consulting physicians and in the high-risk population groups.

Comparison of photometric and weight estimation of Mycobacterium content in homogenous BCG cultures containing Tween 80.

A comparison of the weight and photometric methods of primary assay of BCG vaccine has been made, using a vaccine prepared in albumin-free medium but containing Tween 80. In the weight method, the bacteria were trapped on a membrane filter; for photometry a Pulfrich Elpho photometer and an instrument of Czech origin were used. The photometric results were the more precise, provided that the measurements were made within two days of completion of growth; after this time the optical density of the suspension began to decrease slowly. The lack of precision of the weighing method is probably due to the small weight of culture deposit (which was almost on the limit of accuracy of the analytical balance) and to difficulties in the manipulation of the ultrafilter.