Annual risk of tuberculous infection measured using serial skin testing, Orel Oblast, Russia, 1991–2005
Courtney M. YuenT M KrapivinaBoris Y. KazennyyE. V. KiryanovaВ. А. АксеноваA. V. GordinaAlison FinlayJ. Peter Cegielski
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Abstract:
To compare trends in direct annual risk of tuberculous infection (ARTI) during 1991-2005 in relation to tuberculosis (TB) incidence and to indirect estimates of ARTI derived from the prevalence of tuberculin skin test (TST) positivity in schoolchildren in Orel Oblast, Russia.In 2005, we abstracted annual TST results and vaccination histories from a representative sample of schoolchildren in Orel Oblast, Russia, where bacille Calmette-Guerin (BCG) vaccination and annual TST of children are nearly universal. We calculated direct ARTI based on the percentage of children tested with TST conversions each year, excluding conversions following BCG vaccination.We analysed records from 13 206 children, with a median of 10 recorded TST results per child. The ARTI increased from 0.2% in 1991 to 1.6% in 2000, paralleling trends in TB incidence. Similar results were observed when the ARTI was estimated based on prevalence of infection among children aged 3-5 years using a 12 mm cut-off to define TST positivity. Results differed substantially when 10 or 15 mm cut-offs were used or when prevalence was determined among children aged 6-8 years.ARTI measured through TST conversion increased as TB incidence increased in Orel Oblast. ARTI measured through serial TSTs can thus provide an indicator of changing trends in TB incidence.Keywords:
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Groups of BCG-vaccinated guinea pigs were given a single Mantoux skin test 4 to 69 weeks after vaccination. The skin reactions tended to develop more slowly the longer the interval since BCG vaccination. Relatively quickly developing tuberculin skin reactions may be characteristic not only for repeated testing, but also for skin tests taken shortly after BCG vaccination.
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Abstract Extract Johne's disease of cattle is an important economic problem in many countries. Vaccination offers one of the most promising methods of control, but has the disadvantage that cattle so vaccinated may react to the tuberculin test; vaccination may therefore interfere with tuberculosis eradication. Early French work by Vallée and Rinjard (1926 Vallée, H. and Rinjard, P. 1926. Rev. gén. Méd. vét., 35: 1–1. [Google Scholar]) had indicated that vaccination did not result in a positive reaction to a subsequent mammalian tuberculin test, but Doyle (1945 Doyle, T. M. 1945. Vet. Rec., 57: 385–385. [Google Scholar]), in the United Kingdom, used improved tuberculins (intradermal neck test) and showed that a majority of vaccinated calves gave positive tuberculin reaction 1 to 2 months after vaccination. Buddle (1953 Buddie, M. B. 1953. Private Cominunication [Google Scholar]), in New Zealand, has obtained strong positive mammalian tuberculin reactions in experimental calves 3 months after vaccination. Stephens (1955 Stephens, E. H. 1955. Private Comninnication [Google Scholar]) observed vaccinated New Zealand cattle and reported that cattle one year after vaccination gave strong johnin reactions, slightly less avian tuberculin reactions, and moderate mammalian tuberculin reactions. He believed that any confusion regarding the positive mammalian reaction could be solved by examination for the vaccination nodule and conducting a comparative test; however, Doyle (1953 Doyle, T. M. 1953. Brit. vet. J., 109: 275–275. [Google Scholar]) has shown that goats vaccinated against Johne's disease and infected with tuberculosis may give higher avian tuberculin than mammalian tuberculin reactions; use of a comparative test might, therefore, fail to diagnose tuberculosis in vaccinated cattle.
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Bacillus Calmette Guerin (BCG) vaccination used in the prevention of tuberculosis may cause problems in interpreting the tuberculin skin test (TST), which is commonly used in the diagnosis of infection. A limited number of studies have been undertaken to investigate how length of time after BCG vaccination affects TST results. TST induration values of unvaccinated children were compared with those of children vaccinated once in order to determine the changes in TST responses after BCG vaccination. Mantoux TSTs were administered to 1145 children aged 1–6 y and induration was measured at 72 h. BCG scar status and average TST induration diameters were identified for each age group. Conclusion : Average TST induration in vaccinated children is significantly higher than that in unvaccinated children, and in the vaccinated group there is no statistically significant difference between induration values in the different age groups. BCG vaccination at the age of 0–2 mo affects TST for a long period and this condition does not change until 6 y of age.
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It had been shown earlier, in a retrospective study, that tuberculin sensitivity is stronger in children tested for the second time after vaccination than in those tested for the first time after vaccination. The hypothesis that the tuberculin test itself may reinforce sensitivity to a further test has now been confirmed in 2 strictly controlled prospective studies, which are reported here. The results refer to the tuberculin reactions 5 years after vaccination. These reactions were significantly larger in children who had had an intermediate test (less than 5 years after vaccination) than in those tested for the first time at 5 years. This was found equally for several BCG products, but there was a significant tendency for the PPD batch RT 19-20-21 to have a more pronounced effect than the other tuberculins.It follows from the results of these studies that a possible waning of tuberculin sensitivity cannot be revealed by regular tuberculin testing. Moreover, experiments in guinea-pigs have shown that restoration of sensitivity by means of an injection of tuberculin does not influence the acquired resistance; there are no particular reasons to believe that this should be different in man. Thus the authors consider the very common practice of giving regular tuberculin tests to vaccinated children, in order to decide on possible revaccination, to be devoid of any scientific basis.
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This article demonstrates that BCG revaccination when tuberculin test results are used as the reason for the revaccination of people with doubtful reactions or no reactions at all should be considered outdated. To show this a brief exposition on tuberculin sensitivity and acquired resistance to tuberculosis and then the technical background of the tuberculin test are presented followed by comments concerning tuberculin profiles of general population groups. Individual variations in BCG - induced allergy raise questions about a possible correlation of post-vaccination allergy and resistance. Epidemiological data and experimental facts, however, demonstrate that the degree of protection given the individual is not proportional to the degree of tuberculin skin sensitivity induced by vaccination. Recent findings show that lymphocytes from BCG vaccinated children retain sensitivity to tuberculin years after vaccination and even when skin reactivity has disappeared. Finally, tuberculin testing for the evaluation of BCG vaccination is discussed.
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Bacillus Calmette Guerin (BCG) vaccination used in the prevention of tuberculosis may cause problems in interpreting the tuberculin skin test (TST), which is commonly used in the diagnosis of infection. A limited number of studies have been undertaken to investigate how length of time after BCG vaccination affects TST results. TST induration values of unvaccinated children were compared with those of children vaccinated once in order to determine the changes in TST responses after BCG vaccination. Mantoux TSTs were administered to 1145 children aged 1–6 y and induration was measured at 72 h. BCG scar status and average TST induration diameters were identified for each age group. Conclusion: Average TST induration in vaccinated children is significantly higher than that in unvaccinated children, and in the vaccinated group there is no statistically significant difference between induration values in the different age groups. BCG vaccination at the age of 0–2 mo affects TST for a long period and this condition does not change until 6 y of age.
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Following a policy of BCG vaccination adopted in Kuwait more than 20 yrs ago, children receive their first vaccination just before starting school. Those who have a response of less than 10 mm induration to 2 tu of RT23 PPD, when they are 13 yrs old, are revaccinated. The effects of this revaccination on skin test positivity in a group of 18 yr old senior school children have been investigated. In a random study group 23% were found to have received BCG a second time. Revaccination resulted in a significant increase in positivity to tuberculin, and to the other 6 reagents tested, that was much more than would have been expected due to the passage of time alone in low responders. Scars of the second BCG vaccination were larger than those after the first vaccination, and showed a sex difference, with scars being significantly larger in boys than in girls. Boys also tended to show the largest responses to skin tests, with the notable exception of tuberculin to which girls showed the largest response. In most cases responses to skin tests were larger after revaccination than after a single vaccination. Based on this study, it is impossible to be sure that revaccination improved protective immunity, but the increase in tuberculin responsiveness, and recognition of environmental mycobacterial species may be indirect evidence supporting this conclusion.
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The BCG-Moreau Strain, which has been experimentally studied and used in the vaccination against tuberculosis in Brazil for 30 years, is tolerated so well by human beings that it can be given orally in repeated high doses to individuals in any allergic condition, inclusive of tuberculosis, without any inconvenience and without the glandular enlargements produced by administration of the other BCG strains by mouth. When the BCG-Moreau vaccine is prepared from 10-day cultures and its vitality is properly preserved, a single dose of 100 mg to newborn infants and 200 mg to other individuals with negative tuberculin tests confers cutaneous tuberculin allergy in more than 97% of the cases; so, the oral dose is equivalent to the parenteral methods of BCG vaccination as to the postvaccinal allergization. The protection so conferred against active tuberculosis reduces mortality and morbidity from tuberculosis to levels six and eight times lower. The fortnightly or monthly repetition of such doses until reaching a total of 600 mg (newborns) or 1200 mg (other individuals), i.e., the concurrent BCG vaccination, does not produce lymphadenitis, and generally makes the post vaccinal tuberculin allergy disappear; but the specific protection conferred by the single dose against the forms of the virulent tuberculosis is brought to a maximum by it. The inhibitory effects of the concurrent BCG vaccination can be also observed in patients who continue to be exposed to contagion; these present very low morbidity and mortality from tuberculosis also. The newborn infants who received concurrent BCG vaccination, even those who live with tubercubous people, have presented low morbidity and mortality from tuberculosis since 11 years of age when they were vaccinated; they have not received any additional dose of vaccine. In the individuals vaccinated with concurrent BCG, virulent super-infections frequently cause exacerbation of the tuberculin allergy, but rarely provoke roentgenographic pulmonary signs coinciding with hyperergy, and exceptionally determine progredient tuberculosis on guinea pigs inoculated with gastric contents. Few deaths of children vaccinated with concurrent BCG have been observed; all of them occurred in very infective places ("favelas"). When presenting positive tuberculin tests, children, adolescents and adults tolerate, without any inconvenience, repeated BCG-Moreau doses of 200 to 400 mg, at weekly, fortnightly or monthly intervals, even a total of several 10 gm doses of the vaccinegerm; these vaccinations determine a variable frequency of deallergization coinciding with a manifest increase in the specific resistance against tuberculosis. Children who contracted primary infections of tuberculosis tolerate oral BCG-Moreau vaccination perfectly, even if high doses are repeated; the vaccine gives them variable deallergization, and their specific resistance against the disease is always increased; it is no matter whether they are treated with antibiotics or not. The same facts are being observed regarding the tuberculous reinfection of adults. These data indicate that the original idea of prevention "e sensu strictiori" by the BCG has yielded ground to the concept of true immunization with live bacilli. In the course of this immunization there is both exaltation of the specific resistance (which can reach complete immunity) and attenuation, sometimes extinction, of the allergy which is created at first.
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Mycobacterium tuberculosis infections may be difficult to detect by the tuberculin test in populations where nonspecific tuberculin sensitivity (induced by BCG and "atypical" mycobacteria) is frequent. In those populations, the rate of M. tuberculosis infection can be determined by comparing the levels of sensitivity before and after BCG vaccination, and classifying as infected those who do not show increased sensitivity in the post-vaccination test. To test this method on a BCG-vaccinated population, a survey was carried out in a sample of 1,721 schoolchildren 6 to 10 years of age, from a suburban area of the city of Rio de Janeiro, where BCG vaccination had been carried out on a large scale. The results suggest that the method is valid for BCG-vaccinated populations, although its accuracy may be affected by the intrinsic variability of tuberculin tests and BCG vaccination, by the action of infections with non-tuberculous mycobacteria, and by low infection rates. The tuberculous infection rate found in the sample group (4.13%) was compared with the results of a tuberculin survey carried out in the same area in 1970, and the incidence of infection was found to be decreasing by 7.68% annually. The annual risk of tuberculous infection for 1986 was 0.36 or 0.51%, depending on the mathematical model used for the calculation. These figures are smaller than the official estimates derived from the incidence rates of notified cases or from surveys made before intradermal vaccination was adopted. This may be due to methodological error, inaccuracies of notification data, association between age and risk of infection and/or peculiarities of the surveyed area.
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