Indian Pediatrics 2000;37: 1106-1110
Evaluating Bacillus-Calmette- Guerin Vaccination by Tuberculin Skin Test Response
Tuberculosis (TB) is an important cause of morbidity and mortality throughout the world(1). According to WHO, one-third of the world population (1.7 million persons) are infected with Mycobacterium tuberculosis. There were 7.5 million cases of tuberculosis in 1990 with the majority of them in developing countries(1.2). Despite being a treatable and preventable disease, 90 million cases of tuberculosis will occur throughout the world in the 1990s, and TB will cause an estimated 30 million deaths during the current decade(3,4). TB is a global problem, and increases in case rates are occurring not only in developing countries of the world but also in several industrialized nations(4). The Turkish Republic data from National Tuber-culosis Committee shows that 25% of the population is infected (12 million persons).
For the prevention of TB, BCG vaccine developed by Calmettee and Guerin from bovine type Mycobacterium is used world-wide. The prevention rate varies from 0% to 80% and it has been used successfully for over 60 years(5,6). Repeat BCG immunization has been proposed for developing countries where prevalence of TB infection is high(6). In our country we give BCG immunization four times: In infancy at 2 months after birth, at six to seven years (first class), at eleven to twelve years (fifth class), and sixteen to seventeen years (high school). Using TT for the diagnosis of the disease is difficult because of acquired Mycobacterium tuberculosis, BCG vaccination and the cross-reaction with nontuberculosis mycobacterium infections. After BCG vaccine, response to TT is extremely variable, it depends on the strain used for BCG, scar counts, period after application of the vaccine and nutritional status of the child(7). Repeated BCG vaccination also increases sensitivity to tuberculin and causes extensive induration diameters as a result(8). The current study was conducted to evaluate tuberculin skin test (TT) response, and the relation between induration diameter and number of the scar according to age and period after BCG immunization in students of a first-school.
This study was done in a first-school where the socio-economic level of the students was average and a systematic vaccination program was being used. Before performing the TT, we conducted a physical examination on all children and noted the scar counts. We injected 5 TU of 0.1 ml PPD (Mantoux test) intradermally in lateral 1/3 of the left forearm of 776 children who were divided into eight groups according to age, including the pre-school class. After 72 hours, TT responses were assessed in 662 children by measuring induration diameters. The 114 children who did not come to school when TT responses were evaluated were excluded from the study. Children whose TT responses were 16 mm or more were asked for any contact with TB patient, were evaluated clinically and had chest radiography and ESR analysis.
A total of 662 students were analyzed in this study; 320 of them were girls (48%), and 342 of them were boys (52%). Their ages ranged between 6 to 12 years. Seventeen children were detected to have upper respiratory infection by physical examination before TT. Eight children had few rales and increased bronchial breath sounds during respiratory system examination but no signs of acute lower respiratory tract infection could be detected.
Twenty one of the children had no scar (3.2%), 211 had one, 398 had two, and 32 had three scars. Repeat BCG vaccination had been applied to students of first and fifth classes two months ago.
TT was applied to 662 children and indurations were evaluated after 72 hours. One hundred and forty nine of the 662 children had negative results (no indurations) (22.5%) and 513 of them had induration diameters of 5 mm or more (77.5%). The induration diameter according to age and number of scars are depicted in Tables I and II, respectively. In the pre-school class children, negative response was 85% and in the first class students (after two months of BCG revaccination) it was 3.7% (Table I). When the groups were compared between each other according to the mean induration diameter significant differences were found between preschool class and first class children (p <0.0001), children of first class and other classes (p <0.0001), children studying in second and IIIrd classes (p <0.01), Vth and VIth classes (p <0.001) and Vth and VIIth classes (p <0.001). There was no significant difference between IIIrd and IVth classes (p >0.05), first and Vth classes (p >0.05) and VIth and VIIth classes (p >0.05) according to the mean induration diameters.
When 662 children were assessed according to scar counts (no scar, one scar, two scar and three scar groups), negative response was 61.9% in no scar group, and 6.2% in three scar group (Table II). We observed an increase in the mean induration diameters according to scar counts. Significant differences were found between no scar and two scar groups (p <0.01), no scar and three scar groups (p <0.01) and one scar and two scar groups (p <0.01). There was no significant difference between no scar and one scar group (p >0.05) and two scar and three scar groups (p >0.05) according to the mean induration diameter.
Table I - Induration Diameters According to Age
Table II - Induration Diameters According to Numbers of Scars
Diagnosing TB in children often is difficult and one relies on clinical judgement and use of algorithms that include chest radiography and TT. However, interpretation of TT reactivity can be complicated by many factors such as infection with Mycobacterium tuberculosis, previous BCG vaccination and exposure to nontuberculous mycobacteria.
The aim of vaccination is to increase protection against other pathogenic myco-bacteria(6,9). The protection rate of the vaccine is reported to range from 0% to 80%(5-7). There is a debate about the activity of the vaccine in recent years. In developed countries BCG vaccine had been given up because of low risk of TB infection, and revaccination could considerably alter the TT response and the diagnosis of TB infection(6).
BCG vaccination plays an important role in preventing serious forms of the TB infection in children. BCG induced tuberculin sensitivity is a quantitative characteristic and has been used to compare vaccine efficacy(10). Vaccination of newborns and infants significantly reduces the risk of TB by 50% to 64%. Protection is observed across many populations, study designs, and forms of TB. Rates of protection against cases are as high as 83%(11,12). Age at vaccination did not enhance predictiveness of BCG efficacy(11). Tuberculin sensitivity depends on quality of BCG and strain used for the vaccine, vaccine count, age of repeat BCG, nutritional and immune status of the child and period after recent injection of the vaccine(8). For developing countries (like Turkey) with a higher prevalence of tuberculous infection, usually more than one BCG vaccine is recommended in order to prevent the children from TB infection(6). Repeated vaccination causes a bigger size in induration which correlates with the number of scars(8).
From the available knowledge on the subject, the tuberculin reaction which develops after BCG vaccination usually is not over 10-15 mm and this reactivity rapidly disappears within years(13). BCG doesnt convert the TT significantly when the cut off point is 10 mm in a highly prevalent TB population(14). Close contact with individuals with active TB is a very important factor for PPD skin conversion(15). Positive TT (induarion >10 mm) among children can be attributed to TB infection rather than previous BCG vaccination. Therefore, TT remains useful and it could be a good diagnostic test for TB infection even in vaccinated group(14,16). However, there is little data on the mean induration levels in children with repeated BCG vaccination. There is also no consensus on the cut off level of induration for TB infection in repeatedly vaccinated children.
In our study we evaluated the TT response according to age and found that in preschool class (6 years age once vaccinated) negative response was 85% and mean induration diameter was 1.2 mm; in first class (7 years age) after two months of repeat BCG (IInd dose), there was 3.7% negative response and mean duration diameter was 12.5 mm. During the following years we found that negative response increased as much as 44% and the induration diameter decreased year by year significantly. In the fifth class (11 years age) TT was applied after two months of III dose of BCG and negativity was 3.2% and the mean induration diameter was 13.3 mm. In sixth and seventh classes, the induration diameter was seen to decrease as mentioned above. This reiterates the results of the earlier reports in literature. We observed that the mean induration diameter increased after repeated BCG vaccination and at the same time with increased scar counts(6-8). The tuberculin sensitivity decreases gradually by the age of 4.0-6.3 years(17).
In earlier studies assessing the tuberculin reaction (induration diameter) according to scar counts (no scar, one scar, two scar and three scar) the indurations were 2.3 mm, 6.7 mm, 10.9 mm and 13.2 mm(8); 3.2 mm, 6.3 mm, 10.7 mm, and 14.8 mm(6) respectively. In our study also, the results were similar to the previous reports.
We found that revaccination can alter the TT response and therefore affect the usage of TT in the diagnosis of TB infection in this group of children. The TT response that is accepted as a criteria of TB infection are different among the children who are peviously vaccinated once, twice or third. This condition may be explained as an increase of tuberculin sensitivity. However, the ones who had contact with non-tuberculosis myco-bacteria (NTM) may demonstrate cross reaction and positive response for TT. Therefore, repeated BCG vaccination, contact with Mycobacterium tuberculosis and cross reaction with NTM cause difficulty in interpretation of TT.
We conclude that TT response is affected by many factors including age of child, age of BCG vaccination, scar counts and period after recent vaccination.
Contributors: APU coordinated the study(design and interpretation) and drafted the paper. EB and EB participated in the data collection, and drafting.