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Year : 2014  |  Volume : 11  |  Issue : 2  |  Page : 104-109

Assessment of tuberculin reactivity of BCG-vaccinated infants in Zaria, Nigeria

1 Department of Paediatrics, Bayero University, Aminu Kano Teaching Hospital, Kano, Nigeria
2 Department of Community Medicine, Bayero University, Aminu Kano Teaching Hospital, Kano, Nigeria
3 Department of Paediatrics, Ahmadu Bello University, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Date of Web Publication6-Sep-2014

Correspondence Address:
Dr. Mahmud Jahun Gambo
Department of Paediatrics, Bayero University, Aminu Kano Teaching Hospital, Kano
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0331-8540.140360

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Introduction: Tuberculosis (TB) is a serious public health problem associated with high morbidity and mortality. BCG vaccination as part of TB prevention strategy is faced with many challenges. The study sought to determine post BCG vaccination scarring and tuberculin reactivity, which may serve as useful indicators of routine BCG vaccination in infants. Materials and Methods: The study was descriptive cross-sectional. Infants were selected and physically examined for presence and size of BCG scar. Mantoux test was performed. Data were analyzed using statistical package for the social sciences software (SPSS version 16.0). Chi-square and Fisher's exact tests were used for association between categorical variables while Pearson's correlation co-efficient was used for the correlation between BCG scar size and Mantoux reaction. P ≤ 0.05 was considered significant. Results: The male:female ratio of the subjects was 1.6:1.0 with a mean birth weight of 3.2 ± 0.4kg.Mean age at Mantoux test was 19.0 ± 3.0 weeks and the prevalence of BCG scar was 81.5% with a mean scar size of 5.3 ± 3.2mm. Mantoux test was positive in 202 (56.7%), negative in 133 (37.4%), and indeterminate in 21 (5.9%) infants. The Mantoux reaction was significantly associated with the age interval between BCG administration and time of Mantoux test (χ2 = 54.17, P < 0.05), the infants' gender (χ2 = 31.23, P < 0.05) and their nutritional status (χ2 = 22.60, P < 0.05). The reaction was not significantly associated with the social class of the infants' parents. Conclusion: The study demonstrated high prevalence of BCG scar and high Tuberculin skin test reaction. Regular evaluation of BCG vaccination is recommended using TST and scar observation as adjuncts to strengthen BCG vaccination processes for effective tuberculosis prevention.

Keywords: Bacilli calmette-guérin vaccination, bacilli calmette-guérin scar, infants, tuberculin reactivity

How to cite this article:
Gambo MJ, Lawan UM, Ahmad HR, Ogala WN. Assessment of tuberculin reactivity of BCG-vaccinated infants in Zaria, Nigeria. Niger J Basic Clin Sci 2014;11:104-9

How to cite this URL:
Gambo MJ, Lawan UM, Ahmad HR, Ogala WN. Assessment of tuberculin reactivity of BCG-vaccinated infants in Zaria, Nigeria. Niger J Basic Clin Sci [serial online] 2014 [cited 2022 Jan 17];11:104-9. Available from: https://www.njbcs.net/text.asp?2014/11/2/104/140360

  Introduction Top

Tuberculosis (TB) is a chronic necrotising infection caused by Mycobacterium tuberculosis and rarely by other pathogenic mycobacteria with variable pathological and clinical outcomes, whose diagnosis is especially difficult in infants and young children. [1],[2] BCG vaccination has been found to protect individuals from severe forms of TB disease. Tuberculin skin test (TST) as part of TB diagnostic workup is a reliable evidence of effectiveness of BCG vaccination and also provides an indication of the risk of TB infection. [3],[4],[5],[6] The test indicates hypersensitivity reaction to tubercle bacilli, or inoculation with BCG vaccine. The stronger the reaction, the greater the possibility of infection with M.tuberculosis without necessarily signifying active disease. [7],[8]

A positive post-vaccination tuberculin reaction indicates that vaccination has been properly conducted though, this may not necessarily give a direct measure of level of immunity to tuberculosis. [8],[9],[10] Algorithms for diagnosis of TB in children often includes TST, but prior BCG vaccination complicates the interpretation of TST, most especially in young infants. [11],[12]

Lastly, there is paucity of information regarding BCG vaccination scar formation and tuberculin testing in children in the Zaria area where TB is prevalent [13] and the usefulness of the BCG vaccination scar evaluation and tuberculin reactions has not been assessed as indicator of BCG vaccination uptake. This study therefore, assessed the level of post-vaccination tuberculin reactivity and the prevalence of BCG scar formation among BCG vaccinated infants in Zaria, Nigeria.

  Materials and Methods Top

This study was descriptive cross-sectional and hospital-based. The subjects were apparently healthy infants delivered at Ahmadu Bello University Teaching Hospital (ABUTH), Zaria that received BCG vaccination at first week of life. The sample size of 356 subjects was estimated using the Fisher's formula for calculating minimum sample size for descriptive studies, [14],[15] and a prevalence of 69.8% for the rate of tuberculin conversion following BCG vaccination in a previous study from Lagos. [16] Subjects were recruited at the weekly immunisation clinic of ABUTH, Zaria. Consecutive infants that were 9 to 24 weeks old at the time of tuberculin testing were enrolled for the study after obtaining consent from the mother/guardian. The infants were examined for evidence of acute illness and presence or absence of BCG scar. Those infants that received BCG vaccination after the first week of life and those in obvious state of clinical ill-health (e.g. thriving poorly, persistent thrush) were excluded from the study. Upon recruitment, all eligible infants were subjected to Mantoux test. This was done according to standard by intradermal injection of 0.1ml of purified protein derivative (PPD) RT23 with Tween 80, containing 5TU manufactured by BB-NCIPD Ltd, Sofia, Bulgaria. [10],[11],[12] The presence or absence of induration and the largest transverse diameter was determined by inspection, palpation and outlining, using a ball point pen. [11],[12] The weights and lengths of the infants at the time of Mantoux test administration were also measured and compared with the World Health Organization (WHO) reference values to determine the nutritional status of the subjects. [17]

The data was collected from April 2003 to September 2003, and ethical clearance for the study was obtained from the Ethics Committee of ABUTH. Data were analysed using statistical package for the social sciences (SPSS 16.0) statistical software. Quantitative variables were summarised using mean and standard deviation, whereas categorical variables were summarised as frequencies and percentages. The sizes of the Mantoux indurations were classified into three categories as 0-4mm, 5-9mm and ≥10mm indurations corresponding to negative, intermediate and positive reactions, respectively according to Odujinrin and Onifade. [11],[12],[16] Chi-square and Fisher's exact tests were used to determine association between categorical variables. Pearson's correlation co-efficient was used to determine correlation between BCG scar size and Mantoux reaction. A P ≤ 0.05 was considered statistically significant.

  Results Top

The mean age of the infants studied was 19.0 ± 3.0 weeks. The majority (75.6%) were 17 and 24 weeks old; 219 (61.5%) were males and 276 (77.5%) had good nutritional status. The characteristics of the infants are summarised in [Table 1].
Table 1: Respondent's personal and biological characteristics

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The prevalence of BCG scar was 79.5% among the male infants and 84.7% among the female infants, while the overall prevalence of BCG scar was 81.5%. BCG scar formation was not associated with the gender of the infants (χ2 = 1.52, P > 0.05). However, age at testing was significantly associated with presence of BCG scar in the infants (χ2 = 17.0, P < 0.05) as shown in [Table 2].
Table 2: Factors associated with BCG scar and Mantoux reaction in the infants

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Following the Mantoux test, majority of the subjects 202 (56.8%) reacted positive with induration measuring ≥10mm diameter. In all, 133infants (37.4%) had negative Mantoux reaction (0-4mm induration), while 21 (5.9%) had an indeterminate or borderline positive reaction (induration of 5-9mm).The Mantoux reaction was significantly associated with the age/duration between BCG administration and time of Mantoux test (χ2 = 54.17, P < 0.05), the infants' gender (χ2 = 31.23, P < 0.05) and their nutritional status (χ2 = 22.60, P < 0.05). The Mantoux reaction was not significantly associated with the social class of the infants' parents as depicted in [Table 2].

The relationship of BCG scar sizes and Mantoux induration diameters was also explored using the correlation co-efficient, and a very weak negative correlation was observed (r = -0.128).

  Discussions Top

The rate of BCG scar of 81.5% seen, was higher than that reported by Anochie and Nkanginieme [9] in Port-Harcourt, Nigeria, but slightly lower than rates reported by Odujinrin and Ogunmekan [16] in Lagos and Karalliedde et al. [18] in Sri-Lanka. The differences could be accounted for by variability in the study design and differences in demographic characteristic of subjects e.g. Lagos study enrolled subjects as early as four weeks post BCG vaccination.BCG vaccine's variable bio-activity and perhaps the subjectivity of exactness of administration technique may also account for the observed differences.It has been reported that 20-50% of children do not develop a scar following BCG vaccination, for reasons of insufficient doses. [19],[20] Higher frequency of BCG scar in males in this study contrasts with that of Sedaghatian et al. [21] who observed higher scar rate and TST conversion among female infants.No valid explanation for this sex predilection was suggested at present in infants and young children, but TST may be more sensitive in women than men due to a lesser delayed hypersensitivity (DTH) response in men. [22] Significantly, more subjects with BCG scars in this study had negative, indeterminate and positive responses compared to those without BCG scar. These findings contrasts with that of Karalliedde et al. [18] who reported a higher scar rate of 97% among 740 children and all those without scar had no response to tuberculin.In Odujinrin and Ogunmekan's [16] Lagos study, out of 84.2% of subjects with BCG scar, only 69.8% had developed detectable sensitisation to tuberculin.It may therefore be incorrect to conclude that the absence of BCG scar indicates a lack of BCG vaccination. Similarly, it is possible to have a vigorous local BCG scar and yet a negative TST. This is largely attributed to poor technique and malnutrition among other reasons. [12]

Three major groups of TST reactions were identified in this study.A group of 133 (37.4%) infants with negative TST of 0-4mm is higher than that reported by Sedaghatian and Shana'a, [23] who observed that 37 (14%) of 387 healthy full-term infants vaccinated with BCG at birth gave a negative TST when tested at 6-8 weeks post-vaccination as against 9-24 weeks in this study. Generally, the interval between BCG vaccination and TST affects the rate of tuberculin conversion following BCG vaccination. Therefore, the longer duration following BCG vaccination in this study might account for the higher proportion of negative TST results. Also higher negative TST observed in this study may imply that waning of hypersensitivity to tuberculin had started. Tuberculin reaction post-vaccination has been reported to wane over time, and this waning occurs more rapidly if BCG was given in the neonatal period than at a later date. [10],[11],[20],[24] The percentage of negative responders in this study was also higher than that reported by Omerod and Garnett, [24] whose subjects were tested at an earlier age of 6-9 weeks post-vaccination. However, some of the subjects in Omerod and Garnett [24] study were still TST positive when tested four years later in another follow-up study. [24] In a study, in India, Rajajee [25] showed that 50% of children after neonatal BCG vaccination were negative to TST, but in vitro test for lymphocyte proliferation in response to PPD was significantly higher in vaccinated children compared with non-vaccinated TST negative children. A negative TST post BCG vaccination may not therefore mean ineffective vaccination, as the degree of protection is not necessarily dependent on the degree of tuberculin skin sensitivity induced. [14],[23],[24] Many individuals who receive BCG vaccination were reported to never have a reactive tuberculin test, and in those with a reaction, the size of induration is often <10mm, and wanes after 4-5 years. [19],[20],[23],[24],[25]

In Nigeria, BCG vaccine is given in the neonatal period when the risk of infection is low and morbidity from dissemination during primary TB infection is high. BCG is only 40-70% efficacious for a period of 0-4 years. [2],[6],[19] Subjects with no BCG scar and negative TST may constitute a vulnerable group for severe tuberculosis infection either imminent or already occurring. This, in addition to the waning phenomenon may constitute additional reason for assessing vaccination processes in later childhood and adolescence, in some parts of the world, where BCG vaccination is routine and tuberculosis is prevalent. [6],[19],[20],[25],[26]

An indeterminate reaction of 5-9mm was seen among 21 infants (5.9%) of the infants. This reaction may be attributable to infections with non-tuberculous mycobacteria (NTM), since in areas of high prevalence of NTM, the post-vaccination tuberculin sensitivity was observed by Shehu [27] to be only partly induced by BCG vaccination. [25],[27] Therefore, it may be difficult to differentiate the 5-9mm group of reactors from the 0-4mm group of reactors and ≥10mm as wholly due to BCG vaccination, without dual or differential PPD testing. The prevalence of these NTM is not known in the Zaria area, although, Shehu [27] in 1982 demonstrated a prevalence of 8.5% among Fulani herdsmen, this needs to be further studied in the general population. It has been shown that infection with NTM could induce a protective response similar to that induced by BCG and that this infection could cause suppressive effects such that later response to BCG would be inhibited. [25],[26],[27]

A 3 rd group of 202 infants (56.7%) reacted positively to TST (>10mm) when tested from the age of 9 weeks. Odujinrin and Ogunmekan [16] detected sensitisation as early as 4 weeks after BCG vaccination. Although 84.2% of their subjects had BCG scars, only 69.8% developed detectable sensitisation to TST.Similarly, Hadefield et al. [28] demonstrated a 97.8% positive rate of tuberculin reaction after neonatal BCG vaccination. The figures in this study are therefore correspondingly lower when compared to the previous studies. It has been shown that studies involving different BCG vaccines, population, and age groups have consistently demonstrated that over 90% of BCG vaccine recipients who had a reaction ≥10mm develop the TST reactivity within 8-12 weeks after vaccination. [19],[20],[24],[25],[26] However, an observed induration of ≥10mm is more likely to be attributable to infection with tubercle bacilli and therefore, requires more careful interpretation and further evaluation for tuberculosis disease. [5],[19],[26],[29]

A child may become infected with tubercle bacilli because someone in the family has infectious TB. Also an undetected source of TB may already exist in the family when the child is born, especially during celebrations of the birth of the newborn, which is a common practice in African settings. In this case, even a short delay may result in vaccination coming after infection, [11],[19] giving a tendency to more positive induration following TST. In this study, reactions of 10 to 24mm indurations were considered to be more likely due to recent mycobacterial infection compared to indurations of 9mm or less. [3],[5],[19],[29] Using Mantoux test as an index, the larger the observed reaction, greater the possibility that there is M. tuberculosis infection. [23],[24] Subjects found to have a positive Mantoux test induration 10 to 24mm were therefore referred for further evaluation for active TB disease and subsequent appropriate management. Further follow-up of these groups of infants with positive reaction ≥10mm was not done in this study, as this was not part of the initial design of the study.

More males than females developed various grades of positive Mantoux induration but less negative induration as compared to females. These findings contrast with those of Sedaghatian et al. [21] in SriLanka, who observed a statistically significant higher tuberculin conversion in female term and pre-term infants than their male counterparts. Sex has not been known to affect tuberculin test indurations; this finding may need to be evaluated in further research.

The efficacy of BCG vaccination among malnourished children and the tuberculin response after BCG vaccination was significantly impaired in malnourished children. [30] The findings in the present study agree with those of other studies. [30],[31] Protein under-nutrition has been associated with alterations in immune functions mediated by T-cells and animal studies have also shown that BCG vaccination is less effective in protein-deficient animals than normally nourished controls. [30],[31],[32] In this study, the classification of malnutrition does not effectively differentiate between primaryprotein-deficiency and primary calorie-deficiency. Furthermore, the effect of intrauterine nutrition of the subjects in this study was not taken into consideration. This is because, even though the birth weight of the subjects was known, the lengths of the infants at birth were not available and hence their Ponderal indices, which are a better indicator of intrauterine growth retardation, could not be established. Therefore, the TST as affected by the intrauterine growth of the infants could not be assessed.

Majority of the parents (57.7%) belonged to the lower social classes IV and V, whereas only 34% of the total population were from the higher social classes I and II [Table 1]. A similar, though slightly higher value of the upper social class population was reported by Angyo et al. [33] in Jos. Socio-economic status is usually a reflection of the living condition of individuals. [33] It is assumed that individuals with low socio-economic status will have poor living standards, live in overcrowded conditions and are likely to be more exposed to diseases that could affect nutritional status and therefore response to tuberculin.

In this study, tuberculin test reactivity due to BCG vaccination did not show a significant association with socio-economic status of parents of the study participants [Table 2]. Social class is a reflection of the living standard and general attitude to health. [19],[31],[33] Therefore, it could be expected that subjects of high socio-economic status would probably show a predominant response to tuberculin test because of their expected better nutrition, but this was not so, as no significant association between socio-economic status and tuberculin test was found.

  Conclusion Top

The study demonstrated high prevalence of BCG scar of 81.5% and similarly high TST reaction of 88.0%. Only 12% showed negative TST and absent scar formation. Regular evaluation of BCG vaccination is recommended using TST and scar observation as adjuncts to strengthen BCG vaccination processes for effective tuberculosis prevention.

  References Top

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  [Table 1], [Table 2]


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