|Year : 2013 | Volume
| Issue : 2 | Page : 126-130
BCG status in children with tuberculosis: A multicenter study in northern Nigeria
Adeola A Orogade1, Patience Ahmed2, Sunday O Onazi3, Usman Abubakar4, Halimat Isa5
1 Department of Paediatrics, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
2 Department of Paediatrics, National Hospital, Abuja, Nigeria
3 Department of Paediatrics, Federal Medical Center, Gusau, Nigeria
4 Department of Paediatrics, Federal Medical Center, Bida, Nigeria
5 Department of Paediatrics, Lyons Hospital, Kaduna State, Nigeria
|Date of Web Publication||24-Dec-2013|
Adeola A Orogade
Cardiopulmunology Unit, Department of Paediatrics, Ahmadu Bello University Teaching Hospital, Zaria, PO Box 10142
Source of Support: None, Conflict of Interest: None
Background: Bacille Calmette-Guérin (BCG) vaccine has been in use since 1921, yet childhood TB is still very prevalent in Nigeria. Since BCG efficacy depends in part on appropriate vaccine utilization, this study was designed to investigate the current practice of BCG administration through determination of BCG status.
Methodology: Consecutive HIV negative children with new diagnosis of tuberculosis disease attending five outpatient clinics in Northern Nigeria were recruited over 2 years. Using a structured questionnaire, information with regards to their BCG status was obtained and each child was examined for the presence of a BCG scar. Logistic regression was performed to identify determinants of BCG status.
Results: There were 300 children aged between 1 month and 14 years. More than half of them (mainly residing in rural and semiurban areas) did not receive BCG and only one-third (49/138) of those vaccinated had identifiable BCG scars. Delivery at home was significantly associated with non-receipt of the BCG antigen (OR = 408, z =5.891, P < 0.001). Lack of BCG vaccination was a significant factor for extra pulmonary disease (χ2 = 37.34, OR = 11, P = 0.0001); with a four-fold increase in relative risk. Logistic regression showed that lack of a BCG scar correlated significantly with vaccination in non-governmental facilities (P = 0.006), positive tuberculin skin test (TST) values (P < 0.0001) but not with extra pulmonary disease (P = 0.909).
Conclusion: Childhood TB is still driven to a large extent by low BCG coverage. In a TB endemic region, the absence of a BCG scar in a symptomatic child is an indicator for TB screening.
Keywords: BCG, children, scar, tuberculosis, vaccine
|How to cite this article:|
Orogade AA, Ahmed P, Onazi SO, Abubakar U, Isa H. BCG status in children with tuberculosis: A multicenter study in northern Nigeria. J Med Trop 2013;15:126-30
|How to cite this URL:|
Orogade AA, Ahmed P, Onazi SO, Abubakar U, Isa H. BCG status in children with tuberculosis: A multicenter study in northern Nigeria. J Med Trop [serial online] 2013 [cited 2019 Dec 8];15:126-30. Available from: http://www.jmedtropics.org/text.asp?2013/15/2/126/123597
| Introduction|| |
Nigeria is classified as a high TB, high MDR-TB burden country (WHO, 2012)  Whereas TB infection and disease in children are believed to be sentinel events that indicate level of transmission within a community and effectiveness of TB control programs,  there are few accurate data worldwide on the true incidence of childhood TB. This is due to the paucibacillary nature of the disease and poor case reporting.  In response to these challenges, global TB programs have shifted focus to case detection and treatment while WHO has made attempts to document TB incidence in children under 15 years, albeit in smear positive cases.  However, there remains an unknown burden of smear negative TB in children, who could potentially swell the incidence rates to unknown magnitudes. In view of this, the role of vaccination for TB prevention cannot be overemphasized.
Currently, there is only one vaccine to protect against severe forms of TB, the attenuated live M. bovis vaccine (WHO 2011)  which has been in use since 1921. This vaccine is reported to be of varying efficacy in preventing tuberculosis. Nigerian studies including Babaniyi  and Odujinrin et al.,  showed 69.8% TST sensitivity 4 weeks post BCG, while meta-analysis of BCG efficacy of published studies by Colditz et al.,  using 12 case control and 8 prospective studies revealed a decreasing efficacy of about 50% (OR 0.49, CI 0.38-0.7). More so the factors that had been identified in literature to be responsible for decline in sensitivity include the implementation of vaccine delivery among others.  In recognition of this, a multicenter study was designed to explore the current practice of BCG vaccination across Northern Nigeria as it relates to childhood TB incidence in HIV negative children.
| Methodology|| |
Consecutive HIV negative children presenting with a diagnosis of tuberculosis (using a combination of clinical, radiological, and TST results) in four tertiary hospitals and a private hospital in Northern Nigeria (National Hospital, Abuja, Federal Medical Centre, Bida, Federal Medical Centre, Gusau, Ahmadu Bello University Teaching Hospital, Shika Zaria and Lyons Hospital, Kaduna) from January 2009 to December 2010 were recruited. Ethical approval was obtained from Ethics Committee of the participating institutions. Through the use of a structured questionnaire administered to the guardians (usually the parent) biodata was obtained as well as details of BCG vaccination in the subject such as age when BCG was given, place and the type of TB disease in the subject. The children were thereafter examined for the presence or otherwise of a BCG scar on their left upper arm. Their TST results were reviewed. TST was considered positive at 5 mm and above in children with no BCG scar and 10 mm and above in children with BCG scar. In severely malnourished children, an accelerated BCG response was considered equivalent to a positive TST.
Data were arranged in tables and figures and subjected to statistical analysis using Chi-square and logistic regression to identify determinants of BCG status. A P < 0.05 was considered as significant.
| Results|| |
Three-hundred (300) children aged between 1 month and 14 years were studied. Their median age was 5.5 years with a M:F ratio of 1.2:1. A total of 45% of them were under 5 years [Table 1]. About two-thirds of the study population were born at home and were mainly from rural and semi-urban areas and presenting to Bida, Gusau and Zaria study sites. In Abuja and Kaduna which are cities, more of the subjects were born in government and private hospitals. Pulmonary TB, the commonest presentation across study sites was found in 80% (240/300) of subjects followed by disseminated and spinal TB:8.3% (25/300) and 7% (21/300), respectively. Extra pulmonary disease was present as disseminated disease in infants, while spinal and nodal diseases occurred in the children aged 5-14 years.
[Table 2] illustrates the factors related to BCG vaccination across sites. BCG vaccine was only received by 46% (138/300) of the subjects including all the children from Abuja and most of Kaduna study sites and only a third each of children from Bida, Gusau and Zaria sites, respectively. Only 22 (15.9%) of those vaccinated were immunized within 24 h of life which had a significant impact on incidence (z = 0.564, P = 0.001). Most of the immunizations were done in government facilities, but only one-third (49/138) had visible BCG scars. Tuberculin skin test was diagnostic in 209/289 (69.7%) of cases.
One hundred and sixty-one of 200 children (80.5%) born at home were unvaccinated [Table 3] and odds of not receiving BCG when born at home was 408.69; z = 5.89 (P = 0.0001). Most of the mothers who had home deliveries were not motivated to have their babies immunized for various reasons including ignorance and concerns about immunization safety. Whereas all children but one each with spinal TB and disseminated disease were unvaccinated, 45% (108/240) of children with pulmonary disease were unvaccinated. Extrapulmonary TB was 11 times more likely to occur in the absence of BCG antigen (P <0.0001) with a four-fold higher relative risk, while a positive TST was almost twice as likely in the unvaccinated (OR = 1.7, P = 0.04) [Table 3], [Figure 1].
|Table 3: Bivariate statistical analysis-factors associated with non - receipt of BCG and no BCG scar |
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There was a five times less likelihood of having a BCG scar when vaccination was done in private facilities (P = 0.006). Whereas the absence of a scar was significantly associated with positive TST (OR = 17.72, P <0.0001) [Figure 1], the presence of a scar was not significantly different between pulmonary and extra pulmonary disease (X2 = 0.013, P = 0.909). [Table 3].
| Discussion|| |
In this series, 54% of children newly diagnosed with tuberculosis did not receive BCG. Inadequate BCG coverage is undoubtedly a major driver for childhood TB. In a 2003 National survey  of apparently healthy children in Nigeria (a country of high disease burden) up to 70.7% did not receive the BCG antigen, while WHO/UNICEF estimates  of BCG non-coverage at 2011 in healthy children was about 55%. Although this report is in children with disease, the lower proportion in the latter estimate corresponds to our findings, but these values are still unacceptably high if the goal of childhood TB control is to be achieved.
Delivery at home was significantly associated with non-receipt of BCG and there was a lack of motivation in the mothers to present at a health facility after birth. In this study as well as in previous Nigerian series,  concern about immunization safety, long distance to health facility and long waiting time at health facility have been suggested as reasons for low immunization coverage. Contra-wise knowledge of mothers on immunization benefits contributes to high coverage.  Another study specifically targeted at predictors of BCG status in our setting using behavioral ecological models  revealed other issues such as parental/household factor, community characteristics, and policy environment which were not investigated in this paper. The effect of not having BCG in this study was a four-fold increase in relative risk of incidence of extra pulmonary disease as compared to pulmonary. This supports the dictum that BCG protects against severe forms of TB.
Among the 138 children that had received BCG, only 16% (22/138) were vaccinated within 24 h of birth and another 25.3% (35/138) within the first week of life. In Nigeria the NPI recommendation is that BCG should be administered at birth or at most within the first week of life.  In a study in Zaria in 2003, Wammanda et al.,  found that BCG vaccination rates were 22% and 36.2% at first 3 days and 7 days of life, respectively, which are similar to the findings in this study. That study also identified home delivery as an important contributory factor to delay vaccination. Age at BCG administration impacted significantly on the incidence of disease with 58% occurring in those vaccinated after 1 week (z = 0.564, P = 0.0001). However an Indian study  comparing tuberculin sensitivity in 2 groups of neonates given BCG at birth and between 4 and 6 weeks of life did not find any statistical difference in their mean tuberculin reaction within 10-12 weeks post-inoculation. This seems to suggest comparable protection irrespective of time of administration. Longer follow up of this Indian cohort to determine the period taken for post-vaccinal wane of tuberculin reactions by each group would have been informative since incidence of disease in our series spanned up to 14 years of age in some of the children.
The BCG antigen was obtained mainly from government facilities, but it is noteworthy there was five times more likelihood of not having a BCG scar when vaccination was at private facilities (P = 0.006). Since 2002, there have been efforts at Public-Private Mix Direct Observed Therapy (PPMDOTS) which focuses mainly on case management and treatment with some success recorded.  However, the practice of vaccination in private facilities should be further evaluated in light of availability of trained personnel for BCG vaccine administration as well as appropriate vaccine cold chain adherence. A combination of these two factors might have been responsible for failed vaccine in the private facilities evidenced by "no BCG scar."
The BCG scar, the simplest and most accessible way of determination success of BCG inoculation was unidentifiable in 83.7% (251/300) of our subjects. Of these, over a third, 89/251 (35.5%) was in previously vaccinated children. Lack of a BCG scar in a child suspected to have tuberculosis clinically is therefore an important red flag for further investigation to confirm TB (pulmonary or extra pulmonary) in children. In children who have received BCG and do not have a BCG scar, there has been controversy about revaccination, ,, however in light of this current study where over a third of vaccinated children without BCG scar already had disease, it is necessary in our setting to determine the presence or otherwise of disease before considering revaccination where there is no scar.
Since childhood TB is paucibacillary, immune based tests are useful in diagnosis. The tuberculin skin test (TST) which was introduced about 100 years is still in use as the primary method of diagnosis of latent TB infection and disease. In this study, it was used in addition to clinical presentation and radiology to make a diagnosis. It was found to be more discriminatory in vaccinated children with no BCG scar, P < 0.0001 as compared to those who had had no prior BCG inoculation. In the former group the TST serves as a recall of immunity from previous exposure. In this situation both the prior vaccination and the new infection give rise to a > 10 mm TST reaction. Post-vaccinal tuberculin reactions are expected to wane due to the immaturity of the immune system in the newborn and so having a large size TST in the presence of other clinical and radiological parameters is strongly suggestive of disease.
Childhood TB is still driven to a large extent by low coverage of BCG immunization. The recent initiatives at home based newborn care should incorporate structured health instruction that would culminate in higher BCG coverage. Trained personnel for BCG inoculation should be available at birthing centers: Private or government and timely inoculation should be prioritized. The BCG status of the child in a TB endemic region as indicated especially by the absence of a scar should serve as an early indicator for further clinical and TST screening.
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[Table 1], [Table 2], [Table 3]