|Year : 2020 | Volume
| Issue : 2 | Page : 200-204
Tuberculin reactivity in schoolchildren, Kassala State, Sudan
Fatima Abbas Khalid1, Muataz Mohammed Eldirdery2, Mamoun El-Obeid El-Gasim3, Maowia Mohammed Mukhtar4
1 Department of Biochemistry, Faculty of Medicine and Health Sciences, University of Kassala, Kassala, Sudan
2 Department of Microbiology, Institute of Tropical Medicine, Ibn Sina University, Khartoum, Sudan
3 Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Kassala, Kassala, Sudan
4 Department of Immunology and Molecular Biology, Bioscience Research Institute, Ibn Sina University, Khartoum, Sudan
|Date of Web Publication||29-May-2020|
Fatima Abbas Khalid
Department of Biochemistry, Faculty of Medicine and Health Sciences, University of Kassala, Kassala
Source of Support: None, Conflict of Interest: None
Background: Tuberculin skin test (TST) is widely used for the assessment of Bacillus Calmette–Guérin (BCG) vaccine efficacy and screening of latent TB infection (LTBI). Poor or no data are available on the reactivity of tuberculin in Kassala State. The aim of the present study was to assess the response to the BCG vaccine and to estimate the prevalence of LTBI and the annual rate annual risk of tuberculous infection (ARTI) among vaccinated school children using TST. Methods: School-based cross-sectional study was conducted in three localities of Kassala State during 2016–2018. A cluster random sampling method was used for the enrolment. Five tuberculin units of 0.1 mL were injected intradermally in the left forearm of 2568 school children aged 5–15 years. The test was performed after the assessment of child health, nutrition status, and BCG scar status. Tuberculin reaction size was interpreted after 48–72 h. The collected data were analyzed using SPSS (v 20). The classical method was used to estimate ARTI. Results: Overall, there was no reaction in 81.5% of children. Only 0.66% of children had induration 10 mm–28 mm, indicating the prevalence of latent TB with an annual risk of 0.1%. Tuberculin reactivity was statistically significant affected by child age, gender, geographical location, and nutrition status (P < 0.05), whereas BCG scar status had no effect (P > 0.05). Conclusion: The study documented a high proportion of tuberculin nonreactivity irrespective of BCG vaccination status and provides data on the prevalence of latent infection among studied groups. Further studies are needed to address the reasons of low and nonreactivity of tuberculin, and evaluation of the BCG vaccine is recommended.
Keywords: Bacillus Calmette–Guérin vaccine, children, Sudan, tuberculin
|How to cite this article:|
Khalid FA, Eldirdery MM, El-Gasim ME, Mukhtar MM. Tuberculin reactivity in schoolchildren, Kassala State, Sudan. Int J Mycobacteriol 2020;9:200-4
|How to cite this URL:|
Khalid FA, Eldirdery MM, El-Gasim ME, Mukhtar MM. Tuberculin reactivity in schoolchildren, Kassala State, Sudan. Int J Mycobacteriol [serial online] 2020 [cited 2020 Jul 11];9:200-4. Available from: http://www.ijmyco.org/text.asp?2020/9/2/200/285219
| Introduction|| |
Tuberculosis remains a major public health concern worldwide. It is responsible of 1.5 million deaths and 10.0 million new cases, with the highest incidence in Africa and Asia regions. The disease severity is compounded by an asymptomatic infection in >90% of the infected population latent TB infection (LTBI). Children are at greatest risk for activation of infection, and they represent 11% of notified cases with 13.8% deaths according to the World Health Organization (WHO) estimation. In limited settings, diagnosis and implementation of effective control program and treatment are challenges because of paucibacillary of disease, difficulty to produce sputum or low diagnostic yield of spontaneous sputum. In 2017, Mathematical modeling estimates 32,000 out of 600,000 of rifampicin or multidrug-resistance occur in children worldwide.
Bacillus Calmette–Guérin (BCG) vaccine had been adopted for protection against severe different forms of TB., It is important in countries with a high burden of TB. In Sudan, it has been used as a routine according to BCG immunization policy at birth or a few days after birth. Scar development and tuberculin skin test (TST) are used for the assessment of its coverage and efficacy.,, According to the WHO estimation, the coverage was >80%, while the efficacy varies from 0% to 80% against different forms of TB.
The TST, additional to the efficacy of BCG vaccination assessment, it has been used as an epidemiologic tool to evaluate the prevalence of LTBI besides estimation of the annual risk of tuberculous infection (ARTI). ARTI is the probability of acquiring new tuberculous infection or reinfection over a period of 1 year. Three cutoff points of TST reaction (5, 10, and 15 mm) have been commonly recommended for the diagnosis under different settings. The 10 mm cutoff point is the most commonly used to estimate the prevalence of Mycobacterium tuberculosis infection.
Sudan accounts among the country with high TB burden in the Eastern Mediterranean region with incidence 71/100,000, and mortality rate reaches 11/100,000. The notified cases were 20,638, 10% of them were children.
Kassala accounts among the states of the high prevalence of TB, and it has long suffered from poverty with limited economic resources. Malnutrition is highly prevalent among children.
TB infection among children and the efficacy of the BCG vaccine in Kassala had never been surveyed with TST. Therefore, this study was designed to describe the reactivity of tuberculin among vaccinated school children in Kassala State as a response to BCG vaccination and indicator of the prevalence of LTBI.
| Methods|| |
Study design, population, and sample size
Kassala is one of the Sudan eastern states, neighboring Eretria. Administratively, it is divided into eleven localities; all of them are rural except Kassala and New Halfa. This cross-sectional study was conducted in Kassala and two rural localities, namely West Reefi Kassala and Reefi Kassala. The study comprised public elementary school children age of 5–15 years during 2016–2018.
The sample size was estimated at 3226 pupils using the following formula, based on the minimum prevalence of 10%, the clinical importance level of 15% of the true value, the significant level of 5%, and the design effect (DE) of two. This estimate was increased by 5% as a sampling error.
n = ([1.96]2 × p [1 − p] × DE)/(0.15 × p) 2.
Ethics committee at the Ministry of Health, Kassala State, approved this study in 2016, followed by the agreement of the Ministry of Education in the State.
Data collection and tuberculin skin test
A cluster random sampling method was used for the enrolment. Baseline information was collected by trained teachers aided by children's parents or guardians using a structured questionnaire. Prior filling the questionnaire, verbal consent was obtained from the child's parent/guardian after a clear explanation of the aim and objective of the study. The collected information includes Locality, child age, sex, BCG vaccination history, and socioeconomic status. Children who had a history of chronic disease, symptoms of infectious disease that might interfere with TST reactivity, allergic disease, and incomplete questionnaire at the time of screening, or absent during the period of TST screening were excluded from the study.
Clinical examination was performed by the medical practitioner to detect any sign of active TB, and then all children were nutritionally assessed by measuring weight and height. BCG vaccine scar was checked before the tuberculin test.
TST was performed as described by the manufacturer, briefly by injecting 0.1 mL containing five tuberculin unit purified protein derivative (Tuberculin Diluted, India, Ref. 10 LM005) intradermally in the left forearm after cleaning the skin by 70% ethanol. The induration was measured in millimeter after 48–72 h using a transparent, flexible 15 cm ruler. Each induration was assessed by one reader; when there was doubtand the second reading was done by reference reader. The result of the TST was read for 2568 children using several ranges of induration size (0, 1–4, 5–9, 10–14, and ≥15 mm). Induration ≥10 mm was considered positive for TB infection and referred to the clinic for further TB investigation.
Data entry and analysis were conducted using IBM SPSS Statistics for Windows, version 20 (IBM Corp., Armonk, NY, USA). Age was categorized as 5–9, 10–12, and 13–15 years. TST reaction induration size was categorized at cutoff points of <5 mm, ≥5 mm, ≥10 mm, and ≥15 mm. The results for each variable were presented as frequencies and proportion according to BCG scar status and TST reactivity. At cutoff point ≥10 mm, the annual risk of infection was calculated using the equation 1–(1–P) 1/meanage wherePis the tuberculin positive rate. Chi-squared was used to determine the difference in the case of BCG scar status and tuberculin reactivity. P < 0.05 was considered statistically significant.
| Results|| |
Of 3226 studied children, 658 were excluded from the analysis because of chronic diseases, unwillingness, or absenteeism in the testing and reading days leaving 2568 (79.6%) for complete analysis. They were from rural localities 1580 (61.6%), whereas 988 (38.5%) were urbanized. The boys-to-girls ratio was 1:1.2. Low level of education and socioeconomic status were the most characteristics of parents, as only 13.0% of fathers and 7.8% of mothers were educated. Most of the mothers (92.9%) were homemakers, and 69.5.0% of fathers were daily workers or had no work. The family size ranged from 2 to 17, with a median of 7.0 members. Normal weight was documented for 1416 (55.1%) of children. On clinical examination, no suspected active TB cases were identified [Table 1].
Bacillus Calmette–Guérin coverage and tuberculin reaction
According to mothers' information, all the children were vaccinated against TB. However, the overall prevalence of scar as an indicator of BCG coverage was (65.0%). [Table 2] shows the distribution of the studied population according to BCG scar status regarding gender, age, geographical location, and nutrition status. The proportion of children with BCG scar and without scar did not differ by gender, age, and nutrition status (P = 0.35, 0.882, and 0.56, respectively), but most (71.15%) of children with BCG scar were found in the urban locality (Kassala) (P = 0.00) than rural localities.
|Table 2: Distribution of BCG scar according to gender, age, nutrition status, and geographical location of children|
Click here to view
Following the tuberculin test, most 2100 (81.8%) of children had no detectable induration that recorded as 0 mm, while 468 (18.2%) had induration varied from 1 mm to 28 mm (mean 3.19 mm ± 3.29 and median 2.0). A strong positive reaction (≥10 mm and ≥15 mm) was recorded in 17 (0.66%) of cases [Table 3]. At cutoff ≥10 mm, the overall prevalence of LTBI was (0.66%) with a corresponding annual risk of infection 0.1%.
As shown in [Table 4], the tuberculin reactivity was found to be statistically significantly affected by child age, gender, geographical location, and nutrition status (P < 0.05) but was not affected by the BCG scar status (P > 0.05). It was relatively increased in girls (7.3%) than boys (1.7%). A high prevalence of positive reaction (6.7%) was recorded in old age (13–15 years) compared to 2.7% in the age of 5–9 years.
|Table 4: Tuberculin results according to gender, age, nutrition status, BCG scar status, and geographical location of studied groups|
Click here to view
| Discussion|| |
The present TST survey delineates the pattern of TST reaction in school children in Kassala State. It documented a high proportion of nonresponding (0 mm) or negative (1–4 mm) tuberculin regardless to BCG vaccination status of children. The prevalence of nonreaction with different proportions was reported in different areas: Sudan, Central African Republic, Nigeria, and India where the proportion was very low (9%). Negative or nonreaction of tuberculin may be attributed to the variation of PPD manufacturing and the dose, or to BCG vaccine and age of studied groups. Furthermore, it can be related to the cell-mediated immunity against TB. People with severely weakened immune systems sometimes are unable to mount the inflammatory reaction that causes a positive result and hence, they can have a negative skin test even if they are infected with the bacteria. Low-socioeconomic status and prevalence of malnutrition among studied groups had a negative impact on the immune system. Hence, it is necessary to assess the cell immunity and vaccination processes in later childhood and adolescence in the studied areas where TB is endemic.
The reactivity of TST was associated with child age, gender, nutrition, socioeconomic status, and geographical location. These findings were supported by different studies in different areas.,,, Contrary, other studies determined no association of TST reactivity with nutrition status.,, Low-socioeconomic status reflects poor living conditions and overcrowding, as some family size exceeded ten members. It is worsening that the site of this study, Kassala State, has long suffered chronic poverty, lack of adequate access to basic services such as education and health care, besides the high level of malnutrition. Collectively these factors have a negative impact on the child nutrition status and immunity and, therefore, response to TST.
Poor impact of the BCG vaccine on tuberculin reactivity encourages the use of TST for estimation of the prevalence of TB infection. In our survey, 96.0% of vaccinated children with BCG scar were negative or not reacted. This finding is consistent with those of other studies., Many studies in other countries have demonstrated the usefulness of the TST for the screening of TB infection regardless of BCG status, and BCG vaccine efficacy wanes after about 5 years. The proportion of children who had TST reaction above ≥10 mm cutoff was 0.66% with the annual rate 0.1%, which are less than the finding in the Central African Republic at the same cutoff point and in Iran where the prevalence and ARTI were 3.6% and 0.48%, respectively, and in Hong Kong 1.93%. The prevalence of LTBI and ARTI is expected to be higher than the finding, and this may be due to drop out from school as the study showed decrease the number of students in the old age due to low-socioeconomic status. Children who are not at school are at higher risk for TB because they often live in families of lower socioeconomic status.
| Conclusion|| |
The study documented a high proportion of nonreaction or negative tuberculin test, irrespective of BCG status, and provides data on the prevalence of latent infection and the annual risk. The reactivity of tuberculin was significantly affected by age, gender, nutrition status, and geographical location. Further studies are needed, and the evaluation of the BCG vaccine is recommended.
Financial support and sponsorship
This work is financially supported by the Ministry of Higher Education and Scientific Research, Sudan.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ramos JM, Pérez-Butragueño M, Tisiano G, Yohannes T, Reyes F, Górgolas M. Evaluation of Ziehl-Neelsen smear for diagnosis of pulmonary tuberculosis in childhood in a rural hospital in Ethiopia. Int J Mycobacteriol 2013;2:171-3. [Full text]
Huynh J, Marais BJ. Multidrug-resistant tuberculosis infection and disease in children: A review of new and repurposed drugs. Ther Adv Infect Dis 2019;6:2049936119864737.
Black GF, Fine PE, Warndorff DK, Floyd S, Weir RE, Blackwell JM, et al
. Relationship between IFN-gamma and skin test responsiveness to Mycobacterium tuberculosis
PPD in healthy, non-BCG-vaccinated young adults in Northern Malawi. Int J Tuberc Lung Dis 2001;5:664-72.
Storgaard L, Rodrigues A, Martins C, Nielsen BU, Ravn H, Benn CS, et al
. Development of BCG scar and subsequent morbidity and mortality in rural guinea-bissau. Clin Infect Dis 2015;61:950-9.
World Health Organization. Global Tuberculosis program and global program on vaccines. Statement on BCG revaccination for the prevention of tuberculosis. Wkly Epidemiol Rec 1995;70:229-31.
Gram L, Soremekun S, ten Asbroek A, Manu A, O'Leary M, Hill Z, et al
. Socio-economic determinants and inequities in coverage and timeliness of early childhood immunisation in rural Ghana. Trop Med Int Health 2014;19:802-11.
Gidado S, Nguku P, Biya O, Waziri NE, Mohammed A, Nsubuga P, et al
. Determinants of routine immunization coverage in Bungudu, Zamfara State, Northern Nigeria, May 2010. Pan Afr Med J 2014;18 Suppl 1:9.
Targeted tuberculin testing and treatment of latent tuberculosis infection. American thoracic society. MMWR Recomm Rep 2000;49:1-51.
World Food Program. A Comprehensive Food Security Assessment in Kassala State, Sudan, UN World Food Program, Kassala State Ministry; 2012.
Rieder HL, Chadha VK, Nagelkerke NJ, van Leth F, van der Werf MJ, KNCV Tuberculosis Foundation. Guidelines for conducting tuberculin skin test surveys in high-prevalence countries. Int J Tuberc Lung Dis 2011;15 Suppl 1:S1-25.
Ismaiel WM, Khalil EA, Bygbjerg IC, Osman FM, Musa AM, El-Hassan AM. Coverage and efficacy of BCG vaccination in displaced populations: A measure of effectiveness of an expanded program of immunization. Khartoum Med J 2008;1:30-3.
Gorish BM, Saleh FM, Mohammed FA, Mohammed SA, Ahmed SR, Yousif RA, et al
. Screening of BCG Vaccine efficacy among healthy vaccinated adults in Khartoum, Sudan. Mycobact Dis 2018;8:4.
Minime-Lingoupou F, Ouambita-Mabo R, Komangoya-Nzozo AD, Senekian D, Bate L, Yango F, et al
. Current tuberculin reactivity of schoolchildren in the central African republic. BMC Public Health 2015;15:496.
Gambo MJ, Lawan UM, Ahmad HR, Ogala WN. Assessment of tuberculin reactivity of BCGvaccinated infants in Zaria, Nigeria. Niger J Basic Clin Sci 2014;11:104. [Full text]
Uppada DR, Selvam S, Jesuraj N, Bennett S, Verver S, Grewal HM, et al
. The tuberculin skin test in school going adolescents in South India: Associations of socio-demographic and clinical characteristics with TST positivity and non-response. BMC Infect Dis 2014;14:571.
Jentoft HF, Omenaas E, Eide GE, Gulsvik A. Tuberculin reactivity: Prevalence and predictors in BCG-vaccinated young Norwegian adults. Respir Med 2002;96:1033-9.
Shingadia D, Novelli V. Diagnosis and treatment of tuberculosis in children. Lancet Infect Dis 2003;3:624-32.
Kiwanuka JP. Interpretation of tuberculin skin-test results in the diagnosis of tuberculosis in children. Afr Health Sci 2005;5:152-6.
Pang Y, Kang W, Zhao A, Liu G, Du W, Xu M, et al
. The effect of bacille Calmette-Guérin vaccination at birth on immune response in China. Vaccine 2015;33:209-13.
Chan PC, Chang LY, Wu YC, Lu CY, Kuo HS, Lee CY, et al
. Age-specific cut-offs for the tuberculin skin test to detect latent tuberculosis in BCG-vaccinated children. Int J Tuberc Lung Dis 2008;12:1401-6.
Piñeiro R, Cilleruelo MJ, García-Hortelano M, García-Ascaso M, Medina-Claros A, Mellado MJ. Effect of nutritional status on Tuberculin skin testing. Indian J Pediatr 2013;80:271-5.
Addo KK, van den Hof S, Mensah GI, Hesse A, Bonsu C, Koram KA, et al
. A tuberculin skin test survey among Ghanaian school children. BMC Public Health 2010;10:35.
Raharimanga V, Ratovoson R, Ratsitorahina M, Ramarokoto H, Rasolofo V, Talarmin A, et al
. Tuberculin reactivity in first-year schoolchildren in Madagascar. Trop Med Int Health 2012;17:871-6.
Haghdoost AA, Afshari M, Baneshi MR, Gouya MM, Nasehi M, Movahednia M. Estimating the annual risk of tuberculosis infection and disease in Southeast of Iran using the Bayesian mixture method. Iran Red Crescent Med J 2014;16:e15308.
Leung CC, Yew WW, Tam CM, Chan CK, Chang KC, Law WS, et al
. Tuberculin response in BCG vaccinated schoolchildren and the estimation of annual risk of infection in Hong Kong. Thorax 2005;60:124-9.
[Table 1], [Table 2], [Table 3], [Table 4]