|Year : 2017 | Volume
| Issue : 3 | Page : 94-99
Prevalence of latent pulmonary tuberculosis in children with diabetes mellitus attending a Tertiary Care Hospital in Mansoura: a cross-sectional study
Mahmoud M Bakr1, Ashraf A Elsharkawy1, Yahya M Wahba1, Nermin Y Abo Elkheir2
1 Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||07-Oct-2017|
|Date of Acceptance||01-Nov-2017|
|Date of Web Publication||20-Apr-2018|
Yahya M Wahba
Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516
Source of Support: None, Conflict of Interest: None
Aims Tuberculosis (TB) and diabetes mellitus are closely associated with each other. We conducted a cross-sectional study to assess the prevalence and pattern of latent pulmonary TB in diabetic children using a combined screening tool.
Settings and design A cross-sectional study was carried out in a Tertiary Care Hospital, Mansoura, Egypt, during the period from January to December, 2016.
Materials and methods The study enrolled all diabetic children with the inclusion criteria who were available during the study period and attending the endocrinology outpatient clinics or admitted in the inpatient ward. A total of 70 diabetic patients completed tuberculin skin test (TST) reading, and their results were compared with those of 70 healthy controls. All patients were subjected to detailed medical history, complete physical examination, and laboratory and radiological evaluation. TB screening was done for both groups using TST, sputum microscopy and culture, and chest radiography. We used TST induration diameter more than 6 mm as the cut-off value to determine test positivity.
Results A total of 53 (75.7%) patients of the studied diabetic group were poorly controlled. TST was positive in 30% of the screened diabetic patients. Test positivity was significantly higher among diabetic group when compared with control group. TST positivity was significantly higher in poorly controlled diabetic cases. There was a statistically significant negative correlation between TST induration diameter and HBA1C.
Conclusion Diabetic patients are more vulnerable to latent pulmonary TB. The association between poor glycemic control and latent pulmonary TB among diabetic patients was evident. Combining TST with sputum culture and chest radiography did not improve screening results.
Keywords: diabetes mellitus, Egypt, latent, tuberculin skin test, tuberculosis
|How to cite this article:|
Bakr MM, Elsharkawy AA, Wahba YM, Abo Elkheir NY. Prevalence of latent pulmonary tuberculosis in children with diabetes mellitus attending a Tertiary Care Hospital in Mansoura: a cross-sectional study. Alex J Pediatr 2017;30:94-9
|How to cite this URL:|
Bakr MM, Elsharkawy AA, Wahba YM, Abo Elkheir NY. Prevalence of latent pulmonary tuberculosis in children with diabetes mellitus attending a Tertiary Care Hospital in Mansoura: a cross-sectional study. Alex J Pediatr [serial online] 2017 [cited 2019 Jan 23];30:94-9. Available from: http://www.ajp.eg.net/text.asp?2017/30/3/94/230764
| Introduction|| |
Tuberculosis (TB) and diabetes mellitus (DM) are closely associated with each other as common comorbidities and could be considered together as an epidemic in some countries . DM increases the risk of active TB development following infection compared with nondiabetic patients . DM can complicate TB treatment and/or accelerate TB disease .
The pathophysiological basis for this association is thought to be mediated through alterations in the immune response against Mycobacterium tuberculosis . This occurs through affection of both innate and adaptive immunity . Affection of innate immunity occurs through accumulation of the advanced end-products of glycation that impair functions of phagocytes ,. Regarding adaptive immunity, higher levels of interleukin 2 and T-cell helper 1 (interferon γ) and T-cell helper 17 cytokines and a lower frequency of natural T-regulatory cells (CD4+, CD25+, and CD127−) are found in diabetic patients and increase the likelihood for TB coexistence .
The strong association between DM and TB necessitates bidirectional screening to identify newly diagnosed DM in patients with active TB or latent TB infection in patients with DM . Indeed, in countries with high prevalence of DM, the risk of TB disease development owing to DM exceeds even that of human immune deficiency virus .
In the Middle East region, the WHO reported 1 000 000 TB cases (880 000–1 200 000) . Comparatively, 35 million diabetic patients were reported by the International Diabetes Foundation in this region . In Egypt, TB prevalence ranged from 14 to 44 cases per 100 000, whereas the prevalence of DM was 16.8%. The percentage range of DM in TB cases was 16.4–29.3% ,,,,.
Despite several methods used for screening of latent pulmonary TB, there is no consensus about the standard screening test. Using tuberculin skin test (TST) alone as a screening tool was practiced for a long duration, but low specificity and sensitivity limited its usefulness especially in immunosuppressed patients . Combining TST with other methods including mycobacteria growth indicator tube (MGIT) culture method, Ziehl–Neelsen staining method, and chest radiography was tried to improve screening sensitivity and specificity .
Worldwide, there are several national and international studies focusing on this important comorbidity in adults, but there is a dearth of studies in the pediatric age group. We conducted a cross-sectional study to assess the prevalence and pattern of latent pulmonary TB in diabetic children using a combined screening tool in a Tertiary Care Hospital, Mansoura, Egypt.
| Materials and methods|| |
Our study was carried out in the Endocrinology Unit of a Tertiary Care Hospital, Mansoura, Egypt, during a period from January to December 2016. This is a 420-bed, university-affiliated, public teaching hospital that provides primary to tertiary care in Delta region of Egypt.
The study enrolled all diabetic children who were available during the study period and were attending the endocrinology outpatient clinics or admitted in the inpatient ward. Inclusion criteria were proven diabetic state according to criteria of the American Diabetes Association , both sexes, and age groups of more than 4 years and less than 18 years. Patients with renal or hepatic illnesses and immune compromised children were excluded from the study.
A total of 244 diabetic children initiated screening; 113 failed to expectorate sputum and 61 missed TST reading visit ([Figure 1]). The remaining 70 patients (DG group) were compared with 70 healthy controls (CG group). DG group included 31 males and 39 females, whereas CG group included 34 males and 36 females.
|Figure 1 Tuberculosis screening results among studied children with diabetes mellitus. DM, diabetes mellitus; TB, tuberculosis; TST; tuberculin skin test.|
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The study was accepted by the Research Ethical Committee of Medical Faculty of Mansoura University (code number: MS/898). Written informed consents were obtained from all the participants’ parents or guardians who agreed to be enrolled in the research.
| Methods|| |
All patients were subjected to detailed medical history including age, sex, age of onset of DM, duration of DM, history of prolonged cough (>3 weeks), recurrent chest infection (>12 or more episodes of upper respiratory tract infection per year and recurrent pneumonia if developed three or more attacks over a year) , night sweating, body weight loss (>10% in the past 6 months), contact with patients with TB, history of passive smoking, and family history of chronic chest infection. Complete physical examination, including growth parameters (body weight, height, and BMI) and chest examination, was carried out by the pediatric resident of the endocrinology unit under the supervision of the staff members.
Laboratory investigations were done including complete blood count, fasting blood glucose, postprandial blood glucose, renal and liver function tests, erythrocytes sedimentation rate, C-reactive protein, and HBA1C. The diabetic patients were labeled as good controlled if HBA1C=5.5–6.8%, mild controlled if HBA1C=6.8–7.6%, and poorly controlled if HBA1C less than 7.6% .
TB screening was done for both groups using TST, sputum microscopy and cultures, and chest radiographies. TST was administered by injecting 0.1 ml of two tuberculin units of purified protein derivative (RT 23; Statens Serum Institute, Copenhagen, Denmark) into the volar surface of the forearm (intradermal) with a disposable syringe and a 27 G needle. The maximal transverse size of induration, not the erythema, was read (in millimeters) 48–72 h later with a ball-point pen and a ruler . We used TST more than 6 mm as the cut-off-value to determine TST positivity regardless of Bacillus Calmette–Guérin vaccination status . This procedure was carried out by a well-trained laboratory technician using the Mantoux technique.
Morning sputum samples (minimum 5 ml) were collected. Patients were instructed to rinse the mouth, clear the nose and throat, try a hot drink, and place both hands on the waist. Then they were asked and observed to take three deep breaths and cough up vigorously so that the sputum, not saliva, comes out from the lungs. All the samples were obtained spontaneously without induction, and precautions were taken to avoid contamination from the outside of the collecting tubes . The room, where the samples were collected, was well ventilated with an adequate distance between the participants and the laboratory technicians to avoid transmission of the bacilli .
Specimens were cultured using MGIT method (BD Biosciences, North Carolina, USA). Overall, 0.5 ml of the concentrated specimen suspension was added to MGIT tube, mixed well, incubated at 37°C, and read daily starting on second day of incubation following the procedure ‘Reading the Tubes’ up to 2 weeks . Positive samples were planned to be examined for acid-fast bacilli using the Ziehl–Neelsen method.
Standard chest radiographs were obtained with film-screen for all participants and reviewed independently.
SPSS (statistical package for the social sciences, version 16; SPSS Inc., Chicago, Illinois, USA) was used to analyze data. The data normality was first tested with Kolmogorov–Smirnov test. The studied data were normally distributed. Qualitative data were presented as numbers and percentage and compared using χ2-test. Fisher’s exact test was needed when more than 25% of the cells had expected count less than 5. Quantitative data were presented as mean±SD and compared using Student’s t-test. Person’s correlation coefficient was used to study the correlation between studied variables. P values less than 0.05 were considered to be statistically significant.
| Results|| |
Both groups were homogenous regarding age and sex (P=0.52 and 0.36). The mean ages of DG and CG groups were 10±4.54 and 10.94±4.03 years, respectively. Males represented 44.3% of DG group and 48.6% of CG group. Statistically significant increase in positive body weight loss was found in DG group in comparison with CG group (P=0.001) ([Table 1]). All participants were negative for night sweating, family history of chronic chest infection, and history of contact with patients with TB.
|Table 1 Demographic and clinical parameters of diabetic and control groups|
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The mean age of onset of DM and duration of disease in DG group were 2.9±2.59 and 7.1±4.4 years, respectively. A total of 53 (75.7%) patients of the studied DG group were poorly controlled, 14 (20%) patients were mildly controlled, and only three patients were good controlled.
Statistically insignificant differences were found between both groups regarding laboratory parameters apart from HBA1C, being higher in DG group (P=0.03) ([Table 2]).
[Table 3] revealed that 30% of the screened diabetic children were TST positive, which was statistically higher when compared with CG group (P=0.001). TST positivity was significantly higher in poorly controlled diabetic cases (P=0.001) when compared with sum of good and mild controlled diabetic cases ([Table 4]).
|Table 3 Distribution of participants in diabetic and control groups according tuberculin skin test result|
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|Table 4 Comparison between poorly and sum of good and mild controlled diabetic cases according to tuberculin skin test results|
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[Table 5] showed statistically insignificant correlations between induration diameters of TST and the studied clinical and laboratory variable in DG group, except for HBA1C, where statistically significant negative correlation was detected (r=−0.24 and P=0.042).
|Table 5 Person’s correlation between the studied clinical and laboratory variables and diameter of tuberculin skin test induration in tuberculin skin test positive cases|
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Regarding sputum cultures using MGIT method and chest radiography, all were negative for the studied participants.
| Discussion|| |
In recent decades, with the increasing prevalence of both DM and TB worldwide, the relationship between both diseases is re-emerging as a significant public health problem. The association between both diseases is more evident in developing countries where DM prevalence is rising and TB is an endemic problem .
In the current study, we screened diabetic patients regularly attending the endocrinology inpatient and outpatient clinics in a Tertiary Care Hospital, Mansoura, Egypt, for latent pulmonary TB. TST positivity among diabetic patients was 30%. A recent meta-analysis study involving 13 observational studies reported latent TB prevalence of 22.8% . In studies done in Singapore, Indonesia, and Malaysia, the prevalence of latent TB among diabetic patients was 28.2, 38.9, and 28.5%, respectively ,,. This variability could be explained by different sample sizes, different socioeconomic standards, different screening tools, and different cut-off values for considering TST positivity in the different studies.
In our study, TST positivity was significantly higher among diabetic group in comparison with nondiabetic children which could be explained by the liability of diabetic patients to early TB infection, being an immunosuppressed group. Our findings go hand in hand with the results of previous meta-analysis studies and reviews of literature ,,. In contrast to our results, some studies done in Africa failed to find such association .
In the current research, the high percent of poorly controlled diabetic cases (75.7%) together with the statistically higher TST positivity among the poorly controlled diabetic cases are important observations. These findings supports the positive association between poor glycemic control and coexistence or progression of TB ,.
However, after interpreting the results of sputum cultures using MGIT method and chest radiography, all participants showed negative results. These findings did not exclude the possibility for latent pulmonary TB taking into consideration the difficulty in obtaining ideal sputum samples in the pediatric age group despite following the standard instructions for sputum collection. Our speculation was supported by Datta et al.  in their comparative study where they found that instructions given for sputum collection varied greatly in different studies, and there is no consensus about the ideal method for sputum collection especially in the pediatric age group. We could also add that most cases with latent TB are closed cases, and the culture positivity may be strongly correlated with advanced disease stage.
From our study, the lack of significant correlation between TST positivity and the studied clinical data in the diabetic group copes with a Spanish study where the authors failed to find significant associations between TST positivity and the studied risk factors (prolonged cough, overcrowding, and household contacts) in the pediatric age group. However, in the same study, they reported significant associations between results of the Quantiferon-TB Gold in Tube (QFN-G-IT), Interferon Gamma Release Assay (IGRA), and T-SPOT TB methods and the studied risk factors . Moreover, Pealing et al.  in their study reported that age of onset and duration of DM did not affect the association between TB and DM. Martínez-Aguilar et al.  reported that contact with TB cases, living in prisons, hemoglobin values more than 14 g/dl, and HBA1C more than 7% were significant risk factors. This variability regarding risk factors is explained by different study designs and different population characteristics.Regarding the studied laboratory parameters, no statistically significant correlations were detected with diameter of TST induration in TST positive cases except for HBA1C which was inversely correlated. This means that poor glycemic control (higher HBA1C values) was associated with a smaller diameter of induration in TST positive cases. This is an expected observation especially when knowing that TST induration depends on cellular immune reaction  which is impaired in poorly controlled diabetic cases .
Limitations of the study
Small sample size, single-center study, and limited studied risk factors represented limitations to our research.
| Conclusion|| |
From the current study, we could conclude that diabetic patients attending our Tertiary Care Hospital were more vulnerable to latent pulmonary TB. The association between poor glycemic control and latent pulmonary TB among diabetic patients is evident. Combining TST with sputum culture and chest radiography did not improve screening results. For better screening results, we recommend adding serum tests to TST to overcome the problem of accurate sputum sampling. Among theses, Interferon Gamma Release Assay is a good example.
The authors greatly acknowledge Professor Othman El-Sayed Soliman, Professor of Pediatrics and Infectious Diseases, Faculty of Medicine, Mansoura University, Egypt, for his valuable guide and help.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]