Spectrum of Pediatric Tuberculosis in a Tertiary Care Setting in South India

Spectrum of Pediatric Tuberculosis in a Tertiary Care Setting in South India Abstract Background Pediatric tuberculosis (TB) is often underdiagnosed with poor estimate of its true burden. Availability of Xpert MTB/RIF assay enhances diagnostic capacity of pediatric TB. Methods A 3-year retrospective review of hospital records was done for all children diagnosed with confirmed and unconfirmed TB. Comparison was made between intrathoracic, single-site extrathoracic and disseminated TB. Results In total, 274 children had TB with 130 (47.4%) having confirmed TB. Pulmonary (23.4%), lymph node (23%) and central nervous system (12.8%) TB were the three commonest forms. HIV TB coinfection was 2.9%. Mycobacterial culture was positive in 90 (32.8%) and XPert MTB/RIF in 85 patients (31%). Mycobacterial confirmation was obtained in 45 (56.3%) intrathoracic TB, 69 (45.4%) extrathoracic TB and 16 (38.1%) disseminated TB. Correlation between positive Xpert and mycobacterial culture was poor (kappa 0.38). Rifampicin resistance was present in 25 (19.2%) of the 130 microbiologically confirmed TB. Conclusion Extrathoracic TB is common in children. Mycobacterial confirmation in pediatric TB is improved with use of Xpert. tuberculosis, childhood, pediatric INTRODUCTION The World Health Organization envisages a world free of tuberculosis (TB) and has adopted the End TB strategy since 2015 [1]. However, the problem of TB in children is not fully known, and it cannot be underestimated. Among children in endemic regions, TB remains an important but sometimes unrecognized cause of disease and death [2]. Estimates suggest that 11% of TB burden occur in children aged <15 years. However, underdiagnosis is often the rule, as children get diagnosed and treated only through referral hospitals [3]. Traditional methods of confirming diagnosis in children have depended on smear microscopy and mycobacterial culture, which are positive only in 5–10 and 40%, respectively [4]. In this brief report, we would like to present our experience with pediatric TB over a 3-year period in a tertiary care center in the era of enhanced TB diagnostic capabilities after the availability of Xpert MTB/RIF assay (Xpert). METHODS A retrospective review of the records of all children attending the pediatric infectious clinic and those admitted in the pediatric wards at the Christian Medical College, Vellore between January 2013 and December 2015 and diagnosed to have confirmed and unconfirmed pulmonary TB as per standard clinical case definitions [5], and confirmed extrapulmonary (Mycobacterium tuberculosis confirmed by culture or Xpert) and unconfirmed extra pulmonary TB (bacteriological confirmation not obtained with any two of the following: symptoms/signs suggestive of TB, biopsy consistent with TB, central nervous system (CNS) imaging consistent with TB) was performed. The type of TB, drug susceptibility patterns, HIV testing result, organ systems involved, mode of diagnosis and outcome measures were analyzed. Comparison was made between those with intrathoracic, single-site extrathoracic and disseminated TB (two or more sites involved, congenital and miliary TB). Descriptive statistics for the whole data set and kappa coefficient to measure agreement between Xpert TB polymerase chain reaction (PCR) and mycobacterial culture were performed. RESULTS During the study period, 274 children were diagnosed with TB. Of these, 130 (47.4%) had confirmed TB. The spectrum of TB disease is shown in Table 1. In total, 80 (29.2%) had intrathoracic, 152 (55.5%) had extrathoracic and 42 (15.3%) had disseminated TB. Lymph node (23%), CNS (12.8%), abdominal (9.9%) and musculoskeletal (8.4%) were the commonest forms of single-site extrathoracic TB. The mean age at diagnosis was 9.1 years (SD±5.1 years) for all forms of TB. HIV coinfection was present in 2.9%. Table 1 Distribution of the site of TB and positivity on Xpert and mycobacterial culture Site of TB Number (%) Confirmed diagnosis (Xpert or culture positive) Xpert and culture done Xpert and culture positive Xpert positive culture negative Culture positive Xpert negative Pulmonary 64 (23.4) 39 26 14 9 3 Lymph nodes 63 (23) 26 22 12 9 1 CNS 35 (12.8) 11 10 3 3 4 Abdominal 27 (9.9) 10 8 3 2 3 Bone 23 (8.4) 16 12 5 5 2 Pleural 16 (5.8) 6 3 1 1 1 Congenital TB 5 (1.8) 2 2 0 2 0 miliary 3 (1.1) 1 1 1 0 0 >1 site 34 (12.4) 15 14 6 6 2 Others 4 (1.5) 2 0 0 0 0 Site of TB Number (%) Confirmed diagnosis (Xpert or culture positive) Xpert and culture done Xpert and culture positive Xpert positive culture negative Culture positive Xpert negative Pulmonary 64 (23.4) 39 26 14 9 3 Lymph nodes 63 (23) 26 22 12 9 1 CNS 35 (12.8) 11 10 3 3 4 Abdominal 27 (9.9) 10 8 3 2 3 Bone 23 (8.4) 16 12 5 5 2 Pleural 16 (5.8) 6 3 1 1 1 Congenital TB 5 (1.8) 2 2 0 2 0 miliary 3 (1.1) 1 1 1 0 0 >1 site 34 (12.4) 15 14 6 6 2 Others 4 (1.5) 2 0 0 0 0 Table 1 Distribution of the site of TB and positivity on Xpert and mycobacterial culture Site of TB Number (%) Confirmed diagnosis (Xpert or culture positive) Xpert and culture done Xpert and culture positive Xpert positive culture negative Culture positive Xpert negative Pulmonary 64 (23.4) 39 26 14 9 3 Lymph nodes 63 (23) 26 22 12 9 1 CNS 35 (12.8) 11 10 3 3 4 Abdominal 27 (9.9) 10 8 3 2 3 Bone 23 (8.4) 16 12 5 5 2 Pleural 16 (5.8) 6 3 1 1 1 Congenital TB 5 (1.8) 2 2 0 2 0 miliary 3 (1.1) 1 1 1 0 0 >1 site 34 (12.4) 15 14 6 6 2 Others 4 (1.5) 2 0 0 0 0 Site of TB Number (%) Confirmed diagnosis (Xpert or culture positive) Xpert and culture done Xpert and culture positive Xpert positive culture negative Culture positive Xpert negative Pulmonary 64 (23.4) 39 26 14 9 3 Lymph nodes 63 (23) 26 22 12 9 1 CNS 35 (12.8) 11 10 3 3 4 Abdominal 27 (9.9) 10 8 3 2 3 Bone 23 (8.4) 16 12 5 5 2 Pleural 16 (5.8) 6 3 1 1 1 Congenital TB 5 (1.8) 2 2 0 2 0 miliary 3 (1.1) 1 1 1 0 0 >1 site 34 (12.4) 15 14 6 6 2 Others 4 (1.5) 2 0 0 0 0 Of the 274 patients, mycobacterial culture was positive in 90 (32.8%) and XPert TB PCR positive in 85 (31%). Mycobacterial confirmation was present in 45 (56.3%) of those with intrathoracic TB, 69 (45.4%) with extrathoracic TB and 16 (38.1%) in disseminated TB. Both Xpert TB PCR and mycobacterial culture were done in 176 patients. The kappa between the two was 0.38 [95% confidence interval (CI) 0.248–0.513]. As shown in Table 2, mycobacterial culture was negative in 44.7% of the Xpert TB PCR-positive patients and Xpert TB PCR was negative in 25.4% of the mycobacterial culture-positive patients. Drug susceptibility testing (DST) was available for 76 (84.4%) of the 90 positive cultures. In total, 14 patients (18.4%) with DST had multidrug resistance (MDR), 4 (5.3%) had polydrug resistance to INH and streptomycin, 3 (3.9%) had INH mono-resistance and 1 had rifampicin mono-resistance. Rifampicin resistance by Xpert was found in 21 (24.1%) patients. Two of these children with rifampicin resistance by XPert had susceptibility to rifampicin on phenotypic susceptibility testing. In all, rifampicin resistance, a marker of MDR was present in 25 (19.2%) of the 130 microbiologically confirmed TB patients and 9.1% in all. Table 2 A 2×2 Table of those who had both Xpert MTB/RIF and mycobacterial culture Culture positive Culture negative Total Xpert positive 47 (74.6%) 38 (33.6%) 85 (48.3%) Xpert negative 16 (25.4%) 75 (66.4%) 91 (51.7%) Total 63 (100%) 113 (100%) 176 (100%) Culture positive Culture negative Total Xpert positive 47 (74.6%) 38 (33.6%) 85 (48.3%) Xpert negative 16 (25.4%) 75 (66.4%) 91 (51.7%) Total 63 (100%) 113 (100%) 176 (100%) Table 2 A 2×2 Table of those who had both Xpert MTB/RIF and mycobacterial culture Culture positive Culture negative Total Xpert positive 47 (74.6%) 38 (33.6%) 85 (48.3%) Xpert negative 16 (25.4%) 75 (66.4%) 91 (51.7%) Total 63 (100%) 113 (100%) 176 (100%) Culture positive Culture negative Total Xpert positive 47 (74.6%) 38 (33.6%) 85 (48.3%) Xpert negative 16 (25.4%) 75 (66.4%) 91 (51.7%) Total 63 (100%) 113 (100%) 176 (100%) Only two patients with pulmonary TB were given directly observed short course intermittent therapy. All the other patients received daily therapy. On comparing outcome measures between the three forms of TB: treatment success, ongoing treatment, mortality and loss to follow-up was 84, 5, 4 and 5% for intrathoracic TB; 87, 3, 1 and 9% for extrathoracic TB and 86, 2, 5, 7 for disseminated TB, respectively. All mortality in the extrathoracic TB group occurred in those with TB meningitis. DISCUSSION Our study shows that there is still considerable burden of TB disease in the pediatric population. Intrathoracic TB contributed to only 29% in our study compared with 52% pulmonary TB reported by Gupta et al. [6] from India and 69.9% reported by Marais et al. [7]. The increased contribution from extrathoracic TB in our study is likely to be because of the patients getting referred to our center for unknown diagnosis. Mycobacterial confirmation on 47.4% of the children with TB is higher than the 34.2% obtained by Marais et al. [7] in South Africa. The use of molecular testing in addition to mycobacterial culture has enabled the increased mycobacterial confirmation. Referral bias would have also resulted in sicker children with more advanced disease coming to our hospital and thereby increasing the chance for mycobacterial confirmation. There is little information on bacteriological confirmation in most other pediatric studies that have described spectrum of TB disease [6, 8]. Clinical expertise is still important, despite the availability of Xpert in high TB burden settings [9]. There was poor correlation with a kappa of 0.38 between Xpert MTB/RIF and mycobacterial culture in our study. This is similar to the kappa of 0.44 (95% CI 0.18–0.70) obtained by Bacha et al. [9] in pediatric TB in Tanzania. It may be useful to do both Xpert and mycobacterial culture in the pediatric population to maximize mycobacterial confirmation of TB. The rapid turnaround time for the Xpert is also a big advantage compared with mycobacterial culture in obtaining a definite diagnosis of TB [10]. The proportion of rifampicin resistance (likely MDR) in our study was 9.1%, which is much higher than the 2.2% derived by modeling for the South East Asian region [11]. The 24.1% rifampicin resistance by Xpert MTB/RIF in our study is higher than the 15.4% rifampicin resistance by Xpert MTB/RIF reported across India as part of the National TB program [12]. Referral bias is likely to account for the high proportion of MDR TB in our study. Successful treatment ranged from 84 to 87% in our study depending on the type of TB and is lower than the 91.7% success reported by Alavi et al. [13] in Iran and higher than the 80.1% reported by Hailu et al. [14] from Ethiopia. The low rates of HIV TB coinfection is likely to have resulted in the better outcome in our study compared with the Ethiopian study. In conclusion, there is considerable extrathoracic disease in children with TB, and mycobacterial confirmation in pediatric TB has improved with use of Xpert. Use of both Xpert and mycobacterial cultures will increase mycobacterial confirmation of pediatric TB. REFERENCES 1 post2015_TBstrategy.pdf [Internet]. http://www.who.int/tb/post2015_TBstrategy.pdf? ua=1 (13 April 2017, date last accessed). 2 Tuberculosis in women and children - 1-s2.0-S014067361060579X-main.pdf [Internet]. http://ac.els-cdn.com/S014067361060579X/1-s2.0-S014067361060579X-main.pdf?_tid=4478d9a2-2027-11e7-8306-00000aab0f27&acdnat=1492074048_c1ea6d14a02a50fbacb07db45e3017b3 (13 April 2017, date last accessed). 3 Perez-Velez CM , Marais BJ. Tuberculosis in children . N Engl J Med 2012 ; 367 : 348 – 61 . Google Scholar CrossRef Search ADS PubMed 4 Starke JR. Pediatric tuberculosis: time for a new approach . Tuberculosis 2003 ; 83 : 208 – 12 . Google Scholar CrossRef Search ADS PubMed 5 Graham SM , Cuevas LE , Jean-Philippe P , et al. Clinical case definitions for classification of intrathoracic tuberculosis in children: an update . Clin Infect Dis 2015 ; 61(Suppl. 3) : S179 – 87 . Google Scholar CrossRef Search ADS 6 Gupta R , Garg A , Venkateshwar V , Kanitkar M. Spectrum of childhood tuberculosis in BCG vaccinated and unvaccinated children . Med J Armed Forces India 2009 ; 65 : 305 – 7 . Google Scholar CrossRef Search ADS PubMed 7 Research paper: The spectrum of childhood tuberculosis in a highly endemic area [Internet]. ResearchGate. https://www.researchgate.net/publication/6938158_The_spectrum_of_childhood_tuberculosis_in_a_highly_endemic_area (13 April 2017, date last accessed). 8 Indian Pediatrics - Editorial [Internet]. http://www.indianpediatrics.net/may2002/may-458-462.htm (13 April 2017, date last accessed). 9 Bacha JM , Ngo K , Clowes P , et al. Why being an expert – despite xpert –remains crucial for children in high TB burden settings . BMC Infect Dis 2017 . http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294844/ (17 April 2017, date last accessed). 10 Rufai SB , Singh A , Singh J , et al. Diagnostic usefulness of Xpert MTB/RIF assay for detection of tuberculous meningitis using cerebrospinal fluid . J Infect 2017 ; 75 : 125 – 31 . Google Scholar CrossRef Search ADS PubMed 11 Dodd PJ , Sismanidis C , Seddon JA. Global burden of drug-resistant tuberculosis in children: a mathematical modelling study . Lancet Infect Dis 2016 ; 16 : 1193 – 201 . Google Scholar CrossRef Search ADS PubMed 12 Raizada N , Sachdeva KS , Nair SA , et al. Enhancing TB case detection: experience in offering upfront xpert MTB/RIF testing to pediatric presumptive TB and DR TB cases for early rapid diagnosis of drug sensitive and drug resistant TB . PLoS One 2014 ; 9 : e105346. Google Scholar CrossRef Search ADS PubMed 13 Alavi SM , Salmanzadeh S , Bakhtiyariniya P , et al. Prevalence and treatment outcome of pulmonary and extrapulmonary pediatric tuberculosis in southwestern Iran . Casp J Intern Med 2015 ; 6 : 213 – 19 . 14 Hailu D , Abegaz WE , Belay M. Childhood tuberculosis and its treatment outcomes in Addis Ababa: a 5-years retrospective study . BMC Pediatr 2014 ; 14 : 61 . Google Scholar CrossRef Search ADS PubMed © The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Tropical Pediatrics Oxford University Press

Spectrum of Pediatric Tuberculosis in a Tertiary Care Setting in South India

Journal of Tropical Pediatrics , Volume Advance Article – Feb 13, 2018

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Abstract

Abstract Background Pediatric tuberculosis (TB) is often underdiagnosed with poor estimate of its true burden. Availability of Xpert MTB/RIF assay enhances diagnostic capacity of pediatric TB. Methods A 3-year retrospective review of hospital records was done for all children diagnosed with confirmed and unconfirmed TB. Comparison was made between intrathoracic, single-site extrathoracic and disseminated TB. Results In total, 274 children had TB with 130 (47.4%) having confirmed TB. Pulmonary (23.4%), lymph node (23%) and central nervous system (12.8%) TB were the three commonest forms. HIV TB coinfection was 2.9%. Mycobacterial culture was positive in 90 (32.8%) and XPert MTB/RIF in 85 patients (31%). Mycobacterial confirmation was obtained in 45 (56.3%) intrathoracic TB, 69 (45.4%) extrathoracic TB and 16 (38.1%) disseminated TB. Correlation between positive Xpert and mycobacterial culture was poor (kappa 0.38). Rifampicin resistance was present in 25 (19.2%) of the 130 microbiologically confirmed TB. Conclusion Extrathoracic TB is common in children. Mycobacterial confirmation in pediatric TB is improved with use of Xpert. tuberculosis, childhood, pediatric INTRODUCTION The World Health Organization envisages a world free of tuberculosis (TB) and has adopted the End TB strategy since 2015 [1]. However, the problem of TB in children is not fully known, and it cannot be underestimated. Among children in endemic regions, TB remains an important but sometimes unrecognized cause of disease and death [2]. Estimates suggest that 11% of TB burden occur in children aged <15 years. However, underdiagnosis is often the rule, as children get diagnosed and treated only through referral hospitals [3]. Traditional methods of confirming diagnosis in children have depended on smear microscopy and mycobacterial culture, which are positive only in 5–10 and 40%, respectively [4]. In this brief report, we would like to present our experience with pediatric TB over a 3-year period in a tertiary care center in the era of enhanced TB diagnostic capabilities after the availability of Xpert MTB/RIF assay (Xpert). METHODS A retrospective review of the records of all children attending the pediatric infectious clinic and those admitted in the pediatric wards at the Christian Medical College, Vellore between January 2013 and December 2015 and diagnosed to have confirmed and unconfirmed pulmonary TB as per standard clinical case definitions [5], and confirmed extrapulmonary (Mycobacterium tuberculosis confirmed by culture or Xpert) and unconfirmed extra pulmonary TB (bacteriological confirmation not obtained with any two of the following: symptoms/signs suggestive of TB, biopsy consistent with TB, central nervous system (CNS) imaging consistent with TB) was performed. The type of TB, drug susceptibility patterns, HIV testing result, organ systems involved, mode of diagnosis and outcome measures were analyzed. Comparison was made between those with intrathoracic, single-site extrathoracic and disseminated TB (two or more sites involved, congenital and miliary TB). Descriptive statistics for the whole data set and kappa coefficient to measure agreement between Xpert TB polymerase chain reaction (PCR) and mycobacterial culture were performed. RESULTS During the study period, 274 children were diagnosed with TB. Of these, 130 (47.4%) had confirmed TB. The spectrum of TB disease is shown in Table 1. In total, 80 (29.2%) had intrathoracic, 152 (55.5%) had extrathoracic and 42 (15.3%) had disseminated TB. Lymph node (23%), CNS (12.8%), abdominal (9.9%) and musculoskeletal (8.4%) were the commonest forms of single-site extrathoracic TB. The mean age at diagnosis was 9.1 years (SD±5.1 years) for all forms of TB. HIV coinfection was present in 2.9%. Table 1 Distribution of the site of TB and positivity on Xpert and mycobacterial culture Site of TB Number (%) Confirmed diagnosis (Xpert or culture positive) Xpert and culture done Xpert and culture positive Xpert positive culture negative Culture positive Xpert negative Pulmonary 64 (23.4) 39 26 14 9 3 Lymph nodes 63 (23) 26 22 12 9 1 CNS 35 (12.8) 11 10 3 3 4 Abdominal 27 (9.9) 10 8 3 2 3 Bone 23 (8.4) 16 12 5 5 2 Pleural 16 (5.8) 6 3 1 1 1 Congenital TB 5 (1.8) 2 2 0 2 0 miliary 3 (1.1) 1 1 1 0 0 >1 site 34 (12.4) 15 14 6 6 2 Others 4 (1.5) 2 0 0 0 0 Site of TB Number (%) Confirmed diagnosis (Xpert or culture positive) Xpert and culture done Xpert and culture positive Xpert positive culture negative Culture positive Xpert negative Pulmonary 64 (23.4) 39 26 14 9 3 Lymph nodes 63 (23) 26 22 12 9 1 CNS 35 (12.8) 11 10 3 3 4 Abdominal 27 (9.9) 10 8 3 2 3 Bone 23 (8.4) 16 12 5 5 2 Pleural 16 (5.8) 6 3 1 1 1 Congenital TB 5 (1.8) 2 2 0 2 0 miliary 3 (1.1) 1 1 1 0 0 >1 site 34 (12.4) 15 14 6 6 2 Others 4 (1.5) 2 0 0 0 0 Table 1 Distribution of the site of TB and positivity on Xpert and mycobacterial culture Site of TB Number (%) Confirmed diagnosis (Xpert or culture positive) Xpert and culture done Xpert and culture positive Xpert positive culture negative Culture positive Xpert negative Pulmonary 64 (23.4) 39 26 14 9 3 Lymph nodes 63 (23) 26 22 12 9 1 CNS 35 (12.8) 11 10 3 3 4 Abdominal 27 (9.9) 10 8 3 2 3 Bone 23 (8.4) 16 12 5 5 2 Pleural 16 (5.8) 6 3 1 1 1 Congenital TB 5 (1.8) 2 2 0 2 0 miliary 3 (1.1) 1 1 1 0 0 >1 site 34 (12.4) 15 14 6 6 2 Others 4 (1.5) 2 0 0 0 0 Site of TB Number (%) Confirmed diagnosis (Xpert or culture positive) Xpert and culture done Xpert and culture positive Xpert positive culture negative Culture positive Xpert negative Pulmonary 64 (23.4) 39 26 14 9 3 Lymph nodes 63 (23) 26 22 12 9 1 CNS 35 (12.8) 11 10 3 3 4 Abdominal 27 (9.9) 10 8 3 2 3 Bone 23 (8.4) 16 12 5 5 2 Pleural 16 (5.8) 6 3 1 1 1 Congenital TB 5 (1.8) 2 2 0 2 0 miliary 3 (1.1) 1 1 1 0 0 >1 site 34 (12.4) 15 14 6 6 2 Others 4 (1.5) 2 0 0 0 0 Of the 274 patients, mycobacterial culture was positive in 90 (32.8%) and XPert TB PCR positive in 85 (31%). Mycobacterial confirmation was present in 45 (56.3%) of those with intrathoracic TB, 69 (45.4%) with extrathoracic TB and 16 (38.1%) in disseminated TB. Both Xpert TB PCR and mycobacterial culture were done in 176 patients. The kappa between the two was 0.38 [95% confidence interval (CI) 0.248–0.513]. As shown in Table 2, mycobacterial culture was negative in 44.7% of the Xpert TB PCR-positive patients and Xpert TB PCR was negative in 25.4% of the mycobacterial culture-positive patients. Drug susceptibility testing (DST) was available for 76 (84.4%) of the 90 positive cultures. In total, 14 patients (18.4%) with DST had multidrug resistance (MDR), 4 (5.3%) had polydrug resistance to INH and streptomycin, 3 (3.9%) had INH mono-resistance and 1 had rifampicin mono-resistance. Rifampicin resistance by Xpert was found in 21 (24.1%) patients. Two of these children with rifampicin resistance by XPert had susceptibility to rifampicin on phenotypic susceptibility testing. In all, rifampicin resistance, a marker of MDR was present in 25 (19.2%) of the 130 microbiologically confirmed TB patients and 9.1% in all. Table 2 A 2×2 Table of those who had both Xpert MTB/RIF and mycobacterial culture Culture positive Culture negative Total Xpert positive 47 (74.6%) 38 (33.6%) 85 (48.3%) Xpert negative 16 (25.4%) 75 (66.4%) 91 (51.7%) Total 63 (100%) 113 (100%) 176 (100%) Culture positive Culture negative Total Xpert positive 47 (74.6%) 38 (33.6%) 85 (48.3%) Xpert negative 16 (25.4%) 75 (66.4%) 91 (51.7%) Total 63 (100%) 113 (100%) 176 (100%) Table 2 A 2×2 Table of those who had both Xpert MTB/RIF and mycobacterial culture Culture positive Culture negative Total Xpert positive 47 (74.6%) 38 (33.6%) 85 (48.3%) Xpert negative 16 (25.4%) 75 (66.4%) 91 (51.7%) Total 63 (100%) 113 (100%) 176 (100%) Culture positive Culture negative Total Xpert positive 47 (74.6%) 38 (33.6%) 85 (48.3%) Xpert negative 16 (25.4%) 75 (66.4%) 91 (51.7%) Total 63 (100%) 113 (100%) 176 (100%) Only two patients with pulmonary TB were given directly observed short course intermittent therapy. All the other patients received daily therapy. On comparing outcome measures between the three forms of TB: treatment success, ongoing treatment, mortality and loss to follow-up was 84, 5, 4 and 5% for intrathoracic TB; 87, 3, 1 and 9% for extrathoracic TB and 86, 2, 5, 7 for disseminated TB, respectively. All mortality in the extrathoracic TB group occurred in those with TB meningitis. DISCUSSION Our study shows that there is still considerable burden of TB disease in the pediatric population. Intrathoracic TB contributed to only 29% in our study compared with 52% pulmonary TB reported by Gupta et al. [6] from India and 69.9% reported by Marais et al. [7]. The increased contribution from extrathoracic TB in our study is likely to be because of the patients getting referred to our center for unknown diagnosis. Mycobacterial confirmation on 47.4% of the children with TB is higher than the 34.2% obtained by Marais et al. [7] in South Africa. The use of molecular testing in addition to mycobacterial culture has enabled the increased mycobacterial confirmation. Referral bias would have also resulted in sicker children with more advanced disease coming to our hospital and thereby increasing the chance for mycobacterial confirmation. There is little information on bacteriological confirmation in most other pediatric studies that have described spectrum of TB disease [6, 8]. Clinical expertise is still important, despite the availability of Xpert in high TB burden settings [9]. There was poor correlation with a kappa of 0.38 between Xpert MTB/RIF and mycobacterial culture in our study. This is similar to the kappa of 0.44 (95% CI 0.18–0.70) obtained by Bacha et al. [9] in pediatric TB in Tanzania. It may be useful to do both Xpert and mycobacterial culture in the pediatric population to maximize mycobacterial confirmation of TB. The rapid turnaround time for the Xpert is also a big advantage compared with mycobacterial culture in obtaining a definite diagnosis of TB [10]. The proportion of rifampicin resistance (likely MDR) in our study was 9.1%, which is much higher than the 2.2% derived by modeling for the South East Asian region [11]. The 24.1% rifampicin resistance by Xpert MTB/RIF in our study is higher than the 15.4% rifampicin resistance by Xpert MTB/RIF reported across India as part of the National TB program [12]. Referral bias is likely to account for the high proportion of MDR TB in our study. Successful treatment ranged from 84 to 87% in our study depending on the type of TB and is lower than the 91.7% success reported by Alavi et al. [13] in Iran and higher than the 80.1% reported by Hailu et al. [14] from Ethiopia. The low rates of HIV TB coinfection is likely to have resulted in the better outcome in our study compared with the Ethiopian study. In conclusion, there is considerable extrathoracic disease in children with TB, and mycobacterial confirmation in pediatric TB has improved with use of Xpert. Use of both Xpert and mycobacterial cultures will increase mycobacterial confirmation of pediatric TB. REFERENCES 1 post2015_TBstrategy.pdf [Internet]. http://www.who.int/tb/post2015_TBstrategy.pdf? ua=1 (13 April 2017, date last accessed). 2 Tuberculosis in women and children - 1-s2.0-S014067361060579X-main.pdf [Internet]. http://ac.els-cdn.com/S014067361060579X/1-s2.0-S014067361060579X-main.pdf?_tid=4478d9a2-2027-11e7-8306-00000aab0f27&acdnat=1492074048_c1ea6d14a02a50fbacb07db45e3017b3 (13 April 2017, date last accessed). 3 Perez-Velez CM , Marais BJ. Tuberculosis in children . N Engl J Med 2012 ; 367 : 348 – 61 . Google Scholar CrossRef Search ADS PubMed 4 Starke JR. Pediatric tuberculosis: time for a new approach . Tuberculosis 2003 ; 83 : 208 – 12 . Google Scholar CrossRef Search ADS PubMed 5 Graham SM , Cuevas LE , Jean-Philippe P , et al. Clinical case definitions for classification of intrathoracic tuberculosis in children: an update . Clin Infect Dis 2015 ; 61(Suppl. 3) : S179 – 87 . Google Scholar CrossRef Search ADS 6 Gupta R , Garg A , Venkateshwar V , Kanitkar M. Spectrum of childhood tuberculosis in BCG vaccinated and unvaccinated children . Med J Armed Forces India 2009 ; 65 : 305 – 7 . Google Scholar CrossRef Search ADS PubMed 7 Research paper: The spectrum of childhood tuberculosis in a highly endemic area [Internet]. ResearchGate. https://www.researchgate.net/publication/6938158_The_spectrum_of_childhood_tuberculosis_in_a_highly_endemic_area (13 April 2017, date last accessed). 8 Indian Pediatrics - Editorial [Internet]. http://www.indianpediatrics.net/may2002/may-458-462.htm (13 April 2017, date last accessed). 9 Bacha JM , Ngo K , Clowes P , et al. Why being an expert – despite xpert –remains crucial for children in high TB burden settings . BMC Infect Dis 2017 . http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294844/ (17 April 2017, date last accessed). 10 Rufai SB , Singh A , Singh J , et al. Diagnostic usefulness of Xpert MTB/RIF assay for detection of tuberculous meningitis using cerebrospinal fluid . J Infect 2017 ; 75 : 125 – 31 . Google Scholar CrossRef Search ADS PubMed 11 Dodd PJ , Sismanidis C , Seddon JA. Global burden of drug-resistant tuberculosis in children: a mathematical modelling study . Lancet Infect Dis 2016 ; 16 : 1193 – 201 . Google Scholar CrossRef Search ADS PubMed 12 Raizada N , Sachdeva KS , Nair SA , et al. Enhancing TB case detection: experience in offering upfront xpert MTB/RIF testing to pediatric presumptive TB and DR TB cases for early rapid diagnosis of drug sensitive and drug resistant TB . PLoS One 2014 ; 9 : e105346. Google Scholar CrossRef Search ADS PubMed 13 Alavi SM , Salmanzadeh S , Bakhtiyariniya P , et al. Prevalence and treatment outcome of pulmonary and extrapulmonary pediatric tuberculosis in southwestern Iran . Casp J Intern Med 2015 ; 6 : 213 – 19 . 14 Hailu D , Abegaz WE , Belay M. Childhood tuberculosis and its treatment outcomes in Addis Ababa: a 5-years retrospective study . BMC Pediatr 2014 ; 14 : 61 . Google Scholar CrossRef Search ADS PubMed © The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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Journal of Tropical PediatricsOxford University Press

Published: Feb 13, 2018

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