- ABSTRACT.
- INTRODUCTION
- MATERIALS AND METHODS
- RESULTS
- Search results.
- Quality of included studies.
- Findings.
- Site of TB and clinical features of PR.
- Time interval between starting therapy and development of PR.
- Risk factors for occurrence of PR.
- Effect of PR on clinical outcome.
- Additional duration of therapy after onset of PR.
- Use of immunomodulators and/or immunosuppressants for management of PR.
- DISCUSSION
- CONCLUSION
- Supplemental Materials
- ACKNOWLEDGMENT
- REFERENCES
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization, 2022. Global Tuberculosis Report 2023. Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/publications/i/item/9789240083851. Accessed June 15, 2023.
-
2.
World Health Organization (WHO), 2019. Global Tuberculosis Report 2019. Available at: https://www.who.int/publications/i/item/9789241565714. Accessed June 15, 2023.
-
3.
Pediatric TB Management Guidelines, 2022. National Tuberculosis Elimination Programme. Available at: https://tbcindia-wp.azurewebsites.net/wp-content/uploads/2023/05/9534339438Paediatric_TB_Mangement_Guideline_22082022_V1.pdf. Accessed June 15, 2023.
-
4.
Meintjes G, et al., 2008. Tuberculosis-associated immune reconstitution inflammatory syndrome: Case definitions for use in resource-limited settings. Lancet Infect Dis 8: 516–523.
-
5.
Done MM, Akkerman OW, Al-Kailany W, de Lange WCM, de Jonge G, Kleinnijenhuis J, Stienstra R, van der Werf TS, 2020. Corticosteroid therapy for the management of paradoxical inflammatory reaction in patients with pulmonary tuberculosis. Infection 48: 641–645.
-
6.
Afghani B, Leiberman JM, 1994. Paradoxical enlargement or development of intracranial tuberculomas during therapy: Case report and review. Clin Infect Dis 19: 1092–1099.
-
7.
Cheng VC, Ho PL, Lee RA, Chan KS, Chan KK, Woo PC, Lau SK, Yuen KY, 2002. Clinical spectrum of paradoxical deterioration during antituberculosis therapy in non-HIV-infected patients. Eur J Clin Microbiol Infect Dis 21: 803–809.
-
8.
Bloch S, Wickremasinghe M, Wright A, Rice A, Thompson M, Kon OM, 2009. Paradoxical reactions in non-HIV tuberculosis presenting as endobronchial obstruction. Eur Respir Rev 18: 295–299.
-
9.
Aggarwal D, Bhardwaj M, Kumar A, Saini V, Sawal N, 2020. Immune reconstitution inflammatory syndrome in non-HIV patients with tuberculosis. A case series. Indian J Tuberc 67: 143–147.
-
10.
Page MJ, et al., 2021. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 372: n71.
-
11.
Schiavo JH, 2019. PROSPERO: An international register of systematic review protocols. Med Ref Serv Q 38: 171–180.
-
12.
National Heart, Lung, and Blood Institute (NHLBI), 2021. Study Quality Assessment Tools. Available at: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. Accessed June 15, 2023.
-
13.
Munn Z, Barker TH, Moola S, Tufanaru C, Stern C, McArthur A, Stephenson M, Aromataris E, 2020. Methodological quality of case series studies: An introduction to the JBI critical appraisal tool. JBI Evid Synth 18: 2127–2133.
-
14.
R Foundation for Statistical Computing, 2015 . R: A Language and Environment for Statistical Computing. Available at: https://www.R-project.org/. Accessed December 12, 2023.
-
15.
Zhou Y, Qin Y, Mu T, Zengh H, Cai J, 2022. Magnetic resonance imaging findings of intraspinal tuberculoma in children. Front Neurol 13: 936837.
-
16.
Zhu H, Maoqiang T, Shui L, Xiaomei S, 2021. Risk factors of paradoxical response during anti-tuberculosis treatment in children with tuberculous meningitis. Zhonghua Shiyong Erke Linchuang Zazhi 36: 287–289.
-
17.
Shah I, Bhaskar MV, 2017. Paradoxical reactions in children with tuberculosis. Trop Doct 47: 109–113.
-
18.
Carazo Gallego B, Moreno-Pérez D, Nuñez Cuadros E, Mesa Fernandez A, Martin Cantero M, Obando Pacheco P, Urda Cardona A, 2016. Paradoxical reaction in immunocompetent children with tuberculosis. Int J Infect Dis 51: 15–18.
-
19.
Olive C, Mouchet F, Toppet V, Haelterman E, Levy J, 2013. Paradoxical reaction during tuberculosis treatment in immunocompetent children: Clinical spectrum and risk factors. Pediatr Infect Dis J 32: 446–449.
-
20.
Thampi N, Stephens D, Rea E, Kitai I, 2012. Unexplained deterioration during antituberculous therapy in children and adolescents: Clinical presentation and risk factors. Pediatr Infect Dis J 31: 129–133.
-
21.
Kumar R, Prakash M, Jha S, 2006. Paradoxical response to chemotherapy in neurotuberculosis. Pediatr Neurosurg 42: 214–222.
-
22.
Gupta M, Bajaj BK, Khwaja G, 2003. Paradoxical response in patients with CNS tuberculosis. J Assoc Physicians India 51: 257–260.
-
23.
Kumar S, Puri V, Mehndiratta MM, Gupta S, Bhutani A, Sharma C, 1995. Paradoxical response to antitubercular drugs. Indian J Pediatr 62: 695–701.
-
24.
Teoh R, Humphries MJ, O’Mahony G, 1987. Symptomatic intracranial tuberculoma developing during treatment of tuberculosis: A report of 10 patients and review of the literature. Q J Med 63: 449–460.
-
25.
Müller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M; IeDEA Southern and Central Africa, 2010. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: A systematic review and meta-analysis. Lancet Infect Dis 10: 251–261.
-
26.
Namale PE, Abdullahi LH, Fine S, Kamkuemah M, Wilkinson RJ, Meintjes G, 2015. Paradoxical TB-IRIS in HIV-infected adults: A systematic review and meta-analysis. Future Microbiol 10: 1077–1099.
-
27.
Link-Gelles R, Moultrie H, Sawry S, Murdoch D, Van Rie A, 2014. Tuberculosis immune reconstitution inflammatory syndrome in children initiating antiretroviral therapy for HIV infection: A systematic literature review. Pediatr Infect Dis J 33: 499–503.
-
28.
Bell LC, Breen R, Miller RF, Noursadeghi M, Lipman M, 2015. Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis. Int J Infect Dis 32: 39–45.
-
29.
Geri G, Passeron A, Heym B, Arlet JB, Pouchot J, Capron L, Ranque B, 2013. Paradoxical reactions during treatment of tuberculosis with extrapulmonary manifestations in HIV-negative patients. Infection 41: 537–543.
-
30.
Hawkey CR, Yap T, Pereira J, Moore DA, Davidson RN, Pasvol G, Kon OM, Wall RA, Wilkinson RJ, 2005. Characterization and management of paradoxical upgrading reactions in HIV-uninfected patients with lymph node tuberculosis. Clin Infect Dis 40: 1368–1371.
-
31.
Breen RA, Smith CJ, Bettinson H, Dart S, Bannister B, Johnson MA, Lipman MC, 2004. Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection. Thorax 59: 704–707.
-
32.
Choremis CB, Padiatellis C, Zou Mbou Lakis D, Yannkos D, 1955. Transitory exacerbation of fever and roentgenographic findings during treatment of tuberculosis in children. Am Rev Tuberc 72: 527–536.
-
33.
Quinn CM, Poplin V, Kasibante J, Yuquimpo K, Gakuru J, Cresswell FV, Bahr NC, 2020. Tuberculosis IRIS: Pathogenesis, presentation, and management across the spectrum of disease. Life (Basel) 10: 262.
-
34.
Meintjes G, et al., 2018. Prednisone for the prevention of paradoxical tuberculosis-associated IRIS. N Engl J Med 379: 1915–1925.
-
35.
Wouters E, Stek C, Swartz A, Buyze J, Schutz C, Thienemann F, Wilkinson RJ, Meintjes G, Lynen L, Nöstlinger C, 2022. Prednisone for the prevention of tuberculosis-associated IRIS (randomized controlled trial): Impact on the health-related quality of life. Front Psychol 13: 983028.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 5665 | 5665 | 187 |
| Full Text Views | 118 | 118 | 13 |
| PDF Downloads | 100 | 100 | 10 |
Paradoxical Reaction to Tuberculosis Therapy among HIV-Negative Children: A Systematic Review and Meta-Analysis
Nabaneeta Dash
Nabaneeta Dash
Department of Telemedicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;
Search for other papers by Nabaneeta Dash in
Current site
Google Scholar
PubMed
Search for other papers by Nabaneeta Dash in
Current site
Google Scholar
PubMed
Lovely Jain
Lovely Jain
Advanced Centre for Evidence Based Child Health (ACEBCH), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;
Search for other papers by Lovely Jain in
Current site
Google Scholar
PubMed
Search for other papers by Lovely Jain in
Current site
Google Scholar
PubMed
Meenakshi Malik
Meenakshi Malik
Advanced Centre for Evidence Based Child Health (ACEBCH), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;
Search for other papers by Meenakshi Malik in
Current site
Google Scholar
PubMed
Search for other papers by Meenakshi Malik in
Current site
Google Scholar
PubMed
Pranita Pradhan
Pranita Pradhan
Advanced Centre for Evidence Based Child Health (ACEBCH), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;
Search for other papers by Pranita Pradhan in
Current site
Google Scholar
PubMed
Search for other papers by Pranita Pradhan in
Current site
Google Scholar
PubMed
Monica Choudhary
Monica Choudhary
Advanced Centre for Evidence Based Child Health (ACEBCH), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;
Search for other papers by Monica Choudhary in
Current site
Google Scholar
PubMed
Search for other papers by Monica Choudhary in
Current site
Google Scholar
PubMed
Phani Priya Mandula
Phani Priya Mandula
Department of Telemedicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;
Search for other papers by Phani Priya Mandula in
Current site
Google Scholar
PubMed
Search for other papers by Phani Priya Mandula in
Current site
Google Scholar
PubMed
Kulbir Kaur
Kulbir Kaur
Advanced Centre for Evidence Based Child Health (ACEBCH), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;
Search for other papers by Kulbir Kaur in
Current site
Google Scholar
PubMed
Search for other papers by Kulbir Kaur in
Current site
Google Scholar
PubMed
Abhishek Purohit
Abhishek Purohit
Advanced Centre for Evidence Based Child Health (ACEBCH), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;
Search for other papers by Abhishek Purohit in
Current site
Google Scholar
PubMed
Search for other papers by Abhishek Purohit in
Current site
Google Scholar
PubMed
Joseph L. Mathew
dr.joseph.l.mathew@gmail.com
Joseph L. Mathew
Advanced Centre for Evidence Based Child Health (ACEBCH), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;
Department of Pediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Search for other papers by Joseph L. Mathew in
Current site
Google Scholar
PubMed
Department of Pediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Search for other papers by Joseph L. Mathew in
Current site
Google Scholar
PubMed
ABSTRACT.
Tuberculosis treatment is sometimes associated with clinical deterioration, referred to as paradoxical reaction (PR), especially in those with HIV coinfection. However, the burden and characteristics of PR in children without HIV coinfection are unclear. We undertook a systematic review to estimate the burden and clinical characteristics of PR in HIV-negative children. We searched PubMed, Embase, Web of Science, CINAHL, Scopus, Cochrane Library, ProQuest, and OpenGrey for studies reporting PR in HIV-negative children (<18 years old). We included observational studies including case series with at least five cases. Data on incidence/prevalence, clinical features, risk factors, management strategies, and outcome of PR were extracted. Risk of bias in the included studies was assessed using the NIH’s quality assessment and Joanna Briggs Institute critical appraisal tools. We pooled the prevalence data using random effects meta-analysis. We identified 1,673 studies, of which 10 were eligible for inclusion. They described PR in 133 HIV-negative children. The pooled prevalence was 8.8% (95% CI: 2.9%, 14.6%). Owing to heterogeneity among studies, risk factors for the development of PR could not be identified. Limited data suggested that children developing PR were younger and had neurological or lymph node tuberculosis more often. Most children were treated with corticosteroids, but data were insufficient to identify the optimal management strategy. The review showed that PR affects nearly 1 in 12 HIV-negative children receiving tuberculosis treatment. The paucity of studies emphasizes the need for surveillance/studies to better characterize clinical features, risk factors, appropriate management strategies, and outcome.
- Supplemental Materials (PDF 239.03 KB)
Author Notes
Financial support: The
Authors’ contributions: N. Dash and J. L. Mathew conceived the study idea, analyzed and interpreted the data, and drafted the manuscript. P. Pradhan searched the databases for the studies applying the search terms. N. Dash, L. Jain, P. P. Mandula, M. Malik, and K. Kaur did the initial screening of the study titles and abstracts. N. Dash, L. Jain, and P. P. Mandula did the screening of full texts. N. Dash, L. Jain, P. P. Mandula, and M. Malik assessed the included studies for risk of bias. N. Dash and L. Jain extracted the data. The data extracted were accessed and verified by M. Malik and M. Choudhary, and M. Choudhary, L. Jain, and A. Purohit analyzed the data. J. L. Mathew provided guidance at each step and helped to sort out any issues or differences arising during study screening, selection, and risk of bias assessment. All the authors revised the manuscript and were responsible for the decision to submit the manuscript.
Current contact information: Nabaneeta Dash and Phani Priya Mandula, Department of Telemedicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, E-mails: nabaneetadash@gmail.com and phani.omc93@gmail.com. Lovely Jain, Meenakshi Malik, Pranita Pradhan, Monica Choudhary, Kulbir Kaur, and Abhishek Purohit, Advanced Centre for Evidence Based Child Health (ACEBCH), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, E-mails: lavijain001@gmail.com, meenakshi.malik.acebch@gmail.com, pranita.acebch@gmail.com, monicachoudhary68071@gmail.com, kulbir.acebch@gmail.com, and abhishekpurohit3@gmail.com. Joseph L. Mathew, Advanced Centre for Evidence Based Child Health (ACEBCH), Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India, E-mail: dr.joseph.l.mathew@gmail.com.
- ABSTRACT.
- INTRODUCTION
- MATERIALS AND METHODS
- RESULTS
- Search results.
- Quality of included studies.
- Findings.
- Site of TB and clinical features of PR.
- Time interval between starting therapy and development of PR.
- Risk factors for occurrence of PR.
- Effect of PR on clinical outcome.
- Additional duration of therapy after onset of PR.
- Use of immunomodulators and/or immunosuppressants for management of PR.
- DISCUSSION
- CONCLUSION
- Supplemental Materials
- ACKNOWLEDGMENT
- REFERENCES
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization, 2022. Global Tuberculosis Report 2023. Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/publications/i/item/9789240083851. Accessed June 15, 2023.
-
2.
World Health Organization (WHO), 2019. Global Tuberculosis Report 2019. Available at: https://www.who.int/publications/i/item/9789241565714. Accessed June 15, 2023.
-
3.
Pediatric TB Management Guidelines, 2022. National Tuberculosis Elimination Programme. Available at: https://tbcindia-wp.azurewebsites.net/wp-content/uploads/2023/05/9534339438Paediatric_TB_Mangement_Guideline_22082022_V1.pdf. Accessed June 15, 2023.
-
4.
Meintjes G, et al., 2008. Tuberculosis-associated immune reconstitution inflammatory syndrome: Case definitions for use in resource-limited settings. Lancet Infect Dis 8: 516–523.
-
5.
Done MM, Akkerman OW, Al-Kailany W, de Lange WCM, de Jonge G, Kleinnijenhuis J, Stienstra R, van der Werf TS, 2020. Corticosteroid therapy for the management of paradoxical inflammatory reaction in patients with pulmonary tuberculosis. Infection 48: 641–645.
-
6.
Afghani B, Leiberman JM, 1994. Paradoxical enlargement or development of intracranial tuberculomas during therapy: Case report and review. Clin Infect Dis 19: 1092–1099.
-
7.
Cheng VC, Ho PL, Lee RA, Chan KS, Chan KK, Woo PC, Lau SK, Yuen KY, 2002. Clinical spectrum of paradoxical deterioration during antituberculosis therapy in non-HIV-infected patients. Eur J Clin Microbiol Infect Dis 21: 803–809.
-
8.
Bloch S, Wickremasinghe M, Wright A, Rice A, Thompson M, Kon OM, 2009. Paradoxical reactions in non-HIV tuberculosis presenting as endobronchial obstruction. Eur Respir Rev 18: 295–299.
-
9.
Aggarwal D, Bhardwaj M, Kumar A, Saini V, Sawal N, 2020. Immune reconstitution inflammatory syndrome in non-HIV patients with tuberculosis. A case series. Indian J Tuberc 67: 143–147.
-
10.
Page MJ, et al., 2021. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 372: n71.
-
11.
Schiavo JH, 2019. PROSPERO: An international register of systematic review protocols. Med Ref Serv Q 38: 171–180.
-
12.
National Heart, Lung, and Blood Institute (NHLBI), 2021. Study Quality Assessment Tools. Available at: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. Accessed June 15, 2023.
-
13.
Munn Z, Barker TH, Moola S, Tufanaru C, Stern C, McArthur A, Stephenson M, Aromataris E, 2020. Methodological quality of case series studies: An introduction to the JBI critical appraisal tool. JBI Evid Synth 18: 2127–2133.
-
14.
R Foundation for Statistical Computing, 2015 . R: A Language and Environment for Statistical Computing. Available at: https://www.R-project.org/. Accessed December 12, 2023.
-
15.
Zhou Y, Qin Y, Mu T, Zengh H, Cai J, 2022. Magnetic resonance imaging findings of intraspinal tuberculoma in children. Front Neurol 13: 936837.
-
16.
Zhu H, Maoqiang T, Shui L, Xiaomei S, 2021. Risk factors of paradoxical response during anti-tuberculosis treatment in children with tuberculous meningitis. Zhonghua Shiyong Erke Linchuang Zazhi 36: 287–289.
-
17.
Shah I, Bhaskar MV, 2017. Paradoxical reactions in children with tuberculosis. Trop Doct 47: 109–113.
-
18.
Carazo Gallego B, Moreno-Pérez D, Nuñez Cuadros E, Mesa Fernandez A, Martin Cantero M, Obando Pacheco P, Urda Cardona A, 2016. Paradoxical reaction in immunocompetent children with tuberculosis. Int J Infect Dis 51: 15–18.
-
19.
Olive C, Mouchet F, Toppet V, Haelterman E, Levy J, 2013. Paradoxical reaction during tuberculosis treatment in immunocompetent children: Clinical spectrum and risk factors. Pediatr Infect Dis J 32: 446–449.
-
20.
Thampi N, Stephens D, Rea E, Kitai I, 2012. Unexplained deterioration during antituberculous therapy in children and adolescents: Clinical presentation and risk factors. Pediatr Infect Dis J 31: 129–133.
-
21.
Kumar R, Prakash M, Jha S, 2006. Paradoxical response to chemotherapy in neurotuberculosis. Pediatr Neurosurg 42: 214–222.
-
22.
Gupta M, Bajaj BK, Khwaja G, 2003. Paradoxical response in patients with CNS tuberculosis. J Assoc Physicians India 51: 257–260.
-
23.
Kumar S, Puri V, Mehndiratta MM, Gupta S, Bhutani A, Sharma C, 1995. Paradoxical response to antitubercular drugs. Indian J Pediatr 62: 695–701.
-
24.
Teoh R, Humphries MJ, O’Mahony G, 1987. Symptomatic intracranial tuberculoma developing during treatment of tuberculosis: A report of 10 patients and review of the literature. Q J Med 63: 449–460.
-
25.
Müller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M; IeDEA Southern and Central Africa, 2010. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: A systematic review and meta-analysis. Lancet Infect Dis 10: 251–261.
-
26.
Namale PE, Abdullahi LH, Fine S, Kamkuemah M, Wilkinson RJ, Meintjes G, 2015. Paradoxical TB-IRIS in HIV-infected adults: A systematic review and meta-analysis. Future Microbiol 10: 1077–1099.
-
27.
Link-Gelles R, Moultrie H, Sawry S, Murdoch D, Van Rie A, 2014. Tuberculosis immune reconstitution inflammatory syndrome in children initiating antiretroviral therapy for HIV infection: A systematic literature review. Pediatr Infect Dis J 33: 499–503.
-
28.
Bell LC, Breen R, Miller RF, Noursadeghi M, Lipman M, 2015. Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis. Int J Infect Dis 32: 39–45.
-
29.
Geri G, Passeron A, Heym B, Arlet JB, Pouchot J, Capron L, Ranque B, 2013. Paradoxical reactions during treatment of tuberculosis with extrapulmonary manifestations in HIV-negative patients. Infection 41: 537–543.
-
30.
Hawkey CR, Yap T, Pereira J, Moore DA, Davidson RN, Pasvol G, Kon OM, Wall RA, Wilkinson RJ, 2005. Characterization and management of paradoxical upgrading reactions in HIV-uninfected patients with lymph node tuberculosis. Clin Infect Dis 40: 1368–1371.
-
31.
Breen RA, Smith CJ, Bettinson H, Dart S, Bannister B, Johnson MA, Lipman MC, 2004. Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection. Thorax 59: 704–707.
-
32.
Choremis CB, Padiatellis C, Zou Mbou Lakis D, Yannkos D, 1955. Transitory exacerbation of fever and roentgenographic findings during treatment of tuberculosis in children. Am Rev Tuberc 72: 527–536.
-
33.
Quinn CM, Poplin V, Kasibante J, Yuquimpo K, Gakuru J, Cresswell FV, Bahr NC, 2020. Tuberculosis IRIS: Pathogenesis, presentation, and management across the spectrum of disease. Life (Basel) 10: 262.
-
34.
Meintjes G, et al., 2018. Prednisone for the prevention of paradoxical tuberculosis-associated IRIS. N Engl J Med 379: 1915–1925.
-
35.
Wouters E, Stek C, Swartz A, Buyze J, Schutz C, Thienemann F, Wilkinson RJ, Meintjes G, Lynen L, Nöstlinger C, 2022. Prednisone for the prevention of tuberculosis-associated IRIS (randomized controlled trial): Impact on the health-related quality of life. Front Psychol 13: 983028.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 5665 | 5665 | 187 |
| Full Text Views | 118 | 118 | 13 |
| PDF Downloads | 100 | 100 | 10 |