Prevalence and Diagnosis of Latent Tuberculosis Infection Among Pediatric Household Contacts of Iranian Tuberculosis Cases

Background: Although the World Health Organization has recommended the diagnosis and prophylactic treatment of latent tuberculous infection (LTBI) in child household contacts of tuberculosis (TB) cases, the national programs in high-burden TB regions rarely implement adequate screening of this high-risk group, mainly because of resource limitations. We aimed to evaluate the prevalence of LTBI among pediatric household contacts of TB cases in two high-burden provinces in Iran.Methods: We conducted a cohort study in children who had been in household contact with a TB index. All subjects were assessed for active disease through evaluation of symptoms and if active disease was suspected were investigated by chest radiograph and bacilli detection in sputum or nasogastric lavage. For LTBI diagnosis, tuberculin skin test (TST) and QuantiFERON®-TB Gold Plus (QFT-Plus) were performed at the time of the index TB case diagnosis, as well as, 3, 12, and 18 months, if the first results were negative. In addition, interferon-γ-induced protein-10 (IP-10) concentrations were measured in QFT-Plus supernatants for all participants. Results: A total of 230 children were enrolled, who had contact with an index TB case. Three contacts were diagnosed with active TB. According to the TST/QFT-Plus results, 104 (45.2%) children were identified with LTBI during our study.Conclusion: This study alarmingly illustrates a high prevalence of LTBI among Iranian children exposed to TB cases. We, therefore, emphasize that the children living in close contact with an infectious TB case should be screened effectively and receive prophylactic therapy.

[1]  Y. Qu,et al.  Diagnostic accuracy of interferon-gamma-induced protein 10 for differentiating active tuberculosis from latent tuberculosis: A meta-analysis , 2019, Scientific Reports.

[2]  G. Ippolito,et al.  Evaluation of IP-10 in Quantiferon-Plus as biomarker for the diagnosis of latent tuberculosis infection. , 2018, Tuberculosis.

[3]  P. Tabarsi,et al.  Implementing Tuberculosis Close-contact Investigation in a Tertiary Hospital in Iran , 2018, International journal of preventive medicine.

[4]  Delia Goletti,et al.  Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease , 2018, Respirology.

[5]  G. Ippolito,et al.  Analytical evaluation of QuantiFERON- Plus and QuantiFERON- Gold In-tube assays in subjects with or without tuberculosis. , 2017, Tuberculosis.

[6]  G. Ippolito,et al.  First characterization of the CD4 and CD8 T-cell responses to QuantiFERON-TB Plus. , 2016, The Journal of infection.

[7]  A. Antinori,et al.  Blood and urine inducible protein 10 as potential markers of disease activity. , 2016, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[8]  C. Ascaso,et al.  Prevalence and Diagnosis of Latent Tuberculosis Infection in Young Children in the Absence of a Gold Standard , 2016, PloS one.

[9]  E. Seyhan,et al.  Predictive value of the tuberculin skin test and QuantiFERON-tuberculosis Gold In-Tube test for development of active tuberculosis in hemodialysis patients , 2016, Annals of thoracic medicine.

[10]  H. Dockrell,et al.  The Use of Interferon Gamma Inducible Protein 10 as a Potential Biomarker in the Diagnosis of Latent Tuberculosis Infection in Uganda , 2016, PloS one.

[11]  J. Starke Interferon-γ Release Assays for Diagnosis of Tuberculosis Infection and Disease in Children , 2014, Pediatrics.

[12]  U. Visco-Comandini,et al.  High urine IP-10 levels associate with chronic HCV infection. , 2014, The Journal of infection.

[13]  A. Sanduzzi,et al.  Performance of the Tuberculin Skin Test and Interferon-γ Release Assays: An Update on the Accuracy, Cutoff Stratification, and New Potential Immune-based Approaches , 2014, The Journal of Rheumatology. Supplement.

[14]  E. Hershfield,et al.  Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection , 2013, Pediatric Clinical Practice Guidelines & Policies.

[15]  D. Christopher,et al.  Serial testing using interferon-&ggr; release assays in nursing students in India , 2014, European Respiratory Journal.

[16]  A. Cruz,et al.  Old and new approaches to diagnosing and treating latent tuberculosis in children in low-incidence countries , 2014, Current opinion in pediatrics.

[17]  E. Chiappini,et al.  Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis infection in children: a 2013 update , 2014, BMC Infectious Diseases.

[18]  Delia Goletti,et al.  Mycobacterium tuberculosis‐specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease , 2013, European journal of immunology.

[19]  L. Cuevas,et al.  Use of tuberculin skin test, IFN-&ggr; release assays and IFN-&ggr;-induced protein-10 to identify children with TB infection , 2012, European Respiratory Journal.

[20]  G. Marks,et al.  Contact investigation for tuberculosis: a systematic review and meta-analysis , 2012, European Respiratory Journal.

[21]  P. Ravn,et al.  A Simple Method to Quantitate IP-10 in Dried Blood and Plasma Spots , 2012, PloS one.

[22]  L. Cuevas,et al.  Can Interferon-Gamma or Interferon-Gamma-Induced-Protein-10 Differentiate Tuberculosis Infection and Disease in Children of High Endemic Areas? , 2011, PloS one.

[23]  A. Mandalakas,et al.  Can we accurately diagnose tuberculosis infection in children? , 2011, The Pediatric infectious disease journal.

[24]  A. Mandalakas,et al.  Operational challenges in managing Isoniazid Preventive Therapy in child contacts: A high-burden setting perspective , 2011, BMC public health.

[25]  M. Pai,et al.  Guidelines on interferon-γ release assays for tuberculosis infection: concordance, discordance or confusion? , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[26]  A. Saini,et al.  Latent Tuberculosis in Children: Diagnosis and Management , 2011, Indian journal of pediatrics.

[27]  K. Zaman,et al.  Tuberculosis: A Global Health Problem , 2010, Journal of health, population, and nutrition.

[28]  T. H. Nguyen,et al.  Risk of latent tuberculosis infection in children living in households with tuberculosis patients: a cross sectional survey in remote northern Lao People's Democratic Republic , 2009, BMC infectious diseases.

[29]  B. Kampmann,et al.  Is IP-10 a Better Biomarker for Active and Latent Tuberculosis in Children than IFNγ? , 2008, PloS one.

[30]  P. Hopewell,et al.  Tuberculosis and latent tuberculosis infection in close contacts of people with pulmonary tuberculosis in low-income and middle-income countries: a systematic review and meta-analysis. , 2008, The Lancet. Infectious diseases.

[31]  D. Lewinsohn,et al.  Immunologic Susceptibility of Young Children to Mycobacterium tuberculosis , 2008, Pediatric Research.

[32]  A. Cruz,et al.  Clinical manifestations of tuberculosis in children. , 2007, Paediatric respiratory reviews.

[33]  B. D. de Jong,et al.  Longitudinal Assessment of an ELISPOT Test for Mycobacterium tuberculosis Infection , 2007, PLoS medicine.

[34]  C. Dye Global epidemiology of tuberculosis , 2006, The Lancet.

[35]  P. Andersen,et al.  Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts. , 2004, American journal of respiratory and critical care medicine.

[36]  R. Gie,et al.  The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era. , 2004, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[37]  J. Deeks,et al.  Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak , 2003, The Lancet.

[38]  Elsie Lee,et al.  Evolution and current use of the tuberculin test. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[39]  R. Stein,et al.  Evaluation of a risk assessment questionnaire used to target tuberculin skin testing in children. , 2001, JAMA.

[40]  G W Comstock,et al.  The prognosis of a positive tuberculin reaction in childhood and adolescence. , 1974, American journal of epidemiology.

[41]  J. Chapman Pediatric tuberculosis. , 1956, Medical times.