title: 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.
abstract: BACKGROUND
  Diagnosis of pulmonary tuberculosis (PTB) in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India.
  
  
  METHODS
  The study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm.
  
  
  RESULTS
  4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8-13.8) pediatric PTB were diagnosed. Overall 10.4% (CI 9.5-11.2) of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2-5.4) who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high (98%, CI 90.1-99.9), with no statistically significant variation with respect to past history of treatment.
  
  
  CONCLUSIONS
  Upfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising solution to present-day challenges in the diagnosis of PTB in pediatric patients.
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Raizada
authors.affiliation: Central TB Division, Government of India, New Delhi, India.
authors.forename: Kuldeep Singh
authors.initials: KS
authors.lastname: Sachdeva
authors.affiliation: World Health Organization, Country Office for India, New Delhi, India.
authors.forename: Sreenivas Achuthan
authors.initials: SA
authors.lastname: Nair
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Shubhangi
authors.initials: S
authors.lastname: Kulsange
authors.affiliation: Central TB Division, Government of India, New Delhi, India.
authors.forename: Radhey Shayam
authors.initials: RS
authors.lastname: Gupta
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Thakur
authors.affiliation: World Health Organization, Country Office for India, New Delhi, India.
authors.forename: Malik
authors.initials: M
authors.lastname: Parmar
authors.affiliation: Foundation for Innovative New Diagnostics, Geneva, Switzerland.
authors.forename: Christen
authors.initials: C
authors.lastname: Gray
authors.affiliation: World Health Organization, Country Office for India, New Delhi, India.
authors.forename: Ranjani
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Bhavin
authors.initials: B
authors.lastname: Vadera
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Shobha
authors.initials: S
authors.lastname: Ekka
authors.affiliation: Central TB Division, Government of India, New Delhi, India.
authors.forename: Shikha
authors.initials: S
authors.lastname: Dhawan
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Ameet
authors.initials: A
authors.lastname: Babre
authors.affiliation: World Health Organization, Country Office for India, New Delhi, India.
authors.forename: Mayank
authors.initials: M
authors.lastname: Ghedia
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Umesh
authors.initials: U
authors.lastname: Alavadi
authors.affiliation: World Health Organization, Country Office for India, New Delhi, India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Dewan
authors.affiliation: District Tuberculosis Center, Mumbai, India.
authors.forename: Mini
authors.initials: M
authors.lastname: Khetrapal
authors.affiliation: District Tuberculosis Center, New Delhi, India.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Khanna
authors.affiliation: Foundation for Innovative New Diagnostics, Geneva, Switzerland.
authors.forename: Catharina
authors.initials: C
authors.lastname: Boehme
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Chinnambedu Nainarappan
authors.initials: CN
authors.lastname: Paramsivan
mesh_terms: D000293:Adolescent; D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D024881:Drug Resistance, Bacterial; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D025202:Molecular Diagnostic Techniques / Q000592:standards; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics; D058996:Quality Improvement; D012293:Rifampin / Q000494:pharmacology; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000382:microbiology
chemical_list: D000904:Antibiotics, Antitubercular; D012293:Rifampin