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. 2018 Aug 30;13(8):e0202085.
doi: 10.1371/journal.pone.0202085. eCollection 2018.

Upfront Xpert MTB/RIF testing on various specimen types for presumptive infant TB cases for early and appropriate treatment initiation

Neeraj Raizada  1 , Sunil D Khaparde  2 , Raghuram Rao  2 , Aakshi Kalra  1 , Sanjay Sarin  1 , Virender Singh Salhotra  2 , Soumya Swaminathan  3 , Ashwani Khanna  4 , Kamal Kishore Chopra  5 , M Hanif  5 , Varinder Singh  6 , K R Umadevi  7 , Sreenivas Achuthan Nair  8 , Sophie Huddart  9 , Rajneesh Tripathi  1 , C H Surya Prakash  10 , B K Saha  11 , Claudia M Denkinger  12 , Catharina Boehme  12
Affiliations

Upfront Xpert MTB/RIF testing on various specimen types for presumptive infant TB cases for early and appropriate treatment initiation

Neeraj Raizada et al. PLoS One. .

Abstract

Background: Diagnosis of tuberculosis (TB) in infants is challenging due to non-specific clinical presentations of the disease in this age-group and low sensitivity of widely available TB diagnostic tools, which in turn delays prompt access to TB treatment. Upfront access to Xpert/MTB RIF (Xpert) testing, a highly sensitive and specific rapid diagnostic tool, could potentially address some of these challenges. Under the current project, we assessed the utility and feasibility of applying upfront Xpert for diagnosis of tuberculosis in infants, including for testing of non-sputum specimens.

Methods: A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city, through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all infant (<2 years of age) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities.

Results: A total of 7,994 presumptive infant TB cases were enrolled in the project from April 2014 to October 2016, detecting 465 (5.8%, CI: 5.3-6.4) TB cases. The majority (93.9%; CI: 93.4-94.4) of patient specimens were non-sputum and TB positivity was higher amongst non-sputum specimens. Further, a high proportion (5.6% CI 3.8-8.1) of infant TB cases were found to be rifampicin resistant. Covering large cities with a single lab per city over more than two years, the project demonstrated the feasibility of same-day diagnosis with upfront Xpert testing. This in turn led to prompt treatment initiation, with a two-day median turnaround time to treatment initiation. Case mortality observed in the project cohort of diagnosed TB cases was 11.0% (CI 8.4-14.1), the majority of which was pre- or early treatment mortality, in spite of prompt access to treatment for most diagnosed cases.

Conclusion: The current project demonstrated the feasibility of applying rapid and upfront Xpert testing for presumptive infant TB cases. Rapid TB diagnosis in turn facilitates prompt and appropriate treatment initiation. Further, levels of rifampicin resistance observed in infants TB cases highlight the additional benefit of upfront resistance testing. However, high rates of early case mortality, in spite of prompt diagnosis and treatment initiation, highlight the need for further research in infant patient pathways for overall improvement in TB care for infant populations.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Incremental case detection by testing multiple specimen.
See this image and copyright information in PMC

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