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Thursday, 27 October 2016 08:45

Paper 2016_10.2

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Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure

 

Stephanus T Malherbe, Shubhada Shenai, Katharina Ronacher, Andre G Loxton, Gregory Dolganov, Magdalena Kriel, Tran Van, Ray Y Chen, James Warwick, Laura E Via, Taeksun Song, Myungsun Lee, Gary Schoolnik, Gerard Tromp, David Alland, Clifton E Barry III, Jill Winter, Gerhard Walzl, the Catalysis TB–Biomarker Consortium, Lance Lucas, Gian van der Spuy, Kim Stanley, Lani Theart, Bronwyn Smith, Nelita Du Plessis et al.

 

Nature Medicine 22, 1094–1100 (2016) doi:10.1038/nm.4177

Received 18 December 2015 Accepted 29 July 2016 Published online 05 September 2016 Corrected online 19 October 2016

 

Abstract

The absence of a gold standard to determine when antibiotics induce a sterilizing cure has confounded the development of new approaches to treat pulmonary tuberculosis (PTB). We detected positron emission tomography and computerized tomography (PET–CT) imaging response patterns consistent with active disease, along with the presence of Mycobacterium tuberculosis (MTB) mRNA in sputum and bronchoalveolar lavage samples, in a substantial proportion of adult, HIV-negative patients with PTB after a standard 6-month treatment plus 1 year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of nonresolving and intensifying lesions on PET–CT images might indicate ongoing transcription, suggesting that even apparently curative treatment for PTB may not eradicate all of the MTB bacteria in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies, and better treatment response markers, are probably needed for the successful development of improved and shortened PTB-treatment strategies.

 

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