Anne-Marie Demers1, Soyeon Kim2, Sara McCallum3, Kathleen Eisenach4, Michael Hughes3, Linda Naini5, Alberto Mendoza-Ticona6, Neeta Pradhan7, Kim Narunsky8, Selvamuthu Poongulali9, Sharlaa Badal-Faesen10, Caryn Upton11, Elizabeth Smith12, N Sarita Shah13, Gavin Churchyard14,15, Amita Gupta7,16, Anneke Hesseling1, Susan Swindells17. 1. Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. 2. Department of Biostatistics, Frontier Science Foundation, Brookline, MA, USA. 3. Harvard T.H. Chan School of Public Health, Boston, MA, USA. 4. TB or NOT TB Consulting, LLC, Little Rock, AR, USA. 5. Social & Scientific Systems, Inc., Silver Spring, MD, USA. 6. Barranco Clinical Research Site, Lima, Peru. 7. Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India. 8. UCTLI, Cape Town, South Africa. 9. Chennai Antiviral Research and Treatment (CART) Clinical Research Site, Infectious Diseases Medical Center, Voluntary Health Services, Chennai, India. 10. University of the Witwatersrand Helen Joseph (WITS HJH) CRS, Johannesburg, South Africa. 11. TASK Applied Science, Cape Town, South Africa. 12. DAIDS, NIH, Bethesda, MD, USA. 13. Centers for Disease Control and Prevention, Atlanta, GA, USA. 14. Aurum Institute, Parktown, South Africa. 15. School of Public Health, University of Witwatersrand, Johannesburg, South Africa. 16. Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. 17. Department of Internal Medicine, Section of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, 68198-8106, USA. sswindells@unmc.edu.
Abstract
BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. RESULTS: Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. CONCLUSIONS: RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.
BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. RESULTS: Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. CONCLUSIONS: RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.
Authors: A S Dharmadhikari; M Mphahlele; K Venter; A Stoltz; R Mathebula; T Masotla; M van der Walt; M Pagano; P Jensen; E Nardell Journal: Int J Tuberc Lung Dis Date: 2014-09 Impact factor: 2.373
Authors: Andrea Rachow; Alimuddin Zumla; Norbert Heinrich; Gabriel Rojas-Ponce; Bariki Mtafya; Klaus Reither; Elias N Ntinginya; Justin O'Grady; Jim Huggett; Keertan Dheda; Catharina Boehme; Mark Perkins; Elmar Saathoff; Michael Hoelscher Journal: PLoS One Date: 2011-06-29 Impact factor: 3.240
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Authors: Soumitesh Chakravorty; Ann Marie Simmons; Mazhgan Rowneki; Heta Parmar; Yuan Cao; Jamie Ryan; Padmapriya P Banada; Srinidhi Deshpande; Shubhada Shenai; Alexander Gall; Jennifer Glass; Barry Krieswirth; Samuel G Schumacher; Pamela Nabeta; Nestani Tukvadze; Camilla Rodrigues; Alena Skrahina; Elisa Tagliani; Daniela M Cirillo; Amy Davidow; Claudia M Denkinger; David Persing; Robert Kwiatkowski; Martin Jones; David Alland Journal: mBio Date: 2017-08-29 Impact factor: 7.867