TY - JOUR
T1 - Transmission of extensively drug-resistant tuberculosis in South Africa
AU - Shah, N. Sarita
AU - Auld, Sara C.
AU - Brust, James C.M.
AU - Mathema, Barun
AU - Ismail, Nazir
AU - Moodley, Pravi
AU - Mlisana, Koleka
AU - Allana, Salim
AU - Campbell, Angela
AU - Mthiyane, Thuli
AU - Morris, Natashia
AU - Mpangase, Primrose
AU - Van Der Meulen, Hermina
AU - Omar, Shaheed V.
AU - Brown, Tyler S.
AU - Narechania, Apurva
AU - Shaskina, Elena
AU - Kapwata, Thandi
AU - Kreiswirth, Barry
AU - Gandhi, Neel R.
N1 - Funding Information:
Supported by grants from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) (R01AI089349 and R01AI087465); NIH career development awards and training grants (K24AI114444, to Dr. Gandhi; K23AI083088, to Dr. Brust; and T32 HL116271, to Dr. Auld); and grants from the Emory University Center for AIDS Research (P30AI050409), the Albert Einstein College of Medicine Center for AIDS Research (P30AI051519), and the Albert Einstein College of Medicine Institute for Clinical and Translational Research (UL1 TR001073).
Publisher Copyright:
Copyright © 2017 Massachusetts Medical Society. All rights reserved.
PY - 2017/1/19
Y1 - 2017/1/19
N2 - BACKGROUND Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. METHODS We conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014. Interviews and medical-record reviews were used to elicit information on the participants' history of tuberculosis and HIV infection, hospitalizations, and social networks. Mycobacterium tuberculosis isolates underwent insertion sequence (IS)6110 restriction-fragment- length polymorphism analysis, targeted gene sequencing, and whole-genome sequencing. We used clinical and genotypic case definitions to calculate the proportion of cases of XDR tuberculosis that were due to inadequate treatment of multidrugresistant (MDR) tuberculosis (i.e., acquired resistance) versus those that were due to transmission (i.e., transmitted resistance). We used social-network analysis to identify community and hospital locations of transmission. RESULTS Of the 404 participants, 311 (77%) had HIV infection; the median CD4+ count was 340 cells per cubic millimeter (interquartile range, 117 to 431). A total of 280 participants (69%) had never received treatment for MDR tuberculosis. Genotypic analysis in 386 participants revealed that 323 (84%) belonged to 1 of 31 clusters. Clusters ranged from 2 to 14 participants, except for 1 large cluster of 212 participants (55%) with a LAM4/KZN strain. Person-to-person or hospital-based epidemiologic links were identified in 123 of 404 participants (30%). CONCLUSIONS The majority of cases of XDR tuberculosis in KwaZulu-Natal, South Africa, an area with a high tuberculosis burden, were probably due to transmission rather than to inadequate treatment of MDR tuberculosis. These data suggest that control of the epidemic of drug-resistant tuberculosis requires an increased focus on interrupting transmission.
AB - BACKGROUND Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. METHODS We conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014. Interviews and medical-record reviews were used to elicit information on the participants' history of tuberculosis and HIV infection, hospitalizations, and social networks. Mycobacterium tuberculosis isolates underwent insertion sequence (IS)6110 restriction-fragment- length polymorphism analysis, targeted gene sequencing, and whole-genome sequencing. We used clinical and genotypic case definitions to calculate the proportion of cases of XDR tuberculosis that were due to inadequate treatment of multidrugresistant (MDR) tuberculosis (i.e., acquired resistance) versus those that were due to transmission (i.e., transmitted resistance). We used social-network analysis to identify community and hospital locations of transmission. RESULTS Of the 404 participants, 311 (77%) had HIV infection; the median CD4+ count was 340 cells per cubic millimeter (interquartile range, 117 to 431). A total of 280 participants (69%) had never received treatment for MDR tuberculosis. Genotypic analysis in 386 participants revealed that 323 (84%) belonged to 1 of 31 clusters. Clusters ranged from 2 to 14 participants, except for 1 large cluster of 212 participants (55%) with a LAM4/KZN strain. Person-to-person or hospital-based epidemiologic links were identified in 123 of 404 participants (30%). CONCLUSIONS The majority of cases of XDR tuberculosis in KwaZulu-Natal, South Africa, an area with a high tuberculosis burden, were probably due to transmission rather than to inadequate treatment of MDR tuberculosis. These data suggest that control of the epidemic of drug-resistant tuberculosis requires an increased focus on interrupting transmission.
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U2 - 10.1056/NEJMoa1604544
DO - 10.1056/NEJMoa1604544
M3 - Article
C2 - 28099825
AN - SCOPUS:85010962133
SN - 0028-4793
VL - 376
SP - 243
EP - 253
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 3
ER -
