scholarly journals Social Mixing and Clinical Features Linked With Transmission in a Network of Extensively Drug-resistant Tuberculosis Cases in KwaZulu-Natal, South Africa

2019 ◽  
Vol 70 (11) ◽  
pp. 2396-2402
Author(s):  
Kristin N Nelson ◽  
Samuel M Jenness ◽  
Barun Mathema ◽  
Benjamin A Lopman ◽  
Sara C Auld ◽  
...  
Keyword(s):  
Clinical Features ◽  
Urban Areas ◽  
Sputum Smear ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Social Mixing ◽  
Kwazulu Natal ◽  
Disease Associations ◽  
Smear Negative

Abstract Background Tuberculosis (TB) is the leading infectious cause of death globally, and drug-resistant TB strains pose a serious threat to controlling the global TB epidemic. The clinical features, locations, and social factors driving transmission in settings with high incidences of drug-resistant TB are poorly understood. Methods We measured a network of genomic links using Mycobacterium tuberculosis whole-genome sequences. Results Patients with 2–3 months of cough or who spent time in urban locations were more likely to be linked in the network, while patients with sputum smear–positive disease were less likely to be linked than those with smear-negative disease. Associations persisted using different thresholds to define genomic links and irrespective of assumptions about the direction of transmission. Conclusions Identifying factors that lead to many transmissions, including contact with urban areas, can suggest settings instrumental in transmission and indicate optimal locations and groups to target with interventions.

scholarly journals Pre-detection history of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africa

2019 ◽  
Vol 116 (46) ◽  
pp. 23284-23291 ◽  
Author(s):  
Tyler S. Brown ◽  
Lavanya Challagundla ◽  
Evan H. Baugh ◽  
Shaheed Vally Omar ◽  
Arkady Mustaev ◽  
...  
Keyword(s):  
Public Health ◽  
Public Health Surveillance ◽  
Health Surveillance ◽  
Whole Genome ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Kwazulu Natal ◽  
History Of

Antimicrobial-resistant (AMR) infections pose a major threat to global public health. Similar to other AMR pathogens, both historical and ongoing drug-resistant tuberculosis (TB) epidemics are characterized by transmission of a limited number of predominant Mycobacterium tuberculosis (Mtb) strains. Understanding how these predominant strains achieve sustained transmission, particularly during the critical period before they are detected via clinical or public health surveillance, can inform strategies for prevention and containment. In this study, we employ whole-genome sequence (WGS) data from TB clinical isolates collected in KwaZulu-Natal, South Africa to examine the pre-detection history of a successful strain of extensively drug-resistant (XDR) TB known as LAM4/KZN, first identified in a widely reported cluster of cases in 2005. We identify marked expansion of this strain concurrent with the onset of the generalized HIV epidemic 12 y prior to 2005, localize its geographic origin to a location in northeastern KwaZulu-Natal ∼400 km away from the site of the 2005 outbreak, and use protein structural modeling to propose a mechanism for how strain-specific rpoB mutations offset fitness costs associated with rifampin resistance in LAM4/KZN. Our findings highlight the importance of HIV coinfection, high preexisting rates of drug-resistant TB, human migration, and pathoadaptive evolution in the emergence and dispersal of this critical public health threat. We propose that integrating whole-genome sequencing into routine public health surveillance can enable the early detection and local containment of AMR pathogens before they achieve widespread dispersal.

scholarly journals Genome Analysis of Multi- and Extensively-Drug-Resistant Tuberculosis from KwaZulu-Natal, South Africa

PLoS ONE ◽  
2009 ◽  
Vol 4 (11) ◽  
pp. e7778 ◽  
Author(s):  
Thomas R. Ioerger ◽  
Sunwoo Koo ◽  
Eun-Gyu No ◽  
Xiaohua Chen ◽  
Michelle H. Larsen ◽  
...  
Keyword(s):  
South Africa ◽  
Genome Analysis ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Kwazulu Natal

scholarly journals Extensively drug-resistant tuberculosis in South Africa: genomic evidence supporting transmission in communities

2018 ◽  
Vol 52 (4) ◽  
pp. 1800246 ◽  
Author(s):  
Sara C. Auld ◽  
N. Sarita Shah ◽  
Barun Mathema ◽  
Tyler S. Brown ◽  
Nazir Ismail ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistant ◽  
Community Settings ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Kwazulu Natal ◽  
A Prospective Study ◽  
Casual Contact

Despite evidence that transmission is driving an extensively drug-resistant TB (XDR-TB) epidemic, our understanding of where and between whom transmission occurs is limited. We sought to determine whether there was genomic evidence of transmission between individuals without an epidemiologic connection.We conducted a prospective study of XDR-TB patients in KwaZulu-Natal, South Africa, during the 2011–2014 period. We collected sociodemographic and clinical data, and identified epidemiologic links based on person-to-person or hospital-based connections. We performed whole-genome sequencing (WGS) on theMycobacterium tuberculosisisolates and determined pairwise single nucleotide polymorphism (SNP) differences.Among 404 participants, 123 (30%) had person-to-person or hospital-based links, leaving 281 (70%) epidemiologically unlinked. The median SNP difference between participants with person-to-person and hospital-based links was 10 (interquartile range (IQR) 8–24) and 16 (IQR 10–23), respectively. The median SNP difference between unlinked participants and their closest genomic link was 5 (IQR 3–9) and half of unlinked participants were within 7 SNPs of at least five participants.The majority of epidemiologically-unlinked XDR-TB patients had low pairwise SNP differences with at least one other participant, consistent with transmission. These data suggest that much of transmission may result from casual contact in community settings between individuals not known to one another.

scholarly journals Spatial distribution of extensively drug-resistant tuberculosis (XDR TB) patients in KwaZulu-Natal, South Africa

PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0181797 ◽  
Author(s):  
Thandi Kapwata ◽  
Natashia Morris ◽  
Angela Campbell ◽  
Thuli Mthiyane ◽  
Primrose Mpangase ◽  
...  
Keyword(s):  
South Africa ◽  
Spatial Distribution ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Kwazulu Natal

scholarly journals Extensively Drug-Resistant Tuberculosis in Women, KwaZulu-Natal, South Africa

2011 ◽  
Vol 17 (10) ◽  
pp. 1942-1945 ◽  
Author(s):  
Max R. O’Donnell ◽  
Jennifer Zelnick ◽  
Lise Werner ◽  
Iqbal Master ◽  
Marian Loveday ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Kwazulu Natal

scholarly journals Modeling Missing Cases and Transmission Links in Networks of Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa

2020 ◽  
Vol 189 (7) ◽  
pp. 735-745
Author(s):  
Kristin N Nelson ◽  
Neel R Gandhi ◽  
Barun Mathema ◽  
Benjamin A Lopman ◽  
James C M Brust ◽  
...  
Keyword(s):  
South Africa ◽  
Missing At Random ◽  
Drug Resistant ◽  
Sequencing Data ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Kwazulu Natal ◽  
Incident Cases ◽  
Incomplete Sampling

Abstract Patterns of transmission of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases worldwide in 2017. Modeling TB transmission networks can provide insight into drivers of transmission, but incomplete sampling of TB cases can pose challenges for inference from individual epidemiologic and molecular data. We assessed the effect of missing cases on a transmission network inferred from Mycobacterium tuberculosis sequencing data on extensively drug-resistant TB cases in KwaZulu-Natal, South Africa, diagnosed in 2011–2014. We tested scenarios in which cases were missing at random, missing differentially by clinical characteristics, or missing differentially by transmission (i.e., cases with many links were under- or oversampled). Under the assumption that cases were missing randomly, the mean number of transmissions per case in the complete network needed to be larger than 20, far higher than expected, to reproduce the observed network. Instead, the most likely scenario involved undersampling of high-transmitting cases, and models provided evidence for super-spreading. To our knowledge, this is the first analysis to have assessed support for different mechanisms of missingness in a TB transmission study, but our results are subject to the distributional assumptions of the network models we used. Transmission studies should consider the potential biases introduced by incomplete sampling and identify host, pathogen, or environmental factors driving super-spreading.

scholarly journals Evolving rifampicin and isoniazid mono-resistance in a high multidrug-resistant and extensively drug-resistant tuberculosis region: a retrospective data analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e031663
Author(s):  
Nomonde Ritta Mvelase ◽  
Yusentha Balakrishna ◽  
Keeren Lutchminarain ◽  
Koleka Mlisana
Keyword(s):  
South Africa ◽  
Diagnostic Algorithm ◽  
Multidrug Resistant ◽  
Continuous Phase ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Kwazulu Natal ◽  
Mdr Tb

ObjectivesSouth Africa ranks among the highest drug-resistant tuberculosis (DR-TB) burdened countries in the world. This study assessed the changes in resistance levels in culture confirmed Mycobacterium tuberculosis (MTB) in the highest burdened province of South Africa during a period where major changes in diagnostic algorithm were implemented.SettingThis study was conducted at the central academic laboratory of the KwaZulu-Natal province of South Africa.ParticipantsWe analysed data for all MTB cultures performed in the KwaZulu-Natal province between 2011 and 2014. The data were collected from the laboratory information system.ResultsOut of 88 559 drug susceptibility results analysed, 18 352 (20.7%) were resistant to rifampicin (RIF) and 19 190 (21.7%) showed resistance to isoniazid (INH). The proportion of rifampicin resistant cases that were mono-resistant increased from 15.3% in 2011 to 21.4% in 2014 while INH mono-resistance (IMR) showed a range between 13.8% and 21.1%. The multidrug-resistant tuberculosis (MDR-TB) rates increased from 18.8% to 23.9% and the proportion of MDR-TB cases that had extensively drug-resistant tuberculosis remained between 10.2% and 11.1%. Most drug resistance was found in females between the ages of 15 and 44 years and the northern districts bordering high MDR-TB regions had the highest MDR-TB rates.ConclusionOur findings show increasing RIF mono-resistance (RMR) and a substantial amount of IMR. This highlights a need for an initial test that detects resistance to both these drugs so as to avoid using RIF monotherapy during continuous phase of treatment in patients with IMR. Furthermore, addition of INH will benefit patients with RMR. Although DR-TB is widespread, HIV and migration influence its distribution; therefore, TB control strategies should include interventions that target these aspects.

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