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Durban forms part of the eThekwini Metropolitan Municipality , which includes neighboring towns and has a population of about 3. Archaeological evidence from the Drakensberg mountains suggests that the Durban area has been inhabited by communities of hunter-gatherers since , BC. These people lived throughout the area of present-day KwaZulu-Natal until the expansion of Bantu farmers and pastoralists from the north saw their gradual displacement, incorporation or extermination.
Little is known of the history of the first residents, as there is no written history of the area until it was sighted by Portuguese explorer Vasco da Gama , who sailed parallel to the KwaZulu-Natal coast at Christmastide in while searching for a route from Europe to India. He named the area “Natal”, or Christmas in Portuguese.
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Background: The continued advance of antibiotic resistance threatens the treatment and control of many infectious diseases. Understanding the origins of drug resistance in this fatal outbreak of XDR will inform the control and prevention of drug-resistant TB in other settings. In this study, we used whole genome sequencing and dating analysis to determine if XDR-TB had emerged recently or had ancient antecedents.
Methods and findings: We performed whole genome sequencing and drug susceptibility testing on clinical isolates of Mycobacterium tuberculosis collected in KwaZulu-Natal from to , in addition to three historical isolates, collected from patients in the same province and including an isolate from the Tugela Ferry XDR outbreak, a multidrug-resistant MDR isolate from , and a pansusceptible isolate from We utilized an array of whole genome comparative techniques to assess the relatedness among strains, to establish the order of acquisition of drug resistance mutations, including the timing of acquisitions leading to XDR-TB in the LAM4 spoligotype, and to calculate the number of independent evolutionary emergences of MDR and XDR.
Our sequencing and analysis revealed a member clone of XDR M. We observed frequent de novo evolution of MDR and XDR, with 56 and nine independent evolutionary events, respectively. Isoniazid resistance evolved before rifampicin resistance 46 times, whereas rifampicin resistance evolved prior to isoniazid only twice. We identified additional putative compensatory mutations to rifampicin in this dataset.
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