Spatial Patterns of Extensively Drug-Resistant Tuberculosis Transmission in KwaZulu-Natal, South Africa

Abstract

Background: Transmission is driving the global drug-resistant tuberculosis (TB) epidemic; nearly three-quarters of drug-resistant TB cases are attributable to transmission. Geographic patterns of disease incidence, combined with information on probable transmission links, can define the spatial scale of transmission and generate hypotheses about factors driving transmission patterns.

Methods: We combined whole-genome sequencing data with home Global Positioning System coordinates from 344 participants with extensively drug-resistant (XDR) TB in KwaZulu-Natal, South Africa, diagnosed from 2011 to 2014. We aimed to determine if genomically linked (difference of ≤5 single-nucleotide polymorphisms) cases lived close to one another, which would suggest a role for local community settings in transmission.

Results: One hundred eighty-two study participants were genomically linked, comprising 1084 case-pairs. The median distance between case-pairs' homes was 108 km (interquartile range, 64-162 km). Between-district, as compared to within-district, links accounted for the majority (912/1084 [84%]) of genomic links. Half (526 [49%]) of genomic links involved a case from Durban, the urban center of KwaZulu-Natal.

Conclusions: The high proportions of between-district links with Durban provide insight into possible drivers of province-wide XDR-TB transmission, including urban-rural migration. Further research should focus on characterizing the contribution of these drivers to overall XDR-TB transmission in KwaZulu-Natal to inform design of targeted strategies to curb the drug-resistant TB epidemic.

Figures

Figure 1.

Study flowchart. Abbreviations: KZN, KwaZulu Natal; SNP, single-nucleotide polymorphism; TRAX, Transmission of HIV-Associated XDR-TB study; WGS, whole-genome sequencing; XDR-TB, extensively drug-resistant tuberculosis.

Figure 2.

Black dots indicate locations of reported home residences of TRAX cases who are genomically linked; grey dots indicate those not genomically linked. The eleven districts of KwaZulu-Natal are labeled. The most populous district in KwaZulu-Natal is eThekwini, which includes the city of Durban. Note: As of 2015, Sisonke district is known as Harry Gwala district and as of 2016, Uthungulu district is known as King Cetshwayo district.

Figure 3.

A, Dots indicate home residences of XDR-tuberculosis cases; lines represent genomic links between cases. B, Arrows under histograms indicate the median distance between homes of genomically linked case-pairs at each SNP threshold. Note differences in the y axis range across plots. Abbreviation: SNP, single nucleotide polymorphism.

Figure 4.

The proportion of genomic links between each district out of the total number of links involving that district is represented by the color of the line. Amajuba district, which had only one genomic link, was excluded from this analysis.