Whole Genome Sequencing and Spatial Analysis Identifies Recent Tuberculosis Transmission Hotspots in Ghana.

Prince Asare,Adwoa Asante-Poku,Edmund Bedeley,Miriam Reinhard,Daniela Brites,Audrey Forson,Dorothy Yeboah-Manu,Chloé Loiseau,Sonia Borrell,Kwadwo Ansah Koram,Diana Ahu Prah,Stephen Osei-Wusu,Nyonuku Akosua Baddoo,Sebastien Gagneux,Isaac Darko Otchere

doi:10.3389/fmed.2020.00161

Abstract

Whole genome sequencing (WGS) is progressively being used to investigate the transmission dynamics of Mycobacterium tuberculosis complex (MTBC). We used WGS analysis to resolve traditional genotype clusters and explored the spatial distribution of confirmed recent transmission clusters. Bacterial genomes from a total of 452 MTBC isolates belonging to large traditional clusters from a population-based study spanning July 2012 and December 2015 were obtained through short read next-generation sequencing using the illumina HiSeq2500 platform. We performed clustering and spatial analysis using specified R packages and ArcGIS. Of the 452 traditional genotype clustered genomes, 314 (69.5%) were confirmed clusters with a median cluster size of 7.5 genomes and an interquartile range of 4–12. Recent tuberculosis (TB) transmission was estimated as 24.7%. We confirmed the wide spread of a Cameroon sub-lineage clone with a cluster size of 78 genomes predominantly from the Ablekuma sub-district of Accra metropolis. More importantly, we identified a recent transmission cluster associated with isoniazid resistance belonging to the Ghana sub-lineage of lineage 4. WGS was useful in detecting unsuspected outbreaks; hence, we recommend its use not only as a research tool but as a surveillance tool to aid in providing the necessary guided steps to track, monitor, and control TB.

Highlights

Tuberculosis (TB), a contagious disease of antiquity, affects millions of people annually [1]
A total of 146 genomes constituting eight large clusters (Table 1 and Figures 2, 5) were observed from the clustering analysis with 10 Single-nucleotide polymorphisms (SNPs) threshold. The smallest of these large clusters had a cluster size of seven genomes, whereas the largest had 78 genomes (WGSC5), which formed a quarter of all clustered cases (78/314, 25%)
Major findings from our analysis indicate that [1] estimated recent TB transmission rate using Whole genome sequencing (WGS) at a SNP threshold of 10 remains high at 24.7%, and [2] there is wide spread of a clone of the Cameroon sub-lineage of lineage 4 with an ongoing transmission at hotspots mostly found within the Ablekuma sub-district of the Accra metropolis

Summary

INTRODUCTION

Tuberculosis (TB), a contagious disease of antiquity, affects millions of people annually [1]. In a previous population-based study, we used the combined resolution power of MIRU-VNTR typing and spoligotyping (MIRU/Spoligo) for strain differentiation followed with clustering analysis to estimate the extent of recent transmission in Ghana [10]. It has been indicated that the combined resolution of spoligotyping and MIRU-VNTR may not be enough to distinguish between very closely related strains resulting from recent transmission [7]. In this current study, we used a WGS approach to further resolve large MIRU/Spoligo defined TB clusters (referred to as traditional clusters) and explore epidemiological factors including their spatial distribution

Study Design and Population

RESULTS

DISCUSSION

ETHICS STATEMENT