Spatial Distribution and Clustering of Drug-Resistant <em>Mycobacterium Tuberculosis</em> Infections in Rural Eastern Cape Province of South Africa

Abstract

Tuberculosis (TB), an infectious airborne disease caused by Mycobacterium tuberculosis (Mtb), is a serious public health threat reported as the leading cause of morbidity and mortality worldwide. South Africa is a high TB burden country with TB being the highest infectious disease killer. The study investigated the distribution and clustering of Mtb mutations and spoligotypes in rural Eastern Cape Province. The Mtb isolates included were 1,157 from DR-TB patients and analysed by LPA followed by spoligotyping of 441 isolates, of these, 36 were whole genome sequenced. Distribution of mutations and spoligotypes was done by spatial analysis and clustering analysis was done by Bayesian model-based clustering of allele frequencies at heterozygous sites, using Mclust package in R. The rpoB gene had highest number of mutations. The distribution of rpoB and katG mutations was more prevalent in four health care facilities, inhA mutations were more prevalent in three healthcare facilities and heteroresistant isolates were more prevalent in five healthcare facilities. The Mtb was genetically diverse with Beijing more prevalent and largely distributed. Spatial analysis and mapping of gene mutations and spoligotypes revealed better picture of distribution. Clustering of isolates indicates that there is transmission of mixed infection in this area.

WITHDRAWN: Prevalence ofkatGandinhAmutations in genes associated with isoniazid resistance inMycobacterium tuberculosisclinical isolates in Cameroon

“…The most common mutation in this gene was inhA C-15T seen in 32% and 11.6% of INH-monoresistant and MDR strains respectively. The frequency of the inhA promoter mutation observed in our study is consistent with those found in other studies in South Africa including KwaZulu-Natal (27.5%) [31], the Free State (13.4%) [24] and Eastern Cape (31.2%) [17]. In addition, the result of this study was in concordance with those reported in India (29%) [26], Ghana (11.8%) [14], and Uganda (20%) [25].…”

“…and 95.8% [29]. A more recent systematic review reported the frequency of katG S315T mutation to be 94.9% in Sub-Saharan Africa, 64% in West Africa, 29.3% in Southeast Asia, and 38% in the United States [17]. However, a much lower frequency (23.7%) was documented by Rostamian et al [30].…”

“…Few studies conducted in Africa have produced supporting evidence. Studies conducted in the Eastern Cape and Free State provinces in South Africa revealed a 68.8% [17] and 63.9% [24] katG S315T mutation respectively. Another study from Uganda reported a high prevalence of katG S315T (76%) mutation [25] while a much higher frequency (84.3%) was documented in Ghana [14].…”

“…The high prevalence of HR in this study can be attributed to the presence of mixed infections and the high prevalence of MDR-TB. These conditions can accelerate treatment failure, promote the transmission of drug-resistant MTB strains, and facilitate the acquisition of mutations [17]. The study conducted in the Eastern Cape province in South Africa reported 17.9% HR in drug-resistant isolates of which 58.8% was associated with katG and 12.2% inhA-associated [17].…”

“…These conditions can accelerate treatment failure, promote the transmission of drug-resistant MTB strains, and facilitate the acquisition of mutations [17]. The study conducted in the Eastern Cape province in South Africa reported 17.9% HR in drug-resistant isolates of which 58.8% was associated with katG and 12.2% inhA-associated [17]. In a study from India, a prevalence of HR in 14.5% of MDR isolates, (6.6% associated with katG mutation only) and 13.2% of INH-monoresistant isolates (59.3% associated with katG and 40.7% associated with inhA) [20].…”