Increased Transmission of Mycobacterium tuberculosis Beijing Genotype Strains Associated with Resistance to Streptomycin: A Population-Based Study

Abstract

BackgroundStudies have shown that the Mycobacterium tuberculosis Beijing genotype is an emerging pathogen that is frequently associated with drug resistance. This suggests that drug resistant Beijing strains have a relatively high transmission fitness compared to other drug-resistant strains.Methods and FindingsWe studied the relative transmission fitness of the Beijing genotype in relation to anti-tuberculosis drug resistance in a population-based study of smear-positive tuberculosis patients prospectively recruited and studied over a 4-year period in rural Vietnam. Transmission fitness was analyzed by clustering of cases on basis of three DNA typing methods. Of 2531 included patients, 2207 (87%) were eligible for analysis of whom 936 (42%) were in a DNA fingerprint cluster. The clustering rate varied by genotype with 292/786 (37%) for the Beijing genotype, 527/802 (67%) for the East-African Indian (EAI) genotype, and 117/619 (19%) for other genotypes. Clustering was associated with the EAI compared to the Beijing genotype (adjusted odds ratio (ORadj) 3.4: 95% CI 2.8–4.4). Patients infected with streptomycin-resistant strains were less frequently clustered than patients infected with streptomycin-susceptible strains when these were of the EAI genotype (ORadj 0.6, 95% CI 0.4–0.9), while this pattern was reversed for strains of the Beijing genotype (ORadj 1.3, 95% CI 1.0–1.8, p for difference 0.002). The strong association between Beijing and MDR-TB (ORadj 7.2; 95% CI 4.2–12.3) existed only if streptomycin resistance was present.ConclusionsBeijing genotype strains showed less overall transmissibility than EAI strains, but when comparisons were made within genotypes, Beijing strains showed increased transmission fitness when streptomycin-resistant, while the reverse was observed for EAI strains. The association between MDR-TB and Beijing genotype in this population was strongly dependent on resistance to streptomycin. Streptomycin resistance may provide Beijing strains with a fitness advantage over other genotypes and predispose to multidrug resistance in patients infected with Beijing strains.

Molecular epidemiology of tuberculosis in Cambodian children

“…Strain family and region were independently associated with drug resistance in the multivariable analysis. In the Mekong river delta in Viet Nam, overall a lower transmissibility [18]. Among adults, a genotype analysis of strains from Phnom Penh has shown that among non-multidrugresistant strains, Beijing genotypes accounted for 21% of the total [7] comparable to our 19% from roughly the same area.…”

Epidemiology of Isoniazid Resistance Mutations and Their Effect on Tuberculosis Treatment Outcomes

“…In our study 47% of the Beijing strains were resistant to streptomycin of which 48% also had katG 315 mutations, suggesting that in the Beijing strains streptomycin resistance and katG 315 mutations are often present simultaneously. This correlation is not unexpected; streptomycin resistance was also associated with the Beijing genotype, MDR-TB and increased transmission in the same study area (37). The association between streptomycin resistance and high-level isoniazid resistance and MDR, especially among Beijing strains, needs further study.…”

Consequences of genomic diversity in Mycobacterium tuberculosis

“…Buu et al [189] reported higher genotypic clustering of Lineage 2 compared Lineage 1 in Vietnam. Similarly, a study in Shanghai found Lineage 2 associated with higher clustering and younger age compared to other strains [190].…”

“…Many other studies in various settings have reported a higher fitness of Lineage 2/Beijing strains reflected by increases in their frequency over time [69,159,191–196]. In some cases, the increase of Lineage 2 was associated with drug resistance [189,197]. Yet, several studies observed no such increase and no enhanced transmissibility of Lineage 2 strains [167,198–201].…”