Ethnicity and mycobacterial lineage as determinants of tuberculosis disease phenotype

Abstract

Background Emerging evidence suggests that Mycobacterium tuberculosis (Mtb) lineage and host ethnicity can determine tuberculosis (TB) clinical disease patterns but their relative importance and interaction are unknown. Methods We evaluated prospectively collected TB surveillance and Mtb strain typing data in an ethnically heterogeneous UK population. Lineage assignment was denoted using 15-loci mycobacterial interspersed repetitive units containing variable numbers of tandem repeats (MIRU-VNTR) and MIRU-VNTRplus. Geographical and ethnic associations of the six global Mtb lineages were identified and the influence of lineage and demographic factors on clinical phenotype were assessed using multivariate logistic regression. Results Data were available for 1070 individuals with active TB which was pulmonary only, extrapulmonary only and concurrent pulmonary-extrapulmonary in 52.1%, 36.9% and 11.0% respectively. The most prevalent lineages were Euro-American (43.7%), East African Indian (30.2%), Indo-Oceanic (13.6%) and East Asian (12.2%) and were geo-ethnically restricted with, for example, Indian subcontinent ethnicity inversely associated with Euro-American lineage (OR 0.23; 95% CI 0.14 to 0.39) and positively associated with the East African-Indian lineage (OR 4.04; 95% CI 2.19 to 7.45). Disease phenotype was most strongly associated with ethnicity (OR for extrathoracic disease 21.14 (95% CI 6.08 to 73.48) for Indian subcontinent and 14.05 (3.97 to 49.65) for Afro-Caribbean), after adjusting for lineage. With East Asian lineage as the reference category, the Euro-American (OR 0.54; 95% CI 0.32 to 0.91) and East-African Indian (OR 0.50; 95% CI 0.29 to 0.86) lineages were negatively associated with extrathoracic disease, compared with pulmonary disease, after adjusting for ethnicity. Conclusions Ethnicity is a powerful determinant of clinical TB phenotype independently of mycobacterial lineage and the role of ethnicity-associated factors in pathogenesis warrants investigation.

Clinico-pathological features of tuberculosis due to mycobacterium tuberculosis Uganda genotype in patients with tuberculous lymphadenitis: a cross sectional study

“…Tuberculous lymphadenitis is the commonest form of extra pulmonary TB in high endemic areas [18,37]. Previous evidence also suggest that strains of the Euro-American lineage of M. tuberculosis to which M. tuberculosis Uganda genotype belongs less frequently cause EPTB [11,12].…”

“…tuberculosis has evolved into a number of widely distributed and genetically diverse lineages and sub-lineages [10] exhibiting variable disease phenotypic characteristics demonstrated in epidemiological studies and animal models [11,12]. This together with diversity of the host immunological response may explain the wide clinicalimmunopathological spectrum of disease in those patients who cannot control the infection [13].…”

Correlates between Models of Virulence for Mycobacterium tuberculosis among Isolates of the Central Asian Lineage: a Case for Lysozyme Resistance Testing?

“…tuberculosis isolates found in epidemiologically defined clusters are defined as successful because they transmit and cause TB in more human hosts, in the same population, than the case for other isolates. It is also a generally accepted idea that overall strain success depends on a combination of strain virulence traits and host genetic factors (8,14,16,62,63). The contribution of mycobacterial VFs to establishing disease (TB) or causing pathogenicity, however, was recently reemphasized (42,64); as VFs are likely to be lineage specific (23-25, 38, 43), their existence might have far-reaching impacts on the efficacy of new TB vaccines or drugs (65).…”

“…Within M. tuberculosis itself, single nucleotide polymorphisms (SNPs) and large sequence polymorphisms (LSPs) are used to further classify M. tuberculosis into four (sensu stricto) major lineages, each of which is found to strongly associate with specific geographic human populations (7). While strong lineage associations with specific human populations or regions of the world are well acknowledged (8)(9)(10)(11)(12), the causes and relevance of this to bacterial virulence and clinical presentation are still only partly understood (13)(14)(15)(16). It has become clear, however, that the previously unrecognized genetic diversity among M. tuberculosis isolates has an impact on the outcome of infection (17)(18)(19), and different approaches have been undertaken towards a better understanding of what makes a strain virulent.…”

Presencia del genotipo Beijing entre cepas del complejo Mycobacterium tuberculosis en dos centros de salud de la Región Metropolitana-Chile

“…El genotipo Central-Asia (CAS) o Delhi, localizado en el Medio Oriente, Asia Central, Europa y Australia, lo que lo vincula con los inmigrantes del sur de Asia 1 . El genotipo X, prevalente en América del Norte y regiones de América Central sugiriendo una ascendencia anglosajona o incluso afro-americana 1,6 y por último el genotipo Beijing, endémico y con un claro predominio en ciertas regiones del extremo Oriente, Asia y Oceanía, exceptuando India subcontinental y Sudáfrica 1,8,9 , se ha asociado a alta transmisibilidad, multi-resistencia 8,10 y mayor poder patógeno asociado a la baja inducción de citoquinas inflamatorias, lo que permitiría un mayor crecimiento intracelular del cMtb 2,11 . En los Estados Unidos de América, específicamente en Nueva York, en el año 1991, durante un brote que afectó a ocho pacientes www.sochinf.cl con TBC resistente a isoniacida, rifampicina, etambutol, estreptomicina, kanamicina, etionamida y rifabutina, se identificó el genotipo "W", que fue posteriormente asociado a otros cinco brotes en hospitales del área de Nueva York.…”