Determinants of the Sympatric Host-Pathogen Relationship in Tuberculosis

Abstract

Major contributions from pathogen genome analysis and host genetics have equated the possibility of Mycobacterium tuberculosis co-evolution with its human host leading to more stable sympatric host–pathogen relationships. However, the attribution to either sympatric or allopatric categories depends on the resolution or grain of genotypic characterization. We explored the influence on the sympatric host-pathogen relationship of clinical (HIV infection and multidrug-resistant tuberculosis [MDRTB]) and demographic (gender and age) factors in regards to the genotypic grain by using spacer oligonucleotide typing (spoligotyping) for classification of M. tuberculosis strains within the Euro-American lineage. We analyzed a total of 547 tuberculosis (TB) cases, from six year consecutive sampling in a setting with high TB-HIV coinfection (32.0%). Of these, 62.0% were caused by major circulating pathogen genotypes. The sympatric relationship was defined according to spoligotype in comparison to the international spoligotype database SpolDB4. While no significant association with Euro-American lineage was observed with any of the factors analyzed, increasing the resolution with spoligotyping evidenced a significant association of MDRTB with sympatric strains, regardless of the HIV status. Furthermore, distribution curves of the prevalence of sympatric and allopatric TB in relation to patients’ age showed an accentuation of the relevance of the age of onset in the allopatric relationship, as reflected in the trimodal distribution. On the contrary, sympatric TB was characterized by the tendency towards a typical (standard) distribution curve. Our results suggest that within the Euro-American lineage a greater degree of genotyping fine-tuning is necessary in modeling the biological processes behind the host-pathogen interplay. Furthermore, prevalence distribution of sympatric TB to age was suggestive of host genetic determinisms driven by more common variants.

Mycobacterium tuberculosis Sub-Lineage 4.2.2/SIT149 as Dominant Drug-Resistant Clade in Northwest Ethiopia 2020–2022: In-silico Whole-Genome Sequence Analysis

“… 28 Mtb isolates with sympatric host associations are more likely to be MDR than allopatric genotypes. 29 …”

Epidemiology of Mycobacterium tuberculosis lineages and strain clustering within urban and peri-urban settings in Ethiopia

“…Another comparative study showed that strains of the East African Indian (L3) and Euro-American (L4) lineages were negatively associated with extra thoracic disease as compared to strains of the East Asian lineage (L2) [ 16 ] . These studies thereby suggest that species diversity and their interaction with host biology affects the pathophysiology and natural course of TB disease [ 2 , 17 ] . For example, a study conducted in Tanzania has shown that chronic signs of TB disease, such as weight loss, have been more associated with L4 strains than with strains of the Indo-Oceanic (L1) lineage [ 18 ] .…”

Tracking down the White Plague. Chapter two: The role of endocranial abnormal blood vessel impressions and periosteal appositions in the paleopathological diagnosis of tuberculous meningitis

“…Tuberculosis (TB), also known as the "White Plague", is one of the oldest known infectious diseases that has been afflicting humans and animals for thousands of years [1][2][3]: the earliest recognized and verified human cases with TB [e.g., [4][5][6][7] come from the Neolithic period. Apparently, TB remained relatively sporadic until the 1700s but, as a consequence of increased population density and unsanitary living conditions, started to reach epidemic levels during the Industrial Revolution [8][9][10]. From the second half of the 19 th century, a number of factors (such as the general improvement in living conditions, sanitation, and nutrition) contributed to reducing the number of cases with TB in developed countries [8][9][11][12].…”