title: 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.
authors.affiliation: Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), Lisboa, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: David
authors.affiliation: Instituto Gulbenkian de Ciência (IGC), Oeiras, Portugal; Institute of Biology, Leiden University, Leiden, The Netherlands.
authors.forename: A R A
authors.initials: AR
authors.lastname: Mateus
authors.affiliation: Escola de Ciências e Tecnologia/ Instituto de Ciências Agrárias e Ambientais Mediterrânicas (ICAAM), Universidade de Évora, Évora, Portugal.
authors.forename: Elsa L
authors.initials: EL
authors.lastname: Duarte
authors.affiliation: Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), Lisboa, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Albuquerque
authors.affiliation: Serviço de Patologia Clínica, Hospital Fernando Fonseca, Amadora, Portugal.
authors.forename: Clara
authors.initials: C
authors.lastname: Portugal
authors.affiliation: Serviço de Patologia Clínica, Hospital Fernando Fonseca, Amadora, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Sancho
authors.affiliation: Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), Lisboa, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Lavinha
authors.affiliation: Unidade Multidisciplinar de Investigação Biomédica (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Porto, Portugal.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Gonçalves
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D021901:DNA, Intergenic / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D058974:Phylogeography; D011174:Portugal / Q000453:epidemiology; D012293:Rifampin / Q000627:therapeutic use; D013307:Streptomycin / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D021901:DNA, Intergenic; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin