Allopatric tuberculosis host-pathogen relationships are associated with greater pulmonary impairment

Abstract

Background: Host pathogen relationships can be classified as allopatric, when the pathogens originated from separate, non-overlapping geographic areas from the host; or sympatric, when host and pathogen shared a common ancestral geographic location. It remains unclear if host-pathogen relationships, as defined by phylogenetic lineage, influence clinical outcome. We sought to examine the association between allopatric and sympatric phylogenetic Mycobacterium tuberculosis lineages and pulmonary impairment after tuberculosis (PIAT).

Methods: Pulmonary function tests were performed on patients 16 years of age and older who had received ≥20 weeks of treatment for culture-confirmed M. tuberculosis complex. Forced Expiratory Volume in 1 min (FEV1) ≥80%, Forced Vital Capacity (FVC) ≥80% and FEV1/FVC >70% of predicted were considered normal. Other results defined pulmonary impairment. Spoligotype and 12-locus mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) were used to assign phylogenetic lineage. PIAT severity was compared between host-pathogen relationships which were defined by geography and ethnic population. We used multivariate logistic regression modeling to calculate adjusted odds ratios (aOR) between phylogenetic lineage and PIAT.

Results: Self-reported continental ancestry was correlated with Mycobacterium. tuberculosis lineage (p<0.001). In multivariate analyses adjusting for phylogenetic lineage, age and smoking, the overall aOR for subjects with allopatric host-pathogen relationships and PIAT was 1.8 (95% confidence interval [CI]: 1.1, 2.9) compared to sympatric relationships. Smoking >30 pack-years was also associated with PIAT (aOR: 3.2; 95% CI: 1.5, 7.2) relative to smoking <1 pack-years.

Conclusions: PIAT frequency and severity varies by host-pathogen relationship and heavy cigarette consumption, but not phylogenetic lineage alone. Patients who had disease resulting from allopatric-host-pathogen relationship were more likely to have PIAT than patients with disease from sympatric-host-pathogen relationship infection. Further study of this association may identify ways that treatment and preventive efforts can be tailored to specific lineages and racial/ethnic populations.

Fig. 1

Panel A shows the comparison of the frequency of host–pathogen relationships across all levels of pulmonary impairment in treated patients. Panel B shows the comparison of the frequency of ancient versus modern Mycobacterium tuberculosis genotypes across all levels of pulmonary impairment.