Identification of factors for tuberculosis transmission via an integrated multidisciplinary approach

Department of Epidemiology, School of Public Health, University of Michigan, M5124 SPH II, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA.
Tuberculosis (Edinburgh, Scotland) (Impact Factor: 2.71). 02/2011; 91(3):244-9. DOI: 10.1016/
Source: PubMed


It was reported previously that the major fraction of the recent decrease of tuberculosis incident cases in Arkansas had been due to a decrease in the reactivated infections. Preventing transmission of Mycobacterium tuberculosis is the key to a continued decline in tuberculosis cases. In this study, we integrated epidemiological data analysis and comparative genomics to identify host and microbial factors important to tuberculosis transmission. A significantly higher proportion of cases in large clusters (containing >10 cases) were non-Hispanic black, homeless, less than 65 years old, male sex, smear-positive sputum, excessive use of alcohol, and HIV sero-positive, compared to cases in small clusters (containing 2-5 cases) diagnosed within one year. However, being non-Hispanic black and homeless within the past year were the only two host characteristics that were identified as independent risk factors for being in large clusters. This finding suggests that social behavioral factors have a more important role in transmission of tuberculosis than does the infectiousness of the source. Comparing the genomic content of one of the large cluster strains to that of a non-clustered strain from the same community identified 25 genes that differed between the two strains, potentially contributing to the observed differences in transmission.


Available from: Xinyu Zhang, Sep 08, 2014
  • Source
    • "non-clustered isolates with a high PPP). This selection process is useful to hone in on a crisp phenotype that is necessary to study bacterial factors associated with transmission, by means of genomic comparison in future whole-genome sequencing studies [21]. It would for example be interesting to subject the CDC1551 outbreak to our new approach in order to separate host risk factors from the true bacteriological component. "
    [Show abstract] [Hide abstract]
    ABSTRACT: RationaleUnderstanding the genetic variations among Mycobacterium tuberculosis (MTB) strains with differential ability to transmit would be a major step forward in preventing transmission.ObjectivesTo describe a method to extend conventional proxy measures of transmissibility by adjusting for patient-related factors, thus strengthening the causal association found with bacterial factors.MethodsClinical, demographic and molecular fingerprinting data were obtained during routine surveillance of verified MTB cases reported in the Netherlands between 1993 and 2011, and the phylogenetic lineages of the isolates were inferred. Odds ratios for host risk factors for clustering were used to obtain a measure of each patient's and cluster's propensity to propagate (CPP). Mean and median cluster sizes across different categories of CPP were compared amongst four different phylogenetic lineages.ResultsBoth mean and median cluster size grew with increasing CPP category. On average, CPP values from Euro-American lineage strains were higher than Beijing and EAI strains. There were no significant differences between the mean and median cluster sizes among the four phylogenetic lineages within each CPP category.ConclusionsOur finding that the distribution of CPP scores was unequal across four different phylogenetic lineages supports the notion that host-related factors should be controlled for to attain comparability in measuring the different phylogenetic lineages' ability to propagate. Although Euro-American strains were more likely to be in clusters in an unadjusted analysis, no significant differences among the four lineages persisted after we controlled for host factors.
    PLoS ONE 05/2014; 9(5):e97816. DOI:10.1371/journal.pone.0097816 · 3.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Development of novel diagnostics for tuberculosis has so far been governed by the clinical requirement of improving the detection of patients with paucibacillary forms of the disease. For this aim, serological assays have been evaluated using several antigens, but were found insufficiently sensitive, because antibody production associates with the bacterial load of the disease. Consequently, detection of antibodies against a relatively small number of selected well-defined antigens has a much higher sensitivity for sputum smear-positive pulmonary disease in adult HIV-negative patients. They are the most active in generating and spreading aerosols containing live tubercle bacilli, but their detection is often delayed, thus perpetuating the transmission of the infection and disease in the population. High volume throughput serological screening of clinical suspects with mild clinical symptoms may help to achieve diagnosis earlier, than currently used procedures. Such expanded testing could be done more efficiently in laboratories, than at 'points-of-care' and at a lower cost than other tests. The feasibility of this approach towards reducing the delayed diagnosis of the most infectious cases of pulmonary tuberculosis needs to be ascertained in prospective diagnostic trials, in populations at a high risk. Reducing the transmission of tuberculosis is of key importance for achieving its continued decline and therefore it is proposed, that the aims of serological screening should shift from clinical to public health priorities.
    Tuberculosis (Edinburgh, Scotland) 09/2011; 92(1):31-7. DOI:10.1016/ · 2.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Data are scarce on demographical factors related to the population structure of Mycobacterium tuberculosis in Saudi Arabia. A study was conducted on 902 clinical isolates to explore current trends in the phylogeography and associated demographical factors of tuberculosis by using spoligotyping and 24 loci based MIRU-VNTR typing. Young male patients (aged 16-29 and 30-44) were predominant in this cohort. The phylogenetic diversity among M. tuberculosis isolates was found high, as almost all known genetic lineages were identified. Delhi/CAS (26.4%), EAI (13.7%) and Haarlem (11.3%) were the most common lineages observed, particularly among the low age groups (16-29 and 30-44 years), whereas elderly patients (>60 years) showed a predominance in the lineages S, Ghana, TUR and Uganda-I. A statistically significant association was observed between gender of the patients and lineages of EAI (p value 0.026) and LAM (p value 0.005). Overall, molecular strain cluster rate was 34.4% with an elevated rate among patients aged below 15 years (43.1%), while cases among the elderly (>60 years) showed the lowest degree of clustering (12.5%). The largest level of clustering was noticed among cases caused by strains of the lineages Haarlem (59.8%), Beijing (55.8%) and LAM (42.8%). The current population structure of M. tuberculosis in Saudi Arabia is highly diverse with significant associations to demography, transmission dynamics and origin of the patients. The difference in genotype distributions among low and high aged patients reflects the ongoing change in the strain population structure in the country.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 03/2013; 16. DOI:10.1016/j.meegid.2013.03.019 · 3.02 Impact Factor
Show more