Changing patterns of human migrations shaped the global population structure of Mycobacterium tuberculosis in France.

Mycobacterium tuberculosis (Mtb) exhibits a structured phylogeographic distribution worldwide linked with human migrations. We sought to infer how the interactions between distinct human populations shape the global population structure of Mtb on a regional scale. We applied the recently described timescaled haplotypic density (THD) technique on 638 minisatellite-based Mtb genotypes from French tuberculosis patients. THD with a long-term (200 y) timescale indicated that Mtb population in France had been mostly influenced by interactions with Eastern and Southern Europe and, to a lesser extent, Northern and Middle Africa, consistent with historical migrations favored by geographic proximity or commercial exchanges with former French colonies. Restricting the timescale to 20 y, THD identified a sustained influence of Northern Africa, but not Europe where tuberculosis incidence decreased sharply. Evolving interactions between human populations, thus, measurably influence the local population structure of Mtb. Relevant information on such interactions can be inferred using THD from Mtb genotypes.

Strain-specific estimation of epidemic success provides insights into the transmission dynamics of tuberculosis.

The transmission dynamics of tuberculosis involves complex interactions of socio-economic and, possibly, microbiological factors. We describe an analytical framework to infer factors of epidemic success based on the joint analysis of epidemiological, clinical and pathogen genetic data. We derive isolate-specific, genetic distance-based estimates of epidemic success, and we represent success-related time-dependent concepts, namely epidemicity and endemicity, by restricting analysis to specific time scales. The method is applied to analyze a surveillance-based cohort of 1,641 tuberculosis patients with minisatellite-based isolate genotypes. Known predictors of isolate endemicity (older age, native status) and epidemicity (younger age, sputum smear positivity) were identified with high confidence (P < 0.001). Long-term epidemic success also correlated with the ability of Euro-American and Beijing MTBC lineages to cause active pulmonary infection, independent of patient age and country of origin. Our results demonstrate how important insights into the transmission dynamics of tuberculosis can be gained from active surveillance data.

Combined Genotypic, Phylogenetic, and Epidemiologic Analyses of Mycobacterium tuberculosis Genetic Diversity in the Rhône Alpes Region, France.

BACKGROUND: The present work relates to identification and a deep molecular characterization of circulating Mycobacterium tuberculosis complex (MTBC) strains in the Rhône-Alpes region, France from 2000 to 2010. It aimed to provide with a first snapshot of MTBC genetic diversity in conjunction with bacterial drug resistance, type of disease and available demographic and epidemiologic characteristics over an eleven-year period, in the south-east of France. METHODS: Mycobacterium tuberculosis complex (MTBC) strains isolated in the Rhône-Alpes region, France (n = 2257, 1 isolate per patient) between 2000 and 2010 were analyzed by spoligotyping. MIRU-VNTR typing was applied on n = 1698 strains (with full results available for 974 strains). The data obtained were compared with the SITVIT2 database, followed by detailed genotyping, phylogenetic, and epidemiologic analyses in correlation with anonymized data on available demographic, and epidemiologic characteristics, and location of disease (pulmonary or extrapulmonary TB). RESULTS: The most predominant spoligotyping clusters were SIT53/T1 (n = 346, 15.3%) > SIT50/H3 (n = 166, 7.35%) > SIT42/LAM9 (n = 125, 5.5%) > SIT1/Beijing (n = 72, 3.2%) > SIT47/H1 (n = 71, 3.1%). Evolutionary-recent strains belonging to the Principal Genetic Group (PGG) 2/3, or Euro-American lineages (T, LAM, Haarlem, X, S) were predominant and represented 1768 or 78.33% of all isolates. For strains having drug resistance information (n = 1119), any drug resistance accounted for 14.83% cases vs. 1.52% for multidrug resistance (MDR); and was significantly more associated with age group 21-40 years (p-value<0.001). Extra-pulmonary TB was more common among female patients while pulmonary TB predominated among men (p-value<0.001; OR = 2.16 95%CI [1.69; 2.77]). Also, BOV and CAS lineages were significantly well represented in patients affected by extra-pulmonary TB (p-value<0.001). The origin was known for 927/2257 patients: 376 (40.6%) being French-born vs. 551 (59.4%) Foreign-born. French patients were significantly older (mean age: 58.42 yrs 95%CI [56.04; 60.80]) than Foreign-born patients (mean age: 42.38 yrs. 95%CI [40.75; 44.0]). CONCLUSION: The study underlined the importance of imported TB cases on the genetic diversity and epidemiologic characteristics of circulating MTBC strains in Rhône-Alpes region, France over a large time-period. It helps better understand intricate relationships between certain lineages and geographic origin of the patients, and pinpoints genotypic and phylogenetic specificities of prevailing MTBC strains. Lastly, it also demonstrated a slow decline in isolation of M. africanum lineage in this region between 2000 and 2010.

Gut Health in the era of the human gut microbiota: from metaphor to biovalue.

The human intestinal ecosystem, previously called the gut microflora is now known as the Human Gut Microbiota (HGM). Microbiome research has emphasized the potential role of this ecosystem in human homeostasis, offering unexpected opportunities in therapeutics, far beyond digestive diseases. It has also highlighted ethical, social and commercial concerns related to the gut microbiota. As diet factors are accepted to be the major regulator of the gut microbiota, the modulation of its composition, either by antibiotics or by food intake, should be regarded as a fascinating tool for improving the human health. Scientists, the food industry, consumers and policymakers alike are involved in this new field of nutrition. Defining how knowledge about the HGM is being translated into public perception has never been addressed before. This raises the question of metaphors associated with the HGM, and how they could be used to improve public understanding, and to influence individual decision-making on healthcare policy. This article suggests that a meeting of stakeholders from the social sciences, basic research and the food industry, taking an epistemological approach to the HGM, is needed to foster close, innovative partnerships that will help shape public perception and enable novel behavioural interventions that would benefit public health.

Mycobacterium bovis infection, Lyon, France.

In a 5-year retrospective study, we used spoligotyping and mycobacterial interspersed repetitive units to type 13 strains of Mycobacterium bovis isolated from human sources. Despite the relatively high incidence of human tuberculosis caused by M. bovis (2%), these tools showed no clonal evolution and no relationships between the isolates.

FcgammaRIIIb and complement component C7 codeficiency in a patient with recurrence of fulminant meningococcal septic shock.

Individuals with deficiencies of the late components of complement exhibit a susceptibility to the recurrence of meningococcal disease with a usually mild clinical presentation. We report the recurrence of fulminant meningococcal disease in a complement component C7-deficient patient. We found a total deficiency of FcgammaRIIIb on neutrophils, which could partially explain the unusually severe clinical presentation.

How does susceptibility prevalence impact on the performance of disk diffusion susceptibility testing?

Antimicrobial disk diffusion susceptibility testing, devoted in a clinical context to predicting whether an antibiotic regimen will be effective, should be evaluated through predictive values. This approach implies that the susceptibility prevalence (frequency of susceptible, intermediate, and resistant isolates) affects the predictive value of a result. We quantified the influence of the susceptibility prevalence variation on the disk diffusion method performance through a modeling approach. Simulations based on a resampling procedure from two distinct minimum inhibitory concentration/diameter data sets were performed. Experimental variability on minimum inhibitory concentration and diameters was taken into account in the simulations. Results show that the susceptibility prevalence impact depends on the antibiotic and may be significant when prevalence variation is high enough. Consequences of these results on zone diameter breakpoint determination policy are discussed. This implies that the following should be done: (i) consider more rigorously the susceptibility prevalence in studies dealing with zone diameter breakpoint determination and performance evaluation, (ii) re-evaluate disk diffusion breakpoint consistency when the weight of prevalence variation is noteworthy, (iii) estimate consequences of a breakpoint international consensus on prediction quality and appropriate patient management.

Simple table for estimating confidence interval of discrepancy frequencies in microbiological safety evaluation.

We provide a simple tool to determine discrepancies confidence interval (CI) in microbiology validation studies such as technical accuracy of a qualitative test result. This tool enables to determine exact confidence interval (binomial CI) from an observed frequency when normal approximation is inadequate, that is, in case of rare events. This tool has daily applications in microbiology and we are presenting an example of its application to antimicrobial susceptibility systems evaluation.

What is the relevance of obtaining multiple blood samples for culture? A comprehensive model to optimize the strategy for diagnosing bacteremia.

Through a heuristic and probabilistic approach, we evaluated blood culture operating characteristics (sensitivity, specificity, and predictive values) as a function of several pretest parameters, together with their variability. On the basis of a meta-analysis of quantitative data from the literature, a model was developed and an estimation of the operating characteristics through numerical simulations (Monte Carlo method) was performed. The model evaluates the influence of ordering and drawing parameters on the ability of blood culture to distinguish bacteremic from nonbacteremic patients, regardless of the causative species. By considering the total blood volume to be cultured (six 5-10-mL bottles), results were found to confirm the current guidelines. On the basis of this hypothesis, the results, together with an analysis of the literature, failed to show any benefit of a strategy that involves obtaining multiple samples. The best strategy when performing blood culture is to obtain blood for 6 bottles (for a total volume of 35-42 mL), preferably at the same time.

Antimicrobial susceptibility of Streptococcus species isolated from clinical mastitis in dairy cows.

The antimicrobial susceptibility was determined for 50 Streptococcus uberis, 42 S. dysgalactiae subsp. dysgalactiae and eight S. agalactiae strains isolated from cow mastitis. Only 27% of the strains were susceptible to all antimicrobial compounds tested. Resistance to tetracycline was most frequent (particularly for S. dysgalactiae strains), then macrolide and/or lincomycin resistance. High level resistance to streptomycin and kanamycin was detected. All S. dysgalactiae and S. agalactiae strains were susceptible to beta-lactams but 44% of the S. uberis strains showed an elevated penicillin G MIC. All strains were susceptible to chloramphenicol and rifampicin.