418 research outputs found
Whole-genome sequencing of Mycobacterium tuberculosis as an epidemiological marker
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Annual Mycobacterium tuberculosis infection risk and interpretation of clustering statistics.
No full textSeveral recent studies have used proportions of tuberculosis cases sharing identical DNA fingerprint patterns (i.e., isolate clustering) to estimate the extent of disease attributable to recent transmission. Using a model of introduction and transmission of strains with different DNA fingerprint patterns, we show that the properties and interpretation of clustering statistics may differ substantially between settings. For some unindustrialized countries, where the annual risk for infection has changed little over time, 70% to 80% of all age groups may be clustered during a 3-year period, which underestimates the proportion of disease attributable to recent transmission. In contrast, for a typical industrialized setting (the Netherlands), clustering declines with increasing age (from 75% to 15% among young and old patients, respectively) and underestimates the extent of recent transmission only for young patients. We conclude that, in some settings, clustering is an unreliable indicator of the extent of recent transmission
Emerg Infect Dis
No full textMolecular surveillance of multidrug-resistant tuberculosis (MDR TB) was implemented in Europe as case reporting in 2005. For all new MDR TB cases detected from January 2003 through June 2007, countries reported case-based epidemiologic data and DNA fingerprint patterns of MDR TB strains when available. International clusters were detected and analyzed. From 2003 through mid-2007 in Europe, 2,494 cases of MDR TB were reported from 24 European countries. Epidemiologic and molecular data were linked for 593 (39%) cases, and 672 insertion sequence 6110 DNA fingerprint patterns were reported from 19 countries. Of these patterns, 288 (43%) belonged to 18 European clusters; 7 clusters (242/288 cases, 84%) were characterized by strains of the Beijing genotype family, including the largest cluster (175/288 cases, 61%). Both clustering and the Beijing genotype were associated with strains originating in eastern European countries. Molecular cluster detection contributes to identification of transmission profile, risk factors, and control measures
Novel genetic polymorphisms that further delineate the phylogeny of the Mycobacterium tuberculosis complex.
No full textIn a previous report, we described a PCR protocol for the differentiation of the various species of the Mycobacterium tuberculosis complex (MTC) on the basis of genomic deletions (R. C. Huard, L. C. de Oliveira Lazzarini, W. R. Butler, D. van Soolingen, and J. L. Ho, J. Clin. Microbiol. 41:1637-1650, 2003). That report also provided a broad cross-comparison of several previously identified, phylogenetically relevant, long-sequence and single-nucleotide polymorphisms (LSPs and SNPs, respectively). In the present companion report, we expand upon the previous work (i) by continuing the evaluation of known MTC phylogenetic markers in a larger collection of tubercle bacilli (n = 125), (ii) by evaluating additional recently reported MTC species-specific and interspecific polymorphisms, and (iii) by describing the identification and distribution of a number of novel LSPs and SNPs. Notably, new genomic deletions were found in various Mycobacterium tuberculosis strains, new species-specific SNPs were identified for "Mycobacterium canettii," Mycobacterium microti, and Mycobacterium pinnipedii, and, for the first time, intraspecific single-nucleotide DNA differences were discovered for the dassie bacillus, the oryx bacillus, and the two Mycobacterium africanum subtype I variants. Surprisingly, coincident polymorphisms linked one M. africanum subtype I genotype with the dassie bacillus and M. microti with M. pinnipedii, thereby suggesting closer evolutionary ties within each pair of species than had been previously thought. Overall, the presented data add to the genetic definitions of several MTC organisms as well as fine-tune current models for the evolutionary history of the MTC
The respiratory microbiota: new insights into pulmonary tuberculosis.
No full textPrevious studies demonstrated that the diversity and composition of respiratory microbiota in TB patients were different from healthy individuals. Therefore, the aim of the present analysis was to estimate the relative proportion of respiratory microbiota at phylum and genus levels among TB cases and healthy controls. The PubMed and Google Scholar online databases were searched to retrieve relevant studies for the analysis. The statistical analysis was done using STATA version 11, pooled estimates are presented using graphs. The summary of findings in included studies is also presented in Table 1. The phylum level analysis shows that the pooled proportions of Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Crenarchaeota were determined among tuberculosis patients and healthy controls. In brief, Firmicutes, and Proteobacteria were the most abundant bacterial phyla in both TB cases and healthy controls, composing 39.9 and 22.7% in TB cases and 39.4 and 19.5% in healthy controls, respectively. The genus level analysis noted that Streptococcus (35.01%), Neisseria (27.1%), Prevotella (9.02%) and Veillonella (7.8%) were abundant in TB patients. The Prevotella (36.9%), Gammaproteobacteria (22%), Streptococcus (19.2%) and Haemophilus (15.4%) were largely seen in healthy controls. Interestingly, Veillonella, Rothia, Leuconostoc were unique to TB cases, whereas Lactobacillus, and Gammaproteobacteria, Haemophilus, and Actinobacillus were identified only in healthy controls. The composition of the respiratory microbiota in TB patients and healthy controls were quite different. More deep sequencing studies are needed to explore the microbial variation in the respiratory system in connection with TB
Molecular epidemiology of tuberculosis in selected sites across Papua New Guinea
No full textWith an estimated one third of the global population being infected with latent tuberculosis (TB) and 8.6 million people developing active TB in 2012, this infectious disease remains a major global health concern. Increasing drug resistance (DR) and the HIV pandemic are further challenges to the control of the disease.
Mycobacterium tuberculosis (Mtb) is responsible for most of the TB cases in humans. For a long time it was thought that only environmental factors and the host immune status are the driving forces of TB transmission. Recently, evidence of the influence of the bacterial genetic background on transmission and disease outcome is increasing. Clinical samples from around the globe are required to further analyze the impact of the complex interactions of drug resistance, bacterial and host genetics, as well as environmental and social factors on TB epidemiology and individual patient management.
Even though Papua New Guinea (PNG) is one of the high TB burden countries in the South Pacific, not much data on the local epidemiology of TB exists. Apart from the urgent need to fill such evidence gaps, the country also provides an interesting platform for TB research, considering its population genetic diversity and its isolation in the past. The presented project aimed at providing baseline data about the molecular epidemiology of tuberculosis from specific sites in PNG, including drug resistance and the population structure of Mtb.
Between July and December 2010, active TB case detection surveys were conducted in the catchment area of two health centres in PNG: around Sausi health centre in Madang Province and around East-Cape health centre in Milne Bay Province. Each household in the catchment area was screened for people with chronic productive cough aged 15 years and above. Of household members with chronic productive cough not having received TB treatment yet, three sputum samples were collected. Subsequently, samples were analysed by light microscopy to diagnose pulmonary TB by detecting the presence of acid fast bacilli. Around Sausi, 24 so far undetected pulmonary TB cases were identified, whereas in East-Cape only one additional case was found, reflecting the differences in the performance of the control program between different sites in PNG. Active case detection as a complementary case detection approach turned out to be a useful tool to increase the case detection rate in certain areas, but appeared unsuitable to investigating the prevalence of drug resistance and the genetic background of Mtb. However, operational limitations did not allow obtaining better estimates on the real burden of TB in the country in the frame of our study.
From November 2010 to July 2012, passive case detection was conducted in three provincial hospitals of PNG: Modilon General Hospital in Madang Province, Goroka General Hospital in Eastern Highlands Province and Alotau Provincial Hospital in Milne Bay Province. Three sputum samples were collected from TB suspects aged 15 years and above and subsequently analysed by light and fluorescent microscopy. Furthermore, the level of drug resistance as well as the genetic background of M. tuberculosis strains was determined and findings compared between sites. Of 225 passive case detection samples grown in culture, 212 samples could successfully be tested for drug susceptibility. Overall, 10.8% (23/212) strains were found to be resistant to at least one of the first-line drugs streptomycin, rifampicin, isoniazid, pyrazinamide or ethambutol. Differences between study sites in any type of DR were marginal and ranged from 10% to 12%. Multi-drug resistant (MDR) TB was found in 2.8% (6/212) of cases, the highest percentage of MDR TB being found in Alotau (4.6% compared to 2.2% in Madang and 1.8% in Goroka). These results show a significant amount of DR TB being present in all three sites investigated. It is therefore crucial to make diagnosis of DR TB and second-line treatment more widely available in the country to decrease the delay of diagnosing DR TB as well as the duration of possible transmission and to avoid further DR development.
Genotyping of Mtb could successfully be conducted of 147 samples. These strains could be classified into three of the so far seven known lineages of Mtb: 75/147 (51.0%) of samples belonged to lineage 4 (European-American lineage), 67/147 (45.6%) to lineage 2 (East-Asian lineage) and 5/147 (3.4%) to lineage 1 (Indo-Oceanic lineage). All three lineages were detected in all three sites, but the individual lineage compositions varied significantly between sites (p<0.001). In Madang, lineage 4 was the most prevalent (76.6%), whereas in Alotau lineage 2 was dominant (84.4%). In Goroka, a trend towards a higher prevalence of lineage 2 (60.5%) was found, but the difference between lineage 2 and lineage 4 was not statistically significant and not as high as in Alotau. Lineage 1 was generally only rarely found (5/147). The overall lineage composition found in PNG is similar to what can be observed globally: modern lineages (e.g. lineages 2 and 4) have more successfully spread around the globe and are more prevalent than ancient lineages (e.g. lineage 1). Further molecular subtyping by large sequence polymorphisms, Luminex based SNP-typing and whole genome sequencing revealed that a single introduction of lineage 2 into PNG with a subsequent clonal expansion is most probable, whereas for lineages 4 and 1, several introductions are likely. All three lineages appear to have undergone to a certain degree PNG-specific evolution.
The present study is the first directly comparing DR and Mtb genotyping data between different sites of PNG, discovering the presence of significant differences in DR prevalence and Mtb lineages. However, the reason for these observed differences has yet to be determined. The questions about how and from where TB was introduced into PNG in the first place, and about details on transmission dynamics of TB remain to be answered.
Besides Mtb, also non-tuberculous mycobacteria (NTM) could be detected in a few sputum samples of study patients. NTM were detected in 4% (9/225) of sputum samples grown in culture. Five of these turned out to be samples containing NTM only, the detected species being Mycobacterium fortuitum, Mycobacterium terrae and Mycobacterium intracellulare. Four isolates contained both, Mtb and Mycobacterium avium or Mtb and Mycobacterium intracellulare, respectively. To our knowledge this is the first study describing the presence of NTM in PNG.
A key component of the National TB Program should be the detection and continuous monitoring of DR TB to stop transmission. Our data emphasizes the need of a GeneXpert system for DR diagnosis and monitoring in each province of PNG. Priority should be given to those provinces with an increased proportion of DR TB such as Milne Bay Province. In addition, an in-country capacity to perform TB culturing and DST is urgently required. Implementing both recommendations could assist in achieving a reduction of time to diagnosis of DR TB and consequently decrease the risk of MDR TB transmission
Emerg Infect Dis
No full textIn the Netherlands, 1.4% of tuberculosis (TB) cases are caused by Mycobacterium bovis. After we admitted 3 patients with M. bovis infections to our reference hospital, we conducted a retrospective analysis of all M. bovis disease in the Netherlands during 1993-2007. We analyzed data from 231 patients for clinical, demographic, treatment, and outcome characteristics and for risk factors. Most patients were native Dutch (n = 138; 59.7%) or Moroccan (n = 54; 23.4%). Disease was mainly extrapulmonary (n = 136; 58.9%). Although 95 patients had pulmonary disease, person-to-person transmission did not occur, as shown by structural DNA fingerprinting analysis. Lymph node TB was more likely to develop in women (p<0.0001), whereas pulmonary M. bovis disease developed more frequently in men (p<0.0001). Diagnosis was accurate but delayed and led to inadequate treatment in 26% of the cases. Proportion of deaths from M. bovis disease was higher than that for M. tuberculosis disease
Worldwide occurrence of Beijing/W strains of Mycobacterium tuberculosis: a systematic review.
No full textStrains of the Beijing/W genotype family of Mycobacterium tuberculosis have caused large outbreaks of tuberculosis, sometimes involving multidrug resistance. This genetically highly conserved family of M. tuberculosis strains predominates in some geographic areas. We have conducted a systematic review of the published reports on these strains to determine their worldwide distribution, spread, and association with drug resistance. Sixteen studies reported prevalence of Beijing strains defined by spoligotyping; another 10 used other definitions. Beijing strains were most prevalent in Asia but were found worldwide. Associations with drug resistance varied: in New York, Cuba, Estonia, and Vietnam, Beijing strains were strongly associated with drug resistance, but elsewhere the association was weak or absent. Although few reports have measured trends in prevalence, the ubiquity of the Beijing strains and their frequent association with outbreaks and drug resistance underline their importance
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