Low tuberculosis notification in mountainous Vietnam is not due to low case detection: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Studies show that tuberculosis notification declines with increasing altitude. This can be due to declining incidence or declining case detection. In Vietnam notification rates of new smear-positive tuberculosis in the central mountainous provinces (26/100,000 population) are considerably lower than in Vietnam in general (69/100,000 population). In order to clarify whether this is explained by low incidence or low case detection, we aimed to assess the prevalence of new smear-positive tuberculosis among adults with prolonged cough in three mountainous provinces in central Vietnam.</p> <p>Methods</p> <p>A house-to-house survey of persons (≥ 15 years) was carried out in twelve randomly selected districts in 2003. Three sputum specimens were microscopically examined of persons reporting a prolonged cough (≥ 3 weeks). Case detection was assessed by the ratio between notification and prevalence.</p> <p>Results</p> <p>Of 68,946 included persons (95% response), 1,298 (1.9% 95%CI 1.8–2.2) reported a prolonged cough. Of these, eighteen were sputum smear-positive of whom two had had anti-tuberculosis treatment. The prevalence of new smear-positive tuberculosis was 27/100,000 (95%CI 11–44/100,000) and the notification rate was 44/100,000 among persons ≥ 15 years. The estimated case detection rate was 76%.</p> <p>Conclusion</p> <p>Low tuberculosis notification in this mountainous setting is probably a true reflection of low tuberculosis incidence. Possible causes for low incidence in mountainous areas include low transmission rates or altitude-related differences in pathology.</p

An evaluation of indices for quantifying tuberculosis transmission using genotypes of pathogen isolates

BACKGROUND: Infectious diseases are often studied by characterising the population structure of the pathogen using genetic markers. An unresolved problem is the effective quantification of the extent of transmission using genetic variation data from such pathogen isolates. METHODS: It is important that transmission indices reflect the growth of the infectious population as well as account for the mutation rate of the marker and the effects of sampling. That is, while responding to this growth rate, indices should be unresponsive to the sample size and the mutation rate. We use simulation methods taking into account both the mutation and sampling processes to evaluate indices designed to quantify transmission of tuberculosis. RESULTS: Previously proposed indices generally perform inadequately according to the above criteria, with the partial exception of the recently proposed Transmission-Mutation Index. CONCLUSION: Any transmission index needs to take into account mutation of the marker and the effects of sampling. Simple indices are unlikely to capture the full complexity of the underlying processes

Towards Eliminating Bias in Cluster Analysis of TB Genotyped Data

The relative contributions of transmission and reactivation of latent infection to TB cases observed clinically has been reported in many situations, but always with some uncertainty. Genotyped data from TB organisms obtained from patients have been used as the basis for heuristic distinctions between circulating (clustered strains) and reactivated infections (unclustered strains). Naïve methods previously applied to the analysis of such data are known to provide biased estimates of the proportion of unclustered cases. The hypergeometric distribution, which generates probabilities of observing clusters of a given size as realized clusters of all possible sizes, is analyzed in this paper to yield a formal estimator for genotype cluster sizes. Subtle aspects of numerical stability, bias, and variance are explored. This formal estimator is seen to be stable with respect to the epidemiologically interesting properties of the cluster size distribution (the number of clusters and the number of singletons) though it does not yield satisfactory estimates of the number of clusters of larger sizes. The problem that even complete coverage of genotyping, in a practical sampling frame, will only provide a partial view of the actual transmission network remains to be explored

A Mycobacterium tuberculosis cluster demonstrating the use of genotyping in urban tuberculosis control

Background: DNA fingerprinting of Mycobacterium tuberculosis isolates offers better opportunities to study links between tuberculosis (TB) cases and can highlight relevant issues in urban TB control in low-endemic countries. Methods: A medium-sized molecular cluster of TB cases with identical DNA fingerprints was used for the development of a visual presentation of epidemiologic links between cases. Results: Of 32 cases, 17 (53%) were linked to the index case, and 11 (34%) to a secondary case. The remaining four (13%) could not be linked and were classified as possibly caused by the index patient. Of the 21 cases related to the index case, TB developed within one year of the index diagnosis in 11 patients (52%), within one to two years in four patients (19%), and within two to five years in six patients (29%). Conclusion: Cluster analysis underscored several issues for TB control in an urban setting, such as the recognition of the outbreak, the importance of reinfections, the impact of delayed diagnosis, the contribution of pub-related transmissions and its value for decision-making to extend contact investigations. Visualising cases in a cluster diagram was particularly useful in finding transmission locations and the similarities and links between patients

A Geographically-Restricted but Prevalent Mycobacterium tuberculosis Strain Identified in the West Midlands Region of the UK between 1995 and 2008

Background: We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK.Methodology/Principal Findings: Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the "Mercian" strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95% CI = 4.56-17.87, p 65 years old (OR = 0.25, 95% CI = 0.09-0.67, p < 0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95% CI = 2.00-46.78, p < 0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95% CI = 1.45-27.02, p = .01) were observed as social risk factors for infection.Conclusions/Significance: The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain

A novel approach : the propensity to propagate (PTP) method for controlling for host factors in studying the transmission of Mycobacterium tuberculosis

RATIONALE: Understanding the genetic variations among Mycobacterium tuberculosis (MTB) strains with differential ability to transmit would be a major step forward in preventing transmission. OBJECTIVES: To 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. METHODS: Clinical, 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. RESULTS: Both 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. CONCLUSIONS: Our 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.Portuguese Foundation for Science and Technology (FCT) (SFRH/BD/33902/2009 to HN-G). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Transmission dynamics of pulmonary tuberculosis between autochthonous and immigrant sub-populations

<p>Abstract</p> <p>Background</p> <p>The overall incidence of tuberculosis (TB) in Western Europe has been declining since the 19^thCentury. However, immigrant sub-groups from high-prevalence countries are slowing down this trend. The aim of this study was to describe how immigration influences TB transmission in Germany. For that we prospectively investigated the dynamics of TB transmission between TB high-prevalence immigrant and TB low-prevalence local populations with molecular epidemiological methods and conventional contact investigations. Besides, we assessed transmission in relation to social mixing using an innovative tool that measures the integration of immigrants into the local social environment.</p> <p>Methods</p> <p>A prospective study of confirmed culture positive cases of pulmonary TB and their contacts was carried out in a German federal state from 2003 to 2005. Data for the study included: 1) case data routinely collected by the local public health staff and transmitted to the state health office and the national surveillance centre, 2) a study questionnaire designed to capture social interactions of relevance for TB transmission and 3) molecular genotyping data (IS<it>6110 </it>DNA fingerprint and spoligotyping). The proportion of German cases caused by foreign-born cases, and vice versa, was estimated and an integration index was computed using a selected set of questions from the study questionnaire.</p> <p>Results</p> <p>A total of 749 cases of culture-positive pulmonary tuberculosis voluntarily enrolled in the study, representing 57.8% of all registered cases diagnosed over the study period. Data that included study questionnaire and DNA fingerprinting were available for 41% (n = 308) of the study participants. Forty-seven clusters, defined as a least two cases infected by the same TB strains, were identified by molecular methods and included 132 (17%) of the study participants. Epidemiological links were identified for 28% of the clusters by conventional epidemiological data. In mixed clusters, defined as clusters including German and foreign-born individuals, the probability of cases to be caused by foreign-born cases was estimated at 18.3%. We observed a trend to mixed clusters with increasing time spent by immigrants in the host country. This group also presented comparatively higher integration indexes than immigrants in immigrant-only clusters.</p> <p>Conclusion</p> <p>Our results confirm the findings of other studies that there is no significant TB transmission from TB high-prevalence immigrant to TB low-prevalence autochthonous population. This may be explained by the good performance of tuberculosis screening programmes for certain groups arriving in Germany from high- prevalence countries, by a low degree of mixing of immigrants with the local population or by a combination of both.</p

First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal

BACKGROUND: Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. METHODS AND FINDINGS: We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42-4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43-5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. CONCLUSIONS: We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian reg

Tuberculosis Trends in Saudis and Non-Saudis in the Kingdom of Saudi Arabia – A 10 Year Retrospective Study (2000–2009)

Tuberculosis (TB) remains a public health problem in the Kingdom of Saudi Arabia (KSA), which has a very large labour force from high TB endemic countries. Understanding the epidemiological and clinical features of the TB problem, and the TB burden in the immigrant workforce, is necessary for improved planning and implementation of TB services and prevention measures