Stigma Related to Observable Symptoms, But Not Stimulant Medication Use, in Young Women With ADHD.

OBJECTIVE: ADHD is associated with stigma, but whether stimulant medication use contributes to this is unknown. We examined how perception of a young woman may be influenced by visible ADHD symptoms and/or prescribed stimulant medication use (PSMU). METHOD: Three-hundred-fourteen undergraduates were randomly assigned to watch one of four videos: a woman portraying (a) neither symptoms of ADHD nor PSMU, (b) no ADHD symptoms but disclosing PSMU, (c) ADHD symptoms but no PSMU, or (d) both ADHD symptoms and PSMU. Participants then completed measures of their liking of and desire for affiliation with the woman. RESULTS: Analyses suggest that visible symptoms of ADHD were perceived negatively and are associated with less liking and desire for affiliation. PSMU was associated with negligible additive stigma. CONCLUSION: This supports that noticeable ADHD symptoms may be the primary driver of the stigma associated with the disorder, and specifically that directed at young women with ADHD.

Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, pesticides, and diabetes in the Anniston Community Health Survey follow-up (ACHS II): single exposure and mixture analysis approaches.

Dioxins and dioxin-like compounds measurements were added to polychlorinated biphenyls (PCBs) and organochlorine pesticides to expand the exposure profile in a follow-up to the Anniston Community Health Survey (ACHS II, 2014) and to study diabetes associations. Participants of ACHS I (2005-2007) still living within the study area were eligible to participate in ACHS II. Diabetes status (type-2) was determined by a doctor's diagnosis, fasting glucose ≥125 mg/dL, or being on any glycemic control medication. Incident diabetes cases were identified in ACHS II among those who did not have diabetes in ACHS I, using the same criteria. Thirty-five ortho-substituted PCBs, 6 pesticides, 7 polychlorinated dibenzo-p-dioxins (PCDD), 10 furans (PCDF), and 3 non-ortho PCBs were measured in 338 ACHS II participants. Dioxin toxic equivalents (TEQs) were calculated for all dioxin-like compounds. Main analyses used logistic regression models to calculate odds ratios (OR) and 95 % confidence intervals (CI). In models adjusted for age, race, sex, BMI, total lipids, family history of diabetes, and taking lipid lowering medication, the highest ORs for diabetes were observed for PCDD TEQ: 3.61 (95 % CI: 1.04, 12.46), dichloro-diphenyl dichloroethylene (p,p'-DDE): 2.07 (95 % CI 1.08, 3.97), and trans-Nonachlor: 2.55 (95 % CI 0.93, 7.02). The OR for sum 35 PCBs was 1.22 (95 % CI: 0.58-2.57). To complement the main analyses, we used BKMR and g-computation models to evaluate 12 mixture components including 4 TEQs, 2 PCB subsets and 6 pesticides; suggestive positive associations for the joint effect of the mixture analyses resulted in ORs of 1.40 (95% CI: -1.13, 3.93) for BKMR and 1.32 (95% CI: -1.12, 3.76) for g-computation. The mixture analyses provide further support to previously observed associations of trans-Nonachlor, p,p'- DDE, PCDD TEQ and some PCB groups with diabetes.

Lead and zinc concentrations in household dust and toenails of the residents (Estarreja, Portugal): a source-pathway-fate model.

This paper describes a methodology developed to assess and apportion probable indoor and outdoor sources of potentially toxic elements while identifying chemical signatures in the household dust collected from private homes in an industrial city (Estarreja, central Portugal). Oral bioaccessibility estimates and the chemical composition of toenail clippings were used to assess indoor dust ingestion as a potential exposure pathway and further investigate exposure-biomarker relationships. Indoor and paired outdoor dust samples were collected from each household. A total of 30 individuals, who provided toenail clippings and a self-reported questionnaire, were recruited for the study. Total concentrations of 34 elements, including lead and zinc, were determined in washed toenail samples and household dust via Inductively Coupled Plasma-Mass Spectrometry. The oral bioaccessibility was estimated using the Unified BARGE Method. The enrichment factor shows that lead was enriched (10 < EF < 100) while zinc (EF > 100) was anomalously enriched in the household dust, thus indicating potential exposure in the home environment. The results from principal component analysis coupled to cluster analysis and linear discriminant analysis suggested that mixed contamination derived from multiple sources with a predominance of biomass burning. Stepwise multiple linear regression analysis was performed to model toenail data using the indoor dust elemental composition. Whereas the model obtained for lead was not reliable, indoor dust zinc and antimony contents arose as good predictors of toenail zinc. The exposure-biomarker relationships seem to be influenced by the oral bioaccessibility of the elements.

Investigating relationships between biomarkers of exposure and environmental copper and manganese levels in house dusts from a Portuguese industrial city.

This study reports on data obtained from a pilot survey focusing on house dust and toenail metal(loids) concentrations in residents living in the industrial city of Estarreja. The study design hereby described aims at investigating relationships between human toenails and both copper and manganese levels in settled house dusts. A total of 21 households and 30 individuals were recruited for the pilot study: 19 households corresponding to 27 residents living near the industrial complex, forming the exposed group, plus 2 households and 3 residents from residential areas with no anticipated environmental contaminants that were used for comparison. Factorial analysis was used for source identification purposes. Investigation on the potential influence of environmental factors over copper and manganese levels in the toenails was carried out via questionnaire data and multiple correspondence analysis. The results show that copper concentrations are more elevated in the indoor dusts, while manganese concentrations are more elevated in the outdoor dust samples. The geometrical relationships in the datasets suggest that the backyard soil is a probable source of manganese to the indoor dust. Copper and manganese contents in the toenail clippings are more elevated in children than in adults, but the difference between the two age groups is not statistically significant (p > 0.05). Investigation of environmental factors influencing the exposure-biomarker association indicates a probable relationship between manganese contents in indoor dust and manganese levels in toenail clippings, a result that is partially supported by the bioaccessibility estimates. However, for copper, no relationship was found between indoor dusts and the biomarkers of exposure.

The mobility and human oral bioaccessibility of Zn and Pb in urban dusts of Estarreja (N Portugal).

Twenty-one samples of urban dust were collected from Estarreja city (Portugal). The main objective of this work was to assess the potential availability of Pb and Zn present dust samples from Estarreja city via the oral ingestion exposure route using a combination of geochemical tests: (a) using sequential extraction to identify the fractionation of the Pb and Zn within the geochemical components that make up the dust and (b) in vitro bioaccessibility (BA) measurements to identify which components are the source(s) of the bioaccessible fraction (Bf). These samples were analysed for their quasi-total contents of Pb and Zn by inductively coupled plasma mass spectrometry, for their element solid-phase distribution using selective sequential extraction method and for the Bfs of these elements using a physiologically based extraction test. The study showed that the concentrations of Zn were higher than Pb, but both are site-specific. The sequential extraction test shows that the exchangeable and acid-soluble phases are important bearing phases for Pb and Zn. The BA test showed that a high proportion of the total concentration is available for absorption into the human body (ranges from 22.5 to 84.1% for Pb and 28.7 to 86.3% for Zn).

Geochemistry, mineralogy, solid-phase fractionation and oral bioaccessibility of lead in urban soils of Lisbon.

An urban survey of Lisbon, the largest city in Portugal, was carried out to investigate its environmental burden, emphasizing metallic elements and their public health impacts. This paper examines the geochemistry of lead (Pb) and its influence on human health data. A total of 51 soil samples were collected from urban recreational areas used by children to play outdoors. The semi-quantitative analysis of Pb was carried out by inductively coupled plasma mass spectrometry after an acid digestion. X-ray diffraction was used to characterize the soil mineralogy. The solid-phase distribution of Pb in the urban soils was investigated on a subset of 7 soils, out of a total of 51 samples, using a non-specific sequential extraction method coupled with chemometric analysis. Oral bioaccessibility measurements were obtained using the Unified BARGE Method developed by the Bioaccessibility Research Group of Europe. The objectives of the study are as follows: (1) investigation of Pb solid-phase distribution; (2) interpretation of Pb oral bioaccessibility measurements; (3) integration of metal geochemistry with human health data; and (4) understanding the influence of geochemistry and mineralogy on oral bioaccessibility. The results show that the bioaccessible fraction of Pb is lower when major metal fractions are associated with less soluble soil phases such as Fe oxyhydroxides, and more increased when the metal is in the highly soluble carbonate phase. However, there is some evidence that the proportion of carbonates in the soil environment is also a key control over the oral bioaccessibility of Pb, irrespective of its solid-phase fractionation.

Regional variations of basal cell carcinoma incidence in the U.K. using The Health Improvement Network database (2004-10).

BACKGROUND: Basal cell carcinoma (BCC) is one of the most common types of nonmelanoma skin cancer affecting the white population; however, little is known about how the incidence varies across the U.K. OBJECTIVES: To determine the variation in BCC throughout the U.K. METHODS: Data from 2004 to 2010 were obtained from The Health Improvement Network database. European and world age-standardized incidence rates (EASRs and WASRs, respectively) were obtained for country-level estimates and levels of socioeconomic deprivation, while strategic health-authority-level estimates were directly age and sex standardized to the U.K. standard population. Incidence-rate ratios were estimated using multivariable Poisson regression models. RESULTS: The overall EASR and WASR of BCC in the U.K. were 98.6 per 100,000 person-years and 66.9 per 100,000 person-years, respectively. Regional-level incidence rates indicated a significant geographical variation in the distribution of BCC, which was more pronounced in the southern parts of the country. The South East Coast had the highest BCC rate followed by South Central, Wales and the South West. Incidence rates were substantially higher in the least deprived groups and we observed a trend of decreasing incidence with increasing levels of deprivation (P < 0.001). Finally, in terms of age groups, the largest annual increase was observed among those aged 30-49 years. CONCLUSIONS: Basal cell carcinoma is an increasing health problem in the U.K.; the southern regions of the U.K. and those in the least deprived groups had a higher incidence of BCC. Our findings indicate an increased incidence of BCC for younger age groups below 49 years.

Lead bioaccessibility in topsoils from lead mineralisation and urban domains, UK.

Predictive linear regression (LR) modelling indicates that total Pb is the only highly significant independent variable for estimating Pb bioaccessibility in "mineralisation domains" located in limestone (high pH) and partly peat covered (low pH) shale-sandstone terrains in England. Manganese is a significant minor predictor in the limestone terrain, whilst organic matter and sulphur explain 0.5% and 2% of the variance of bioaccessible Pb in the peat-shale-sandstone terrain, compared with 93% explained by total Pb. Bootstrap resampling shows that LR confidence limits overlap for the two mineralised terrains but the limestone terrain has a significantly lower bioaccessible Pb to total Pb slope than the urban domain. A comparison of the absolute values of stomach and combined stomach-intestine bioaccessibility provides some insight into the geochemical controls on bioaccessibility in the contrasting soil types.

Relapse more common than reinfection in recurrent tuberculosis 1-2 years post treatment in urban Uganda.

OBJECTIVE: To determine the proportion of recurrent tuberculosis (TB) due to relapse with the patient's initial strain or reinfection with a new strain of Mycobacterium tuberculosis 1-2 years after anti-tuberculosis treatment in Uganda, a sub-Saharan TB-endemic country. DESIGN: Records of patients with culture-confirmed TB who completed treatment at an urban Ugandan clinic were reviewed. Restriction fragment length polymorphism (RFLP) patterns were used to determine relapse or reinfection. Associations between human immunodeficiency virus (HIV) positivity and type of TB recurrence were determined. RESULTS: Of 1701 patients cured of their initial TB episode with a median follow-up of 1.24 years, 171 (10%) had TB recurrence (8.4 per 100 person-years). Rate and risk factors for recurrence were similar to other studies from sub-Saharan Africa. Insertion sequence (IS) 6110-based RFLP of paired isolates from 98 recurrences identified 80 relapses and 18 reinfections. Relapses among HIV-positive and -negative patients were respectively 79% and 85% of recurrences. CONCLUSIONS: Relapse was more common and presented earlier than reinfection in both HIV-positive and -negative TB patients 1-2 years after completing treatment. These findings impact both the choice of retreatment drug regimen, as relapsing patients are at higher risk for acquired drug resistance, and clinical trials of new TB regimens with relapse as clinical endpoint.

Modelling lead bioaccessibility in urban topsoils based on data from Glasgow, London, Northampton and Swansea, UK.

Predictive linear regression (LR) modelling between bioaccessible Pb and a range of total elemental compositions and soil properties was executed for the Glasgow, London, Northampton and Swansea urban areas in order to assess the potential for developing a national urban bioaccessible Pb dataset for the UK. LR indicates that total Pb is the only highly significant independent variable for estimating the bioaccessibility of Pb. Bootstrap resampling shows that the relationship between total Pb and bioaccessible Pb is broadly the same in the four urban areas. The median bioaccessible fraction ranges from 38% in Northampton to 68% in London and Swansea. Results of this study can be used as part of a lines of evidence approach to localised risk assessment but should not be used to replace bioaccessibility testing at individual sites where local conditions may vary considerably from the broad overview presented in this study.

Anthropogenic and geogenic impacts on arsenic bioaccessibility in UK topsoils.

Predictive linear regression (LR) modelling between bioaccessible arsenic (B-As) and a range of total elemental compositions and soil properties was executed in order to assess the potential for developing a national B-As dataset for the UK. LR indicates that total arsenic (As) is the only highly significant independent variable for estimating B-As in urban areas where it explains 75-92% of the variance. The broad compatibility of the London, Glasgow and Swansea regression models suggests that application of these models to estimate bioaccessible As in UK soils impacted by diffuse anthropogenic urban contamination and non-ferrous metal processing should be relatively accurate. In areas dominated by Jurassic ironstones and associated clays and limestones, total As, P and pH are significant, accounting for 53, 14 and 5%, respectively, of the B-As variance. Models based on total As as the sole predictor in the combined Jurassic and Cretaceous sedimentary ironstones datasets explain about 40% of the B-As variance. The median As bioaccessible fraction (%As-BAF) is 19 to 28% in the anthropogenic contamination impacted urban domains, but much lower (5-9%) in geogenic terrains dominated by ironstones. Results of this study can be used as part of a lines of evidence approach to localised risk assessment but should not be used to replace bioaccessibility testing at individual sites where local conditions may vary considerably from the broad overview presented in this study.

Identification of factors for tuberculosis transmission via an integrated multidisciplinary approach.

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.

Soil radium, soil gas radon and indoor radon empirical relationships to assist in post-closure impact assessment related to near-surface radioactive waste disposal.

Least squares (LS), Theil's (TS) and weighted total least squares (WTLS) regression analysis methods are used to develop empirical relationships between radium in the ground, radon in soil and radon in dwellings to assist in the post-closure assessment of indoor radon related to near-surface radioactive waste disposal at the Low Level Waste Repository in England. The data sets used are (i) estimated ²²6Ra in the < 2 mm fraction of topsoils (eRa226) derived from equivalent uranium (eU) from airborne gamma spectrometry data, (ii) eRa226 derived from measurements of uranium in soil geochemical samples, (iii) soil gas radon and (iv) indoor radon data. For models comparing indoor radon and (i) eRa226 derived from airborne eU data and (ii) soil gas radon data, some of the geological groupings have significant slopes. For these groupings there is reasonable agreement in slope and intercept between the three regression analysis methods (LS, TS and WTLS). Relationships between radon in dwellings and radium in the ground or radon in soil differ depending on the characteristics of the underlying geological units, with more permeable units having steeper slopes and higher indoor radon concentrations for a given radium or soil gas radon concentration in the ground. The regression models comparing indoor radon with soil gas radon have intercepts close to 5 Bq m⁻³ whilst the intercepts for those comparing indoor radon with eRa226 from airborne eU vary from about 20 Bq m⁻³ for a moderately permeable geological unit to about 40 Bq m⁻³ for highly permeable limestone, implying unrealistically high contributions to indoor radon from sources other than the ground. An intercept value of 5 Bq m⁻³ is assumed as an appropriate mean value for the UK for sources of indoor radon other than radon from the ground, based on examination of UK data. Comparison with published data used to derive an average indoor radon: soil ²²6Ra ratio shows that whereas the published data are generally clustered with no obvious correlation, the data from this study have substantially different relationships depending largely on the permeability of the underlying geology. Models for the relatively impermeable geological units plot parallel to the average indoor radon: soil ²²6Ra model but with lower indoor radon: soil ²²6Ra ratios, whilst the models for the permeable geological units plot parallel to the average indoor radon: soil ²²6Ra model but with higher than average indoor radon: soil ²²6Ra ratios.

Does the lipR gene of tubercle bacilli have a role in tuberculosis transmission and pathogenesis?

Mycobacterium tuberculosis lipases, a diverse class of enzymes involved in lipid metabolism, may have an important role in tuberculosis (TB) pathogenesis. We explored the association of large sequence polymorphism (LSP) in one of the M. tuberculosis lipase-encoding genes, lipR (Rv3084), with patient characteristics using a population-based sample of clinical isolates to elucidate the potential role of lipR in TB pathogenesis. LSP in lipR was found in 104 (15.6%) of 665 isolates, of which 96% belonged to principal genetic group 3. When linkage by molecular type and epidemiologic evidence were compared, molecularly clustered cases infected with a lipR LSP isolate were more often epidemiologically linked than clustered cases infected with a lipR wild-type isolate. Further epidemiologic and functional studies are necessary to determine if the association between this lipR LSP and recent transmission we identified in this population reflects a functional role of lipR in TB transmission and pathogenesis or other unidentified mechanisms.

Mycobacterium tuberculosis PE_PGRS16 and PE_PGRS26 genetic polymorphism among clinical isolates.

The Mycobacterium tuberculosis PE_PGRS multigene family is thought to be involved in antigenic variation, which can be generated by differential regulation of expression and a high frequency of genetic polymorphism. PE_PGRS16 and PE_PGRS26 are inversely regulated during persistent M. tuberculosis infection, suggesting that differential regulation of the expression of these two PE_PGRS genes may have a role in latency. To understand how genetic diversity, in addition to differential regulation, contributes to antigenic variability, we investigated the sequence variations in the PE_PGRS16 and PE_PGRS26 genes among 200 clinical M. tuberculosis strains, in comparison to the sequenced laboratory strain H37Rv, using PCR and DNA sequencing. Among the 200 strains, 102 (51%) and 100 (50%) had sequence variations within the PE_PGRS16 gene and the PE_PGRS26 gene, respectively. In-frame insertions and deletions, frameshifts, and SNPs were observed in both the PE_PGRS16 gene and the PE_PGRS26 gene. However, the frequency of frameshifts and in-frame deletions differed between the two PE_PGRS genes. Examining the profile of the PE_PGRS16, PE_PGRS26, and the previously investigated PE_PGRS33 amino acid sequences for each of the 200 strains, 72 different profiles were observed with frequencies ranging from 0.5% to 13%. In conclusion, a remarkable level of genetic diversity exists in the PE_PGRS16 and PE_PGRS26 genes of M. tuberculosis clinical strains. The significant sequence variations in the two PE_PGRS genes observed in this study could impact the function of these two PE_PGRS proteins and be associated with differences in the ability of the tubercle bacilli to remain persistent within the host.

Beijing family Mycobacterium tuberculosis strains differ in their intracellular growth in THP-1 macrophages.

SETTING: Previous studies have shown that isolates from cases in IS6110 restriction fragment length polymorphism (RFLP) clusters that have persisted over several years and are widely distributed grow significantly faster in macrophages than isolates from cases with unique RFLP patterns. As members of the Beijing family of Mycobacterium tuberculosis are widely distributed and have been responsible for several large outbreaks, it has been suggested that this genotype may have a selective advantage over other strains. OBJECTIVE: To determine whether rapid growth in macrophages is a common characteristic of Beijing family strains. DESIGN: T-helper precursor-1 human macrophages were infected with various Beijing family strains, and intracellular growth and tumor necrosis factor alpha (TNF-alpha) secretion were assessed. Strains differed in their genotype, with IS6110 copy number ranging from 9 to 22. RESULTS: Strains demonstrated a range of growth phenotypes over the 7-day infection period. Three grew significantly more slowly than the other strains, whereas the fastest growth was observed consistently with isolates of strain 210. CONCLUSION: Rapid growth in macrophages is not a common characteristic of all Beijing strains. Few Beijing strains are as virulent as strain 210. The growth advantage is consistent with strain 210 having persisted many years in different locations and having caused many outbreaks.

What's driving the decline in tuberculosis in Arkansas? A molecular epidemiologic analysis of tuberculosis trends in a rural, low-incidence population, 1997 2003.

Incident cases of tuberculosis may result from a recently acquired Mycobacterium tuberculosis infection or from the reactivation of a latent infection acquired in the remote past. The authors used molecular fingerprinting data to estimate the relative contributions of recent and remotely acquired infection to the yearly incidence of tuberculosis in Arkansas, a state with a largely rural population where the incidence of tuberculosis declined from 7.9 cases per 100,000 population to 4.7 cases per 100,000 between 1997 and 2003. The authors used a time-restricted definition of clustering in addition to the standard definition in order to increase the specificity of the clustering measure for recent transmission. The greatest overall declines were seen in non-Hispanic Blacks (from 13.8 cases per 100,000 in 1997 to 6.5 cases per 100,000 in 2003) and persons aged 65 years or more (from 19.9 cases per 100,000 in 1997 to 8.5 cases per 100,000 in 2003). In both groups, the incidence of nonclustered cases declined more dramatically than the incidence of clustered cases. This suggests that the decline in rates resulted primarily from declining rates of disease due to reactivation of past infections. Declines in the overall incidence of tuberculosis in a population may not necessarily result from declines in active transmission.

Factors predicting complete necrosis rate after ultrasound-guided percutaneous laser thermoablation of small hepatocellular carcinoma tumors in cirrhotic patients: a multivariate analysis.

PURPOSE: To assess factors affecting the effectiveness of percutaneous laser ablation (PLA) under ultrasound (US) guidance in terms of complete ablation achievement. MATERIAL AND METHODS: The clinical records of 86 hepatocellular carcinoma (HCC) tumors (mean diameter 23.7 mm) in 60 cirrhotic patients (mean age 68.3 years; 36 males; 57 HCV+; 53 Child's class A, seven Child's class B) treated by means of PLA were reviewed. PLA was performed with a continuous-wave Nd:YAG laser by a single operator who positioned two to four 300-microm optic fibers advanced in 21-gauge needles into target lesions under US guidance. Triphasic computed tomography (CT) studies were used to verify treatment effectiveness 1 month after PLA completion. The association between characteristics of the lesion and outcome (complete or incomplete ablation) was evaluated by logistic regression, taking into account the following predictive factors: tumor size, pattern of growth (infiltrating or not) at imaging, location, first diagnosis of HCC (naïve tumors vs. non-naïve tumors), number of sessions (1/ > 1), total delivered energy, and years of treatment in 2001-2002 (first period) vs. 2003-2004 (second period). RESULTS: Complete ablation was obtained in 62 nodules (72%). Statistically significant predictors of incomplete ablation after the first PLA course at both univariate and multivariate analysis included: infiltrating growth pattern (odds ratio (OR) 12.3, P<0.002), non-naïve tumors (OR 8.7, P<0.001), and first period of treatment (OR 10.3, P<0.002). CONCLUSION: The effectiveness of US-guided PLA for HCC tumors < or =4 cm turned out to be negatively affected by both operator-related (the beginning of the operator's experience with the technique) and tumor-related factors (non-naïve, infiltrating HCC tumors).

Association of Mycobacterium tuberculosis PE PGRS33 polymorphism with clinical and epidemiological characteristics.

There is evidence that some members of the Mycobacterium tuberculosis PE PGRS gene subfamily, including PE PGRS33, may have a specific function in M. tuberculosis persistence. The impact of naturally-occurring PE PGRS33 genetic variations on the virulence and transmissibility of clinical M. tuberculosis isolates is not known. We used PCR and DNA sequencing to identify genetic variations in the PE PGRS33 gene in comparison with the sequenced laboratory strain, H37Rv, among 649 isolates from a population-based sample. The PE PGRS33 alleles were placed into two groups, based on the effect of the sequence variations on the PE PGRS33 protein, and their associations with clinical and epidemiological characteristics were assessed using multivariate logistic regression to control for potential confounding of host-related factors. Of the 639 isolates for which sequence data were obtained, 139 (21.8%) had PE PGRS33 alleles that would result in a significant change to the PE PGRS33 protein due to large insertions/deletions or frameshift mutations. These isolates were significantly associated with clustering based on genotype and absence of cavitations in the lungs, compared to isolates having PE PGRS33 alleles that would result in no or minimal change to the PE PGRS33 protein. The association of significant changes to PE PGRS33 with clinical and epidemiological characteristics suggests that PE PGRS33 may have an important role in M. tuberculosis persistence.

Tuberculosis genotyping in six low-incidence States, 2000-2003.

BACKGROUND: As tuberculosis incidence declines in the United States, a new tool for TB control efforts is Mycobacterium tuberculosis genotyping. Colorado, Iowa, Montana, New Hampshire, West Virginia, and Wisconsin began routine genotyping of all culture-confirmed TB cases in October 2000. METHODS: M. tuberculosis isolates from cases reported October 2000 through December 2003 were genotyped by spoligotyping, mycobacterial interspersed repetitive units, and IS6110-based restriction fragment length polymorphism methods. Genotyping results were linked to demographic variables from national surveillance records. Patients who were in genotype clusters were interviewed and their records reviewed to determine possible transmission links among clustered patients. Final analysis was completed during April 2004 through June 2005. RESULTS: Of 971 reported TB cases, 774 (80%) were culture-confirmed, of which 728 (94%) were genotyped. Most genotyped isolates (634 [87%]) were unique. Within 36 clusters linking 94 individuals, four clusters involved both U.S.- and foreign-born individuals. For eight clusters, genotyping results led to the discovery of previously unsuspected transmission. Transmission links between individuals were established in 21 (58%) of the 36 clusters. CONCLUSIONS: In these six low-incidence states, most isolates had unique genotypes, suggesting that most cases arose from activation of latent infection. Few TB clusters involved the foreign-born. For 58% of genotype clusters, epidemiologic investigation ascertained that clustering represented recent M. tuberculosis transmission.