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B Foxman

Publications and source records attributed to B Foxman.

At least 19 recordsLinked to original sources

Association between Mycobacterium tuberculosis Beijing/W lineage strain infection and extrathoracic tuberculosis: Insights from epidemiologic and clinical characterization of the three principal genetic groups of M. tuberculosis clinical isolates.

Clinical strains of Mycobacterium tuberculosis can be divided into three principal genetic groups based on the single-nucleotide polymorphisms at the katG gene codon 463 and the gyrA gene codon 95. One subgroup of genetic group 1, the Beijing/W lineage, has been widely studied because of its worldwide distribution and association with outbreaks. In order to increase our understanding of the clinical and epidemiological relevance of the genetic grouping of M. tuberculosis clinical strains and the Beijing/W lineage, we investigated the genetic grouping of 679 clinical isolates of M. tuberculosis, representing 96.3% of culture-confirmed tuberculosis cases diagnosed in Arkansas between January 1996 and December 2000 using PCR and DNA sequencing. We assessed the associations of infections by different genetic groups of M. tuberculosis strains and infection by the Beijing/W lineage strains with the clinical and epidemiological characteristics of the patients using chi-square tests and multivariate logistic regression analysis. Of the 679 study isolates, 676 fell into one of the three principal genetic groups, with 63 (9.3%) in group 1, 438 (64.8%) in group 2, and 175 (25.9%) in group 3. After adjusting for potential confounding of age, gender, race/ethnicity, human immunodeficiency virus serostatus, and plcD genotype in a multivariate logistic regression model, patients infected by the Beijing/W lineage isolates were nearly three times as likely as patients infected with the non-Beijing/W lineage isolates to have an extrathoracic involvement (odds ratio [95% confidence interval], 2.85 [1.33, 6.12]). Thus, the Beijing/W lineage strains may have some special biological features that facilitate the development of extrathoracic tuberculosis.

Adolescent↗

Distribution of novel and previously investigated virulence genes in colonizing and invasive isolates of Streptococcus agalactiae.

Although Streptococcus agalactiae has emerged as an important cause of invasive disease, relatively little is known regarding the genetic basis of virulence of this organism. Three novel genes with characteristics suggesting a role in virulence were identified via comparison of sequenced genomes of S. agalactiae. The presence of these genes and of the previously identified genes bac, bca, rib, and spb1 was determined, and isolates were assigned a binary genetic signature. It was found that isolates containing spb1, previously suggested to be limited to serotype III-3, were represented by 18 different genetic signatures and several serotypes, and that the presence of both sbp1 and rib was more predictive of invasive disease than spb1 alone. Additionally, bac-positive isolates, reported to be genetically homogeneous, were represented by 14 different genetic signatures. Finally, the majority of serotype V isolates examined contained zero or only one of the genes tested, suggesting that much remains undiscovered regarding important virulence factors in isolates of this serotype.

Aged↗

Probe hybridization array typing: a binary typing method for Escherichia coli.

The ability to distinguish between Escherichia coli strains is critical for outbreak investigations. Binary typing, based on the presence or absence of genetic material, provides a high-throughput alternative to gel- and PCR-based typing techniques that generate complex banding patterns and lack uniform interpretation criteria. We developed, validated, and determined the discriminatory power of an E. coli binary typing method, probe hybridization array typing (PHAT). In PHAT, the absence or presence of genetic material is identified by using DNA hybridization to produce a reproducible and portable fingerprint for each genome. PHAT probes were generated from genome subtractive hybridization experiments. We PHAT typed the ECOR collection of strains from a variety of geographical locations, and 33 rectal E. coli strains selected from college-aged women with urinary tract infection. In the set of 33 human rectal strains, the discriminatory power of PHAT (98%) equaled that of multilocus sequence typing (MLST) and pulsed-field gel electrophoresis. However, for ECOR strains, which include nonhuman strains, the current set of PHAT probes was less discriminating than MLST, ribotyping, and enterobacterial repetitive intergenic consensus sequence PCR (80% versus 97, 92, and 97%, respectively). When we limited the analysis to ECOR strains of B2 and D lineage, which are associated with human infection, current PHAT probes were highly discriminatory (94%). PHAT can be applied in a high-throughput format (i.e., "library on a slide"), the discriminatory ability can be varied based on the probe set, and PHAT is readily adapted to other bacterial species with high variation in genetic content.

Adolescent↗

Ethical conflicts in public health research and practice: antimicrobial resistance and the ethics of drug development.

Since the 1960s, scientists and pharmaceutical representatives have called for the advancement and development of new antimicrobial drugs to combat infectious diseases. In January 2005, Senate Majority Leader Bill Frist (R-TN), MD, introduced a biopreparedness bill that included provisions for patent extensions and tax incentives to stimulate industry research on new antimicrobials. Although government stimulus for private development of new antimicrobials is important, it does not resolve long-standing conflicts of interest between private entities and society. Rising rates of antimicrobial resistance have only exacerbated these conflicts. We used methicillin-resistant Staphylococcus aureus as a case study for reviewing these problems, and we have suggested alternative approaches that may halt the vicious cycle of resistance and obsolescence generated by the current model of antimicrobial production.

Anti-Bacterial Agents↗

Population-based study of deletions in five different genomic regions of Mycobacterium tuberculosis and possible clinical relevance of the deletions.

Regions of difference (RDs) have been described in clinical isolates of Mycobacterium tuberculosis, but the potential epidemiological and clinical relevance of the genotypes of these RDs remains to be investigated. We screened a population-based sample of 648 isolates for the deletion of five RDs, designated RD105, RD181, RD142, RD150, and RD239, using microarray-based hybridization, PCR, and DNA sequencing and assessed the associations between the RD deletions and the clinical characteristics of the patients using chi-square analysis and multivariate logistic regression model. Of the 648 isolates, 18 (2.8%) had the RD239 deletion and 39 (6.0%) had the RD105 deletion. The deletions of RD142, RD150, and RD181 subdivided the isolates with the RD105 deletion into four groups comprising a group with concurrent deletions of RD105, RD181, and RD142 (n = 13); a group with concurrent deletions of RD105, RD181, and RD150 (n = 5); a group with concurrent deletions of RD105 and RD181 (n = 13); and a group with a deletion of RD105 only (n = 8). Extrathoracic tuberculosis is statistically significantly associated with infection with the isolates with concurrent deletions of RD105, RD181, and RD142 (adjusted odds ratio [OR] = 3.05; 95% confidence interval [CI] = 1.58, 5.90) and the isolates with concurrent deletions of RD105, RD181, and RD150 (adjusted OR = 11.09; 95% CI = 4.27, 28.80), after controlling for the previously identified risk factors for extrathoracic tuberculosis (human immunodeficiency virus serostatus, race, gender, and the genotype of the plcD gene). These two combinations of RD deletions have the potential for predicting the clinical presentation of M. tuberculosis infection in the human host.

Adolescent↗

Distribution of insertion- and deletion-associated genetic polymorphisms among four Mycobacterium tuberculosis phospholipase C genes and associations with extrathoracic tuberculosis: a population-based study.

The Mycobacterium tuberculosis genome contains four phospholipase C (PLC)-encoding genes, designated plcA, plcB, plcC, and plcD, respectively. Each of the four genes contributes to the overall PLC activity of M. tuberculosis. PLC is hypothesized to contribute to M. tuberculosis virulence. Infection of M. tuberculosis strains carrying a truncated plcD gene is associated with the occurrence of extrathoracic tuberculosis. However, whether the other three plc genes are also associated with extrathoracic tuberculosis remains to be assessed. We investigated the insertion- and deletion-associated genetic diversity in all four plc genes among 682 epidemiologically and clinically well-characterized M. tuberculosis clinical isolates using PCR, DNA sequencing, and Southern hybridization. Two hundred sixty-six (39%) of the 682 isolates had an interruption in at least one of the four plc genes, most often associated with an IS6110 insertion. The plcD gene interruption was the most common: it was observed in 233 (34%) of the isolates, compared to 4.7%, 4.1%, and 5.9% for plcA, plcB, and plcC gene interruption, respectively. The association between the plc gene genotypes and disease presentation was adjusted for clustering using generalized estimating equations for both bivariate and multivariate analyses. After controlling for the genotypes of the plcABC genes and the host-related risk factors, interruption in the plcD gene remained significantly associated with extrathoracic tuberculosis (odds ratio, 3.27; 95% confidence interval, 1.32 to 8.14). The data suggest that the plcD gene might play a more important role in the pathogenesis of thoracic TB than it does in the pathogenesis of extrathoracic TB.

Bacterial Proteins↗

Identification of the lipooligosaccharide biosynthesis gene lic2B as a putative virulence factor in strains of nontypeable Haemophilus influenzae that cause otitis media.

Nontypeable (NT) strains of Haemophilus influenzae are an important cause of acute otitis media (OM). The pathogenic process by which NT H. influenzae strains cause OM is poorly understood. In order to identify specific virulence factors important for OM pathogenesis, genomic subtraction of the NT H. influenzae middle ear isolate G622 against H. influenzae strain Rd was conducted and the resulting subtraction products were used to screen a panel of H. influenzae isolates. Subtraction identified 36 PCR fragments unique to strain G622, which were used in a preliminary screen of 48 middle ear isolates and 46 nasopharyngeal and throat isolates to identify genes found more frequently among middle ear isolates. These experiments identified a PCR fragment with high homology to the lipooligosaccharide biosynthesis gene lic2B (originally identified in an H. influenzae type b strain) among 52% of the middle ear isolates and 9% of nasopharyngeal and throat isolates. The lic2B gene cloned from NT H. influenzae strain G622 was 99% identical at the amino acid level to that of the H. influenzae type b strain RM7004. The lic2B gene was used to screen a larger panel of H. influenzae isolates including the original 48 middle ear isolates, 40 invasive type b isolates, 90 NT H. influenzae throat isolates from children attending day care, and 32 NT H. influenzae nasopharyngeal clinical isolates. The lic2B gene was found 3.7 times more frequently among middle ear isolates than in throat isolates from children attending day care. These data suggest that a specific NT H. influenzae gene is associated with OM.

Bacterial Proteins↗

Use of pulsed-field gel electrophoresis, enterobacterial repetitive intergenic consensus typing, and automated ribotyping to assess genomic variability among strains of nontypeable Haemophilus influenzae.

We compared 75 nontypeable (NT) Haemophilus influenzae isolates by pulsed-field gel electrophoresis (PFGE), enterobacterial repetitive intergenic consensus (ERIC)-PCR, and automated ribotyping. PFGE was the most discriminatory of the techniques. ERIC-PCR provides a useful screen but should not replace other techniques as the sole method to group NT H. influenzae strains.

Bacterial Typing Techniques↗

Widespread distribution of urinary tract infections caused by a multidrug-resistant Escherichia coli clonal group.

BACKGROUND: The management of urinary tract infections is complicated by the increasing prevalence of antibiotic-resistant strains of Escherichia coli. We studied the clonal composition of E. coli isolates that were resistant to trimethoprim-sulfamethoxazole from women with community-acquired urinary tract infections. METHODS: Prospectively collected E. coli isolates from women with urinary tract infections in a university community in California were evaluated for antibiotic susceptibility, O:H serotype, DNA fingerprinting, pulsed-field gel electrophoretic pattern, and virulence factors. The prevalence and characteristics of an antibiotic-resistant clone were evaluated in this group of isolates and in those from comparison cohorts in Michigan and Minnesota. RESULTS: Fifty-five of the 255 E. coli isolates (22 percent) from the California cohort were resistant to trimethoprim-sulfamethoxazole as well as other antibiotics. There was a common pattern of DNA fingerprinting, suggesting that the isolates belonged to the same clonal group (clonal group A), in 28 of 55 isolates with trimethoprim-sulfamethoxazole resistance (51 percent) and in 2 of 50 randomly selected isolates that were susceptible to trimethoprim-sulfamethoxazole (4 percent, P<0.001). In addition, 11 of 29 resistant isolates (38 percent) from the Michigan cohort and 7 of 18 (39 percent) from the Minnesota cohort belonged to clonal group A. Most of the clonal group A isolates were serotype O11:H(nt) or O77:H(nt), with similar patterns of virulence factors, antibiotic susceptibility, and electrophoretic features. CONCLUSIONS: In three geographically diverse communities, a single clonal group accounted for nearly half of community-acquired urinary tract infections in women that were caused by E. coli strains with resistance to trimethoprim-sulfamethoxazole. The widespread distribution and high prevalence of E. coli clonal group A has major public health implications.

Adolescent↗

Molecular epidemiology: focus on infection.

Molecular biology techniques have become increasingly integrated into the practice of infectious disease epidemiology. The term "molecular epidemiology" routinely appears in the titles of articles that use molecular strain-typing ("fingerprinting") techniques-regardless of whether there is any epidemiologic application. What distinguishes molecular epidemiology is both the "molecular," the use of the techniques of molecular biology, and the "epidemiology," the study of the distribution and determinants of disease occurrence in human populations. The authors review various definitions of molecular epidemiology. They then comment on the range of molecular techniques available and present some examples of the benefits and challenges of applying these techniques to infectious agents and their affected host using tuberculosis and urinary tract infection as examples. They close with some thoughts about training future epidemiologists to best take advantage of the new opportunities that arise from integrating epidemiologic methods with modern molecular biology.

Communicable Diseases↗

Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors.

OBJECTIVE: To assess the effects of hormone therapy on urinary tract infection frequency and to examine potential risk factors. METHODS: We used data from the Heart and Estrogen/Progestin Replacement Study, a randomized, blinded trial of the effects of hormone therapy on coronary heart disease events among 2763 postmenopausal women aged 44-79 with established coronary heart disease. Participants were randomly assigned to 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate or placebo and followed for a mean of 4.1 years. History of physician-diagnosed urinary tract infections and risk factors were assessed by self-report at baseline and each annual visit. RESULTS: Urinary tract infection frequency was higher in the group randomized to hormone treatment, although the difference was not statistically significant (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.99, 1.37). Statistically significant risk factors for urinary tract infections in multivariable analysis included: women with diabetes on treatment (insulin OR 1.81, 95% CI 1.40, 2.34), oral medications OR 1.44, 95% CI 1.09, 1.90), poor health (OR 1.34, 95% CI 1.14, 1.57), childbirth (OR 1.38, 95% CI 1.00, 1.90), vaginal itching (OR 1.63, 95% CI 1.07, 2.50), vaginal dryness (OR 1.30, 95% CI 1.04, 1.67), and urge incontinence (OR 1.51, 95% CI 1.30, 1.75). Urinary tract infections in the previous year were strongly associated with a single urinary tract infection (OR 7.00, 95% CI 5.91, 8.29) as well as multiple urinary tract infections (OR 18.51, 95% CI 14.27, 24.02). CONCLUSIONS: Oral hormone therapy did not reduce frequency of urinary tract infections. Potentially modifiable risk factors in postmenopausal women are different from those in younger women, and include diabetes, vaginal symptoms, and urge incontinence.

Adult↗

Optimization of a fluorescent-based phosphor imaging dot blot DNA hybridization assay to assess E. coli virulence gene profiles.

To increase the efficiency and consistency in screening Escherichia coli for virulence genes, a Phosphor Imager was adopted for signal detection in Dot Blot DNA hybridization replacing X-ray film read by eye. We assessed not only the reliability of the instrument-based procedure, but the impact of going from an outcome measured by visualization on a semi-quantitative scale to a digitized readout on an interval scale. We analyzed technical and biological variability of the assay and the factors contributing to the variability. In spite of high variability both within and between membranes in the Phosphor Imager readings, we were able to define classification rules for gene presence that were remarkably consistent. Using the X-ray film signal detection procedure with Southern confirmation as a gold standard, we obtained a sensitivity and specificity of 87-99% for a rule requiring no retesting for all but one gene probe.

Autoradiography↗

Urinary tract infection among women aged 40 to 65: behavioral and sexual risk factors.

We conducted a case-control study to explore the role of health behavior and sexual and medical history on urinary tract infection (UTI) risk among otherwise healthy women aged 40-65. Cases and controls were recruited from nine practices and clinics in Michigan and a single clinic in Israel. In both countries, several factors were reported significantly more frequently among UTI cases than controls: a previous UTI within 12 months, incontinence symptoms, a recent episode of 30-plus minutes of cold hands, feet, back or buttocks, and recent antibiotic use. Cases were less likely than controls to report recent estrogen use, but the results were only statistically significant in Michigan. Sexual activity during the previous 2 weeks and having ceased menses were modestly, but not statistically significantly, protective at both study sites. Risk factors for UTI among women 40-65 differ from those for younger women and these differences cannot be attributed solely to changes in menopausal status.

Adult↗

Prevalence and co-colonization with group b streptococcus (Gbs) Among heterosexual college couples.

PURPOSE: Maternal colonization with GBS is a major cause of neonatal sepsis and meningitis. While GBS transmission is assumed to be fecal-oral or person-to-person direct contact including possible sexual transmission, risk factors for colonization and carriage are poorly described. Basic descriptive epidemiologic information is needed in order to implement a prevention program such as the development of an effective vaccine.METHODS: As part of a study of heterosexual transmission of urinary tract infection (UTI), we describe the prevalence and co-colonization of GBS among college couples. Self-collected vaginal, urine and rectal specimens were cultured from women with UTI and their current sex partners ("case couples"), and from women without UTI and their current sex partners ("control couples").RESULTS: Thirty-four percent (98/285) of case women and 31% (56/182) of control women had at least one GBS isolate. 25% (45/177) of case men and 26% (32/122) of control men had at least one GBS isolate. Given that GBS was present in one partner, 45% of case (34/75) and 57% of control (24/42) couples were co-colonized. Using pulsed-field gel electrophoresis (PFGE) analysis, GBS isolates shared within couples were identical in most cases, but PFGE patterns differed across couples.CONCLUSIONS: Prevalence of GBS is high among sexually active college students and sexual contact is associated with increased transmission.

Journal Article↗

Risk factors for second urinary tract infection among college women.

To better understand the etiology of recurrent urinary tract infection (UTI), the authors followed a cohort of 285 female college students with first UTI for 6 months or until second UTI. A first UTI due to Escherichia coli was followed by a second UTI three times more often than was a non-E. coli first UTI (24 vs. 8%; p = 0.02). In a logistic regression analysis limited to the 224 women from the University of Michigan Health Service and the University of Texas at Austin Health Service from September 1992 to December 1994, with a first UTI due to E. coli, vaginal intercourse increased the risk of a second UTI with both a different (odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.19, 2.15) and the same (OR = 1.37, 95% CI: 0.91, 2.07) uropathogen, as did using a diaphragm, cervical cap, and/or spermicide (same uropathogen: OR = 1.53, 95% CI: 0.95, 2.47; different uropathogen: OR = 1.77, 95% CI: 1.22, 2.58). Condom use decreased the risk of a second UTI caused by a different uropathogen (OR = 0.68, 95% CI: 0.48, 0.99) but had no effect on a second UTI caused by the same E. coli (OR = 0.99; 95% CI: 0.66, 1.50). Type or duration of treatment was not associated with a second UTI. Although the risk of second UTI is strongly influenced by sexual behavior, women with a first UTI caused by E. coli are more likely than are those with a non-E. coli first UTI to have a second UTI within 6 months.

Adolescent↗

Oral Chlamydia trachomatis in patients with established periodontitis.

Periodontitis is considered a consequence of a pathogenic microbial infection at the periodontal site and host susceptibility factors. Periodontal research supports the association of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, and Bacteroides forsythus, and periodontitis; however, causality has not been demonstrated. In pursuit of the etiology of periodontitis, we hypothesized that the intracellular bacteria Chlamydia trachomatis may play a role. As a first step, a cross-sectional study of dental school clinic patients with established periodontitis were assessed for the presence of C. trachomatis in the oral cavity, and in particular from the lining epithelium of periodontal sites. C. trachomatis was detected using a direct fluorescent monoclonal antibody (DFA) in oral specimens from 7% (6/87) of the patients. Four patients tested positive in specimens from the lining epithelium of diseased periodontal sites, one patient tested positive in healthy periodontal sites, and one patient tested positive in the general mucosal specimen. In conclusion, this study provides preliminary evidence of C. trachomatis in the periodontal sites. Planned studies include the use of a more precise periodontal epithelial cell collection device, the newer nucleic acid amplification techniques to detect C. trachomatis, and additional populations to determine the association of C. trachomatis and periodontitis.

Adult↗