Bacterial Community Modifies Host Genetics Effect on Early Childhood Caries.

By age 5, approximately one-fifth of children have early childhood caries (ECC). Both the oral microbiome and host genetics are thought to influence susceptibility. Whether the oral microbiome modifies genetic susceptibility to ECC has not been tested. We test whether the salivary bacteriome modifies the association of a polygenic score (PGS, a score derived from genomic data that summarizes genetic susceptibility to disease) for primary tooth decay on ECC in the Center for Oral Health Research in Appalachia 2 longitudinal birth cohort. Children were genotyped using the Illumina Multi-Ethnic Genotyping Array and underwent annual dental examinations. We constructed a PGS for primary tooth decay using weights from an independent, genome-wide association meta-analysis. Using Poisson regression, we tested for associations between the PGS (high versus low) and ECC incidence, adjusting for demographic characteristics (n = 783). An incidence-density sampled subset of the cohort (n = 138) had salivary bacteriome data at 24 mo of age. We tested for effect modification of the PGS on ECC case status by salivary bacterial community state type (CST). By 60 mo, 20.69% of children had ECC. High PGS was not associated with an increased rate of ECC (incidence rate ratio, 1.09; 95% confidence interval [CI], 0.83-1.42). However, having a cariogenic salivary bacterial CST at 24 mo was associated with ECC (odds ratio [OR], 7.48; 95% CI, 3.06-18.26), which was robust to PGS adjustment. An interaction existed between the salivary bacterial CST and the PGS on the multiplicative scale (P = 0.04). The PGS was associated with ECC (OR, 4.83; 95% CI, 1.29-18.17) only among individuals with a noncariogenic salivary bacterial CST (n = 70). Genetic causes of caries may be harder to detect when not accounting for cariogenic oral microbiomes. As certain salivary bacterial CSTs increased ECC risk across genetic risk strata, preventing colonization of cariogenic microbiomes would be universally beneficial.

Plaque Microbiome in Caries-Active and Caries-Free Teeth by Dentition.

OBJECTIVE: Describe associations between dental caries and dental plaque microbiome, by dentition and family membership. METHODS: This cross-sectional analysis included 584 participants in the Center for Oral Health Research in Appalachia Cohort 1 (COHRA1). We sequenced the 16S ribosomal RNA gene (V4 region) of frozen supragingival plaque, collected 10 y prior, from 185 caries-active (enamel and dentinal) and 565 caries-free (no lesions) teeth using the Illumina MiSeq platform. Sequences were filtered using the R DADA2 package and assigned taxonomy using the Human Oral Microbiome Database. RESULTS: Microbiomes of caries-active and caries-free teeth were most similar in primary dentition and least similar in permanent dentition, but caries-active teeth were significantly less diverse than caries-free teeth in all dentition types. Streptococcus mutans had greater relative abundance in caries-active than caries-free teeth in all dentition types (P < 0.01), as did Veillonella dispar in primary and mixed dentition (P < 0.01). Fusobacterium sp. HMT 203 had significantly higher relative abundance in caries-free than caries-active teeth in all dentition types (P < 0.01). In a linear mixed model adjusted for confounders, the relative abundance of S. mutans was significantly greater in plaque from caries-active than caries-free teeth (P < 0.001), and the relative abundance of Fusobacterium sp. HMT 203 was significantly lower in plaque from caries-active than caries-free teeth (P < 0.001). Adding an effect for family improved model fit for Fusobacterium sp. HMT 203 but notS. mutans. CONCLUSIONS: The diversity of supragingival plaque composition from caries-active and caries-free teeth changed with dentition, but S. mutans was positively and Fusobacterium sp. HMT 203 was negatively associated with caries regardless of dentition. There was a strong effect of family on the associations of Fusobacterium sp. HMT 203 with the caries-free state, but this was not true for S. mutans and the caries-active state. KNOWLEDGE TRANSFER STATEMENT: Patients' and dentists' concerns about transmission of bacteria within families causing caries should be tempered by the evidence that some shared bacteria may contribute to good oral health.

Genome-wide Scan of Dental Fear and Anxiety Nominates Novel Genes.

Dental care-related fear and anxiety (DFA) is prevalent, affects oral health care utilization, and is related to poor oral health and decreased quality of life. In addition to learned and cultural factors, genetics is hypothesized to contribute to DFA. Therefore, we performed a genome-wide association study to identify genetic variants contributing to DFA. Adult and adolescent participants were from 4 cohorts (3 from the US-based Center for Oral Health Research in Appalachia, n = 1,144, 1,164, and 535, and the UK-based Avon Longitudinal Study of Parents and Children [ALSPAC], n = 2,078). Two self-report instruments were used to assess DFA: the Dental Fear Survey (US cohorts) and Corah's Dental Anxiety Scale (ALSPAC). Genome-wide scans were performed for the DFA total scores and subscale scores (avoidance, physiological arousal, fear of dental treatment-specific stimuli), adjusting for age, sex, educational attainment, recruitment site, and genetic ancestry. Results across cohorts were combined using meta-analysis. Heritability estimates for DFA total and subscale scores were similar across cohorts and ranged from 23% to 59%. The meta-analysis revealed 3 significant (P < 5E-8) associations between genetic loci and 2 DFA subscales: physiological arousal and avoidance. Nearby genes included NTSR1 (P = 3.05E-8), DMRTA1 (P = 4.40E-8), and FAM84A (P = 7.72E-9). Of these, NTSR1, which was associated with the avoidance subscale, mediates neurotensin function, and its deficiency may lead to altered fear memory in mice. Gene enrichment analyses indicated that loci associated with the DFA total score and physiological arousal subscale score were enriched for genes associated with severe and persistent mental health (e.g., schizophrenia) and neurocognitive (e.g., autism) disorders. Heritability analysis indicated that DFA is partly explained by genetic factors, and our association results suggested shared genetic underpinnings with other psychological conditions.

Dietary Patterns and Risk of a New Carious Lesion Postpartum: A Cohort Study.

Dental caries (cavities), one of the most common infectious diseases, is caused by a number of factors. Oral microbes, dietary practices, sociodemographic factors, and dental hygiene all inform caries risk. Assessing the impact of diet is complicated as individuals eat foods in combinations, and the interactions among the foods may alter caries risk. Our study aimed to prospectively assess the association between dietary patterns and caries risk in the postpartum period, a potentially sensitive period for caries development. We analyzed in-person dental assessments and telephone food frequency questionnaires (FFQs) from 879 Caucasian women participating in the Center for Oral Health Research in Appalachia Cohort 2 (COHRA2) that were collected biannually for up to 6 y. One-week recall of food intake frequency was assessed using a Likert scale. We used principal component analysis to summarize the FFQ data; the top 2 components described 15% and 12% of the variance in FFQ data. The first component was characterized by high consumption of fruits and vegetables, while the second component was heavily influenced by desserts and crackers. We used a modified Poisson model to predict the risk of an increase in the number of decayed, missing, and filled teeth in the postpartum period by 1) dietary patterns and 2) individual foods and beverages at the previous study visit, after controlling for other known risk factors, including history of carious lesions. Eating a dietary pattern high in desserts and crackers was associated with a 20% increase in the number of decayed, missing, and filled teeth in the postpartum period (95% confidence interval, 1.03-1.39). However, this effect was attenuated among those who also consumed a dietary pattern high in fruits and vegetables. Dietary patterns should be considered when devising interventions aimed at preventing dental caries.

Opposition to Early Dental Visit by Dentists: A Qualitative Study on Mothers' Social Networks.

OBJECTIVES: To examine whether information that mothers received from dentists in their social network was consistent with professional recommendations for the first dental visit at age 1 y. METHODS: We performed a cross-sectional qualitative study on mothers in Pennsylvania and West Virginia from 2018 to 2020 to explore how their social networks influence their children's dental service utilization. In-person, semistructured interviews were conducted with 126 mothers of children ages 3 to 5 y. Qualitative data were transcribed, coded, and analyzed using NVivo 12. Two investigators analyzed data using grounded theory and the constant comparative method. RESULTS: Over half of mothers reported a professional relationship with a dentist as part of their social network on children's oral health. Mothers described the following themes: 1) mothers contacted dentists in their social network for child dental information and to schedule their child's first dental visit, 2) mothers described dentists' justifications for the timing of the first dental visit older than age 1 y, 3) mothers described the impact of the dentist declining to see her child, and 4) after the dentist declined to see her child, some mothers did not comply with the dentist's recommendation of delayed child dental visits because they were given alternative information that encouraged early dental visits. CONCLUSIONS: Our findings indicate a need for dentists to reinforce mothers' dental-seeking behavior for young children and adhere to recommendations on the age 1 dental visit. KNOWLEDGE TRANSFER STATEMENT: Qualitative data on mothers' social networks show that dentists play a key role in access to early dental visits, particularly when dentists decline to see the mother's child for visits.

Maternal Oral Health Influences Infant Salivary Microbiome.

Oral microbiomes vary in cariogenic potential; these differences may be established early in life. A major concern is whether mothers transmit cariogenic bacteria to their children. Here we characterize early salivary microbiome development and the potential associations of that development with route of delivery, breastfeeding, and mother's oral health, and we evaluate transmission of microbes between mother and child. We analyzed saliva and metadata from the Center for Oral Health Research in Appalachia. For this cohort study, we sequenced the V6 region of the 16S rRNA gene and used quantitative polymerase chain reaction to detect Streptococcus mitis, Streptococcus sobrinus, Streptococcus mutans, Streptococcus oralis, and Candida albicans in the saliva from mothers and their infants, collected at 2, 9, and 12 mo (Pennsylvania site) and 2, 12, and 24 mo (West Virginia site). Breastfed children had lower relative abundances of Prevotella and Veillonella. If mothers had decayed, missing, or filled teeth, children had greater abundances of Veillonella and Actinomyces. There was little evidence of maternal transmission of selected microbes. At 12 mo, children's microbiomes were more similar to other children's than to their mothers'. Infants' salivary microbiomes became more adult-like with age but still differed with mothers' microbiomes at 12 mo. There was little evidence supporting transmission of selected microbes from mothers to children, but risk of colonization was associated with tooth emergence. Children are likely to acquire cariogenic bacteria from a variety of sources, including foods and contact with other children and adults.

Bayesian Analysis of the Association between Family-Level Factors and Siblings' Dental Caries.

We conducted a Bayesian analysis of the association between family-level socioeconomic status and smoking and the prevalence of dental caries among siblings (children from infant to 14 y) among children living in rural and urban Northern Appalachia using data from the Center for Oral Health Research in Appalachia (COHRA). The observed proportion of siblings sharing caries was significantly different from predicted assuming siblings' caries status was independent. Using a Bayesian hierarchical model, we found the inclusion of a household factor significantly improved the goodness of fit. Other findings showed an inverse association between parental education and siblings' caries and a positive association between households with smokers and siblings' caries. Our study strengthens existing evidence suggesting that increased parental education and decreased parental cigarette smoking are associated with reduced childhood caries in the household. Our results also demonstrate the value of a Bayesian approach, which allows us to include household as a random effect, thereby providing more accurate estimates than obtained using generalized linear mixed models.

Co-colonization by Streptococcus pneumoniae and Staphylococcus aureus in the throat during acute respiratory illnesses.

Pneumonia due to either Streptococcus pneumoniae (Sp) or Staphylococcus aureus (Sa) accounts for most mortality after influenza and acute respiratory illness (ARI). Because carriage precedes infection, we estimated Sp and Sa carriage to examine the co-colonization dynamics between Sp, Sa and respiratory viruses in the presence of ARI in the oropharynx. We tested oropharyngeal specimens of community subjects (aged ⩾2 years) with ARI for the presence of influenza A and B, 11 other common respiratory viruses, Sp and Sa, using real-time PCR. A total of 338 participants reported 519 ARI episodes of which 119 (35%) carried Sp, 52 (13%) carried Sa and 25 (7%) carried both. Thirty-five subjects tested positive for influenza, of which 14 (40%) carried Sp and six (17%) carried Sa, significantly more than in the influenza-negative group (P = 0·03 and P = 0·04, respectively). In subjects infected by any virus compared to those with no virus, Sp carriage (39·2% vs. 27·9%, P = 0·03) but not Sa carriage (11·6% vs. 14%, P = 0·6) was more frequent. For children, when Sa was present, Sp carriage tended to be less frequent than expected given the presence of viral infection, but not significantly [observed relative risk 1·14, 95% confidence interval (CI) 0·4-3·1; with a relative excess risk due to interaction of -0·11]. Independent of age, Sp carriers were more likely to return that season with subsequent ARI (odds ratio 2·14, 95% CI 1·1-4·3, P = 0·03). Both Sp and Sa carriage rates in the oropharynx increase during influenza infection in children. However, no negative interaction between Sp and Sa was observed. Sp carriers are more likely to suffer subsequent ARI episodes than non-carriers.

High-throughput quantitative method for assessing coaggregation among oral bacterial species.

UNLABELLED: This paper describes a high-throughput method that relies upon a microplate reader to score coaggregation 60 min postmixing, and use of a high-speed real-time imaging technology to describe the rate of coaggregation over time. The results of visual, microplate, and FlowCam(™) aggregation scores for oral bacteria Streptococcus gordonii, Streptococcus oralis, and Actinomyces oris, whose ability to coaggregate are well characterized, are compared. Following mixing of all possible pairs, the top fraction of the supernatant was added to a microplate to quantify cell-density. Pairs were also passed through a flow cell within a FlowCam(™) to quantify the rate of coaggregation of each pair. Results from both the microplate and FlowCam(™) approaches correlated with corresponding visual coaggregation scores and microscopic observations. The microplate-based assay enables high-throughput screening, whereas the FlowCam(™) -based assay validates and quantifies the extent that autoaggregation and coaggregation occur. Together these assays open the door for future in-depth studies of autoaggregation and coaggregation among large panels of test strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Coaggregation between bacterial species is integral to multi-species biofilm development. Difficulties in rapidly and reproducibly identifying and quantifying coaggregation have limited mechanistic studies. This paper demonstrates two complementary quantitative methods to screen for coaggregation. The first approach uses a microplate-based high-throughput approach and the other uses a FlowCam(™) device. The microplate-based approach enables rapid detection of coaggregation between candidate coaggregating pairs of strains simultaneously while controlling for variation between replicates. The FlowCam(™) approach allows for in-depth analysis of the rates of coaggregation and size of aggregates formed.

High prevalence of Neisseria gonorrhoeae in a remote, undertreated population of Namibian pastoralists.

The highly remote pastoralist communities in Kaokoland, Namibia, have long been presumed to have high gonorrhoea prevalence. To estimate gonorrhoea prevalence and correlates of infection, we conducted a cross-sectional study of 446 adults across 28 rural villages. Gonorrhoea status was determined from urethral and vaginal swabs via qPCR assay. All participants answered a closed-ended interview about demographics, sexual behaviour and symptom history. Sixteen per cent of participants had high-level infections (⩾ID(50) dose) and 48% had low-level infections (

Emerging fluoroquinolone resistance in Streptococcus agalactiae in South Korea.

The goal of this study was to determine the prevalence of fluoroquinolone resistance in Streptococcus agalactiae and the serotype distribution of this resistant bacterium. S. agalactiae strains collected from 221 asymptomatic pregnant women (35-37 weeks of gestation) and 838 patients with S. agalactiae infection in Korea, from 2006 to 2008, were tested for susceptibility to four fluoroquinolones. Rates of resistance of S. agalactiae to ciprofloxacin, levofloxacin, and moxifloxacin were 9.3 %, 9.5 %, and 0.8 %, respectively; greater than 94 % of S. agalactiae strains were resistant to norfloxacin. Resistance to ciprofloxacin and levofloxacin increased between 2006 and 2008. All strains were susceptible to penicillin. Resistance to ciprofloxacin and levofloxacin was higher in the clinical strains of S. agalactiae isolated from infections than in colonizing strains isolated from pregnant women. Mutations in the quinolone resistance-determining regions of gyrase and topoisomerase genes were detected in strains resistant to ciprofloxacin, levofloxacin, and moxifloxacin; no such mutations were found in strains resistant only to norfloxacin. There was a strong correlation between the minimum inhibitory concentrations and the presence of mutations in gyrase and topoisomerase genes. In conclusion, the prevalence of fluoroquinolone resistance was unexpectedly high. Strain serotypes were not associated with susceptibility to fluoroquinolones.

Caries resistance as a function of age in an initially caries-free population.

Using data from the Center for Oral Health Research in Appalachia Study, we examined variability in susceptibility to dental caries among children and adolescents in rural Appalachia. Among 210 participants who were caries-free at the initial visit, age at the baseline visit can be used as a proxy for the degree of caries resistance; probability of caries development at the tooth level decreased as age at the baseline visit increased. Participants who stayed caries-free for a longer period during childhood and adolescence experienced less extensive caries, as measured by the number of carious teeth. However, the probability of becoming caries-positive did not correlate with age at the baseline visit. For children between 1 and 18 years of age, there was not a "threshold age" after which a caries-free child's risk of caries onset is significantly reduced.

Epidemiology of group B streptococcus in Korean pregnant women.

Between January 2006 and May 2008, 2624 pregnant S. Korean women between 35-37 weeks gestation were screened for group B streptococcus (GBS). Resistance to antimicrobials was tested by disk diffusion and serotype determined using co-agglutination assays and microarray methods. Overall, 8% of pregnant women were colonized. Serotype III was the predominant serotype (43.8%), followed by serotypes V (20.3%), Ia (12.1%), and Ib (9.5%). GBS was frequently resistant to clindamycin (54.0%) and erythromycin (25.6%); 3.7% were resistant to cefazolin. More than three-quarters of serotype V were resistant to clindamycin or erythromycin or both, and 71% of serotype III were resistant to clindamycin but only 12% were resistant to erythromycin. GBS prevalence exceeded earlier reports by one-third. This is the first report of cefazolin resistance in Korea. These results underscore the need to establish screening measures and chemoprophylaxis guidelines regarding GBS infections in Korea.

Comparative whole-genome analysis of Streptococcus mutans isolates within and among individuals of different caries status.

INTRODUCTION: Genotypic analyses of Streptococcus mutans using fingerprinting methods depend on a few genetic loci being different but do not reveal the underlying genome-wide differences between strains. METHODS: We used comparative genomic hybridization (CGH) with 70-mer oligonucleotide microarrays containing open reading frames (ORFs) from S. mutans strain UA159 to examine the genetic diversity of 44 isolates from nine children selected from a local study population in Eastern Iowa. RESULTS: Unique strains (clones) within each child initially identified by arbitrary-priming polymerase chain reaction were confirmed by CGH. There was a wide range of variation in the hybridization patterns of the 1948 ORFs among the test isolates examined. Between 87 and 237 ORFs failed to give a positive signal among individual isolates. A total of 323 of the UA159 ORFs were absent from one or more of the test strains. These 323 variable genes seemed to be distributed across the entire UA159 genome and across all the predicted functional categories. CONCLUSION: This set of very close geographically and temporally collected S. mutans isolates had a degree of gene content variation as high as a previously examined global set of strains. Comparing the frequency of these variable genes, the majority of which have unknown function, among strains of different origins (i.e. different caries status) could help to determine their relevance in S. mutans cariogenicity.

Streptococcus agalactiae pulsed-field gel electrophoresis patterns cross capsular types.

Streptococcus agalactiae is a genetically diverse organism; when typed by pulsed-field gel electrophoresis (PFGE), multiple types appear within a single serotype. We tested whether S. agalactiae PFGE types correspond to a specific serotype within individuals, and different individuals from the same geographic area. A total of 872 S. agalactiae isolates from 152 healthy individuals were classified by PFGE and capsular serotype. Serotype V was the most homogeneous (Simpson's diversity index 0.54); and types III, II and Ib were mostly heterogeneous (Simpson's diversity index 0.90). Within an individual, isolates with the same PFGE patterns had identical capsular types, but across individuals the same PFGE types sometimes occurred in different serotypes. Capsular type alone is insufficient to define epidemiological relatedness. Although PFGE types appear to be a valid surrogate for capsular typing of isolates from the same individual, it is not a valid surrogate for serotype in isolates from different individuals.

Risk factors for group B streptococcal colonization: potential for different transmission systems by capsular type.

PURPOSE: Group B Streptococcus (GBS) is a common inhabitant of the bowel and vaginal flora, with known transmission routes including sexual contact and vertical transmission from mother to infant. Food-borne transmission is also possible, as GBS is a known fish and bovine pathogen. We conducted a prospective cohort study in order to identify risk factors for acquisition. METHODS: We identified risk factors for GBS acquisition among college women (n = 129) and men (n = 128) followed at 3-week intervals for 3 months. RESULTS: A doubling in sex acts significantly increased incidence of GBS capsular type V by 80% (95% confidence interval [CI]: 1.19, 2.58), and other non-Ia or -Ib types combined by 40% (95% CI: 1.00, 2.06; incidence of capsular type Ia (odds ratio [OR] = 1.2; 95% CI: 0.71, 1.88; p = 0.57) and Ib (OR = 1.5, 95% CI: 0.75, 2.86; p = 0.27) were elevated, although not significantly. After adjustment for sexual activity and sexual history, gender, and eating venue, fish consumption increased risk of acquiring capsular types Ia and Ib combined 7.3 fold (95% CI: 2.34, 19.50), but not of acquiring other capsular types. Beef and milk were not associated with GBS incidence. CONCLUSIONS: Different GBS capsular types may have different transmission routes.

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.

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.

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.

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.