Gerald J. Adams

Virulence control in group A Streptococcus by a two-component gene regulatory system: Global expression profiling and in vivo infection modeling

Two-component gene regulatory systems composed of a membrane-bound sensor and cytoplasmic response regulator are important mechanisms used by bacteria to sense and respond to environmental stimuli. Group A Streptococcus, the causative agent of mild infections and life-threatening invasive diseases, produces many virulence factors that promote survival in humans. A two-component regulatory system, designated covRS (cov, control of virulence; csrRS), negatively controls expression of five proven or putative virulence factors (capsule, cysteine protease, streptokinase, streptolysin S, and streptodornase). Inactivation of covRS results in enhanced virulence in mouse models of invasive disease. Using DNA microarrays and quantitative RT-PCR, we found that CovR influences transcription of 15% (n = 271) of all chromosomal genes, including many that encode surface and secreted proteins mediating host–pathogen interactions. CovR also plays a central role in gene regulatory networks by influencing expression of genes encoding transcriptional regulators, including other two-component systems. Differential transcription of genes influenced by covR also was identified in mouse soft-tissue infection. This analysis provides a genome-scale overview of a virulence gene network in an important human pathogen and adds insight into the molecular mechanisms used by group A Streptococcus to interact with the host, promote survival, and cause disease.

Gender, Perceived Parental Monitoring, and Behavioral Adjustment: Influences on Adolescent Alcohol Use

This study examined relationships among gender, perceived parental monitoring, externalizing behaviors, and adolescent alcohol use in a 2-wave longitudinal study. Females reported more perceived parental monitoring and less alcohol use than males. Perceived maternal and paternal monitoring were related to less alcohol use over time. Increases in alcohol use were associated with increases in externalizing behaviors over time. Perceived maternal monitoring mediated the relationship between gender and youth drinking and was also a significant predictor of changes in adolescent drinking over time. Perceived paternal monitoring was not a predictor of adolescent drinking in the context of perceived maternal monitoring and externalizing behaviors. The importance of gender in implementation of prevention programs is discussed.

Complex Transmission Dynamics of Clonally Related Virulent Mycobacterium tuberculosis Associated with Barhopping by Predominantly Human Immunodeficiency Virus-Positive Gay Men

Limited data suggest that measures to reduce tuberculosis transmission should be based on locations rather than on personal contacts. Molecular epidemiologic methods (analysis of IS6110 patterns, spoligotypes, variable numbers of tandem DNA repeats, and automated DNA sequence data) identified a cohort of 48 persons who were infected with progeny of the same Mycobacterium tuberculosis strain. Epidemiologic investigation documented that a large proportion of the patients were gay white human immunodeficiency virus-positive men. Most practiced barhopping, an activity that involved patronizing many bars in the same neighborhood each night. Few subjects were directly linked to more than 1 or 2 other persons by conventional investigation methods, which shows that the transmission dynamics were unusually complex compared with most previously described episodes of strain spread. The data support the concept that identification of locations where pathogen dissemination likely occurs may provide additional strategies for targeted tuberculosis control.

Using a Cox Regression Model to Examine Voluntary Teacher Turnover

Abstract A Cox regression model was used to examine the career paths of 2,327 elementary teachers. The teachers were 1st-year teachers hired by a large Texas school district between August 1985 and November 1991. Five variables were investigated to determine their relationship with teacher survival: sex, age, ethnicity, education, and certification route (traditionally or alternatively certified). Little research has been done comparing attrition rates of alternatively and traditionally certified teachers. The methods used in the analysis are discussed as well as why these methods are more appropriate than traditional methods for examining teacher survival.

Epidemiologic Differences between United States— and Foreign-Born Tuberculosis Patients in Houston, Texas

The proportion of foreign-born tuberculosis patients in the United States is increasing. To analyze the epidemiology of tuberculosis in foreign-born people, culture-positive patients with tuberculosis in Houston, Texas, were interviewed from October 1995 through September 1998, and their isolates were molecularly characterized. Of the 1131 patients included in the study, 795 (70.3%) were US born and 336 (29.7%) were foreign born. The decrease in tuberculosis case rate among US-born people was 3.5 times that of foreign-born people. Significantly more US-born than foreign-born patients belonged to strain clusters (71.3% vs. 29.5%; P<.001). Risk factors associated with strain clustering were as follows: black ethnicity, low income, and homelessness in US-born patients and homelessness in foreign-born patients. Isolates from foreign-born patients were more likely to be resistant to >/=1 drug (15.4% vs. 8.4%; P=.001) and to be multidrug resistant (2.4% vs. 0.7%; P=.027) than isolates from US-born patients. These observations warrant increased emphasis on this distinct subpopulation of tuberculosis patients.

Outcomes of Heart Failure–Related Hospitalization in Adults with Congenital Heart Disease in the United States

BACKGROUND Heart failure (HF) accounts for >3 million hospital admissions annually in adults with acquired cardiovascular disease, but there are limited data on HF admissions in adults with congenital heart disease (ACHD). The purpose of this study was to test the hypotheses that HF admissions are common in ACHD and associated with significant morbidity and mortality. METHODS The 2007 Nationwide Inpatient Sample was used to assess national prevalence, morbidities, and risk factors for mortality during hospitalizations among ACHD with HF. RESULTS Of the 84,308 (95% CI 71,345-97,272) ACHD admissions in the United States in 2007, 17,193 (95% CI 14,157-20,229) had a diagnosis of HF (20%). ACHD with HF was associated with an increased risk of death compared to ACHD without HF (OR 3.3, 95% CI 2.6-4.1). On multivariable analysis independent risk factors for mortality included nonoperative intubation (OR 6.1, 95% CI 3.3-11.4), sepsis (OR 4.3, 95% CI 2.4-7.4), and acute myocardial infarction (OR 3.2, 95% CI 1.8-5.7). Cardiac defects associated with an increased risk of mortality included ventricular septal defects (VSDs) (OR 1.8, 95% CI 1.0-3.4). CONCLUSIONS In this large population-based study, HF-related hospitalizations were common in ACHD and associated with an increased risk of death compared to non-HF admissions. The risk of mortality is increased with the diagnoses of VSDs and the presence of specific comorbidities such as respiratory failure and sepsis.

Effect of financial incentives on improvement in medical quality indicators for primary care

Purpose:The efficacy of rewarding physicians financially for preventive services is unproven. The objective of this study was to evaluate the effect of a physician pay-for-performance program similar to the Medicare Physician Quality Reporting Initiative program on quality of preventive care in a network of community health centers. Methods:A retrospective review of administrative data was done to evaluate a natural quasi-experiment in a network of publicly funded primary care clinics. Physicians in 6 of 11 clinics were given a financial incentive twice the size of the current Centers for Medicare and Medicaid Services’ incentive for achieving group targets in preventive care that included cervical cancer screening, mammography, and pediatric immunization. They also received productivity incentives. Six years of performance indicators were compared between incentivized and nonincentivized clinics. We also surveyed the incentivized clinicians about their perception of the incentive program. Results:Although some performance indicators improved for all measures and all clinics, there were no clinically significant differences between clinics that had incentives and those that did not. A linear trend test approached conventional significance levels for Papanicolaou smears (P = .08) but was of very modest magnitude compared with observed nonlinear variations; there was no suggestion of a linear trend for mammography or pediatric immunizations. The survey revealed that most physicians felt the incentives were not very effective in improving quality of care. Conclusion:We found no evidence for a clinically significant effect of financial incentives on performance of preventive care in these community health centers. Based on our findings and others, we believe there is great need for more research with strong research designs to determine the effects, both positive and negative, of financial incentives on clinical quality indicators in primary care.

Human Immune Response to Streptococcal Inhibitor of Complement, a Serotype M1 Group A Streptococcus Extracellular Protein Involved in Epidemics

Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular protein made by serotype M1 group A Streptococcus strains that contributes to bacterial persistence in the mammalian upper respiratory tract. New variants of the Sic protein arise very rapidly by positive selection in human populations during M1 epidemics. The human antibody response to Sic was analyzed. Of 636 persons living in diverse localities, 43% had anti-Sic serum antibodies, but only 16.4% had anti-M1 protein serum antibody. Anti-Sic antibody was also present in nasal wash specimens in high frequency. Linear B cell epitope mapping showed that serum antibodies recognized epitopes located in structurally variable regions of Sic and the amino terminal hypervariable region of the M1 protein. Phage display analyses confirmed that the polymorphic regions of Sic are primary targets of host antibodies. These results support the hypothesis that selection of Sic variants occurs on mucosal surfaces by a mechanism that involves acquired host antibody.

Interactive Effects of Individuation, Family Factors, and Stress on Adolescent Alcohol Use

A prospective, school-based study of increasing alcohol use in a multi-ethnic sample of 7,540 adolescents showed that the effects of stress, family conflict, and parental monitoring were differentially moderated by two modes of individuation. The effects of stress were moderated by ethnic status and individuation. Implications for prevention and intervention are discussed.

Molecular Genetic Analysis of 675 Group A Streptococcus Isolates Collected in a Carrier Study at Lackland Air Force Base, San Antonio, Texas

Contemporary molecular genetic analysis methods have not been used to study large samples of carriage isolates of group A Streptococcus. To determine the emm types causing asymptomatic carriage and pharyngitis in a closed population, we analyzed 675 isolates recovered from a population-based surveillance study of 10,634 recruits at Lackland Air Force Base, Texas, during 4 months in 1993-1994. Strains with emm1 and emm6 alleles accounted for only 22% of the isolates recovered from asymptomatic recruits at entrance to training. However, these 2 emm types caused 69% of the pharyngitis cases identified during training and represented 51% of the isolates recovered from the throat on exit from training. Sequence analysis of the hypervariable sic gene documented that distinct emm1 subclones disseminated in specific training groups called flights. The preferential increase in the prevalence of emm1 and emm6 isolates during the 6-week training period indicates an enhanced ability of these strains to disseminate and cause disease in this population.