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Item Analyzing Chlamydia and Gonorrhea Health Disparities from Health Information Systems: A Closer Examination Using Spatial Statistics and Geographical Information Systems(2022-05) Lai, Patrick T. S.; Jones, Josette; Dixon, Brian E.; Wilson, Jeffrey; Wu, Huanmei; Shih, PatrickThe emergence and development of electronic health records have contributed to an abundance of patient data that can greatly be used and analyzed to promote health outcomes and even eliminate health disparities. However, challenges exist in the data received with factors such as data inconsistencies, accuracy issues, and unstructured formatting being evident. Furthermore, the current electronic health records and clinical information systems that are present do not contain the social determinants of health that may enhance our understanding of the characteristics and mechanisms of disease risk and transmission as well as health disparities research. Linkage to external population health databases to incorporate these social determinants of health is often necessary. This study provides an opportunity to identify and analyze health disparities using geographical information systems on two important sexually transmitted diseases in chlamydia and gonorrhea using Marion County, Indiana as the geographical location of interest. Population health data from the Social Assets and Vulnerabilities Indicators community information system and electronic health record data from the Indiana Network for Patient Care will be merged to measure the distribution and variability of greatest chlamydia and gonorrhea risk and to determine where the greatest areas of health disparities exist. A series of both statistical and spatial statistical methods such as a longitudinal measurement of health disparity through the Gini index, a hot-spot and cluster analysis, and a geographically weighted regression will be conducted in this study. The outcome and broader impact of this research will contribute to enhanced surveillance and increased effective strategies in identifying the level of health disparities for sexually transmitted diseases in vulnerable localities and high-risk communities. Additionally, the findings from this study will lead to improved standardization and accuracy in data collection to facilitate subsequent studies involving multiple disparate data sources. Finally, this study will likely introduce ideas for potential social determinants of health to be incorporated into electronic health records and clinical information systems.Item Chlamydia muridarum Genital and Gastrointestinal Infection Tropism Is Mediated by Distinct Chromosomal Factors(American Society for Microbiology, 2018-06-21) Morrison, Sandra G.; Giebel, Amanda M.; Toh, Evelyn C.; Spencer, Horace J., III; Nelson, David E.; Morrison, Richard P.; Microbiology and Immunology, School of MedicineSome members of the genus Chlamydia, including the human pathogen Chlamydia trachomatis, infect multiple tissues, including the genital and gastrointestinal (GI) tracts. However, it is unknown if bacterial targeting to these sites is mediated by multifunctional or distinct chlamydial factors. We previously showed that disruption of individual large clostridial toxin homologs encoded within the Chlamydia muridarum plasticity zone were not critical for murine genital tract infection. Here, we assessed whether cytotoxin genes contribute to C. muridarum GI tropism. Infectivity and shedding of wild-type (WT) C. muridarum and three mutants containing nonsense mutations in different cytotoxin genes, tc0437, tc0438, and tc0439, were compared in mouse genital and GI infection models. One mutant, which had a nonsense mutation in tc0439, was highly attenuated for GI infection and had a GI 50% infectious dose (ID50) that was 1,000 times greater than that of the WT. GI inoculation with this mutant failed to elicit anti-chlamydial antibodies or to protect against subsequent genital tract infection. Genome sequencing of the tc0439 mutant revealed additional chromosomal mutations, and phenotyping of additional mutants suggested that the GI attenuation might be linked to a nonsense mutation in tc0600 The molecular mechanism underlying this dramatic difference in tissue-tropic virulence is not fully understood. However, isolation of these mutants demonstrates that distinct chlamydial chromosomal factors mediate chlamydial tissue tropism and provides a basis for vaccine initiatives to isolate chlamydia strains that are attenuated for genital infection but retain the ability to colonize the GI tract and elicit protective immune responses.Item Findings From a Scoping Review: Presumptive Treatment for Chlamydia trachomatis and Neisseria gonorrhoeae in the United States, 2006–2021(American Sexually Transmitted Diseases Association, 2023-04) Allen, Katie S.; Hinrichs, Rachel J.; Heumann, Christine L.; Titus, Melissa K.; Duszynski, Thomas J.; Valvi, Nimish R.; Wiensch, Ashley; Tao, Guoyu; Dixon, Brian E.Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are the 2 most common reported sexually transmitted infections in the United States. Current recommendations are to presumptively treat CT and/or GC in persons with symptoms or known contact. This review characterizes the literature around studies with presumptive treatment, including identifying rates of presumptive treatment and overtreatment and undertreatment rates. Of the 18 articles that met our inclusion criteria, 6 pertained to outpatient settings. In the outpatient setting, presumptive treatment rates, for both asymptomatic and symptomic patients, varied from 12% to 100%, and the percent positive of those presumptively treated ranged from 25% to 46%. Three studies also reported data on positive results in patients not presumptively treated, which ranged from 2% to 9%. Two studies reported median follow-up time for untreated, which was roughly 9 days. The remaining 12 articles pertained to the emergency setting where presumptive treatment rates, for both asymptomatic and symptomic patients, varied from 16% to 91%, the percent positive following presumptive treatment ranged from 14% to 59%. Positive results without presumptive treatment ranged from 4% to 52%. Two studies reported the percent positive without any treatment (6% and 32%, respectively) and one reported follow-up time for untreated infections (median, 4.8 days). Rates of presumptive treatment, as well as rates of overtreatment or undertreatment vary widely across studies and within care settings. Given the large variability in presumptive treatment, the focus on urban settings, and minimal focus on social determinants of health, additional studies are needed to guide treatment practices for CT and GC in outpatient and emergency settings.Item Findings From a Scoping Review: Presumptive Treatment for Chlamydiatrachomatis and Neisseria gonorrhoeae in the United States, 2006-2021(Wolters Kluwer, 2023) Allen, Katie S.; Hinrichs, Rachel; Heumann, Christine L.; Titus, Melissa K.; Duszynski, Thomas J.; Valvi, Nimish R.; Wiensch, Ashley; Tao, Guoyu; Dixon, Brian E.; University LibraryChlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are the two most common reported sexually transmitted infections in the USA. Current recommendations are to presumptively treat CT and/or GC in persons with symptoms or known contact. This review characterizes the literature around studies with presumptive treatment, including identifying rates of presumptive treatment and over- and under-treatment rates. Of the 18 articles that met our inclusion criteria, six pertained to outpatient settings. In the outpatient setting, presumptive treatment rates, for both asymptomatic and symptomic patients, varied from 12% - 100%, and the percent positive of those presumptively treated ranged from 25% - 46%. Three studies also reported data on positive results in patients not presumptively treated, which ranged from 2% - 9%. Two studies reported median follow-up time for untreated, which was roughly nine days. The remaining 12 articles pertained to the emergency setting where presumptive treatment rates, for both asymptomatic and symptomic patients, varied from 16% - 91%, the percent positive following presumptive treatment ranged from 14% - 59%. Positive results without presumptive treatment ranged from 4% - 52%. Two studies reported the percent positive without any treatment (6% and 32% respectively) and one reported follow-up time for untreated infections (median: 4.8 days). Rates of presumptive treatment, as well as rates of over- or under- treatment vary widely across studies and within care settings. Given large variability in presumptive treatment, the focus on urban settings, and minimal focus on social determinants of health, additional studies are needed to guide treatment practices for CT and GC in outpatient and emergency settings.Item The Haemophilus ducreyi SAP Transporter Contributes to Antimicrobial Peptide Resistance(2009-09-30T19:56:19Z) Mount, Kristy Lee Beavers; Margaret E. Bauer, PhDHaemophilus ducreyi is the causative agent of the genital ulcer disease chancroid, which has been shown to facilitate the transmission of HIV. H. ducreyi is likely exposed to multiple sources of antimicrobial peptides in vivo. APs are small, cationic molecules with both bactericidal and immunomodulatory functions. Because H. ducreyi is able to establish and maintain an infection in an environment rich with antimicrobial peptides, we hypothesized that the bacterium was resistant to the bactericidal effects of these peptides. Using a 96-well AP bactericidal assay, we examined H. ducreyi susceptibility to eight human APs likely to be encountered at the site of infection, including the α-defensins human neutrophil peptide-1, human neutrophil peptide-2, human neutrophil peptide-3, and human defensin 5, the β-defensins human β defensin-2, human beta defensin-3, and human beta defensin-4, and the human cathelicidin, LL-37. H. ducreyi survival was compared to the survival of Escherichia coli ML35, a strain known to be susceptible to several antimicrobial peptides. H. ducreyi was significantly more resistant than E. coli ML35 to the bactericidal effects of all peptides tested. Furthermore, we found that representative class I and class II strains of H. ducreyi were each resistant to APs of each functional category, indicating that resistance to antimicrobial peptides could represent a conserved method of pathogenesis for H. ducreyi as a species. The H. ducreyi genome contains a homolog for the Sap influx transporter. To study the role of the H. ducreyi Sap transporter in AP resistance, we generated an isogenic sapA mutant and used the 96-well AP bactericidal assay to compare the AP susceptibility profiles of wild-type H. ducreyi, the sapA mutant and the sapA trans-complement to α-defensins, β-defensins, and LL-37. We observed a 25% decrease in the survival of the sapA mutant when it was exposed to LL-37. These findings suggest that the H. ducreyi Sap transporter plays a role in H. ducreyi resistance to LL-37, but it is likely that other AP resistance mechanisms co-exist within the bacterium.Item Human papillomavirus vaccination status association with subsequent health behaviors(2016-04-28) Kasting, Monica Louise; Zimet, Gregory D.Human papillomavirus (HPV) infection results in serious health issues including cervical, anal, vulvar, penile and oropharyngeal cancers. There are three vaccines against HPV but vaccination rates in the United States remain low. One barrier to uptake is a concern that individuals who are vaccinated may increase their risky sexual behaviors or decrease their use of cervical cancer screenings, an adjustment in perceived level of risk for HPV that can be studied using risk compensation theory. Methods Three distinct studies examined risk compensation after HPV vaccination. A systematic review examined literature from January 1, 2008-June 30, 2015, using three databases. A qualitative study using semi-structured interviews of 22 healthcare providers that assessed their beliefs regarding sexual disinhibition and cervical cancer screening following vaccination. A cross-sectional survey that assessed cervical cancer screening practices, awareness and comfort with recommendations, and knowledge regarding the purpose of a Papanicolaou (Pap) test. Results Twenty articles were included in the systematic review. None of the studies of sexual behaviors and/or biological outcomes found evidence of riskier behaviors after HPV vaccination. Instead, the studies found vaccinated individuals were less likely to report risky sexual behaviors, sexually transmitted infections (STIs), and pregnancy. Qualitative interviews found no healthcare providers believed the HPV vaccine would result in increased risky sexual behavior or decreased cervical cancer screening, and these concerns would not influence their vaccination recommendations. The survey included 291 women 21-35 years old; 62% were non-Hispanic black, 84% had a Pap test in the last three years, and 33% had at least one HPV vaccine. Logistic regression showed that vaccinated women did not have greater odds of having a Pap test in the past three years (OR=1.32; 95% CI=0.66-2.65; p=0.427). However, this odds ratio was significant when controlling for age and race (AOR=3.06; 95% CI=1.37-6.83; p=0.006). Conclusion These studies found no evidence of increased risky sexual behaviors or decreased cervical cancer screening rates after HPV vaccination. Furthermore, vaccinated women showed less evidence of risk compensation. These results should alleviate concerns about administering the HPV vaccination among parents and providers.Item Measuring and Visualizing Chlamydia and Gonorrhea Inequality: An Informatics Approach Using Geographical Information Systems(University of Illinois at Chicago, 2019-09-19) Lai, Patrick T.S.; Wilson, Jeffrey S.; Wu, Huanmei; Jones, Josette; Dixon, Brian E.; Geography, School of Liberal ArtsBackground: Health inequality measurements are vital in understanding disease patterns in identifying high-risk patients and implementing effective intervention programs to treat and manage sexually transmitted diseases. Objectives: To measure and identify inequalities among chlamydia and gonorrhea rates using Gini coefficient measurements and spatial visualization mapping from geographical information systems. Additionally, we seek to examine trends of disease rate distribution longitudinally over a ten-year period for an urbanized county. Methods: Chlamydia and gonorrhea data from January 2005 to December 2014 were collected from the Indiana Network for Patient Care, a health information exchange system that gathers patient data from electronic health records. The Gini coefficient was used to calculate the magnitude of inequality in disease rates. Spatial visualization mapping and decile categorization of disease rates were conducted to identify locations where high and low rates of disease persisted and to visualize differences in inequality. A multiple comparisons ANOVA test was conducted to determine if Gini coefficient values were statistically different between townships and time periods during the study. Results: Our analyses show that chlamydia and gonorrhea rates are not evenly distributed. Inequalities in disease rates existed for different areas of the county with higher disease rates occurring near the center of the county. Inequality in gonorrhea rates were higher than chlamydia rates. Disease rates were statistically different when geographical locations or townships were compared to each other (p < 0.0001) but not for different years or time periods (p = 0.5152). Conclusion: The ability to use Gini coefficients combined with spatial visualization techniques presented a valuable opportunity to analyze information from health information systems in investigating health inequalities. Knowledge from this study can benefit and improve health quality, delivery of services, and intervention programs while managing healthcare costs.Item Relative contributions of the stringent response mediators (p)ppGpp and DksA to Haemophilus ducreyi virulence in humans(2015-06-17) Holley, Concerta Leigh; Spinola, Stanley M.; Bauer, Margaret E.; Yang, X. Frank; Goebl, Mark G.Haemophilus ducreyi causes chancroid, a sexually transmitted genital ulcerative disease that facilitates the transmission of HIV-1. H. ducreyi also causes non-sexually transmitted cutaneous ulcers in children in tropical regions. During human infection, H. ducreyi is subject to a variety of stresses. The stringent response is a bacterial stress response system induced by nutrient limiting conditions and mediated by guanosine tetra- and pentaphosphate [(p)ppGpp] and the transcriptional regulator DksA. (p)ppGpp and DksA jointly interact with RNA polymerase to regulate genes critical for bacterial survival. We hypothesized that the stringent response is required for H. ducreyi virulence in humans. A ΔrelAΔspoT mutant, which is unable to synthesize (p)ppGpp, was partially attenuated for abscess formation in human volunteers. Loss of (p)ppGpp increased bacterial resistance to phagocytosis and stationary phase survival; however, the mutant was more sensitive to oxidative stress. A ΔdksA mutant was also partially attenuated in humans. The ΔdksA mutant behaved like the (p)ppGpp mutant in stationary phase survival and sensitivity to oxidative stress, but exhibited decreased resistance to phagocytosis. Both mutants had decreased adherence to fibroblasts, but the mechanisms underlying the adherence defect were distinct. To better understand the roles of (p)ppGpp and DksA in regulating gene expression, we performed transcriptome analysis of the parent and mutant strains. (p)ppGpp and DksA deficiency resulted in dysregulation of multiple genes including several known virulence determinants. At stationary phase, (p)ppGpp and DksA targets were not identical but significantly overlapped; as the mutants were phenotypically distinct, this finding underscores both the unique and joint roles DksA and (p)ppGpp play in regulation of H. ducreyi virulence. We conclude that (p)ppGpp and DksA play significant roles in H. ducreyi pathogenesis. This is the first study to show that the stringent response has a direct role in the ability of a bacterial pathogen to cause disease in humans.Item Sexual learning among East African adolescents in the context of generalized HIV epidemics: A systematic qualitative meta-synthesis(PLOS, 2017-03-09) Knopf, Amelia S.; McNealy, Kim R.; Al-Khattab, Halima; Carter-Harris, Lisa; Oruche, Ukamaka M.; Naanyu, Violet; Burke Draucker, Claire; IU School of NursingBackground AIDS-related illness is the leading cause of mortality for adolescents in sub-Saharan Africa. Together, Kenya, Tanzania, and Uganda account for 21% of HIV-infected adolescents in sub-Saharan Africa. The United Nations framework for addressing the epidemic among adolescents calls for comprehensive sexual and reproductive health education. These HIV prevention efforts could be informed by a synthesis of existing research about the formal and informal sexual education of adolescents in countries experiencing generalized epidemics. The purpose of this study was to describe the process of sexual learning among East African adolescents living in the context of generalized HIV epidemics. Methods Qualitative metasynthesis, a systematic procedure for integrating the results of multiple qualitative studies addressing a similar phenomenon, was used. Thirty-two research reports met study inclusion criteria. The reports were assessed in a four-step analytic process: appraisal, classification of findings, synthesis of findings, and construction of a framework depicting the process of sexual learning in this population. Results The framework includes three phases of sexual learning: 1) being primed for sex, 2) making sense of sex, and 3) having sexual experiences. Adolescents were primed for sex through gender norms, cultural practices, and economic structures as well as through conversations and formal instruction. They made sense of sex by acquiring information about sexual intercourse, reproduction and pregnancy, sexually transmitted infections, and relationships and by developing a variety of beliefs and attitudes about these topics. Some adolescents described having sexual experiences that met wants or needs, but many experienced sex that was coerced or violent. Whether sex was wanted, coerced, or violent, adolescents experienced worry about sexually transmitted infections or premarital pregnancy. Conclusions The three phases of sexual learning interact to shape adolescents’ sexual lives and their risk for HIV infection. This framework will contribute to the development of sexual education programs that address HIV risk within the broader context of sexual learning.Item Validation of International Classification of Diseases, Tenth Revision, Clinical Modification Codes for Identifying Cases of Chlamydia and Gonorrhea(Wolters Kluwer, 2021) Ho, Yenling Andrew; Rahurkar, Saurabh; Tao, Guoyu; Patel, Chirag G.; Arno, Janet N.; Wang, Jane; Broyles, Andrea A.; Dixon, Brian E.; Epidemiology, School of Public HealthBackground: While researchers seek to use administrative health data to examine outcomes for individuals with sexually transmitted infections (STIs), the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes used to identify persons with chlamydia and gonorrhea have not been validated. Objectives were to determine the validity of using ICD-10-CM codes to identify individuals with chlamydia and gonorrhea. Methods: We used data from electronic health records gathered from public and private health systems from October 1, 2015, to December 31, 2016. Patients were included if they were aged 13 to 44 years and received either (1) laboratory testing for chlamydia or gonorrhea or (2) an ICD-10-CM diagnosis of chlamydia, gonorrhea, or an unspecified STI. To validate ICD-10-CM codes, we calculated positive and negative predictive values, sensitivity, and specificity based on the presence of a laboratory test result. We further examined the timing of clinical diagnosis relative to laboratory testing. Results: The positive predictive values for chlamydia, gonorrhea, and unspecified STI ICD-10-CM codes were 87.6%, 85.0%, and 32.0%, respectively. Negative predictive values were high (>92%). Sensitivity for chlamydia diagnostic codes was 10.6%, and gonorrhea was 9.7%. Specificity was 99.9% for both chlamydia and gonorrhea. The date of diagnosis occurred on or after the date of the laboratory result for 84.8% of persons with chlamydia, 91.9% for gonorrhea, and 23.5% for unspecified STI. Conclusions: Disease-specific ICD-10-CM codes accurately identify persons with chlamydia and gonorrhea. However, low sensitivities suggest that most individuals could not be identified in administrative data alone without laboratory test results.