New Insights into Neisseria gonorrhoeae (NG): Geographic heterogeneity in Black-White disparities and spatiotemporal trends among US females and the role of azithromycin use for STI treatment in antibiotic resistance

Gonorrhea (caused by the Neisseria gonorrhoeae (NG) bacterium) is the second most-commonly reported sexually transmitted infection (STI) in the United States (US) and can cause serious, permanent reproductive sequalae in females. Gonorrhea rates have increased rapidly in the US throughout the last 3 decades, while profound racial disparities have stubbornly persisted with non-Hispanic Black (NHB) populations experiencing the greatest burden of disease. In geographic depictions of gonorrhea rates, the US Southeast is highlighted as the area of highest morbidity. Concerningly, NG has developed antimicrobial resistance (AMR) to nearly all drugs historically used for treatment. AMR NG is more common among men who have sex with men (MSM), which may be related to the more frequent use of antibiotics for STI treatment in this population. While racial disparities in gonorrhea rates are well-described, our understanding of variation in the magnitude of these disparities within the US is lacking. Reduction of racial disparities is a core goal of the 2021-2015 US National Strategic Plan for STIs; it is therefore imperative that national and local public health programs know where such disparities are greatest for interventions to have greatest impact. Similarly, national data demonstrating increases in gonorrhea rates among females may obscure informative variation in localized trends. Areas with later or earlier increases in gonorrhea rates, with high or low rates of disease, may share characteristics influential in gonorrhea epidemiology. There is also currently conflicting evidence about the role of individual-level antibiotic use on the development of AMR gonorrhea. A study of Dutch clinic attendees identified an association between AZM use and AZM resistance, while two reviews of surveillance data from the UK found no such association. In this dissertation, we sought to fill these gaps in our knowledge of gonorrhea epidemiology through several related but distinct analyses. First, we examined the geographic variation in county-level gonorrhea rates among NHB and non-Hispanic White (NHW) females using national gonorrhea surveillance data obtained from the US Centers for Disease Control and Prevention. We created a series of maps to depict the spatial distribution of within- and between-race disparities (relative and absolute) in gonorrhea rates. We then used group-based trajectory models to identify and characterize distinct groups of counties with similar trajectories of NG rates in these populations separately. Lastly, we examined the association between individual-level receipt of AZM for sexually transmitted infection treatment and subsequent NG infection with reduced susceptibility to AZM among attendees of the Public Health Seattle-King County Sexual Health Clinic (SHC). We found that nearly all US counties had NHB female gonorrhea rates ≥3x those in NHW females, with NHB females in most highly populated counties experienced ≥9-fold difference in gonorrhea rates. Additionally, NHB females in counties in the south had lower rates of gonorrhea compared to NHB females in the Midwest and West. In our analysis of county-level spatiotemporal gonorrhea trends, we identified 9 distinct gonorrhea trajectories for NHB, 3 of which experienced declines in case rates from 2003-2018; conversely, all 7 identified trajectories among NHW females were characterized by stable or increasing rates of gonorrhea. Furthermore, counties with similar gonorrhea trajectories were sometimes, but not always, in close proximity. Finally, we found evidence for an association between receipt of AZM in the prior 30 days and having an AMR NG infection among SHC attendees. Our first analysis highlights pervasive yet variable racial disparities in gonorrhea; further, these disparities are often greater outside the US south. These findings counter damaging regional stereotypes, provide evidence to refocus prevention efforts to areas of highest disparities, and suggest that monitoring racial disparities can function as an actionable public health metric. Our second analysis confirmed that national data do obscure a highly heterogenous gonorrhea epidemic for both NHW and NHB females. These two exploratory analyses should prompt further analysis into the differential drivers of gonorrhea morbidity. Lastly, our finding of an association between AZM use and AZM-resistance underscore the timeliness of updated STI treatment guidelines that reduce the utilization of AZM in populations at high risk for AMR NG.