Why are gonorrhea diagnoses declining in the US? Kirstin I. Oliveira Roster1, Peter J. White2*, Yonatan H. Grad1*† 1 Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston MA, USA 2 MRC Centre for Global Infectious Disease Analysis, and NIHR Health Protection Research Unit in Health Analytics & Modelling, Imperial College London, London, UK * co-senior authors † corresponding author Abstract After a decade of rising cases, the US CDC reported a decline in the rate of gonorrhea diag- noses for two years in a row in 2022 and 2023, especially among young adults. Primary and secondary syphilis rates also declined, yet chlamydia remains steady and STI diagnoses around the world continue to rise. Although declining gonorrhea diagnoses are encouraging, the reasons for the reductions remain unclear. Here, we enumerate potential drivers, the evi- dence that argues for or against each one, and the data needed to clarify their roles. Introduction Until recently, cases of the three most prevalent bacterial sexually transmitted infections (STIs) – chlamydia, gonorrhea, and syphilis – had been rising rapidly for over a decade (Figure 1) (1). Diagnosis rates increased in all demographic groups and geographic regions of the US, with young adults and the South bearing the greatest burden (2). While diagnosis rates of STIs have common drivers – such as levels of screening and sexual activity – they are concentrated in different populations: Chlamydia diagnoses are more common among women than men (Figures 2a and 3a). Gonorrhea is most frequently diagnosed in men, with highest prevalence in men who have sex with men (MSM) (Figures 2b and 3b) (2). Syphilis was also most common in MSM (2) but has recently increased in heterosexual populations (Figures 2c and 3c) (2,3). Chlamydia is widespread, yet syphilis, and to a lesser extent gonorrhea, tend to be concen- trated in a smaller subset of the population, for example those with high partner change rates (4–6). All three STIs tend to be more widespread in MSM and more concentrated in hetero- sexual populations, as measured by Gini coefficients (7). After over a decade of increasing incidence, the rate of gonorrhea diagnoses in the US de- clined for the second year in a row. Cases per 100,000 are down from a recent peak of 214.0 in 2021 to 179.5 cases in 2023, per the latest reports from the US Centers for Disease Control and Prevention (CDC) (Figure 1) (1). This is welcome news, as is the report that the rate of primary and secondary syphilis declined 10.7% to 15.8 per 100,000 from 2022 to 2023 and chlamydia has remained roughly at a plateau for several years, with a rate of 492.2 per 100,000 in 2023. But while these trends have been interpreted to mean that policies imple- mented to control the incidence of STIs may finally be working, it is not clear to what extent the trends are due to successful policies or to other factors, especially as STI diagnoses around the world continue to rise (8–12). Enumerating the possibilities and the data and anal- yses we need to quantify the contributions of different drivers is critical to understanding the forces shaping STI trends. It also lays the foundation to build on these gains and expand effective interventions in the US and globally. Here, we discuss potential drivers, the evidence that argues for or against each one, and studies that could clarify their roles (Table 1, Figure 4). Figure 1. National diagnosis rates of gonorrhea, chlamydia, and syphilis (1990-2023). Source: CDC Figure 2. National diagnosis rates of gonorrhea, chlamydia, and syphilis, by sex (2014-2023). Source: CDC. Figure 3. Male-to-female ratio of diagnosis rates, by STI (2014-2023). Source: CDC. Table 1. Expected impacts of potential mechanisms on gonorrhea, chlamydia, and syphilis in- fections. Potential mechanism Popula- tion Impact on: Potential timing of impact: Gonorrhea Chlamydia Syphilis 2019 2020 2021 2022 Dr ive r s o f i nc id en ce Reduction in sexual contact (due to COVID-19) MSM ¯ ¯ ¯ ¯ ¯ MSW ¯ ¯ ¯ ¯ Women ¯ ¯ ¯ ¯ Reduction in sexual contact (due to mpox) MSM ¯ ¯ ¯ ¯¯ MSW 0 0 0 Women 0 0 0 Immunity from 4CMenB vac- cine MSM ¯ 0 0 MSW ¯ 0 0 Women ¯ 0 0 Doxy-PEP MSM ¯ ¯ ¯ ¯ ¯ MSW 0 0 0 Women 0 0 0 Increased ceftriaxone dose in gonorrhea treatment guide- lines MSM ¯ 0 0 MSW ¯ 0 0 Women ¯ 0 0 Dr ive rs o f d ia gn os es Less screening MSM 0 MSW 0 Women 0 More screening MSM 0 MSW 0 Women 0 Worse diagnostic accuracy MSM ¯¯ 0 0 MSW ¯ 0 0 Women ¯ 0 0 Reduction in case reporting MSM ¯ ¯ ¯ MSW ¯ ¯ ¯ Women ¯ ¯ ¯ Abbreviations: Doxy-PEP: doxycycline post-exposure prophylaxis; MSM: men who have sex with men; MSW: men who have sex with women. Symbols: ¯ : decrease; : decrease followed by increase; : increase followed by decrease; 0 : no effect. Figure 4. Conceptual diagram of potential drivers of changes in gonorrhea transmission, diag- nosis, and reporting. 1. Inaccurate or incomplete data A first explanation for the apparent recent change from increasing to decreasing gonorrhea diagnoses is not a decrease in actual infections, but rather under-reporting or under-ascer- tainment of infections (Figure 4). National STI incidence in the US is reported by the CDC, based on notifiable disease reports submitted by states (13). Several factors could lead to a discrepancy between observed and true cases, including variable testing volumes, lag time in case reporting, or changes in the US population between census years (2). As noted in the CDC’s STI report, observed gonorrhea and chlamydia cases reflect not only the true incidence but also screening practices, diagnostic accuracy, and reporting (1). 1A. Less screening. Many gonococcal infections are asymptomatic and their detection de- pends on asymptomatic screening (14,15). Reductions in screening—and hence detection of gonorrhea—could be due to patient behavior and to clinical practice, either because of a re- duced size of the screened population or reduced screening frequency. The timing of the im- pact on STIs depends on the underlying cause of reduced screening (Table 1). Are individuals presenting for screening less frequently, resulting in fewer diagnoses? The lockdowns and home isolation associated with COVID-19 in 2020 and, to a lesser degree in 2021, reduced screening frequency and raised test positivity (16,17). Surveillance data indi- cates a dip both in chlamydia cases (Figure 1) and in the male-to-female ratio of diagnoses of chlamydia and gonorrhea (Figure 2), suggesting that any pandemic effects – such as changes in screening or sexual behavior – were more pronounced in women (or heterosexual networks) than in men. Gonorrhea diagnoses did not decline until 2022 and 2023. As behavior change during the COVID-19 pandemic should have had an immediate effect, reduced screening in 2020 is an unlikely cause for the observed gonorrhea declines. Moreover, the rates of chla- mydia were stable in 2022-23, whereas reduced screening would be expected to impact re- porting of both gonorrhea and chlamydia cases, as isolates are typically tested for both con- ditions simultaneously (16). Are clinical providers screening fewer patients (narrowing the eligibility criteria for screening) or screening those who are eligible less frequently? Recently, a call to reconsider the effec- tiveness of screening for chlamydia and gonorrhea has gained a growing chorus of voices (18–21). It is not clear to what extent there has already been a change in practice patterns in the US. Gonorrhea and chlamydia are more common in different populations—gonorrhea in men who have sex with men (MSM) and chlamydia in heterosexual populations—and differ- ences in diagnosis rates might be due to varying screening practices. However, since 2021, the rate of gonorrhea has decreased most noticeably among women aged 20-29 (1), for whom screening is still encouraged (22) and who exhibit higher rates of chlamydia than gonococcal infection. National data on testing volumes, stratified by age, sex, sex of partners, geography, symptom status, and reason for testing, would help clarify whether any changes in screening might explain the reported STI patterns and when the declines in screening may have started. 1B. Worse diagnostic accuracy. The steps for diagnosis include sample collection and sam- ple testing. The vast majority of diagnoses in the US are made by nucleic acid amplification tests (NAATs). Clinical labs use a range of manufacturer’s platforms, including Roche Cobas, Aptima, GeneXpert, and others (23). Interest in and access to at-home sample collection for STI diagnosis is expanding (24). Self-collection of specimens at home performs as well as clinician collection in office settings when subjected to nucleic acid amplification (24,25), indi- cating that even if there were changes in the fraction of samples collected by the patient as compared to the clinician this should not impact the overall diagnosis rate. While diagnostic platforms for home testing are being developed and rolled out (26), none is yet widely availa- ble. Therefore, a change in diagnostic technologies would not explain the observed trend. Has the pathogen evolved to escape NAAT diagnostics? Gonorrhea and chlamydia NAATs require the presence of a fragment of DNA or RNA with a specific nucleotide sequence. In several instances, however, both N. gonorrhoeae and C. trachomatis have evolved to escape these diagnostics by dropping or altering the targeted genetic fragment (27,28). To produce the simultaneous decline in gonorrhea incidence in three of four census regions, the diagnostic escape mutation would have had to emerge in multiple locations around the same time or spread very rapidly (29). This hypothesis could be evaluated by assessing whether the abso- lute decline and the change in the fraction of positive tests are seen across testing platforms. Whole genome sequencing to determine changes in the targets of nucleic acid amplification tests among culture-positive gonorrhea cases may help further assess the diagnostic escape hypothesis. 1C. Reduction in case reporting. The simplest potential explanation may be that there was a shift in the completeness of case reporting that varies geographically, given that the decline in gonorrhea incidence was reported in the South, Midwest, and West, but not the Northeast census regions (1). One approach to assessing this possibility of incomplete notifications is to quantify the trends in the number of tests performed and the test positivity by state and by census region. 2. Changes in sexual behavior. Assuming that the decline in gonorrhea diagnoses reflects a real decline in incidence, several possible mechanisms remain to explain STI patterns (Table 1). Lower sexual activity and a smaller sexually active population could reduce gonorrhea incidence and opportunities for transmission of N. gonorrhoeae. 2A. COVID-19 pandemic. The frequency of sexual encounters and the number of sexual partners decreased during the first years of the COVID-19 pandemic (from 2020 onwards) (30–33). Yet while chlamydia diagnoses fell sharply in 2020, gonorrhea diagnoses did not decline until 2022 and 2023, at which point chlamydia diagnoses had stabilized (Figure 1). Syphilis diagnoses also continued to increase through the pandemic period. It is unclear which mechanisms led to the divergence of gonorrhea and chlamydia diagnosis rates from 2020 onwards, though groups with varying prevalence of each STI could have adjusted their sexual behavior in different ways. 2B. Mpox epidemic. Clade II of the mpox virus began spreading globally in May 2022, with over 33,000 cases reported in the US by August 2024, especially in MSM (34,35). The mpox epidemic in MSM led to behavioral changes that contributed to decreased contact rates and increased use of barrier methods, largely in 2022, though behavior changes continued into 2023 (36,37). Yet, this mechanism is at odds with increasing diagnosis rates of STIs, including gonorrhea, outside the US, notably in Europe (38), where similar patterns in behavior change in response to the mpox outbreak were observed (36). We would also expect mpox-associated behavior change among MSM to impact gonorrhea diagnosis rates in men more than in women, but the decline in gonorrhea diagnoses was most pronounced in women (1). 2C. Later sexual debut. Increasingly, adolescents and young adults are initiating sexual ac- tivity at an older age and have fewer sexual partners (39). This age group had the most rapid decline in gonorrhea incidence in 2022-23 and also saw a 2.8% drop in chlamydia diagnoses in 2023 (1). Prevalence estimates, behavioral surveys, test volume, and data on co-infections may help illuminate the role of behavior changes in explaining declining gonorrhea incidence. 3. Immunity from N. meningitidis serogroup B vaccination. The observation that only gon- orrhea diagnoses began to decline after 2021, raises the possibility that the reduction was driven by interventions specifically affecting N. gonorrhoeae. One such intervention is vac- cination with the 4CMenB (Bexsero) OMV-based Neisseria meningitidis serogroup B vaccine, which retrospective studies indicate confers protection against infection with N. gonorrhoeae (40,41) and may reduce the prevalence of symptoms (42). The 4CMenB vaccine was intro- duced in the US in 2015, reaching 31.4% coverage among 17-year-olds in 2021 (43). Protec- tion appears modest at around 33-47% vaccine effectiveness (44,45). The Northeast had higher menB vaccine uptake than other US regions (43) but reported a continued rise in gon- orrhea incidence rates (1). These geographic patterns of vaccine uptake and gonorrhea inci- dence rates are inconsistent, unless the Northeast relied more heavily on the MenB-FHbp (Trumenba) vaccine – which does not protect against gonorrhea – instead of the 4CMenB vaccine, relative to other US regions. The 4CMenB vaccine may explain some of the decline in gonorrhea diagnoses among adolescents and young adults, with limited spillover to other age groups, though other mechanisms are needed to account for geographic variation and the total national decline, especially in older age groups. As we await further RCT evidence of 4CMenB’s efficacy against gonorrhea, one could ask whether the age and geographic distri- butions of the declining gonorrhea incidence are consistent with the rates of vaccine uptake and the expected direct and indirect effects of vaccination. Such analyses may be challenging, given the limited available data on vaccination rates by age and demography. 4. Doxy-PEP. Doxycycline post-exposure prophylaxis (doxy-PEP) is effective at preventing bacterial STIs, especially chlamydia and syphilis (46–48). In 2024, the CDC recommended doxy-PEP for use in MSM and transgender women (TGW) who were diagnosed with an STI in the past 12 months (49), though some locations, such as San Francisco, recommended use as early as 2022 (50–52). An increase in off-label use of doxycycline as prophylaxis before publication of official guidelines could have also contributed to reductions in bacterial STI in- cidence (53). Interest in and uptake of doxy-PEP among eligible populations has been high (54,55), as reflected for example in Google search patterns (56) and data from sexual health clinics suggesting a decline in test positivity, diagnoses, and number of visits for gonorrhea, but even more so for chlamydia and syphilis (57,58). In the short term, doxy-PEP use would be expected to reduce the incidence of both symptomatic and asymptomatic gonococcal in- fections, thus reducing diagnosis rates (59). It is still unclear how doxy-PEP may impact screening, as a doxy-PEP prescription should be accompanied by regular asymptomatic screening, though fewer STIs may also lower the frequency of screening. More research is needed to understand whether doxy-PEP users are screened less frequently, particularly those using it outside of official programs. As studies in women are incomplete and not yet part of guidelines, we would not expect to see reductions in incidence in women from the direct use of doxy-PEP or from indirect effects from use in MSM and TGW, even assuming success- ful reductions in incidence in MSM and TGW. Yet, national gonorrhea rates are declining in women. To assess the impact of doxy-PEP on gonorrhea incidence, we would need more granular data on doxycycline use, asymptomatic screening, and incidence of STIs stratified by sex and sex of partners, extending prior to the introduction of doxy-PEP. 5. Changes in antibiotic treatment guidelines. In 2020, the CDC changed gonorrhea treat- ment guidelines from a single intramuscular dose of ceftriaxone 250mg to 500mg (60). While this change was in response to concern over rising ceftriaxone resistance globally, most iso- lates tested in the US still have low ceftriaxone MICs (MIC ≤ 0.008 µg/mL) (61). In this hypoth- esis, the switch in treatment would result in more time over the MIC and more robust killing of the infecting gonococcal population, leading to a shorter duration of infectiousness. The time to clearance after treatment has been estimated to be 1-6 days (62–64), with some pharyngeal infections being NAAT-positive for over 12 days (65,66), though it is unclear whether these NAAT-positive infections are still transmissible. The temporal relationship between the in- crease in treatment dose and the observed decline in incidence may support this hypothesis. However, gonorrhea declines have not been seen in the UK or other places where the recom- mended treatment is 1g ceftriaxone, twice the dose in the US (67). Experiments assaying antibiotic tolerance and persistence in circulating strains and their geographic variation could help test this hypothesis. In July 2021, the CDC also updated guidelines for treatment of chlamydia from a single dose of azithromycin to a 7-day course of doxycycline (68). As gonorrhea and chlamydia are treated empirically, we would expect most gonococcal infections to be exposed to the new chlamydia treatment. Given rising prevalence of azithromycin resistance in N. gonorrhoeae isolates (5.8% in 2020) (61), the new chlamydia treatment may be more effective at curing gonococcal infections and co-infections of gonorrhea and chlamydia. 6. Increased screening of asymptomatic individuals. Quarterly screening visits are recom- mended for those on HIV pre-exposure prophylaxis (PrEP) and doxy-PEP. With more uptake of both interventions, increased rates of screening could be identifying asymptomatic cases and interrupting transmission. Similar effects might have occurred in response to heightened awareness and screening during the mpox epidemic or greater adherence to screening rec- ommendations for women under 25 (22). Increased screening would be expected to first raise diagnosis rates, as a greater portion of cases is detected, before reducing onward transmis- sion. Under this hypothesis, screening would have had to increase before the 2022-23 decline in gonorrhea diagnosis rates. As with other hypotheses, one might expect that an increase in screening would also extend to chlamydia, unless interventions and infections are concen- trated in separate populations. Additionally, it is unclear how commonly doxy-PEP is used without a prescription or shared with partners (69), resulting in use without associated screen- ing. Further, HIV PrEP use could be accompanied by other behavioral changes, such as re- duced condom use, which would increase, rather than decrease, STI incidence despite screening (70). 7. Changes in relative sizes of demographic and behavioral groups. Finally, it is conceiv- able that while per capita incidence and testing rates were unchanged, relative sizes of popu- lations with different STI prevalence shifted to the extent that national gonorrhea rates were affected, for example through population aging (71) or changes in relative proportions of MSM, men who have sex with women (MSW), women who have sex with men (WSM), and women who have sex with women (WSW). Analysis of STI diagnoses, stratified by demography, age, sex, and sex of partners, as well as assessment of the extent of overlap in populations with gonorrhea, chlamydia, and syphilis diagnoses would help test this hypothesis. 8. Other drivers There are other conceivable drivers, including the role of immunity (72) or changes in inci- dence rates associated with injection drug use. STI diagnosis rates are higher in people who inject drugs (PWID), especially for syphilis but also gonorrhea (3). Fentanyl overdoses de- clined in 2024 for the first time since 2018 (73), which may be linked to reduced injection-drug use and could contribute to a reduction in STI incidence. Conclusion It is not yet clear why gonorrhea diagnoses are declining in the United States. We have out- lined possible mechanisms for the decline, and the answer is likely multifactorial. A critical first step in improving the interpretation of gonorrhea surveillance data is ruling out the possibility of biased reporting and quantifying the roles of the potential drivers, which include changes in sexual behavior, immunity from the 4CMenB vaccine, new antibiotic treatment guidelines, im- proved screening, and demographic shifts. Setting up systems to facilitate tracking not only the incidence trends but also the potential drivers of those trends will help reduce uncertainty in observed signals. This could include recurring surveys that monitor antibiotic use and vac- cination rates at a fine enough geographic scale to achieve robust conclusions. As outlined above, we would expect many of the possible drivers to affect all bacterial STIs simultane- ously, yet varying concentrations of gonorrhea, chlamydia, and syphilis in different sexual net- works could explain differences in diagnosis patterns. Routine collection of more metadata, including the reason for testing (symptomatic diagnosis, asymptomatic screening), anatomical site(s) tested (74,75), sex of patients and their partners, partner change rates, and demo- graphic variables, could help better attribute reductions in diagnoses to their drivers. Collecting data on testing volumes also emerged as key to testing many of the hypotheses we outlined above, including capturing changes in screening and care seeking. Finally, we need an ana- lytical framework to quantify the relative contributions of each factor to the overall trends, in- cluding the possibility of complex interactions among factors (74). By identifying the drivers shaping changes in gonorrhea incidence, we will be better positioned to focus efforts to ex- pand effective interventions and achieve sustained reductions in STI burden. Acknowledgments PJW is funded by UK Medical Research Council (MRC) Centre for Global Infectious Disease Analysis (grant number MR/X020258/1); this award comes under the Global Health EDCTP3 Joint Undertaking. PJW is also funded by the National Institute for Health and Care Research (NIHR) Health Protection Research Unit (HPRU) in Health Analytics and Modelling, which is a partnership between the UK Health Security Agency (UKHSA), London School of Hygiene & Tropical Medicine (LSHTM), and Imperial College London. PJW was supported by the NIHR HPRU in Modelling and Health Economics, which was a partnership between UKHSA, Impe- rial College London, and LSHTM (grant code NIHR200908). The funders had no role in study design, the writing of the report, or in the decision to submit the paper for publication. The views expressed are those of the authors and not necessarily those of the UK Department of Health and Social Care; Foreign, Commonwealth and Development Office; European Un-ion; MRC; NIHR; or UKHSA. This work was supported by CDC contract number 200-2016-91779 to Y. H. G. The findings, conclusions, and views expressed are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Preven- tion (CDC). References 1. CDC. Sexually Transmitted Infections Surveillance, 2023 [Internet]. 2024 Nov [cited 2025 Jan 19]. Available from: https://www.cdc.gov/sti-statistics/annual/index.html 2. 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