Madeline Sankaran’s research while affiliated with San Francisco Department of Public Health and other places

Background Centers for Disease Control and Prevention recommends test-of-cure (TOC) for persons with pharyngeal gonorrhea (GC) 7–14 days after treatment. We investigated the yield and feasibility of routine pharyngeal GC TOC to detect treatment failures. Methods During May 2021–July 2022, four U.S. STD clinics implemented pharyngeal GC TOC. Sites collected demographic, clinical, and behavioral data on all treated pharyngeal GC and positive TOC cases. Cases were dispositioned with the suspected reason for positive TOC. To assess perceived feasibility, sites participated in qualitative interviews. Results During the study period, 1,968 pharyngeal GC infections were diagnosed. Among 1,829 treated cases, 97.3% (n = 1,777) received ceftriaxone and 45.7% (n = 836) returned for TOC, varying by site (range: 35.5%– 70.8%). Among those with TOC, 4.7% (n = 39) were positive by NAAT. Of these, 48.7% had culture attempted; six positive TOC (15.4%) were also positive by culture. Most positive TOC (66.7%) were attributed to re-infection (n = 13) or false-positive results (n = 13). Six (15.4%) were treatment failures. Four failed recommended treatment and had a positive culture: two were susceptible to ceftriaxone and two did not have antimicrobial susceptibility results. Seven positive TOC (17.9%) had insufficient data to disposition. Sites perceived TOC to be feasible, though substantial resources were required. Conclusion Routine pharyngeal GC TOC yielded 5% positivity, though treatment failure was rare (<1%), and no cases of cephalosporin-resistant GC were identified. Low TOC return rates, limited culture collection, and limited culture yield highlight challenges to determining the cause of a positive TOC and the limitations of TOC in identifying cephalosporin resistance.

Importance Increasing rates of sexually transmitted infections (STIs) have been associated with rises in serious morbidity. While doxycycline postexposure prophylaxis (doxyPEP), a strategy in which individuals take doxycycline, 200 mg, after condomless sex to prevent bacterial STIs, has been shown to be efficacious in randomized clinical trials, doxyPEP’s potential effect on population-level STI incidence is unknown. Objective To assess the association of citywide doxyPEP guideline release with reported chlamydia, gonorrhea, and early syphilis cases in men who have sex with men (MSM) and in transgender women in San Francisco, California. Design, Setting, and Participants This population-level interrupted time series analysis of reported San Francisco STI cases measured monthly cases of chlamydia, gonorrhea, and early syphilis prior to (July 2021-October 2022) and after (November 2022-November 2023) release of citywide doxyPEP guidelines in October 2022. All reported chlamydia, gonorrhea, and early syphilis cases among MSM and transgender women in San Francisco during the period of analysis were included. Data were analyzed November 2023 to July 2024. Exposure Release of doxyPEP citywide guidelines. Main Outcomes and Measures The primary outcome was the percentage change between projected and observed chlamydia, gonorrhea, and early syphilis cases in the 13-month postexposure period. Results Citywide, there were 6694 cases of chlamydia, 9603 cases of gonorrhea, and 2121 cases of early syphilis among MSM and transgender women during the analytic period. STI cases among MSM and transgender women decreased significantly compared with model projections for chlamydia (−6.58% per month; 95% CI, −7.99% to −5.16%) and early syphilis (−2.68% per month; 95% CI, −3.75% to −1.60%) after doxyPEP implementation. By the end of the 13-month postperiod in November 2023, chlamydia and early syphilis cases decreased −49.64% (95% CI, −59.05% to −38.06%) and −51.39% (95% CI, −58.21% to −43.46%), respectively, compared with projected cases. There was a significant increase in monthly gonorrhea cases compared with projections (1.77% per month; 95% CI, 0.87% to 2.67%). Conclusions and Relevance This study suggests that San Francisco’s doxyPEP guideline release was associated with decreases in reported cases of chlamydia and early syphilis, but not gonorrhea, among MSM and transgender women in San Francisco. Further analyses are needed to assess whether declines are sustained and monitor for adverse consequences, including antimicrobial resistance. Supporting doxyPEP implementation for MSM and transgender women at risk for STIs could have a significant impact on the nationwide STI epidemic.

We found that the odds of return clinic visits for persistent non-gonococcal urethritis (pNGU) were significantly lower (OR 0.4, 95% CI 0.3-0.6, p < 0.0001) after implementing: (1) testing for Mycoplasma genitalium during initial evaluations for non-gonococcal urethritis (NGU) and (2) switching from azithromycin to doxycycline as first-line NGU treatment.

Associations between vaccine breakthrough cases and infection by different SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analysed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from 1 February to 30 June 2021, of which 125 (9.1%) were vaccine breakthrough infections. Vaccine breakthrough infections were more commonly associated with circulating antibody-resistant variants carrying ≥1 mutation associated with decreased antibody neutralization (L452R/Q, E484K/Q and/or F490S) than infections in unvaccinated individuals (78% versus 48%, P = 1.96 × 10⁻⁸). Differences in viral loads were non-significant between unvaccinated and fully vaccinated cases overall (P = 0.99) and according to lineage (P = 0.09–0.78). Symptomatic vaccine breakthrough infections had comparable viral loads (P = 0.64), whereas asymptomatic breakthrough infections had decreased viral loads (P = 0.023) compared with infections in unvaccinated individuals. In 5 cases with serial samples available for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to an immunocompromised state or infection by an antibody-resistant lineage. Taken together, our results show that vaccine breakthrough infections are overrepresented by antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may be as efficient in spreading COVID-19 as unvaccinated infections, regardless of the infecting lineage.

Background The extent to which vaccinated persons diagnosed with COVID-19 can transmit to other vaccinated and unvaccinated persons is unclear. Methods Using data from the San Francisco Department of Public Health (SFDPH), this report describes outcomes of household contact tracing during January 29–July 2, 2021, where fully vaccinated COVID-19 patients were the index case in the household. Results Among 248 fully vaccinated patients with breakthrough infections, 203 (82%) were symptomatic and 105 were identified as the index patient within their household. Among 179 named household contacts, 71 (40%) contacts tested, over half (56%) were fully vaccinated and the secondary attack rate was 28%. Overall transmission from a symptomatic fully vaccinated patient with breakthrough infection to household contacts was suspected in 14 of 105 (13%) of households. Viral genomic sequencing of samples from 44% of fully vaccinated patients showed that 82% of those sequenced were infected by a variant of concern or interest, and 77% by a variant carrying mutation(s) associated with resistance to neutralizing antibodies. Conclusions Transmission from fully vaccinated symptomatic index patients to vaccinated and unvaccinated household contacts can occur. Indoor face masking and timely testing of all household contacts should be considered when a household member receives a positive test result in order to identify and interrupt transmission chains.

Associations between vaccine breakthrough cases and infection by SARS coronavirus 2 (SARS-CoV-2) variants have remained largely unexplored. Here we analyzed SARS-CoV-2 whole-genome sequences and viral loads from 1,373 persons with COVID-19 from the San Francisco Bay Area from February 1 to June 30, 2021, of which 125 (9.1%) were vaccine breakthrough infections. Fully vaccinated were more likely than unvaccinated persons to be infected by variants carrying mutations associated with decreased antibody neutralization (L452R, L452Q, E484K, and/or F490S) (78% versus 48%, p = 1.96e-08), but not by those associated with increased infectivity (L452R and/or N501Y) (85% versus 77%, p = 0.092). Differences in viral loads were non-significant between unvaccinated and fully vaccinated persons overall (p = 0.99) and according to lineage (p = 0.09 - 0.78). Viral loads were significantly higher in symptomatic as compared to asymptomatic vaccine breakthrough cases (p < 0.0001), and symptomatic vaccine breakthrough infections had similar viral loads to unvaccinated infections (p = 0.64). In 5 cases with available longitudinal samples for serologic analyses, vaccine breakthrough infections were found to be associated with low or undetectable neutralizing antibody levels attributable to immunocompromised state or infection by an antibody-resistant lineage. These findings suggest that vaccine breakthrough cases are preferentially caused by circulating antibody-resistant SARS-CoV-2 variants, and that symptomatic breakthrough infections may potentially transmit COVID-19 as efficiently as unvaccinated infections, regardless of the infecting lineage.

Introduction: The CDC implemented Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) to build local detection and response capacity and evaluate responses to antibiotic-resistant gonorrhea outbreaks, including partner services for gonorrhea. We evaluated outcomes of traditional partner services conducted under SURRG, which involved (1) counseling index patients and eliciting sexual partners, (2) interviewing, testing and treating partners, and (3) providing partner services to partners newly diagnosed with gonorrhea. We also evaluated outcomes of enhanced partner services, which additionally involved interviewing and testing partners of persons who tested negative, and social contacts of index patients and partners. Methods: We analyzed partner services investigation data from eight jurisdictions participating in SURRG from 2017 through 2019. We summed total index patients, partners from traditional partner services, and partners and contacts from enhanced partner services, and calculated partner services outcomes among partners and contacts. We also visualized sexual networks from partner services data. Results: Of 1,242 index patients identified, 506 named at least one sexual partner. Traditional partner services yielded 1,088 sexual partners and 105 were newly diagnosed with gonorrhea. Enhanced partner services yielded an additional 59 sexual partners and 52 social contacts. Of those partners and contacts, 3 were newly diagnosed with gonorrhea. Network visualization revealed sparse networks with few complex partnership clusters. Conclusions: Traditional partner services for gonorrhea may be useful for eliciting, notifying, and diagnosing partners of index patients in an outbreak setting. Enhanced partner services are unlikely to be effective for eliciting, notifying, and diagnosing a substantial number of additional people.

Background: While most gonorrhea (GC) cases in the US are detected using nucleic acid amplification tests (NAATs), isolation of Neisseria gonorrhoeae (NG) using culture specimens is needed for antibiotic susceptibility testing (AST). We present data on NAATs and cultures collected before and during the CDC demonstration project (SURRG) to describe a process to define culture criteria for NG isolation for surveillance of NG with reduced susceptibility. Methods: For STI clinics in New York City, NY, San Francisco, CA, and Milwaukee, WI, we calculated NAAT positivity by anatomic site in 2016 (pre-SURRG) across three groups: 1) sex partners of persons with GC; 2) patients with symptoms (e.g., urethral or cervical discharge); 3) patients who had tested positive and were returning for GC treatment, and compared it with positivity among all other patients. We then examined SURRG-period NAAT positivity among patients from whom a culture was or was not collected, and culture positivity, by specimen site and jurisdiction. Results: Pre-SURRG, NAAT positivity across the three select groups was at least twice that of patients who did not meet any criteria. SURRG-period NAAT positivity was higher among patients from whom a culture was also collected. Overall culture positivity was relatively high (NYC:34.8%, SF:26.7%, Milwaukee:24.8%); the proportion of specimens tested widely varied (range 5.7%-26.5%) by jurisdiction. Conclusions: NAAT data evaluation can inform the establishment of criteria for culture collection for AST. Routine evaluation and quality improvement activities related to culture collection/isolation techniques could increase NG isolation for AST.

Background: Sexual networks are difficult to construct due to incomplete sexual partner data. The proximity of people within a network may be inferred from genetically similar infections. We explored genomic data combined with partner services investigation (PSI) data to extend our understanding of sexual networks affected by Neisseria gonorrhoeae (NG). Methods: We used 2017-2019 PSI and whole-genome sequencing (WGS) data from eight jurisdictions participating in CDC's Strengthening the United States Response to Resistant Gonorrhea (SURRG) project. Clusters were identified from sexual contacts and through genetically similar NG isolates. Sexual mixing patterns were characterized by describing the clusters by the individual's gender and gender of their sex partners. Results: Our study included 4,627 diagnoses of NG infection (81% sequenced), 2,455 people received a PSI, 393 people were negative contacts of cases, and 495 contacts with unknown NG status. We identified 823 distinct clusters using PSI data combined with WGS data. Of cases that were not linked to any other case using PSI data, 37% were linked when using WGS data. Overall, 40% of PSI cases were allocated to a larger cluster when PSI and WGS data were combined compared with PSI data alone. Mixed clusters containing women, men who report sex with women, and men who report sex with men were common when using the WGS data either alone or in combination with the PSI data. Conclusions: Combining PSI and WGS data improves our understanding of sexual network connectivity.

Background/Purpose In 2016 the U.S. Centers for Disease Control and Prevention (CDC) initiated Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) in local jurisdictions to enhance antibiotic resistant gonorrhea (ARGC) rapid detection and response infrastructure and evaluate the impact of key strategies. Approach Eight jurisdictions were funded for five years to establish or enhance local specimen collection for gonococcal cultures in STD and community clinics, conduct rapid antibiotic susceptibility testing (AST) using Etest® in local public health laboratories, modify surveillance systems for enhanced data collection and rapid communication of AST results, and initiate partner services and investigations among patients with GC demonstrating reduced susceptibility (RS) to ceftriaxone, cefixime or azithromycin. Outcomes/Impact SURRG grantees incorporated robust genital, pharyngeal, and rectal gonococcal culture collection from all genders at participating clinics. During 2018–2019, grantees performed AST on >10,700 isolates with a five-day median turnaround time from specimen collection to reporting AST results to providers. Fifty-nine percent of patients with RS GC returned for a test-of-cure; no resistance-related treatment failures were detected. Among 4,511 isolates, we found ≥95% concordance (within one doubling dilution) between AST performed locally using Etest® compared to agar dilution (reference method) for ceftriaxone, cefixime and azithromycin. We conducted investigations among cases and partners, identifying >100 new GC cases. Finally, we merged epidemiologic and partner data with isolate genomic data to further explore sexual networks with GC transmission and identify opportunities for local interventions. Innovation and Significance SURRG successfully built clinic, laboratory, and epidemiological capacity for local ARGC rapid detection and response. Notable outcomes/innovations include establishing best practices for collecting and transporting gonococcal culture specimens, implementing Etest® in local jurisdictions, and measuring the value of containing ARGC spread through partner services. Lessons learned and project-informed identification of additional ARGC control needs at the local and national level are being used to inform CDC’s ongoing ARGC control efforts.