Kelika Konda’s research while affiliated with Universidad Peruana Cayetano Heredia and other places

Introduction The Peruvian public healthcare system is characterized by various shortcomings that adversely affect healthcare quality as perceived by the general and minority populations, including the Afro-Peruvian community. This population has demonstrated reduced healthcare access due to discrimination and differential treatment, reflecting broader societal inequities. Objective This study explores the experiences and perceptions of Afro-Peruvian individuals regarding the treatment they receive from public primary healthcare providers in metropolitan Lima. Methods In-depth qualitative interviews were conducted with Afro-Peruvian individuals recruited from Lima. They were selected based on their responses to a survey conducted in a previous study, which indicated a high or low perception of intercultural adaptation in healthcare. The interviews explored their experiences with healthcare services and their perceptions about their interactions with health providers. The qualitative analysis involved topic coding to interpret the data. Results We interviewed 19 Afro-Peruvians, including 15 women and 4 men, ages 26 to 70. The findings reveal that Afro-Peruvians generally experience mistreatment in the healthcare system. In their opinion, this is associated with systemic issues such as poor infrastructure, low salaries, and insufficient time allocated for patient care. Furthermore, participants perceive receiving poor quality and inefficient service not only from providers but also from the system presents difficulties in other processes, such as getting the appointment. Conclusions This study highlights significant areas for improvement in the public healthcare system, specifically enhancing the quality of patient care, improving communication, and upgrading healthcare infrastructure to serve the Afro-Peruvian community better. These insights could guide the development of targeted policy recommendations and practical interventions to address healthcare disparities and improve access to quality healthcare services for minority populations.

Background Syphilis has reemerged as a global health concern. The standard treatment for all stages of syphilis is injectable benzathine penicillin G. Cefixime is an FDA-approved, oral antibiotic widely available, low-cost, and safe in pregnancy. A previous pilot study showed cefixime was likely efficacious in treating early syphilis. This study aims to evaluate the efficacy of cefixime in comparison to benzathine penicillin G. Methods We are conducting a randomized, multisite, open-label, non-inferiority clinical trial to compare the effectiveness of cefixime (400mg, orally, twice daily for 10 days) to benzathine penicillin G (2.4 million units, intramuscularly) in 400 participants from 12 clinical sites in the United States and Peru, including participants living with and without human immunodeficiency virus (HIV) infection. In the event of a penicillin shortage, participants randomized to penicillin receive doxycycline hyclate (100mg, orally, twice daily for 14 days). Participants undergo follow-up visits post-treatment at 3-, 6-, and 9-months, involving clinical evaluation and rapid plasma reagin (RPR) testing. The primary outcome is a ≥4-fold decrease in the RPR compared to the initial RPR titer at enrollment, assessed at either 3 or 6 months after treatment. Results As of May 1, 2024, 134 participants are enrolled, 67.2% living with HIV. The current cefixime adherence rate is 92.3% (60/65) at the 10 day mark. Evaluable data is available from 104 participants with 3- or 6-month follow-up visits, including 52 cefixime, 45 penicillin, and 7 doxycycline participants. By 3- or 6-month post-treatment, 88.5% (95% CI, 76.5% - 95.6%; 46/52) of cefixime participants, 88.9% (95% CI, 75.6% - 96.3%; 40/45) of penicillin participants, and 100.0% (95% CI, 59.0% - 100%; 7/7) of doxycycline participants achieved a ≥4-fold RPR titer decrease. Conclusion Comparable effectiveness was observed among the treatment arms. Enrollment and data collection continue, with study completion expected by June 2026. Disclosures Jeffrey Klausner, MD MPH, Direct Diagnostics: Advisor/Consultant

Background Syphilis rates have been increasing. At the same time, important shortages of benzathine penicillin G have been reported. Existing alternatives, doxycycline, tetracycline, and azithromycin are inadequate to treat syphilis in all patients due to the absence of safety data in pregnancy and children, or antibiotic resistance, respectively. Linezolid is an FDA-approved, safe, low-cost, oral antibiotic that crosses the blood-brain barrier. It has shown efficacy against Treponema pallidum in vitro and in animal studies. Although a recent clinical study evaluating of 600mg Linezolid once daily for 5 days showed limited success, pharmacological simulations show that a longer regimen may be efficacious. We aimed to assess the efficacy of linezolid 600mg, twice a day for 10 days for the treatment of early syphilis. Methods We are conducting a randomized, non-comparative, pilot study enrolling 24 adult patients (18 linezolid, 6 penicillin) with primary, secondary, or early latent syphilis in Chicago, Illinois, and Jackson, Mississippi. The experimental arm receives oral linezolid 600mg twice daily for ten days, while the control arm receives benzathine penicillin G 2.4 million units intramuscularly once. The main outcome is a ≥4-fold RPR titer decline by 6 months after treatment. Linezolid participants are monitored for adherence and adverse events during treatment. Clinical and serological response is evaluated at 1-, 3-, and 6-month follow-up visits. Results Currently, six out of 24 participants are enrolled in the study; four in the linezolid arm, and two in the penicillin arm. All participants had early latent syphilis. All participants receiving linezolid adhered 100%. One penicillin participant (enrollment RPR 1:16, 3-month RPR 1:2) and one linezolid participant (enrollment RPR 1:64, 3-month RPR 1:16) have completed their 3-month follow-up. No serious adverse reactions have been reported. Conclusion Studies of new treatment options for syphilis are underway Disclosures Jeffrey Klausner, MD MPH, Direct Diagnostics: Advisor/Consultant

Background Benzathine penicillin is the antimicrobial treatment of choice for syphilis, but worldwide shortages have caused disruptions in patient care. Therefore, the is a need for new antimicrobial compounds that are effective at curing Treponema pallidum subsp. pallidum (Tp) infections that are not subject to the same supply chain issues currently effecting benzathine penicillin availability. To this end, we tested the in vitro susceptibility of four different strains of Tp (Nichols, Mexico A, UW231B, and UW249B) to linezolid. Methods There are two genetically distinct subgroups of Tp: the Nichols group and the SS14 group. The SS14 group is currently predominant worldwide, so we tested three different strains from this group (Mexico A, UW231B, and UW249B). Tp cultured in TpCM2 medium were exposed to linezolid concentrations ranging from 0 to 4 µg/mL for 1 week, then the number of Tp per culture and motility were assessed by darkfield microscopy. Results Multiplication was completely inhibited (fold increase ≤1) in cultures treated with 0.5 - 4 µg/mL linezolid and motility was significantly decreased. In vitro MICs for linezolid ranged from 0.32 to 0.36 µg/mL in the four strains tested, with no difference between the Nichols strain (0.32 µg/mL) and the SS14 subgroup strains (0.34 - 0.36 µg/mL). The MIC range determined in vitro is compatible with the blood serum ranges reported in patients given therapeutic doses of linezolid. Conclusion Further studies are ongoing to determine if linezolid is an effective antimicrobial compound for the treatment of syphilis. Disclosures Jeffrey Klausner, MD MPH, Direct Diagnostics: Advisor/Consultant

Perceived risk for HIV acquisition among gay, bisexual, and other men who have sex with men (GBMSM) may not align with their actual sexual HIV exposure. Factors associated with low/moderate perceived risk among GBMSM eligible for pre-exposure prophylaxis (PrEP) (based on their high estimated HIV exposure) have been poorly described in Latin America. This is a secondary analysis of a 2018 web-based cross-sectional survey in Brazil, Mexico, and Peru. Participants were ≥ 18 years old, cisgender men, not living with HIV, had sex with other men in the previous six months, and had an HIV Incidence Risk Index for MSM score ≥ 10. We performed a multivariable logistic regression to identify factors associated with low/moderate perceived risk for HIV acquisition for each country. A total of 9900 GBMSM were included, and the majority (85.7%) reported low/moderate perceived risk for HIV acquisition. The mean age was 28.8 (SD = 7.7) years, and 77.7% had high school or more. Having ≥ 5 sex partners, daily use of geosocial networking (GSN) apps, and having sex (including condomless insertive anal sex) with a person living with HIV decreased the odds of low/moderate perceived risk for HIV acquisition, but an HIV test in the last year increased the odds only in Mexico. Latin GBMSM with high sexual HIV exposure (eligible to use PrEP) showed a massive gap with their perceived risk. HIV prevention counseling should explore HIV testing history and the frequency of use of GSN apps to promote an objective self-assessment of HIV exposure among Latin GBMSM.

Background The global burden of sexually transmitted infections (STIs) poses a challenge in the context of HIV pre-exposure prophylaxis (PrEP) programmes. We aimed to explore factors associated with prevalent, incident, and recurrent STIs in men who have sex with men (MSM) and transgender women on PrEP in Brazil, Mexico, and Peru. Methods ImPrEP was a prospective, single-arm, open-label, multicentre study that enrolled MSM and transgender women in the context of the public health systems of Brazil (14 sites), Mexico (four sites), and Peru (ten sites) between February, 2018, and June, 2021. Eligibility criteria followed regional PrEP guidelines at the study start, including participants aged 18 years and older, not living with HIV, and reporting at least one of the following in the previous 6 months: condomless anal sex (CAS), anal sex with partner(s) living with HIV, any bacterial STI, or transactional sex. Eligible participants were screened and enrolled on the same day to receive daily oral PrEP (tenofovir disoproxil fumarate 300 mg and emtricitabine 200 mg). We assessed three outcomes: prevalent bacterial STIs, incident bacterial STIs, and recurrent bacterial STIs. Testing occurred at baseline and quarterly for syphilis, anorectal chlamydia, and anorectal gonorrhoea. Behavioural data were collected at baseline and quarterly. The study was registered with the Brazilian Registry of Clinical Trials, U1111-1217-6021. Findings Among all 9509 participants included in the ImPrEP study (3928 [41·3%] in Brazil, 3288 [34·6%] in Mexico, and 2293 [24·1%] in Peru), 8525 (89·7%) had available STI results at baseline and were included in the prevalent STI analysis, and 7558 (79·5%) had available STI results during follow-up and were included in the incident and recurrent STI analyses. 2184 (25·6%) of 8525 participants had any bacterial STI at baseline. STI incidence during follow-up was 31·7 cases per 100 person-years (95% CI 30·7–32·7), with the highest rate for anorectal chlamydia (11·6 cases per 100 person-years, 95% CI 11·0–12·2), followed by syphilis (10·5 cases per 100 person-years, 9·9–11·1) and anorectal gonorrhoea (9·7 cases per 100 person-years, 9·2–10·3). Although only 2391 (31·6%) of 7558 participants had at least one STI during follow-up, 915 (12·1%) participants had recurrent diagnoses, representing 2328 (61·2%) of 3804 incident STI diagnoses. Characteristics associated with prevalent, incident, and recurrent STIs included younger age, multiple sex partners, receptive CAS, substance use, and previous STI diagnoses at baseline (incident or recurrent only). Interpretation Our findings underscore the nuanced dynamics of STI transmission among MSM and transgender women across Latin America, highlighting an urgent need for tailored interventions to mitigate STI burden effectively, especially among the most susceptible individuals. Funding Unitaid, WHO, and ministries of health (Brazil, Mexico, and Peru). Translations For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

The New Pathways in Syphilis Vaccine Development meeting was held prior to the start of the STI & HIV 2023 World Congress as a pre-meeting symposium to highlight recent advances in the development of an effective syphilis vaccine and discuss the challenges still faced by investigators. Internationally renowned public health officials, clinical investigators, and basic researchers from academia, government, and community-based organizations met on the 24 th of July 2023 in Chicago, Illinois. Four speakers discussed key research findings in syphilis vaccine development, which included antigen selection, identification of epitopes associated with protective immunity, and delivery platforms, with great emphasis on development of chimeric antigens. Significant progress was also shown on the elucidation of Treponema pallidum genomes from virtually all continents to assess the diversity in vaccine candidates of the syphilis spirochete.

The Peruvian public healthcare system has various shortcomings that impact the experiences and perceptions of quality among the general population and, particularly, among minority populations, including the Afro-Peruvian community. In this context, understanding the population's experiences in healthcare services and their perceptions regarding the treatment received from healthcare providers is crucial for developing improvement recommendations. Through in-depth interviews, our study explored the usage experiences and perceptions regarding the treatment received from public primary healthcare providers among 19 Afro-Peruvian individuals in Lima. Our analysis revealed that, in general, there is mistreatment of healthcare providers. This is not only recognized as a deficiency of the providers (human resources) but also as a consequence of a system that does not promote the quality of care, including issues such as inadequate infrastructure, low salaries, and limited time for patient care. Additionally, expressions of discrimination based on differences, primarily socioeconomic, were identified. Our findings provide insights for enhancing healthcare services in terms of treatment, effective communication, and infrastructure at the primary healthcare level.

With growing maternal and congenital syphilis epidemics and shortages of benzathine penicillin, alternative syphilis treatments are needed. Linezolid has shown efficacy against syphilis in animal models. This review found no teratogenic effects. Some adverse effects were seen in animals, but none were reported in a small number of human studies.

To the Editor—We read with great interest the manuscript by Marra et al that described the attenuation of syphilis detection in the blood and cerebrospinal fluid (CSF) in subsequent episodes of syphilis [1]. The authors describe how asymptomatic infection significantly increased with the number of prior syphilis episodes, and that the odds of detecting Treponema pallidum DNA in blood or CSF at the index episode were lower in those with prior syphilis. This information validates prior studies we have conducted, which found differences in cytokine expression among individuals with serofast and treated syphilis [2]. In our studies, we identified 20 pairs of cytokines that differed between active and treated syphilis and identified 3 cytokine networks that could potentially be useful for identifying active syphilis [3]. As an extension of this work, we are currently investigating how the immune response changes in subsequent episodes of syphilis in a cohort study enrolling individuals with active early syphilis who have documentation of prior syphilis or of being syphilis-naive, who are then followed for 12 months [4]. To improve understanding of rapid plasma reagin (RPR) titer variation after treatment, we evaluated the time to treatment success (4-fold RPR titer decline) from active early syphilis diagnosis comparing the prior syphilis and syphilis-naive groups.