Access to Benzathine Penicillin G Treatment for Persons With Syphilis, Maricopa County, Arizona, 2021.

BACKGROUND: As the incidence of syphilis continues to increase, examining benzathine penicillin G (BPG) treatment data provides valuable insight for public health strategies. This study analyzed the trends of where BPG is administered relative to the initial clinical site of syphilis diagnosis. Our findings are timely in the context of recent national BPG shortages. METHODS: The analysis included persons diagnosed with any syphilis stage in Maricopa County, Arizona, from January 1, 2021, to December 31, 2021. The Arizona surveillance database (PRISM) was the source of demographic, testing, and treatment data. RESULTS: Of a total of 4028 persons with syphilis, 3038 (75.4%) received at least 1 injection of BPG. Among persons who received an initial BPG injection, only 1719 (56.6%) were diagnosed and treated at the same clinical site type. The Maricopa County Sexually Transmitted Disease Clinic administered BPG to 48.8% (n = 1483) of persons with syphilis who received an initial injection. CONCLUSIONS: Our findings analyze trends in BPG administration that are likely due to treatment referral practices and medication cost. Administration of BPG is not guaranteed at the clinical site of diagnosis, highlighting concerns regarding access to BPG. A burden is placed on patients who are required to leave their diagnosing provider to seek syphilis treatment at other health facilities that administer BPG.

Building knowledge using a novel web-based intervention to promote HPV vaccination in a diverse, low-income population.

OBJECTIVES: HPV vaccination rates remain suboptimal despite proven efficacy. Data suggest misconceptions or lack of knowledge are leading barriers. Our study aimed to develop and pilot a novel interactive education resource designed to educate parents and patients about HPV vaccines. METHODS: This is a prospective pilot study conducted in an urban teaching hospital pediatric clinic. The Patient Activated Learning System (PALS) intervention included 3 web-based videos with HPV vaccine-related educational content. Participants were parents of adolescent patients, aged 11-17 years, and young adult patients, aged 18-26 years. Enrolled participants completed an HPV vaccine knowledge survey before and after watching PALS; paired scores were evaluated. Acceptability and participant-reported impact of PALS modules were measured via Likert-scale surveys. RESULTS: 132 individuals were approached; 101 (76%) enrolled and completed the study. Participants self-identified as Hispanic (50%), non-Hispanic Black (23%), non-Hispanic White (7%), Asian (6%), American/Alaskan/Hawaiian Native or Pacific Islander (5%). Half reported earning ≤$40,000 annually; 57% had only a high school education. Post-intervention knowledge scores were increased compared to baseline (9.87/27 points vs 17.53/27 points, p < 0.01). PALS modules were reported as enjoyable to use and understandable (89% and 93%, respectively), and improved participants' understanding of the importance of HPV vaccination (90%). Of the 18 patients unvaccinated at baseline, 39% received 1 shot of the HPV vaccine within one month. CONCLUSION: The PALS HPV vaccine educational intervention was feasible, acceptable, and improved knowledge among a diverse, underserved population. Our intervention may positively influence HPV vaccination rates, with potential to overcome HPV vaccine hesitancy.

Design and Modification of COVID-19 Case Investigation and Contact Tracing Interview Scripts Used by Health Departments Throughout the COVID-19 Pandemic.

OBJECTIVES: We sought to (1) document how health departments (HDs) developed COVID-19 case investigation and contact tracing (CI/CT) interview scripts and the topics covered, and (2) understand how and why HDs modified those scripts. DESIGN: Qualitative analysis of CI/CT interview scripts and in-depth key informant interviews with public health officials in 14 HDs. Collected scripts represent 3 distinct points (initial, the majority of which were time stamped May 2020; interim, spanning from September 2020 to August 2021; and current, as of April 2022). SETTING: Fourteen state, local, and tribal health jurisdictions and Centers for Disease Control and Prevention (CDC). PARTICIPANTS: Thirty-six public health officials involved in leading CI/CT from 14 state, local, and tribal health jurisdictions (6 states, 3 cities, 4 counties, and 1 tribal area). MAIN OUTCOME MEASURE: Interview script elements included in CI/CT interview scripts over time. RESULTS: Many COVID-19 CI/CT scripts were developed by modifying questions from scripts used for other communicable diseases. Early in the pandemic, scripts included guidance on isolation/quarantine and discussed symptoms of COVID-19. As the pandemic evolved, the length of scripts increased substantially, with significant additions on contact elicitation, vaccinations, isolation/quarantine recommendations, and testing. Drivers of script changes included changes in our understanding of how the virus spreads, risk factors and symptoms, new treatments, new variants, vaccine development, and adjustments to CDC's official isolation and quarantine guidance. CONCLUSIONS: Our findings offer suggestions about components to include in future CI/CT efforts, including educating members of the public about the disease and its symptoms, offering mitigation guidance, and providing sufficient support and resources to help people act on that guidance. Assessing the correlation between script length and number of completed interviews or other quality and performance measures could be an area for future study.

Isolation and Quarantine for Coronavirus Disease 2019 in the United States, 2020-2022.

BACKGROUND: Public health programs varied in ability to reach people with coronavirus disease 2019 (COVID-19) and their contacts to encourage separation from others. For both adult case patients with COVID-19 and their contacts, we estimated the impact of contact tracing activities on separation behaviors from January 2020 until March 2022. METHODS: We used a probability-based panel survey of a nationally representative sample to gather data for estimates and comparisons. RESULTS: An estimated 64 255 351 adults reported a positive severe acute respiratory syndrome coronavirus 2 test result; 79.6% isolated for ≥5 days, 60.2% isolated for ≥10 days, and 79.2% self-notified contacts. A total of, 24 057 139 (37.7%) completed a case investigation, and 46.2% of them reported contacts to health officials. More adults who completed a case investigation isolated than those who did not complete a case investigation (≥5 days, 82.6% vs 78.2%, respectively; ≥10 days, 69.8% vs 54.8%; both P < .05). A total of 84 946 636 adults were contacts of a COVID-19 case patient. Of these, 73.1% learned of their exposure directly from a case patient; 49.4% quarantined for ≥5 days, 18.7% quarantined for ≥14 days, and 13.5% completed a contact tracing call. More quarantined among those who completed a contact tracing call than among those who did not complete a tracing call (≥5 days, 61.2% vs 48.5%, respectively; ≥14 days, 25.2% vs 18.0%; both P < .05). CONCLUSIONS: Engagement in contact tracing was positively correlated with isolation and quarantine. However, most adults with COVID-19 isolated and self-notified contacts regardless of whether the public health workforce was able to reach them. Identifying and reaching contacts was challenging and limited the ability to promote quarantining, and testing.

Home-Based Testing and COVID-19 Isolation Recommendations, United States.

Using a nationally representative panel survey, we examined isolation behaviors among persons in the United States who had positive SARS-CoV-2 test results during January 2021-March 2022. Compared with persons who received provider-administered results, persons with home-based results had 29% (95% CI 5%-47%) lower odds of following isolation recommendations.

Treatment Completion With Three-Dose Series of Benzathine Penicillin Among People Diagnosed With Late Latent and Unknown Duration Syphilis, Maricopa County, Arizona.

BACKGROUND: Syphilis is a public health concern as cases are rising each year. If untreated, syphilis is associated with significant morbidity and risk of vertical transmission during pregnancy. For people with late latent and unknown duration stages, 3 injections of benzathine penicillin G (BPG) at 1-week intervals are recommended. Our study quantified treatment for people diagnosed with late latent and unknown duration syphilis in Maricopa County, Arizona with a secondary analysis of pregnant women to assess completion of 3 injections of BPG in multiple time intervals. METHODS: Maricopa County syphilis case data were extracted from the state-run database (PRISM). Records were reviewed for people with late latent and unknown duration syphilis during January 1, 2016, to December 31, 2021. Treatment types and time intervals between treatments were analyzed. RESULTS: Of a total of 14,924 people with syphilis reported in Maricopa County, 5372 (36.0%) were staged as late latent or unknown duration syphilis. Completion of 3 BPG injections in the time frame of 7 to 9 days was 42.9% (n = 2302). Completion among pregnant women (n = 406) with 3 injections was 68.7% (n = 279). CONCLUSIONS: The completion rate of 3 BPG injections for people with late latent or unknown duration syphilis is low. An unmet need exists to identify barriers to treatment including access to BPG and public health follow-up after the first injection. Prioritized effort is needed to identify and classify patients as having earlier stages of syphilis that require only 1 BPG injection.

Possible Exposures Among Mpox Patients Without Reported Male-to-Male Sexual Contact - Six U.S. Jurisdictions, November 1-December 14, 2022.

The extent to which the 2022 mpox outbreak has affected persons without a recent history of male-to-male sexual contact (MMSC) is not well understood. During November 1-December 14, 2022, CDC partnered with six jurisdictional health departments to characterize possible exposures among mpox patients aged ≥18 years who did not report MMSC during the 3 weeks preceding symptom onset. Among 52 patients included in the analysis, 14 (27%) had a known exposure to a person with mpox, including sexual activity and other close intimate contact (eight) and household contact (six). Among 38 (73%) patients with no known exposure to a person with mpox, self-reported activities before illness onset included sexual activity and other close intimate contact (17; 45%), close face-to-face contact (14; 37%), attending large social gatherings (11; 29%), and being in occupational settings involving close skin-to-skin contact (10; 26%). These findings suggest that sexual activity remains an important route of mpox exposure among patients who do not report MMSC.

Mpox Cases Among Cisgender Women and Pregnant Persons - United States, May 11-November 7, 2022.

Monkeypox (mpox) cases in the 2022 outbreak have primarily occurred among adult gay, bisexual, and other men who have sex with men (MSM); however, other populations have also been affected (1). To date, data on mpox in cisgender women and pregnant persons have been limited. Understanding transmission in these populations is critical for mpox prevention. In addition, among pregnant persons, Monkeypox virus can be transmitted to the fetus during pregnancy or to the neonate through close contact during or after birth (2-5). Adverse pregnancy outcomes, including spontaneous abortion and stillbirth, have been reported in previous mpox outbreaks (3). During May 11-November 7, 2022, CDC and U.S. jurisdictional health departments identified mpox in 769 cisgender women aged ≥15 years, representing 2.7% of all reported mpox cases.† Among cases with available data, 44% occurred in cisgender women who were non-Hispanic Black or African American (Black), 25% who were non-Hispanic White (White), and 23% who were Hispanic or Latino (Hispanic). Among cisgender women with available data, 73% reported sexual activity or close intimate contact as the likely route of exposure, with mpox lesions most frequently reported on the legs, arms, and genitals. Twenty-three mpox cases were reported in persons who were pregnant or recently pregnant§; all identified as cisgender women based on the mpox case report form.¶ Four pregnant persons required hospitalization for mpox. Eleven pregnant persons received tecovirimat, and no adverse reactions were reported. Continued studies on mpox transmission risks in populations less commonly affected during the outbreak, including cisgender women and pregnant persons, are important to assess and understand the impact of mpox on sexual, reproductive, and overall health.

Case Investigation and Contact Tracing Efforts From Health Departments in the United States, November 2020 to December 2021.

BACKGROUND: Sixty-four state, local, and territorial health departments (HDs) in the United States report monthly performance metrics on coronavirus disease 2019 (COVID-19) case investigation and contact tracing (CI/CT) activities. We describe national CI/CT efforts from 25 October 2020 through 24 December 2021, which included 3 peaks in COVID-19 case reporting. METHODS: Standardized CI/CT data elements submitted by the 64 HDs were summarized as monthly performance metrics for each HD and the nation. These included measures of CI/CT completeness, timeliness, and workloads. We calculated contact tracing efficacy as the proportion of new cases that occurred in persons identified as contacts within the 14 days before the case was reported. RESULTS: A total of 44 309 796 COVID-19 cases were reported to HDs, with completed HD interviews in 18 153 353 (41%). Less than half of interviews yielded ≥1 contact. A total of 19 939 376 contacts were identified; 11 632 613 were notified (58%), with 3 618 846 undergoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing within 14 days of notification. Of the total reported cases, 2 559 383 occurred in recently identified contacts. CONCLUSIONS: We document the resource-intense nationwide effort by US HDs to mitigate the impact of COVID-19 through CI/CT before and after vaccines became widely available. These results document the coverage and performance of CI/CT despite case surges and fluctuating workforce and workloads.

WHO method for estimating congenital syphilis to inform surveillance and service provision, Paraguay.

Problem: In Paraguay, incomplete surveillance data resulted in the burden of congenital syphilis being underestimated, which, in turn, led to missed opportunities for infant diagnosis and treatment. Approach: The prevalence of congenital syphilis, as defined by the World Health Organization (WHO), was estimated for Paraguay using the WHO congenital syphilis estimation tool. This tool was also used to monitor progress towards the elimination of mother-to-child transmission of syphilis. Local setting: The burden of syphilis in Paraguay has historically been high: its prevalence in pregnant women was estimated to be 3% in 2018. Relevant changes: The incidence rate of congenital syphilis estimated using the WHO tool was around nine times the reported prevalence. Subsequently, Paraguay: (i) provided training to improve diagnosis and case reporting; (ii) strengthened information systems for case monitoring and reporting; and (iii) procured additional rapid dual HIV-syphilis and rapid plasma reagin tests to increase syphilis testing capacity. In addition, the Ministry of Health prepared a new national plan for eliminating mother-to-child transmission of syphilis, with clear monitoring milestones. Lessons learnt: Health-care providers' reporting and surveillance procedures for congenital syphilis may not adequately reflect national and international case definitions. Use of the WHO congenital syphilis estimation tool in Paraguay drew attention to congenital syphilis as a national public health problem and highlighted the importance of comprehensive national surveillance systems and accurate data. Ongoing use of the WHO tool can track progress towards the elimination of mother-to-child transmission of syphilis by helping improve syphilis service coverage and national surveillance.

Creating a path forward: understanding the context of sexual health and sexually transmitted infections in American Indian/Alaska Native populations – a review.

This review assessed sexual health and sexually transmitted infection (STI) burden among American Indian/Alaska Native (AI/AN) peoples within the context of current clinical and public health services. We conducted a review of published literature about sexual health and bacterial STIs among AI/AN populations in the United States using Medline (OVID), CINAHL (EbscoHost) and Scopus. Peer-reviewed journals published during 1 January 2005-2 December 2021 were included and supplemented by other publicly available literature. A total of 138 articles from reference lists met inclusion criteria, including 85 peer-review articles and 53 additional references. Results indicate a disproportionate burden of STIs is carried by AI/AN populations compared to non-Hispanic Whites. Risk for STIs in AI/AN people has origins in historical trauma and structural and social determinants of health. STI services are available for AI/AN populations, but many barriers to care exist. Community-based sexual health programming has been successful, but has thus far focused primarily on adolescents and young adults. A myriad of factors contributes to high rates of STIs among AI/AN populations. Longstanding disparities show a clear need to increase the availability of integrated, low-barrier STI prevention and treatment services. Implementation of multi-level (individual, physician, clinic, healthcare organisation, and/or community level), culturally relevant sexual health and STI interventions should be community-based and person-centred, acknowledge social determinants of health, and grounded in deep respect and understanding of AI/AN histories and cultures.

Eliminating mother-to-child transmission of human immunodeficiency virus, syphilis and hepatitis B in sub-Saharan Africa.

Triple elimination is an initiative supporting the elimination of mother-to-child transmission of three diseases - human immunodeficiency virus (HIV) infection, syphilis and hepatitis B. Significant progress towards triple elimination has been made in some regions, but progress has been slow in sub-Saharan Africa, the region with the highest burden of these diseases. The shared features of the three diseases, including their epidemiology, disease interactions and core interventions for tackling them, enable an integrated health-systems approach for elimination of mother-to-child transmission. Current barriers to triple elimination in sub-Saharan Africa include a lack of policies, strategies and resources to support the uptake of well established preventive and treatment interventions. While much can be achieved with existing tools, the development of new products and models of care, as well as a prioritized research agenda, are needed to accelerate progress on triple elimination in sub-Saharan Africa. In this paper we aim to show that health systems working together with communities in sub-Saharan Africa could deliver rapid and sustainable results towards the elimination of mother-to-child transmission of all three diseases. However, stronger political support, expansion of evidence-based interventions and better use of funding streams are needed to improve efficiency and build on the successes in prevention of mother-to-child transmission of HIV. Triple elimination is a strategic opportunity to reduce the morbidity and mortality from HIV infection, syphilis and hepatitis B for mothers and their infants within the context of universal health coverage.

La triple élimination est une initiative visant à soutenir l'éradication de la transmission mère-enfant de trois maladies ­ l'infection au virus de l'immunodéficience humaine (VIH), la syphilis et l'hépatite B. Bien que des avancées considérables aient été observées en ce sens dans certaines régions, les progrès demeurent lents en Afrique subsaharienne, pourtant durement touchée par ces maladies. Les caractéristiques communes aux trois affections, notamment leur épidémiologie, les interactions entre elles et les principales interventions nécessaires à leur prise en charge permettent aux systèmes de santé d'adopter une approche intégrée pour éviter la transmission mère-enfant. Plusieurs obstacles entravent actuellement la triple élimination en Afrique subsaharienne, parmi lesquels l'absence de politiques, de stratégies et de ressources pour garantir la disponibilité de traitements préventifs et curatifs bien établis. Les outils existants offrent déjà de nombreuses solutions; mais pour accélérer la progression de cette triple élimination en Afrique subsaharienne, il est indispensable de développer de nouveaux produits et modèles de soins, ainsi qu'un programme de recherche prioritaire. Dans le présent document, nous voulons montrer que si les systèmes de santé collaborent avec les communautés en Afrique subsaharienne, ils pourront obtenir des résultats rapides et durables en vue d'éradiquer la transmission mère-enfant des trois maladies susmentionnées. Néanmoins, une telle démarche implique un soutien politique massif, l'expansion des interventions fondées sur des données scientifiques, et une meilleure utilisation des sources de financement afin d'améliorer l'efficacité et de s'appuyer sur les réussites en matière de prévention de la transmission du VIH de la mère à l'enfant. La triple élimination représente une occasion stratégique de réduire la morbidité et la mortalité liées à l'infection au VIH, à la syphilis et à l'hépatite B, tant chez les mères que chez les nourrissons, dans un contexte de couverture maladie universelle.

La triple eliminación es una iniciativa que apoya la eliminación de la transmisión maternoinfantil de tres enfermedades: la infección por el virus de la inmunodeficiencia humana (VIH), la sífilis y la hepatitis B. En algunas regiones se han logrado avances significativos hacia la triple eliminación, pero los progresos se han desarrollado con mayor lentitud en el África subsahariana, la región con la mayor carga de estas enfermedades. Las características comunes de las tres enfermedades, como su epidemiología, las interacciones entre ellas y las intervenciones básicas para combatirlas, permiten un enfoque integrado de los sistemas de salud para la eliminación de la transmisión maternoinfantil. Los obstáculos actuales para la triple eliminación en el África subsahariana incluyen la falta de políticas, estrategias y recursos para apoyar la adopción de intervenciones preventivas y de tratamiento bien establecidas. Aunque se puede lograr mucho con las herramientas existentes, se necesita el desarrollo de nuevos productos y modelos de atención, así como una agenda de investigación prioritaria, para acelerar el progreso de la triple eliminación en el África subsahariana. En este documento pretendemos demostrar que los sistemas de salud que trabajan conjuntamente con las comunidades del África subsahariana podrían obtener resultados rápidos y sostenibles hacia la eliminación de la transmisión maternoinfantil de las tres enfermedades. Sin embargo, se necesita un mayor apoyo político, la ampliación de las intervenciones basadas en la evidencia y un mejor uso de los flujos de financiación para mejorar la eficiencia y aprovechar los éxitos en la prevención de la transmisión maternoinfantil del VIH. La triple eliminación es una oportunidad estratégica para reducir la morbilidad y la mortalidad de la infección por el VIH, la sífilis y la hepatitis B para las madres y sus hijos en el contexto de la cobertura sanitaria universal.

COVID-19 Case Investigation and Contact Tracing Efforts from Health Departments - United States, June 25-July 24, 2020.

Case investigation and contact tracing are core public health tools used to interrupt transmission of pathogens, including SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19); timeliness is critical to effectiveness (1,2). In May 2020, CDC funded* 64 state, local, and territorial health departments† to support COVID-19 response activities. As part of the monitoring process, case investigation and contact tracing metrics for June 25-July 24, 2020, were submitted to CDC by 62 health departments. Descriptive analyses of case investigation and contact tracing load, timeliness, and yield (i.e., the number of contacts elicited divided by the number of patients prioritized for interview) were performed. A median of 57% of patients were interviewed within 24 hours of report of the case to a health department (interquartile range [IQR] = 27%-82%); a median of 1.15 contacts were identified per patient prioritized for interview§ (IQR = 0.62-1.76), and a median of 55% of contacts were notified within 24 hours of identification by a patient (IQR = 32%-79%). With higher caseloads, the percentage of patients interviewed within 24 hours of case report was lower (Spearman coefficient = -0.68), and the number of contacts identified per patient prioritized for interview also decreased (Spearman coefficient = -0.60). The capacity to conduct timely contact tracing varied among health departments, largely driven by investigators' caseloads. Incomplete identification of contacts affects the ability to reduce transmission of SARS-CoV-2. Enhanced staffing capacity and ability and improved community engagement could lead to more timely interviews and identification of more contacts.

Treatment administered to newborns with congenital syphilis during a penicillin shortage in 2015, Fortaleza, Brazil.

BACKGROUND: Between 2014 and 2016, Brazil experienced a severe shortage in penicillin supply, resulting in a lack of treatment among some pregnant women and newborns with syphilis and the use of non-evidence-based regimens. This study evaluated all live births in Fortaleza reported with CS in 2015 in order to identify the different therapeutic regimens used in newborns during this period of penicillin shortage. METHODS: A retrospective cross-sectional study design was conducted using manually extracted data from medical chart review of maternal and infant cases delivered in 2015 from all public maternity hospitals in the city of Fortaleza. Data collection occurred from June 2017 to July 2018. RESULTS: A total of 575 congenital syphilis cases were reported to the municipality of Fortaleza during 2015 and 469 (81.5%) were analyzed. Of these, only 210 (44.8%) were treated with a nationally-recommended treatment. As alternative therapeutic options, ceftriaxone was used in 65 (13.8%), Cefazolin in 15 (3.2%) and the combination of more than one drug in 179 (38.2%). Newborns with serum VDRL titers ≥1:16 (p = 0.021), who had some clinical manifestation at birth (p = 0.003), who were born premature (p <  0.001), with low birth weight (p = 0.010), with jaundice indicative of the need for phototherapy (p = 0.019) and with hepatomegaly (p = 0.045) were more likely to be treated with penicillin according to national treatment guidelines compared to newborns treated with other regimens. CONCLUSION: During the period of shortage of penicillin in Fortaleza, less than half of the infants reported with CS were treated with a nationally-recommended regimen, the remaining received treatment with medications available in the hospital of birth including drugs that are not part of nationally or internationally-recommended treatment recommendations.

Support for living well with long-term conditions: How people manage.

AIMS AND OBJECTIVES: To explore how people self-manage their long-term conditions and the support enabling them to do so. BACKGROUND: People with long-term conditions are required to engage in daily self-management with the support of health practitioners, family and friends. DESIGN: A qualitative interview study. METHODS: Thirty-two New Zealand European and Pacific people with long-term conditions were interviewed about how they manage their condition/s at home with support from family, neighbours, agencies and general practice doctors and nurses. Interviews were recorded, transcribed, checked and analysed for thematic content. The COREQ checklist was used. RESULTS: Three themes emerging from the data were as follows: 'acceptance' of conditions, limitations, support and advice; 'making it work' regarding life with long-term conditions; and the need for health practitioners to 'work alongside me'. CONCLUSIONS: People with long-term conditions struggle with acceptance of a diagnosis and symptoms, and acceptance of help which conflicts with their need to maintain independence and personal control. They self-manage every day, learning to plan, choose what and what not to do and negotiate with others to get tasks done and maintain quality of life. They manage better with support from understanding health practitioners, especially advanced nurses, with whom they have established a positive, sustained relationship. RELEVANCE TO CLINICAL PRACTICE: Active support for people to self-manage has been shown to assist people to achieve their goals and improve overall health and well-being. Nurses are well positioned to provide self-management support for people with long-term conditions but require allocated time and system changes to enable this. Practitioners need to acknowledge that it is difficult for people to accept diagnoses and symptoms and provide individualised support for this process. The desire to remain independent may limit acceptance of help, making it harder for people to maintain life quality. A change in length and content of consultations is required in order for practitioners to really get to know people and provide the self-management support they need to meet their goals.

Effectiveness and Tolerability of Oral Amoxicillin in Pregnant Women with Active Syphilis, Japan, 2010-2018.

We conducted a nationwide retrospective study in Japan to evaluate the effectiveness of oral amoxicillin or ampicillin as alternatives to injectable benzathine penicillin G for treating pregnant women with syphilis and preventing congenital syphilis (CS). We investigated 80 pregnant women with active syphilis treated with amoxicillin or ampicillin during 2010-2018. Overall, 21% (15/71) had pregnancies resulting in CS cases, and 3.8% (3/80) changed therapies because of side effects. Among 26 patients with early syphilis, no CS cases occurred, but among 45 with late syphilis, 15 (33%) CS cases occurred. Among 57 patients who started treatment >60 days before delivery, 8 (14%) had CS pregnancy outcomes. We found oral amoxicillin potentially ineffective for preventing CS cases among pregnant women with late syphilis but potentially effective in those with early syphilis. Prospective studies are needed to definitively evaluate the efficacy of amoxicillin for the treatment of pregnant women with syphilis to prevent CS.

Characterization of HIV-1 uncoating in human microglial cell lines.

BACKGROUND: After viral fusion with the cell membrane, the conical capsid of HIV-1 disassembles by a process called uncoating. Previously we have utilized the CsA washout assay, in which TRIM-CypA mediated restriction of viral replication is used to detect the state of the viral capsid, to study the kinetics of HIV-1 uncoating in owl monkey kidney (OMK) and HeLa cells. Here we have extended this analysis to the human microglial cell lines CHME3 and C20 to characterize uncoating in a cell type that is a natural target of HIV infection. METHODS: The CsA washout was used to characterize uncoating of wildtype and capsid mutant viruses in CHME3 and C20 cells. Viral fusion assays and nevirapine addition assays were performed to relate the kinetics of viral fusion and reverse transcription to uncoating. RESULTS: We found that uncoating initiated within the first hour after viral fusion and was facilitated by reverse transcription in CHME3 and C20 cells. The capsid mutation A92E did not significantly alter uncoating kinetics. Viruses with capsid mutations N74D and E45A decreased the rate of uncoating in CHME3 cells, but did not alter reverse transcription. Interestingly, the second site suppressor capsid mutation R132T was able to rescue the uncoating kinetics of the E45A mutation, despite having a hyperstable capsid. CONCLUSIONS: These results are most similar to previously observed characteristics of uncoating in HeLa cells and support the model in which uncoating is initiated by early steps of reverse transcription in the cytoplasm. A comparison of the uncoating kinetics of CA mutant viruses in OMK and CHME3 cells reveals the importance of cellular factors in the process of uncoating. The E45A/R132T mutant virus specifically suggests that disrupted interactions with cellular factors, rather than capsid stability, is responsible for the delayed uncoating kinetics seen in E45A mutant virus. Future studies aimed at identifying these factors will be important for understanding the process of uncoating and the development of interventions to disrupt this process.

Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra).

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016.

OBJECTIVE: To generate estimates of the global prevalence and incidence of urogenital infection with chlamydia, gonorrhoea, trichomoniasis and syphilis in women and men, aged 15-49 years, in 2016. METHODS: For chlamydia, gonorrhoea and trichomoniasis, we systematically searched for studies conducted between 2009 and 2016 reporting prevalence. We also consulted regional experts. To generate estimates, we used Bayesian meta-analysis. For syphilis, we aggregated the national estimates generated by using Spectrum-STI. FINDINGS: For chlamydia, gonorrhoea and/or trichomoniasis, 130 studies were eligible. For syphilis, the Spectrum-STI database contained 978 data points for the same period. The 2016 global prevalence estimates in women were: chlamydia 3.8% (95% uncertainty interval, UI: 3.3-4.5); gonorrhoea 0.9% (95% UI: 0.7-1.1); trichomoniasis 5.3% (95% UI:4.0-7.2); and syphilis 0.5% (95% UI: 0.4-0.6). In men prevalence estimates were: chlamydia 2.7% (95% UI: 1.9-3.7); gonorrhoea 0.7% (95% UI: 0.5-1.1); trichomoniasis 0.6% (95% UI: 0.4-0.9); and syphilis 0.5% (95% UI: 0.4-0.6). Total estimated incident cases were 376.4 million: 127.2 million (95% UI: 95.1-165.9 million) chlamydia cases; 86.9 million (95% UI: 58.6-123.4 million) gonorrhoea cases; 156.0 million (95% UI: 103.4-231.2 million) trichomoniasis cases; and 6.3 million (95% UI: 5.5-7.1 million) syphilis cases. CONCLUSION: Global estimates of prevalence and incidence of these four curable sexually transmitted infections remain high. The study highlights the need to expand data collection efforts at country level and provides an initial baseline for monitoring progress of the World Health Organization global health sector strategy on sexually transmitted infections 2016-2021.

Multistate Syphilis Outbreak Among American Indians, 2013 to 2015.

This article summarizes a multistate outbreak of heterosexual syphilis, including 134 cases of syphilis in adults and adolescents and at least 2 cases of congenital syphilis, which occurred on an American Indian reservation in the United States during 2013-2015. In addition to providing salient details about the outbreak, the article seeks to document the case-finding and treatment activities undertaken, their relative success or failure, and the lessons learned from a coordinated, multiagency response. Of 134 adult cases of syphilis, 40% were identified by enhanced, interagency contact tracing and partner services, 26% through symptomatic testing, and 16% through screening of asymptomatic individuals as the result of an electronic medical record screening prompt. A smaller proportion of cases were identified by community screening events in high-morbidity communities; high-risk venue-based screening events; other screening, including screening upon request; and prenatal screening at first trimester, third trimester, and day of delivery. Future heterosexual syphilis outbreak responders should act quickly to coordinate a package of high-yield case-finding and treatment activities-potentially including activities that seek to do the following: (1) increase prenatal screening, (2) improve community awareness and symptomatic test seeking, (3) educate providers and improve general screening for syphilis, (4) implement electronic medical record reminders for providers, (5) screen high-morbidity communities and at high-risk venues, and (6) form novel partnerships to accomplish partner services work when the context does not allow for traditional, disease intervention specialist-only partner services.