OBJECTIVE: The objective of this study was to explore the factors and outcomes associated with gestational syphilis in Peru.
METHODS: Women from the miscarriage, vaginal delivery, and C-section wards from a large maternity hospital in Lima with or without syphilis diagnosis were enrolled and their pregnancy outcomes compared. Maternal syphilis status using maternal blood and child serostatus using cord blood were determined by rapid plasma reagin (RPR) and rapid syphilis tests. The newborns\' clinical records were used to determine congenital syphilis.
RESULTS: A total of 340 women were enrolled, 197 were positive and 143 were negative for RPR/rapid syphilis tests. Antibody titers in sera from cord and maternal blood were comparable with RPR titers and were highly correlated (rho = 0.82, P <0.001). Young age (P = 0.009) and lower birth weight (P = 0.029) were associated with gestational syphilis. Of the women with gestational syphilis, 76% had received proper treatment. Mothers of all newborns with congenital syphilis also received appropriate treatment. Treatment of their sexual partners was not documented.
CONCLUSIONS: Syphilis during pregnancy remains a major cause of the fetal loss and devastating effects of congenital syphilis in newborns.

BACKGROUND: International guidelines recommend routine screening for syphilis (aetiological agent: Treponema pallidum subspecies pallidum) amongst key populations and vulnerable populations using tests detecting treponemal and non-treponemal antibodies. Whilst treponemal tests have high sensitivities and specificities, they differ regarding subjective or objective interpretation, throughput and workload. Chemiluminescence immunoassays (CLIAs) are cost- and time-effective automated methods for detecting treponemal antibodies. The Treponema pallidum particle agglutination assay (TPPA) has been considered the \"gold standard\" treponemal assay, however, this includes a highly manual procedure, low throughput and subjective interpretation. The present multi-country study evaluated the ADVIA Centaur® Syphilis CLIA (Siemens Healthcare) assay compared to the reference SERODIA-TP·PA® (Fujirebio Diagnostics) for the serodiagnosis of syphilis amongst men who have sex with men (MSM).
METHODS: 1,485 MSM were enrolled in Brighton (UK), Malta, and Verona (Italy) as part of a larger WHO multi-country and multi-site ProSPeRo study. Ethical approval was obtained. Serum was tested with the ADVIA Centaur® Syphilis CLIA assay and SERODIA-TP·PA®, in accordance with the manufacturers\' instructions, for a first round of validation. A second round of validation was carried out for discrepant results that were additionally tested with both Western Blot (Westernblot EUROIMMUN®) and an Immunoblot (INNO-LIA, Fujirebio Diagnostics). Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratios (positive/negative), and the Diagnostic Odds Ratio (DOR)/pre-post-test probability (Fagan\'s nomogram) were calculated.
RESULTS: Out of 1,485 eligible samples analysed in the first phase, the SERODIA-TP·PA® identified 360 positive and 1,125 negative cases. The ADVIA Centaur® Syphilis CLIA assay (Siemens) identified 366 positives, missclassifying one TPPA-positive sample. In the second phase, the ADVIA Centaur® Syphilis CLIA resulted in 1 false negative and 4 false positive results. Considering the syphilis study prevalence of 24% (95% CI: 22-26.7), The sensitivity of the ADVIA Centaur® Syphilis CLIA assay was 99.7% (95% CI: 98.5-100), and the specificity was 99.4% (95% CI: 98.7-99.7). The ROC area values were 0.996 (95% CI: 0.992-0.999), and both the PPV and NPV values were above 98% (PPV 98.1%, 95% CI: 96.1-99.2; NPV 99.9%, 95% CI: 99.5-100).
CONCLUSIONS: The ADVIA Centaur® Syphilis CLIA assay showed similar performance compared to the SERODIA-TP·PA®. Considering the study is based on QUADAS principles and with a homogeneous population, results are also likely to be generalisable to MSM population but potentially not applicable to lower prevalence populations routinely screened for syphilis. The automated CLIA treponemal assay confirmed to be accurate and appropriate for routine initial syphilis screening, i.e. when the reverse testing algorithm is applied.

BACKGROUND: Sexually transmitted infections (STIs) such as syphilis and HIV remain to be a significant public health issue worldwide. Dual rapid point-of-care tests (POCTs) have shown promise for detecting antibodies to HIV and syphilis but have not been fully evaluated in the field. Our study supported the WHO ProSPeRo study on Sexually Transmitted Infection Point-of-Care Testing (STI POCT) by providing external quality assessment (EQA) for HIV and syphilis testing in reference laboratories and their associated clinical sites in seven countries.
METHODS: HIV/syphilis serum liquid and dried tube specimen (DTS) panels were prepared by CDC. Liquid panels were distributed to the reference laboratories for three rounds of testing using commercially and locally available laboratory-based serological tests. DTS panels were sent to the clinical testing sites for 8 rounds of POC testing using the Abbott SD BIOLINE HIV/Syphilis Duo test (hereafter referred to as SD BIOLINE) and the Chembio Dual Path Platform (DPP) HIV-Syphilis assay. EQA panels were tested at CDC using the Rapid Plasma Reagin (RPR) test and the Treponema pallidum Particle Agglutination assay (TP-PA) for syphilis antibodies. Genetic Systems HIV-1/HIV-2 Plus O EIA, Geenius HIV Supplemental Assay and the Oraquick Advance HIV test were used to detect HIV antibodies in the EQA panels. Results from the reference laboratories and POCT sites were compared to those obtained at the CDC and a percentage agreement was calculated.
RESULTS: Qualitative RPR and TP-PA performed at the reference laboratories demonstrated 95.4-100% agreement with CDC results while quantitative RPR and TP-PA tests demonstrated 87.7% and 89.2% agreement, respectively. A 93.8% concordance rate was observed for qualitative HIV testing in laboratories. EQA testing at clinical sites using dual tests showed 98.7% and 99.1% agreement for detection of HIV antibodies and eight out of 10 sites had > 95.8% agreement for syphilis testing. However, two clinical sites showed only 65.0-66.7% agreement for SD BIOLINE and 84.0-86.7% for DPP, respectively, for syphilis testing.
CONCLUSIONS: Overall, laboratories demonstrated high EQA performance in this study. Both HIV/syphilis POCTs gave expected results in the clinic-based evaluations using DTS. However, testing errors were identified in a few testing sites suggesting the necessity for continuous training and monitoring the quality of POC testing.

OBJECTIVE: We evaluated the field diagnostic accuracy of a syphilis rapid test (RDT), using serum and whole blood by non-laboratorians in two Canadian Arctic communities.
METHODS: We implemented a multisite prospective field evaluation wherein patients were screened by an RDT containing treponemal and non-treponemal components (Chembio DPP® Syphilis Screen & Confirm) between January 2020 and December 2021. Venous whole blood and serum were collected for rapid testing and compared with laboratory-based serology reference testing using a reverse sequence algorithm of treponemal and rapid plasma reagin (RPR) testing.
RESULTS: Overall, 135 whole blood and 139 serum specimens were collected from 161 participants during clinical encounters. Treponemal-RDT sensitivity against a treponemal-reference standard (38/161 confirmed cases) was similar for serum (78% [95% CI: 61-90%]) and whole blood (81% [95% CI: 63-93%]). In those with RPR titres ≥1:8 (i.e. suggestive of recent/active infection), sensitivity increased to 93% (95% CI: 77-99%) for serum and 92% (95% CI: 73-99%) for whole blood. Treponemal-RDT specificity was excellent (99% [95% CI: 95-100%]) for both specimen types. Non-treponemal-RDT sensitivity against RPR was 94% (95% CI: 80-99%) for serum and 79% (95% CI: 60-92%) for whole blood. Sensitivity increased to 100% (95% CI: 88-100%) for serum and 92% (95% CI: 73-99%) for whole blood when RPR titres ≥1:8. RDT performance with whole blood was similar to that with serum.
CONCLUSIONS: Non-laboratorians using the RDT accurately identified individuals with infectious syphilis under real-world conditions in an intended-use setting at the point of care. Implementing the RDT can eliminate treatment delays and may enhance disease control.

OBJECTIVE: Single-visit testing and treatment for syphilis can reduce follow-up visits. The objectives of this study were to evaluate the performance and treatment outcomes of two dual syphilis/HIV point-of-care tests (POCTs).
METHODS: Participants aged 16 years and older were offered concurrent syphilis/HIV POCTs with fingerstick blood sampling using two extremely rapid (<5 minutes) devices (MedMira Multiplo Rapid TP/HIV test and INSTI Multiplex HIV-1/HIV-2/Syphilis Antibody Test). Those with positive POCT results were offered same-day syphilis treatment and linkage to HIV care. Nurses performed testing at two emergency departments, a First Nations community, a correctional facility, and a sexually transmitted infection clinic. POCT results were compared with those of standard serological testing. Sensitivity and specificity were calculated.
RESULTS: Between August 2020 and February 2022, 1526 visits were completed. Both POCTs accurately identified participants with HIV (sensitivity, 100% [24 of 24]; 95% CI, 86.2-100%; specificity, 99.6% [1319 of 1324]; 95% CI, 99.1-99.8%), linking 24 HIV cases to care. Both tests were most sensitive with a rapid plasma reagin (RPR) of ≥1:8 dilutions (Multiplo: sensitivity, 98.3% [231 of 235]; 95% CI, 95.7-99.3%; specificity, 99.5% [871 of 875]; 95% CI, 98.8-99.8%; INSTI Multiplex: sensitivity, 97.9% [230 of 235]; 95% CI, 95.1-99.1%; specificity, 99.8% [873 of 875]; 95% CI, 99.2-99.9%) and least sensitive with non-reactive RPR (Multiplo: sensitivity, 54.1% [59 of 109]; 95% CI, 44.8-63.2%; specificity, 99.5% [871 of 875]; 95% CI, 98.8-99.8%; INSTI Multiplex: sensitivity, 28.4% [31 of 109]; 95% CI, 20.8-37.5%; specificity, 99.8% [873 of 875]; 95% CI, 99.2-99.9%). Eighty-five percent of participants with infectious syphilis were treated on the same day as the positive POCT result.
CONCLUSIONS: Two extremely rapid (<5 minutes) dual syphilis/HIV POCTs showed excellent sensitivity and specificity for the diagnosis of active syphilis (RPR, ≥1:8 dilutions) and HIV and confirmed the ability to offer single-visit testing and treatment for syphilis and linkage to HIV care in diverse clinical settings.

Syphilis, a sexually transmitted infection, has reemerged in many vulnerable groups around the world. The objective of the current study was to determine the prevalence and incidence of syphilis among people who attended a specialized HIV clinic in Mexico from 2011 to 2015. Databases from the laboratory were analyzed, and the following four groups were formed: people seeking HIV-1 voluntary counseling and testing (VCT), people in prison (PPr), people living with HIV (PLWH), and patients from primary care clinics (others). The diagnosis of syphilis was made using the reverse algorithm; antibody titers were examined to determine the stage of infection. Baseline data were analyzed and, with follow-up information, a retrospective dynamic cohort was formed. Factors associated with the seroprevalence of syphilis and active syphilis were evaluated by the chi-square test. Moreover, risk factors for the incidence of syphilis were described. A total of 81,863 baseline individuals were analyzed. The seroprevalence of syphilis was 9.9% in the VCT group, 8.2% in the PPr group, 37.0% in the PLWH group, and 8.7% in the others group; the prevalence of active syphilis was 1.7-13.1%. A total of 11,124 people were followed up. The incidence (cases per 100 person-years) was 3.5 among the VCT group, 16.0 among the PLWH group, and < 0.1 among both the PPr and others groups, respectively; moreover, the frequency of reinfections was 11.1-24.4%. The high prevalence and incidence of syphilis, active syphilis, and reinfections among men, transgender people, individuals aged 20-39 years, and people with a history of HIV or hepatitis B suggest that it is critical to improve prevention, diagnosis, and treatment measures to stop the reemergence of syphilis. There are also new factors such as methamphetamine use, group sex, or contacting partners over the internet that are associated with syphilis. In addition, HIV preexposure prophylaxis could contribute to the increased incidence of syphilis by providing false security in the prevention of STIs, thereby increasing risky sexual behaviors.

Intense transmission of syphilis has emerged in some Canadian Arctic communities despite screening and prevention efforts. The remoteness of most communities and limited diagnostic infrastructure yield long delays (≥14 days) between screening and treatment of cases. These hamper syphilis control efforts and may contribute to sustained transmission. Syphilis rapid diagnostic tests (RDTs) have been developed to make screening more accessible and to inform clinical decision-making within the same clinical encounter. These RDTs have been successfully deployed in several countries, but not yet in Canada.
We describe the methodology of the \"Stopping Syphilis Transmission in Arctic Communities Through Rapid Diagnostic Testing\" (STAR) study, wherein the clinical and epidemiological impact of deploying a dual syphilis RDT in the context of ongoing transmission in Nunavut and Nunavik will be evaluated. In this prospective multisite field evaluation, sexually active individuals aged ≥14 years at risk for syphilis will be offered screening by an RDT at the point-of-care by non-laboratory trained registered nurses. Whole blood and serum specimens will be concurrently collected, when feasible, for rapid testing with an RDT containing both treponemal and non-treponemal components (Chembio DPP® Syphilis Screen & Confirm) and compared to laboratory-based reference testing according to a reverse sequence algorithm. The diagnostic accuracy of the RDT, using both whole blood and centrifuged serum specimens, will be validated under real-world conditions in remote Northern settings, outside of specialized laboratories. Additionally, screening-to-treatment time, case detection rates, and the number of infectious contacts averted by using the RDT relative to reference testing will be estimated. The impact of both diagnostic approaches on syphilis transmission dynamics will also be modeled.
This study will provide much needed evidence for strengthening rapid responses to emerging syphilis outbreaks in remote Arctic regions, by supplementing traditional diagnostic strategies with an RDT to rapidly triage patients likely in need of treatment. These results will also inform the development and tailoring of future diagnostic strategies and public health responses to emerging outbreaks in the North.

UNASSIGNED: Congenital syphilis (CS) is the infection of an infant or fetus with Treponema pallidum. The aim of this study was to investigate the clinical features and outcomes of serology reversion in infants diagnosed with confirmed or suspected congenital syphilis (CS).
UNASSIGNED: Infants admitted to the neonatal department of Children\'s Hospital of Fudan University from 2013 to 2016 who met the case definition of CS or suspected CS were included in this study. Follow-up was performed in an outpatient clinic until reversion to non-reactivity of both toluidine red unheated serum test (TRUST) and Treponemal pallidum particle agglutination (TPPA). Follow-up data were collected until up to the end of 2019, when the last infant with CS reached 3 years of age.
UNASSIGNED: In total, 682 infants were enrolled in this study, including 63 in the CS group and 619 in the suspected CS group. Forty-seven infants (74.6%) in the CS group had symptoms, and 57 (90.5%) had abnormal laboratory and/or long bone X-ray findings. By 6 months of age, TRUST results were negative in 53.3% of the infants with CS and in 100% of the infants with suspected CS. All the infants in the CS group returned to TRUST non-reactivity by 18 months of age. The TPPA results at 18 months of age showed that only 10.0% (3/30) of the patients in the CS group returned to non-reactivity, while a 99.6% (548/550) non-reactivity rate was observed in the suspected CS group. All the infants in the CS group returned to 19S-IgM-TPPA non-reactivity by 6 months of age.
UNASSIGNED: Although CS is an burdensome disease that may cause fetal and neonatal death, CS responds well to treatment when diagnosed and treated promptly, even when symptoms or lab/X-ray findings are present at birth.

OBJECTIVE: To develop and trial a dried tube specimen (DTS) panel for proficiency testing of dual HIV/syphilis rapid diagnostic tests (RDTs) at clinical sites.
RESULTS: DTS panels were prepared using plasma samples with known HIV and syphilis results, to give varying reactivity for syphilis and HIV test lines on RDTs. Laboratory DTS panels were stable for a minimum 4-week period at ambient temperatures with no inter-reader variability of results. Field testing of panels with Standard Diagnostics Bioline HIV/Syphilis duo showed 100% correlation with laboratory results, and excellent mean pair agreement between the two clinical sites (k = 1.0). With Chembio Dual Path Platform HIV-Syphilis, there were two false negative results for HIV and syphilis, respectively, at one site; and good mean pair agreement between the two sites (k = 0.9).
CONCLUSIONS: It is feasible and practicable to incorporate DTS panels into a field proficiency testing scheme for dual HIV/syphilis RDTs.

Syphilis, a disease once in decline, has made a resurgence worldwide. New Zealand has had increasing syphilis rates since enhanced syphilis surveillance was initiated in 2013. This study reports epidemiologic, descriptive and treatment data on management of infants prenatally exposed or vertically infected with syphilis across New Zealand as reported by pediatricians.
Over a 26-month period from April 2018 to May 2020 (inclusive), pediatricians throughout New Zealand notified potential, probable and confirmed cases of congenital syphilis to the New Zealand Pediatric Surveillance Unit. National reporting numbers were concurrently ascertained to demonstrate reporting accuracy.
Thirty-two cases were notified, comprised of 25 infants born to women with positive antenatal syphilis serology (5 whom developed congenital syphilis), and 7 infants diagnosed with congenital syphilis after birth where syphilis was not diagnosed in pregnancy. There were 12 cases of congenital syphilis; an incidence rate of 9.4 cases per 100,000 live births. Nine of the 12 infants had clinical features of congenital syphilis. One-third of maternal infections were early syphilis, and the women who gave birth to infected infants were less likely to have received antenatal care, adequate treatment and follow-up monitoring of treatment for syphilis during pregnancy.
This study quantifies an important burden of disease from congenital syphilis in our population. Case finding and treatment of syphilis in pregnancy are critical to prevent this. Our findings support the urgent need for measures such as repeat maternal syphilis screening in early third trimester; whether by affected region or instituted for all, in the context of rising cases.