Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p.pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides.

Recent studies have demonstrated a suboptimal humoral response to SARS-CoV-2 mRNA vaccines in patients diagnosed with hematologic malignancies, however data about cellular immunogenicity is scarce. In this study we aimed to evaluate both the humoral and cellular immunogenicity one month after the second dose of the mRNA-1273 vaccine. Antibody titers were measured by the Elecsys and LIAISON Anti-SARS-CoV-2 S assay while T-cell response was assessed by Interferon-Gamma-Release-immuno-Assay technology. Overall, 76.3% (184/241) of patients developed humoral immunity and the cellular response rate was 79% (184/233). Hypogammaglobulinemia, lymphopenia, active hematological treatment and anti-CD20 therapy during the last 6 months were associated with an inferior humoral response. Conversely, age over 65 years, active disease, lymphopenia and immunosuppressive treatment for GvHD were associated with an impaired cellular response. A significant dissociation between humoral and cellular response was observed in patients treated with anti-CD20 therapy, being the humoral response of 17.5% whereas the cellular response was 71.1%. In these patients B-cell aplasia was confirmed while T cell counts were preserved. In contrast, humoral response was observed in 77.3% of patients under immunosuppressive treatment for GvHD, while only 52.4% had cellular response. The cellular and humoral response to the SARS-CoV-2 mRNA-1273 vaccine in patients with hematological malignancies is highly influenced by the presence of treatments like anti-CD20 therapy and immunosuppressive agents. This observation has implications for the further management of these patients.

Introducción: Es fundamental evaluar los niveles de protección inmune en infectados o tras la vacunación frente a SARS-CoV-2. La medición de la respuesta inmune celular T puede complementar la determinación de anticuerpos. Nuestro objetivo fue evaluar la viabilidad de un ensayo comercial validado de respuesta celular T. Métodos: Se incluyeron veinte trabajadores sanitarios (TS). Medimos anticuerpos contra proteínas N y S de SARS-CoV-2 en paralelo con un ensayo de liberación de interferón-gamma (IFNγ) en sangre completa (IGRA) para péptidos de la proteína S. IFNγ se determinó mediante dos métodos de detección: CLIA y ELISA. Resultados: IGRA detectó respuesta celular T en TS tanto infectados como vacunados. La correlación de los dos métodos de detección de IFNγ fue muy alta (R>0,8) y la sensibilidad y la especificidad variaron entre 100 y 86% y 100-73% respectivamente. Hubo una concordancia muy alta entre los niveles de anticuerpos específicos y el ensayo IGRA aunque la correlación cuantitativa fue relativamente baja. En el pequeño grupo de infectados, una dosis de vacuna fue suficiente para alcanzar la meseta de respuesta inmune. IGRA fue claramente positivo en un profesional vacunado inmunosuprimido que presentaba anticuerpos contra la proteína S negativos. Conclusiones: IGRA frente a péptidos de la proteína-S es susceptible de automatización y constituye una herramienta prometedora para medir la respuesta inmune celular frente a SARS-CoV-2; es aplicable a un gran número de muestras y puede servir para valorar la protección, particularmente en los grupos vulnerables en riesgo de volver a exponerse a la infección, como los TS.