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Introduction Weight gain, together with the onset of overweight and obesity, is a relevant emerging health issue among people living with HIV (PLWH). A large body of literature recognises this issue as a part of the secondary effects of some antiretroviral therapy (ART), but little is known about the role of lifestyle. In order to assess the role of modifiable aspects of lifestyle in addition to ART on the onset of overweight and obesity, we designed a prospective observational study among PLWH.Methods and analysis This is a prospective observational study among PLWH aged 18–65 years attending the Clinic of Infectious Diseases of Spedali Civili, Brescia, Italy, and on ART for at least 24 months. According to the sample size computation, 175 PLWH will be enrolled. PLWH willing to participate in the study are invited to a scheduled clinical visit to collect anthropometric measures, dietary habits and physical activity levels. During the visit, standardised and validated questionnaires are administered regarding emotional distress, food insecurity, use of food supplements, sleep quality, smoking habit and alcohol consumption/risk of addiction. After the interviews, bioimpedance analysis is performed and blood pressure and heart rate are assessed. After 12 months from baseline, each participant will be asked to participate in a further visit, with the same assessments as at baseline. The primary objective of the study is to assess the role of the modifiable factors of lifestyle in the onset of overweight and/or obesity among on-treatment PLWH experiencing weight gain, focusing on diet and physical activity.Ethics and dissemination The study research protocol and informed consent procedures were approved by Ethics Committee of Brescia Province (Italy) on 23 May 2023 (NP5892). Informed consent will be obtained from participants. Results will be submitted for publication in international peer-reviewed journals and summaries will be provided annually to the funders.

ABSTRACTFew papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly recombinant vaccine (RZV) was recently introduced and approved for HZ prevention among adults. PLWH represents a population on which a particular attention should be applied, in order to guarantee the vaccine efficacy and safety. We performed a literature search in USNLM, PubMed, PubMed Central, PMC and Cochrane Library. From all the publications found eligible, data were extracted and processed per population, vaccine type, immunogenicity and ADRs. The review of the 13 included studies shows that both RZV and VZL are immunogenic and have an acceptable safety profile in adults and children living with HIV. However, given the lack of research available about vaccine efficacy in preventing VZV and HZ in PLWH, additional studies need to be performed, in order to achieve a full completeness of data.

Abstract Background Orf virus (ORFV) is the pathogen responsible for Orf, a zoonotic viral infection that can be spread to humans from sheep and goats. Here, we present a case of human Orf complicated by an immune-related reaction, to raise awareness of this under-recognized disease avoiding unnecessary investigations and overtreatment. Case report A 51-year-old woman with no previous medical history presented with a one-week history of three asymptomatic swelling nodules with a grey necrotic center and red outer halo on her index finger. At physical examination there was also a pruritic papulovesicular eruption on her hands and feet. She reported a recent contact with a goat which had a similar nodular lesion in its mouth. A biopsy of the lesions was performed and a diagnosis of Orf complicated by widespread erythema multiforme was made based on the clinical and histopathological features. The lesions spontaneously resolved within the next 2 weeks. Conclusions Orf is not very prevalent in our region, so we performed a biopsy of the lesion to guide us toward a diagnosis. However, we should remember that the diagnosis of ecthyma relies on clinical evaluation and epidemiological criteria.

Dolutegravir (DTG) is one of the most prescribed antiretroviral drugs for treating people with HIV infection, including women of child-bearing potential or pregnant. Nonetheless, neuropsychiatric symptoms are frequently reported. Early reports suggested that, probably in relation to folic acid (FA) shortage, DTG may induce neural tube defects in infants born to women taking the drug during pregnancy. Subsequent reports did not definitively confirm these findings. Recent studies in animal models have highlighted the association between DTG exposure in utero and congenital anomalies, and an increased risk of neurologic abnormalities in children exposed during in utero life has been reported. Underlying mechanisms for DTG-related neurologic symptoms and congenital anomalies are not fully understood. We aimed to deepen our knowledge on the neurodevelopmental effects of DTG exposure and further explore the protective role of FA by the use of zebrafish embryos. We treated embryos at 4 and up to 144 h post fertilization (hpf) with a subtherapeutic DTG concentration (1 μM) and observed the disruption of the anterior–posterior axis and several morphological malformations in the developing brain that were both prevented by pre-exposure (2 hpf) and rescued by post-exposure (10 hpf) with FA. By whole-mount in situ hybridization with riboprobes for genes that are crucial during the early phases of neurodevelopment (ntl, pax2a, ngn1, neurod1) and by in vivo visualization of the transgenic Tg(ngn1:EGFP) zebrafish line, we found that DTG induced severe neurodevelopmental defects over time in most regions of the nervous system (notochord, midbrain–hindbrain boundary, eye, forebrain, midbrain, hindbrain, spinal cord) that were mostly but not completely rescued by FA supplementation. Of note, we observed the disruption of ngn1 expression in the dopaminergic regions of the developing forebrain, spinal cord neurons and spinal motor neuron projections, with the depletion of the tyrosine hydroxylase (TH)+ dopaminergic neurons of the dorsal diencephalon and the strong reduction in larvae locomotion. Our study further supports previous evidence that DTG can interfere with FA pathways in the developing brain but also provides new insights regarding the mechanisms involved in the increased risk of DTG-associated fetal neurodevelopmental defects and adverse neurologic outcomes in in utero exposed children, suggesting the impairment of dopaminergic pathways.

Background: West Nile virus (WNV) infection is a seasonal arbovirosis with the potential to cause severe neurological disease. Outcomes of the infection from WNV depend on viral factors (e.g., lineage) and host-intrinsic factors (e.g., age, sex, immunocompromising conditions). Immunity is essential to control the infection but may also prove detrimental to the host. Indeed, the persistence of high levels of pro-inflammatory cytokines and chemokines is associated with the development of blood–brain barrier (BBB) damage. Due to the importance of the inflammatory processes in the development of West Nile neuroinvasive disease (WNND), we reviewed the available literature on the subject. Methods: According to the 2020 updated PRISMA guidelines, all peer-reviewed articles regarding the inflammatory response associated with WNND were included. Results: One hundred and thirty-six articles were included in the data analysis and sorted into three groups (in vitro on-cell cultures, in vivo in animals, and in humans). The main cytokines found to be increased during WNND were IL-6 and TNF-α. We highlighted the generally small quantity and heterogeneity of information about the inflammatory patterns associated with WNND. Conclusions: Further studies are needed to understand the pathogenesis of WNND and to investigate the extent and the way the host inflammatory response either helps in controlling the infection or in worsening the outcomes. This might prove useful both for the development of target therapies and for the development of molecular markers allowing early identification of patients displaying an inflammatory response that puts them at a higher risk of developing neuroinvasive disease and who might thus benefit from early antiviral therapies.

Leclercia adecarboxylata is a gram-negative bacillus, a ubiquitous microorganism, which may be found in both aquatic environments and soil, it was first described by H. Leclerc in 1962 and was reclassified thanks to more sensitive testing methods. L. adecarboxylata has been recently recognized as an emerging pathogen that causes several clinical syndromes not only in immunocompromised patients.

The natural history of occult hepatitis B virus infection (OBI) and the mechanism involved in HBV reactivation are only partially understood. As regards people living with HIV (PLWH), HBV reactivation is estimated to occur with an incidence ratio of 0.019 cases per 100 person-year. Here we report the case of OBI reactivation in a HIV/HCV co-infected patient followed for 25 years at our Infectious Diseases Unit, but, unfortunately, lost to follow-up about 19 months after Direct-acting antivirals (DAAs) treatment. At re-engagement, blood tests showed high replication of plasmatic HIV-RNA along with severe immunosuppression and normal levels of liver enzymes. However, 3 months after ART reintroduction, an immune reconstitution inflammatory syndrome (IRIS) was diagnosed with high detectable HBV-DNA load and transaminase elevation. Our case report shows how the balance between the virus and the host immune system is quite a dynamic process that might significantly impact the course of the disease. The aim of this case report is to bring to the attention of physicians that, although OBI reactivation is a rather rare occurrence, even amongst PLWH, its potential consequences compel to a high alertness on the matter. Therefore, especially in patients with an impaired immune system and on a tenofovir or lamivudine-sparing regimen, HBV serological and virological markers should always be strictly monitored, even in the absence of a hepatitis flare.

There are scarce data regarding influenza vaccination among people with HIV infection (PWHIV). The goal of this explorative study is to assess hesitancy toward influenza vaccination in a group of PWHIV during the COVID-19 pandemic. A questionnaire was administered to 219 patients vaccinated at our clinic during the 2020–2021 campaign. It evaluated subjects’ adherence to influenza vaccine over the last three seasonal vaccination campaigns, vaccine confidence, complacency and convenience, and the effect of the pandemic on the choice to become vaccinated. The population was divided into two groups: fully adherent to influenza vaccine (all three campaigns, 117 patients) and non-fully adherent (one or two campaigns, 102 patients). Adherence increased in the non-fully adherent group in 2020–2021, but the pandemic did not affect the choice. Misbeliefs emerged: the influenza vaccine was considered protective against SARS-CoV-2 (22.8% of the total population); almost half of all patients thought the influenza vaccine could improve their CD4 T cell level (57.3% in fully adherent, 40.2% in non-fully adherent, p

Background: Approved for acute bacterial skin and skin structure infections, dalbavancin (DBV) has gradually acquired over the years a role as an off-label treatment for several infections caused by Gram-positive bacteria even in other anatomical sites. Osteoarticular (OA) infections are one of the most difficult-to-treat infections and, since the absence of recommendations, clinicians use different and heterogenic DBV dosing schedule regimens for the off-label treatment of osteomyelitis, spondylodiscitis, and septic arthritis. Our aim is to systematically review the current literature to describe DBV administration schedules and their outcome in OA infections. Methods: According to the 2020 updated PRISMA guidelines, all peer-reviewed articles regarding the use of DBV in OA infections were included. We conducted a literature search on PubMed and Cochrane Controlled Trials. Results: A total of 23 studies and 450 patients were included, prevalently male (144/195, 73.8%) and diabetic (53/163, 32.5%). Overall, 280 (280/388, 72.2%) osteomyelitis, 79 (79/388, 20.4%) spondylodiscitis, and 29 (29/388, 7.5%) septic arthritis were considered. Staphylococcus aureus (164/243, 67.5%) was the most common pathogen isolated. A previous treatment failure (45/96, 46.9%) was the main reason for a switch to a long-acting antibiotic. Most patients were successfully cured with DBV (318/401, 79.3%). A source control was performed in most patients with a favourable outcome (80.4%), while MRSA was prevalently isolated in people with an unfavourable outcome (57%). While a higher percentage of success was found in people who received three doses of DBV 1 week apart (92.3%), a higher rate of treatment failure was recorded in cases of when the DBV cycle was composed of less than two or more than four doses (27.8%). Conclusions: DBV has shown to be effective as a treatment for OA infections. The most favourable outcome was found in patients receiving three doses of DBV and with an adequate surgical management prior to antibiotic treatment. Although a rigorous administration schedule does not exist, DBV is a viable treatment option in the management of OA infections.

In the past, one of the most widely used non-nucleoside reverse transcriptase inhibitors (NNRTI) in first-line antiretroviral therapy (ART) of HIV infection was efavirenz (EFV), which is already used as a cost-effective treatment in developing countries due to its efficacy, tolerability, and availability. However, EFV also demonstrates several adverse effects, like hepatotoxicity, altered lipid profile, neuropsychological symptoms, and behavioral effects in children after in utero exposure. In 2018, another NNRTI, doravirine (DOR), was approved due to its similar efficacy but better safety profile. Preclinical safety studies demonstrated that DOR is not genotoxic and exhibits no developmental toxicity or effects on fertility in rats. Zebrafish (Danio rerio) embryos have been widely accepted as a vertebrate model for pharmacological and developmental studies. We used zebrafish embryos as an in vivo model to investigate the developmental toxicity of DOR compared to EFV. After exposure of the embryos to the drugs from the gastrula stage up to different developmental stages (30 embryos for each arm, in three independent experiments), we assessed their survival, morphology, hatching rate, apoptosis in the developing head, locomotion behavior, vasculature development, and neutral lipid distribution. Overall, DOR showed a better safety profile than EFV in our model. Therapeutic and supra-therapeutic doses of DOR induced very low mortality [survival rates: 92, 90, 88, 88, and 81% at 1, 5, 10, 25, and 50 μM, respectively, at 24 h post fecundation (hpf), and 88, 85, 88, 89, and 75% at the same doses, respectively, at 48 hpf] and mild morphological alterations compared to EFV exposure also in the sub-therapeutic ranges (survival rates: 80, 77, 69, 63, and 44% at 1, 5, 10, 25, and 50 μM, respectively, at 24 hpf and 72, 70, 63, 52, and 0% at the same doses, respectively, at 48 hpf). Further, DOR only slightly affected the hatching rate at supra-therapeutic doses (97, 98, 96, 87, and 83% at 1, 5, 10, 25, and 50 μM, respectively, at 72 hpf), while EFV already strongly reduced hatching at sub-therapeutic doses (83, 49, 11, 0, and 0% at 1, 5, 10, 25, and 50 μM, respectively, at the same time endpoint). Both DOR at therapeutic doses and most severely EFV at sub-therapeutic doses enhanced apoptosis in the developing head during crucial phases of embryo neurodevelopment and perturbed the locomotor behavior. Furthermore, EFV strongly affected angiogenesis and disturbed neutral lipid homeostasis even at sub-therapeutic doses compared to DOR at therapeutic concentrations. Our findings in zebrafish embryos add further data confirming the higher safety of DOR with respect to EFV regarding embryo development, neurogenesis, angiogenesis, and lipid metabolism. Further studies are needed to explore the molecular mechanisms underlying the better pharmacological safety profile of DOR, and further human studies are required to confirm these results in the zebrafish animal model.

Anti-cytokine autoantibodies and, in particular, anti-type I interferons are increasingly described in association with immunodeficient, autoimmune, and immune-dysregulated conditions. Their presence in otherwise healthy individuals may result in a phenotype characterized by a predisposition to infections with several agents. For instance, anti-type I interferon autoantibodies are implicated in Coronavirus Disease 19 (COVID-19) pathogenesis and found preferentially in patients with critical disease. However, autoantibodies were also described in the serum of patients with viral, bacterial, and fungal infections not associated with COVID-19. In this review, we provide an overview of anti-cytokine autoantibodies identified to date and their clinical associations; we also discuss whether they can act as enemies or friends, i.e., are capable of acting in a beneficial or harmful way, and if they may be linked to gender or immunosenescence. Understanding the mechanisms underlying the production of autoantibodies could improve the approach to treating some infections, focusing not only on pathogens, but also on the possibility of a low degree of autoimmunity in patients.

Background: Orf is a highly contagious zoonosis caused by Orf virus (ORFV), which is endemic in sheep and goats worldwide. Human Orf is usually a self-limiting disease, but potential complications, including immune-mediated reactions, may occur. Methods: We included all articles regarding Orf-associated immunological complications published in peer-reviewed medical journals. We conducted a literature search of the United States National Library of Medicine, PubMed, MEDLINE, PubMed Central, PMC, and the Cochrane Controlled Trials. Results: A total of 16 articles and 44 patients were included, prevalently Caucasian (22, 95.7%) and female (22, 57.9%). The prevailing immunological reaction was erythema multiforme (26, 59.1%), followed by bullous pemphigoid (7, 15.9%). In most cases, the diagnosis was made on the basis of clinical and epidemiological history (29, 65.9%), while a biopsy of secondary lesions was performed in 15 patients (34.1%). A total of 12 (27.3%) patients received a local or systemic treatment for primary lesions. Surgical removal of primary lesion was described in two cases (4.5%). Orf-immune-mediated reactions were treated in 22 cases (50.0%), mostly with topical corticosteroids (12, 70.6%). Clinical improvement was reported for all cases. Conclusions: Orf-related immune reactions can have a varied clinical presentation, and it is important for clinicians to be aware of this in order to make a prompt diagnosis. The main highlight of our work is the presentation of complicated Orf from an infectious diseases specialist’s point of view. A better understanding of the disease and its complications is essential to achieve the correct management of cases.

Background: Syphilis infection does not confer definitive and protective immunity against reinfection, and crucial aspects of repeated episodes of syphilis are far from being understood, especially among people living with HIV (PLWH). Methods: In order to explore the burden of syphilis in a large cohort of HIV-negative patients and PLWH, this retrospective study describes the demographics, clinical presentation and treatment outcome of patients with syphilis treated at our clinic from 2013 to 2021. Results: Within the study period, 1859 syphilis episodes (827, 44.5% first infections and 1032, 55.5% reinfections) were recorded. A total of 663 patients, of whom 347 (52%) had PLWH, were considered. Syphilis was mostly diagnosed in males (77%) and European (79%) patients. More than half of syphilis episodes were recorded during the late latent stage (64%) or during follow-up/screening visits for other diseases, while symptomatic stages led to a diagnosis in almost half of HIV-negative patients (p < 0.001). PLWH with syphilis infection were predominantly homo/bisexual (p < 0.001). A significantly higher rate of syphilis reinfection was observed in PLWH, who also demonstrated a higher range of subsequent episodes. The serofast state was found to be similar at the 6- and 12-month follow-up visits. The multivariate analysis carried out in the HIV-positive group showed that an RPR titre >1:16 was an independent predictor for serological non-response. Conclusions: Syphilis reinfections are predominantly diagnosed in HIV-positive MSM. The high rate of asymptomatic presentation among PLWH supports the role of periodical syphilis screening. In PLWH, the only baseline factor associated with an increased risk of non-response was an RPR titre >1:16, while assessment at 12 months after treatment increased the possibility of detecting a serological response, indicating that PLWH have a slower serological response to treatment.

Background: Gram-negative bacteria are causative agents of endogenous endophthalmitis (EBE). We aim to systematically review the current literature to assess the aetiologies, risk factors, and early ocular lesions in cases of Gram-negative EBE. Methods: All peer-reviewed articles between January 2002 and August 2022 regarding Gram-negative EBE were included. We conducted a literature search on PubMed and Cochrane Controlled Trials. Results: A total of 115 studies and 591 patients were included, prevalently Asian (98; 81.7%) and male (302; 62.9%). The most common comorbidity was diabetes (231; 55%). The main aetiologies were Klebsiella pneumoniae (510; 66.1%), Pseudomonas aeruginosa (111; 14.4%), and Escherichia coli (60; 7.8%). Liver abscesses (266; 54.5%) were the predominant source of infection. The most frequent ocular lesions were vitreal opacity (134; 49.6%) and hypopyon (95; 35.2%). Ceftriaxone (76; 30.9%), fluoroquinolones (14; 14.4%), and ceftazidime (213; 78.0%) were the most widely used as systemic, topical, and intravitreal anti-Gram-negative agents, respectively. The most reported surgical approaches were vitrectomy (130; 24.1%) and evisceration/exenteration (60; 11.1%). Frequently, visual acuity at discharge was no light perception (301; 55.2%). Conclusions: Gram-negative EBEs are associated with poor outcomes. Our systematic review is mainly based on case reports and case series with significant heterogeneity. The main strength is the large sample spanning over 20 years. Our findings underscore the importance of considering ocular involvement in Gram-negative infections.

The emergence SARS-CoV-2 in late 2019 and early 2020 has caused a pandemic of unprecedented proportions. Management of COVID-19 became emergent public health priorities, and the impact on other public health initiatives, such as expanded HIV screening and linkage to care, remain largely unknown. In this Single-Center retrospective observational study, we describe the characteristics and circumstance of the new HIV cases during 2020 compared to 2019. We observed a decrease of HIV diagnosis during this period. Interestingly, median age at HIV diagnosis decreased of one decade and percentage of female patients was higher. In addition, more patients received diagnosis during hospitalization and more AIDS-defining conditions, such as Pneumocystis pneumonia, were detected. We express our concern that HIV new diagnoses will increase as a result of people's inability to get tested or treated in this period. More efforts are needed to improve local screening programs both during and after COVID-19 pandemic.

Among the Poxviridae family, orthopoxvirus is the most notorious genus. Several DNA viruses belonging to this group are known to produce human disease from the life-threatening variola virus (VARV) (the causative agent of smallpox), monkeypox virus (MPXV), cowpox virus (CPXV), and vaccinia virus (VACV). These orthopoxviruses still remain a public health concern as VACV or CPXV still cause emerging endemic threads, especially in developing countries. MPXV is able to cause sporadic human outbreaks of a smallpox-like zoonotic disease and, in May 2022, hundreds of cases related to MPXV have been reported from more than 30 countries around the globe. At the end of July, monkeypox (MPX) outbreak was even declared a global health emergency by the World Health Organization (WHO). Many aspects remain unclear regarding this outbreak and a deep understanding of orthopoxvirus might have crucial and evident implications. During the era in which people under 45 years old are not protected against VACV, the potential use of orthopoxviruses as a biological weapon raises global concern considering the rapid spreading of the current MPX outbreak in vulnerable populations. Hence, we review the most recent evidence about phylogenesis, pathogenesis, prevention, and treatment for this concerning disease.

The epidemic curve of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is silently rising again. Worldwide, the dominant SARS-CoV-2 variant of concern (VOC) is Omicron, and its virological characteristics, such as transmissibility, pathogenicity, and resistance to both vaccine- and infection-induced immunity as well as antiviral drugs, are an urgent public health concern. The Omicron variant has five major sub-lineages; as of February 2022, the BA.2 lineage has been detected in several European and Asian countries, becoming the predominant variant and the real antagonist of the ongoing surge. Hence, although global attention is currently focused on dramatic, historically significant events and the multi-country monkeypox outbreak, this new epidemic is unlikely to fade away in silence. Many aspects of this lineage are still unclear and controversial, but its apparent replication advantage and higher transmissibility, as well as its ability to escape neutralizing antibodies induced by vaccination and previous infection, are rising global concerns. Herein, we review the latest publications and the most recent available literature on the BA.2 lineage of the Omicron variant.

In Winter 2020, Italy, and in particular the Lombardy region, was the first country in the Western hemisphere to be hit by the COVID-19 pandemic. Plasma from individuals recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first therapeutic tool adopted to counteract the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this retrospective cohort study, we report the experience of the city hospital of Mantua, Lombardy region, on the compassionate use of CCP in patients hospitalized for severe COVID-19. Between April 2020 and April 2021, 405 consecutive COVID-19 patients received 657 CCP units with a median anti-SARS-CoV-2 neutralizing antibody (nAb) titer of 160 (interquartile range (IQR), 80–320). Their median age was 68 years (IQR, 56–78 years), and 62% were males. At enrollment, 55% of patients had an increased body mass index (BMI), and 25.6% had at least three comorbidities. The 28-day crude mortality rate was 12.6% (51/405). Young age (

The Coronavirus disease 2019 (COVID-19) pandemic poses a great threat to global public health. The original wild-type strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has genetically evolved, and several variants of concern (VOC) have emerged. On 26 November 2021, a new variant named Omicron (B.1.1.529) was designated as the fifth VOC, revealing that SARS-CoV-2 has the potential to go beyond the available therapies. The high number of mutations harboured on the spike protein make Omicron highly transmissible, less responsive to several of the currently used drugs, as well as potentially able to escape immune protection elicited by both vaccines and previous infection. We reviewed the latest publication and the most recent available literature on the Omicron variant, enlightening both reasons for concern and high hopes for new therapeutic strategies.

Monoclonal antibodies (mAbs) have been known since the 1970s. However, their therapeutic potential in the medical field has recently emerged, with the advancement of manufacturing techniques. Initially exploited mainly in the oncology field, mAbs have become increasingly relevant in Infectious Diseases. Numerous mAbs have been developed against SARS-CoV 2 and have proven their effectiveness, especially in the management of the mild-to-moderate disease. In this review, we describe the monoclonal antibodies currently authorized for the treatment of the coronavirus disease 19 (COVID-19) and offer an insight into the clinical trials that led to their approval. We discuss the mechanisms of action and methods of administration as well as the prophylactic and therapeutic labelled indications (both in outpatient and hospital settings). Furthermore, we address the critical issues regarding mAbs, focusing on their effectiveness against the variants of concern (VoC) and their role now that a large part of the population has been vaccinated. The purpose is to offer the clinician an up-to-date overview of a therapeutic tool that could prove decisive in treating patients at high risk of progression to severe disease.

In 2021 the scientific community’s efforts have been focused on solving the back-breaking challenge of the COVID-19 pandemic, but sexually transmitted infections (STI) are still one of the most common global health problems. Syphilis is a systemic disease caused by the spirochaete Treponema pallidum (TP) and is one of the oldest known diseases. Its incidence has increased in the last few years and syphilis still remains a contemporary plague that continues to afflict millions of people worldwide. Despite research improvements, syphilis pathogenesis is not completely clear; clinical presentation is very heterogeneous and the diagnosis can sometimes be difficult. Furthermore, few therapeutic options are available, and a vaccine has not been found yet. In this review, we describe the most recent evidence concerning the clinical manifestation, diagnosis, treatment and vaccine prospectives for this disease.