A sex and gender perspective for neglected zoonotic diseases

Sex-driven and gender-driven diversities in health and diseases should be considered to promote equitable and more effective health for all. Nevertheless, these diversities are not sufficiently taken into consideration when approaching diseases, including infectious diseases. Neglected infectious diseases (NIDs) are a group of diseases, more prevalent in - but not limited to - tropical areas, that are almost absent from the global health agenda. NIDs are related to poverty, associated with stigma and social exclusion and prone to perpetuate health inequities from different perspectives including sex and gender. There is consensus that women and men are differently affected by NIDs. Many epidemiological studies have shown that being a man is a risk factor for several infectious diseases; a number of evidences indicate that sex-related hormonal and chromosomal factors contribute to distinct host’s response to infections in males and females. Conversely, women and girls experience a greater share of the NID burden due to their disproportionate poverty, illiteracy, lower education and social status particularly in low- and middle-income countries. More generally, different professional and environmental exposure can also influence dissimilar disease burden in men and women, but these aspects are seldom considered in clinical practice and in epidemiological surveillance. This opinion paper has the objective of describing the role of sex and gender-based differences for the management and control of NIDs with the scope of orientating research, clinical management and public health strategies towards a gender- and sex- balanced approach. Various NIDs will be examined as examples (case studies) to describe the biological features as well as organizational structures in healthcare and cultural aspects that should be considered for a gender-neutral management of these diseases as well as for the development of individualized anti-infectious treatments that take sex-specific host factors into account. An increased focus on sex together with gender diversities in health and health care services for NIDs is crucial to develop personalized and targeted therapeutic approaches but also to maximize the impact of interventions and public health strategies aimed at eliminating some of them by 2030

Screening strategies for the diagnosis of asymptomatic Leishmania infection in dialysis patients as a model for kidney transplant candidates

Despite being considered a tropical disease, visceral leishmaniasis (VL) caused by L. infantum is also endemic in the Mediterranean Europe and represents an increasing cause of morbidity and mortality in solid organ transplant (SOT) recipients. VL occurring in kidney transplant recipients is a severe event, often worsening the renal damage and leading to poor outcome. It is believed that most of VL cases in transplant recipients are caused by reactivation of a pre-existent, dormant leishmanial infection induced by the immunosuppressive drugs. Nevertheless, the prevalence of asymptomatic Leishmania infection in candidates to kidney transplant residing in or visiting endemic areas is unknown. As L. infantum is highly circulating in northeastern Italy, we aimed to examine the occurrence of this parasitic infection in 119 dialysis patients living in the mentioned area, 71 of whom were potential candidates to kidney transplant. By employing a combination of sensitive serological and molecular methods, we observed a prevalence of 15.9% asymptomatic Leishmania infection in the study cohort. This finding emphasizes the need of further evaluating potential screening strategies for Leishmania infection in solid organ transplant candidates residing in or visiting endemic areas

Updated diagnosis and graft involvement for visceral leishmaniasis in kidney transplant recipients: a case report and literature review

Visceral leishmaniasis (VL) has become a rising concern to transplantation teams, being associated with graft dysfunction and reduced survival of renal transplant recipients. Here, we describe a case of VL occurring in a kidney transplant (KT) recipient in Italy, a country in which Leishmania infantum is endemic and we reviewed the literature on the clinical course and diagnosis of VL in KT recipients residing or travelling to southern Europe

Identification of asymptomatic Leishmania infection in patients undergoing kidney transplant using multiple tests

Objectives: In immunocompromised patients, asymptomatic Leishmania infection can reactivate, and evolve to severe disease. To date, no test is considered the gold standard for the identification of asymptomatic Leishmania infection. A combination of methods was employed to screen for Leishmania infection in patients undergoing kidney transplant (KT). Methods: We employed polymerase chain reaction for the detection of parasitic DNA in peripheral blood, Western blot to identify serum immunoglobulin G and whole blood assay to detect cytokines/chemokines after stimulation of whole blood with parasitic antigen. Results: One-hundred twenty patients residing in Italy were included in the study at the time of KT. Each patient that tested positive to at least one test was considered as Leishmania positive. Fifty out of 120 patients (42%) tested positive for one or more tests. The detection of specific cell-mediated response (32/111, 29%) was the most common marker of Leishmania infection, followed by a positive serology (24/120, 20%). Four patients (3%) harbored parasitic DNA in the blood. Conclusion: Our findings underline the high prevalence of asymptomatic Leishmania infection in patients undergoing KT in Italy, who are potentially at-risk for parasite reactivation and can benefit from an increased vigilance. Understanding the clinical relevance of these findings deserves further studies.This work was supported by the Italian Ministry of Health (grant number RF-2016-02361931)S

Leishmaniasis in the immunocompromised population: evaluation of strategies for screening and monitoring

Leishmaniasis is a vector-borne disease caused by an intracellular parasite of the genus Leishmania. The clinical features of leishmaniasis include a wide range of manifestation from asymptomatic infections to different levels of disease severity. In most cases individuals do not develop clinical symptoms, but Leishmania parasites can persist lifelong in the host after an acute infection and easily reactivate under immunosuppressive conditions, causing severe disease with high mortality rate. The aim of this study was to identify Leishmania infection in selected groups of immunocompromised (IC) patients, including newly diagnosed HIV infected individuals, patients receiving kidney transplant (KT) and patients undergoing immunosuppressive therapies for immune-mediated diseases (IMD). Our study focused on the validation of a combination of methods to be used for the screening of asymptomatic Leishmania infection. The selected methods included high sensitive Real-Time PCR for detection of parasitic kinetoplast (k)DNA in peripheral blood, Western Blot (WB) for detection of specific IgG and Whole Blood Assay (WBA) to evaluate the anti-leishmanial T-cell response by quantifying the production of IFN-γ, IL-2 and IP-10 after stimulation of patients’ blood with Leishmania specific antigens. The methods have been validated on a cohort of immunocompetent individuals living in an endemic area of the Bologna province. Among 145 individuals recruited and screened with WB, Real-Time PCR and WBA, 24 subjects tested positive (17%) to one or more methods, thus confirming the high circulation of the parasite in the selected area. Given the high prevalence of asymptomatic infection in immunocompromised patients in endemic regions such as Italy, it seems essential to develop a plan for screening and follow-up of Leishmania infection. The screening algorithm that we tested in this study appears to be effective to identify accurately quiescent parasitic infection

Test combination to detect latent Leishmania infection: a prevalence study in a newly endemic area for L. infantum, northeastern Italy [Dataset]

Background: Most people infected with Leishmania remain asymptomatic, which is a common element that may promote the resurgence of clinically evident leishmaniasis in individuals with impaired cell-mediated immune responses. Unfortunately, there is no universally accepted assay to identify asymptomatic infection. This cross-sectional study focuses on the employment of three methods targeting different features of the parasitic infection to be used in combination for the screening of latent leishmaniasis in a newly endemic area of northeastern Italy. Methodology/Principle findings: The selected methods included highly sensitive Real-Time PCR for detection of parasitic kinetoplast (k)DNA in peripheral blood, Western Blot (WB) for detection of specific IgG, and Whole Blood stimulation Assay (WBA) to evaluate the anti-leishmanial T-cell response by quantifying the production of IL-2 after stimulation of patients’ blood with Leishmania specific antigens. Among 145 individuals, living in a municipality of the Bologna province, northeastern Italy, recruited and screened for Leishmania infection, 23 subjects tested positive (15.9%) to one or more tests. Positive serology was the most common marker of latent leishmaniasis (15/145, 10%), followed by the detection of specific cell-mediated response (12/145, 8%), while only few individuals (6/145, 4%) harbored parasitic DNA in the blood. Conclusions/Significance: Combining different tests substantially increased the yield of positivity in detecting latent Leishmania infection. The test combination that we employed in this study appears to be effective to accurately identify latent leishmaniasis in an endemic area.S

Asymptomatic Leishmania infantum infection in blood donors living in an endemic area, northeastern Italy

Objectives: Human leishmaniasis can be severe and fatal, yet in the Mediterranean region only a small percentage of infections progress to clinical disease. We evaluated the percentage of asymptomatic Leishmania infection in the Bologna province, northeastern Italy. Methods: We examined the presence of specific antibodies by Western Blot (WB) and parasitic DNA by real time PCR in peripheral blood of 240 blood donors residing in the Bologna province. Results: Anti-Leishmania IgG were detected by WB in 27 subjects (11.2%, 95% CI 7%-15%), while Leishmania kinetoplast DNA was detected in peripheral blood specimens of 4 out of 240 donors (1.7%, 95% CI 0.2%-3.2%). Overall, the prevalence of Leishmania infection in the blood donor cohort was 12.5%, thus indicating an elevated cumulative exposure to the Leishmania parasite in the examined municipality. Conclusions: Our results suggest that a surveillance system for monitoring Leishmania infection in blood donors and/or strategies of protozoan inactivation in whole blood should be taken into consideration in areas with circulation of the Leishmania parasite

Organic Electrochemical Transistors as Versatile Tool for Real-Time and Automatized Viral Cytopathic Effect Evaluation

In-vitro viral studies are still fundamental for biomedical research since studying the virus kinetics on cells is crucial for the determination of the biological properties of viruses and for screening the inhibitors of infections. Moreover, testing potential viral contaminants is often mandatory for safety evaluation. Nowadays, viral cytopathic effects are mainly evaluated through end-point assays requiring dye-staining combined with optical evaluation. Recently, optical-based automatized equipment has been marketed, aimed at the real-time screening of cell-layer status and obtaining further insights, which are unavailable with end-point assays. However, these technologies present two huge limitations, namely, high costs and the possibility to study only cytopathic viruses, whose effects lead to plaque formation and layer disruption. Here, we employed poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (Pedot:Pss) organic electrochemical transistors (OECTs) for the real-time, electrical monitoring of the infection of cytolytic viruses, i.e., encephalomyocarditis virus (EMCV), and non-cytolytic viruses, i.e., bovine coronavirus (B-CoV), on cells. OECT data on EMCV were validated using a commercially-available optical-based technology, which, however, failed in the B-CoV titration analysis, as expected. The OECTs proved to be reliable, fast, and versatile devices for viral infection monitoring, which could be scaled up at low cost, reducing the operator workload and speeding up in-vitro assays in the biomedical research field