Human leptospirosis cases in Palermo Italy. The role of rodents and climate

Many regions of the world are increasingly exposed to leptospirosis due to poverty, global warming and high urban density. Here, we report a molecular survey for pathogenic Leptospira spp. in rodents and two symptomatic human cases of leptospirosis in the city of Palermo, Italy.Four rodent species were captured in six areas of the city, and a molecular analysis for pathogenic Leptospira spp. on DNA from the kidney samples showed a different prevalence of leptospirosis in all the species of rodents. In addition, two human cases that occurred in May and October of 2009 in the city were also reported. A 67-year-old woman recovered after antibiotic treatment, whereas a 71-year-old woman did not survive. The weather during both of those times was notable for a violent cloudburst that caused street flooding.For the past several years, the incidence of leptospirosis has remained steady at 9 human cases every 10 years across the entire island of Sicily, with a population of almost 5 million inhabitants.The high prevalence of leptospirosis in rodents and the simultaneous presence of known risk factors, such as a mild/wet climate, street flooding and garbage accumulation, could explain the two cases of leptospirosis within the same city in the same year. This occurrence should raise awareness of this under-estimated zoonosis among public health authorities, especially given the potential fatality among elderly and immune-compromised individuals in urban settings in developed countries. Keywords: Human leptospirosis, Rodents, Climate change, Socio-economic welfare, Public health concer

New Insight into Immunity and Immunopathology of Rickettsial Diseases

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecular Rickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene expression. The roles of innate and adaptive immune responses are discussed, and potential new targets for therapies to block host-pathogen interactions and pathogen virulence mechanisms are considered

The Renaissance of KRAS Targeting in Advanced Non-Small-Cell Lung Cancer: New Opportunities Following Old Failures

: Non-small cell lung cancer (NSCLC) represents the perfect paradigm of 'precision medicine' due to its complex intratumoral heterogeneity. It is truly characterized by a range of molecular alterations that can deeply influence the natural history of this disease. Several molecular alterations have been found over time, paving the road to biomarker-driven therapy and radically changing the prognosis of 'oncogene addicted' NSCLC patients. Kirsten rat sarcoma (KRAS) mutations are present in up to 30% of NSCLC (especially in adenocarcinoma histotype) and have been identified decades ago. Since its discovery, its molecular characteristics and its marked affinity to a specific substrate have led to define KRAS as an undruggable alteration. Despite that, many attempts have been made to develop drugs capable of targeting KRAS signaling but, until a few years ago, these efforts have been unsuccessful. Comprehensive genomic profiling and wide-spectrum analysis of genetic alterations have only recently allowed to identify different types of KRAS mutations. This tricky step has finally opened new frontiers in the treatment approach of KRAS-mutant patients and might hopefully increase their prognosis and quality of life. In this review, we aim to highlight the most interesting aspects of (epi)genetic KRAS features, hoping to light the way to the state of art of targeting KRAS in NSCLC

Cryptic Leishmania infantum infection in Italian HIV infected patients

<p>Abstract</p> <p>Background</p> <p>Visceral leishmaniasis (VL) is a protozoan diseases caused in Europe by <it>Leishmania (L.) infantum</it>. Asymptomatic <it>Leishmania </it>infection is more frequent than clinically apparent disease. Among HIV infected patients the risk of clinical VL is increased due to immunosuppression, which can reactivate a latent infection. The aims of our study were to assess the prevalence of asymptomatic <it>L. infantum </it>infection in HIV infected patients and to study a possible correlation between <it>Leishmania </it>parasitemia and HIV infection markers.</p> <p>Methods</p> <p>One hundred and forty-five HIV infected patients were screened for the presence of anti-<it>Leishmania </it>antibodies and <it>L. infantum </it>DNA in peripheral blood. Statistical analysis was carried out by using a univariate regression analysis.</p> <p>Results</p> <p>Antibodies to <it>L. infantum </it>were detected in 1.4% of patients. <it>L. infantum </it>DNA was detected in 16.5% of patients. Significant association for PCR-<it>Leishmania </it>levels with plasma viral load was documented (p = 0.0001).</p> <p>Conclusion</p> <p>In our area a considerable proportion of HIV infected patients are asymptomatic carriers of <it>L. infantum </it>infection. A relationship between high HIV viral load and high parasitemic burden, possibly related to a higher risk of developing symptomatic disease, is suggested. PCR could be used for periodic screening of HIV patients to individuate those with higher risk of reactivation of <it>L. infantum </it>infection.</p

Imported arboviral infections in Italy, July 2014-October 2015: A National Reference Laboratory report

BACKGROUND: Imported cases of infections due to Dengue (DENV) and Chikungunya (CHIKV) viruses and, more recently, Zika virus (ZIKV) are commonly reported among travelers returning from endemic regions. In areas where potentially competent vectors are present, the risk of autochthonous transmission of these vector-borne pathogens is relatively high. Laboratory surveillance is crucial to rapidly detect imported cases in order to reduce the risk of transmission. This study describes the laboratory activity performed by the National Reference Laboratory for Arboviruses (NRLA) at the Italian National Institute of Health in the period from July 2014 to October 2015. METHODS: Samples from 180 patients visited/hospitalized with a suspected DENV/CHIKV/ZIKV infection were sent to the NRLA from several Italian Hospitals and from Regional Reference Laboratories for Arboviruses, in agreement with the National Plan on human surveillance of vector-borne diseases. Both serological (ELISA IgM test and Plaque Reduction Neutralization Test-PRNT) and molecular assays (Real Time PCR tests, RT-PCR plus nested PCR and sequencing of positive samples) were performed. RESULTS: DENV infection was the most frequently diagnosed (80 confirmed/probable cases), and all four genotypes were detected. However, an increase in imported CHIKV cases (41 confirmed/probable cases) was observed, along with the detection of the first ZIKV cases (4 confirmed cases), as a consequence of the recent spread of both CHIKV and ZIKV in the Americas. CONCLUSIONS: Main diagnostic issues highlighted in our study are sensitivity limitations of molecular tests, and the importance of PRNT to confirm serological results for differential diagnosis of Arboviruses. The continuous evaluation of diagnostic strategy, and the implementation of laboratories networks involved in surveillance activities is essential to ensure correct diagnosis, and to improve the preparedness for a rapid and proper identification of viral threats

Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs

Background: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk