Outbreaks of autochthonous Dengue in Lazio region, Italy, August to September 2023: preliminary investigation.

Between August and September 2023, three distinct autochthonous dengue virus transmission events occurred in Lazio, Italy, with the main event in Rome. The events involved three different dengue serotypes. No link with previous imported cases was identified. Here we describe the epidemiological and phylogenetic analysis of the first autochthonous cases and the implemented control actions. The multiple transmission events call for a strengthening of the vector control strategies and future research to better characterise the risk in countries like Italy.

Correction to: A challenging case of carbapenemase-producing Klebsiella pneumoniae septic thrombophlebitis and right mural endocarditis successfully treated with ceftazidime/avibactam.

The given names and family names of all authors were transposed in the original publication. The original article has been corrected.

A challenging case of carbapenemase-producing Klebsiella pneumoniae septic thrombophlebitis and right mural endocarditis successfully treated with ceftazidime/avibactam.

INTRODUCTION: The emergence of carbapenemase-producing Klebsiella pneumonia (KPC-Kp) has become a significant problem in terms of public health and clinical outcome in many hospitals in Southern Europe. Treatment options are usually limited and effective treatment of infections caused by these pathogens is a considerable challenge for clinicians. Ceftazidime-avibactam has been recently approved for the treatment of difficult-to-treat infections due to aerobic Gram-negative organisms in patients with limited treatment options. CASE REPORT: We reported the first case of KPC-Kp septic thrombophlebitis and right atrial endocarditis associated with metastatic lung abscesses successfully treated with a prolonged ceftazidime/avibactam plus ertapenem treatment course, suggesting that this combination therapy could be safe and effective for serious Gram-negative infections. Interestingly, we also observed an apparent discrepancy between clinical and microbiological courses: the patient became rapidly afebrile; hemodynamically stable and his procalcitonin levels showed a prompt decreasing trend. Nevertheless, blood cultures remained persistently positive for a prolonged period. CONCLUSION: In conclusion, ceftazidime-avibactam plus ertapenem was a safe and effective therapy of serious endovascular infection due to KPC-Kp. Moreover, in this setting, follow-up blood cultures might represent an irreplaceable tool to guide the therapy.

Autochthonous acute hepatitis E: treatment with sofosbuvir and ribavirin.

INTRODUCTION: Hepatitis E virus (HEV) is an emerging cause of autochthonous-acute-hepatitis and acute-on-chronic-liver-failure in western countries. Treatment is not routinely used, despite ribavirin has a good antiviral effect. In vitro sofosbuvir inhibits HEV replication, but clinical data are lacking. CASE REPORT: We report a case of acute-on-chronic-liver-failure due to HEV treated with sofosbuvir and ribavirin. The treatment was capable of rapidly inducing both HCV and HEV viral suppression. CONCLUSION: In conclusion, although more data are required before firm conclusions could be drawn, the combination of sofosbuvir and ribavirin in not immunosuppressed patients with acute hepatitis E may be able to clear HEV infection.

Lung Infections in Systemic Rheumatic Disease: Focus on Opportunistic Infections.

Systemic rheumatic diseases have significant morbidity and mortality, due in large part to concurrent infections. The lung has been reported among the most frequent sites of infection in patients with rheumatic disease, who are susceptible to developing pneumonia sustained both by common pathogens and by opportunistic microorganisms. Patients with rheumatic disease show a peculiar vulnerability to infectious complications. This is due in part to intrinsic disease-related immune dysregulation and in part to the immunosuppressive treatments. Several therapeutic agents have been associated to a wide spectrum of infections, complicating the management of rheumatic diseases. This review discusses the most frequent pulmonary infections encountered in rheumatic diseases, focusing on opportunistic agents, consequent diagnostic challenges and appropriate therapeutic strategies.

Anti-HBs seroconversion during treatment with entecavir in a patient with chronic hepatitis B virus infection on hemodialysis.

Hepatitis B (HBV) virus infection is one of the most important causes of liver disease in patients with end-stage renal failure on hemodialysis. The natural history of chronic HBV infection acquired in childhood starts with an immune tolerant phase, followed by an immune clearance phase that may lead to the inactive carrier state or the development of chronic liver disease. Information on antiviral therapy administered very early during the immune clearance phase are lacking and no data exist on the treatment of early immune activation in the hemodialysis setting. This report describes the case of a patient affected by end-stage renal failure and HBeAg-positive chronic HBV virus infection treated very early during the immune clearance phase of HBV infection with an adjusted-dose of nucleoside analogue entecavir. The patient achieved a very rapid HBV-DNA undetectability, anti-HBe, and anti-HBs seroconversion. This is the first report of antiviral therapy with entecavir started during the immune reactive phase of HBV infection in a patient on hemodialysis and it suggests that antiviral treatment can enhance the effects of host immune activation resulting in biochemical, serological, and viral response, even in end-stage renal failure patients with partial immunodeficiency. Antiviral therapy with entecavir in the setting of hemodialysis was safe and well tolerated.

Genomic and Epidemiologic Surveillance of SARS-CoV-2 in the Pandemic Period: Sequencing Network of the Lazio Region, Italy.

Since the beginning of the COVID-19 pandemic, large-scale genomic sequencing has immediately pointed out that SARS-CoV-2 has rapidly mutated during the course of the pandemic, resulting in the emergence of variants with a public health impact. In this context, strictly monitoring the circulating strains via NGS has proven to be crucial for the early identification of new emerging variants and the study of the genomic evolution and transmission of SARS-CoV-2. Following national and international guidelines, the Lazio region has created a sequencing laboratory network (WGSnet-Lazio) that works in synergy with the reference center for epidemiological surveillance (SERESMI) to monitor the circulation of SARS-CoV-2. Sequencing was carried out with the aims of characterizing outbreak transmission dynamics, performing the genomic analysis of viruses infecting specific categories of patients (i.e., immune-depressed, travelers, and people with severe symptoms) and randomly monitoring variant circulation. Here we report data emerging from sequencing activities carried out by WGSnet-Lazio (from February 2020 to October 2022) linked with epidemiological data to correlate the circulation of variants with the clinical and demographic characteristics of patients. The model of the sequencing network developed in the Lazio region proved to be a useful tool for SARS-CoV-2 surveillance and to support public health measures for epidemic containment.

A Whole Genome Sequencing-Based Epidemiological Investigation of a Pregnancy-Related Invasive Listeriosis Case in Central Italy.

Listeriosis is currently the fifth most common foodborne disease in Europe. Most cases are sporadic; however, outbreaks have also been reported. Compared to other foodborne infections, listeriosis has a modest incidence but can cause life-threatening complications, especially in elderly or immunocompromised people and pregnant women. In the latter case, the pathology can be the cause of premature birth or spontaneous abortion, especially if the fetus is affected during the first months of gestation. The causative agent of listeriosis, Listeria monocytogenes, is characterized by the innate ability to survive in the environment and in food, even in adverse conditions and for long periods. Ready-to-eat food represents the category most at risk for contracting listeriosis. This study presents the result of an investigation carried out on a case of maternal-fetal transmission of listeriosis which occurred in 2020 in central Italy and which was linked, with a retrospective approach, to other cases residing in the same city of the pregnant woman. Thanks to the use of next-generation sequencing methodologies, it was possible to identify an outbreak of infection, linked to the consumption of ready-to-eat sliced products sold in a supermarket in the investigated city.

Urinary metabolomics of HCV patients with severe liver fibrosis before and during the sustained virologic response achieved by direct acting antiviral treatment.

Hepatitis C virus (HCV) infection induces a long-term inflammatory response and oxidative-stress in the liver microenvironment, leading to hepatic fibrosis and metabolic alterations. Direct-acting-antiviral-agents (DAAs) induce HCV-clearance, even though liver damage is only partially restored. In this context, understanding the impact of viral-eradication on liver metabolic activities could allow optimizing the metabolic care of the patient. The present prospective longitudinal study aims at characterizing the urinary metabolic profile of HCV-induced severe liver fibrosis and the metabolic changes induced by DAAs and HCV-clearance by nuclear magnetic resonance-based metabolomics. The urinary metabolic profile of 23 HCV males with severe liver fibrosis and 20 age-matched healthy-controls was analyzed by NMR-based-metabolomics before starting DAAs, at the end-of-therapy, after one and three months of follow-up. The urinary metabolic profile of patients with severe liver fibrosis was associated to pseudouridine, hypoxanthine, methylguanidine and dimethylamine, highlighting a profile related to oxidative damage, and to tyrosine and glutamine, related to a decreased breakdown of aromatic aminoacids and ammonia detoxification, respectively. 1-methylnicotinamide, a catabolic intermediate of nicotinamide-adenine-dinucleotide, was significantly increased in HCV-patients and restored after HCV-clearance, probably due to the reduced hepatic inflammation. 3-hydroxy-3-methylbutyrate, an intermediate of leucine-catabolism which was permanently restored after HCV-clearance, suggested an improvement of skeletal muscle protein synthesis. Finally, 3-hydroxyisobutyrate and 2,3-dihydroxy-2-methylbutyrate, intermediates of valine-catabolism, glycine and choline increased temporarily during therapy, resulting as potential biomarkers of DAAs systemic effects.

Importance of Surveillance of New Delhi Metallo-Beta-Lactamase Klebsiella pneumoniae: Molecular Characterization and Clonality of Strains Isolated in the Lazio Region, Italy.

INTRODUCTION: New Delhi metallo-ß-lactamase producing Klebsiella pneumoniae (NDM-Kpn) strains have been causing healthcare-associated infections worldwide. The aim of this study was to describe the molecular mechanisms of antimicrobial resistance and to analyze the clonality of NDM-Kpn isolates collected between January 2019 and June 2020 from patients admitted to hospitals from the Lazio region, Italy. METHODS: We performed a retrospective cohort study. Whole-genome sequencing (WGS) was performed on all NDM-Kpn strains; clonality and genetic relationships were further investigated. RESULTS: During the surveillance period, 17 NDM-Kpn isolates were obtained from 17 patients admitted to seven different hospitals. Eight different sequence types (STs) were detected: ST147 (n = 4), ST383 (n = 4), ST15 (n = 3), ST11 (n = 2), ST17 (n = 1), ST29 (n = 1), ST307 (n = 1) and the newly identified ST4853 (n = 1). Genetic relationships were further investigated by the WGS-based core genome MLST (cgMLST) scheme, and 5 cluster types (CTs) were identified. Whereas a substantial overall heterogeneity among isolates was detected (8 different STs were identified out of 17 isolates), the strains within each cluster showed a very high level of genome similarity. DISCUSSION: Our study highlights the key role of surveillance, which allowed taking a picture of a part of the NDM-Kpn strains circulating in Italy, adding further insight into their molecular features.

A Nosocomial Outbreak of Invasive Listeriosis in An Italian Hospital: Epidemiological and Genomic Features.

Listeria monocytogenes (L. monocytogenes) is a widespread opportunistic pathogen that causes the listeriosis foodborne disease. This bacterium has become a common contaminant of handled food, and a relevant public health issue. Here we describe a nosocomial outbreak of listeriosis caused by an ST451 strain of L. monocytogenes involving three cancer and one immunocompromised patients hospitalized in different units from the same hospital during September and October 2020. The epidemiological investigation was conducted using traditional microbiological methodology combined with a whole genome sequencing approach. The source of contamination was identified in the kitchen hospital, where a meat slicer used to prepare patients' meals was tested positive to the same sequence type (ST) of L. monocytogenes. This is the first report of an outbreak of listeriosis caused by ST451 in Italy.

Impact of HCV Eradication on Lipid Metabolism in HIV/HCV Coinfected Patients: Data from ICONA and HepaICONA Foundation Cohort Study.

OBJECTIVES: HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use. METHODS: HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested. RESULTS: six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively (p < 0.001), after SVR, whereas there was no evidence for a change in HDL-C (p = 0.45) and triglycerides (p = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction-p value = 0.002). CONCLUSIONS: complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.

The Pregnancy Outcomes Among Newly Arrived Asylum-Seekers in Italy: Implications of Public Health.

BACKGROUND: Migration has a significant impact on overall health and pregnancy outcome. Despite the fact that growing volume of migration flows significantly engaging the public health system of European host countries, there is a lack of evidence concerning pregnancy outcomes of newly arrived asylum-seeking women. METHODS: Data about pregnant asylum seekers hosted in the Italian Reception Centers between the 1 st June 2016 and the 1st June 2018 were retrospectively collected and analysed in the present study. We examined the following pregnancy outcomes: miscarriage, self-induced abortion, voluntary pregnancy termination, live-birth; and studied potentially related socio-demographic factors. RESULTS: Out of the 110 pregnant women living in the reception centers, 44 (40%) had eutocic delivery, 8 (7.3%) dystocic delivery, 15 (13.6%) miscarriage, 17 (15.5%) self-induced abortion and 26 (23.6%) underwent voluntary pregnancy termination. Nigerian women were at a significantly higher risk of abortive outcomes for voluntary pregnancy termination (p < 0.001), miscarriage (p = 0.049) and self-induced abortion (p < 0.001). Being unmarried was significantly associated with voluntary pregnancy termination and self-induced abortion. Women who chose to undergo unsafe abortion did not result to have significantly lower educational levels, compared to women who preferred medical abortion. CONCLUSION: This study offers first insights into pregnancy outcomes among asylum-seeking women in Italy. The country of origin and marital status seem to significantly impact on pregnancy outcome. We identified sub-groups of migrant women at increased risk of abortive outcomes, and highlight the need to improve care in order to promote migrant women's reproductive health.

Virological and Serological Characterisation of SARS-CoV-2 Infections Diagnosed After mRNA BNT162b2 Vaccination Between December 2020 and March 2021.

BACKGROUND: Vaccines for coronavirus disease 2019 (COVID-19) are proving to be very effective in preventing severe illness; however, although rare, post-vaccine infections have been reported. The present study focuses on virological and serological features of 94 infections that occurred in Lazio Region (Central Italy) between 27 December 2020, and 30 March 2021, after one or two doses of mRNA BNT162b2 vaccine. METHODS: We evaluated clinical features, virological (viral load; viral infectiousness; genomic characterisation), and serological (anti-nucleoprotein Ig; anti-Spike RBD IgG; neutralising antibodies, nAb) characteristics of 94 post-vaccine infections at the time of diagnosis. Nasopharyngeal swabs (NPSs) and serum samples were collected in the framework of the surveillance activities on SARS-CoV-2 variants established in Lazio Region (Central Italy) and analysed at the National Institute for Infectious Diseases "L. Spallanzani" in Rome. RESULTS: The majority (92.6%) of the post-vaccine infections showed pauci/asymptomatic or mild clinical course, with symptoms and hospitalisation rate significantly less frequent in patients infected after full vaccination course as compared to patients who received a single dose vaccine. Although differences were not statistically significant, viral loads and isolation rates were lower in NPSs from patients infected after receiving two vaccine doses as compared to patients with one dose. Most cases (84%) had nAb in serum at the time of infection diagnosis, which is a sub-group of vaccinees, were found similarly able to neutralise Alpha and Gamma variants. Asymptomatic individuals showed higher nAb titres as compared to symptomatic cases (median titre: 1:120 vs. 1:40, respectively). Finally, the proportion of post-vaccine infections attributed either to Alpha and Gamma variants was similar to the proportion observed in the contemporary unvaccinated population in the Lazio region, and mutational analysis did not reveal enrichment of a defined set of Spike protein substitutions depending on the vaccination status. CONCLUSION: Our study conducted using real-life data, emphasised the importance of monitoring vaccine breakthrough infections, through the characterisation of virological, immunological, and clinical features associated with these events, in order to tune prevention measures in the next phase of the COVID-19 pandemic.

Follow-up blood cultures in Gram-negative bacilli bacteremia: are they needed for critically ill patients?

BACKGROUND: Gram-negative bacilli bacteremias (GNB-Bs) represent a major cause of morbidity and mortality in Intensive Care Unit (ICU) patients. Aim of this study was to investigate the role of follow-up blood cultures (FUBCs) and the clinical significance of persistent bacteremia (PB) in these settings. METHODS: We retrospectively analyzed clinical data and outcome of GNB-Bs that occurred in ICU patients over a span of 1 year. In particular we sought information on development and clinical details of PB, defined as repeatedly positive FUBCs after ≥96 hours of appropriate antibiotic treatment and ≥48 hours after removal of endovascular devices. RESULTS: Among 307 ICU patients, 69 (22.4%) developed 107 GNB-Bs. Of these, 78 (73%) could be eventually analyzed: 50 of 78 (64.1%) were non-PBs from 26 patients and 28 of 78 (35.9%) were PBs from 23 patients. Duration of fever and bacteremia, time to procalcitonin normalization and weaning from vasopressors were longer in episodes of PBs than non-PBs (P=0.04, P<0.001, P=0.02 and P=0.004, respectively). Primary bacteremia was more frequent in non-PBs than in PBs (29 of 50, 58% vs. 3/28, 10.7%, P=0.0001), whereas septic thrombus infection (STI) was the source of infection in 14 of 28 (50%). Finally, clinical features and 30-day mortality did not differ between patients with PB and those who developed only non-PB episodes. CONCLUSIONS: Among our ICU patients, more than one third of GNB-Bs for which FUBCs were performed resulted PB. This condition is often associated with the presence of STI; therefore, FUBCs seem useful for the optimal management of GNB in this clinical setting.