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.

A biohybrid synapse with neurotransmitter-mediated plasticity.

Brain-inspired computing paradigms have led to substantial advances in the automation of visual and linguistic tasks by emulating the distributed information processing of biological systems1. The similarity between artificial neural networks (ANNs) and biological systems has inspired ANN implementation in biomedical interfaces including prosthetics2 and brain-machine interfaces3. While promising, these implementations rely on software to run ANN algorithms. Ultimately, it is desirable to build hardware ANNs4,5 that can both directly interface with living tissue and adapt based on biofeedback6,7. The first essential step towards biologically integrated neuromorphic systems is to achieve synaptic conditioning based on biochemical signalling activity. Here, we directly couple an organic neuromorphic device with dopaminergic cells to constitute a biohybrid synapse with neurotransmitter-mediated synaptic plasticity. By mimicking the dopamine recycling machinery of the synaptic cleft, we demonstrate both long-term conditioning and recovery of the synaptic weight, paving the way towards combining artificial neuromorphic systems with biological neural networks.

Worldwide Effects of Coronavirus Disease Pandemic on Tuberculosis Services, January-April 2020.

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic.

Spatial modes for transmission of chikungunya virus during a large chikungunya outbreak in Italy: a modeling analysis.

BACKGROUND: The spatial spread of many mosquito-borne diseases occurs by focal spread at the scale of a few hundred meters and over longer distances due to human mobility. The relative contributions of different spatial scales for transmission of chikungunya virus require definition to improve outbreak vector control recommendations. METHODS: We analyzed data from a large chikungunya outbreak mediated by the mosquito Aedes albopictus in the Lazio region, Italy, consisting of 414 reported human cases between June and November 2017. Using dates of symptom onset, geographic coordinates of residence, and information from epidemiological questionnaires, we reconstructed transmission chains related to that outbreak. RESULTS: Focal spread (within 1 km) accounted for 54.9% of all cases, 15.8% were transmitted at a local scale (1-15 km) and the remaining 29.3% were exported from the main areas of chikungunya circulation in Lazio to longer distances such as Rome and other geographical areas. Seventy percent of focal infections (corresponding to 38% of the total 414 cases) were transmitted within a distance of 200 m (the buffer distance adopted by the national guidelines for insecticide spraying). Two main epidemic clusters were identified, with a radius expanding at a rate of 300-600 m per month. The majority of exported cases resulted in either sporadic or no further transmission in the region. CONCLUSIONS: Evidence suggest that human mobility contributes to seeding a relevant number of secondary cases and new foci of transmission over several kilometers. Reactive vector control based on current guidelines might allow a significant number of secondary clusters in untreated areas, especially if the outbreak is not detected early. Existing policies and guidelines for control during outbreaks should recommend the prioritization of preventive measures in neighboring territories with known mobility flows to the main areas of transmission.

Coronavirus disease (COVID-19) in a paucisymptomatic patient: epidemiological and clinical challenge in settings with limited community transmission, Italy, February 2020.

Data concerning the transmission of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) in paucisymptomatic patients are lacking. We report an Italian paucisymptomatic case of coronavirus disease 2019 with multiple biological samples positive for SARS-CoV-2. This case was detected using the World Health Organization protocol on cases and contact investigation. Current discharge criteria and the impact of extra-pulmonary SARS-CoV-2 samples are discussed.

[Spatial analysis for detecting clusters of cases during the COVID-19 emergency in Rome and in the Lazio Region (Central Italy)]. / Analisi spaziale per l'identificazione di cluster di casi durante l'emergenza COVID-19 a Roma e nel Lazio.

BACKGROUND: one of the most affected European countries by the COVID-19 epidemic is Italy; data show the strong geographical heterogeneity of the epidemic. OBJECTIVES: to propose an analysis strategy to ascertain the non-random nature of the spatial spread of COVID-19 cases infection and identify any territorial aggregations, in order to enhance contact tracing activities in specific areas of the Lazio Region (Central Italy) and a large urban area as Rome. METHODS: all cases of COVID-19 of the Lazio Region notified to the Regional Service for Epidemiology, Surveillance, and Control of Infectious Diseases (Seresmi) with daily updates from the beginning of the epidemic to April 27, 2020 were considered. The analyses were carried out considering two periods (the first from the beginning of the epidemic to April 6 and the second from the beginning of the epidemic to April 27) and two different levels of spatial aggregation: the entire Lazio region excluding the Municipality of Rome, where the 377 municipalities represent the area units, and the Municipality of Rome, where the area units under study are the 155 urban areas (ZUR). The Scan statistic of Kulldorff was used to ascertain the non-random nature of the spatial spread of infected cases and to identify any territorial aggregations of cases of COVID-19 infection, using a retrospective spatial analysis in two overlapping periods. RESULTS: analysis was conducted at regional level in the two survey periods and revealed the presence of 7 localized clusters. In the Municipality of Rome, a single cluster (Historic Centre) was identified in the first period which includes 7 urban areas, while in the second period two distinct clusters (Omo and Farnesina) were observed. CONCLUSIONS: Scan statistics are an important surveillance tool for monitoring disease outbreaks during the active phase of the epidemic and a useful contribution to epidemiological surveillance during the COVID-19 epidemic in a specific territory.

Early improvement of glycaemic control after virus clearance in patients with chronic hepatitis C and severe liver fibrosis: a cohort study.

HCV has been recognized as the cause of chronic hepatitis C (CHC) since 1990. CHC is associated with progressive liver damage and extrahepatic conditions. Direct antiviral agents (DAAs), approved in 2014, have shown effectiveness in eradicating HCV in most patients. However, little is known about the effect of viral eradication on hepatic and extra-hepatic damage. We performed a historical cohort study of patients with HCV-related liver diseases who achieved SVR from March 2015 to October 2016 at INMI Lazzaro Spallanzani liver Unit in Rome (Italy). Repeated measures of glycaemia were analysed through a multilevel analysis framework to assess short time kinetics of blood glucose level at different times after therapy and for different levels of HCV viremia. The analysis included 205 patients. A model assessing temporal kinetics and variation of glycaemia according to HCV viremia provided evidence that blood glucose levels significantly dropped in patients with diabetes achieving SVR. Most of the variations occurred at 3-5 weeks of therapy (-17.96 mg/dL; p<0.001) and in coincidence with HCV clearance (-13.92 mg/dL; p<0.001). A weak, non-statistically significant reduction was observed in normoglycemic patients. Our study provides evidence that DAAs therapy may significantly improve glycaemic control in patients with CHC achieving SVR even when liver diseases are already established.

Molecular Characterization of Autochthonous Chikungunya Cluster in Latium Region, Italy.

We report partial molecular characterization of isolates from an autochthonous chikungunya virus cluster in Latium Region. E1 sequences from 3 patients differ substantially from sequences from the 2007 outbreak in Italy and lack the A226V substitution associated with increased viral fitness in the Aedes albopictus mosquito vector.

Impact of new DAA therapy on real clinical practice: a multicenter region-wide cohort study.

BACKGROUND: Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. METHODS: The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient's level and random slope at the level of the time; i.e. either before or after therapy. RESULTS: Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient's baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12. CONCLUSION: Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis.

HIV rapid testing in community and outreach sites: results of a nationwide demonstration project in Italy.

BACKGROUND: Globally the access to HIV testing has greatly increased over the past 30 years. Nonetheless, a high proportion of people living with HIV remains undiagnosed, even in resource rich countries. To increase the proportion of people aware of their HIV serostatus and their access to medical care, several strategies have been proposed including HIV rapid test programs offered outside health facilities. The aim of this project was to evaluate the feasibility and efficacy of the HIV rapid testing offered in community and outreach settings in Italy. METHODS: We conducted a national demonstration project on HIV rapid tests offered in community and outreach settings, including nongovernmental organization (NGO) facilities, primary care services for migrants and low-threshold services or mobile units for drug users (DU services). HIV rapid test on oral fluid (OraQuick®; Orasure Technologies) was anonymously offered to eligible people who presented themselves at the selected sites. Those with reactive results were referred to a specialized outpatient unit for confirmatory testing and medical care. RESULTS: Over a period of six months a total of 2949 tests were performed and 45.2% of individuals tested had not been previously tested. Overall 0.9% (27/2949) of tested people had a preliminary positive test. In NGO facilities the positivity rate was 1%. All subjects who performed their confirmatory test were confirmed as positive. In services for migrants the positivity rate was 0.5 and 80% were referred to care (with 1 false positive test). In DU services we observed the highest positivity rate (1.4%) but the lowest linkage to care (67%), with 1 false positive test. CONCLUSION: Our project showed that the offering of an HIV rapid testing program in community and outreach settings in Italy is feasible and that it may reach people who have never been tested before, while having a significant yield in terms of new HIV diagnoses as well.

Enterovirus D68-Associated Acute Flaccid Myelitis in Immunocompromised Woman, Italy.

In Italy in 2016, acute flaccid myelitis developed in a woman who had received a hematopoietic stem cell transplant. Enterovirus D68 viral genome was detected in respiratory and cerebrospinal fluid samples, and the viral protein 1 sequence clustered with lineage B3. Immunocompromised adults may be at risk for enterovirus D68-associated neurologic complications.

An outbreak of chickenpox in an asylum seeker centre in Italy: outbreak investigation and validity of reported chickenpox history, December 2015-May 2016.

An outbreak of chickenpox occurred between December 2015 and May 2016 among asylum seekers in a reception centre in Latium, Italy. We describe the epidemiological and laboratory investigations, control measures and validity of reported history of chickenpox infection. Serological screening of all residents and incoming asylum seekers was performed, followed by vaccine offer to all susceptible individuals without contraindication. Forty-six cases were found and 41 were associated with the outbreak. No complications, hospitalisations or deaths occurred. Serological testing was performed in 1,278 individuals and 169 were found to be susceptible, with a seroprevalence of 86.8%. A questionnaire was administered to 336 individuals consecutively attending the CARA health post to collect their serological result. The sensitivity, specificity and the positive and negative predictive value (PPV and NPV) of the reported history of chickenpox were 45.0%, 76.1%, 88.3% and 25.6%, respectively. We observed an increasing trend for the PPV and decreasing trend for the NPV with increasing age. Our report confirms that, in the asylum seeker population, chickenpox history is not the optimal method to identify susceptible individuals. Our experience supports the need for additional prevention and control measures and highlights the importance of national and local surveillance systems for reception centres.

Three cases of Zika virus imported in Italy: need for a clinical awareness and evidence-based knowledge.

BACKGROUND: Since early 2015, a large epidemic of Zika Virus (ZIKV) is spreading across South and Central America. An association between congenital neurological malformations (mainly microcephaly), other neurological manifestations such as Guillain-Barrè Syndrome, and ZIKV infection is suspected. CASE PRESENTATION: Three confirmed cases of ZIKV in travelers returning from Brazil between May 2015 and January 2016 are described. All patients had mild symptoms with no neurological complications. CONCLUSIONS: An increasing awareness among clinicians about this emerging disease is advisable, both for the need to provide correct additional information to the patients and to travelers, with a special focus on pregnant women, and for the presence of the competent vector in Southern Europe.

Short-term economic impact of the Zika virus outbreak.

Zika virus (ZIKV) is mainly transmitted by mosquitoes bites. However, transmission by sexual contacts has been reported in 11 non endemic countries. The rapid spread of ZIKV in Latin American and Caribbean Countries (LCR), person-to-person transmission and perceived risk on people's well being can affect the emerging economies of LCR which historically dependent on truism. Here we present an analysis on economic outputs for assessing the current impact of ZIKV on markets. Our analysis show an unexpected resilience of LCR markets to international alerts. This positive response represents an opportunity to scale-up interventions for preventing the further spreading of the ZIKV epidemic.

Rapid and preemptive evaluation of individual anti-hepatitis C virus treatment outcome capability by a short-term autologous liver tissue culture system.

Hepatitis C virus (HCV) standard of care (SOC) therapy is not effective in a large percentage of patients and its efficacy may be evaluated only after several weeks. The aim of this work was to set up an in vitro liver culture assay able to preemptively predict SOC outcome by using residual liver samples from HCV patients. The in vitro response to SOC was found associated with the in vivo treatment outcome with a concordance of 100%. A wider clinical trial on a larger patient group is necessary to fully evaluate the impact of this procedure on the clinical management of untreated HCV patients.

Hepatitis E virus genotype 4 outbreak, Italy, 2011.

During 2011, 5 persons in the area of Lazio, Italy were infected with a monophyletic strain of hepatitis E virus that showed high sequence homology with isolates from swine in China. Detection of this genotype in Italy parallels findings in other countries in Europe, signaling the possible spread of strains new to Western countries.

HCV infected prisoners: should they be still considered a difficult to treat population?

BACKGROUND: The prevalence of chronic hepatitis C virus (HCV) infection in the Italian correctional population is estimated to be around 38%. In this setting HCV infection treatment is controversial because of several factors such as active drug substance abuse, psychiatric illness, length of treatment, risk of re-infection, poor adherence and low success rate. METHODS: A retrospective data review of 159 inmates, positive for anti-Hepatitis C virus (HCV) antibody, evaluated to National Institute for Infectious Diseases "L. Spallanzani" (INMI) from January 2006 to December 2009, was conducted to evaluate rate of completion (feasibility) and outcome efficacy of chronic Hepatitis C Virus (HCV) infection treatment with Pegylated Interferon and Ribavirin in five correctional facilities in Rome. RESULTS: Of the 159 inmates evaluated in the study period, 50, all male (median age 39 years) were treated. Twenty patients (40%) did not complete treatment: 15 showed no response and therapy was stopped, 5 patients (10%) interrupted treatment because of adverse reactions. The global feasibility was 60%. The overall sustained virologic response (SVR) was 50% (32% for genotype 1 and 68% for genotype other than 1). The main predictors of SVR at the Multivariable Logistic Regression Odds Ratio (MLR-OR) were a better pretreatment histological diagnosis (absence of bridging fibrosis or cirrhosis [MLR-OR 11.85; 95% CI 1.96-71.62) and a HCV genotype other than 1 (MLR-OR 5.87; 95% CI 1.49-23.17). CONCLUSIONS: Chronic HCV infection treatment in correctional facilities is feasible and effective and should be strongly recommended, in combination with preventive measures, in appropriately screened patients because it represents an important opportunity to treat a population with a high prevalence of chronic HCV infection among whom treatment options post incarceration may be limited.

The potential impact of routine testing of individuals with HIV indicator diseases in order to prevent late HIV diagnosis.

BACKGROUND: The aim of our work was to evaluate the potential impact of the European policy of testing for HIV all individuals presenting with an indicator disease, to prevent late diagnosis of HIV. We report on a retrospective analysis among individuals diagnosed with HIV to assess whether a history of certain diseases prior to HIV diagnosis was associated with the chance of presenting late for care, and to estimate the proportion of individuals presenting late who could have been diagnosed earlier if tested when the indicator disease was diagnosed. METHODS: We studied a large cohort of individuals newly diagnosed with HIV infection in 13 counselling and testing sites in the Lazio Region, Italy (01/01/2004-30/04/2009). Considered indicator diseases were: viral hepatitis infection (HBV/HCV), sexually transmitted infections, seborrhoeic dermatitis and tuberculosis. Logistic regression analysis was performed to estimate association of occurrence of at least one indicator disease with late HIV diagnosis. RESULTS: In our analysis, the prevalence of late HIV diagnosis was 51.3% (890/1735). Individuals reporting at least one indicator disease before HIV diagnosis (29% of the study population) had a lower risk of late diagnosis (OR = 0.7; 95%CI: 0.5-0.8) compared to those who did not report a previous indicator disease. 52/890 (5.8%) late presenters were probably already infected at the time the indicator disease was diagnosed, a median of 22.6 months before HIV diagnosis. CONCLUSIONS: Our data suggest that testing for HIV following diagnosis of an indicator disease significantly decreases the probability of late HIV diagnosis. Moreover, for 5.5% of late HIV presenters, diagnosis could have been anticipated if they had been tested when an HIV indicator disease was diagnosed.However, this strategy for enhancing early HIV diagnosis needs to be complemented by client-centred interventions that aim to increase awareness in people who do not perceive themselves as being at risk for HIV.

How habitat factors affect an Aedes mosquitoes driven outbreak at temperate latitudes: The case of the Chikungunya virus in Italy.

BACKGROUND: Outbreaks of Aedes-borne diseases in temperate areas are not frequent, and limited in number of cases. We investigate the associations between habitat factors and temperature on individuals' risk of chikungunya (CHIKV) in a non-endemic area by spatially analyzing the data from the 2017 Italian outbreak. METHODOLOGY/PRINCIPAL FINDINGS: We adopted a case-control study design to analyze the association between land-cover variables, temperature, and human population density with CHIKV cases. The observational unit was the area, at different scales, surrounding the residence of each CHIKV notified case. The statistical analysis was conducted considering the whole dataset and separately for the resort town of Anzio and the metropolitan city of Rome, which were the two main foci of the outbreak. In Rome, a higher probability for the occurrence of CHIKV cases is associated with lower temperature (OR = 0.72; 95% CI: 0.61-0.85) and with cells with higher vegetation coverage and human population density (OR = 1.03; 95% CI: 1.00-1.05). In Anzio, CHIKV case occurrence was positively associated with human population density (OR = 1.03; 95% CI: 1.00-1.06) but not with habitat factors or temperature. CONCLUSION/SIGNIFICANCE: Using temperature, human population density and vegetation coverage data as drives for CHIKV transmission, our estimates could be instrumental in assessing spatial heterogeneity in the risk of experiencing arboviral diseases in non-endemic temperate areas.