Autochthonous Dengue Fever in 2 Patients, Rome, Italy.

Since August 2023, outbreaks of dengue virus (DENV) infection have occurred in Italy. We report 2 autochthonous case-patients and their extended follow-up. Despite persistent DENV detected in blood by PCR, results for antigenomic DENV RNA were negative after day 5, suggesting that a 5-day isolation period is adequate to avoid secondary cases.

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.

Early Estimates of Monkeypox Incubation Period, Generation Time, and Reproduction Number, Italy, May-June 2022.

We analyzed the first 255 PCR-confirmed cases of monkeypox in Italy in 2022. Preliminary estimates indicate mean incubation period of 9.1 (95% CI 6.5-10.9) days, mean generation time of 12.5 (95% CI 7.5-17.3) days, and reproduction number among men who have sex with men of 2.43 (95% CI 1.82-3.26).

Infectious Toscana Virus in Seminal Fluid of Young Man Returning from Elba Island, Italy.

We report detecting infectious Toscana virus in the seminal fluid of a 25-year-old man from Italy returning from Elba Island. The presence of infectious virus in human semen adds Toscana virus to the long list of viruses detected in this genital fluid and indicates a potential for sexual transmission.

Epidemiological, clinical and virological characteristics of four cases of monkeypox support transmission through sexual contact, Italy, May 2022.

Since May 2022, an outbreak of monkeypox has been ongoing in non-endemic countries. We report four cases in Italy in young adult men reporting condomless sexual intercourse. The patients are in good clinical condition with no need for specific antiviral drugs. Biological samples from seminal fluid were positive for monkeypox viral DNA. For many other viruses found in semen there is no evidence of sexual transmission. The possibility of sexual transmission of monkeypox virus needs to be investigated.

[Impact of the COVID-19 epidemic on total and cause-specific mortality in Rome (Italy) in 2020]. / Impatto dell'epidemia di COVID-19 sulla mortalità totale e per causa a Roma nel 2020.

OBJECTIVES: to estimate the impact of the COVID-19 epidemic on total and cause-specific mortality in people residing and dead in the Municipality of Rome (Italy) in 2020, and to describe the causes of death of subjects with SARS-CoV-2 infection confirmed by molecular test. DESIGN: descriptive analysis of total and cause-specific mortality in 2020 in Rome and comparison with a reference period (2015-2018 for total mortality and 2018 for cause-specific mortality); descriptive analysis of cause-specific mortality in the cohort of SARS-CoV-2 infected subjects. SETTING AND PARTICIPANTS: 27,471 deaths registered in the Lazio mortality-cause Registry, relating to people residing and died in the municipality of Rome in 2020, 2,374 of which died from COVID-19.MAIN OUCOME MEASURES: all-cause mortality by month, gender, age group and place of death, cause-specific mortality (ICD-10 codes). RESULTS: in the municipality of Rome in 2020, an excess of mortality from all causes equal to +10% was observed, with a greater increase in the months of October-December (+27%, +56%, and +26%, respectively) in people aged 50+, with the greatest contribution from the oldest age groups (80+) who died in the nursing homes or at home. Lower mortality was observed in the age groups 0-29 years (-30%) and 40-49 years (-13%). In 2020, COVID-19 represents the fourth cause of death in Rome after malignant tumours, diseases of the circulatory system, and respiratory diseases. Excess mortality was observed from stroke and pneumonia (both in men and women), from respiratory diseases (in men), from diabetes, mental disorders, dementia and Parkinson's disease (in women). On the contrary, mortality is lower for all cancers, for diseases of the blood and haematopoietic organs and for the causes of the circulatory system. The follow-up analysis of SARS-CoV-2 positive subjects residing in Rome shows that a share of deaths (about 20%) reports other causes of death such as cardiovascular diseases, malignant tumours, and diseases of the respiratory system on the certificate collected by the Italian National Statistics Institute. CONCLUSIONS: the 2020 mortality study highlighted excesses for acute and chronic pathologies, indicative of possible delays in the diagnosis or treatment of conditions indirectly caused by the pandemic, but also a share of misclassification of the cause of death that is recognized as COVID-19 death.

[Mortality and impact of COVID-19 by citizenship in seven Italian Regions from the beginning of the pandemic to mid-July 2021]. / Mortalità per COVID-19 nella popolazione immigrata in sette Regioni italiane da inizio pandemia a metà luglio 2021.

OBJECTIVES: to quantify the variability of COVID-19 mortality from the beginning of the pandemic to mid-July 2021, in relation to the immigrant status and by Region and period. DESIGN: observational incidence study. SETTING AND PARTICIPANTS: the study population consists of the residents at the beginning of 2020 in seven Regions (Piedmont, Lombardy, Veneto, Emilia-Romagna, Tuscany, Lazio, Sicily) aged <=74 years. MAIN OUTCOME MEASURES: absolute frequency of deaths occurred in subjects who tested positive for SARS-CoV-2, crude and standardized rates (standard: Italian population at the beginning of 2020), and mortality rates ratios (obtained using Poisson models), by immigrant status and stratified by gender, Region of residence, and period. The study period was divided into 5 subperiods: 22.02.2020-25.05.2020, 26.05.2020-02.10.2020, 03.10.2020-26.02.2021, 27.02.2021-16.07.2021. RESULTS: the study includes more than one half of the Italian population and most of the immigrants residing in the country, who are younger than Italians and experienced fewer COVID-19 deaths. Deaths among those who tested positive varied greatly between Regions and periods; standardized rates showed considerable increases over time among immigrants. In terms of rate ratios, there were excesses among immigrant males in the third period (MRR: 1.46; 95%CI 1.30-1.65) and in the fourth period (MRR: 1.55; 95%CI 1, 34-1.81). Among immigrant females, there is an indication of lower risk in the third period (MRR: 0.79; 95%CI 0.65-0.97) and of greater risk in the fourth period (MRR: 1. 46; 95%CI 1.21-1.77). Finally, the effect is modified by the Region of residence, both in the third and in the fourth period for males and only in the fourth period for females. CONCLUSIONS: the risk of premature mortality due to COVID-19 is linked to immigrant status and with an intensity that varies by gender, Region, and period. More accessible tools for prevention, diagnosis and early healthcare can support immigrant communities in managing the risk factors linked to the spread of infections and, in particular, counteract their evolution into more severe disease outcomes.

Basic Reproduction Number of Chikungunya Virus Transmitted by Aedes Mosquitoes.

We estimated the weighted mean basic reproduction number (R0) of chikungunya virus based on outbreak size. R0 was 3.4 (95% CI 2.4-4.2) and varied for 2 primary chikungunya mosquito vectors: 4.1 (95% CI 1.5-6.6) for Aedes aegypti and 2.8 (95% CI 1.8-3.8) for Ae. albopictus.

SARS-CoV-2 Phylogenetic Analysis, Lazio Region, Italy, February-March 2020.

We report phylogenetic and mutational analysis of severe acute respiratory syndrome coronavirus 2 virus strains from the Lazio region of Italy and provide information about the dynamics of virus spread. Data suggest effective containment of clade V strains, but subsequently, multiple waves of clade G strains were circulating widely in Europe.

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.

COVID-19: viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection.

BACKGROUND: Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. METHODS: We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was carried out in order to provide a theoretic host-pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein-protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. RESULTS: Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. CONCLUSIONS: In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets.

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.

Clinical management of imported malaria in Italy: results from a national cross-sectional survey in 2015.

In Italy, malaria continues to be one of the most common imported parasitoses; therefore, continuous surveillance of epidemiological data and clinical management is needed. In 2016, the National Institute for Infectious Diseases 'Lazzaro Spallanzani' in Rome promoted a retrospective questionnaire-based survey to assess the clinical management of imported malaria cases in Italy in 2015. The questionnaire was sent to 104 Tropical and/or Infectious Diseases Units in the country, and 37 of them filled out and returned the questionnaires. A total of 399 malaria cases were reported in 2015, mostly caused by Plasmodium falciparum and imported from Africa. Malaria chemoprophylaxis was correctly used by a minority of patients. Most patients presented with uncomplicated malaria and were treated orally. In severe cases, intravenous artesunate or quinine alone or in combination were administered, although one third of these severe cases received oral treatment. This retrospective survey reveals a lack of homogeneity in management of malaria-imported cases in Italy. Improvement of malaria chemoprophylaxis, standardization of clinical management of malaria cases and harmonization of oral and intravenous drug availability are needed throughout the country.

[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.

Secondary Autochthonous Outbreak of Chikungunya, Southern Italy, 2017.

In 2017, a chikungunya outbreak in central Italy later evolved into a secondary cluster in southern Italy, providing evidence of disease emergence in new areas. Officials have taken action to raise awareness among clinicians and the general population, increase timely case detection, reduce mosquito breeding sites, and promote mosquito bite prevention.

Expanding Usutu virus circulation in Italy: detection in the Lazio region, central Italy, 2017 to 2018.

Blood donation screening for West Nile virus (WNV) was mandatory in the Lazio region in 2017 and 2018 (June-November) according to the national surveillance plan. In these years, all five donations reactive in WNV nucleic acid amplification tests harboured instead Usutu virus (USUV). Clade 'Europe 2' was identified in four blood donations and a 2018 mosquito pool. The cocirculation of WNV and USUV in Lazio warrants increased laboratory support and awareness of possible virus misidentification.

Unexpected human cases of cutaneous anthrax in Latium region, Italy, August 2017: integrated human-animal investigation of epidemiological, clinical, microbiological and ecological factors.

On 31 August, a veterinarian and a farmworker were hospitalised for skin lesions. Both had been exposed to a dead cow on 19 August on a farm near Rome, where eight further cattle died of confirmed anthrax later the same month. At admission, the first case showed a black depressed eschar and another smaller lesion on one hand. The second case presented deep infection of the skin, with involvement of both arms. Anthrax diagnosis was confirmed by detection of B. anthracis DNA in eschar fragments from both patients. T-cell specific immunity was studied by flow cytometry and Elispot assay after stimulation with B. anthracis secretome in blood samples collected from Case 1. Immunoglobulin production was detected by complement fixation assay. In Case 1, specific CD4+ T-cell activation was detected, without antibody production. Specific antibodies were detected only in the second patient with severe cutaneous illness. Both patients recovered. The two human anthrax cases were epidemiologically linked, but anthrax was not suspected at admission in either case. The veterinarian had initially unrecognised professional exposure and the exposed farmworker did initially not report exposure to affected animals. A One Health strategy integrating human and animal investigations was essential to confirm the diagnosis.

Relationship Between Viremia and Specific Organ Damage in Ebola Patients: A Cohort Study.

Background: Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage. Methods: We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilità Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated prothrombin time (aPTT), international normalized ratio (INR), creatinine, and blood urea nitrogen (BUN) were recorded. Patients were followed up from admission until death or discharge. Results: One hundred patients (49 survivors and 51 nonsurvivors) were included in the analysis. Unadjusted analysis to compare survivors and nonsurvivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in nonsurvivors than in survivors. Multivariable mixed-effects models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT, and INR. In contrast, no direct linear association was found between viremia and either creatinine, BUN, or bilirubin. Conclusions: This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not find strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease.

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.

Persistence of ZIKV-RNA in the cellular fraction of semen is accompanied by a surrogate-marker of viral replication. Diagnostic implications for sexual transmission.

As asymptomatic infections represent 80% of ZIKV-infected individuals, sexual transmission is a rising concern. Recent studies highlighted a preferential association of ZIKV with the cellular fraction (CF) of different specimen types. Our aim was to evaluate the presence of ZIKV-RNA in different body fluids, focusing on semen specimens to assess the ZIKV-RNA content in either the unfractionated sample, its CF or seminal plasma (SP). In addition, to establish if the presence of ZIKV genome was associated with active virus replication, we measured the levels of negative-strand ZIKV-RNA. ZIKV total-RNA was detected in blood, urine and unfractionated semen, and neg-RNA in semen CF and SP samples longitudinally collected from two ZIKV-positive men followed at the National Institute for Infectious Diseases "L. Spallanzani", Italy. In both patients, ZIKV total-RNA was detected in CF with ct values always lower than in the corresponding unfractionated samples, and was observed even in the CF from negative unfractionated semen samples. In Patient 2, neg-RNA was also detected in CF, suggesting ongoing viral replication. Our results demonstrate higher clinical sensitivity of CF as compared to whole semen testing, emphasizing the need to extend ZIKV-RNA testing to CF, to rule out virus presence and the possible risk of sexual transmission.