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).

Co-circulation of SARS-CoV-2 Alpha and Gamma variants in Italy, February and March 2021.

BackgroundSeveral SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains.AimWe aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility.MethodsWe conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains.ResultsThe Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55-1.57 times the level of historical lineages (95% CrI: 1.45-1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03-1.23) with complete immune evasion to 1.39 (95% CrI: 1.26-1.56) for complete cross-protection.ConclusionWe assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility.

Tracking the progressive spread of the SARS-CoV-2 Omicron variant in Italy, December 2021 to January 2022.

BackgroundThe SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021.AimTo comprehensively describe Omicron spread in Italy in the 2 subsequent months and its impact on the overall SARS-CoV-2 circulation at population level.MethodsWe analyse data from four genomic surveys conducted across the country between December 2021 and January 2022. Combining genomic sequencing results with epidemiological records collated by the National Integrated Surveillance System, the Omicron reproductive number and exponential growth rate are estimated, as well as SARS-CoV-2 transmissibility.ResultsOmicron became dominant in Italy less than 1 month after its first detection, representing on 3 January 76.9-80.2% of notified SARS-CoV-2 infections, with a doubling time of 2.7-3.3 days. As of 17 January 2022, Delta variant represented < 6% of cases. During the Omicron expansion in December 2021, the estimated mean net reproduction numbers respectively rose from 1.15 to a maximum of 1.83 for symptomatic cases and from 1.14 to 1.36 for hospitalised cases, while remaining relatively stable, between 0.93 and 1.21, for cases needing intensive care. Despite a reduction in relative proportion, Delta infections increased in absolute terms throughout December contributing to an increase in hospitalisations. A significant reproduction numbers' decline was found after mid-January, with average estimates dropping below 1 between 10 and 16 January 2022.ConclusionEstimates suggest a marked growth advantage of Omicron compared with Delta variant, but lower disease severity at population level possibly due to residual immunity against severe outcomes acquired from vaccination and prior infection.

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.

People living with undiagnosed HIV infection and a low CD4 count: estimates from surveillance data, Italy, 2012 to 2014.

Background and aimsLate HIV diagnosis is associated with onward HIV transmission, higher morbidity, mortality and healthcare costs. In Italy, more than half of people living with HIV were diagnosed late during the last decade, with a CD4 count < 350 cells/mm3 at diagnosis. We aimed to determine the number and characteristics of people living with undiagnosed HIV infection and low CD4 counts in Italy. Methods: Data on newly reported HIV diagnoses from 2012 -2014 were obtained from the national HIV surveillance system. We used the European Centre for Disease Prevention and Control HIV modelling tool to calculate the undiagnosed prevalence and yearly diagnosed fraction (YDF) in people with low CD4 count. Results: The estimated annual number undiagnosed HIV infections with low CD4 count was on average 6,028 (95% confidence interval (CI): 4,954-8,043) from 2012-2014. In 2014, most of the undiagnosed people with low CD4 count were men (82.8%), a third acquired HIV through sex between men (MSM) (35.0%), and heterosexual transmission (33.4%), respectively. The prevalence of undiagnosed HIV infection was 11.3 (95% CI: 9.3-14.9) per 100,000 residents ranging from 0.7 to 20.8 between Italian regions. Nationally the prevalence rate was 280.4 (95% CI: 173.3-450.2) per 100,000 MSM, 8.3 (95% CI: 4.9-13.6) per 100,000 heterosexual men, and 3.0 (95% CI: 1.4-5.6) per 100,000 women. The YDF was highest among heterosexual women (27.1%; 95% CI: 16.9-45.2%). Conclusions: These findings highlight the importance of improving efforts to identify undiagnosed HIV infections primarily among men, both MSM and heterosexual men.

In-depth analysis of compartmentalization of HIV-1 matrix protein p17 in PBMC and plasma.

HIV-1 p17 plays an important role in the virus life-cycle and disease pathogenesis. Recent studies indicated a high heterogeneity of p17. A high number of insertions in the p17 carboxy-terminal region have been more frequently detected in patients with non-Hodgkin lymphoma (NHL), suggesting a role of altered p17 in lymphomagenesis. Based on p17 heterogeneity, possible PBMC/plasma compartmentalization of p17 variants was explored by ultra-deep pyrosequencing in five NHL patients. The high variability of p17 with insertions at the carboxy-terminal region was confirmed in plasma and observed for the first time in proviral genomes. Quasispecies compartmentalization was evident in 4/5 patients. Further studies are needed to define the possible role of p17 quasispecies compartmentalization in lymphomagenesis.

Diagnostic performance of hepatitis E virus antigen assay in hepatitis E virus acute infection.

The aim of this study was to analyze the sensitivity of hepatitis E virus antigen (HEV-Ag) to determine acute E hepatitis. Ninety-four serum samples resulting anti-HEV IgM by DIA.PRO assay were analyzed with Wantai assay to check for HEV-Ag. Thirty samples were anti-HEV IgM positive and HEV-RNA positive, 19 samples harbored genotype 3, whereas 11 samples were genotype 1. Overall, 16% of anti-HEV IgM samples resulted HEV-Ag positive and 33.3% of HEV-RNA positive were also HEV-Ag positive. Among 64 HEV-RNA negative samples, 5 (7.8%) were HEV-Ag positive. The concordance of HEV-RNA and HEV-Ag was low (Cohen's Kappa=0.36). The Bland-Altman plot revealed a low agreement between HEV-RNA viral load and HEV-Ag, confirmed by a not significant Spearman's correlation coefficient (rho=0.137, p>0.05). Moreover, the HEV-Ag showed 100% specificity. In genotype 3f samples with a viral load >800 cp/ml HEV-Ag was positive in 80% of samples, whereas all patients harboring genotype 3e were HEV-Ag-negative irrespective of HEV-RNA viral load. Among genotype 1, HEV-Ag positivity was observed only in 27.7% patients and in all samples the viremia was >2000 cp/ml. These data suggest that anti-HEV IgM positivity represents the main biological marker of hepatitis E acute infection in clinical real life settings in developed countries.

Triple therapy for hepatitis C improves viral response but also increases the risk of severe infections and anaemia: a frequentist meta-analysis approach.

This meta-analysis assesses the efficacy and safety of triple therapy with either boceprevir or telaprevir compared to the standard of care (SoC), pegylated interferon plus ribavirin, in patients chronically infected with genotype 1 hepatitis C virus (HCV). We included 10 randomized controlled trials comprising 33 individual treatment arms which enrolled 5,312 subjects. Meta-analysis for sustained virologic response (SVR) provided evidence that triple therapy with either boceprevir or telaprevir increased response by 1.76 times (CI-95% 1.63-1.89) in comparison with SoC. However, heterogeneity was strong (I-2 79.7% p for heterogeneity <0.001). Meta-analyses for severe adverse reactions (SAE) indicated that triple therapy increased the risk of any SAE, severe anaemia and severe infections by 1.52 (CI-95% 1.23-1.88), 2.29 (CI-95% 1.49-3.52) and 1.87 (CI-95% 1.19-2.95) times, respectively, with no detectable heterogeneity. Additional analyses showed that the exposure to previous interferon treatment may explain all the heterogeneity found in the SVR meta-analysis. Meta-analysis for dose response found that both SVR and SAE have a direct log-linear association with telaprevir exposure. This study provides evidence that triple therapy with boceprevir and telaprevir can remarkably increase both the proportion of SVR and the occurrence of SAEs.

The decline of the 2022 Italian mpox epidemic: Role of behavior changes and control strategies.

In 2022, a global outbreak of mpox occurred, predominantly impacting men who have sex with men (MSM). The rapid decline of this epidemic is yet to be fully understood. We investigated the Italian outbreak by means of an individual-based mathematical model calibrated to surveillance data. The model accounts for transmission within the MSM sexual contact network, in recreational and sex clubs attended by MSM, and in households. We indicate a strong spontaneous reduction in sexual transmission (61-87%) in affected MSM communities as the possible driving factor for the rapid decline in cases. The MSM sexual contact network was the main responsible for transmission (about 80%), with clubs and households contributing residually. Contact tracing prevented about half of the potential cases, and a higher success rate in tracing contacts could significantly amplify its effectiveness. Notably, immunizing the 23% of MSM with the highest sexual activity (10 or more partners per year) could completely prevent new mpox resurgences. This research underscores the importance of augmenting contact tracing, targeted immunization campaigns of high-risk groups, and fostering reactive behavioral changes as key strategies to manage and prevent the spread of emerging sexually transmitted pathogens like mpox within the MSM community.

HIV incidence estimate combining HIV/AIDS surveillance, testing history information and HIV test to identify recent infections in Lazio, Italy.

BACKGROUND: The application of serological methods in HIV/AIDS routine surveillance systems to identify persons with recently acquired HIV infection has been proposed as a tool which may provide an accurate description of the current transmission patterns of HIV. Using the information about recent infection it is possible to estimate HIV incidence, according to the model proposed by Karon et al. in 2008, that accounts for the effect of testing practices on the number of persons detected as recently infected. METHODS: We used data from HIV/AIDS surveillance in the period 2004-2008 to identify newly diagnosed persons. These were classified with recent/non-recent infection on the basis of an avidity index result, or laboratory evidence of recently acquired infection (i.e., previous documented negative HIV test within 6 months; or presence of HIV RNA or p24 antigen with simultaneous negative/indeterminate HIV antibody test). Multiple imputation was used to impute missing information. The incidence estimate was obtained as the number of persons detected as recently infected divided by the estimated probability of detection. Estimates were stratified by calendar year, transmission category, gender and nationality. RESULTS: During the period considered 3,633 new HIV diagnoses were reported to the regional surveillance system. Applying the model, we estimated that in 2004-2008 there were 5,465 new infections (95%CI: 4,538-6,461); stratifying by transmission category, the estimated number of infections was 2,599 among heterosexual contacts, 2,208 among men-who-have-sex-with-men, and 763 among injecting-drug-users. In 2008 there were 952 (625-1,229) new HIV infections (incidence of 19.9 per 100,000 person-years). In 2008, for men-who-have-sex-with-men (691 per 100,000 person-years) and injecting drug users (577 per 100,000 person-years) the incidence remained comparatively high with respect to the general population, although a decreasing pattern during 2004-2008 was observed for injecting-drug-users. CONCLUSIONS: These estimates suggest that the transmission of HIV infection in Lazio remains frequent and men-who-have-sex-with men and injecting-drug-users are still greatly affected although the majority of new infections occurs among heterosexual individuals.

Modulating mental state recognition by anodal tDCS over the cerebellum.

Increasing evidence from neuroimaging and clinical studies has demonstrated cerebellar involvement in social cognition components, including the mentalizing process. The aim of this study was to apply transcranial direct current stimulation (tDCS) to modulate cerebellar excitability to investigate the role the cerebellum plays in mental state recognition. Forty-eight healthy subjects were randomly assigned to different groups in which anodal, cathodal, or sham tDCS (2 mA for 20 min) was delivered centering the electrode on the vermis to stimulate the posterior portion of the cerebellum. The ability to attribute mental states to others was tested before and after tDCS using a digital version of the 'Reading the Mind in the Eyes test', which includes visual perceptive and motor stimuli as control conditions. Correct response and reaction times (RTs) were recorded. The results revealed a significant reduction in RTs between the baseline and post-stimulation sessions after cerebellar anodal tDCS only for mental state stimuli (Wilcoxon test p = 0.00055), whereas no significant effect was found in the cathodal or sham conditions or for visual perceptive and motor stimuli. Overall, our study suggests that cerebellar anodal tDCS might selectively improve mental state recognition and constitute an effective strategy to positively modulate the mentalizing process.

Effectiveness of vaccination against SARS-CoV-2 Omicron variant infection, symptomatic disease, and hospitalization: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aims to assess the effectiveness of the current Sars-Cov2 vaccine regimens against Omicron infection. A secondary endpoint aims to investigate the waning effectiveness of primary vaccination against symptomatic infection and related hospitalization. RESEARCH DESIGN AND METHODS: The systematic review started on 1 December 2021 and was concluded on 1 March 2022. Random-effects frequentist meta-analyses and multiple meta-regressions were performed. RESULTS: In total, 15 studies are included in the quantitative synthesis. According to the meta-analysis results, the overall risk of Sars-Cov2 infection in vaccinated individuals is on average 31 · 5% lower than the infection risk in unvaccinated while vaccinated with one booster dose have a 70 · 4% risk reduction of Omicron infection compared to unvaccinated. In particular, one booster dose significantly decreases by 69% the risk of symptomatic Omicron infection with respect to unvaccinated. Six months after the primary vaccination, the average risk reduction declines to 22% against symptomatic infection and to 55% against hospitalization. CONCLUSIONS: Primary vaccination does not provide sufficient protection against symptomatic Omicron infection. Although the effectiveness of the primary vaccination against hospitalization due to Omicron remains significantly above 50% after 3 months, it dramatically fades after 6 months.

The effect of COVID-19 vaccination in Italy and perspectives for living with the virus.

COVID-19 vaccination is allowing a progressive release of restrictions worldwide. Using a mathematical model, we assess the impact of vaccination in Italy since December 27, 2020 and evaluate prospects for societal reopening after emergence of the Delta variant. We estimate that by June 30, 2021, COVID-19 vaccination allowed the resumption of about half of pre-pandemic social contacts. In absence of vaccination, the same number of cases is obtained by resuming only about one third of pre-pandemic contacts, with about 12,100 (95% CI: 6,600-21,000) extra deaths (+27%; 95% CI: 15-47%). Vaccination offset the effect of the Delta variant in summer 2021. The future epidemic trend is surrounded by substantial uncertainty. Should a pediatric vaccine (for ages 5 and older) be licensed and a coverage >90% be achieved in all age classes, a return to pre-pandemic society could be envisioned. Increasing vaccination coverage will allow further reopening even in absence of a pediatric vaccine.

Determinants of loss to care and risk of clinical progression in PLWH who are re-engaged in care after a temporary loss.

The risk of developing AIDS is elevated not only among those with a late HIV diagnosis but also among those lost to care (LTC). The aims were to address the risk of becoming LTC and of clinical progression in LTC patients who re-enter care. Patients were defined as LTC if they had no visit for ≥ 18 months. Of these, persons with subsequent visits were defined as re-engaged in care (RIC). Factors associated with becoming LTC and RIC were investigated. The risk of disease progression was estimated by comparing RIC with patients continuously followed. Over 11,285 individuals included, 3962 became LTC, and of these, 1062 were RIC. Older age, presentation with AIDS and with higher HIV-RNA were associated with a reduced risk of LTC. In contrast, lower education level, irregular job, being an immigrant and injecting-drug user were associated with an increased LTC probability. Moreover, RIC with HIV-RNA > 200 copies/mL at the re-entry had a higher risk of clinical progression, while those with HIV-RNA ≤ 200 copies/mL had a higher risk of only non-AIDS progression. Patients re-entering care after being LTC appeared to be at higher risk of clinical progression than those continuously in care. Active strategies for re-engagement in care should be promoted.

Demographic and socio-economic determinants of poor HIV-risk perception at first HIV diagnosis: analysis of the HIV Surveillance data, Italy 2010-2016.

INTRODUCTION: HIV infections in Italy has not undergone a substantial decline over recent years. For this reason, we analysed risk-factors and socio-economic indicators of HIV-risk perception in HIV surveillance data. METHODS: An observational study was conducted and HIV-risk perception was estimated on the basis of reasons for undergoing testing. Ordinal logistic models were applied with three groups of response corresponding to three ordered levels of HIV-risk perception. RESULTS: The study included 18 055 individuals: 27% with low, 40% moderate and 33% with high perception. A low risk perception was estimated in both areas, least deprived and highly deprived [Adjusted Odds Ratio (AOR) = 1.58, CI: 1.14-2.18 and AOR = 2.33, CI: 1.39-3.90]; for heterosexuals (AOR = 1.96, CI: 1.83-2.11), Injecting Drug Users (IDU) (AOR =1.82, CI: 1.59-2.08), low education (AOR = 1.74. CI: 1.20-2.54), age > 40 years (AOR = 1.59, CI: 1.50-1.69), males (AOR = 1.30, CI: 1.20-1.40). CONCLUSIONS: In Italy there is a high percentage of HIV-infected people with poor HIV-risk perception. Poorer HIV-risk perception was associated with both, least and high deprivation, low education, older age, male gender, heterosexual and IDU groups. Our results could be relevant to address targeted HIV testing policies at both local and national levels.

Acute Traumatic and Ischemic Spinal Cord Injuries Have a Comparable Course of Recovery.

Background. The relative rarity of ischemic compared with traumatic spinal cord injury (SCI) has limited a comparison of the outcomes of these conditions. Objective. To investigate the neurological and functional recovery of ischemic compared with traumatic acute SCI. Methods. Data were derived from the European Multicenter Study Spinal Cord Injury database. Patients with ischemic (iSCI) or traumatic SCI (tSCI), aged 18 years or older were evaluated at different time points from incidence: at about 1 month, 3 months, and 6 months. The neurological status was assessed at each time point by the International Standards for Neurological Classification of Spinal Cord Injury and the functional status by the Spinal Cord Independence Measure. Walking ability was evaluated by Walking Index for Spinal Cord Injury, 10-Meter Walk Test, and 6-Minute Walk Test. Because of the imbalances of the 2 groups in respect to size and lesion severity, a matching procedure according to age, neurological level, and severity of injury was performed. Outcomes evaluation was performed by means of a 2-way repeated-measures ANOVA. Results. The matching procedure resulted in 191 pairs. Both groups significantly improved from about 15 days after the lesion to 6 months. No differences were found in the course of neurological and functional recovery of iSCI compared with tSCI. Conclusions. This analysis from a representative cohort of participants revealed that from 15 days following the cord damage onward, the outcomes after iSCI and tSCI are comparable. This finding supports the potential enrolment of patients with acute iSCI into clinical trials from that point in time after the event and an evaluation up to 6 months afterward.

Household transmission and disease transmissibility of a large HAV outbreak in Lazio, Italy, 2016-2017.

A major outbreak of Hepatitis A Virus (HAV) has swept through Europe between mid-2016 and 2017, mainly within the community of men who have sex with men (MSM). Over the same period, about 1000 outbreak-related cases of acute Hepatitis A (AHA) were recorded in Lazio region, Italy. We calibrated a Bayesian model to reconstruct likely transmission events within all 44 households where multiple infections were recorded, representing a total of 103 cases from the HAV outbreak in Lazio. Based on information on the observed times of symptom onset, we estimated the probability distribution function of the HAV generation time and used it to compute the effective and instantaneous reproduction numbers for the considered outbreak from the overall epidemic curve (N = 998 cases). We estimated a mean generation time of 30.2 days (95%CI: 25.2-33.0) and an effective reproduction number of about 1.63 (95% CI: 1.35-1.94). Transmissibility peaked in January 2017, shortly before targeted awareness and vaccination campaigns were put in place by health authorities; however, transmission remained above the epidemic threshold until June 2017. Within households, children (0-15) and young adults (16-30) infected preferentially individuals of the same age class, whereas transmission within older age groups was substantially homogeneous. These results suggest that the implemented interventions were able to slow down HAV transmission, but not to bring it rapidly to a halt. According to our estimates of the HAV transmissibility, about 50% of the at-risk persons should be immunized to prevent similar outbreaks in the future. Our results also indicate spillover from community transmission to household members, suggesting the opportunity of vaccinating household contacts of cases to prevent further spread of the epidemics.

Non-inferiority versus superiority trial design for new antibiotics in an era of high antimicrobial resistance: the case for post-marketing, adaptive randomised controlled trials.

Antimicrobial resistance is one of the most important threats to global health security. A range of Gram-negative bacteria associated with high morbidity and mortality are now resistant to almost all available antibiotics. In this context of urgency to develop novel drugs, new antibiotics for multidrug-resistant Gram-negative bacteria (namely, ceftazidime-avibactam, plazomicin, and meropenem-vaborbactam) have been approved by regulatory authorities based on non-inferiority trials that provided no direct evidence of their efficacy against multidrug-resistant bacteria such as Enterobacteriaceae spp, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia cepacia, and Acinetobacter baumannii. The use of non-inferiority and superiority trials, and selection of appropriate and optimal study designs, remains a major challenge in the development, registration, and post-marketing implementation of new antibiotics. Using an example of the development process of ceftazidime-avibactam, we propose a strategy for a new research framework based on adaptive randomised clinical trials. The operational research strategy has the aim of assessing the efficacy of new antibiotics in special groups of patients, such as those infected with multidrug-resistant bacteria, who were not included in earlier phase studies, and for whom it is important to establish an appropriate standard of care.

The THI questionnaire: psychometric data for reliability and validity of the Italian version.

The main objective of this study was to determine reliability, validity, and reproducibility of the Italian version of the Tinnitus Handicap Inventory (THI) self-administered questionnaire aimed at evaluating the impact of tinnitus on the quality of life of subjects affected by this symptom. The questionnaire was presented to a sample of 443 subjects (285 men and 158 women; ages 19-86; mean age, 53) who were referred to our Tinnitus Centre in Rome and came from the entire national territory. All subjects reported as their main problem a tinnitus that had persisted for at least 6 months. Statistical analysis carried out on THI questionnaire results showed high internal consistency and reliability for the total scale (Cronbach's alpha = .94). Despite the poor number of items, the THI proved useful for the functional scale (0.86), the emotional scale (0.89), and the catastrophic scale (0.75).