Do We Know the True Burden of Tick-Borne Encephalitis? A Cross-Sectional Study.

INTRODUCTION: Tick-borne encephalitis (TBE) is an acute human arboviral infection of the central nervous system caused by a virus that is transmitted to humans mainly by tick bites. TBE is endemic in Europe and has become an increasingly important public health concern in recent years. Cases of TBE in Italy have occurred mainly in the north-east and central parts of the country. Vaccination is recommended for people who live in or visit areas at higher risk of tick bites. OBJECTIVE: The aim of our study was to ascertain the burden of TBE in the Veneto Region (north-east Italy). METHODS: Cases of TBE occurring in the region from January 1, 2007, to December 31, 2018, were extracted from the database of the mandatory notification system (MNS) and from hospital discharge records (HDRs) of admissions relating to a diagnostic code 063 according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Capture-recapture methods were used to estimate the completeness of each data source (as a percentage of cases). Records including diagnostic codes 322.9 (Meningitis, unspecified) and 323.9 (Unspecified cause of encephalitis, myelitis, and encephalomyelitis) were also extracted from the HDR database. Municipalities were grouped by location, based on their elevation above sea level, as "mountains," "hills," or "lowlands". After selecting only the municipalities where cases of TBE had occurred, the proportion of cases of TBE out of the total cases of encephalitis and meningitis identified was calculated and used to estimate the number of cases of TBE potentially occurring in the municipalities that reported none. Then the observed and adjusted TBE rates per 100,000 population were calculated. RESULTS: During the 12 years considered, a total of 281 cases of TBE were identified; 155 emerged from the HDRs and the MNS, 89 only from the MNS database, and 37 only from the HDRs. The degree of completeness of the data was 93.0% for the MNS and HDRs combined, 80.8% for the MNS alone, and 63.6% for the HDRs alone. The observed annual rate of TBE in the Veneto in recent years was calculated at 0.48 per 100,000 population, with the highest standardized rate in the province of Belluno (5.95 per 100,000 population). A significant rising trend in the number of cases observed in the latest period (2015-2018) was apparent for the mountainous areas in the region (average annual percent changes: 43.7 [95% CI 19.0-73.5]). The number of cases peaked in the mountains in the month of June (0.89 per 100,000), in hilly areas in July (0.23 per 100,000) and in the lowlands in October (0.04 per 100,000). CONCLUSIONS: Our findings seem to confirm an underreporting of the cases of TBE and inadequate TBE surveillance in the Veneto, despite the clinical severity of the disease and the fact that it is mandatory to report all cases. The routine integration of different databases is crucial to the successful implementation and assessment of targeted prevention strategies and fundamental to public health decision-making on this issue.

High rate of transmission in a pulmonary tuberculosis outbreak in a primary school, north-eastern Italy, 2019.

Italy is a low-incidence country for tuberculosis (TB). We describe a TB outbreak in a primary school in north-eastern Italy, involving 10 cases of active pulmonary disease and 42 cases of latent infection. The index case was detected in March 2019, while the primary case, an Italian-born schoolteacher, was likely infectious since January 2018. Administration of a pre-employment health questionnaire to school staff with sustained contact with children should be considered in low-incidence countries.

Extended screening for infectious diseases among newly-arrived asylum seekers from Africa and Asia, Verona province, Italy, April 2014 to June 2015.

Background and aimManagement of health issues presented by newly-arrived migrants is often limited to communicable diseases even though other health issues may be more prevalent. We report the results of infectious disease screening proposed to 462 recently-arrived asylum seekers over 14 years of age in Verona province between April 2014 and June 2015. Methods: Screening for latent tuberculosis (TB) was performed via tuberculin skin test (TST) and/or QuantiFERON-TB Gold in-tube assay and/or chest X-ray. An ELISA was used to screen for syphilis. Stool microscopy was used to screen for helminthic infections, and serology was also used for strongyloidiasis and schistosomiasis. Screening for the latter also included urine filtration and microscopy. Results: Most individuals came from sub-Saharan Africa (77.5%), with others coming from Asia (21.0%) and North Africa (1.5%). The prevalence of viral diseases/markers of human immunodeficiency virus (HIV) infection was 1.3%, HCV infection was 0.85% and hepatitis B virus surface antigen was 11.6%. Serological tests for syphilis were positive in 3.7% of individuals. Of 125 individuals screened for TB via the TST, 44.8% were positive and of 118 screened via the assay, 44.0% were positive. Of 458 individuals tested for strongyloidiasis, 91 (19.9%) were positive, and 76 of 358 (21.2%) individuals from sub-Saharan Africa were positive for schistosomiasis. Conclusions: The screening of viral diseases is questionable because of low prevalence and/or long-term, expensive treatments. For opposing reasons, helminthic infections are probably worth to be targeted by screening strategies in asylum seekers of selected countries of origin.

Epidemiology of Strongyloides stercoralis in northern Italy: results of a multicentre case-control study, February 2013 to July 2014.

Strongyloides stercoralis is a soil-transmitted helminth widely diffused in tropical and subtropical regions of the world. Autochthonous cases have been also diagnosed sporadically in areas of temperate climate. We aimed at defining the epidemiology of strongyloidiasis in immigrants and Italians living in three northern Italian Regions. Screening for S. stercoralis infection was done with serology, confirmation tests were a second serological method or stool agar culture. A case-control approach was adopted and patients with a peripheral eosinophil count ≥ 500/mcL were classified as cases. Of 2,701 individuals enrolled here 1,351 were cases and 1,350 controls; 86% were Italians, 48% women. Italians testing positive were in 8% (97/1,137) cases and 1% (13/1,178) controls (adjusted odds ratio (aOR) 8.2; 95% confidence interval (CI): 4.5-14.8), while positive immigrants were in 17% (36/214) cases and in 2% (3/172) controls (aOR 9.6; 95% CI: 2.9-32.4). Factors associated with a higher risk of infection for all study participants were eosinophilia (p < 0.001) and immigration (p = 0.001). Overall, strongyloidiasis was nine-times more frequent in individuals with eosinophilia than in those with normal eosinophil count.

Human and entomological surveillance of West Nile fever, dengue and chikungunya in Veneto Region, Italy, 2010-2012.

BACKGROUND: Since 2010 Veneto region (North-Eastern Italy) planned a special integrated surveillance of summer fevers to promptly identify cases of West Nile Fever (WNF), dengue (DENV) and chikungunya (CHIKV). The objectives of this study were (i) To increase the detection rate of imported CHIKV and DENV cases in travellers from endemic areas and promptly identify potential autochthonous cases.(ii) To detect autochthonous cases of WNF, besides those of West Nile Neuroinvasive Disease (WNND) that were already included in a national surveillance. METHODS: Human surveillance: a traveler who had returned within the previous 15 days from endemic countries, with fever >38°C, absence of leucocytosis (leukocyte count <10,000 µL), and absence of other obvious causes of fever, after ruling out malaria, was considered a possible case of CHIKV or DENV. A possible autochthonous case of WNF was defined as a patient with fever >38°C for <7 days, no recent travel history and absence of other obvious causes of fever. Entomologic surveillance: for West Nile (WNV) it was carried out from May through November placing CDC-CO2 traps in five provinces of Veneto Region, while for DENV and CHIKV it was also performed around residences of viremic cases. RESULTS: Human surveillance: between 2010 and 2012, 234 patients with fever after travelling were screened, of which 27 (11,5%) were found infected (24 with DENV and 3 with CHIKV). No autochthonous case of DENV or CHIKV was detected. Autochthonous patients screened for WNF were 408, and 24 (5,9%) were confirmed cases. Entomologic surveillance: the WNV was found in 10, 2 and 11 pools of Culex pipiens from 2010 to 2012 respectively, in sites of Rovigo, Verona, Venezia and Treviso provinces). No infected Aedes albopictus with DENV or CHIKV was found. CONCLUSIONS: Veneto is the only Italian region reporting WNV human cases every year since 2008. WNV is likely to cause sporadic cases and unforeseeable outbreaks for decades. Including WNF in surveillance provides additional information and possibly an early alert system. Timely detection of DENV and CHIKV should prompt vector control measures to prevent local outbreaks.

Surveillance for West Nile, dengue, and chikungunya virus infections, Veneto Region, Italy, 2010.

In 2010, in Veneto Region, Italy, surveillance of summer fevers was conducted to promptly identify autochthonous cases of West Nile fever and increase detection of imported dengue and chikungunya in travelers. Surveillance highlighted the need to modify case definitions, train physicians, and when a case is identified, implement vector control measures.

Latent Tuberculosis Infection Cascade of Care among Asylum Seekers in Verona, Italy.

Our study aimed to assess latent tuberculosis infection (LTBI) prevalence, screening uptake, adherence to preventive treatment, and their predictors in a large cohort of asylum seekers. We retrospectively analysed data of migrants screened in 2015-2017 at the Migrant's Service in Verona, Italy. Sequential interferon-gamma-release-assay (IGRA) was performed to confirm only tuberculin-skin-test (TST) results ranking from 5 to 14 mm. Among 2,486 asylum seekers, screening adherence was 89.74% and LTBI prevalence was 28.8% (CI95% 27.0;30.5). Predictors of LTBI diagnosis were: male gender (OR 1.62), age 24 years or older (OR 1.47) and African origin (OR 1.78). Therapy completion rate was 69.6% and resulted associated with African origin (OR 1.75) and being older than 24 years (OR 2.89). Sequential IGRA testing, given its expensiveness, could be used to confirm only intermediate TST results, thus enabling further LTBI cases to be detected and avoiding unnecessary preventive treatments.

Emergence of Lyme borreliosis in the province of Verona, Northern Italy: Five-years of sentinel surveillance.

We investigated the epidemiology, clinical manifestations, laboratory data and antibiotic treatment of Lyme borreliosis in the province of Verona, Northern Italy, during the period 2015-2019. One hundred and 29 cases of Lyme borreliosis were diagnosed in a single hospital representing 27 % of all cases reported in the Veneto region in the same period. The mean annual incidence of Lyme borreliosis was 0.992/100,000 inhabitants. A peak incidence of 2/100,000 inhabitants was observed in 2018. Early localized Lyme borreliosis was the most common presentation (74 %), followed by early disseminated Lyme borreliosis (21 %). One possible early Lyme neuroborreliosis and two cranial neuropathies were diagnosed. IgM and/or IgG borrelia antibodies were positive in 90 % of the cases. This significant increase of Lyme borreliosis incidence in the province of Verona highlights the need to increase knowledge on its epidemiology and clinical manifestation among both the general population and clinicians to allow early diagnosis and treatment.

A One-Health evaluation of the burden of cystic echinococcosis and its prevention costs: Case study from a hypo-endemic area in Italy.

An integrated model, based on a One Health approach, was implemented to estimate the epidemiological and economic outcomes of cystic echinococcosis (CE) in Veneto region, an hypo-endemic area of Northern Italy, and the costs for its prevention. Data and information needed to populate the model were retrieved from published literature, official statistics, expert opinions, or actively searched through data mining (i.e., Hospital and slaughterhouse data), when fundamental data were not available. Human-health and animal-health costs, both public and private, were considered. The overall impact of CE in the study area was estimated in an yearly cost of about 0.5 million €, due to an average of 19.5 human hospitalized cases and about 200 infected animals among cattle and sheep, per year. The human:animal costs ratio was about 8:1. Most of the infected animals were autochthonous, while the identification of an autochthonous source of the infection for the human cases was extremely difficult, and unlikely in most cases. No specific action resulted to be in place for human surveillance, while veterinary surveillance accounted for a yearly cost of about 22,000 €. Sheepherders were found to pay privately an overall amount of around 2000 € for the preventive treatment of their dogs every year, but the applied protocol proved to be sub-optimal. The source of most of the human cases was likely external to the study area, and their economic impact accounts for a cost that is far exceeding that of surveillance and preventive actions in place in the veterinary sector. Although autochthonous human cases appeared to be very rare, the strengthening of preventive actions and surveillance systems can reduce the risk of their increment.

Socioeconomic Determinants in Vaccine Hesitancy and Vaccine Refusal in Italy.

Childhood vaccination has been a milestone in the control of infectious diseases. However, even in countries offering equal access to vaccination, a number of vaccine-preventable diseases have re-emerged. Suboptimal vaccination coverage has been called into question. The aim was to explore socioeconomic inequalities in vaccine hesitancy and outright refusal. Families with at least one child aged between 3 months and 7 years were involved through an online survey. Families were classified as provaccine, hesitant, or antivaccine. The association between socioeconomic determinants and hesitancy/refusal was investigated with a logistic-regression model. A total of 3865 questionnaires were collected: 64.0% of families were provaccine, 32.4% hesitant, and 3.6% antivaccine. Rising levels of perceived economic hardship were associated with hesitancy (adjusted odds ratio (AOR) from 1.34 to 1.59), and lower parental education was significantly associated with refusal (AOR from 1.89 to 3.39). Family economic hardship and parental education did not move in parallel. Economic hardship was a determinant of hesitancy. Lower education was a predictor of outright refusal without affecting hesitancy. These findings may serve as warnings, and further explanations of socioeconomic inequities are needed even in universal healthcare systems. Insight into these factors is necessary to improve convenience and remove potential access issues.

Effectiveness and Impact of the 4CMenB Vaccine against Group B Meningococcal Disease in Two Italian Regions Using Different Vaccination Schedules: A Five-Year Retrospective Observational Study (2014-2018).

BACKGROUND: A few years after the introduction in Italy of a four-component anti-meningococcal B vaccine (4CMenB), we evaluated the effectiveness and impact of vaccination in two regions using different schedules (2, 4, 6, 12 months in Tuscany vs. 7, 9, 15 months in Veneto) through an observational retrospective study. METHODS: Vaccination started in 2014 in Tuscany and in 2015 in Veneto; the data collected referred to the period 2006-2018 for Tuscany and 2007-2018 for Veneto. Cases of invasive meningococcal disease due to N. Meningitidis B were identified by culture and/or real-time PCR. RESULTS: In Tuscany, pre-vaccine incidence was 1.96 (95% CL 1.52; 2.40) and dropped to 0.62 (95% CL 0.60; 0.64) in the post-4CMenB era. Evaluating only vaccinated children, post-4CMenB incidence was 0.12 (95% CL 0.08; 0.15). In Veneto pre-vaccine incidence was 1.94 (95% CL 1.92; 1.96) and dropped to 1.34 (95% CL 1.31; 1.38) in the post-4CMenB era. In the vaccinated population, MenB incidence was 0.53 (95% CL 0.50; 0.56). Vaccine effectiveness was 93.6% (95% CL 55.4; 99.1) in Tuscany and 91.0% (95% CL 59.9; 97.9) in Veneto, with mean vaccine coverages of 83.9% and 81.7%, respectively. The overall impact (evaluating both vaccinated and unvaccinated children) was 0.68 (95% CL 0.10; 0.89) in Tuscany and 0.31 (95% CL -0.56; 0.69) in Veneto; the total impact (evaluating only vaccinated children) was 0.94 (95% CL 0.56; 0.99) and 0.90 (95% CL 0.57; 0.97), respectively. The relative case reduction (RCR) was 65% in Tuscany and 31% in Veneto. Considering the vaccinated population, the RCR was equal to 91% and 80%, respectively. CONCLUSION: In conclusion, 4CMenB appears to have a very high effectiveness in Italy; the impact of vaccination appears greater where the immunization program is started early.