1. IntroductionWest Nile virus (WNV) is a mosquito-borne RNA virus (genus Flavivirus, family Flaviviridae) that, since 1962 and similarly to other arboviruses (e.g., tick-borne encephalitis virus or TBEV) [1,2], has progressively become endemic in large areas of continental Europe [3,4,5,6,7,8], where it is mainly carried by endogenous mosquito species of the genus Culex (C. pipiens, C. peregrinus, and C. modestus) [7,9,10], with a more limited role for Aedes spp. [11,12,13]. Arthropod vectors then sustain the enzootic “amplification” cycle within the main hosts, migratory birds [5,6,7,9,14]. Even though WNV can infect mammalians, including humans, and particularly large mammalians such as horses, the latter only represent incidental and dead-end hosts, as the viremia that WNV infections can reach in mammalians is insufficient to sustain an amplification cycle [9]. Nonetheless, interhuman transmission has been reported, but only through blood transfusion or organ transplants, with significant consequences from a public health point of view, but a limited role on the epidemiology of WNV infections [8,9,15,16,17,18,19].Human WNV infections usually follow the bite of infected mosquitos, exhibiting a distinctive seasonal trend from April to November, which mirrors the ecology of hosts and vectors [20,21]. Most of cases are usually asymptomatic; however, according to available statistics, up to 20% of them may develop a mild influenza-like syndrome: West Nile fever (WNF) [22,23]. Eventually, an even lesser share of WNV infection cases (around 1% of all cases) may develop a neuroinvasive disorder, i.e., West Nile neuroinvasive disease (WNND), whose main risk factors are represented by belonging to older age groups, being affected by chronic diseases such as solid tumors and chronic kidney disease, and immunodeficiency [22,23,24,25]. After the first outbreak in the Tuscany region in 1998, WNV subsequently re-emerged in eight provinces from three regions of Northern Italy (i.e., Lombardy, Emilia-Romagna, and Veneto) during 2008 [19,26,27,28,29]; and since 2010, Northern Italy has become one of the most heavily affected areas in the European Union, with new cases of WNV/WNF and WNND regularly reported every year [8,19,30,31]. Geographic and climatic factors that are particularly favorable to the mosquito vectors of WNV are commonly present in large areas of Northern Italy, and particularly in the Po River Valley, an area including 5 out of 20 Italian regions (Piedmont, Lombardy, Veneto, Emilia-Romagna, and Friuli-Venezia Giulia), and around 41.9% of total Italian population [19,32]. The high occurrence of WNV infections has therefore prompted the implementation of the National WNV Surveillance Plan, which consists of environmental and epidemiological surveillance by integrating veterinary, entomological, and epidemiological data, and includes the routinary screening of WNV in blood samples for transfusion [10,26,27]. The underlying framework of the National Surveillance Plan is guaranteeing the early identification of WNV in the environment [33,34,35], among suitable vectors (i.e., mosquitoes), and main hosts (birds, horses), allowing for the prompt implementation of mitigation measures for reducing the risk of viral transmission through blood transfusions and blood donations by implementing systematic individual blood donation nucleic acid amplification tests (NAAT) until the end of transmission season [26,27,28,36,37].According to a recently published review [19], a total of 1145 WNV infection cases were diagnosed between 2012 and 2020, for an incidence rate ranging between 0.090 cases per 100,000 persons (95% confidence intervals [95%CI] % 0.068 to 0.118) to 1.009 per 100,000 persons (95%CI 0.930 to 1.092), with 42.5% of them developing WNND. The very high share of WNND cases over the total of notified of WNV infections, as well as the particularly high detection rates among blood donors (annual incidence rates ranging between 1.353 cases per 100,000 specimens, 95% confidence intervals [95%CI] 0.279–3.953, to 19.069; 95%CI 13.494 to 26.174) led the authors to suspect a substantial underreporting of milder cases. After a relatively reduced notification of new incident cases during calendar year 2020 and 2021 [38,39], summer season 2022 was characterized by the unprecedented peak of new diagnoses of WNV, WNF, and complicated WNND [40,41,42]. For instance, by end of August 2022, a total of 440 WNV infections had been officially reported (49.0% of them characterized as WNND, 33.9% WNF), with 24 deaths [43].Despite the increasing relevance of WNV as a human pathogen [8], and promising results from veterinary vaccines [44], neither human vaccines nor specific antiviral treatments have been licensed to date [45,46], and treatment options remain currently limited to the symptomatic care, benefiting from early and proper diagnosis from involved medical professionals [17,23]. As the physicians’ understanding of a certain disorder is also critical in modeling the acceptance of clinical options, including preventive practices where available [32,47,48], we specifically inquired a sample of Italian medical professionals on their understanding of WNV infections and tentative vaccines. Our aim is to characterize whether the extensive knowledge gaps that were previously identified [48] in the general population from endemic areas [32], as well as in a sample of occupational physicians [48], were also shared by medical professionals that could potentially care for incident WNF infection cases. 4. DiscussionIn the present cross-sectional study performed on 254 Italian medical professionals during summer season 2022, WNV infections were associated with a relatively unsatisfying knowledge status (with a potential range 0 to 100%, actual GKS was estimated to an average of 59.6% ± 16.0). Risk perception and knowledge status were not only correlated (Spearman’s rho = 0.156; p value = 0.013), but scoring a better knowledge status was identified as a positive effector for reporting higher risk perception (aOR 2.92, 95%CI 1.60 to 5.30). Still, even though the present study was performed during an unprecedent reporting season for WNV [41,42], participants were characterized by a relatively low risk perception (RPS 37.7% ± 17.5). In fact, WNV infections were generally considered as a lesser threat for public health than more “conventional” pathogens such as Mycobacterium tuberculosis and HIV, as well as SARS-CoV-2. Even though the potential burden of WNV infections was perceived akin to that associated with an important pathogen such as seasonal influenza, the latter is often underscored as a relatively indolent disorder, not only in the general population but also among Italian medical professionals [50,51,52], and the correspondent vaccine has been in turn often discredited by media [53,54,55,56,57,58,59]. A possible explanation may be found in the coverage of conventional and new media on the ongoing WNV outbreak in Northern Italy [40,41,42]. While an accurate measurement of the qualitative and quantitative coverage of a specific topic by conventional media remains particularly difficult to achieve, with obvious consequences on the eventual modeling of knowledge, beliefs, and perceptions of targeted study group, a proxy for new media has been developed and provided by GoogleTM through Google Trends™ and the calculation of relative search volumes (RSV). Google TrendsTM is an open online tool developed by GoogleTM for reporting web interest in a specific keyword or search topic [60,61,62]. Research interest is reported as RSV, which is a normalized value ranging from 0 to 100 and proportional to the ratio between the keyword-related queries and the total of web queries. Therefore, in order to rule out the potential bias represented by the overreporting of WNV in conventional media, we assessed whether any correlation did exist between knowledge status and risk perception on the one hand, and RSV on WNV from 1 August to 10 September 2022 (i.e., the exact timeframe where the web survey was made available) on the other hand. Eventually, during the study period, no substantial correlation with RSV on WNV was found for RPS (Spearman’s rho = 0.048; p = 0.451), GKS (rho −0.078, p = 0.217), and even for the perceived disease burden (rho = 0.041, p = 0.419 Figure A1) [61,62]. In other words, knowledge status, risk perception, and perceived disease burden of study participants were not seemly influenced by media coverage.In fact, higher risk perception was also associated with individual factors such as reporting a seniority ≥ 10 years (aOR 2.39, 95%CI 1.34 to 4.28), having previously managed cases of WNV infections (aOR 3.65, 95%CI 1.14 to 14.20), being favorable towards a hypothetic vaccine (aOR 2.16, 95%CI 1.15 to 4.04), and perceiving WNV infections as potentially affecting daily activities (aOR 2.57, 95%CI 1.22 to 5.42). Interestingly enough, the majority of respondents was either favorable or even highly favorable to receiving a hypothetical WNV vaccine, but the share of uninterested respondents was substantial (around 1/5 of the whole sample). As an effective vaccine against WNV is still unavailable [46,63], having inquired the attitudes towards a tentative vaccine may appear somehow marginal to the main objectives of the present study (i.e., assessing KAP of Italian medical professionals on WNF infections), but there is an extensive base of evidence that a more positive attitude towards a certain vaccine is in turn associated with a better understanding of the prevented infectious diseases, and a more appropriate awareness of potential issues associated with communicable disorders [47,64,65]. Also in our study, exhibiting a positive attitude towards a tentative vaccine was characterized as a substantial affector of higher risk perception, being not only associated with higher knowledge status (See Table A3), but also with a proactive attitude towards immunizations for other infectious diseases such as SIV and SARS-CoV-2.When dealing with our results, it should be stressed that the present study was deliberately designed in order to assess the actual understanding of epidemiological, clinical, and diagnostic features of WNV infections among Italian healthcare providers. Therefore, we did not inquire of study participants about common behavioral and environmental preventive options [32,48], whose knowledge and eventual acceptance has been previously inquired about in previous reports targeting both general population and selected occupational groups, including Italian occupational physicians [48,66,67,68,69]. This design was motivated by the lack of similar studies on medical professionals, and particularly from endemic areas of continental Europe. Even though WNV has progressively become an endemic pathogen to Northern Italy, and particularly to the Po River Valley [27,28,30,42,70,71,72,73], the actual understanding of WNV infections among Italian healthcare providers has been only scarcely inquired. Shortly before the inception of SARS-CoV-2 pandemic, a KAP study on 174 Italian occupational physicians [48] identified a relatively satisfying understanding of WNV infections and their preventive measures, still stressing the extensive underestimation of their actual occurrence in the general population and their severity as well. Despite a similar working definition for the risk perception, medical professionals participating into the present study reported a substantially higher risk perception on the potential severity of WNV infections, which was acknowledged as a severe one by 48.4% of participants compared to 8.6% of the previous survey. On the contrary, while in 2019 around 30.5% of respondents acknowledged WNV infections as frequent or highly frequent, the correspondent share dropped to 17.7% in the present study. Some explanations may be found in the characteristics of targeted professionals [74,75], as the individual expertise of occupational physicians—medical professionals primarily involved in health surveillance and preventive interventions in the workplaces—can be hardly compared to that of other medical professionals [47,48,75,76,77]. Another substantial factor could be identified in the decrease in notification rates for WNV infections between 2020 and 2021 [19,38,39], which was then followed by the unprecedented reporting season 2022, which was also characterized by a particularly high case fatality ratio [40,41,42]. In other words, after two reporting seasons with a low or even a very low circulation of the pathogen, participants may have been led to the perception of WNV as a relatively uncommon disorder, while the high lethality reported in 2022 could have inflated the perceived severity of WNV infections.Not coincidentally, higher risk perception was associated with reporting greater seniority and with having any previous experience in the management of WNV infection cases. This latter remark is both consistent with some previous KAP studies on WNV infections [32,48,67,69] and with the underlying Health Belief Model (HBM) [78,79]. HBM was originally developed in the 1950s but remains one of the most widely used theories in health behavior research [80,81,82]. Its basic assumption is that the beliefs about the susceptibility to a certain health threat, correspondent perceptions on the potential severity of that threat, and perceived benefits (and conversely, barriers) associated with a particular intervention will determine whether or not an individual would adopt that action [83,84]. Interestingly enough, usual proxies for the better understanding of health threats and appropriate preventative options, such as the acceptance of certain vaccinations (e.g., SIV and SARS-CoV-2), were unrelated with higher risk perception for WNV infections [85,86,87,88]. Conversely (see Appendix A Table A3), both practices were associated with a favorable attitude towards a tentative WNV vaccine, alongside any previous interaction with WNV infections, which is consistent with HBM and currently acknowledged models for antecedents of vaccinations [65,80,81].Limits. Despite its potential interest, the present article is affected by several limitations. First of all, the overall sample is quite small when compared not only to the whole of the Italian medical workforce (i.e., around 650,000 individuals in 2019) [89] but also to the potentially targeted medical professionals, as it included only 2.9% of individuals participating into the parent discussion group. Even though we were able to collect a total of 254 participants, potentially satisfying initial estimates for a minimum sample [48], the present study was hardy generalizable, for several reasons. For one, the sample size was calculated on the only KAP study on WNV infections previously performed on Italian medical professionals, but it only included occupational physicians, whose familiarity with WNV is hardly comparable with that of other caregiver workplaces [90,91], and whose representativity of the general medical workforce may be also reasonably questioned [47,91,92,93]. Moreover, Italy is characterized by distinctive regional patterns in background healthcare settings, and even in school-specific training during the residency programs [88]; as our study was characterized by a certain oversampling of participants from areas considered at higher risk for WNV infections, a potential overestimation of perceived burden of disease and risk perception cannot be ruled out. Still, as our study was performed during an unprecedented outbreak of WNV infections in the whole of the country [19,40,41,42], the present study may contribute to our understanding of baseline knowledge, attitudes and practices of medical professionals involved in the early identification and monitoring of this potentially serious infectious disease. As the large majority of WNV infections cases may occur without suggestive clinical signs and symptoms [17,23,94,95,96], assessing the actual understanding of WNV among healthcare providers may contribute to a better appreciation of the effective burden of disease in the general population [8,17,18,97].Second, the present survey was designed as a web-based one, and this design is notably affected by several shortcomings, most notably including the potential “self-selection” of participants [98,99], and particularly those having greater familiarity with the Internet and social media, and more easily sharing personal information through the Internet and social media. In this regard, the mean age of our final sample was well under 40 years, with a reduced share of respondents aged 50 year or older, and these estimates are quite inconsistent with the demographics of the Italian medical workforce [89,100]. It is therefore reasonable that having targeted medical professionals participating in an internet discussion group may have led to the preventive selection of younger individuals that may fail to be representative of all Italian medical professionals, urging a very cautious interpretation of our results in more general terms. Likewise, having inquired a very specific topic (i.e., West Nile virus infection), the potential oversampling of subjects that were more familiar with the assessed topic than those not participating into the study is quite reasonable [98], as suggested by similarly designed cross-sectional studies [51,93,101].

Third, as the questionnaire was not externally validated, we cannot rule out that some of the respondents did not fully adhere to our inclusion, with a further impairment in the representativity of the sample. Nonetheless, discussion groups involved in the recruitment of the study participants did perform a preventive selection of their members by only including qualified medical professionals and eventually improving the reliability of our sample, at least when dealing with two of three inclusion criteria (i.e., being a licensed medical professional, and living and working in Italy).

Fourth, we cannot rule out that our results may have been influenced by some shortcomings in the implementation of current evidence in the Italian guidelines for WNV/WNF/WNND surveillance. More precisely, the Italian case definition of WNF has been recently revised and implemented in the Italian National Plan for the Prevention, Surveillance, and Response to Arboviruses 2020–2025 [102], consistently with the updated EU case definition [103]. Notably, the revised case definition acknowledged that fever does not represent an invariable and necessary feature of WNF [104], but only half of participants had any awareness that WNF may occur without noticeable fever. As the corresponding item in the knowledge test is clearly counter-intuitive, it possibly reflects the actual understanding of this topic by participants, that in turn may represent a lack of knowledge on the current medical evidence, or the misunderstanding of official guidelines. Interestingly, while the current EU case definition includes as clinical criteria for WNV infection at least one of the following three [103]: fever, encephalitis, and meningitis, correspondent Italian guidelines seemingly prioritize fever over encephalitis, meningitis, neuritis, and acute flaccid paralysis, the latter being considered alternative to the primary feature of fever [102].Fifth, it is important to stress that the epidemiology of WNV in Italy should be ascertained in the more complex framework of flavivirus infections, whose understanding may be scarcely appreciable for professionals not involved in the prevention of infectious diseases, and particularly when dealing with laboratory diagnosis [2,19,39,105,106]. Flavivirus are structurally quite similar, which leads to some crossreactivity upon infection [107]. In Italy, viral pathogens such as Zika, dengue and yellow fever viruses are mostly associated with travel-related infections [108,109,110,111], but autochthonous transmission of dengue has recently occurred in the Veneto Region [112], and cocirculation of WNV and TBEV in the same Italian regions has been documented [19,106,108]. Even though a substantial share of diagnoses are based on serology, medical professionals should be aware that the very same National Guidelines warn about the potential impact of previous interactions with other flaviviruses, either as previous infections or vaccinations, recommending the preferential referral to molecular diagnostics (i.e., nucleic acid amplification test or NAAT) in certain settings, e.g., blood donors from high-risk areas [102]. As a consequence, participants with a limited understanding of these features of flavivirus infections may have improperly underestimated the potential lack of specificity of serology in Italian settings (and particularly in the Veneto Region, where a potential cocirculation of WNV, dengue virus, and TBEV cannot be ruled out a priori) [29,108,113]. On the other hand, international readers should be particularly careful in the generalization of this item of the knowledge test and of its meaning, particularly in settings where WNV is the main or even the sole circulating flavivirus.

Eventually, despite the knowledge score and risk perception score being seemingly unaffected by background media coverage on the ongoing WNV outbreak, our estimates should be acknowledged as strictly dependent on the exact timeframe of this study, while we cannot rule out that a follow-up study would lead to a very different outcome.