Naturally developed HPV16 antibodies and risk of newly detected cervical HPV infection outcomes.

Little is known about the protection conferred by antibodies from natural human papillomavirus (HPV) infection. Our objective was to evaluate the association between HPV16 seroreactivity and HPV16 redetection, newly detected HPV infections, and loss of HPV DNA detection during follow-up. We analyzed data from 2462 unvaccinated Brazilian women. HPV16 IgG and neutralizing antibodies at baseline were assessed by enzyme-linked immunosorbent assay (n = 1975) and by the pseudovirus-based papillomavirus neutralization assay (n = 487). HPV detection, genotyping, and viral load were assessed by PCR-based methods. The associations were analyzed by Cox proportional hazards models. We observed a positive association between HPV16 IgG seroreactivity and redetection of HPV16 infections. Age-adjusted hazard ratios (HR) with 95% confidence intervals (CI) ranged from 2.45 (1.04-5.74) to 5.10 (1.37-19.00). Positive associations were also observed between HPV16 IgG antibodies and (1) newly detected HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.32 [1.08-1.2]) and (2) loss of detection of HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.24 [1.03-1.50]). Naturally developed HPV16 antibodies do not prevent recurrent HPV infections. Overall HPV16 IgG and neutralizing antibodies seem to be serological markers for latent or past infections.

Do we protect ourselves against West Nile Virus? A systematic review on knowledge, attitudes, and practices and their determinants.

BACKGROUND: West Nile virus (WNV) is a mosquito-borne flavivirus. In humans, 80% of infections are asymptomatic, while approximately 20% experience influenza-like symptoms. Fewer than 1% develop the neuroinvasive form which can lead to encephalitis, meningitis, acute flaccid paralysis, and even death. The global spread of the virus to areas where it was not previously present has become a growing concern. Since the 2000 s, there have been numerous outbreaks affecting local and travelling populations worldwide. Given the lack of a vaccine, preventative measures are primarily focused on surveillance, vector control, and the use of personal protective behaviours (PPBs). The importance of PPBs is central to public health recommendations. However, translating these messages into coherent action by the public can prove challenging, as the uptake of such measures is inevitably influenced by socio-economic factors, awareness, knowledge, and risk perception. METHODS: A PRISMA-based systematic research was conducted on EMBASE, PubMed/MEDLINE, and Web of Science databases. PROSPERO registration number CRD42023459714. Quality of studies included in the final stage was evaluated using the Critical Appraisal Checklist for Cross-Sectional Study (CEBMa). RESULTS: 2963 articles were screened, and 17 studies were included in the final round. Out of these, six were deemed of high quality, ten were of medium quality, and one was of low quality. In almost all studies considered, both awareness and knowledge of WNV transmission were above 90%, while concern about WNV ranged from 50% to 80%. Concern about the safety of repellents, either with or without DEET, ranged from 27% to 70%. The percentage of people actually using repellents ranged from 30% to 75%, with the lowest usage reported among individuals over 60 years old (29%) and pregnant women (33%), and the highest among students aged 9-11 (75%). Concern for West Nile Virus (WNV) was consistently linked to an increase in taking preventative measures, including the use of repellents, by two to four times across studies. The school-based intervention was effective in increasing the practice of removing standing water (AOR=4.6; 2.7-8.0) and wearing long clothing (AOR=2.4; 95%CI: 1.3-4.3), but did not have a significant impact on the use of repellents. CONCLUSIONS: The present systematic review provides an overview of the knowledge, attitudes, and practices (KAP) of WNV and their determinants. While concern about West Nile Virus (WNV) and its effects can be a significant motivator, it is important to promote evidence-based personal protective behaviours (PPBs) to counter unwarranted fears. For example, the use of repellents among the most vulnerable age groups. Given the geographical expansion of WNV, it is necessary to target the entire population preventively, including those who are difficult to reach and areas not yet endemic. The findings of this investigation could have significant implications for public health and support well-informed and effective communication strategies and interventions.

Emergency Department Syndromic Surveillance to Monitor Tick-Borne Diseases: A 6-Year Small-Area Analysis in Northeastern Italy.

Tick-borne diseases (TBD) are endemic in Europe. However, surveillance is currently incomplete. Alternative strategies need to be considered. The aim of this study was to test an Emergency Department Syndromic Surveillance (EDSyS) system as a complementary data source to describe the impact of tick bites and TBD using a small-area analysis approach and to monitor the risk of TBD to target prevention. ED databases in the Local Health Authority 8 District (Veneto, Italy) were queried for tick-bite and TBD-related visits between January 2017 and December 2022. Hospitalisations were also collected. Events involving the resident population were used to calculate incidence rates. A total of 4187 ED visits for tick-bite and 143 for TBD were recorded; in addition, 62 TBD-related hospitalisations (of which 72.6% in over 50 s and 22.6% in over 65 s). ED visits peaked in spring and in autumn, followed by a 4-week lag in the increase in hospital admissions. The small-area analysis identified two areas at higher risk of bites and TBD. The use of a EDSyS system allowed two natural foci to be identified. This approach proved useful in predicting temporal and geographic risk of TBD and in identifying local endemic areas, thus enabling an effective multidisciplinary prevention strategy.

Comparison of Adverse Effects of Two SARS-CoV-2 Vaccines Administered in Workers of the University of Padova.

Introduction: In Italy, on December 2020, workers in the education sector were identified as a priority population to be vaccinated against COVID-19. The first authorised vaccines were the Pfizer-BioNTech mRNA (BNT162b2) and the Oxford-AstraZeneca adenovirus vectored (ChAdOx1 nCoV-19) vaccines. Aim: To investigate the adverse effects of two SARS-CoV-2 vaccines in a real-life preventive setting at the University of Padova. Methods: Vaccination was offered to 10116 people. Vaccinated workers were asked to voluntarily report symptoms via online questionnaires sent to them 3 weeks after the first and the second shot. Results: 7482 subjects adhered to the vaccination campaign and 6681 subjects were vaccinated with ChAdOx1 nCoV-19 vaccine and 137 (fragile subjects) with the BNT162b2 vaccine. The response rate for both questionnaires was high (i.e., >75%). After the first shot, the ChAdOx1 nCoV-19 vaccine caused more fatigue (p < 0.001), headache (p < 0.001), myalgia (p < 0.001), tingles (p = 0.046), fever (p < 0.001), chills (p < 0.001), and insomnia (p = 0.016) than the BNT162b2 vaccine. After the second dose of the BNT162b2 vaccine, more myalgia (p = 0.033), tingles (p = 0.022), and shivers (p < 0.001) than the ChAdOx1 nCoV-19 vaccine were elicited. The side effects were nearly always transient. Severe adverse effects were rare and mostly reported after the first dose of the ChAdOx1 nCoV-19 vaccine. They were dyspnoea (2.3%), blurred vision (2.1%), urticaria (1.3%), and angioedema (0.4%). Conclusions: The adverse effects of both vaccines were transient and, overall, mild in severity.

Factors influencing long-term persistence of anti-HBs after hepatitis B vaccination.

Long-term immunity after HBV vaccination is still debated. When assessing immune persistence, several variables must be considered, the clear definition of which is crucial. Our aim was to assess protection 10-20 years after primary vaccination and to estimate the effect of age at first dose, sex and time elapsed between doses on long-term protection. We conducted a retrospective cohort study between January 2004 and December 2020. Antibody titres above 10 IU/L were considered protective. Geometric mean titres (GMT) were calculated. The effect of the above variables on long-term protection was assessed by logistic regression analysis. Included participants were 9459. Among those vaccinated during infancy, GMT gradually increased from 11 IU/L (first dose in 1st trimester of life) to 68 IU/L (4th trimester), while the proportion of individuals <10 IU/L remained stable between 1st and 2nd trimester (51%) and it decreased substantially in 3rd (28%) and even more so in the 4th (18%). A one-month delay in first and third dose administration was correlated with a -16% (AOR: 0.84; 95% CI: 0.78-0.91) and a -11% (AOR: 0.89; 95% CI: 0.85-0.94) risk of a titre <10 IU/L, respectively, ~20 years after immunisation. In contrast, similar changes do not comparably affect vaccination in adolescence. The start of vaccination at the third month of age is a compromise between the development of acceptable immunogenicity and the need to protect the infant as early as possible. However, the chance of slightly delaying the vaccine administration within the first year of life may be considered given the impact on long-term persistence of anti-HBs.

Body Mass Index and Antibody Persistence after Measles, Mumps, Rubella and Hepatitis B Vaccinations.

Overweight and obesity may cause a reduced response to vaccination. The purpose of the present research was to study the relationship between current body mass index (BMI) and antibody persistence after vaccination against measles, mumps, and rubella (MMR) and hepatitis B virus (HBV) given during childhood, as per the current vaccination schedule. The study was conducted on 2185 students at the School of Medicine, University of Padua, Italy. The mean age of the participants was 20.3 years. After adjusting for sex, age at first dose of vaccine administered, age at last dose, and age at study enrollment, no significant association was found between lack of serologic protection and BMI for either the HBV vaccine or each component of the MMR vaccine. For the first time, the absence of this relationship was demonstrated for the MMR vaccine. Given the evidence currently available, further research on BMI and vaccines in general remains desirable.

Rubella Serosurvey Among Future Healthcare Workers.

Objective: Rubella is a very diffusive but relatively benign infectious disease unless contracted during pregnancy, when it causes congenital rubella syndrome. The aim of this research was to determine the prevalence and titer of antirubella antibodies in a population of future healthcare workers (students at the school of medicine). Methods: The cohort consisted of 11,022 students who underwent antibody analysis after the presentation of a vaccine certificate. Results: Vaccination compliance was very high, particularly in younger students (born after 1995), reaching almost 100% (at least one dose). Unvaccinated students born before 1990 had high seropositivity (>95%), but this percentage dropped to zero among the youngest students. Variables affecting antibody titer included year of birth and sex. Considering only vaccinated students, a greater antibody response was observed if the vaccine was administered between 8 and 10 years of age. Female sex was associated with more significant (p < 0.0001) positivity and higher antibody titer after one and two doses. However, this difference appeared less consistent in relation to year of birth. Conclusions: The studied population exhibited excellent vaccination compliance, high seropositivity, and high antibody titer. Vaccine and immune coverage were higher than what is deemed necessary to achieve herd immunity.

Uptake of Non-Mandatory Vaccinations in Future Physicians in Italy.

In 2017 in Italy, a number of vaccinations became mandatory or started to be recommended and offered free of charge. In this study, we aimed at assessing the coverage rates for those vaccinations in the pre-mandatory era among students at the School of Medicine of Padua University studying the degree course in medicine and surgery (future physicians) on the basis of the vaccination certificates presented during health surveillance. The vaccinations considered were those against pertussis, rubella, mumps, measles, varicella, Haemophilus influenzae type b (which became mandatory in 2017), pneumococcus, meningococcus C and meningococcus B (only suggested and offered for free since 2017). The study enrolled 4706 students of medicine and surgery. High vaccine uptake was observed, especially in younger students (born after 1990), with vaccines against pertussis, rubella, mumps and measles. Good completion for Haemophilus influenzae type b and meningococcus C was also observed. Very low coverage rates (all under 10%) for vaccination against varicella, pneumococcus and meningococcus B were observed. In conclusion, uptake for some non-mandatory vaccines was below the recommended threshold, although younger generations showed a higher uptake, possibly as a results of policy implemented at the national level. Our findings support the idea to consider health surveillance visits also as an additional opportunity to overcome confidence and convenience barriers and offer vaccine administration.

Future Healthcare Workers and Hepatitis B Vaccination: A New Generation.

Before the introduction of universal vaccination, hepatitis B caused high morbidity and mortality, especially among healthcare workers. In the present study, the immune status against hepatitis B was assessed in a cohort of 11,188 students of the degree courses of the School of Medicine of the University of Padua (Italy) who had been subjected to mandatory vaccination in childhood or adolescence and who will be future healthcare workers. The variables that influence the antibody response to vaccination are mainly the age at which the vaccine was administered and sex. If vaccination was administered before one year of age, there is a high probability (around 50%) of having an antibody titer lower than 10 IU/L compared to those vaccinated after one year of age (12.8%). The time between vaccine and analysis is not decisive. Furthermore, female sex, but only if vaccination was administered after one year of age, shows a significant (p = 0.0008) lower percentage of anti-HBs below 10 IU/L and a greater antibody titer (p < 0.0001). In conclusion, the differences related to the age of vaccination induce more doubts than answers. The only plausible hypothesis, in addition to the different immune responses (innate and adaptive), is the type of vaccine. This is not easy to verify because vaccination certificates rarely report it.

Response to Vaccination against Mumps in Medical Students: Two Doses Are Needed.

Mumps is a vaccine-preventable infectious disease diffuse worldwide. The implementation of mumps vaccination reduced largely the spread of infection. On 11,327 Medical School students the prevalence of mumps positive antibodies was evaluated according to dose/doses of vaccine, year of birth and sex. Compliance to mumps vaccine was low in students born before 1990 but increased consistently after this year, above all compliance to two doses, due to the implementation of the vaccine offer. Positivity of mumps antibodies is significantly (p < 0.0001) lower in students vaccinated once (71.2%) compared to those vaccinated twice (85.4%). In addition, students born after 1995, largely vaccinated twice, showed a seropositivity near to 90%. Further, females had a significantly (p < 0.0001) higher proportion of positive antibodies after vaccination than males, both one (74.6% vs. 64.7%) and two doses (86.8% vs. 82.9%). Finally, seropositivity after two vaccine doses remains high (86.1%) even 15 years after the second dose. In conclusion, the research highlighted that vaccination against mumps reaches a good level of coverage only after two doses of vaccine persisting at high levels over 15 years and induces a more significant response in females.

Laboratory Diagnosis of Porphyria.

Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis. Such dysfunctions result in the excessive production and excretion of the intermediates of the heme biosynthesis pathway in the blood, urine, or feces, and these intermediates are responsible for specific clinical presentations. Porphyrias continue to be underdiagnosed, although laboratory diagnosis based on the measurement of metabolites could be utilized to support clinical suspicion in all symptomatic patients. Moreover, the measurement of enzymatic activities along with a molecular analysis may confirm the diagnosis and are, therefore, crucial for identifying pre-symptomatic carriers. The present review provides an overview of the laboratory assays used most commonly for establishing the diagnosis of porphyria. This would assist the clinicians in prescribing appropriate diagnostic testing and interpreting the testing results.

Neurofibromin Deficiency and Extracellular Matrix Cooperate to Increase Transforming Potential through FAK-Dependent Signaling.

Plexiform neurofibromas (Pnfs) are benign peripheral nerve sheath tumors that are major features of the human genetic syndrome, neurofibromatosis type 1 (NF1). Pnfs are derived from Schwann cells (SCs) undergoing loss of heterozygosity (LOH) at the NF1 locus in an NF1+/- milieu and thus are variably lacking in the key Ras-controlling protein, neurofibromin (Nfn). As these SCs are embedded in a dense desmoplastic milieu of stromal cells and abnormal extracellular matrix (ECM), cell-cell cooperativity (CCC) and the molecular microenvironment play essential roles in Pnf progression towards a malignant peripheral nerve sheath tumor (MPNST). The complexity of Pnf biology makes treatment challenging. The only approved drug, the MEK inhibitor Selumetinib, displays a variable and partial therapeutic response. Here, we explored ECM contributions to the growth of cells lacking Nfn. In a 3D in vitro culture, NF1 loss sensitizes cells to signals from a Pnf-mimicking ECM through focal adhesion kinase (FAK) hyperactivation. This hyperactivation correlated with phosphorylation of the downstream effectors, Src, ERK, and AKT, and with colony formation. Expression of the GAP-related domain of Nfn only partially decreased activation of this signaling pathway and only slowed down 3D colony growth of cells lacking Nfn. However, combinatorial treatment with both the FAK inhibitor Defactinib (VS-6063) and Selumetinib (AZD6244) fully suppressed colony growth. These observations pave the way for a new combined therapeutic strategy simultaneously interfering with both intracellular signals and the interplay between the various tumor cells and the ECM.

Development and evaluation of a new non-competitive Luminex immunoassay detecting antibodies against human papillomavirus types 6, 11, 16 and 18.

Serum antibody levels can be used to measure the humoral immune response against human papillomaviruses (HPV). We developed and validated a rapid, technically simple and relatively inexpensive multiplex non-competitive Luminex-based immunoassay (ncLIA) to measure total IgG antibody levels against four HPV types. For the assay's solid phase, virus-like particles (VLPs) of HPV6, 11, 16 and 18 were bound to heparin-coated beads. HPV serum antibody levels binding to the VLPs were quantified using a phycoerithrin-conjugated secondary polyclonal donkey anti-human IgG antibody. Standardization and validation of the ncLIA were performed using 96 paired serum and genital samples from participants in the HITCH cohort study, including young women (aged 18-24 years) and their male sexual partners (aged 18+) in Montreal, Canada. Results from the ncLIA were compared to a validated Luminex immunoassay from PPD laboratories using Pearson's correlation coefficients, receiver operating characteristic curves and logistic regression. Our assay had good inter- and intra-assay variability. The correlation of serum antibody levels between the ncLIA and validation assay was highest for HPV16 and HPV11 (r=0.90), followed by HPV6 (r=0.86) and HPV18 (r=0.67). The ncLIA was better able to predict HPV DNA positivity in genital samples than the validation assay for HPV16 [area under the curve (AUC) 0.65 versus 0.52, P=0.001] and HPV18 [AUC 0.71 versus 0.57, P=0.024]. AUCs for HPV6 and HPV11 were similar between the two assays (0.70 versus 0.71, P=0.59, and 0.88 versus 0.96, P=0.08, respectively). The developed ncLIA is useful for measuring total IgG antibody response following natural infection or vaccination against four HPV VLPs included in the quadrivalent vaccine.

Vaccination and Immunity toward Measles: A Serosurvey in Future Healthcare Workers.

Measles is a very contagious infectious disease, and vaccination is the only medical aid to counter the spread of the infection. The aim of this study was to evaluate the influence of vaccination schedule and type of vaccine, number of doses, and sex on the immune response. In a population of Italian medical students (8497 individuals born after 1980 with certificate of vaccination and quantitative measurement of antibodies against measles), the prevalence of positive antibodies to measles and antibody titer was measured. Vaccination schedule such as number of doses and vaccine type (measles alone or combined as measles, mumps and rubella (MMR)) and sex were the variables considered to influence the immune response. The vaccination schedule depends on the year of birth: students born before 1990 were prevalently vaccinated once and with measles vaccine alone (not as MMR). One dose of vaccine induces a significantly (p < 0.0001) higher positive response and antibody titer than two doses, in particular when measles alone is used (p < 0.0001). Females have a significantly higher percentage of positive response (p = 0.0001) than males but only when the MMR formulation was used. Multiple linear regression confirms that sex significantly influences antibody titer when only MMR is used, after one (p = 0.0002) or two (p = 0.0060) doses. In conclusion, vaccination schedule and, partially, sex influence immune response to measles vaccination. Most notably, the measles vaccine alone (one dose) is more effective than one and two doses of MMR.

Persistence of Anti-Hbs after up to 30 Years in Health Care Workers Vaccinated against Hepatitis B Virus.

The burden of hepatitis B virus (HBV) infection is a serious public health problem all over the world. Vaccination remains the most effective prevention measure, and safe and effective HBV vaccines have been available since 1982. Health care workers (HCWs) vaccinated against HBV and prospectively followed up for at least 14 years were classified by their antibody titers after primary vaccination as: poor responders (10-99 mIU/mL); moderate responders (100-999 mIU/mL); and good responders (≥1000 mIU/mL). The incidence of antibody loss was calculated for 1000 person-years and the anti-HBs persistence was calculated. The analysis concerned 539 HCWs: 494 good responders (91.7%); 37 moderate responders (6.9%); and eight poor responders (1.5%). The incidence of anti-HBs loss was 52.1 per 1000 person-years for the poor responders, 11.3 per 1000 person-years for the moderate responders, and 1.4 per 1000 person-years for the good responders. The mean persistence of anti-HBs differed significantly between the three groups, being: 19.2 years (95% CI: 15.6-22.8), 25.4 years (95% CI: 23.0-27.9), and 31.0 years (95% CI: 30.5-31.5) for the poor, moderate and good responders, respectively. In conclusion, our findings demonstrate a good persistence of protective anti-HBs titers in HCWs exposed to occupational risk for up to 30 years after a primary vaccination cycle (even without a booster dose) if their titer was initially higher than 100 mIU/mL.

Course of Metal Ions after a Revision of Malfunctioning Metal-on-Metal Total Hip Prostheses.

The present research evaluated the course of cobalt and chromium in the blood and urine after the revision of metal-on-metal with a ceramic-on-polyethylene total hip arthroplasty. Seven patients were enrolled for hip prosthesis revision owing to ascertained damage of the implant. Metals in the blood and urine were evaluated before and after the hip revision. The double measurement before the total hip revision revealed high levels of metal ions (on average, 88.1 µg/L of cobalt in the blood, 399.0 µg/g of creatinine cobalt in the urine, 46.8 µg/L of chromium in the blood, and 129.6 µg/g of creatinine chromium in the urine at the first measurements), with an increasing trend between the first and second dosage. Within a week after the hip revision, the levels of metal ions significantly decreased by approximately half. Four to six months after the operation, the cobalt levels were found near to the reference values, whereas the chromium levels reached 25% of the values measured before the revision. The revision of malfunctioning metal-on-metal implants produced a dramatic decrease of metal ions in biological fluids, although it did not completely rescue the chromium level.

Filling the gap between risk assessment and molecular determinants of tumor onset.

In the past two decades, a ponderous epidemiological literature has causally linked tumor onset to environmental exposure to carcinogens. As consequence, risk assessment studies have been carried out with the aim to identify both predictive models of estimating cancer risks within exposed populations and establishing rules for minimizing hazard when handling carcinogenic compounds. The central assumption of these works is that neoplastic transformation is directly related to the mutational burden of the cell without providing further mechanistic clues to explain increased cancer onset after carcinogen exposure. Nevertheless, in the last few years, a growing number of studies have implemented the traditional models of cancer etiology, proposing that neoplastic transformation is a complex process in which several parameters and crosstalk between tumor and microenvironmental cells must be taken into account and integrated with mutagenesis. In this conceptual framework, the current strategies of risk assessment that are solely based on the 'mutator model' require an urgent update and revision to keep pace with advances in our understanding of cancer biology. We will approach this topic revising the most recent theories on the biological mechanisms involved in tumor formation in order to envision a roadmap leading to a future regulatory framework for a new, protective policy of risk assessment.

Metal Ion Release, Clinical and Radiological Outcomes in Large Diameter Metal-on-Metal Total Hip Arthroplasty at Long-Term Follow-Up.

Total hip arthroplasty (THA) with metal-on-metal (MoM) bearings have shown problems of biocompatibility linked to metal ion release at the local level causing an adverse reaction to metal debris (ARMD) and at a systemic level. The aim of this study was to evaluate clinical and radiological outcomes, and metal ion concentrations in the blood and urine of patients who underwent THA with the LIMA Met-Met hip system. Patients with ceramic-on-ceramic (CoC) bearings were included as a control group. In this study, 68 patients were enrolled: 34 with MoM THAs and 34 with CoC THAs. Patients were evaluated clinically (Harris Hip Score, SF-36) and radiologically at a median of 7.4 years after surgery. Whole blood and urinary cobalt and chromium levels were also assessed. Both types of implants were comparable in terms of clinical and functional results. Ion levels were significantly higher in the MoM group compared with CoC group 7 years after surgery. No correlations were found between metal ion levels and patient demographics, functional and radiological outcomes, and prosthesis features. Patient monitoring is thus advised to establish if prosthesis revision is necessary, especially in the case of MoM THA.