The Italian Mandatory Notification System: An Important Public Health Tool For Continuous Monitoring Of Infectious Diseases.

Infectious diseases still register significant morbidity and mortality worldwide. Surveillance through a mandatory notification system allows the continuous analysis of the situation even at a local level and its importance has been highlighted by the recent COVID-19 pandemic. This paper aimed to outline the importance of the mandatory notification system as a Public Health tool in the continuous monitoring of infectious diseases. To this aim, we carried out a cross-sectional study examining the notifications reported in the Italian territory of Messina, Sicily, in the period 2001-2020. The institutional websites were examined and the notification data were used to obtain the incidences. Overall, a significant reduction of the incidence notification trend was observed. Chickenpox was by far the most notified infectious disease, followed by scabies, pediculosis, and brucellosis. Outbreaks of brucellosis, measles and hepatitis A occurred. All the diseases decreased over time, except syphilis, for which a significant increase was observed. Surveillance of infectious diseases through a mandatory notification system remains a bulwark of public health despite underreporting. Our study reflects the situation of a typical high-income area, although some unexpected criticisms are highlighted. Continuous information about correct behaviors through education campaigns are crucial in order to improve the situation. Keywords: mandatory notifications, infectious diseases, surveillance, public health Corresponding author: Alessio Facciolà, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Italy. Email: afacciola@unime.it.

Vaccine hesitancy: An overview on parents' opinions about vaccination and possible reasons of vaccine refusal.

Background. Vaccine hesitancy has increased worldwide with a subsequent decreasing of vaccination rates and outbreaks of vaccine-preventable diseases (i.e. measles, poliomyelitis and pertussis) in several developed countries, including Italy. Design and Methods. We conducted a survey to investigate the attitudes of a parents' sample about vaccinations by the distribution of questionnaires in six lower secondary schools of the Italian city of Messina. Results. Regarding vaccinations carried out on children, the declared vaccination coverage rates ranged widely between good coverage percentages for some vaccinations (Measles-Mumps-Rubella, Diphtheria-Tetanus-Pertussis), and very low coverage rates for others, especially for "new" vaccinations (HPV, meningococcal, pneumococcal). The vaccinations carried out correlated negatively with both parents' age and their level of education. Moreover, a favourable parents' opinion was strongly influenced by a favourable opinion of the physician, while an unfavourable parents' opinion seemed conditioned by a direct or indirect knowledge of people harmed by vaccines. In addition, our data show that parents do not often know or partially know the real composition of the vaccines and the diseases prevented by vaccinations. Conclusions. Data analysis shows that parents are, theoretically, favourable towards vaccinations but have little knowledge of such practices, sometimes not being unaware of the types of vaccines administrated to their children. Health education and communication of correct information are certainly the cornerstones to improve the situation and to fight the widespread and non-grounded fears about vaccines.

Prevalence of human papillomavirus in saliva of women with HPV genital lesions.

BACKGROUND: The human papilloma viruses (HPVs) are DNA viruses associated with benign and malignant lesions of skin and mucous membranes. The HPVs has been implicated as the cause of virtually all cervical cancers worldwide but studies showed that these viruses can cause numerous cancers in several tissues including Oral Squamous Cell Carcinoma (OSCC). At least 90 % of HPV-positive OSCCs are associated with high-risk (or oncogenic) HPV-16 and oral infection confers an approximate 50-fold increase in risk for HPV-positive OSCC. HPV-positive OSCCs are associated with sexual behaviors in contrast to HPV-negative OSCCs that are associated with chronic tobacco and alcohol use. The aim of this study was to estimate the prevalence of HPV-DNA in saliva samples collected from women in which it has been previously established the HPV infection of the cervix with relative genotyping and, then, to study the possible correlation. METHODS: Saliva samples were collected from 100 women with HPV cervical lesions, aged between 22 and 52 years old, and 25 healthy women with normal cytology (control group), aged between 20 and 49 years old. PCR assay was used to detect HPV DNA. RESULTS: The prevalence of oral HPV infection in saliva samples was 24 % in women with HPV cervical lesions while in the control group was 8 %. It has been demonstrated a strong association between high grade squamous intraepithelial lesion and oral infection due to HPV16 and 18, that are the most frequently detected HPV genotypes. CONCLUSION: This study shows that patients with genital HPV infection are at risk for oral infection and, consequently, for the development of OSCC.

Higher levels of oxidative DNA damage in cervical cells are correlated with the grade of dysplasia and HPV infection.

The Human papillomavirus is responsible for the most common sexually transmitted infection and is also known to be an oncogenic virus that is associated with cervical, anogenital, and head-neck cancers. The present study aims to assess whether oxidative DNA damage is correlated with the grade of HPV-related lesions. Moreover, we evaluated clinical data and unhealthy lifestyles to verify their possible influence on the genesis of oxidative DNA damage in cervical cells. We quantified the amount of 8-Oxo-2'-deoxyguanosine in DNA as a biomarker of oxidative damage in women with and without HPV infection. We also correlated oxidative damage with different stages of cervical lesions and available clinical data (e.g., HPV genotypes). To identify HPV infections, in which proteins with a transforming potential are produced, we performed a qualitative detection of HPV E6/E7 mRNA. Our results showed greater oxidative damage in HPV-related dysplastic cervical lesions compared to samples with normal cytology, especially in women with high-grade squamous intraepithelial lesions. The latter showed a closed link with high-risk HPV genotypes. Reactive oxygen species can induce DNA double-strand breaks in both the host DNA and in the circular viral episome; this could facilitate the integration of the virus, promoting HPV carcinogenesis. Therefore, in HPV-infected women, it could be useful to reduce additional resources of reactive oxygen/nitrogen species (RONS) with a healthy lifestyle.

Mitochondrial dysfunction by pro-oxidant vanadium: ex vivo assessment of individual susceptibility.

The aim was to assess the individual susceptibility to mitochondrial impairment induced by ex vivo exposure to vanadium, an airborne pro-oxidant pollutant. In lymphocyte cultures V(IV)-treated of forty-five healthy subjects, we evaluated the mitochondrial transmembrane potential (Δψm) and the H2O2 in comparison to background values. As variables, we included both lifestyle factors and genetic polymorphisms (GSTM1 and GSTT1 variants, and C677T and A1298C variants of methylenetetrahydrofolate reductase MTHFR). H2O2 mitochondrial content increased significantly (P<0.05) after metal exposure while, in comparison to basal Δψm, both depolarisation and hyperpolarisation were recorded. This underlined the mitochondrial dysfunction vanadium-induced that worsens the redox imbalance by endogenous ROS overproduction. Only age was found to contribute significantly to the high inter-individual variability, as assessed by multivariate analysis. In older subjects, the H2O2/Δψm values underline the organelle impairment and, under V-exposure, Δψm values were inversely related to age (R=-0.591; P=0.012).

HIV genomic mutations causing resistance to antiretroviral drugs in seropositive Sicilians.

Through the use of highly active antiretroviral therapy a significant reduction occurred in mortality and morbidity caused by Human Immunodeficiency Virus. The use of antiretroviral drugs resulted in the emergence of resistant viral strains due to mutations that cause a selective advantage to the virus. The aim of our study is to monitor the HIV-1 infection in Sicilians patients evaluating the presence of mutations that make the virus resistant to the therapy. The QIAGEN QIAamp Viral RNA Mini Kit was used to extract HIV-1 viral RNA from 300 patients while the TRUGENE HIV-1 Genotyping Kit and the OpenGene DNA Sequencing System determined viral mutations in the RNA samples. The analysis showed that from 300 subjects, 116 developed Antiretroviral Drug Resistance. The percentage of patients with resistance to nucleoside reverse transcriptase inhibitor (NRTI), non nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor was 26%, 23% and 20%, respectively. Comparison between drug resistances and mutations showed that 134 individuals had mutations in genes codifying for reverse transcriptase but a little more than 50% were associated with resistance to reverse transcriptase inhibitors, in particular 78 and 68 subjects developed drug resistances to NRTI and NNRTI classes respectively. Subjects that showed mutations in genes codifying for protease were 216 but only 59 of these were associated with resistance to protease inhibitors. Our findings emphasize the importance of continued resistance surveillance. Monitoring of transmitted resistance continues to be needed among treatment-exposed patients because of the benefit it provides for the development of drugs effective against the most frequently found drug-resistant viruses.

Bioenergetics of T cell activation and death in HIV type 1 infection.

Regressive morphological lesions, found in peripheral lymphocytes from HIV(+) patients, clearly conflict with normal cycle progression and with the execution of basic housekeeping and immune functions. With these lesions, circulating lymphocytes are destined to spontaneous and energy-independent cell lysis. By means of confocal microscopy and morphometry, we have quantified the rate of circulating T cells that are probably destined to emocatheresis in vivo. This rate includes lymphocytes in which nucleolin fragments have been scattered out of the nuclear region as a result of prelethal alterations in the nuclear membrane permeability. In terms of bioenergetics, these cells show evident anomalies in the energy production machinery that make them unable to carry out ATP-requiring functions. The extent of damaged cell fraction in peripheral blood reflects the frequency with which T lymphocytes leave lymphoid tissue to be cleared in hemocatheretic processes.

Multigenerational mitochondrial alterations in pneumocytes exposed to oil fly ash metals.

Oil fly ash (OFA), containing high amounts of transition metals, is among the most reactive airborne particulate matter emissions, which have been associated with several diseases, such as chronic obstructive pulmonary diseases (COPD), lung cancer, and cardiovascular diseases. The aim of the present study was to evaluate mitochondrial alterations in OFA-exposed cultured pneumocytes and in their progeny. Alveolar epithelial cells (A549 line) were exposed either to an OFA water solution, containing 68.8 µM vanadium (V), 110.4 µM iron (Fe), and 18.0 µM nickel (Ni), or to the individual metal solutions. Structural and functional mitochondrial parameters were determined in exposed cultures and in 3 consecutive subcultures. OFA, V and Fe solutions caused a time-dependent loss of mitochondrial enzymatic activity, glutathione depletion, generation of lipid hydroperoxides, hydrogen peroxide and other reactive oxygen species, especially in G(0)-G(1) phase cells, accompanied by a decrease in mitochondrial mass and transmembrane potential. Mitochondrial alterations were partly transmissible to daughter cells for up to 3 generations. Fe and especially V were responsible for the observed mitochondrial alterations in pneumocytes exposed to OFA. Spread of mitochondrial dysfunctions to daughter cells is expected to amplify oxidative stress in the respiratory epithelium and to play an important role in the pathogenesis of respiratory diseases.

Intracellular accumulation of cell cycle regulatory proteins and nucleolin re-localization are associated with pre-lethal ultrastructural lesions in circulating T lymphocytes: the HIV-induced cell cycle dysregulation revisited.

The HIV-induced demise of CD4-T cells is thought to be a result of the execution of genetically programmed cell death that occurs in lymphoid tissue, where many resident T cells are chronically hyperactivated. Since HIV-induced alterations of cell cycle control has been often indicated as prominent mechanism of immune hyper activation and cause of apoptotic death, the signal pathway involved in cell cycle dysregulation of T lymphocytes from HIV infected patients was extensively studied. Here, we also demonstrate that circulating T lymphocytes leave lymphoid tissues with diffused regressive lesions (vacuolization, blebbing, nuclear evanescence and organelle swelling). Equally diffused are biochemical anomalies that accompany the overall disarrangement of cell structure, particularly the fragmentation and diffusion into the cytoplasm of C23/nucleolin, the intracellular accumulation of short lived regulatory proteins and the decrease in expression of membrane proteins. All this is something more than a cell cycle-related remodelling of cell morphology and biochemical mechanisms, and rather recalls a necrotic/oncotic cell damage. Since these changes are associated with adaptive mechanisms to hypoxia, we give evidence for alteration of cell cycle control developing in conditions of scarce energy supply.

Prevalence of SENV-H and SENV-D virus: epidemiological study in blood donors and dialysis patients.

INTRODUCTION: Recently, the identification of the SEN virus as a possible etiological agent of parental transmission hepatitis led to the study of the prevalence of such pathogen agents, particularly SENV-H, in our population. This paper compares the rate prevalence in high-risk subjects, such as dialysis patients, and low-risk subjects, such as blood donors. MATERIAL AND METHODS: The study was carried out on SEN virus DNA extracted from serum of dialysis patients and blood donors, and the presence of viral genomes was performed by the nested PCR method. RESULTS: The results showed a higher prevalence in male blood donors, supporting the hypothesis of an epidemiological role for sexual and also parental transmission, as is clearly demonstrated by the high prevalence in dialysis patients. The result reduced the importance of the possible etiological role of the SEN virus due to the high percentage of positivity in healthy population, and it induces one to consider poorly significant the pathogenicity of such viral agents. CONCLUSION: For this instance, the authors, in agreement with the phylogenically related TT virus, described SEN viruses as absolutely not pathogens and considered them as "simple guests."

Aeromonas hydrophila exotoxin induces cytoplasmic vacuolation and cell death in VERO cells.

Many organisms are able to cause cell vacuolation, but it is unclear if this can be considered a step of apoptosis or necrosis, or a distinct form of cell death. In this study VERO cells were used to evaluate the relationship between vacuolation and cell death pattern caused by exotoxins produced by environmental strains of A. hydrophila. Cell damage has been evaluated morphologically as well as biochemically. Cytotoxic and vacuolating titres were strictly correlated and the vacuolation has to be considered an early indicator of cytotoxicity that causes cell apoptosis or necrosis in relation to the dose. Signs of apoptosis (chromatin condensation and blebbing) were observed at low concentration and TGase activity, referable to apoptosis induction, confirms morphological observations. In fact, putrescine incorporation was related both to cytotoxin concentration and time of incubation. Moreover, the observed doubling cells with necrotic features permit us to suppose that cell sensitivity and death pattern could change during the different phases of cellular cycle.