Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence.

In 2014, the Food and Drug Administration approved a new human papillomavirus 9-valent vaccine (9vHPV), targeting nine HPV types: HPV types 6, 11, 16, and 18, which are also targeted by the quadrivalent HPV vaccine (qHPV), plus five additional high cancer risk HPV types (HPV types 31, 33, 45, 52, and 58). The aim of the current study was to systematically retrieve, qualitatively and quantitatively pool, as well as critically appraise all available evidence on 9vHPV from randomized controlled trials (RCTs). We conducted a systematic review of the literature on 9vHPV efficacy, immunogenicity and safety, as well as a systematic search of registered, completed, and ongoing RCTs. We retrieved and screened 227 records for eligibility. A total of 10 publications reported on RCTs' results on 9vHPV and were included in the review. Sixteen RCTs on 9vHPV have been registered on RCT registries. There is evidence that 9vHPV generated a response to HPV types 6, 11, 16 and 18 that was non-inferior to qHPV. Vaccine efficacy against five additional HPV type-related diseases was directly assessed on females aged 16-26 years (risk reduction against high-grade cervical, vulvar or vaginal disease = 96·7%, 95% CI 80·9%-99·8%). Bridging efficacy was demonstrated for males and females aged 9-15 years and males aged 16-26 years (the lower bound of the 95% CIs of both the geometric mean titer ratio and difference in seroconversion rates meeting the criteria for non-inferiority for all HPV types). Overall, 9vHPV has been proved to be safe and well tolerated. Other RCTs addressed: 9vHPV co-administration with other vaccines, 9vHPV administration in subjects that previously received qHPV and 9vHPV efficacy in regimens containing fewer than three doses. The inclusion of additional HPV types in 9vHPV offers great potential to expand protection against HPV infection. However, the impact of 9vHPV on reducing the global burden of HPV-related disease will greatly depend on vaccine uptake, coverage, availability, and affordability.

Climate, demographic factors and geographical variations in the incidence of invasive meningococcal disease in Italy.

We investigated the effect of climatic, demographic factors and intra-country geographical variations on the incidence of invasive meningococcal disease (IMD) in Italy. For this purpose, incidence rates of IMD cases reported in Italy between 1994 and 2012 were calculated, and a cluster analysis was performed. A geographical gradient was determined, with lower incidence rates in central and southern Italy, compared to the northern parts, where most clusters were observed. IMD rates were higher in medium-sized towns than in villages. Adults were at lower risk of IMD than children aged ⩽4 years. IMD incidence tended to decrease with increasing monthly mean temperatures (incidence rate ratio 0·94, 95% confidence interval 0·90-0·99). In conclusion, geographical variations in IMD incidence were found, where age and temperature were associated with disease occurrence. Whether geographical variations should be considered in national intervention plans is still a matter for discussion.

Continuous increase in HIV-1 incidence after the year 2000 among men who have sex with men in Rome: insights from a 25-year retrospective cohort study.

To assess trends in HIV-1 incidence and risk factors for seroconversion among men who have sex with men (MSM) resident in Rome, Italy, a retrospective longitudinal cohort study was conducted over 25 years. Incidence rates and trends were modelled using Poisson regression and risk factors were assessed by multivariate Cox models. Of 1,862 HIV-1-negative individuals, 347 seroconverted during follow-up. HIV-1 incidence rates increased from 5.2/100 persons/year (p/y) in 1986 (95% confidence interval (CI): 2.3­11.5) to 9.2/00 p/y in 1992 (95% CI: 6.4­13.0), decreased to 1.3/100 p/y in 2001 and increased until 2009 (11.7/100 p/y; 95% CI: 7.4­18.6). The risk of HIV-1 seroconversion increased during the study period in younger MSM (incidence rate ratio (IRR) = 17.18; 95% CI: 9.74­30.32 in 16­32 year-olds and IRR = 5.09; 95% CI: 2.92­8.87 in 33­41 year-olds) and in those who acquired syphilis (IRR = 7.71; 95% CI: 5.00­11.88). In contrast, the risk of seroconversion decreased among highly educated MSM (IRR = 0.54; 95% CI: 0.35­0.82) and those without Italian citizenship (IRR = 0.45; 95% CI: 0.28­0.71). The HIV epidemic in MSM living in Rome continues to expand. Targeted prevention programmes against sexually transmitted infections to enhance knowledge transfer and behavioural skills are urgently required.

Investigation of an imported case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Florence, Italy, May to June 2013.

On 31 May 2013, the first case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Italy was laboratory confirmed in a previously healthy adult man, who developed pneumonia with moderate respiratory distress after returning from a holiday in Jordan. Two secondary cases were identified through contact tracing, among family members and colleagues who had not previously travelled abroad. Both secondary cases developed mild illness. All three patients recovered fully.

HIV treatment as prevention: population effect vs. individual protection?

There are compelling data suggesting that antiretroviral (ARV) drugs can prevent the transmission of HIV: 1) ARV therapy reduces the intrinsic risk of transmission by cutting down the viral load in infected people; 2) ARVs may be used to prevent transmission in uninfected subjects who experienced high risk exposures. Despite these encouraging preliminary results, there are several questions that need to be answered before recommending the use of ARV among uninfected subjects: 1) the efficacy of these strategies amongst women is not yet established; 2) the cost-effectiveness of pre-exposure prophylaxis (PrEP) in the long term is undefined since PrEP efficacy may depend on adherence; 3) treating uninfected individuals may be counter-effective, as it may increase risky behavior due to the belief that ARV drugs have unlimited protective power. In conclusion, the public-health use of ARV drugs represents a new paradigm in the field of HIV prevention. However, ARV treatment cannot be considered as a substitute for other measures for preventing transmission but a complement to individual protection. In particular, post-exposure prophylaxis may be used in selected cases, whereas PrEP appears to be a highly costly method with limited public-health potential and possible safety concerns.

Probable autochthonous introduced malaria cases in Italy in 2009-2011 and the risk of local vector-borne transmission.

We describe two cases of probable autochthonous introduced Plasmodium vivax malaria that occurred in 2009 and 2011 in two sites of South-Central Italy. Although the sources of the infections were not detected, local transmission could not be disproved and therefore the cases were classified as autochthonous. Sporadic P. vivax cases transmitted by indigenous vectors may be considered possible in some areas of the country where vector abundance and environmental conditions are favourable to malaria transmission.

Epidemiological surveillance of West Nile neuroinvasive diseases in Italy, 2008 to 2011.

We describe the geographical and temporal distribution of West Nile neuroinvasive diseases (WNND) cases in Italy from 2008 to 2011. The increasing number of confirmed human cases from eight in 2008 to 18 in 2009 and the occurrence of the virus in a larger geographical area in 2009 (moving from east to west) prompted the Ministry of Health to publish, in spring 2010, a national programme for WNND human surveillance, comprising veterinary and vector surveillance. Subsequently, in 2011, a new national plan on integrated human surveillance of imported and autochthonous vector-borne diseases (chikungunya, dengue and West Nile disease) was issued. Between 2008 and 2011, 43 cases of WNND were reported from five regions in Italy with a case fatality rate of 16%. The incidence of WNND during the entire study period was 0.55 per 100,000 population (range: 0.06­0.23 per 100,000). During 2011, two new regions (Friuli-Venezia Giulia and Sardinia) reported confirmed cases in humans. Integrated human, entomological and animal surveillance for West Nile virus is a public health priority in Italy and will be maintained during 2012.

Few Italian drug users undergo HIV testing.

We estimated the proportion of drug users at treatment centres in Italy who had undergone HIV testing and the correlates of testing. Of the 1,917 drug injectors, 37.4% had been tested in the current year; of the 665 non-injectors, 28% had been tested. Among injectors, testing was associated with: being older than 35, foreign nationality, residing in central Italy, drug use for over 2 years, and having undergone both pharmacological and psychological treatment. Among non-injectors, an association was found for foreign nationality and not having been treated at other facilities. The results stress the need to facilitate access to testing.

Prevalence of IgM and IgG antibodies to West Nile virus among blood donors in an affected area of north-eastern Italy, summer 2009.

Following reports of West Nile neuroinvasive disease in the north-eastern area of Italy in 2009, all blood donations dating from the period between 1 August and 31 October 2009 in the Rovigo province of the Veneto region were routinely checked to exclude those with a positive nucleic acid test for West Nile virus (WNV). Only one of 5,726 blood donations was positive (17.5 per 100,000 donations; 95% confidence interval (CI): 0.4­97.3). In addition, a selection of 2,507 blood donations collected during the period from 20 July to 15 November 2009 were screened by ELISA for IgG and IgM antibodies against WNV. A positive result was received for 94 of them. The positive sera were further evaluated using immunofluorescence and plaque reduction neutralisation test (PRNT), in which only 17 sera were confirmed positive. This corresponds to a prevalence of 6.8 per 1,000 sera (95% CI: 4.0­10.9). In a case-control study that matched each of the 17 PRNT-positive sera with four negative sera with the same date of donation and same donation centre, we did not find a significant association with age and sex of the donor; donors who worked mainly outdoors were significantly more at risk to have a positive PRNT for WNV.

Dental hygienists behaviour towards HIV-positive patients in highly active antiretroviral therapy era: a pilot survey.

OBJECTIVES: Literature reports highlighted the presence of discriminatory episodes towards individuals infected with human immunodeficiency virus (HIV) on behalf of dental care workers. The purpose of this study was to assess hygienists' attitude when treating HIV-infected individuals in the era of highly active antiretroviral therapy (HAART). METHODS: A national observational study was carried out on all the members of an Italian hygienist association. An anonymous questionnaire was mailed to 1247 hygienists: the questionnaire investigated demographic data, the relationship between the hygienists and HIV-infected persons, to identify the presence of discriminatory behaviour, the hygienists' scientific knowledge of HIV-related problems and the precautions normally used in the office to prevent cross-infections. RESULTS: Of the 1247 questionnaires that were delivered to hygienists, 287 (23%) were completed and returned within a 6-month period. A total of 287 hygienists answered the question 'Did you ever deny treatment to an HIV-infected persons?' and 17 hygienists (5.9%) replied 'Yes'. Protective eyewear [odds ratio (OR), 0.036; 95% confidence interval (CI), 0.002-0.818; P = 0.037] and public practice [OR, 2.93; 95% CI, 0.97-8.87; P = 0.057] were associated with refusing to treat HIV-infected persons. CONCLUSION: Our findings highlight the existence of episodes of discrimination by some hygienists towards HIV-infected individuals. From clinical point of view, this discriminatory behaviour may expose the dental health care workers and their patients to a greater risk of cross-infection.

Molecular surveillance of pandemic influenza A(H1N1) viruses circulating in Italy from May 2009 to February 2010: association between haemagglutinin mutations and clinical outcome.

Haemagglutinin sequences of pandemic influenza A(H1N1) viruses circulating in Italy were examined, focusing on amino acid changes at position 222 because of its suggested pathogenic relevance. Among 169 patients, the D222G substitution was detected in three of 52 (5.8%) severe cases and in one of 117 (0.9%) mild cases, whereas the D222E mutation was more frequent and evenly distributed in mild (31.6%) and severe cases (38.4%). A cluster of D222E viruses among school children confirms reported human-to-human transmission of viruses mutated at amino acid position 222.

Viral hepatitis, HIV, human herpes virus and Treponema pallidum infection in haemodialysis patients from Kosovo, 2005.

The serological status of hepatitis viruses and other infectious diseases in the 66 dialysed patients of one haemodialysis unit in Kosovo were studied, comparing the data with a large group of blood donors and out-patients. All dialysed patients were hepatitis A virus (HAV) positive. Prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies (anti-HBs), and hepatitis B core antibodies (anti-HBc) was 14 of 66, 21% (95% confidence interval (CI): 12-33%), 5 of 66, 8% (95%CI: 5-22%), and 50 of 66, 76% (95%CI: 64-85%), respectively. Antibodies to hepatitis C virus (anti-HCV) prevalence was 57 of 66, 86% (95%CI: 76-94%). No human immunodeficiency virus (HIV) positive case was found. Prevalence of past herpes simplex virus type 2 (HSV-2) infection was 29% (95%CI: 18-41%). Two patients (3%, 95%CI: 0-10%) were positive for Treponema pallidum and 18% (95%CI: 10-30%) were human herpesvirus 8 (HHV-8) antibody positive. Four hundred and fifty-two subjects were recruited for comparison. Markers of past HAV infection was associated with haemodialysis (Fisher s exact test p-value=0.037). Dialysed patients were at a higher risk of being HBsAg positive than others: the sex- and age-adjusted odds ratio (OR) was 5.18 (95%CI: 1.87-14.32). Anti-HBc positivity was strongly associated with haemodialysis: the sex- and age-adjusted OR was 6.43 (95%CI: 3.22-12-85). Anti-HCV positivity was 86% and 1% in presence and absence of haemodialysis, respectively. The Fisher s exact test for association proved a strong association between haemodialysis and HCV (p-value<0.0001). The OR for association between haemodialysis and HSV-2 positivity was 3.20 (95%CI: 1.46-7.00). Significant associations were also observed between haemodialysis status and antibodies to Treponema pallidum (Fisher s exact test p-value=0.044). In Kosovo, the prevalence of viral hepatitis infection and other viral infections and Treponema pallidum among dialysed patients is high, indicating major ongoing nosocomial transmission.

West Nile virus transmission with human cases in Italy, August - September 2009.

In 2009, to date 16 human cases of West Nile neuroinvasive disease (WNND) have been reported in Italy, in three regions: Veneto, Emilia-Romagna and Lombardia. The number of cases is higher compared with last year when nine cases were identified (eight cases of WNND and one case of West Nile fever) and the geographical distribution indicates spread from east to west.

An outbreak of severe invasive meningococcal disease due to a capsular switched Neisseria meningitidis hypervirulent strain B:cc11.

OBJECTIVES: The aim was to investigate an outbreak of invasive meningococcal disease (IMD) in Southern Sardinia. METHODS: Epidemiological and microbiological investigations were performed. The latter included antimicrobial susceptibility testing and whole-genome sequencing (WGS). RESULTS: Seven individuals with severe IMD were found to be infected with serogroup B (MenB) Neisseria meningitidis in the first quarter of 2018. Five of the seven cases (five males; mean age 19 years; range 18-21 years; CFR 40%) were due to a unique strain B:P1.5-1,10-8:F3-6:ST-11(cc11), probably switched from the hypervirulent C-cc11, as confirmed by WGS. All five patients had attended the same nightclub in the 2 weeks prior to symptom onset. Public health measures, including chemoprophylaxis of contacts and active immunization against MenB, were implemented. CONCLUSIONS: We observed five IMD cases due to the same switched MenB strain. The hypervirulent B:P1.5-1,10-8:F3-6:ST-11(cc11) strain, probably switched from C-cc11, is of concern due to the observed high virulence and case fatality rates. All the patients shared the same place of probable exposure. The molecular characterization of the invasive strain allowed the outbreak to be confirmed, which was then controlled through timely public health action.

Infection with chikungunya virus in Italy: an outbreak in a temperate region.

BACKGROUND: Chikungunya virus (CHIKV), which is transmitted by Aedes spp mosquitoes, has recently caused several outbreaks on islands in the Indian Ocean and on the Indian subcontinent. We report on an outbreak in Italy. METHODS: After reports of a large number of cases of febrile illness of unknown origin in two contiguous villages in northeastern Italy, an outbreak investigation was done to identify the primary source of infection and modes of transmission. An active surveillance system was also implemented. The clinical case definition was presentation with fever and joint pain. Blood samples were gathered and analysed by PCR and serological assays to identify the causal agent. Locally captured mosquitoes were also tested by PCR. Phylogenetic analysis of the CHIKV E1 region was done. FINDINGS: Analysis of samples from human beings and from mosquitoes showed that the outbreak was caused by CHIKV. We identified 205 cases of infection with CHIKV between July 4 and Sept 27, 2007. The presumed index case was a man from India who developed symptoms while visiting relatives in one of the villages. Phylogenetic analysis showed a high similarity between the strains found in Italy and those identified during an earlier outbreak on islands in the Indian Ocean. The disease was fairly mild in nearly all cases, with only one reported death. INTERPRETATION: This outbreak of CHIKV disease in a non-tropical area was to some extent unexpected and emphasises the need for preparedness and response to emerging infectious threats in the era of globalisation.

Bacterial isolates from severe infections and their antibiotic susceptibility patterns in Italy: a nationwide study in the hospital setting.

The most frequent agents of severe bacterial infections and their antibiotic susceptibility patterns were determined in patients admitted to 45 Italian hospitals over the years 2002-2003. The most common diagnoses were: sepsis (33.8%), pneumonia (9.4%), intravascular catheter-associated infections (9.3%) and ventilator-associated pneumonia (8.1%). Overall, 5115 bacterial isolates were identified from 4228 patients. Three bacterial species, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, accounted for more than 50% of the isolates. Other prevalent bacterial isolates were Staphylococcus epidermidis and Enterococcus faecalis, while Acinetobacter baumanii ranked third among all Intensive Care Unit (ICU) isolates. 7% of S. aureus had intermediate resistance to vancomycin. Although E. faecalis displayed no vancomycin resistance, 34% of vancomycin-resistant isolates were found among Enterococcus faecium, one of the highest rates found to date, emphasizing the difference between these two enterococcal species. All the Gram-positive pathogens were susceptible to linezolid, with the exception of approximately 2% of the enterococcal isolates that were intermediate with a minimum inhibitory concentration (MIC)=4 microg/ml. Almost 10% of Escherichia coli, 14% of Klebsiella pneumoniae, 22% of Serratia marcescens and 50% of Enterobacter cloacae were non-susceptible to cefotaxime. Amikacin was the most active antibiotic against P. aeruginosa that showed lack of susceptibility to ceftazidime, gentamicin, piperacillin and ciprofloxacin ranging from 20 to 35%. Finally, Acinetobacter baumanii showed a high level of resistance to all the antibiotics tested including imipenem (58%). The results obtained in this study, the first of its kind in Italy, offer indications for guiding empirical therapy and implementing specific interventions to fight antibiotic-resistant bacterial infections and their transmission in the hospital setting in Italy.

Immunosuppression and cancer: A comparison of risks in recipients of organ transplants and in HIV-positive individuals.

The comparison of cancers occurring excessively among HIV-infected and transplanted individuals may help to elucidate the relationship between immune surveillance, viral infections, and cancer. A longitudinal study was conducted on 2002 HIV-infected Italian subjects, 6072 HIV-infected French individuals, and 2878 Italian recipients of solid organ transplants. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were computed to quantify the risk for cancer, compared with the French and Italian general populations. The SIRs for all cancers were 9.8 (95% CI: 9.0-10.6) for HIV-infected individuals versus 2.2 (95% CI: 1.9-2.5) for transplant recipients. In both groups, most of the excess risk was attributable to virus-related cancers, such as Kaposi's sarcoma (KS; SIR = 451 in HIV-positive individuals, 125 in transplant recipients), non-Hodgkin's lymphoma (NHL; SIR = 62.1 and 11.1, respectively), and liver cancer (SIR = 9.4 and 4.1, respectively). Significantly increased SIRs for anal cancer and Hodgkin's lymphoma were found only among HIV-positive individuals. Among women younger than 40 years of age, a more than 10-fold increase in cervical cancer risk was found in both groups. Among HIV-infected individuals treatment with highly active antiretroviral therapies drastically reduced SIRs for KS and NHL only. These results show that HIV-infected individuals and transplant recipients share a similar pattern of cancer risk, largely due to virus-related cancers.