Search

IntroductionFertility preservation (FP) and monitoring has considerable relevance in the multidisciplinary approach to cancer patients. In these consensus-based practical recommendations, the scientific societies Fondazione Italiana Linfomi (FIL) and Società Italiana della Riproduzione Umana (SIRU) reviewed the main aspects and identified the optimal paths which aim to preserve and monitor fertility in patients diagnosed with lymphoma at the different phases of the disease and during long-term survivorship.MethodsFor the Panel, eleven experts were selected for their expertise in research and clinical practice on onco-fertility and lymphoma. The Panel’s activity was supervised by a chairman. A series of rank-ordering key questions were proposed according to their clinical relevance and discussed among the Panel, focusing on patients diagnosed with non-Hodgkin’s lymphomas and Hodgkin lymphoma. Agreement among all the Panelists on the content and terminology of the statements was evaluated by a web-based questionnaire according to the Delphi methodology.ResultsFrom the literature review a total of 78 questions or sentences, divided into the 6 areas of interest, were identified. By applying the Gwet's AC, k was: Section 1: 0,934 (Very good); Section 2: 0,958 (Very good); Section 3: 0,863 (Very good); Section 4: 0,649 (Good); Section 5: 0,936 (Very good); Section 6 raw agreement 100%. Two rounds of Delphi allowed to provide the maximum agreement. All statements were newly discussed in a round robin way and confirmed for the drafting of the final recommendations.DiscussionThese recommendations would be useful for onco-hematologists, gynecologists, urologists, and general practice physicians who take care of young lymphoma patients to guarantee an evidence-based oncofertility assessment and treatment during the oncologic pathway.

Affordable, polyvalent meningococcal vaccines are needed for use in emergency reactive immunization campaigns. A phase IV randomized, observer-blind, controlled study compared the safety and immunogenicity of a quadrivalent meningococcal polysaccharide vaccine (MPV-4, MPV ACYW135) and quadrivalent meningococcal ACWY conjugate vaccine (MCV-4, Menactra®). Healthy, 2- to 10-year-old children in Bamako, Mali, were randomized 1:1 to receive one dose of MPV-4 or MCV-4. Safety outcomes were evaluated for 6 months post-immunization. Immunogenicity for all serogroups was assessed for non-inferiority between MPV-4 and MCV-4 30 days post immunization by serum bactericidal antibody assay using baby rabbit complement (rSBA). From December 2020 to July 2021, 260 healthy subjects were consented and randomized. At Day 30 post-immunization, the proportions of subjects with rSBA titers ≥ 128 for all serogroups in the MPV-4 group were non-inferior to those in MCV-4 group. The proportions of subjects with rSBA ≥ 4-fold increase and rSBA titers ≥ 8 for all serogroups were similar among vaccine groups (P > .05). Geometric Mean Titers and Geometric Mean Fold Increases for all serogroups in both vaccine groups were similar (P > .05). Few local and systemic post-immunization reactions of similar severity and duration were observed within 7 days and were similar in both groups (P > .05). All resolved without sequelae. Unsolicited adverse events were similar in both groups regarding relationship to study vaccine, severity and duration. No serious adverse events were reported during the study period. MPV ACYW135 showed a non-inferior immunogenicity profile and a comparable reactogenicity profile to MCV-4 in Malian children aged 2–10 years. Clinical Trial Registration: NCT04450498.

Antibodies elicited by a triple homologous or heterologous vaccination regimen or following natural SARS-CoV-2 infection combined with a two-dose vaccine course, result in highest neutralization capacity against the Omicron variant BA.1.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity whose neoplastic cells retain a B-cell phenotype with expression of CD20. Radiotherapy is recommended for favorable stage IA disease while for other stages guidelines suggest therapeutic strategies similar to those used for classic HL. The role of rituximab, although quite widespread, is not completely elucidated. We retrospectively analyzed baseline characteristics of 308 consecutive patients with NLPHL diagnosed in 19 Italian centers from 2000 to 2018. With a median follow-up of 8.4 years (interquartile range: 4.5–12.4) for treated patients, median overall survival (OS) was not reached and estimated 5-year OS was 97.8% and 5-year progression-free survival (PFS) was 84.5%. Five-year cumulative incidence of histological transformation was 1.4%, 95% confidence interval (CI), 0.5%-3.8%. After adjusting for lymphocyte count, splenic involvement, bulky disease and B symptoms (fever, drenching night sweats, unintentional loss >10% of body weight within the preceding 6 months), patients with stage II or more showed superior PFS with immunochemotherapy in comparison to chemotherapy alone (hazard ratio = 0.4, 95% CI, 0.2-0.8; P = 0.015). Our data suggest an advantage of the use of rituximab combined with chemotherapy ± radiotherapy in the treatment of stage II–III–IV NLPHL.

Vaccine development, in most cases, is a long, complex process, often lasting years and involving a combination of public and private stakeholders. Particularly, the vaccine clinical development process is highly regulated by several guidelines, regulatory pathways and science-based recommendations from experts. Designing and executing a successful clinical development plan for any candidate vaccine requires a solid scientific, medical, operational and regulatory knowledge and expertise, to comply with regulations and assure adequate benefit-risk balance for the product to be used in mass vaccination of healthy populations.The purpose of this study was to assess the approaches and practices related to Clinical Development functions, and related activities among vaccine manufacturers based in emerging countries, and to identify industry needs in terms of organizational development and training needs. A structured questionnaire designed specifically for assessing indicators of clinical activities, in the last five years, comprised of four sections aimed to collect information on (1) the organizational structure and the activities conducted by the clinical functions; (2) the clinical trial design ability and the management of clinical trial documents; (3) the clinical trial management and monitoring activities; (4) the quality aspects of clinical activities. The results suggest that the great majority of respondents is engaged in intense clinical development activities, as indicated by the high number of licensed vaccines available and supplied in the national markets or in foreign markets, including vaccines with WHO prequalification status.Areas to further strengthen the clinical activities and medical research preparedness were identified. Greater engagements of stakeholders’ and investments will be required to expand the clinical basis in vaccine R&D, and to support achieving a high level of preparedness in emerging countries, for development of new vaccines against future regional epidemics and global pandemics.

In March 2020, the first pandemic caused by a coronavirus was declared by the World Health Organization. Italy was one of the first and most severely affected countries, particularly the northern part of the country. The latest evidence suggests that the virus could have been circulating, at least in Italy, before the first autochthonous SARS-COV-2 case was detected in February 2020. The present study aimed to investigate the presence of antibodies against SARS-CoV-2 in human serum samples collected in the last months of 2019 (September–December) in the Apulia region, Southern Italy. Eight of 455 samples tested proved positive on in-house receptor-binding-domain-based ELISA. Given the month of collection of the positive samples, these findings may indicate early circulation of SARS-CoV-2 in Apulia region in the autumn of 2019. However, it cannot be completely ruled out that the observed sero-reactivity could be an unknown antigen specificity in another virus to which subjects were exposed containing an epitope adventitiously cross-reactive with an epitope of SARS-CoV-2.

The rapid replacement of Omicron BA.1 by BA.2 sublineage is very alarming, raising the question of whether BA.2 can escape the immunity acquired after BA.1 infection. We compared the neutralizing activity toward the Omicron BA.1 and BA.2 sub-lineages in five groups: COVID-19 patients; subjects who had received two doses of mRNA vaccine; subjects naturally infected with SARS-CoV-2 who had received two doses of mRNA; and subjects who had received three doses of homologous or heterologous vaccine. The results obtained highlight the importance of vaccine boosters in eliciting neutralizing antibody responses against Omicron sub-lineages, and suggest that the adenovirus vectored vaccine elicits a lower response against BA.1 than against BA.2 sub-lineage.

Background. The recently emerged SARS-CoV-2 Omicron variant exhibits several mutations on the spike protein, enabling it to escape the immunity elicited by natural infection or vaccines. Avidity is the strength of binding between an antibody and its specific epitope. The SARS-CoV-2 spike protein binds to its cellular receptor with high affinity and is the primary target of neutralizing antibodies. Therefore, protective antibodies should show high avidity. This study aimed at investigating the avidity of receptor-binding domain (RBD) binding antibodies and their neutralizing activity against the Omicron variant in SARS-CoV-2 infected patients and vaccinees. Methods. Samples were collected from 42 SARS-CoV-2 infected patients during the first pandemic wave, 50 subjects who received 2 doses of mRNA vaccine before the Omicron wave, 44 subjects who received 3 doses of mRNA vaccine, and 35 subjects who received heterologous vaccination (2 doses of adenovirus-based vaccine plus mRNA vaccine) during the Omicron wave. Samples were tested for the avidity of RBD-binding IgG and neutralizing antibodies against the wild-type SARS-CoV-2 virus and the Omicron variant. Results. In patients, RBD-binding IgG titers against the wild-type virus increased with time, but remained low. High neutralizing titers against the wild-type virus were not matched by high avidity or neutralizing activity against the Omicron variant. Vaccinees showed higher avidity than patients. Two vaccine doses elicited the production of neutralizing antibodies, but low avidity for the wild-type virus; antibody levels against the Omicron variant were even lower. Conversely, 3 doses of vaccine elicited high avidity and high neutralizing antibodies against both the wild-type virus and the Omicron variant. Conclusions. Repeated vaccination increases antibody avidity against the spike protein of the Omicron variant, suggesting that antibodies with high avidity and high neutralizing potential increase cross-protection against variants that carry several mutations on the RBD.

Abstract Purpose We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials. Patients and methods Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression‐free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT). Results About 1227 patients were included. The 7‐year OS was 84.3% (95% CI 80.8‐87.2) for ABVD vs 87.7% (95% CI 84.5‐90.2) for BEACOPP. Two follow‐up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP = 1.59; 95% CI 1.09‐2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7‐year PFS was 71.1% (95% CI 67.1‐74.6) for ABVD vs 81.1% (95% CI 77.5‐84.2) for BEACOPP (P

Prevention of congenital rubella is achieved by vaccination of susceptible women of childbearing age. In Italy, the National Plan for Measles and Congenital Rubella Elimination 2010–2015 implemented catch-up vaccination activities targeting susceptible adolescents and young adults, including women of childbearing age. The aim of this study was to assess the immunity against rubella in women of childbearing age in Tuscany (Central Italy) and Apulia (Southern Italy) and pregnant women in Apulia after the implementation of the National Plan for Measles and Congenital Rubella Elimination. Overall, anti-rubella IgG prevalence in women of childbearing age samples was 88.6% in Tuscany and 84.3% in Apulia. The lowest prevalence was observed in samples of 26–35 years old women of childbearing age in Apulia with 77.8%. Only 62.7% of samples from 26–35 years old pregnant women had IgG against rubella, and one sample out of 95 was positive to IgM. The findings of this study highlight the need for increasing awareness on the risk of contracting rubella infection during pregnancy and implement vaccination strategies to create opportunities for administration of rubella containing vaccines in young girls and women of childbearing age.

Background: Recombinant pertussis vaccines inducing long-lasting immune responses could help to control the rise in pertussis. We here report on persisting antibody responses 2 and 3 years after booster vaccination with a new generation recombinant acellular pertussis vaccine. Methods: Participants of a phase 2/3 randomised-controlled clinical trial with a monovalent pertussis vaccine containing genetically inactivated pertussis toxin (aPgen) or its tetanus and diphtheria toxoids combination (TdaPgen), or a chemically detoxified comparator vaccine (Tdapchem), (originally conducted between July and August 2015) were invited to participate in observational studies of persisting antibody responses 2 and 3 years after vaccination. Serum IgG against pertussis toxin (PT-IgG) and filamentous hemagglutinin (FHA-IgG) were assessed by ELISA, and PT-neutralising antibodies (PT-Nab) by Chinese Hamster Ovary cell assay. Findings: Waning of antibodies stabilised in aPgen and TdaPgen vaccinees 2 and 3 years after vaccination. Three years post-vaccination PT-neutralising antibodies remained 4·6-fold (95% Confidence Interval (CI) 2·6–8·1) and 3·7-fold (95% CI 2·2–6·1) higher, PT-IgG antibodies 3·0-fold (95% CI 2·2–4·1) and 2·5-fold (95% CI 1·9–3·3) higher, and FHA-IgG antibodies 1·8-fold (95% CI 1·3–2·5) and 1·6-fold (95% CI 1·2–2·1) higher than baseline in aPgen and TdaPgen recipients, respectively. In the Tdapchem group, PT-neutralising and PT-IgG and FHA-IgG antibodies were back at baseline levels 2 years post-vaccination. Three years post-vaccination seroconversion rates for PT-neutralising antibodies were 65·0% (95% CI 44·1–85·9) and 55·0% (95% CI 33·2–76·8) in aPgen and TdaPgen recipients, respectively. Interpretation: Considering the persistence of elevated antibody responses 3 years post-booster vaccination, genetically detoxified monovalent aPgen and TdaPgen vaccines can be expected to induce longer-lasting protection than chemically inactivated Tdap vaccines. Funding: BioNet-Asia

Measles in pregnancy may lead to serious sequelae for newborns and mothers. In Italy assessment of immunity against measles is not recommended as pregnancy screening. This study aimed to assess the immunity against measles in pregnant women from Apulia Region in Southern Italy between 2016 and 2017. Overall, 96.9% of pregnant women were positive for anti-measles IgG, younger women aged 19–29 years had a seroprevalence below 90%. No samples were positive for anti-measles IgM. In conclusion, younger pregnant women showed to be at higher risk of contracting measles during pregnancy. These findings have implication for measles vaccination policy and highlight the need for measles antibody testing in pregnancy screening in Italy.

Italy was the second country affected by the SARS-CoV-2 pandemic; the virus spread mainly in Northern Italy with a subsequent diffusion to the center and southern part of the country. In this study, we aimed to assess the prevalence of antibodies against SARS-CoV-2 in the general population of the Siena province in the Tuscany region (Central Italy) during 2020. A total of 2480 serum samples collected from January to December 2020 were tested for IgM and IgG antibodies against SARS-CoV-2 by a commercial ELISA. Positive and borderline samples were further tested for the presence of anti-receptor-binding domain (RBD) IgM and IgG antibodies by an in-house ELISA and by a micro-neutralization assay. Out of the 2480 samples tested by the commercial ELISA, 81 (3.3%) were found to be positive or borderline for IgG and 58 (2.3%) for IgM in a total of 133 samples (5.4%) found to be positive or borderline for at least one antibody class. When the commercial ELISA and in-house ELISA/micro-neutralization assay results were combined, 26 samples (1.0%) were positive for RBD IgG, 11 (0.4%) for RBD IgM, and 23 (0.9%) for a neutralizing antibody. An increase in seroprevalence was observed during the year 2020, especially from the end of summer, consistent with the routine epidemiological surveillance of COVID-19 cases.

Influenza is a vaccine preventable disease and vaccination remains the most effective method of controlling the morbidity and mortality of seasonal influenza, especially with respect to risk groups. To date, three types of influenza vaccines have been licensed: inactivated, live-attenuated, and recombinant haemagglutinin vaccines. Effectiveness studies allow an assessment of the positive effects of influenza vaccines in the field. The effectiveness of current influenza is suboptimal, being estimated as 40% to 60% when the vaccines strains are antigenically well-matched with the circulating viruses. This review focuses on influenza viruses and vaccines and the role of vaccine effectiveness studies for evaluating the benefits of influenza vaccines. Overall, influenza vaccines are effective against morbidity and mortality in all age and risk groups, especially in young children and older adults. However, the effectiveness is dependent on several factors such as the age of vaccinees, the match between the strain included in the vaccine composition and the circulating virus, egg-adaptations occurring during the production process, and the subject’s history of previous vaccination.

For more than a century, epidemic meningococcal disease mainly caused by serogroup A Neisseria meningitidis has been an important public health problem in sub-Saharan Africa. To address this problem, an affordable meningococcal serogroup A conjugate vaccine, MenAfriVac®, was developed specifically for populations in the African meningitis belt countries. MenAfriVac® was licensed based on safety and immunogenicity data for a population aged 1–29 years. In particular, the surrogate markers of clinical efficacy were considered to be the higher immunogenicity and the ability to prime immunological memory in infants and young children compared to a polysaccharide vaccine. Because of the magnitude of serogroup A meningitis epidemics and the high morbidity and mortality burden, the World Health Organization (WHO) recommended the MenAfriVac® deployment strategy, starting with mass vaccination campaigns for 1–29-year-olds to rapidly interrupt serogroup A person-to-person transmission and establish herd protection, followed by routine immunization of infants and toddlers to sustain protection and prevent epidemics. After licensure and WHO prequalification of MenAfriVac®, campaigns began in December 2010 in Burkina Faso, Mali, and Niger. By the middle of 2011, it was clear that the vaccine was highly effective in preventing serogroup A carriage and disease. Post introduction meningitis surveillance revealed that serogroup A meningococcal disease had disappeared from all age groups, suggesting that robust herd immunity had been achieved.

The introduction of a new Group A meningococcal conjugate vaccine, MenAfriVacR, has been a important public health success. Group A meningococcal meningitis has disappeared in all countries where the new Men A conjugate vaccine has been used at public health scale. However, continued control of Group A disease in sub-Saharan Africa will require that community immunity against Group A meningococci be maintained. Modeling studies have shown that unless herd immunity is maintained Group A meningococcal disease will return. To ensure that African populations remain protected birth cohorts must be protected with an EPI formulation of MenAfriVacR (5 mcg) given at 9 months with Measles 1. In addition, populations born after the initial 1-29 year old campaigns and consequently not yet immunized with the new Men A conjugate vaccine, will have to be immunized in country-specific catch-up campaigns. Countries with poor EPI coverage (Measles 1 coverage < 60%) will likely need quinquennial vaccination campaigns aimed at covering 1-4 year olds. Implementing these strategies is the only sure way of ensuring that Group A meningococcal meningitis epidemics will not recur. A second problem that requires urgent attention is the challenge of dealing with Non-A meningococcal meningitis epidemics in sub-Saharan Africa. Groups C, W and X meningococci are well-established circulating strains in sub-Saharan Africa and are responsible for yearly focal meningitis epidemics that vary in severity and remain unpredictable as to size and geographic distribution. For this reason, polyvalent meningococcal conjugate vaccines that are affordable and appropriate for the African context must be developed and introduced. These new meningococcal vaccines when combined with more affordable pneumococcal conjugate vaccines offer the promise of a meningitis-free Sub-Saharan Africa.

The recent spreading of new SARS-CoV-2 variants, carrying several mutations in the spike protein, could impact immune protection elicited by natural infection or conferred by vaccination. In this study, we evaluated the neutralizing activity against the viral variants that emerged in the United Kingdom (B.1.1.7), Brazil (P.1), and South Africa (B.1.351) in human serum samples from hospitalized patients infected by SARS-CoV-2 during the first pandemic wave in Italy in 2020. Of the patients studied, 59.5% showed a decrease (≥2 fold) in neutralizing antibody titer against B.1.1.7, 83.3% against P.1, and 90.5% against B.1.351 with respect to the original strain. The reduction in antibody titers against all analyzed variants, and in particular P.1 and B.1.351, suggests that previous symptomatic infection might be not fully protective against exposure to SARS-CoV-2 variants carrying a set of relevant spike mutations.

Although in humans West Nile virus is mainly the cause of mild or sub-clinical infections, in some cases a neuroinvasive disease may occur predominantly in the elderly. In Italy, several cases of West Nile virus infection are reported every year. Tuscany was the first Italian region where the virus was identified; however, to date only two cases of infection have been reported in humans. This study aimed at evaluating the prevalence of antibodies against West Nile virus in the area of Siena Province to estimate the recent circulation of the virus. Human serum samples collected in Siena between 2016 and 2019 were tested for the presence of antibodies against West Nile virus by ELISA. ELISA positive samples were further evaluated using immunofluorescence, micro neutralization, and plaque reduction neutralization assays. In total, 1.9% (95% CI 1.2–3.1) and 1.4% (95% CI 0.8–2.4) of samples collected in 2016–2017 were positive by ELISA and immunofluorescence assay, respectively. Neutralizing antibodies were found in 0.7% (95% CI 0.3–1.5) of samples. Additionally, 0.9% (95% CI 0.4–1.7) and 0.65% (95% CI 0.3–1.45) of samples collected in 2018–2019 were positive by ELISA and immunofluorescence assay, respectively. The prevalence of neutralizing antibodies was 0.5% (95% CI 0.2–1.3). Although no human cases of West Nile infection were reported in the area between 2016 and 2019 and virus prevalence in the area of Siena Province was as low as less than 1%, the active asymptomatic circulation confirms the potential concern of this emergent virus for human health.

Background: Adult patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) have prolonged survival but face the risk of treatment-induced impaired fertility. This systematic review, conducted by Fondazione Italiana Linfomi (FIL) researchers, aims to evaluate the incidence of treatment-related infertility, fertility preservation options, fertility assessment measures, and the optimal interval between the end of treatment and conception. Methods: MEDLINE, the Cochrane Library, and EMBASE were systematically searched up to September 2020 for published cohort, case–control, and cross-sectional studies on fertility issues. Results: Forty-five eligible studies were identified. Gonadotoxicity was related to sex, type and dosage of treatment, and, in females, to age. After receiving alkylating-agent-containing regimens, less than 30% of males recovered spermatogenesis, and 45% of females ≥30 years in age retained regular menstrual cycles. Sperm cryopreservation was offered to the majority of patients; sperm utilization resulted in a 33–61% pregnancy rate. After ovarian tissue transplantation, the spontaneous pregnancy and live birth rates were 38% and 23%; after IVF, the live birth rate was 38.4%. No data could be extracted on the utilization rate of cryopreserved mature oocytes. The results of studies on GnRH analogs are controversial; therefore, their use should not be considered an alternative to established cryopreservation techniques. Sperm count, FSH, and inhibin-B levels were appropriate measures to investigate male fertility; serum AMH levels and antral follicle count were the most appropriate markers for ovarian reserve. No data could be found regarding the optimal interval between the end of treatment and conception. Conclusions: The risk of infertility should be discussed with adult lymphoma patients at the time of diagnosis, and fertility preservation options should be proposed before first-line treatment with alkylating-agent-containing regimens.

Background: An acellular Pertussis (aP) vaccine containing recombinant genetically detoxified Pertussis Toxin (PTgen), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) has been developed by BioNet-Asia (BioNet). We present here the results of the first clinical study of this recombinant aP vaccine formulated alone or in combination with tetanus and diphtheria toxoids (TdaP). Methods: A phase I/II, observer-blind, randomized controlled trial was conducted at Mahidol University in Bangkok, Thailand in healthy adult volunteers aged 18–35 y. The eligible volunteers were randomized to receive one dose of either BioNet's aP or Tetanus toxoid-reduced Diphtheria toxoid-acellular Pertussis (TdaP) vaccine, or the Tdap Adacel® vaccine in a 1:1:1 ratio. Safety follow-up was performed for one month. Immunogenicity was assessed at baseline, at 7 and 28 d after vaccination. Anti-PT, anti-FHA, anti-PRN, anti-tetanus and anti-diphtheria IgG antibodies were assessed by ELISA. Anti-PT neutralizing antibodies were assessed also by CHO cell assay. Results: A total of 60 subjects (20 per each vaccine group) were enrolled and included in the safety analysis. Safety laboratory parameters, incidence of local and systemic post-immunization reactions during 7 d after vaccination and incidence of adverse events during one month after vaccination were similar in the 3 vaccine groups. One month after vaccination, seroresponse rates of anti-PT, anti-FHA and anti-PRN IgG antibodies exceeded 78% in all vaccine groups. The anti-PT IgG, anti-FHA IgG, and anti-PT neutralizing antibody geometric mean titers (GMTs) were significantly higher following immunization with BioNet's aP and BioNet's TdaP than Adacel® (P< 0.05). The anti-PRN IgG, anti-tetanus and anti-diphtheria GMTs at one month after immunization were comparable in all vaccine groups. All subjects had seroprotective titers of anti-tetanus and anti-diphtheria antibodies at baseline. Conclusion: In this first clinical study, PTgen-based BioNet's aP and TdaP vaccines showed a similar tolerability and safety profile to Adacel® and elicited significantly higher immune responses to PT and FHA.

According to the World Health Organization, the entire African continent is at risk of a Zika outbreak. To increase data availability on the epidemiology of Zika virus circulation in Africa, we evaluated the immunity to Zika virus in a selected cohort of subjects from West Africa between 2007 and 2012. Human serum samples were collected in 2007 and in 2011/2012 from a cohort of 2–29-year-old subjects from Mali, Senegal, and The Gambia. A sample that tested positive by Zika virus IgG ELISA and by Zika virus microneutralization test was defined as positive. In 2007, the highest prevalence was 21.9%, found in Senegal among 18–29-year-old subjects. In 2011/2012, the highest prevalence, 22.7%, was found still in Senegal, but in 11–17-year-old subjects. During both study periods, the lowest prevalence was found in Mali, where few positive cases were found only in 18–29-year-old subjects. The Gambia showed an intermediate prevalence. In the three countries, prevalence was strongly associated with increasing age. This study contributes to understanding Zika virus circulation within three different ecological and demographic contexts with scarce or no data currently available. Results showed that Zika virus circulated actively in West Africa between the period 2007 and 2011/2012, but with some geographic specificity.

Before its recent spread, serological investigations conducted between the 1960s and the 1990s showed the wide presence of Zika virus in Africa. According to the World Health Organization, the entire Africa continent is at risk of Zika outbreak due to the presence of the virus, competent vectors, and the low capacity for surveillance and containment of an epidemic. However, limited data are available on the recent prevalence in the African population. The aim of this study was to evaluate the immunity against Zika virus in samples of a selected cohort from West Africa, in order to investigate the circulation of the virus in the region during the first years of its emergence in the Pacific. Human serum samples were collected in 2007 and between 2011 and 2012 from a cohort of subjects from Mali, Senegal, and The Gambia. The samples were tested using an enzyme-linked immunosorbent assay (ELISA) detection kit and positives were further confirmed by microneutralization test. The results indicate that Zika virus is present and actively circulating in Senegal and The Gambia, with prevalence values of 13.7% and 6.9% in 2012, respectively. Although no significant differences in prevalence were found for the considered time period, seroconversion of some subjects showed the active circulation of Zika virus in the West African area. Analysis by age showed an increase in immunity in relation to increasing age, demonstrating that the population is consistently exposed to the virus throughout life and with a high possibility of being infected during reproductive age. In conclusion, the obtained results allow for better knowledge of the circulation of Zika virus within three different ecological and demographic contexts, and represent an update to the limited data currently available.

Varicella is a highly contagious, infectious disease caused by the varicella-zoster virus. Those at higher risk of severe complications are immunocompromised individuals, adults, non-immune pregnant women, and newborns. According to the gestational time, when varicella-zoster virus infection is acquired during pregnancy, serious complications can potentially occur for both the woman and the fetus. The present study was conducted to assess the profile of varicella susceptibility in pregnant women in Apulia, a large region in Southern Italy, from 2016 to 2019. The data showed that pregnant women between the age of 15–24 and 40–49 years, the youngest and the oldest, respectively, are the most protected against varicella-zoster virus infection, exceeding the prevalence rate of 90%. Conversely, pregnant women between the age of 25 and 34 years seem to be the most vulnerable and the most at risk for acquiring varicella-zoster virus infection during pregnancy. Analysis of the immunity status against varicella should be introduced as a screening test before pregnancy, together with a strategic vaccination campaign targeting non-immune women of childbearing age, in order to reduce the risk of congenital and perinatal varicella.

Treatment intensification to maximize disease control and reduced intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the meta-analysis herein, based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto’s method as time-to-event outcomes. For progression-free and overall survival, hazard ratios derived from each trial using Cox regression were combined by inverse-variance weighting. Five study questions (combined-modality treatment vs. chemotherapy alone; more extended vs. involved-field radiotherapy; radiation at higher doses vs. radiation at 20 Gy; more vs. fewer cycles of the same chemotherapy protocol; standard-dose chemotherapy vs. intensified chemotherapy) were investigated. After a median follow-up of 7.4 years, dose-intensified chemotherapy resulted in better progression-free survival rates (P=0.007) as compared with standard-dose chemotherapy, but was associated with an increased risk of therapy-related acute myeloid leukemia/myelodysplastic syndromes (P=0.0028). No progression-free or overall survival differences were observed between combined-modality treatment and chemotherapy alone, but more secondary malignant neoplasms were seen after combined-modality treatment (P=0.010). For the remaining three study questions, outcomes and secondary malignancy rates did not differ significantly between treatment strategies. The results of this meta-analysis help to weigh up efficacy and secondary malignancy risk for the choice of first-line treatment for Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up.

A retrospective, international, multicenter study was undertaken to assess: (i) the prognostic role of ‘interim’ positron emission tomography performed during treatment with doxorubicin, bleomycin, vinblastine and dacarbazine in patients with Hodgkin lymphoma; and (ii) the reproducibility of the Deauville five-point scale for the interpretation of interim positron emission tomography scan. Two hundred and sixty patients with newly diagnosed Hodgkin lymphoma were enrolled. Fifty-three patients with early unfavorable and 207 with advanced-stage disease were treated with doxorubicin, bleomycin, vinblastine and dacarbazine ± involved-field or consolidation radiotherapy. Positron emission tomography scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. An international panel of six expert reviewers independently reported the scans using the Deauville five-point scale, blinded to treatment outcome. Forty-five scans were scored as positive (17.3%) and 215 (82.7%) as negative. After a median follow up of 37.0 (2–110) months, 252 patients are alive and eight have died. The 3-year progression-free survival rate was 83% for the whole study population, 28% for patients with interim positive scans and 95% for patients with interim negative scans (P

Clinical trial results indicate that brentuximab vedotin brings considerable promise for the treatment of patients with relapsed or refractory Hodgkin’s lymphoma. A retrospective multicenter study was conducted on 65 heavily pretreated patients who underwent therapy through a Named Patient Program in Italy (non trial-setting). The primary study endpoint was the objective response rate; secondary endpoints were safety, overall survival and progression-free survival. The best overall response rate (70.7%), including 21.5% complete responses, was observed at the first restaging after the third cycle of treatment. After a median follow up of 13.2 months, the overall survival rate at 20 months was 73.8% while the progression-free survival rate at 20 months was 24.2%. Globally nine patients are in continuous complete response with a median follow up of 14 months (range, 10–19 months). Four patients proceeded to autotransplantation and nine to allotransplantation. The most frequent extra-hematologic toxicity was peripheral neuropathy, observed in 21.5% of cases (9 patients with grade 1/2 and 5 patients with grade 3/4); neurological toxicity led to discontinuation of treatment in three patients and to dose reduction in four. In general the treatment was well tolerated and toxicities, both hematologic and extra-hematologic, were manageable. This report indicates and confirms that brentuximab vedotin as a single agent is effective and safe also when used in standard, everyday clinical practice outside a clinical trial. Best overall responses were recorded after three or four cycles and showed that brentuximab vedotin provides an effective bridge to further therapeutic interventions.