Safety and immunogenicity of a 4-component GMMA-based Shigella vaccine in healthy European adults: Stage 1 of a randomized, controlled phase I/II clinical trial.

BACKGROUND: We report data from Stage 1 of an ongoing two-staged, phase I/II randomized clinical trial (NCT05073003) with a 4-component Generalized Modules for Membrane Antigens-based vaccine against Shigella sonnei and S. flexneri 1b, 2a and 3a (altSonflex1-2-3, GSK). METHODS: 18-50-year-old Europeans (N=102) were randomized (2:1) to receive two injections of altSonflex1-2-3 or placebo at 3- or 6-month interval. Safety and immunogenicity were assessed at pre-specified timepoints. RESULTS: The most common solicited administration-site event (until 7 days post-each injection) and unsolicited adverse event (until 28 days post-each injection) were pain (altSonflex1-2-3: 97.1%; Placebo: 58.8%) and headache (32.4%; 23.5%), respectively. All serotype-specific functional IgG antibodies peaked 14-28 days post-injection 1 and remained substantially higher than pre-vaccination at 3 or 6 months post-vaccination; the second injection did not boost but restored the initial immune response. The highest seroresponse rates (≥4-fold increase in titers over baseline) were obtained against S. flexneri 2a (ELISA: post-injection 1: 91.0%; post-injection 2 [Day {D}113; D197]: 100%; 97.0%; serum bactericidal activity (SBA): post-injection 1: 94.4%; post-injection 2: 85.7%; 88.9%) followed by S. sonnei (ELISA: post-injection 1: 77.6%; post-injection 2: 84.6%; 78.8%; SBA: post-injection 1: 83.3%; post-injection 2: 71.4%; 88.9%). Immune responses against S. flexneri 1b and S. flexneri 3a, as measured by both ELISA and SBA, were numerically lower compared to those against S. sonnei and S. flexneri 2a. CONCLUSIONS: No safety signals or concerns were identified. altSonflex1-2-3 induced functional serotype-specific immune responses, allowing further clinical development in the target population.

What is the context? Shigella bacteria cause severe and often bloody diarrhea, called shigellosis, that affects mostly young children and can be life-threatening. Shigellosis is particularly common in low- and middle-income countries due to inadequate sanitation and limited access to healthcare. Since the immune response to Shigella is serotype-specific, an ideal vaccine should include multiple Shigella serotypes to ensure broad protection. What is new? We developed a novel vaccine against Shigella that includes Shigella sonnei and three prevalent Shigella flexneri serotypes. In Stage 1 (phase I) of the study, healthy European adults received two vaccine injections given 3 or 6 months apart. We found that: The vaccine was well tolerated, and no safety signals or concerns were identified.Regardless of the interval between injections, specific antibodies were elicited against all four Shigella serotypes, with highest levels against Shigella flexneri 2a and Shigella sonnei.Functional antibody levels peaked after the first injection, remaining higher than the baseline up to 6 months. A second injection did not boost responses but restored functional antibody levels to those after the first injection. What is the impact? The vaccine can now be tested in Stage 2 (phase II) of the study in Africa, a region highly affected by shigellosis.

Mpox: Awareness, knowledge and information channels used by individuals accessing a sexually transmitted infections Helpline.

Background: Up until recently, monkeypox (mpox) was considered to be a rare zoonotic infection restricted to Central and West Africa. However, in July 2022, the World Health Organization declared mpox to be a public health emergency of international concern, after there were several outbreaks in non-endemic countries. This study assessed the information channels used by individuals accessing the "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse" of Istituto Superiore di Sanità (National Institute of Health in Italy) with regard to mpox. We also evaluated their awareness, and knowledge about mpox focusing on transmission and prevention. Methods: This is a cross-sectional study conducted on "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse" users, between January and April 2023. The target population was helpline users who were older than 18 years of age, and were phoning the service for the first time (i.e. who have not phoned in the last 12 months). Participants were interviewed using a questionnaire containing 19 questions filled by the interviewer. Collected data were analysed through descriptive statistics, and significance testing. Results: From January to April 2023, "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse" received 2,389 phone calls, 216 of which participated in this study. Most of these were male (85.2%; n=186), single (79.2%; n=171) and in employment (72.2%; n=156). Awareness about mpox was high (71.3%; n=154), with the central and south/islands regional areas having the highest percentage of participants who heard about the virus (84.3%; n=43 vs 72.4%; n=42; p=0.078). Television was the most frequently mentioned source of information about mpox by participants (63%; n=97; p<0.001). This medium was also the most preferred source of information about mpox (39%; n=60; p=0.109). The majority of participants stated that they did not know what mpox is (67.6%; n=146), and less than half knew that it is preventable (42.4%; n=89). Of those who stated that mpox is a preventable illness, less than half knew about the existence of a vaccine (44.9%; n=40; p<0.001). Conclusions: This study provides insights into the awareness, knowledge, prevention tools and information channels of individuals who contacted the "Telefono Verde AIDS e Infezioni Sessualmente Trasmesse". Useful indications for defining future information campaigns were obtained.

Therapeutic hypothermia is limited in preventing developmental impairments after neonatal hypoxia-ischemia.

The only current treatment for neonatal hypoxia-ischemia (HI) is therapeutic hypothermia (TH), which still shows some limitations. Specific effects of TH in the several processes involved in brain injury progression remain unclear. In this study, the effects of TH treatment on developmental parameters, behavioral outcomes, and peripheral leukocytes were evaluated in neonatal male and female rats. In P7, animals were submitted to right common carotid artery occlusion followed by hypoxia (8% oxygen). TH was performed by reducing the animal scalp temperature to 32°C for 5 h. Behavioral parameters and developmental landmarks were evaluated. Animals were euthanized at P9 or P21, and cerebral hemispheres, spleen, and thymus were weighed. White blood cells (WBC) were counted in blood smears. There was a reduction in the weight of the brain hemisphere ipsilateral to the carotid occlusion in HI and TH groups, as well as a reduction in body weight gain and a delay in the opening of the ipsilateral eye. Latency in negative geotaxis was increased by HI at P12. TH did not prevent brain weight loss, developmental impairments, or WBC number changes but prevented negative geotaxis impairment and spleen weight reduction. These data reinforce that a better understanding of the events that occur after HI and TH in both males and females is necessary and would allow the development of more adequate and sex-specific therapeutic approaches.

A next-generation GMMA-based vaccine candidate to fight shigellosis.

Shigellosis is a leading cause of diarrheal disease in low-middle-income countries (LMICs). Effective vaccines will help to reduce the disease burden, exacerbated by increasing antibiotic resistance, in the most susceptible population represented by young children. A challenge for a broadly protective vaccine against shigellosis is to cover the most epidemiologically relevant serotypes among >50 Shigella serotypes circulating worldwide. The GMMA platform has been proposed as an innovative delivery system for Shigella O-antigens, and we have developed a 4-component vaccine against S. sonnei, S. flexneri 1b, 2a and 3a identified among the most prevalent Shigella serotypes in LMICs. Driven by the immunogenicity results obtained in clinic with a first-generation mono-component vaccine, a new S. sonnei GMMA construct was generated and combined with three S. flexneri GMMA in a 4-component Alhydrogel formulation (altSonflex1-2-3). This formulation was highly immunogenic, with no evidence of negative antigenic interference in mice and rabbits. The vaccine induced bactericidal antibodies also against heterologous Shigella strains carrying O-antigens different from those included in the vaccine. The Monocyte Activation Test used to evaluate the potential reactogenicity of the vaccine formulation revealed no differences compared to the S. sonnei mono-component vaccine, shown to be safe in several clinical trials in adults. A GLP toxicology study in rabbits confirmed that the vaccine was well tolerated. The preclinical study results support the clinical evaluation of altSonflex1-2-3 in healthy populations, and a phase 1-2 clinical trial is currently ongoing.

A Pilot Study of Family-Integrated Care (FICare) in Critically Ill Preterm and Term Infants in the NICU: FICare Plus.

Family-integrated care (FICare) is associated with improved developmental outcomes and decreased parental mental health risks in stable preterm infants. However, less is known about its application in critically ill infants who are at greater risk for adverse outcomes. The objective of this study was to assess the safety and feasibility of implementation of an augmented FICare program, FICare Plus, in critically ill infants in the first few weeks of life. Resources were specifically developed for staff and parents to support earlier parental engagement in infant care. Infant health outcomes and standardized measures of parental stress, anxiety and parenting self-efficacy were also collected using standardized questionnaires: State -Trait Anxiety Inventory (STAI), Parental Stressor Scale: NICU (PSS: NICU), Perceived Parenting Self-Efficacy Tool and Family Centered Care Survey. The t-test or Wilcoxon rank-sum test were used to compare continuous variables, while the Chi-square or Fisher exact test were used for categorical variables, respectively. In this prospective cohort study, 41 critically ill infants were enrolled: 17 in standard care (SC) and 24 in the FICare Plus group. The tools and procedures developed for FICare Plus successfully supported greater engagement in the care of their infants with no increase in adverse events and no increase in parental stress. Parents in the FICare Plus cohort felt confident to participate in their infant's care. The staff also found this model of care acceptable and well adopted. Preliminary measures of infant efficacy were similar in both groups. Total anxiety scores were high among all parents at enrollment (87 (67-94) vs. 70.5 (66-86); p-value 0.22). However, the scores prior to discharge were lower in FICare Plus group (78 (71-90) vs. 63 (52-74.5); p-value 0.02). This pilot study showed that it is feasible and safe to implement family-integrated care in critically ill infants.

History and Function of the Lactate Receptor GPR81/HCAR1 in the Brain: A Putative Therapeutic Target for the Treatment of Cerebral Ischemia.

GPR81 is a G-protein coupled receptor (GPCR) discovered in 2001, but deorphanized only 7 years later, when its affinity for lactate as an endogenous ligand was demonstrated. More recently, GPR81 expression and distribution in the brain were also confirmed and the function of lactate as a volume transmitter has been suggested since then. These findings shed light on a new function of lactate acting as a signaling molecule in the central nervous system, in addition to its well-known role as a metabolic fuel for neurons. GPR81 seems to act as a metabolic sensor, coupling energy metabolism, synaptic activity, and blood flow. Activation of this receptor leads to Gi-mediated downregulation of adenylyl cyclase and subsequent reduction in cAMP levels, regulating several downstream pathways. Recent studies have also suggested the potential role of lactate as a neuroprotective agent, mainly under brain ischemic conditions. This effect is usually attributed to the metabolic role of lactate, but the underlying mechanisms need further investigation and could be related to lactate signaling via GPR81. The activation of GPR81 showed promising results for neuroprotection: it modulates many processes involved in the pathophysiology of ischemia. In this review, we summarize the history of GPR81, starting with its deorphanization; then, we discuss GPR81 expression and distribution, signaling transduction cascades, and neuroprotective roles. Lastly, we propose GPR81 as a potential target for the treatment of cerebral ischemia.

Short-term effects of therapeutic hypothermia following hypoxia-ischemia in neonatal male and female rats.

Nowadays, the only treatment for human babies suffering from hypoxia-ischemia (HI) is therapeutic hypothermia (TH). However, a better understanding of the specific effects of TH in males and females is important to improve its clinical application. The present study evaluated the short-term effects of TH on the brain injury and behavioral outcomes in male and female neonatal rats submitted to neonatal HI. Seven-day-old Wistar rats underwent a surgery for unilateral occlusion of the right common carotid artery and were exposed to a hypoxic atmosphere (8% oxygen) for 75 min. Then, the animals in the TH group were submitted to TH (scalp temperature of 32°C) for 5 h. In the behavioral tests, no remarkable differences triggered by HI or TH were observed relative to SHAM animals. Only females of the HI group presented lower latency to complete the righting reflex test. TH reduced the volume of brain injury in males, but not in females. The animals of the HI group showed a reduction in the number of neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus and TH partially prevented neuronal death. In the CA1 region of the hippocampus, animals from the HI group showed more degenerating cells relative to the SHAM, which was reversed by TH. In the DG, animals from the HI group showed an increase in the number of degenerating neurons, which was partially reversed by TH only in males. Our data show that HI leads to a brain injury, which was attenuated by TH in a sex-dependent way and clarify the importance of the assessment of males and females in order to outline specific strategies for the treatment of each sex in newborns suffering from HI.

Lethal Hydrogen Sulfide poisoning in open space: An atypical case of asphyxiation of two workers.

Hydrogen sulfide is one of the most dangerous toxic gases that has led to the deaths in confined spaces of many workers. We report an atypical case of a fatal accident of H2S poisoning in an open space when two workers died during the opening of a hatch on a tanker truck filled with leachate water. Despite being outdoors, the two workers, were suddenly and quickly overwhelmed by a lethal cloud of H2S, which escaped like a geyser from the hatch and hovered over the top of the tanker making it impossible for them to survive. The first operator was engulfed by the sudden flow of lethal gas near the hatch while the second worker, who came to his aid, immediately lost consciousness and fell off the tanker onto the ground. Environmental toxicological analyses were carried out on the air near the hatch and inside the tanker 2h, 20 days and 70 days after the accident. Toxicological analyses on the blood were also carried out but unfortunately, no urine sample was available. The thiosulfate, detected by GC/MS analysis after derivatization of PFBBr, was found to be 0.01 and 0.04mM/L. These values are included in the medium-low lethal values of occupational fatalities involving H2S reported in the literature.

A blended training programme for healthcare professionals aimed at strengthening territorial networks for the prevention and contrast of gender-based violence.

OBJECTIVES: a blended training programme combining residential meetings (de visu) and distance training course (DTC) have been developed in order to provide the key elements for prevention, individuation, and care of women victims of violence. DESIGN: the Project involved the identification and testing of a systematic methodology of blended training addressed to social and health operators of 28 Emergency Room (ER) Units in 4 Italian regions (Lombardy - Northern Italy, Lazio - Central Italy, Campania and Sicily - Southern Italy). Tuscany region (Central Italy) collaborated through experts in the field from the Grosseto Task Force. This training approach specifically aimed to increase the professional competences for diagnosis, management and treatment of gender-based violence, as well as to strengthen multidisciplinary territorial networks against violence. SETTING AND PARTICIPANTS: in this Project, 28 ERs in the four Italian regions mentioned above were selected because of their involvement in managing gender-based violence. This selection was performed by a coordinator, one for each region, who also coordinated the recruitment of personnel to be involved in the training programme. The programme has therefore been proposed to social and health operators and police officers in the ERs recruited. In each ER, two referents were identified (a doctor and a nurse) in order to ensure a constant connection between the course participants and the experts involved in the management of the Project and the DTC platform. MAIN OUTCOME MEASURES: evaluation of the increase of knowledge relatively to gender-based violence issue in the ER professionals who have concluded the blended training programme. A systematic analysis and comparison of all accesses concerning women aged ≥14 years in the period 1 July-31 December 2014 (before the blended training programme) and in the period 1 July-31 December 2016 (after the blended training program). RESULTS: among the 866 registered professionals, 636 participants (73.5%) completed the course, 202 (23.3%) professionals did not complete it, 21 (2.4%) did not pass the certification test, and 7 (0.8%) participated as Auditors. Among the participants who completed the course, most of them (70.8%) were females; the average age was 45 for both males and females. The most represented professional role was the nurse (61%), followed by the medical doctor (27.2%). Based on our data, in the post-training period, an increased number of cases of violence were correctly recorded in comparison to the pre-training period. CONCLUSION: the Project allowed to define a training strategy for health professionals of the ERs who respond daily to the health needs of women who are victims of violence. The blended training programme combining residential meetings (de visu) and distance training course has been developed in order to provide the key elements for prevention, individuation, and care of women victims of violence. The observed improvement in the recording and management of cases of gender-based violence is probably due to a greater competence in the awareness and use of specific diagnostic codes by ER professionals.

Communication and basic health counselling skills to tackle vaccine hesitancy.

The Italian law 119/2017 mandates ten childhood vaccinations to allow population aged 0-16 attend educational places and state school. This law enforcement is due to low coverage rates for some vaccine-preventable diseases and to a complex phenomenon known as vaccine hesitancy. Basic health counselling skills represent relevant resources to let healthcare workers effectively address vaccine hesitancy in the population. We indicated recommended communication approaches and basic health counselling skills to be applied by public health professionals according to the specific target population with vaccine deficit that means people not at all or partially reached by vaccinations. Public health professionals are called to know, acquire, use, and adapt basic health counselling skills to effectively address vaccine hesitancy diversely affecting different groups of population.

Health inequalities: a Research Positioning Exercise at the National Institute of Health, Italy.

BACKGROUND: The Italian National Institute of Health (Istituto Superiore di Sanità, ISS) considers health inequalities (HI) an important area of activity. As the scientific and technical body of the Ministry of Health and the National Health Service, ISS may play a key role to reduce HI. In order to enable ISS in addressing the new and crucial HI challenge, a Research Positioning Exercise was designed and implemented. METHODS: The Exercise included: (i) workshop to strengthen the institutional interest in the field of HI; (ii) review and analysis of ISS publications (years 2000-2017) to identify HI research topics; (iii) survey among ISS researchers regarding main research challenges to address HI in the coming years; and (iv) analysis of input on research challenges from HI international experts. RESULTS: The results of this Exercise suggest that the following points should be included in the future ISS agenda planning: (i) themes which ISS should continue working on (e.g. migrants/vulnerable groups); (ii) themes to be improved: (a) relationship between social determinants and mechanism of HI generation and (b) relationship between risk factors exposure and social determinants; and (iii) new themes to be addressed: (a) mechanisms underlying the resilience observed in Italy; (b) new socioeconomic indicators for HI monitoring; and (c) evidence-based policies aimed at reducing HI. CONCLUSION: Findings of this Exercise show that ISS researchers identified relevant areas, addressing inequalities in addressing the health. Because of ISS structural peculiarity that includes multidisciplinary expertise, the ISS could provide a significant contribution to HI research challenges and knowledge gaps.

Lethal endomyocarditis caused by chronic "Krokodil" intoxication.

"Krokodil" is a home-made opioid drug obtained by synthesizing desomorphine from codeine and combining it with other low-cost additives. Initially introduced in the former Soviet countries, it was then imported to Western Europe as a heroin substitute. To our knowledge, this is the first report of an Italian case of lethal krokodil abuse, that occurred in a 39-year-old man, who died suddenly after transportation to the Emergency Department (ED) for hyperthermia associated with sweating, dyspnoea and tachycardia. Post-mortem examination revealed extensive necrotic ulcerative lesions on the forearms, and autopsy showed a hypertrophic heart with ample endocardial vegetation on the aortic valve and patency of the foramen ovale. Histopathological examination of the heart showed ulcero-vegetative lesions of the aortic valve with an abscess on the annulus and extension to the periaortic adipose tissue, as well as diffuse myocardial interstitial inflammatory neutrophilic infiltrates. Toxicological analysis demonstrated a desomorphine metabolite in urine. On the basis of all these findings the cause of death was ruled to be congestive heart failure caused by endocarditis and myocarditis, correlated with chronic abuse of krokodil.

The role of vaccines and vaccine decision-making to achieve the goals of the Grand Convergence in public health.

On 17 and 18 July 2015, a meeting in Siena jointly sponsored by ADITEC and GlaxoSmithKline (GSK) was held to review the goals of the Global Health 2035 Grand Convergence, to discuss current vaccine evaluation methods, and to determine the feasibility of reaching consensus on an assessment framework for comprehensively and accurately capturing the full benefits of vaccines. Through lectures and workshops, participants reached a consensus that Multi-Criteria-Decision-Analysis is a method suited to systematically account for the many variables needed to evaluate the broad benefits of vaccination, which include not only health system savings, but also societal benefits, including benefits to the family and increased productivity. Participants also agreed on a set of "core values" to be used in future assessments of vaccines for development and introduction. These values include measures of vaccine efficacy and safety, incident cases prevented per year, the results of cost-benefit analyses, preventable mortality, and the severity of the target disease. Agreement on this set of core assessment parameters has the potential to increase alignment between manufacturers, public health agencies, non-governmental organizations (NGOs), and policy makers (see Global Health 2035 Mission Grand Convergence [1]). The following sections capture the deliberations of a workshop (Working Group 4) chartered to: (1) review the list of 24 parameters selected from SMART vaccines (see the companion papers by Timmis et al. and Madhavan et al., respectively) to determine which represent factors (see Table 1) that should be taken into account when evaluating the role of vaccines in maximizing the success of the Global Health 2035 Grand Convergence; (2) develop 3-5 "core values" that should be taken into account when evaluating vaccines at various stages of development; and (3) determine how vaccines can best contribute to the Global Health 2035 Grand Convergence effort.

The role of vaccines and vaccine decision-making to achieve the goals of the grand convergence in public health

On 17 and 18 July 2015, a meeting in Siena jointly sponsored by ADITEC and GlaxoSmithKline (GSK) was held to review the goals of the Global Health 2035 Grand Convergence, to discuss current vaccine evaluation methods, and to determine the feasibility of reaching consensus on an assessment framework for comprehensively and accurately capturing the full benefits of vaccines. Through lectures and workshops, participants reached a consensus that Multi-Criteria-Decision-Analysis is a method suited to systematically account for the many variables needed to evaluate the broad benefits of vaccination, which include not only health system savings, but also societal benefits, including benefits to the family and increased productivity. Participants also agreed on a set of "core values" to be used in future assessments of vaccines for development and introduction. These values include measures of vaccine efficacy and safety, incident cases prevented per year, the results of cost-benefit analyses, preventable mortality, and the severity of the target disease. Agreement on this set of core assessment parameters has the potential to increase alignment between manufacturers, public health agencies, non-governmental organizations (NGOs), and policy makers (see Global Health 2035 Mission Grand Convergence [1]). The following sections capture the deliberations of a workshop (Working Group 4) chartered to: (1) review the list of 24 parameters selected from SMART vaccines (see the companion papers by Timmis et al. and Madhavan et al., respectively) to determine which represent factors (see Table 1) that should be taken into account when evaluating the role of vaccines in maximizing the success of the Global Health 2035 Grand Convergence; (2) develop 3–5 "core values" that should be taken into account when evaluating vaccines at various stages of development; and (3) determine how vaccines can best contribute to the Global Health 2035 Grand Convergence effort.

Information needs of young Italians accessing the AIDS/STI Helpline at the Italian National Institute of Health.

INTRODUCTION: HIV/AIDS and sexually transmitted infections (STI) have a relevant impact on health and sexual behavior of adolescents and young adults (range of age between 13 and 19 years). The AIDS and sexual transmitted infections (STI) Helpline of the Italian Istituto Superiore di Sanità (National Institute of Health), and also funded by the Italian Ministry of Health, has been active since 1987 providing personalized counselling interventions on HIV/AIDS and STI. AIM AND METHODS: The present study gathered data and questions issues from calls at AIDS/STI Helpline in the period 1987-2014, with the specific aim of assessing the level of awareness and information needs on HIV/AIDS and STI among people aged under 25 years, in relation to potential risky behavior. RESULTS: Data show that young subjects who called the helpline in the period considered are about the 26% of the total users, with a decreasing trend over the years. The 28% of young users reported a "risky behavior" for STI, with a chance statistically higher in the age range 15-19 years and in the MSM (men who have sex with men)/bisexuals users, which tended to decrease in the last years. Of note, a marked increase of the amount of young users not displaying behaviors at risk for HIV or STI has been observed in the years.

Production of a Shigella sonnei Vaccine Based on Generalized Modules for Membrane Antigens (GMMA), 1790GAHB.

Recently, we developed a high yield production process for outer membrane particles from genetically modified bacteria, called Generalized Modules of Membrane Antigens (GMMA), and the corresponding simple two step filtration purification, enabling economic manufacture of these particles for use as vaccines. Using a Shigella sonnei strain that was genetically modified to produce penta-acylated lipopolysaccharide (LPS) with reduced endotoxicity and to maintain the virulence plasmid encoding for the immunodominant O antigen component of the LPS, scale up of the process to GMP pilot scale was straightforward and gave high yields of GMMA with required purity and consistent results. GMMA were formulated with Alhydrogel and were highly immunogenic in mice and rabbits. In mice, a single immunization containing 29 ng protein and 1.75 ng of O antigen elicited substantial anti-LPS antibody levels. As GMMA contain LPS and lipoproteins, assessing potential reactogenicity was a key aspect of vaccine development. In an in vitro monocyte activation test, GMMA from the production strain showed a 600-fold lower stimulatory activity than GMMA with unmodified LPS. Two in vivo tests confirmed the low potential for reactogenicity. We established a modified rabbit pyrogenicity test based on the European Pharmacopoeia pyrogens method but using intramuscular administration of the full human dose (100 µg of protein). The vaccine elicited an average temperature rise of 0.5°C within four hours after administration, which was considered acceptable and showed that the test is able to detect a pyrogenic response. Furthermore, a repeat dose toxicology study in rabbits using intramuscular (100 µg/dose), intranasal (80 µg/dose), and intradermal (10 µg/dose) administration routes showed good tolerability of the vaccine by all routes and supported its suitability for use in humans. The S. sonnei GMMA vaccine is now in Phase 1 dose-escalation clinical trials.

Simplified low-cost production of O-antigen from Salmonella Typhimurium Generalized Modules for Membrane Antigens (GMMA).

The Novartis Vaccines Institute for Global Health is developing vaccines using outer membrane particles, known as Generalized Modules for Membrane Antigens (GMMA). These are blebs of outer membrane and periplasm, shed from the surface of living Gram-negative bacteria following the targeted deletion of proteins involved in maintaining the integrity of the inner and outer membranes. The current study investigates the use of GMMA as starting material for extraction of membrane components, focusing on the O-antigen polysaccharide portion of lipopolysaccharide from Salmonella Typhimurium. We show that the amount of O-antigen extracted from GMMA by acid hydrolysis is comparable to the quantity extracted from whole wild type bacteria, but with less protein and DNA contaminants. Compared to conventional purification, GMMA enabled a reduction in the number of purification steps required to obtain the O-antigen polysaccharide with the same purity. Purification processes from GMMA and bacteria were characterised by similar final yields. Use of GMMA as starting material provides the possibility to simplify the purification process of O-antigen, with a consequent decrease in manufacturing costs of O-antigen-based glyconjugate vaccines against Salmonella strains and potentially other Gram-negative bacteria.

Sex workers clients in Italy: results of a phone survey on hiv risk behaviour and perception.

INTRODUCTION: Sex workers (SW) clients represent a bridge population for HIV transmission from high risk to low risk general population. MATERIALS AND METHODS: A cross-sectional anonymous telephone survey was carried out at the AIDS and Sexually Transmitted Infections Helpline of National Institute of Health in Italy. The questionnaire was proposed on a voluntary basis to a sample of 119 subjects from helpline users. RESULTS: The 119 participants were all males, aged between 19 and 59 years and mostly accessed female prostitutes. Vaginal intercourses with SW were more frequently reported, followed by passive oral, active oral sex and active anal intercourses. Cumulatively, 86.6% and 84.6% of vaginal and anal intercourses were respectively reported as regularly protected by condom. DISCUSSION: The telephone interview allowed an eased access, a high response rate and a standardised evaluation of questions. CONCLUSIONS: It is necessary a constant monitoring of the characteristics, behaviour, risk perception and testing of SW clients in Italian and other populations.

Communication and cultural interaction in health promotion strategies to migrant populations in Italy: the cross-cultural phone counselling experience.

INTRODUCTION: In the last 10 years migration processes have progressively increased worldwide and in Italy about 5 millions of residing migrants are estimated. To meet health needs of these new residents, effective relational and communication tools, which allow a reciprocal intercultural interaction within health care structures, are therefore necessary. AIM: This article faces the main features of the relational-communication processes associated with health promotion and care in the migrant population in Italy to the aim of identifying the key and critical points within the interaction between different cultures, focusing on the role of specific professional figures, including cultural mediators and health educators. RESULTS: Within the activity of HIV phone counselling operated by Psycho-sociobehavioural, Communication and Training Operating Unit of National Institute of Health in Italy, an intercultural approach was successfully experienced in a project targeted to migrants (2007-2008). Specifically, the presence of cultural mediators answering in the languages of main migrants' groups allowed the increase of calls from migrant people and of the information provided.

Sexual behaviours of clients of sex workers reported within phone calls at HIV/AIDS/STIs Italian Helpline.

BACKGROUND: Clients of sex workers represent a relevant target for interventions aimed at the prevention of HIV and sexually transmitted infections (STIs). Within prevention strategies, the AIDS and sexually transmitted infections helpline (Telefono Verde AIDS/ IST, TVA-IST) of National Institute of Health in Italy has provided, since 1987, specific information and counselling interventions. AIM: The present study reports data on anagraphical characteristics and behaviours of clients of sex workers, anonymously reported at TVA-IST in the period 1987-2010. DISCUSSION: Among 95 149 phone calls (14% of the total) considered 99.5% came from males, over 80% aged under 37 years and prevalently from Northern Italy. Among sexual behaviours, unprotected sexual intercourses were reported in the 26% of the calls. Subjects under 27 years reported a higher frequency of unprotected anal intercourse, while they used protection with oral and vaginal intercourses in a greater extent than older ones. Due to differential behaviours within clients of sex workers, specific informative strategies for this targeted population should adequately consider age-related differences.