Immunogenicity of meningococcal polysaccharide ACWY vaccine in primary immunized or revaccinated adults.

Meningococcal polysaccharide (Men-Ps) vaccine immunogenicity following either primary immunization or revaccination in adults was evaluated. The study population consisted of subjects who have received tetravalent Men-Ps vaccine once (group 1) or at least twice, with a 2-6 dose range (group 2). Human leucocyte antigen (HLA)-typing was performed by polymerase chain reaction and specific immunoglobulin (Ig)G was measured by enzyme-linked immunosorbent assay. Nine months post-immunization, the percentages of individuals with levels of anti-Men-Ps IgG ≥ 2 µg/ml were comparable in both groups, with the exception of anti-Men-PsW135 IgG, which were significantly higher in group 2. The percentage of subjects doubling IgG levels at 9 months was significantly higher in group 1. The high baseline anti-Men-Ps antibody levels negatively influenced the response to revaccination, suggesting a feedback control of specific IgG. The calculated durability of anti-Men-Ps IgG was 2·5-4·5 years, depending on the Men-Ps, following a single vaccine dose. No interference by other vaccinations nor HLA alleles association with immune response were observed. This study confirms that Men-Ps vaccine in adults is immunogenic, even when administered repeatedly, and underlines the vaccine suitability for large-scale adult immunization programmes that the higher costs of conjugate vaccines may limit in developing countries.

Safety and immunogenicity of co-administered MF59-adjuvanted 2009 pandemic and plain 2009-10 seasonal influenza vaccines in rheumatoid arthritis patients on biologicals.

Rheumatoid arthritis (RA) patients under immunosuppressive therapy are particularly susceptible to infections, mainly of the respiratory tract, thus vaccination may represent a strategy to reduce their incidence in this vulnerable population. In the 2009-10 influenza season, the safety and immunogenicity of co-administered non-adjuvanted seasonal and MF59-adjuvanted pandemic influenza vaccines were evaluated in this study in 30 RA patients under therapy with anti-tumour necrosis factor (TNF)-α agents or Abatacept and in 13 healthy controls (HC). Patients and HC underwent clinical and laboratory evaluation before (T0), 1 (T1) and 6 months (T2) after vaccinations. No severe adverse reactions, but a significant increase in total mild side effects in patients versus HC were observed. Both influenza vaccines fulfilled the three criteria of the Committee for Proprietary Medicinal Products (CPMP). Seroconversion rate for any viral strain in patients and HC was, respectively, 68 versus 45 for H1-A/Brisbane/59/07, 72 versus 81 for H3-A/Brisbane/10/07, 68 versus 54 for B/Brisbane/60/08 and 81 versus 54 for A/California/7/2009. A slight increase in activated interferon (IFN)-γ-, TNF-α- or interleukin (IL)-17A-secreting T cells at T1 compared to T0, followed by a reduction at T2 in both patients and HC, was registered. In conclusion, simultaneous administration of adjuvanted pandemic and non-adjuvanted seasonal influenza vaccines is safe and highly immunogenic. The largely overlapping results between patients and HC, in terms of antibody response and cytokine-producing T cells, may represent further evidence for vaccine safety and immunogenicity in RA patients on biologicals.

A case of dengue type 3 virus infection imported from Africa to Italy, October 2009.

In October 2009, a traveller returning from Africa to Italy was hospitalised with symptoms suggestive of a haemorrhagic fever of unknown origin. The patient was immediately placed in a special biocontainment unit until laboratory investigations confirmed the infection to be caused by a dengue serotype 3 virus. This case reasserts the importance of returning travellers as sentinels of unknown outbreaks occurring in other countries, and highlights how the initial symptoms of dengue fever resemble those of other haemorrhagic fevers, hence the importance of prompt isolation of patients until a final diagnosis is reached.

Detection of interleukin-2 in addition to interferon-gamma discriminates active tuberculosis patients, latently infected individuals, and controls.

Effective control of tuberculosis (TB) includes discrimination of subjects with active TB from individuals with latent TB infection (LTBI). As distinct interferon (IFN)-gamma and interleukin (IL)-2 profiles of antigen-specific T-cells have been associated with different clinical stages and antigen loads in several viral and bacterial diseases, we analysed these cytokines in TB using a modified QuantiFERON-TB Gold In Tube test. Detection of IL-2 in addition to IFN-gamma distinguishes not only Mycobacterium tuberculosis-infected subjects from healthy controls, but also individuals with LTBI from active TB patients. This may help to improve diagnostic tests for TB.

Influenza vaccine administration in rheumatoid arthritis patients under treatment with TNFalpha blockers: safety and immunogenicity.

Twenty-eight patients with low-moderate, stable rheumatoid arthritis (RA), under treatment with tumor necrosis factor (TNF) alpha blockers, were immunized at least once with non-adjuvanted trivalent influenza vaccine during three consecutive influenza seasons. Antibodies toward A influenza antigens significantly increased and reached protective levels, still detectable 6 months after vaccination, both in RA patients and healthy controls. Response to B antigen instead was only observed from the second year for healthy controls and in the third year for patients. No significant difference in disease activity and anti-nuclear antibodies was observed as a consequence of vaccine administration, whereas T regulatory cells showed a significant increase 30 days after immunization in RA patients. This study confirms safety of influenza vaccine administration in RA patients treated with TNFalpha blockers. The cohort follow-up revealed the overcoming of poor B vaccine antigen immunogenicity via repeated vaccinations. Finally, protective antibody response was still observed 6 months after vaccination.

European concepts for the domestic transport of highly infectious patients.

Highly infectious diseases involve clinical syndromes ranging from single to multiorgan infections and pose a constant threat to the public. In the absence of a definite treatment for most causative agents, patients benefit from maximum supportive care as clinical conditions may deteriorate in the short term. Hence, following initial case identification and isolation, rapid transportation to a specialized treatment unit must be considered in order to minimize the risk of secondary infections, but this is limited by available infrastructure, accessible care en route and the patient's clinical condition. Despite the development of consensus curricula for the clinical management of highly infectious patients, medical transportation lacks a common European approach. This article describes, as examples, three current European concepts for the domestic relocation of highly infectious patients by ground vehicles and aircraft with respect to national legislation and geography.

Influenza vaccine administration in patients with systemic lupus erythematosus and rheumatoid arthritis. Safety and immunogenicity.

OBJECTIVE: To evaluate immunological safety and immunogenicity of influenza vaccine administration in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). PATIENTS AND METHODS: Twenty-four patients with low and/or stable disease activity 14 with SLE (mean age 43.42+/-12.18 years; 13 women) and 10 with RA (mean age 51+/-14.57 years; 9 women), diagnosed on the basis of the American College of Rheumatology criteria, have been immunized with trivalent split influenza vaccine without adjuvant. Further 24 non-vaccinated patients, 14 with SLE and 10 with RA, and 10 vaccinated healthy subjects, all age- and sex-matched, were used as controls. The patients underwent clinical and laboratory (specific anti-influenzavirus antibodies, auto-antibodies, peripheral blood lymphocyte subpopulations) evaluation before and 30 days after vaccination; auto-antibodies were also assessed at 90 days and disease activity at 90 and 180 days. RESULTS: The specific antibody response towards the three used antigens (A/New Caledonia/20/99, A/Moscow/10/99, and B/Shangdong/7/97) significantly increased in both patients and healthy controls, without any significant difference between them. No significant difference could instead be observed on the clinical activity, auto-antibodies, and peripheral blood lymphocyte subpopulations before and after vaccination, and between patients and controls. CONCLUSIONS: Trivalent split influenza vaccine without adjuvant seems to be safe and immunogenic in patients with SLE and RA, provided that only patients with low and/or stable disease activity are selected.

Modified autonomic balance in offsprings of diabetics detected by spectral analysis of heart rate variability.

This study was performed to evaluate the influence of family history for non-insulin-dependent diabetes mellitus (NIDDM) on autonomic balance. The latter was assessed by spectral analysis of heart rate variability (SA-HRV) and by analyzing the relative contribution of low-frequency (LF) and high-frequency (HF) components. Twenty glucose normotolerant offsprings of NIDDM parents and 20 controls underwent a 1-hour continuous electrocardiogram (ECG). LF and HF (mean +/- SEM in normalized units [NU]), respectively increased and decreased in offspring versus controls. The LF/HF ratio (mean +/- SEM) significantly increased (LF/HF = 3.25 +/- 0.7 v 1.45 +/- 0.5, P <.0001 offsprings v controls). To test a stimulated response, a passive tilting (+ 90 degrees ) after 30 minutes of bed rest (0 degrees ) was performed in a subsample of subjects (10 offsprings v 10 controls). During bed rest, we found significantly higher values of the LF/HF ratio in offsprings versus controls (1.93 +/- 0.3 v 1.08 +/- 0.2, P <.05), whereas in the head-up position, the LF/HF ratio value increased to the same levels in the 2 groups (6.48 +/- 1.3 v 6.89 +/- 1.4, not significant [NS]). NIDDM family history is characterized in the basal condition by an imbalance of the autonomic system, which, compared with controls, is expressed by a higher weight of sympathetic and a lower weight of parasympathetic components. No significant differences can be found under stimulated conditions.

A global review of legislation on HIV/AIDS: the issue of HIV testing.

OBJECTIVE: Critical review of worldwide legislation on HIV/AIDS, with a focus on the issue of HIV testing, mainly in a military context. DESIGN: Analysis of health legislation on HIV/AIDS among 121 of the 191 member states of the World Health Organization (WHO), representing 85% of the world's population. METHODS: The WHO Directory of Legal Instruments Dealing with HIV Infection and AIDS has been the main source consulted. Relevant findings of two global surveys were used to examine HIV testing in the military. RESULTS: AIDS cases are reportable in 60% of the 121 countries, whereas HIV infections in no more than 26%. Notifications are kept confidential by law in 20% of countries. Only 17% have developed HIV-specific legislation against social discrimination, whereas 10% have passed legislation establishing financial reimbursement to those who have acquired HIV infection after injection of HIV-contaminated biologic material, support for occupational risk, and/or social protection for patients. Only 42% of the 121 countries report having legal instruments that require screening of donated blood. Legislative measures that address, generally in a prescriptive but sometimes also in a protective way, vulnerable groups, such as commercial sex workers, men who have sex with men, injecting drug users, and recipients of multiple transfusions of blood or blood-derivatives, are reported in 27% of countries. Other categories considered potentially vulnerable, for which specific legislation has been passed, include immigrants (17% of countries), prisoners (5%), and health personnel (14%). Further legislative measures for HIV prevention address testing pregnant women in the prenatal period (7% of countries), supporting condom promotion (11%), measures requiring quarantine, isolation, or coercive hospitalization of HIV-infected people or AIDS patients (9%), or imposing penal sanctions for HIV-infected people who deliberately expose others to the risk of transmission (10%). A National AIDS Committee responsible for addressing issues related to HIV/AIDS has been established by law in 39% of the 121 countries. Global surveys show that 27 countries carry out compulsory HIV screening on recruitment of military personnel. CONCLUSIONS: These data represent a useful tool to make governments aware of the problem of underreporting of legal instruments to the WHO and of the need to promote legislation in line with the idea that public health and human rights are complementary, not conflicting, goals.

Neuronal ceroid lipofuscinosis: an ultrastructural, genetic, and clinical study report.

The term "neuronal ceroid lipofuscinosis" (NCL) describes a complex of inherited neurodegenerative conditions associated with storage of lipopigments in brain tissue. In 1989 Dyken proposed a classification of NCL based on the age, clinical symptoms, and ultrastructural aspects of the lipopigments. At the ultrastructural level it is possible to distinguish 5 different patterns of osmiophilic lipopigments: usual lipofuscin, fingerprint deposits, granular profiles, curvilinear bodies, and microtubular aggregates. The concept that each ultrastructural pattern was the counterpart of a specific clinical type has been proved not to be true. Advances in molecular genetic techniques have allowed the identification of defective genes and their protein products in several NCL clinical forms. Ceroid lipofuscin deposits may be ultrastructurally observed not only in neuronal cells, but also in several other sites, such as trophoblastic cells, thus permitting prenatal diagnosis. In spite of recent advances in immunohistochemical identification of biochemical markers, the ultrastructural identification of lipofuscinic pigments remains the gold standard to identify NCL, together with clinical aspects and respective gene defects. This study describes the ultrastructural aspects observed in 8 cases of NCL syndromes (3 juvenile, 3 infantile, 1 late infantile, and 1 congenital clinical form). In these patients, genetic analysis was also performed.

Surveillance of infectious diseases in the Italian military as pre-requisite for tailored vaccination programme.

Surveillance and control of infectious diseases in the Italian military include prompt reporting of all occurring cases and prophylaxis through compulsory vaccination practices. The last mandatory immunisation programme in the Italian military was launched in 1998 (more than 10 years after the previous programme was introduced in 1986-1987) and it was planned according to the epidemiological data herein reported. The incidence rates (number of cases x 100000 subjects) of infectious diseases notified during the period 1976-1980 were compared with the corresponding figures notified 15 years later (1991-1995). An increase of three airborne-transmitted viral diseases--varicella, rubella and measles--counterbalanced by a decrease of other infectious diseases, such as mumps, typhoid fever, tuberculosis, viral hepatitis, scabies, syphilis and gonorrhea, was observed. This may be related to improvements in the general hygienic conditions and more responsible sexual behaviour among Italian military recruits. Moreover, incidence rates of cases notified in the military were compared with those notified in the general population of the same sex- and similar age-range (15-24 years) over a 12-year period (1986-1997), to monitor the epidemiological situation in relation to (a) potential risk factors specifically linked to military life and (b) protective effects induced by specific vaccinations. Airborne-transmitted viral diseases, such as varicella, rubella, measles and mumps--which are usually underreported among civilians--show higher incidence rates in the military. Meningococcal meningitis shows higher incidence rates in the military in 1986 and 1987 (before the introduction of mandatory specific vaccination) as well as in 1995-1997 (main etiologic agent N. meningitidis serogroup B); similar rates were instead observed in the other years. Incidence rates for typhoid fever are generally lower in the military, despite the community life, probably reflecting the protective efficacy of specific vaccine. Hepatitis A and B show similar rates between military and civilian population. Finally, pulmonary tuberculosis generally shows higher rates in the military. These data therefore allow the conclusion that the only infectious diseases, for which possible risk factors in the military life may be hypothesised, seem to be meningococcal meningitis and perhaps pulmonary tuberculosis. Epidemiological surveillance of infectious diseases in the military as a pre-requisite for appropriate public health intervention strategy represents a good model to be followed also in larger contexts.

Chylomicron retention disease--the role of ultrastructural examination in differential diagnosis.

Three children with malabsorption presumably caused by celiac disease had undergone jejunal biopsy. While a histological examination revealed microvacuolization of enterocytes in the absence of celiac lesions, an ultrastructural investigation disclosed numerous chylomicrons and larger lipid vacuoles inside the cytoplasm of enterocytes, mostly in the supranuclear region. No chylomicrons were evident in the interstitium between adjacent enterocytes, as observed in normal subjects. These ultrastructural findings allowed for the diagnosis of "Chylomicron retention disease" (CRD). CRD was described for the first time by Anderson in 1961, and it is included in the group of disorders of biosynthesis and secretion of B apolipoproteins (apoB). This disease, in particular, appears to result from a specific defect involving the secretion of lipoproteins containing apoB-48 from the gut, with the complete absence of post prandial chylomicrons in the sera. CRD needs to be recognized early because of its adverse effects on growth and its potential for neurological and ocular complications, and the ultrastructural identification of chylomicron-size lipid droplets clustered in the enterocytes, with the absence of fat outside the cells, represents the gold standard to identify CRD. together with clinical aspects and laboratory measurements. In this study, we describe the histological and ultrastructural aspects observed in three pediatric cases of CRD.

Tuberculin skin reactivity in Italian military recruits tested in 1996-1997.

In 1996-1997 data was collected and a Mantoux tuberculin test performed in 2882 Italian military recruits aged 18-23 years in order to establish the prevalence of tuberculin reactivity. In addition, the annual risk of infection, defined as the probability that a non-infected individual would be infected during the following year, was calculated. Of the 2882 recruits, 513 had received a BCG vaccination, the remaining 2369 had not. The overall prevalence of subjects with a tuberculin skin reaction size >5 mm (the cut-off point for positivity corresponding to the antimode in the reaction size frequency curve) was 6.1% (144/2369). The prevalence of skin reactivity increased with age but remained similar when related to area of residence, duration of father's school education and family size. The same general trend was observed if the standard pre-established cut-off point of 10 mm was used. In this case the overall prevalence of a positive skin reaction was 4% (95/2369). The annual risk of infection was 0.3% for a prevalence of tuberculin skin reactivity of 6.1% (cut-off point 5 mm) and 0.19% for a prevalence of 4% (cut-off point 10 mm). Analysis of the population sample vaccinated with BCG showed a lack of correlation between the positive reaction after vaccination reported retrospectively by the subject and the current skin reaction observed by the physician in this study (K = 0.254). Moreover, a significant difference was observed between the skin reaction in subjects vaccinated with BCG in 1993-1994 (average size 12.5 mm) and that of subjects vaccinated in 1995-1996 (average size 10.1 mm, P<0.01), probably as a consequence of mycobacteria circulating in the general population which act as a natural booster in people already vaccinated with BCG. A booster effect of tuberculin in Mantoux assays also cannot be excluded.

Myofibroblastic tumours: neoplasias with divergent behaviour. Ultrastructural and flow cytometric analysis.

Myofibroblasts are spindle cells having ultrastructural features in common with smooth muscle cells and fibroblasts. In the last few years, tumours have been described in which myofibroblasts represent not only a reactive mechanism but also a true neoplastic component. They constitute new nosologic entities which might be termed "myofibroblastic tumours". Tumours with benign and, rarely, malignant behaviour are reported to belong to this group of lesions. Recently, a third tumour type with borderline biological course, named "inflammatory myofibroblastic tumour" (IMT), has been identified, a condition that has been regarded as a benign and reactive disorder for a long time. Only in recent reports has been demonstrated that, in spite of an apparently benign morphological pattern, some cases of IMT have a malignant course. In this connection, DNA analysis by flow cytometry is a valuable diagnostic tool, because it allows identification of the ploidy status, a procedure that is often useful for predicting the nature and the biological behaviour of the lesion. In this study, 11 cases of myofibroblastic tumours were examined retrospectively by evaluating clinicopathological features and DNA ploidy status by flow cytometry. The diagnosis of myofibroblastic tumour was confirmed by performing histology, immunohistochemistry, and electron microscopy in all patients. In detail, these 11 cases were composed of 1 benign myofibroblastoma, 1 myofibrosarcoma and 9 IMTs. Among these myofibroblastic tumours, all those with local recurrence or distant metastases (one myofibrosarcoma and three IMT) showed an aneuploid cell population demonstrable by flow cytometric analysis, whereas the other cases with benign course (one benign myofibroblastoma and six IMT) exhibited an euploid DNA content. These data suggest the following: a) Besides the rare myofibroblastomas and myofibrosarcomas, IMTs represent a larger group of lesions with potentially different biological and clinical course. b) DNA flow cytometric analysis is a reliable tool that support histopathological examination in characterizing those cases of IMT that, though being malignant, mimic benign lesions. Consequently, it establishes the basis for a different therapeutic approach according to the euploid or aneuploid DNA content.

Incidence of Helicobacter pylori infection in a cohort of Italian military students.

Prevalence and incidence of Helicobacter pylori infection among 250 Italian military students were studied using specific IgG antibodies. Subjects susceptible at enrollment were evaluated during a 10-month follow-up period, when two serum samples were collected after 5 and 10 months, respectively. Samples were also analyzed for anti-CagA (a protein associated with virulent H. pylori strains) IgG antibodies. Finally, spectrotypic analysis by isoelectric focusing and reverse blotting (IEFRB) was performed in the majority of positive samples. Forty-three out of 250 (17.2%) were positive at the time of enrollment, a seroprevalence rate very similar to that observed in a larger Italian military population 5 years earlier. Among the 207 susceptible subjects, two seroconverted at 5 months after enrollment; they were still positive at the end of follow-up (incidence rate of 1.16 per 100 person/years of exposure). This data suggests a spread of H. pylori in the Italian military population that is not negligible. Nearly all anti-H. pylori-positive subjects were also CagA antibody positive (agreement percentage: 97.6%; K = 0.91), suggesting that the large majority of H. pylori strains were of the virulent type. Sixty-four percent of positive sera presented an oligoclonal spectrotype, which seems to be a hallmark of humoral immune response to H. pylori.