Epidemiological and molecular assessment of a rubella outbreak in North-Eastern Italy.

From January to June 2008, a rubella outbreak involving 111 laboratory confirmed cases occurred in the Friuli Venezia Giulia (FVG) region of North-Eastern Italy. The outbreak occurred initially in two residential homes for young adults disabled mentally and physically. Subsequently, the epidemic spread to the general population. Young adult cohorts were mostly affected and the mean age of the patients was 26.8 years; the majority of cases were male (73.8%), with a mean age of 26.6 years in males and 27.4 in females. Three pregnant women had a primary infection and two had their pregnancies terminated. Genotyping of 16 isolates showed the circulation of RUBV 2B, a genotype originating from Asia and South Africa and now present in Europe. In addition, molecular analysis revealed a well defined space-temporal spread of two viruses showing distinct sequences. A seroepidemiological survey carried out in a city within the same geographical area showed that the proportion of women of childbearing age still susceptible to rubella virus was 5.5%, fairly close to the figure (<5%) expected by 2010.

HHV-6 infection of tonsils and adenoids in children with hypertrophy and upper airway recurrent infections.

OBJECTIVE: Human herpes virus 6 (HHV-6), the agent of a self-limiting exanthematic disease in childhood, persists in a silent state in the secondary lymphoid organs and the reactivation is characterized by HHV-6-induced inflammatory cytokines. This study investigates the possible etiological role of HHV-6 in children affected by tonsil and adenoid hypertrophy. METHODS: 55 tonsils, 80 adenoids fresh tissues and 74 blood samples were collected from 80 children (mean age 4.8 years, 43.5% female) undergoing elective tonsillectomy and/or adenoidectomy for tissue hypertrophy. Moreover, patients with <5 years old documented upper airway recurrent infections not related to relapsing of acute tonsillitis. Specific IgG antibodies and virus detection (by PCR, variant A/B enzymatic genotyping and real-time PCR) were performed. RESULTS: In our series, HHV-6 seroprevalence was tested at 50%. HHV-6 variant B was the unique strain finding in 25% of adenoids, in 12.7% of tonsils and in 4% of peripheral blood mononuclear cells (PBMCs). HHV-6-B was prevalent in tonsils of children affected by upper airway infections (17.8% vs 7.4%) while the adenoids represented the more frequent reservoir (30.7% vs 19.5%) in patients with hypertrophy. HHV-6 viral load was low, ranging from 80 to 600 copies/10(6) cells suggesting a latent/persistent phase of infection. CONCLUSION: These results reinforce the role of the secondary lymphoid organs as an important reservoir for HHV-6B. Nevertheless, infection of lymphoid cells, sustained by a low level of replication, could be sufficient to increase the local injury through an autologous mechanism of inflammation.

HHV-6 is frequently detected in dried cord blood spots from babies born to HIV-positive mothers.

Intrauterine transmission of HHV-6 is well established in immunocompetent women while few data are available on infections in babies born to HIV-positive mothers. To assess the rate of HHV-6 vertical transmission in comparison to CMV, we analyzed cord blood spots dried on cards (Dried Blood Spots, DBS) collected during a multi-center study on HIV congenital infections in Italy. DBS were tested by PCR for HHV-6 and CMV footprints. HHV-6 amplimers were sequenced and characterized. As control group, cards taken from babies born to HIV-negative mothers were analyzed. DBS of 187 babies born to HIV-positive and 372 to HIV-negative mothers were analyzed. The prevalence of HHV-6 was 3.2% in babies born to HIV-positive mothers. CMV was found in the HIV-positive group with a prevalence rate of 1.6%. In newborns of control pregnant women, HHV-6 prevalence rate was 1.1% (p=0.09), while CMV was not detected (p=0.04). Sequence analysis could distinguish between HHV-6 A and B variant in both groups and one A/B coinfection was found in a baby born to a HIV-positive mother. HIV-infected mothers transmit HHV-6 and CMV viruses to their babies more frequently than uninfected women.

Hepatitis B virus genotypes, core promoter variants, and precore stop codon variants in patients infected chronically in North-Eastern Italy.

The hepatitis B virus (HBV) genotypes distribution and the core promoter (CP)/precore (PC) variability were evaluated by a line probe assay in 272 patients infected chronically enrolled consecutively in an area of the North-Eastern Italy. Seven out of the eight genotypes were detected. Italian subjects (83% of the sample) were infected mainly by genotype D (73%) and A (26%); genotype F, and genotype H, were detected only in one subject. In foreigners, the genotype distribution reflected the distribution described for the areas of origin, that is, in Asia genotypes B, C, and D; in Africa genotypes A and E. CP and PC variants prevalence rates were 51% and 60%, respectively, and were significantly higher in Italian patients, probably in relation to their older age. In the analysis restricted to genotypes A and D, PC wild type was linked strongly to genotype A (OR = 4.08, 95% CI = 3.07-5.43, P < 0.0001). In genotype A-infected patients, only e seroconversion was associated significantly with CP variants. In genotype D-infected subjects, CP variants were linked significantly to older age and to a higher e seroconversion rate, while PC variants also showed a strong relationship with an ALT lower activity and a lower viral load. In multivariate analysis, HBeAg positivity was associated strongly and independently with younger age, genotype A and CP wild type. Independent determinants of higher viral loads were recognized by increasing age, in male gender and concomitant presence of HBeAg and the CP wild type virus.

A rational use of laboratory tests in the diagnosis and management of hepatitis C virus infection.

The prevalence of HCV infection is very diversified according to geographical areas and ranges from 1% in the Northern regions of the world to more than 20% as we move South. Due to the presence of HCV-associated liver diseases and the development of effective treatments, the diagnosis of HCV infection is a growing medical need. Several tests are available, from simple screening to identify the presence of anti-HCV antibodies to the more sophisticated quantification of viral load and genotyping. However, these tests are to be used in a logical, consequential and cost-effective manner. This review article will report on the protocol in use in the North-Eastern part of Italy for the screening and diagnosis of HCV infection. The protocol is based on a consensus among several experts and may be the basis for a more rational approach in this rapidly growing field.

Changing molecular epidemiology of hepatitis C virus infection in Northeast Italy.

To assess HCV genotype distribution and its determinants, 318 consecutive HCV RNA positive patients were examined. Subtype 1b infection was the most prevalent (35.5%), followed by subtype 1a (22%), 3a (21.4%) and 2 genotype (21.3%). Subtypes 1a, 1b and 3a had a comparable prevalence (30-35%) in the 0-15-, 16-30- and 31-45-year age groups. In subjects older than 45 years, genotype 2 prevalence increased, whereas subtype 1a and 3a infections decreased markedly. In this age group types 1b and 2 accounted for a prevalence of more than 90% in a comparable proportion. Genotype prevalence rates according to different risk factors were different statistically (P < 0.001): subtype 1a and 3a infections were predominant in injection drug users (42.9% and 37.7%, respectively), whereas community acquired infections and infections in patients with a history of transfusion were caused mainly by subtype 1b (38.5% and 66.6%, respectively). Logistic regression showed that age and injection drug use are independent determinants of genotype distribution.

Mother-to-infant transmission of hepatitis C virus: rate of infection and assessment of viral load and IgM anti-HCV as risk factors.

One hundred twenty-six mother-infant couples were studied and 105 exposed babies were monitored for at least 12 months to define the risk of mother-to-infant HCV transmission. Infection occurred in 5 out of 76 infants (6.6%) born to 69 viraemic mothers and in none of 29 born to 26 non-viraemic mothers. Only one child was HCV RNA positive one month after birth, while the remaining children became positive at the 3rd to 4th month. HCV genotypes of the babies matched those of their mothers. No difference was found between women who transmitted the virus and those who did not with regard to age, history of drug abuse, HIV infection, ALT abnormal values, HCV genotype, type of delivery, and breast-feeding. Four out of 5 infected infants were born to mothers with IgM anti-HCV (P = 0.04). The mean viral titre in transmitting women (10(7.2)) was higher than in non-transmitting (10(6.5)), and the proportion of mothers with viral load > or = 10(7) was statistically higher in transmitting than non-transmitting women (P = 0.03). These data show that HCV perinatal infection is a rare event and suggest that IgM positivity and high viral load (> or = 10(7)) in the mother are independent variables correlated with HCV transmission (O.R. = 14.5; 95% CI: 1.3-160.7 and O.R. = 16.3; 95% CI: 1.5-179.9, respectively).