Neuropsychological and behavioral disorders as presentation symptoms in two brothers with early-infantile niemann-pick type C

Background: Niemann-Pick disease type C (NPC) is a lysosomal storage disease caused by mutations in NPC1 or NPC2 genes. Case presentation: We present two brothers with the same compound heterozygous variants in exon 13 of the NPC1 gene (18q11.2), the first one (c.1955C> G, p. Ser652Trp), inherited from the mother, the second (c.2107T>A p.Phe703Ile) inherited from the father, associated to the classical biochemical phenotype of NPC. The two brothers presented unspecific neurologic symptoms with difference in age of onset: one presented and previously described dyspraxia and motor clumsiness at age 7 years, the other showed a systemic presentation with hepatosplenomegaly noted at the age of two months and neurological symptoms onset at age 4 with speech disturbance. Clinical evolution and neuroimaging data led to the final diagnosis. Systemic signs did not correlate with the onset of neurological symptoms. Miglustat therapy was started in both patients. Conclusions: We highlight the extreme phenotypic heterogeneity of NP-C in the presence of the same genetic variant and the unspecificity of neurologic signs at onset as previously reported. We report some positive effects of miglustat on disease progression assessed also with neuropsychological follow-up, with an age-dependent response

Influenza surveillance in birds in Italian wetlands (1992-1998): is there a host restricted circulation of influenza viruses in sympatric ducks and coots?

We report the results of a 6-year serological and virological monitoring performed in ducks and coots in Italy, in order to assess the degree of influenza A virus circulation in these birds during wintering. A total of 1039 sera collected from 1992 to 1998 was screened by a double antibody sandwich blocking ELISA (NP-ELISA): seroprevalence of antibodies to influenza A viruses was significantly higher in ducks compared to coots (52.2% vs. 7.1%, respectively). The hemagglutination-inhibition (HI) assay, performed on NP-ELISA positive sera, showed that 16.9% of these duck sera and 33.3% of these coot sera had antibodies to at least one influenza virus HA subtype: ducks showed HI antibodies against most of the HA subtypes, except for the H3, H4, H7, and H12; coots were seropositive to the H3 and H10 subtypes, only. From 1993 to 1998, 22 virus strains were obtained from 802 cloacal swabs, with an overall virus isolation frequency of 2.7%. Viruses belonging to the H1N1 subtype were by far the most commonly circulating strains (18/22) and were isolated mainly from ducks (17/18). The remaining viruses were representative of the H10N8, H5N2 and H3N8 subtypes. Our data indicate some differences between influenza A virus circulation in sympatric ducks and coots and a significant antigenic diversity between some reference strains and viruses recently isolated in Italy

Influenza virus circulation in wild aquatic birds in Italy during H5N2 and H7N1 poultry epidemic periods (1998 to 2000)

Two epidemics of avian influenza due to H5 and H7 highly pathogenic viruses occurred in poultry in Italy in 1997/98 and 1999/2000, respectively. The circulation of these serotypes in wild aquatic birds was investigated examining 638 cloacal swabs and 621 sera collected from 150 gulls, 162 coots, and 326 ducks trapped in Italian wetlands from 1998 to 2000. Seroprevalences against influenza A viruses, detected by a doubleantibody sandwich-blocking enzyme-linked immunosorbent assay (ELISA), were 11% in gulls, 16% in coots, and 45% in ducks. Among the Anatidae group, duck species wintering in Mediterranean areas showed significantly higher values than ducks wintering in South-Saharan areas of Africa. In order to detect H5 and H7 antibodies, the haemagglutination-inhibition assay and two competitive ELISA tests (H5-ELISA and H7-ELISA) using monoclonal antibodies specific for H5 and H7 subtypes were performed. None of the aquatic bird species were found seropositive for H7 subtype, whereas H5-positive sera were found by both the haemagglutination-inhibition and ELISA assays in ducks only. The highest H5 seroprevalences were detected by H5-ELISA; overall, 5% (10/201) of duck species wintering in Mediterranean areas tested positive by this assay, with annual seroprevalences ranging from 2% (2/123) to 12% (6/51). In the present study, only five viruses belonging to H1N1, H11N6, and H2N3 subtypes were isolated from ducks. However, the H5 seroconversion observed in one mallard duck at the beginning of 1998 indicates that H5 virus circulation also occurred in the study area

Influenza virus circulation in wild ducks and coots in Italy during H5N2 and H7N3 poultry epidemic periods (1998- 1999)

With regard to the role of wild ducks and coots as a source of viruses potentially pathogenic for domestic poultry we observed some differences: in coots, no evidence of H5 and H7 virus circulation was found either at serological or virological level whereas ducks serologically positive to H5 virus were detected every year. In the present study, the highest H5 antibody frequencies that were observed in DWMA during the first sampling period overlapped with the H5N2 Italian poultry epidemic (Donatelli et al., 2001). Moreover, even if no H5 viruses were isolated during the present study period, seroconversion observed in a mallard indicated that circulation of H5 subtype viruses occurred in the sampling area during the first sampling period (Table 2). Unlike H5 AIVs, no evidence of H7 virus circulation was found either at serological or virological level in ducks trapped in the area under study (Table 1). Thus it appears that no H7 viruses circulated among ducks sampled in the study area since 1992 (De Marco et al., 2004). In particular, duck sera resulted negative for H7 subtype both before and after the beginning of the catastrophic Italian poultry epidemic due to the H7N1 serovar (Capua & Alexander, 2004), suggesting a possible implication of other bird reservoirs. With regard to virus circulation, the H1N1 subtype appears to be endemic in Italian wetlands since 1992 (De Marco et al., 2004). H2N3 and H11N6 strains were isolated for the first time, even though ducks serologically positive to both subtypes had been found in previous years in the same study area (De Marco et al., 2004). The present results, together with data obtained before and after this study period in the same study area (De Marco et al., 2004, Campitelli et al., 2004b), suggest a perpetuation of H5 AIVs in the wild duck reservoir in Italy. This evidence is all the more relevant when we consider that the duck populations we analysed are representative of waterfowl populations that very likely make use of wetlands of Northern Italian regions (where H5N2, H7N1 and H7N3 poultry epidemics occurred in recent years) during their migrations northward in spring and southward in autumn (De Marco et al., 2000). The identification in 2001, in these wetlands, of H7N3 duck viruses almost identical to H7N3 strains affecting domestic poultry in Northern Italy in 2002-03 (Campitelli et al., 2004a) supports the existence of an epidemiological connection between these two areas and confirms the importance of maintaining an active influenza surveillance program in wild waterfowl reservoirs

INFLUENZA SURVEILLANCE IN BIRDS IN ITALY (1999-2002): PRELIMINARY MOLECULAR CHARACTERISATION OF VIRUS ISOLATES

During influenza surveillance activities carried out from 1999 to 2001 in wild ducks, 311 cloacal swabs were collected in Central Italy. A total of 20 avian influenza viruses (AIVs) were isolated, that belonged to eight different subtypes. Five of these subtypes had never been isolated before in the area under study, including two viruses obtained from mallards in Autumn 2001. One year after, outbreaks of AI caused by H7N3 LP viruses occurred and rapidly spread among commercial poultry farms in Northern Italy. We compared the H7N3 duck strains with the first two H7N3 turkey isolates, and a high level of similarity between the two viruses was found in all genes, except for the NA. The N3 genes of domestic poultry strains showed a 23-aminoacid deletion in the stalk region, indicating an initial adaptation of wild waterfowl viruses to terrestrial bird species. Phylogenetic data are also discussed. This is the first report in which a domestic poultry AIV and its direct wild bird counterpart are described

Influenza surveillance in birds in Italy (1999\u20132002): preliminary molecular characterisation of virus isolates

During influenza surveillance activities carried out from 1999 to 2001 in wild ducks, 311 cloacal swabs were collected in Central Italy. A total of 20 avian influenza viruses (AIVs) were isolated, that belonged to eight different subtypes. Five of these subtypes had never been isolated before in the area under study, including two H7N3 viruses obtained from mallards in Autumn 2001. One year after, outbreaks of AI caused by H7N3 LP viruses occurred and rapidly spread among commercial poultry farms in Northern Italy. We compared the H7N3 duck strains with the first two H7N3 turkey isolate, and a high level of similarity between the two viruses was found in all genes, except for the NA. The N3 genes of domestic poultry strains showed a 23- amino acid deletion in the stalk region, indicating an initial adaptation of wild waterfowl viruses to terrestrial bird species. Phylogenetic data are also discussed. This is the first report in which a domestic poultry AIV and its direct wild bird counterpart are described. D 2004 Elsevier B.V. All rights reserved

Antigenic and genetic evolution of swine influenza A (H3N2) viruses in Europe

In the early 1970s, a human influenza A/Port Chalmers/1/73 (H3N2)-like virus colonized the European swine population. Analyses of swine influenza A (H3N2) viruses isolated in The Netherlands and Belgium revealed that in the earl

Interspecies transmission of an H7N3 influenza virus from wild birds to intensively reared domestic poultry in Italy

Since the "bird flu" incident in Hong Kong SAR in 1997, several studies have highlighted the substantial role of domestic birds, such as turkeys and chickens, in the ecology of influenza A viruses. Even if recent evidence suggests that chickens can maintain several influenza serotypes, avian influenza viruses (AIVs) circulating in domestic species are believed to be introduced each time from the wild bird reservoir. However, so far the direct precursor of influenza viruses from domestic birds has never been identified. In this report, we describe the antigenic and genetic characterization of the surface proteins of H7N3 viruses isolated from wild ducks in Italy in 2001 in comparison to H7N3 strains that circulated in Italian turkeys in 2002-2003. The wild and domestic avian strains appeared strictly related at both phenotypic and genetic level: homology percentages in seven of their genes were comprised between 99.8% (for PB2) and 99.1% (for M), and their NA genes differed mainly because of a 23-aminoacid deletion in the NA stalk. Outside this region of the molecule, the NAs of the two virus groups showed 99% similarity. These findings indicate that turkey H7N3 viruses were derived "in toto" from avian influenza strains circulating in wild waterfowl 1 year earlier, and represent an important step towards the comprehension of the mechanisms leading to interspecies transmission and emergence of potentially pandemic influenza viruses