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D J Alexander

Publications and source records attributed to D J Alexander.

At least 37 records · Page 2Linked to original sources
PubMed2001

Rapid pathotyping of Newcastle disease virus (NDV) using fluorogenic probes in a PCR assay.

Hybridisation of PCR fragments with fluorogenic probes specific for pathotype allowed an estimation of pathogenicity of Newcastle disease virus (NDV) isolates using a modified TaqMan procedure. Six probes were used, designed to recognise nucleotide sequences in the fusion protein gene sequence corresponding to the precursor protein F0 cleavage site of both virulent and avirulent viruses. Forty-three of the 45 isolates tested, including 18 examined in a blind study were pathotyped successfully and rapidly, with close correlation between cleavage site nucleotide sequences, TaqMan results and intracerebral pathogenicity index (ICPI) values. One isolate, which could not be pathotyped by nucleotide sequencing, was shown using the TaqMan system to be a mixture of virulent and avirulent NDV. The results of this study suggest that using this modified TaqMan protocol, the likely virulence of most ND isolates can be determined rapidly and reproducibly.

Animals↗
PubMed2001

Changes in the haemagglutinin and the neuraminidase genes prior to the emergence of highly pathogenic H7N1 avian influenza viruses in Italy.

Outbreaks of avian influenza due to an H7N1 virus of low pathogenicity occurred in domestic poultry in northern Italy from March 1999 until December 1999 when a highly pathogenic avian influenza (HPAI) virus emerged. Nucleotide sequences were determined for the HA1 and the stalk region of the neuraminidase (NA) for viruses from the outbreaks. The HPAI viruses have an unusual multibasic haemagglutinin (HA) cleavage site motif, PEIPKGSRVRRGLF. Phylogenetic analysis showed that the HPAI viruses arose from low pathogenicity viruses and that they are most closely related to a wild bird isolate, A/teal/Taiwan/98. Additional glycosylation sites were present at amino acid position 149 of the HA for two separate lineages, and at position 123 for all HPAI and some low pathogenicity viruses. Other viruses had no additional glycosylation sites. All viruses examined from the Italian outbreaks had a 22 amino acid deletion in the NA stalk that is not present in the N1 genes of the wild bird viruses examined. We conclude that the Italian HPAI viruses arose from low pathogenicity strains, and that a deletion in the NA stalk followed by the acquisition of additional glycosylation near the receptor binding site of HA1 may be an adaptation of H7 viruses to a new host species i.e. domestic poultry.

Amino Acid Motifs↗
PubMed2001

A survey for paramyxoviruses in caged birds, wild birds, and poultry in New Zealand.

AIMS: To determine the presence of avian paramyxovirus (APMV) types 1, 2, and 3 in caged and wild birds, and APMV-2 and -3 in poultry in New Zealand. METHODS: Blood samples collected from caged (231) and wild birds (522) from various regions of New Zealand in 1997-99 were tested by haemagglutination inhibition (HI) test for antibodies to APMV types 1, 2, and 3. Blood samples collected from 1778 commercial poultry in 1996-99 were tested for APMV-2 and APMV-3 antibodies and the samples that reacted with APMV-3 antigen were tested for antibodies to APMV-1. Isolation of APMV was attempted from cloacal swabs collected from 116 of the caged birds and 175 of the wild birds sampled. RESULTS: Antibodies to APMV types 1, 2, and 3 were detected in 4.8, 1.7, and 2.6%, respectively, of caged bird samples. The majority of these caged birds were 'exotic' or 'fancy' poultry breeds. Amongst wild birds, 4.2% had titres to APMV-2 and over half of these were passerine birds; 1.7% of the samples had titres to APMV-1 and 0.8% to APMV-3 antigen. No virus was isolated from any of the cloacal swabs tested. Of the 1778 poultry serum samples tested, only 5 reacted with APMV-3 antigen and these were later found to be cross-reactions to APMV-1. No reactions were detected with APMV-2 antigen. CONCLUSIONS: APMV-1 is present in caged birds, wild birds, and poultry of New Zealand. There is no conclusive evidence of the presence of APMV-2 and APMV-3 in poultry or APMV-3 in wild birds. The results do not provide conclusive evidence for the presence of APMV-2 in wild birds in New Zealand.

Journal Article↗
PubMed2001

Gordon Memorial Lecture. Newcastle disease.

1. In this paper several historical and contemporary aspects of Newcastle disease (ND) are reviewed, with particular reference to the greater understanding which modern techniques have allowed. 2. Virulent ND viruses were generally thought to have emerged in 1926 as a result of transfer from a wild bird host reservoir but there is evidence that the virulent virus may have existed in poultry before 1926. Recent findings suggest that the virulent virus may emerge in poultry as a result of mutations in viruses of low virulence. 3. The history of ND in Great Britain reflects the four known panzootics that have occurred and serves as a model for the impact this disease may have on poultry populations. 4. Attempts to control and eradicate ND are not as straightforward as it may appear; in particular vaccination, while preventing deaths and disease, on challenge may not prevent virus replication and could therefore lead to the virulent virus becoming endemic. 5. Village chickens are extremely important assets in most developing countries, representing a significant source of protein in the form of eggs and meat but endemic ND can cause mortality of up to 60% in village chickens.

Animals↗
PubMed2000

H9N2 subtype influenza A viruses in poultry in pakistan are closely related to the H9N2 viruses responsible for human infection in Hong Kong.

Following the outbreak of H5N1 "bird flu" in Hong Kong in 1997, the isolation of H9N2 subtype viruses from patients in southern China and Hong Kong SAR once again raised the spectre of a possible influenza pandemic. H9N2 viruses have recently been responsible for disease in poultry in various parts of the world and preliminary studies of the H9 haemagglutinin (HA) genes of viruses isolated during 1998 and 1999 in Germany, Iran, Pakistan, and Saudi Arabia showed a close relationship to the HA genes of the viruses that infected two children in Hong Kong SAR. Analysis of the complete genome of a Pakistan isolate, A/chicken/Pakistan/2/99, showed that it is closely related in all eight genes (97-99% homology) to the human H9N2 isolates and furthermore that the six genes encoding internal components of the virus are similar to the corresponding genes of the H5N1 viruses that caused 6 (out of 18) fatal cases of human infection. Thus H9N2 viruses similar to those that caused human infections in Hong Kong are circulating more widely in other parts of the world. Whether or not these H9N2 viruses also have features that facilitate avian-to-human transmission is not known. Since avian H9N2 viruses are currently perceived to represent a significant threat to human health it is important to determine whether or not viruses of this subtype circulating in poultry in various parts of the world have the potential to infect people.

Animals↗
PubMed2000

Similarity of avian paramyxovirus serotype 1 isolates of low virulence for chickens obtained from contaminated poultry vaccines and from poultry flocks.

At present Denmark has the status of a 'non-vaccinating' country for Newcastle disease and its poultry population should therefore be free of antibodies to avian paramyxovirus 1 (APMV-1). Three live avian vaccines against infectious bronchitis, avian encephalomyelitis, and chick anaemia which had been found to be contaminated with APMV-1 viruses of low virulence for chickens were examined. The vaccines were produced by the same company and the affected batches had been used in Denmark in 1996/97. Furthermore, APMV-1 isolates of low virulence were obtained from three commercial broiler breeder flocks, one of which had been vaccinated with two of the contaminated vaccines. The flocks belonged to the same hatchery organisation. A comparison of viral F0 gene sequences and typing of virus isolates with a panel of monoclonal antibodies showed that the vaccine and field isolates were identical.

Animals↗
PubMed2000

A review of avian influenza in different bird species.

Only type A influenza viruses are known to cause natural infections in birds, but viruses of all 15 haemagglutinin and all nine neuraminidase influenza A subtypes in the majority of possible combinations have been isolated from avian species. Influenza A viruses infecting poultry can be divided into two distinct groups on the basis of their ability to cause disease. The very virulent viruses cause highly pathogenic avian influenza (HPAI), in which mortality may be as high as 100%. These viruses have been restricted to subtypes H5 and H7, although not all viruses of these subtypes cause HPAI. All other viruses cause a much milder, primarily respiratory disease, which may be exacerbated by other infections or environmental conditions. Since 1959, primary outbreaks of HPAI in poultry have been reported 17 times (eight since 1990), five in turkeys and 12 in chickens. HPAI viruses are rarely isolated from wild birds, but extremely high isolation rates of viruses of low virulence for poultry have been recorded in surveillance studies, giving overall figures of about 15% for ducks and geese and around 2% for all other species. Influenza viruses have been shown to affect all types of domestic or captive birds in all areas of the world, but the frequency with which primary infections occur in any type of bird depends on the degree of contact there is with feral birds. Secondary spread is usually associated with human involvement, probably by transferring infective faeces from infected to susceptible birds.

Amino Acid Sequence↗
PubMed2000

A rat nasal epithelial model for predicting upper respiratory tract toxicity: in vivo-in vitro correlations.

An in vitro model of the rat nasal cavity has been used to compare the responses of nasal tissues in vitro, using loss of intracellular ATP and potassium as indices of toxicity, with the pathological changes occurring following in vivo exposure to four test compounds. Turbinates were incubated in vitro with the test compounds for 4 h, for 24 h or for 4 h followed by 20 h in fresh medium. Titanium dioxide caused little or no loss of ATP in either olfactory epithelium (OE) or respiratory epithelium (RE). Sodium carbonate decreased olfactory, but not respiratory ATP, while acetic acid and 3-methylindole markedly decreased ATP in both tissues. Intracellular potassium concentrations were generally affected to a lesser degree. In vivo, no morphological changes were observed in the nasal cavity following inhalation exposure to either titanium dioxide or sodium carbonate. Inhalation of acetic acid resulted in a very focal lesion in the RE of the dorsal meatus of level 1, while administration of 3-methylindole by intraperitoneal injection caused severe degeneration of OE. In further experiments olfactory turbinates were exposed to a range of concentrations (0-100 mM) of sodium carbonate, acetic acid and 3-methylindole for 4 h and ATP concentrations determined. Concentration-dependent decreases in ATP were observed for sodium carbonate and 3-methylindole, with EC(50) values estimated as 2.57 and 0.91 mM, respectively. Acetic acid only decreased ATP significantly at the 100-mM concentration. In summary, this in vitro model has predicted the nasal toxicity of several compounds, including both direct-acting agents (sodium carbonate, acetic acid) and one requiring metabolic activation (3-methylindole). However, the lack of airflow-dependent dosimetry, results in some lack of discrimination between the different regions of the nasal cavity and may make this model overly sensitive.

Acetic Acid↗
PubMed2000

Human safety and pharmacokinetics of the CFC alternative propellants HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3, 3-heptafluoropropane) following whole-body exposure.

HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3, 3-heptafluoropropane) are used to replace chlorofluorocarbons (CFCs) in refrigerant and aerosol applications, including medical use in metered-dose inhalers. Production and consumption of CFCs are being phased out under the Montreal Protocol on Substances that Deplete the Ozone Layer. The safety and pharmacokinetics of HFC 134a and HFC 227 were assessed in two separate double-blind studies. Each HFC (hydrofluorocarbon) was administered via whole-body exposure as a vapor to eight (four male and four female) healthy volunteers. Volunteers were exposed, once weekly for 1 h, first to air and then to ascending concentrations of HFC (1000, 2000, 4000, and 8000 parts per million (ppm)), interspersed with a second air exposure and two CFC 12 (dichlorodifluoromethane) exposures (1000 and 4000 ppm). Comparison of either HFC 134a or HFC 227 to CFC 12 or air gave no clinically significant results for any of the measured laboratory parameters. There were no notable adverse events, there was no evidence of effects on the central nervous system, and there were no symptoms of upper respiratory tract irritation. HFC 134a, HFC 227, and CFC 12 blood concentrations increased rapidly and in an exposure-concentration-dependent manner, although not strictly proportionally, and approached steady state. Maximum blood concentrations (C(max)) tended to be higher in males than females; in the HFC 227 study, these were statistically significantly (P < 0. 05) higher in males for each HFC 227 and CFC 12 exposure level. In the HFC 134a study, the gender difference in C(max) was only statistically significant (P < 0.05) for CFC 12 at 4000 ppm and HFC 134a at 8000 ppm. Following the end of exposure, blood concentrations declined rapidly, predominantly biphasically and independent of exposure concentration. For the HFC 134a study, the t(1/2)alpha (alpha elimination half-life) was short for both CFC 12 and HFC 134a (<11 min). The t(1/2)beta (beta elimination half-life) across all exposure concentrations was a mean of 36 and 42 min for CFC 12 and HFC 134a, respectively. Mean residence time (MRT) was an overall mean of 42 and 44 min for CFC 12 and HFC 134a, respectively. In the HFC 227 study, t(1/2)alpha for both CFC 12 and HFC 227, at each exposure level, was short (<9 min) and tended to be lower in males than females. For CFC 12 mean t(1/2)beta ranged from 23 to 43 min and for HFC 227 the mean range was 19-92 min. The values tended to be lower for females than males for HFC 227. For both CFC 12 and HFC 227, MRT was statistically significantly lower (P < 0.05) in males than females and independent of exposure concentration. For CFC 12, MRT was a mean of 37 and 45 min for males and females, respectively, and for HFC 227 MRT was a mean of 36 and 42 min, respectively. Exposure of healthy volunteers to exposure levels up to 8000 ppm HFC 134a, 8000 ppm HFC 227, and 4000 ppm CFC 12 did not result in any adverse effects on pulse, blood pressure, electrocardiogram, or lung function.

Administration, Inhalation↗
PubMed2000

Phylogenetic analysis of H7 haemagglutinin subtype influenza A viruses.

A 945 nucleotide region (bases 76-1020) of the HA1 part of the HA gene was obtained for 31 influenza viruses of H7 subtype isolated primarily from Europe, Asia and Australia over the last 20 years. These were analysed phylogenetically and compared with sequences of the same region from 23 H7 subtype viruses available in Genbank. The overall results showed two geographically distinct lineages of North American and Eurasian viruses with major sublineages of Australian, historical European and equine viruses. Genetically related sublineages and clades within these major groups appeared to reflect geographical and temporal parameters rather than being defined by host avian species. Viruses of high and low virulence shared the same phylogenetic branches, supporting the theory that virulent viruses are not maintained as a separate entity in waterfowl.

Amino Acid Sequence↗
PubMed2000

A serological survey for avian infectious bronchitis virus and Newcastle disease virus antibodies in backyard (free-range) village chickens in Mexico.

The commercial flocks in Yucatan, Mexico are free of Newcastle disease virus (NDV) in its velogenic viscerotropic form, but little is known about the disease status of backyard poultry. A seroprevalence survey in 30 villages using haemagglutination inhibition (HI) tests for infectious bronchitis virus (IBV) and NDV antibodies was carried out from December 1997 to June 1998. The seroprevalences were 56.5% (95% CI 50-63%) for IBV and 2.2% (95% CI 0.5-3.8%) for NDV. All the villages had chickens that were positive for antibodies to IBV and nine of the villages had chickens that were positive for antibodies to NDV. This suggests that IBV may be responsible for a large proportion of the respiratory disease observed in backyard chickens in Yucatan. The implications of these findings are discussed, including the highly susceptible status of the backyard chickens in Yucatan to NDV and the possibility of this virus being one cause of the syndrome known as mortandad by the local people.

Animals↗
PubMed2000

Recent zoonoses caused by influenza A viruses.

Influenza is a highly contagious, acute illness which has afflicted humans and animals since ancient times. Influenza viruses are part of the Orthomyxoviridae family and are grouped into types A, B and C according to antigenic characteristics of the core proteins. Influenza A viruses infect a large variety of animal species, including humans, pigs, horses, sea mammals and birds, occasionally producing devastating pandemics in humans, such as in 1918, when over twenty million deaths occurred world-wide. The two surface glycoproteins of the virus, haemagglutinin (HA) and neuraminidase (NA), are the most important antigens for inducing protective immunity in the host and therefore show the greatest variation. For influenza A viruses, fifteen antigenically distinct HA subtypes and nine NA subtypes are recognised at present; a virus possesses one HA and one NA subtype, apparently in any combination. Although viruses of relatively few subtype combinations have been isolated from mammalian species, all subtypes, in most combinations, have been isolated from birds. In the 20th Century, the sudden emergence of antigenically different strains in humans, termed antigenic shift, has occurred on four occasions, as follows, in 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 1977 (H1N1), each resulting in a pandemic. Frequent epidemics have occurred between the pandemics as a result of gradual antigenic change in the prevalent virus, termed antigenic drift. Currently, epidemics occur throughout the world in the human population due to infection with influenza A viruses of subtypes H1N1 and H3N2 or with influenza B virus. The impact of these epidemics is most effectively measured by monitoring excess mortality due to pneumonia and influenza. Phylogenetic studies suggest that aquatic birds could be the source of all influenza A viruses in other species. Human pandemic strains are thought to have emerged through one of the following three mechanisms: genetic reassortment (occurring as a result of the segmented genome of the virus) of avian and human influenza A viruses infecting the same host direct transfer of whole virus from another species the re-emergence of a virus which may have caused an epidemic many years earlier. Since 1996, the viruses H7N7, H5N1 and H9N2 have been transmitted from birds to humans but have apparently failed to spread in the human population. Such incidents are rare, but transmission between humans and other animals has also been demonstrated. This has led to the suggestion that the proposed reassortment of human and avian viruses occurs in an intermediate animal with subsequent transference to the human population. Pigs have been considered the leading contender for the role of intermediary because these animals may serve as hosts for productive infections of both avian and human viruses and, in addition, the evidence strongly suggests that pigs have been involved in interspecies transmission of influenza viruses, particularly the spread of H1N1 viruses to humans. Global surveillance of influenza is maintained by a network of laboratories sponsored by the World Health Organization. The main control measure for influenza in human populations is immunoprophylaxis, aimed at the epidemics occurring between pandemics.

Animals↗
PubMed2000

Newcastle disease and other avian paramyxoviruses.

Newcastle disease (ND), caused by avian paramyxovirus serotype 1 (APMV-1) viruses, is included in List A of the Office International des Epizooties. Historically, ND has been a devastating disease of poultry, and in many countries the disease remains one of the major problems affecting existing or developing poultry industries. Even in countries where ND may be considered to be controlled, an economic burden is still associated with vaccination and/or maintaining strict biosecurity measures. The variable nature of Newcastle disease virus strains in terms of virulence for poultry and the different susceptibilities of the different species of birds mean that for control and trade purposes, ND requires careful definition. Confirmatory diagnosis of ND requires the isolation and characterisation of the virus involved. Assessments of virulence conventionally require in vivo testing. However, in vitro genetic characterisation of viruses is being used increasingly now that the molecular basis of pathogenicity is more fully understood. Control of ND is by prevention of introduction and spread, good biosecurity practices and/or vaccination. Newcastle disease viruses may infect humans, usually causing transient conjunctivitis, but human-to-human spread has never been reported. Eight other serotypes of avian paramyxoviruses are recognised, namely: APMV-2 to APMV-9. Most of these serotypes appear to be present in natural reservoirs of specific feral avian species, although other host species are usually susceptible. Only APMV-2 and APMV-3 viruses have made a significant disease and economic impact on poultry production. Both types of viruses cause respiratory disease and egg production losses which may be severe when exacerbated by other infections or environmental stresses. No reports exist of natural infections of chickens with APMV-3 viruses.

Animals↗
PubMed1999

Antigenic and genetic characterisation of Newcastle disease viruses isolated from outbreaks in domestic fowl and turkeys in Great Britain during 1997.

Antigenic and genetic analyses of viruses from the 11 outbreaks of Newcastle disease in Great Britain, 12 of the outbreaks in Northern Ireland and the single outbreak in the Republic of Ireland which occurred in 1997, indicated that they were all essentially similar. In addition, the viruses from the British Isles were very similar to viruses isolated from three outbreaks in pheasants in Denmark between August and November 1996, from a goosander in Finland in September 1996, from an outbreak in chickens in Norway in February 1997, and from an outbreak in chickens in Sweden in November 1997. Viruses from outbreaks in other countries during 1995 to 1997 could be distinguished antigenically and/or genetically from the 1996 to 1997 Scandinavian/British Isles isolates, as could viruses responsible for two separate outbreaks in caged birds in quarantine premises in Great Britain in March 1997. Minor nucleotide differences in the 413-base region of the fusion gene and the 187-base region of the haemagglutinin-neuraminidase gene sequenced in this study allowed the 1996 to 1997 Scandinavian/British Isles isolates to be divided into groups. These groups broadly corresponded to the clusters of disease outbreaks, but suggested that the discrete outbreak in Scotland was probably the result of virus spread from Northern Ireland. Overall, the antigenic and genetic analyses of these viruses were consistent with the theory that the virus was introduced into the British Isles by migratory birds moving from north-east Europe. However, it was not possible to rule out other sources, such as the movement of pheasants from Denmark.

Animals↗
PubMed1999

Comparative biotransformation studies of MeIQx and PhIP in animal models and humans.

MeIQx and PhIP are putative carcinogenic heterocyclic amines formed during the cooking of meat and fish. Using accelerator mass spectrometry, we have investigated the metabolism and macromolecule binding of 14C-labelled MeIQx and PhIP in human cancer patients compared to the rat. Following oral administration of MeIQx and PhIP, more DNA adducts were formed in human colon tissue compared with rats. Differences were also observed between rats and humans in the metabolite profile and urine excretion for these compounds. These results suggest humans metabolise heterocyclic amines differently to laboratory rodents and question their use as models of human risk.

Animals↗
PubMed1999

Hepatobiliary cystadenoma presenting with intermittent inferior vena caval obstruction.

Hepatobiliary cystadenomas are rare benign tumours. They form as multilocular cysts in and around the liver. Their presentation is usually at a late stage when their size causes symptoms. We report a case of a 44-year-old woman presenting with abdominal pain, which was attributed to a multiloculate liver cyst. After intially refusing surgery she relented once intermittent inferior vena caval obstruction had developed. The cyst was found to be a hepatic cystadenoma.

Adult↗