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Biomedical subjects

I H Brown

Publications and source records attributed to I H Brown.

At least 19 recordsLinked to original sources
PubMed2006

Recent epidemiology and ecology of influenza A viruses in avian species in Europe and the Middle East.

There have been at least ten distinct outbreaks of LPAI or HPAI in poultry caused by H5 or H7 viruses in the last eight years in Europe and the Middle East. There appears to be an increased occurrence of such episodes consistent with global trends. As a result, surveillance systems have been enhanced to facilitate early detection of infection in poultry, together with active surveillance of wild bird populations. These complementary activities have resulted in the detection of a number of viruses in wild bird populations, including some with high genetic similarity to newly detected viruses in poultry, for example, H7N3 in Italy and H7N7 in the Netherlands. Furthermore, there is evidence for continued circulation of H5 and H7 viruses in wild Anseriformes, thereby presenting a real and current threat for the introduction of viruses to domestic poultry, especially those reared in outdoor production systems. Viruses of H9N2 subtype continue to circulate widely in the Middle East and are associated with significant disease problems in poultry. The epidemiology has the potential to be complicated further by introduction of novel viruses through illegal importation of captive birds, such as was detected with H5N1 in Belgium in 2004. Continual genetic exchange in the avian virus gene pool and independent evolution of all gene segments either within an individual host species or among wild bird hosts suggests that these viruses are not in evolutionary stasis in the natural reservoir.

Animals↗
PubMed2006

Advances in molecular diagnostics for avian influenza.

Recent outbreaks of avian influenza (AI) have highlighted the necessity to improve existing tests and to develop new methods, in order to detect spread or new outbreaks more quickly, which is vital for the early and successful implementation of control strategies. Conventionally, the time between clinical suspicion and laboratory confirmation of AI can be relatively long because of the logistics of sending samples to laboratories and their capacity for providing high throughput of sensitive and specific assays. Increasingly, new-generation assays based on molecular diagnostics have become available and applied successfully to disease investigation or active surveillance programmes. There has been widespread application of techniques based on the amplification of specific nucleic acid sequences by polymerase chain reaction (PCR), ligase chain reaction and nucleic acid sequence-based amplification (NASBA). The approaches generally offer high specificity and sensitivity. One of the most promising technologies is real-time PCR, which enables amplification of nucleic acids and detection of the amplified products through specific probes at the same time. A rapid diagnosis can be achieved, together with potential for high throughput resulting from process automation. Currently, microarray technology is developing rapidly and has been applied to diagnosis of influenza A virus but generally lacks the necessary sensitivity for direct application to clinical specimens. In addition, these new technologies have been increasingly applied to rapid and reliable subtyping of AI viruses. The application of molecular technologies to the "field" is now potentially an option, through the availability of portable machines for conducting such tests, with prospects for radically changing diagnostic approaches for AI in the future.

Animals↗
PubMed2004

Genetic subtyping of influenza A viruses using RT-PCR with a single set of primers based on conserved sequences within the HA2 coding region.

Influenza A viruses are subtyped conventionally according to the antigenic characteristics of the external glycoproteins, haemagglutinin (HA) and neuraminidase (NA). To date 15 HA and 9 NA subtypes have been described. There is a need to develop fast, accurate and reliable methods to identify influenza virus subtypes, which may be associated with disease outbreaks. An RT-PCR is described using a single primer pair based on a conserved region of the HA2 gene that can detect all 15 HA influenza A subtypes. The assay was validated initially using a panel of 12 known standard prototype strains of influenza virus representing 6 HA subtypes and subsequently in a blind study using a panel of 30 strains. Selected viruses represented all known HA subtypes derived from avian, swine and human hosts separated both geographically and with time Sequence analysis of RT-PCR product showed complete correlation with results obtained using conventional serological methods. It is concluded that this RT-PCR is a reliable, robust and reproducible tool for the rapid identification of a wide range of all the HA subtypes of influenza A viruses.

DNA Primers↗
PubMed2003

Pathogenesis of H7 influenza A viruses isolated from ostriches in the homologous host infected experimentally.

Infections of ostriches with avian influenza A viruses are generally associated with clinical disease, but the occasional high mortality in young birds does not appear to be related directly to virus pathotype. In this study we investigated the pathogenesis of two H7 viruses for 11-wk-old ostriches inoculated intranasally, and clinical symptoms, virus excretion, and immune response were studied. One of the viruses (A/Ostrich/Italy/1038/00) was highly pathogenic for chickens, whereas the other (A/Ostrich/South Africa/1609/91) was of low pathogenicity for chickens. Clinical signs in ostriches receiving virulent virus were slight depression and hemorrhagic diarrhea, while the group receiving avirulent virus was clinically normal except for green diarrhea. Both viruses were transmitted to in-contact sentinel birds housed with the infected groups 3 days postinfection. Postmortem examination of the birds infected (including the sentinel bird) with virus highly pathogenic for chickens were grossly normal except for localized pneumonic lesions. The results of the study are presented and discussed.

Amino Acid Sequence↗
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

The epidemiology and evolution of influenza viruses in pigs.

Pigs serve as major reservoirs of H1N1 and H3N2 influenza viruses which are endemic in pig populations world-wide and are responsible for one of the most prevalent respiratory diseases in pigs. The maintenance of these viruses in pigs and the frequent exchange of viruses between pigs and other species is facilitated directly by swine husbandry practices, which provide for a continual supply of susceptible pigs and regular contact with other species, particularly humans. The pig has been a contender for the role of intermediate host for reassortment of influenza A viruses of avian and human origin since it is the only domesticated mammalian species which is reared in abundance and is susceptible to, and allows productive replication, of avian and human influenza viruses. This can lead to the generation of new strains of influenza, some of which may be transmitted to other species including humans. This concept is supported by the detection of human-avian reassortant viruses in European pigs with some evidence for subsequent transmission to the human population. Following interspecies transmission to pigs, some influenza viruses may be extremely unstable genetically, giving rise to variants which could be conducive to the species barrier being breached a second time. Eventually, a stable lineage derived from the dominant variant may become established in pigs. Genetic drift occurs particularly in the genes encoding the external glycoproteins, but does not usually result in the same antigenic variability that occurs in the prevailing strains in the human population. Adaptation of a 'newly' transmitted influenza virus to pigs can take many years. Both human H3N2 and avian H1N1 were detected in pigs many years before they acquired the ability to spread rapidly and become associated with disease epidemics in pigs.

Animals↗
PubMed2000

Isolation and characterization of H4N6 avian influenza viruses from pigs with pneumonia in Canada.

In October 1999, H4N6 influenza A viruses were isolated from pigs with pneumonia on a commercial swine farm in Canada. Phylogenetic analyses of the sequences of all eight viral RNA segments demonstrated that these are wholly avian influenza viruses of the North American lineage. To our knowledge, this is the first report of interspecies transmission of an avian H4 influenza virus to domestic pigs under natural conditions.

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↗
PubMed1998

Multiple genetic reassortment of avian and human influenza A viruses in European pigs, resulting in the emergence of an H1N2 virus of novel genotype.

Novel H1N2 influenza A viruses which were first detected in pigs in Great Britain in 1994 were examined antigenically and genetically to determine their origins and establish the potential mechanisms for genetic reassortment. The haemagglutinin (HA) of all swine H 1 N2 viruses examined was most closely related to, but clearly distinguishable both antigenically and genetically from, the HA of human H1N1 viruses which circulated in the human population during the early 1 980s. Phylogenetic analysis of the HA gene revealed that the swine H 1 N2 viruses formed a distinct branch on the human lineage and were probably introduced to pigs shortly after 1980. Following apparent transfer to pigs the HA gene underwent genetic variation resulting in the establishment and cocirculation of genetically and antigenically heterogeneous virus populations. Genetic analyses of the other RNA segments of all swine H1N2 viruses indicated that the neuraminidase gene was most closely related to those of early 'human-like' swine H3N2 viruses, whilst the RNA segments encoding PB2, PB1, PA, NP, M and NS were related most closely to those of avian viruses, which have been circulating recently in pigs in Northern Europe. The potential mechanisms and probable progenitor strains for genetic reassortment are discussed, but we propose that the swine H1N2 viruses examined originated following multiple genetic reassortment, initially involving human H1N1 and 'human-like' swine H3N2 viruses, followed by reassortment with 'avian-like' swine H1N1 virus. These findings suggest multiple reassortment and replication of influenza viruses may occur in pigs many years before their detection as clinical entities.

Animals↗
PubMed1997

Genetic characterisation of an influenza A virus of unusual subtype (H1N7) isolated from pigs in England.

An H1N7 influenza A virus, isolated from pigs in England in 1992, was examined genetically to determine the characteristics and probable origin of the eight gene segments. Six of the RNA segments encoding PB2, PB1, PA, HA, NP and NS were related most closely to those of human viruses, whilst two of the RNA segments (NA and M) were related most closely to those of equine viruses. The HA gene was most similar to that of A/USSR/90/77 (H1N1) but amino acid differences suggested independent genetic drift. In contrast, there were relatively few changes in the NA and M genes compared to those of A/equine/Prague/1/56 (H7N7).

Animals↗
PubMed1997

Antigenic and genetic analyses of H1N1 influenza A viruses from European pigs.

H1N1 influenza A viruses isolated from pigs in Europe since 1981 were examined both antigenically and genetically and compared with H1N1 viruses from other sources. H1N1 viruses from pigs and birds could be divided into three groups: avian, classical swine and 'avian-like' swine viruses. Low or no reactivity of 'avian-like' swine viruses in HI tests with monoclonal antibodies raised against classical swine viruses was associated with amino acid substitutions within antigenic sites of the haemagglutinin (HA). Phylogenetic analysis of the HA gene revealed that classical swine viruses from European pigs are most similar to each other and are closely related to North American swine strains, whilst the 'avian-like' swine viruses cluster with avian viruses. 'Avian-like' viruses introduced into pigs in the UK in 1992 apparently originated directly from strains in pigs in continental Europe at that time. The HA genes of the swine viruses examined had undergone limited variation in antigenic sites and also contained fewer potential glycosylation sites compared to human H1N1 viruses. The HA exhibited antigenic drift which was more marked in 'avian-like' swine viruses than in classical swine strains. Genetic analyses of two recent 'avian-like' swine viruses indicated that all the RNA segments are related most closely to those of avian influenza A viruses.

Amino Acid Sequence↗
PubMed1995

Serological studies of influenza viruses in pigs in Great Britain 1991-2.

Samples from a sow serum bank representative of the pig population of Great Britain collected during 1991-2, were examined for antibodies to influenza A, B and C viruses, using viruses which had been isolated from a variety of hosts. For influenza A viruses there was evidence of the continued circulation of classical swine H1N1 virus (26%) seroprevalence), and human H3N2 viruses (39%) which are antigenically most closely-related to A/Port Chalmers/1/73 virus. In addition antibodies were detected to A/swine/England/201635/92 (8%), a strain of H3N2 virus which appears to have arisen by antigenic drift from conventional H3N2 swine strains. Specific antibodies (2%) were detected to an H1N1 virus (A/swine/England/195852/92) related most closely to avian H1N1 strains. In tests with human H1N1 and H3N2 viruses, excluding isolates from pigs, the highest seroprevalence was detected to the prevailing strains from the human population. Serological tests with avian H4 and H10, human H2, equine 1 and 2 influenza A viruses were all negative. Seven pigs seropositive by haemagglutination-inhibition, virus neutralization and immunoblotting assays for antibody to influenza B virus, were randomly distributed geographically suggesting that influenza B viruses may be transmitted to pigs but fail to spread. The seroprevalence to influenza C viruses was 9.9% indicating that these viruses are widespread in pigs. These results provide further evidence that the pig can be infected by a number of influenza viruses, some of which may have significance in the epidemiology of human influenza.

Animals↗
PubMed1995

Infantile osteopetrosis; bone marrow transplantation from a cousin donor.

The successful correction of infantile osteopetrosis in an Asian child by bone marrow transplantation (BMT) from an HLA-A,B matched cousin donor is reported. Retrospective HLA molecular analysis revealed that patient and donor were incompatible for HLA-DPB1. Donor type cells detected in the patient after transplantation indicate successful engraftment. The patient is currently alive and well.

Bone Marrow Transplantation↗