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					Respiratory viral diseases
 – lessons to be learned?
by Richard C. Jones, University of Liverpool, Dept of Veterinary Pathology, Leahurst Neston, South Wirral CH64 7TE, UK.



R
       espiratory diseases caused by          strains cause a range of effects in poultry     level of virulence. However, as a general
       viruses continue to be a major cause   ranging from inapparent infection to mild       rule, vaccines with themselves a higher
       of economic loss to the poultry sec-   respiratory disease and falls in egg pro-       level of virulence (mesogenic) may be
tor. Losses are encountered in several        duction. Usually, mortality is low in           necessary against more virulent field
ways, including mortalities, reduced          uncomplicated cases, but disease can be         strains. An important epidemiological
weight gain, loss of egg production and       more severe and prolonged where bacte-          aspect of ND is that the disease has a very
quality, carcase downgrading, costs of        ria, mycoplasmas and perhaps other              wide host range and as many as 250
vaccines, antimicrobial treatment for sec-    viruses are present.                            species of wild birds are capable of being
ondaries and diagnosis.                         In contrast to the lentogenic strains, the    infected and long distance migrators can
  The most important virus diseases are       more virulent ones (mesogenic and velo-         play an important part in transmission.
those caused by Newcastle disease virus,      genic) alone produce much more severe             This means that it is virtually impossible
influenza virus, infectious bronchitis        episodes which can have high mortality.         to keep infection out of a region and out
virus, infectious laryngotracheitis and         Disease may be systemic and several           of poultry unless they are kept in bird
avian pneumovirus.                            organs (respiratory, enteric, nervous etc.)     proof conditions.
  Other viruses may be associated with        are affected. The highly pathogenic NDV           The most recent outbreaks of ND in the
respiratory disease manifestations, such as   strains are on the Office International des     UK were thought to have been caused by
poxviruses, adenoviruses and reoviruses,      Epizooties (OIE) A list of diseases.            infected waterfowl flying further west than
but these will not be covered. The pur-         Globally, ND is widespread and in 2001        they would normally do. Recent work in
pose of this article is to look at what       it was reported in some 63 countries or         the USA has shown that strains of NDV
lessons we have learned about these dis-      territories. The highly virulent strains have   from birds such as doves after passage in
eases. In fact several lessons have been      a considerable negative impact on inter-        chickens can become virulent for poultry.
learned, from clinical experience, from       national trade.                                   This fact highlights the importance of
careful experimental research and epi-          The OIE states that they have ‘potential      biosecurity, which, in simple terms,
demiological observation.                     for very serious and rapid spread irrespec-     means applying procedures that minimise
  One overriding lesson is that we are not    tive of national borders which are of seri-     or completely prevent the spread of infec-
good at completely eradicating these dis-     ous socio-economic or public health             tion. This is a recurring theme for all these
eases. So, although most of them have         consequence and which are of major              diseases.
been known for as long as the commer-         importance in the international trade of
cial poultry sector has been in existence,    animals and animal products’.
we still live with them, despite many           While the lentogenic strains are not on       Essential lessons learned from ND
years of research by outstanding scien-       list A, they can, nonetheless, have an
tists.                                        impact on trade between countries. Most         NDV has a single serotype which is help-
                                              outbreaks of high virulence NDV have            ful for diagnosis and vaccine strategies.
                                              resulted from high virulence NDV circu-         There are different levels of virulence and
Newcastle disease                             lating in poultry, although there is one        different levels of aggressive control may
                                              reported example from Australia of a low        be necessary in different regions, depend-
This disease is worldwide and is probably     virulence NDV mutating to a virulent            ing on the strain.
the most important because of the severity    state.                                            NDV has a very wide avian host range
of disease that some strains of virus can       Diagnosis of ND of whatever virulence         and wild birds can be very important in
cause. Newcastle disease virus (NDV) is       is strictly not possible without resorting to   spread of infection. Finally, good surveil-
capable of infecting many species of birds    laboratory methods, since they may              lance and biosecurity are essential.
including wild birds.                         resemble diseases caused by other path-
  NDV has a single linear negative sense      ogens. Virus isolation is relatively easy in
RNA genome coding for six proteins            9-10 day old fertile eggs and confirmation      Avian influenza
including the haemagglutinin-neu-             can be done by haemagglutination (HA)
raminidase (HN) protein. Antibodies to        or haemagglutination inhibition (HI) with       Avian influenza (AI) is frequently gener-
this are the basis for haemaagglutination-    specific antiserum.                             alised in terms of organs affected, but
inhibition serology. NDV is less likely to      Other methods for diagnosis are               effects on the respiratory tract are a part of
mutate than AI and over the years has         immunofluorescence staining of tissues          the disease so it is, therefore, included
remained relatively stable. There is only     and the reverse transcriptase polymerase        here. It is caused by a type A orthomyx-
one serotype of NDV which simplifies          chain reaction (RT-PCR). HI and ELISA are       ovirus. AI viruses have eight segments of
diagnosis and vaccination strategies.         used for serological surveillance.              RNA, coding for 10 proteins, among
  NDV strains differ in their ability to        The main approach to control of ND is         which are two on the surface, the haem-
cause disease and there are three patho-      to use vaccines and implementation of           agglutinin (H) and the neuraminidase (N).
types, the lentogenic viruses, which have     various biosecurity measures. Since there         On the basis of the H and N, AI viruses
low virulence and mesogenic and velo-         is only one serotype, the current empiri-       are classified into 15H and 9N subtypes.
genic viruses which have medium and           cally produced vaccines give good pro-          AI viruses can readily undergo random
high virulence. The lentogenic NDV            tection against NDV strains of whatever                               Continued on page 12


International Poultry Production — Volume 12 Number 4                                                                                   11
Continued from page 11                         AI is caused by a virus with several sub-       is the more important than the serotypic
mutations within gene segments as well         types and broadly two levels of patho-          or even genotypic relationships when it
as reassortment of segments between dif-       genicity.                                       comes to establishing vaccine efficacy.
ferent AI viruses. Immunity is primarily         The subtypes do not cross protect.              Considerable advances have been made
against the specific H subtypes, so that       Mutations can occur from time to time.          in recent years in the understanding of the
there is no cross-protection between them      This makes planned vaccination virtually        molecular structure of IBV strains and of
and this complicates any vaccine formu-        impossible. Humans can occasionally             immune mechanisms to the virus which
lations.                                       become infected with the viruses and            will contribute significantly to control of
   AI viruses are broadly divided into two     wild birds are an important part of trans-      the disease in the future.
groups according to the nature of the dis-     mission of infection. The main approach            For example, the recent production of a
ease they cause – low pathogenicity            to control is eradication of affected flocks.   full length infectious clone of IBV should
(LPAI) or high pathogenicity (HPAI).                                                           lead to safe, non-reverting designer vac-
  LPAI strains cause various problems                                                          cines for this disease, which will enable
ranging from clinically inapparent infec-      Infectious bronchitis                           appropriate inserts to meet the challenge
tions, to mild respiratory disease with loss                                                   of new variants.
of egg production.                             Infectious bronchitis (IB) was first reported     Work on immunity to different compo-
  Mortality rates are usually low. How-        some 71 years ago. Despite intensive            nents of the virus has shown that immu-
ever, with HPAI, fatal systemic disease        research, especially during the last 20         nity is not solely related to the S1 spike
can be caused involving many organs in         years, it is a disease which we live with       protein, but to other important compo-
the body.                                      and control by the use of empirically pro-      nents of the virus.
  It is known that some LPAI H5 and H7         duced vaccines. IB has a relatively narrow        This, in addition to the fact that cell-
subtypes can mutate in the field to be-        host range (chicken and pheasant, but           mediated immunity plays an important
come HPAI. This was shown in several           not, as far as we know, wild birds) but         role, helps to explain how some IB vac-
outbreaks, including Italy in 1999-2000        nonetheless is worldwide in distribution        cines can be protective against apparently
and in Chile in 2002. Such mutations           and likely to be present wherever chick-        unrelated variants.
have been shown to occur in the labora-        ens are kept in numbers. Its widespread           Molecular advances have also enabled
tory also.                                     nature is partly due to its highly infectious   the use of the polymerase chain reaction
  HPAI can sometimes be important for          nature and rapid local spread, although         with RFLP or sequencing to take its place
human health. In 1997, there were six          we can only speculate as to how some            increasingly in diagnostic laboratories as
human deaths in the outbreak in Hong           strains are found in different continents       the method of choice for identifying IBV
Kong with the H5N1 HPAI virus. In the          while others are not.                           strains in affected flocks.
recent outbreak in Holland (H7N7) there          There is some evidence of long term             This does not mean the demise of con-
was one death, but there appeared to be        persistence in the chicken but the signifi-     ventional isolation methods since secur-
predisposing factors. AI viruses can infect    cance of this is unknown. IB is considered      ing the live virus is essential for patho-
wild birds and they are an important           to be primarily a disease of the respiratory    genesis studies and where required, new
means of introducing the virus into a new      tract and it can be exacerbated by several      vaccine development.
area.                                          other factors including other pathogens,          Recent work has also shown that coron-
  Diagnosis of AI is done by growing the       although certain strains of the causal          aviruses from enteritis in turkeys are
virus using fertile eggs and agar gel im-      coronavirus (IBV) have a predilection for       related to IBV strains but are different.
munodiffusion, HI or ELISA to identify the     the kidneys and cause deaths in young           This is of particular interest, since a rela-
H and N subtypes. PCR is becoming more         birds. These nephropathogenic strains           tively overlooked aspect of IB in chickens
widely used for this now.                      seem to be more localised and spread less       is that many strains replicate in the intes-
  Eradication of AI is the main thrust of      than the conventional respiratory ones.         tine normally without causing patholog-
control in most cases. Vaccination is            Eradication of IB at present seems            ical changes.
sometimes used but it is essential to have     improbable, if not impossible, but existing       We have speculated that the propensity
a vaccine that matches the H and N sub-        vaccines work well provided that they are       for IBV strains to mutate could, at some
typings of the infecting virus.                administered accurately to each bird.           future date, lead to variants which cause
  Once in an area, vaccination can be            The biggest challenge to control strate-      disease in unexpected systems in the
used for surrounding flocks, but generally,    gies is the variation in the amino acid         chicken such as the gut or liver – targets
the appearance of AI is so unpredictable       sequences of the S1 spike gene which            for coronaviruses for other species.
that the value of pre-emptive vaccination      leads to the irregular emergence of new           Perhaps then we should now consider
is questionable. In any case, vaccination      variants, which are antigenically different     whether the title ‘infectious bronchitis
may only reduce the load of virus shed-        to existing vaccine strains.                    viruses’ is still appropriate.
ding rather than preventing it.                  Most variants are unimportant and dis-          Undoubtedly the body of information on
  Good biosecurity is vital for AI control     appear, but occasionally a variant such as      IB and current and novel vaccines for the
since the virus can be easily spread by        the recent one in Europe variously called       disease have attracted the attention of
movement of personnel and vehicles. AI         793B, 4/91 or CR88 appears which is             human virologists working on SARS.
viruses are excreted in the faeces in addi-    pathogenic, persistent and sufficiently dif-
tion to via the respiratory tract.             ferent antigenically to warrant a new vac-
   In the recent outbreak in Holland,          cine.                                           Essential lessons learned from IB
where the density of poultry populations         Fortunately, not all variants need new
is very high, there were 50 farms within       vaccines and while laboratory cross-neu-        IBV has a relatively narrow host range
one kilometre of the first outbreak and        tralisation tests have traditionally been a     compared with ND or AI, but is highly
much of the spread in the locality was         guide to in vivo interrelationships be-         infectious. The virus can mutate, due to
undoubtedly due to human movement.             tween IBV strains, we now know that it is       variation in the sequences of the amino
                                               how the bird vaccinated with a conven-          acids in the S1 spike gene and this can
                                               tional vaccine perceives a novel strain,        lead to variants, against some of which
Essential lessons learned from AI              rather than its ‘serotype’.                     existing vaccines are not protective.
                                                 In other words, the protectotypic effect        Good surveillance is vital, including the

12                                                                     International Poultry Production — Volume 12 Number 4
ability to detect new variants and molecu-       infected or live vaccinated birds for life.    cine and this phenomenon is being stud-
lar methods are now available to achieve           Given a marker vaccine, there are realis-    ied for other respiratory vaccines.
this. Modern molecular methods offer             tic prospects for eradication of ILT in cer-     Recent evidence from Minnesota indi-
hope of being able to carefully design IBV       tain regions.                                  cates that wild birds may play a part in
vaccines to meet the challenge of new                                                           the transmission of APV, although whether
variants. However, for the foreseeable                                                          they develop disease is less clear. It may
future, we may always be one step                Avian pneumovirus infection                    be that APVs have a very wide host range
behind in our attempts to control the dis-                                                      like Newcastle disease and influenza but
ease.                                            APV or more correctly avian metapneu-          this needs further investigation.
                                                 moviruses, are the cause of turkey rhino-        Alternative approaches to vaccination
                                                 tracheitis (TRT) and avian pneumovirus         have been attempted for APV infections
Infectious laryngotracheitis                     infection in chickens, which is sometimes      including vector vaccines and DNA vac-
                                                 followed by swollen head syndrome. TRT         cines. Another approach under investiga-
ILT or LT is another ‘old’ disease (1925),       has been arguably, the most important          tion is the use of reverse genetics to pro-
principally of chickens but again also able      disease of turkeys in the last 20 years.       duce an infectious clone.
to affect pheasants and sometimes,                 Infection with these viruses was des-          As with other diseases, the intention is to
turkeys. However, there are some con-            cribed only in the late 1970s in South         devise a safe, replicating non-revertant
trasts with IB. Although it is worldwide, it     Africa, so these are new diseases, relative    vaccine but which will be able to com-
spreads less easily than IB. This leads to       to IB and LT. APV was subsequently             pete in price with the existing ones.
the situation where in some countries LT         described in Europe, Asia and South and          Eradication of APV infection does seem
is endemic in certain areas, but absent          Central America and it was shown ini-          a reality under some conditions, where
from others.                                     tially that two subtypes of the virus (A and   flock density is low, the geography is
  The virus, a herpesvirus, has a single         B) existed, based on differences in G (gly-    favourable and biosecurity is high.
serotype, which simplifies vaccine strate-       coprotein) genes.
gies. Tissue distribution is restricted to the     It was not until 1996 that APV infection
respiratory tract with regard to disease,        was described in the USA where the virus       Essential lessons learned from APV
although the causal herpesvirus becomes          was found to differ in the M and F protein
latent and persists in the trigeminal gan-       genes and has been called type C. Viruses      While APV causes TRT, a very important
glia. From here, it can track back to the        isolated in France from ducks which are        disease of turkeys, its role in the chickens
respiratory tissues and be re-excreted after     non-A, non-B have been called type D           is less clear. Existing vaccines against sub-
stress, such as movement or sexual matu-         viruses.                                       types A and B are effective but it is impor-
rity. Such re-excreters may show no signs          The American virus, initially described      tant to apply them correctly.
of disease and can act as an unrecognised        in and eradicated from Colorado (hence           Subtypes A, B, C and non-A – non-B (D)
source of infection. Live vaccines can           ‘C’) is localised in Minnesota and sur-        are known; whether others will emerge is
similarly become latent and show similar         roundings, where there are huge popula-        unknown. There is evidence of infection
re-excretion patterns. Indeed, it seems          tions of commercial turkeys. Australia and     in wild birds but their role in spread is not
likely that in many instances, disease has       Canada remain free of infection. The type      yet clear.
been due to re-excreted vaccine virus,           C virus is more closely related to the
after latency, reverting to a virulent form.     recently described human metapneu-
  In view of the important features of the       movirus than A or B.                           Summary of lessons learned
virus and the disease outlined above, a            Early work in Europe was centred on
persuasive case has been made for LT             development of live and killed vaccines,       These viral respiratory diseases are hard
being a candidate for eradication, pro-          the former after attenuation of field          to eradicate and we live with most of
vided that the vaccines used were engi-          viruses. These generally are very effective    them, using vaccines for control.
neered to have a deletion, so that an            provided that delivery is accurate.              The vaccines are generally effective
appropriate ELISA could distinguish vacci-         The two subtypes each protect against        when given properly. AI is controlled in
nal antibodies from those due to field           both homologous and heterologous chal-         most instances by eradication alone,
infection.                                       lenge and the differences are of greater       although this is expensive.
  Molecular approaches have studied the          significance for ELISA serology, where           In the case of IB, new variant viruses
LT herpesvirus in great detail, the holy         incorrect selection of antigen can lead to     appear sporadically and some may war-
grail being the development of a safe vac-       false negatives. TRT in turkeys is clearly     rant a change in vaccine strategy.
cine which does not go latent. Recently,         an important respiratory pathogen, but the       Devising effective vaccine programmes
the thymidine kinase gene has been               role of APV in chickens is less apparent.      can be difficult, since some live vaccines
shown to be responsible for virulence. In          While APV infection is exacerbated in        may interfere with others if given simulta-
diagnosis, PCR has again been shown to           chickens by Mycoplasma gallisepticum,          neously or close together.
be the most sensitive system for use and         E. coli and Ornithobacterium rhinotra-           All these respiratory diseases can be
the addition of RFLP enables vaccine             cheale (ORT), virulent IBV interferes with     exacerbated by co-infection with other
strains to be differentiated from field virus.   the replication of APV in the trachea and      agents such as E. coli, ORT and myco-
                                                 this has also been shown with commer-          plasmas, so control of these other agents
                                                 cial vaccines. This highlights the impor-      is very important. For ND, AI and perhaps
Essential lessons learned from ILT               tance of timing of vaccine delivery.           APV infections, wild birds can be impor-
                                                   In contrast, recent American work            tant in introducing infection into new
ILTV has a narrow host range and exists in       showed that virulent type C virus acts syn-    regions.
only single serotype. Diagnosis and vac-         ergistically with virulent Newcastle dis-        For all these diseases good biosecurity
cine strategies have been relatively easy.       ease virus in poults.                          should always be maintained, even when
Disease can range from subclinical to per-         The timing of the use of live APV vac-       a new disease threat is not immediate. s
acute. Latency of the virus is one of the        cines can be important. Use of live APV
main problems, since ILTV is a herpes-           and IBV vaccines simultaneously shows
virus. Virus probably persists in naturally      that IBV inhibits the efficacy of APV vac-

International Poultry Production — Volume 12 Number 4                                                                                     13

				
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Description: respiratory viruses respiratory disease