Review on Newcastle Disease in Poultry and its Public Health Importance

: Newcastle disease is a contagious bird disease affecting many domestic and wild avian species and it is a zoonotic disease. It is caused by avian paramyxovirus serotype 1 virus which, with viruses of the other eight serotypes (avian paramyxovirus1-9) has been placed in the genus Avulavirus , sub-family Paramyxovirinae , family Paramyxoviridae . Virulent Newcastle disease virus strains are endemic in poultry in most of Asia, Africa, and some countries of North and South America. Other countries, including the united state of America and Canada, are free of those strains in poultry. Highest prevalence of Newcastle disease is recorded in cross breeds of chickens than local breed and the low altitudes do have higher prevalence than the mid and high altitudes. The transmission of Newcastle disease occurs through respiratory aerosols, exposure to fecal and other excretions from infected birds, through newly introduced birds, selling and giving away sick birds and contacts with contaminated feed, water, equipment and clothing. The strain of Newcastle pathogenecity can be classified into five pathotype: Asymptomatic enteric strain; Lentogenic strain; Mesogenic strain; Viscerotropic velogenic strain and Neurotropic velogenic strain. Clinical signs are extremely variable depending on the strain of virus, species and age of bird, concurrent disease, and preexisting immunity caused by paramixovirus with worldwide distribution affecting chickens (all poultry and birds are susceptible) of All age group are susceptible. Symptoms from the respiratory tract are gasping, coughing, sneezing and rales. Signs from the nervous system include tremors, paralyzed wings and legs, twisted necks, circling, clonic spasms and sometimes complete paralysis. Other general symptoms that can be seen are greenish diarrhea, depression and inappetence, partial or complete drop in egg production and an increased production of deformed eggs. Clinical diagnosis based on history, signs and lesions may establish a strong index of suspicion but the laboratory confirmation must be done. The general approaches to the control of Newcastle disease are hygiene and vaccination. Humans are among the many species that can be infected by Newcastle disease in addition to avian species. Newcastle disease may cause conjunctivitis in humans, when a person has been exposed to large quantities of the virus. Recently, the disease which decreases the development of poultry production for industry is the infectious diseases, among infection disease Newcastle is the one which causes economical lose of poultry and its product. The objective of this review is to understand the Newcastle disease causative agent, pathogenecity, clinical sign and how to prevent and control the Newcastle disease, which concerned with the currently published or reported research.


INTRODUCTION
domestic animal stock inthe world [2]. Poultry represents Poultry, the largest livestock group, account for more flocks representing a huge majority, especially in the than 30% of all animal protein. However, this production developing countries. In these countries, villagers raise is mainly based on commercial poultry, which accounts poultry to meet household food demands and as for only 20% of the total poultry population [1]. Based on additional sources of incomes. Backyard production the number of animals, poultry represents the largest methods imply low biosecurity measures and high risk of an important sector in animal production, with backyard infectious diseases, such as Newcastle disease (ND) or diseases worldwide. The disease can vary from mild to zoonosis such as Highly Pathogenic Avian Influenza severe. A highly contagious and severe form of the (HPAI) [3]. Newcastle disease is a contagious bird disease disease, called exotic Newcastle disease(END), is so affecting many domestic and wild avian species; it is deadly that many birds die suddenly without showing any transmissible to humans [4]. Newcastle diseaseis an signs of disease [14]. important infectious disease of the poultry that is caused by virulent strains of Avian Paramyxovirus-1, which is a Aetiology: Newcastle disease is caused by avian single strand non-segmented negative sense RNA virus paramyxovirus serotype 1 [APMV-1] viruses, which with [5].
viruses of the other eight APMV serotypes (APMV-2 to The epizootics of Newcastle Disease in poultry APMV-9), have been placed in the genus Avulavirus, continue to occur in Asia, Africa, Central and South sub-family Paramyxovirinae, family Paramyxoviridae, America while in Europe, sporadic epizootics occur [6].
in the current taxonomy [15,16]. Newcastle disease In developing countries, human diet is deficient in the belongs to order Mononegavirales, family animal proteins; approximately 66% population has Paramyxoviridae, subfamily Paramyxovirinae and genus protein deficient diet [7]. Newcastle disease is an Avulavirus which are negative sense single stranded economically important disease and also a major threat to and non-segmented RNA genomes [17]. All the avian poultry industry [ 8]. According to variation in strains of paramyxoviruses (APMVs) are part of genus NDV, the rate of mortality and morbidity in a flock [9].
Avulavirus. Virions are roughly spherical, 150 nm or more Pathotyping of NDV by reverse transcriptase polymerase in diameter and filamentous [18]. The genome is about chain reaction(RT-PCR) and restriction enzyme analysis 15.2 kb in length [19,20] that codes for six structural and along with decrease in egg production [10]. Isolation of two non-structural proteins [10]. Rule of six should be virus and serological diagnostics, such as followed by genome because it should be of poly hemagglutination inhibition (HI) Test, Enzyme linked hexameric length to replicate rapidly. It encodes for six immune-sorbent assay (ELISA) and molecular diagnostic proteins in 3' to 5' direction; these are Nucleoprotein tests like real time PCR confirmed the presence of (NP), Large RNA polymerase (L), Fusion (F), velogenic NDV [11]. The economic importance of Hemagglutinin Neuraminidase(HN), Matrix(M) and Newcastle disease may affect on the meat quality of phosphoprotein (P) [21,22]. The proteins W and V are poultry. In developing countries, the broiler meat is the additionally created within the P gene during cheapest source of animal protein. Availability of egg is transcription of mRNA at editing site by insertion of increasing at rate of round about 4% annually [12].
guanines [22,23]. In virus particles, NP is the most White meat's essential nutrients are same as red meat, but abundant protein which provides the NDVs core helical white meat has the advantage of containing less nucleocapsid structure. NP is the main regulator in cholesterol and saturated fat. In most developing replication of viral genome [25]. The genomic RNA is countries, meat is a very important protein sources in diet associated with NP, P and L proteins to form RNP of people because it is affordability and has high quality complex, which serve as template for RNA synthesis [24]. protein [13]. The objective of this review is to understand NP is found to be highly immunogenic, as it induces the Newcastle disease causative agent, pathogenecity, antibody responses in chickens [26]. clinical sign and how to prevent and control the Newcastle disease, which concerned with the currently Molecular Basis for Pathogenicity: During the replication published or reported research. Recently, the disease of NDV, the functionally important fusion protein is which decreases the development of poultry production produced as a precursor glycoprotein, F0, which has to be for industry is the infectious diseases, Newcastle is the cleaved to F1 and F2 for the progeny virus particles to be one of theinfectious disease which causes economical infectious [27]. This post translation cleavage is lose of poultry and its product. mediated by host cell proteases [28]. If cleavage fails to

Literature Review
Trypsin can cleave F0 for all NDV strains, and in General Description of Poultry Newcastle Disease: vitrotreatment of non-infectious virus will restore Newcastle disease is a contagious viral disease of birds infectivity [29]. The importance of F0 cleavage was easily and considered one of the most important poultry demonstrated, because viruses normally unable to take place, non infectious virus particles are produced.
replicate or produce plaques in cell culture systems were basic amino acid at residue 113. In contrast, all velogenic able to do both if trypsin was added to the agar overlay or or mesogenic viruses had phenylalanine at residue 117 culture fluid. Although all viruses could replicate and and, with one exception, basic amino acids at residues 115 produce infectious progeny in the allantoic cavity, the and 112 in addition to those at113 and 116. The exception viruses pathogenic for chickens could replicate in a wide was the pigeon variant PMV-1 virus, which was identical range of cell types in vitrowith or without added trypsin, to the virulent viruses but lacked a basic amino acid at where as strains of low virulence could replicate only position 112. when trypsin is added [30]. Thus, F0 molecules of virulent viruses can be cleaved by a host protease or proteases The Strain of Newcastle Pathogenecity: The strain of found in a wide range of cells and tissues, but F0 Newcastle pathogenecity can be classified into five molecules in viruses of low virulence were restricted in pathotype: Asymptomatic enteric strain a form that has their sensitivity to cleavage by specific host enzymes.
sub-clinical enteric infection without clear symptoms; Consequently, these viruses can grow only in certain host Lentogenic strain which virus present with the mild cell types. Early reports of the deduced amino acid respiratory infections; Mesogenic stain which virus sequences of the F0 precursor, obtained from nucleotide presents with rare nervous and respiratory signs while sequencing of the F gene fora number of NDV strains mortality rate is related with the age of susceptible [31,32], enabled comparison of viruses of low birds(young birds are more susceptible as compare to virulence to those that were velogenic or mesogenic. adults) ; Viscerotropic velogenic strain which virus cause For all viruses, the amino acid at residue 116, the C haemorrhagic intestinal lesions and it is highly terminus of the F2 protein at the site of cleavage, was pathogenic; Neurotropic velogenic strain which virus arginine. The viruses of low virulence all had leucine at cause high mortalities followed by respiratory and residue 117, the N-terminus of the F1 protein, and another nervous signs [33].
Epidemiology of Newcastle Disease: Virulent NDV strains disease is very contagious and is easily spread from one are endemic in poultry in most of Asia, Africa, and some bird to another. The infection is usually transmitted by countries of North and South America. Other countries, direct contact with sick birds or unaffected birds carrying including the USA and Canada, are free of those strains the virus. Even vaccinated birds that are clinically healthy in poultry and maintain that status with import restrictions can excrete virulent virus after they have been exposed. and eradication by destroying infected poultry.
Virus can also be transmitted indirectly by people, other Cormorants, pigeons, and imported psittacine species are animals, equipment, vehicles, contaminated poultry more commonly infected with vNDV and have also been products, feed and water [42]. sources of vNDV infections of poultry. NDV strains of The infection takes place by inhalation or ingestion low virulence are prevalent in poultry and wild birds, of the virus or by contact with mucous membranes, especially waterfowl. Infection of domestic poultry with specially the conjunctiva. Infected birds shed virus in loNDV contributes to lower productivity [35]. ND virus is aerosol, respiratory discharge and feces. Infected birds infective for almost all avian species, both domestic and start to excrete virus during the incubations period and wild. Chickens are highly susceptible to infection with continue to excrete virus for a varying but limited time Newcastle disease virus, including the pigeon variant of during convalescence [42]. During the course of infection APMV-1.
of most birds with NDV, large amounts of virus are Newcastle disease virus is heat stable when excreted in the feces. Ingestion of feces results in compared with most of paramyxovirus. It remain infectious infection; this is likely to be the main method of bird to in bone marrow and muscle of slaughtered chicken at least bird spread for avirulent enteric NDV and the pigeon six month at -20°C and for up to four month in refregrator variant virus, neither of which normally produces temperature and also infectious virus may survive for respiratory signs in infected birds [43]. months at room temperature in eggs laid by infected hens Vertical transmission (i.e., passing of virus from and for over year at 4°C [36]. Higher prevalence of ND is parent toprogeny via the embryo) remains controversial. during dry season than wet season. However, rare higher The true significance of such transmission in epizootics prevalence of ND is also seen during wet season that may of ND is not clear. Experimental assessment using virulent be related to Ethiopian holidays(Filseta, Enkutatesh etc) viruses is usually hamperedby cessation of egg laying in celebrated during wet season. Human activity and infected birds. Infected embryos have been reported increased turnover in the chicken markets during dry during naturally occurring infections of laying hens with season could leads to outbreaks of Newcastle disease virulent virus [44], but this generally results in the death (NCD) that have been attributed to high prevalence of the infected embryo during incubation. Cracked or during dry season [37,38]. As studies reported on broken infected eggs may serve as a source of virusfor Newcastle disease that indicated high significant newly hatched chicks, as may virus-laden feces difference in Newcastle disease (NCD) prevalence contaminating the outside of eggs. Virus may also between local and cross breeds of chickens. Highest penetrate the shell after laying [45], further complicating prevalence's are recorded in cross breeds of chickens the assessment of true vertical or transovarian than local breed [39]. The low altitudes do have higher transmission. Infected chicks may be hatched from eggs prevalence than the mid and high [38][39][40] In general, the younger the chicken, the more acute the spread is usually attributed to the movement of chickens disease. With virulent viruses in the field, young chickens through chicken markets and traders [41]. Newcastle may experience sudden deaths without major clinical greatly with the host. Chickens are highly susceptible, but signs; however, inolder birds the disease may be more Pathology protracted and with characteristic clinical signs. Breed or genetic stock does not appear to have a significant effect on the susceptibility of chickens to thedisease [48].

Clinical Signs:
The clinical signs in birds infected with ND virus vary greatly from very high morbidity and mortality to asymptomatic carriers. The severity of an infection is dependent on factors like the virulence and tropism of the virus, host species, age of host, immune status, other diseases and environmental conditions [49]. Symptoms from the respiratory tract are gasping, coughing, sneezing and rales. Signs from the nervous system include tremors, paralyzed wings and legs, twisted necks, circling, complete drop in egg production and an increased production of deformed eggs [49]. Clinical sign and course of disease can be grouped into four different pathotypes based on the strains of Newcastle disease virus [50]. These all four pathotypes are listed as follow: Viscerotropic Velogenic: That can be seen are obvious depression, inappetence, substantial drop in egg production, increased respiration, a profuse greenishyellow diarrhoea that rapidly leads to dehydration and collapse, swollen heads and cyanotic combs. Mortality can be up to 90% and infected birds usually die within one or two days. Birds that survive the initial phase often develop nervous signs. Sometimes birds dieperacutely without previous clinical signs.
Neuroptopic Velogenic: Acute signs from the respiratory tract and nervous system dominate. Sudden depression, inappetence and drop in egg production are seen together with coughing and other signs from the respiratory tract, followed by nervous signs within a few days. Mortality is usually around 10-20% for adult birds but can be higher for young birds.

Mesogenic:
Coughing and other signs from the respiratory tracts dominate. Other symptoms are depression, loss of weight and decreased egg production for up to three weeks. Signs from the nervous system can develop late in the disease. Mortality is around10%.
Lentogenic: Are often subclinical but mild respiratory signs and a small drop in egg production can be seen. No nervous signs and mortality is usually negligible.

Gross Lesions:
As with clinical signs, the gross lesions and the organs affected in birds infected with NDV are dependent on the strain and pathotype of the infecting virus, in addition to the host and all the other factors that may affect the severity of the disease. No pathognomonic lesions are associated with any form of the disease. Gross lesions may also be absent. Nevertheless, the presence of hemorrhagic lesions in the intestine of infected chickens has been used to distinguish Velogenic viscerotropic Newcastle disease (VVND) viruses from Neurotropic velogenic Newcastle disease (NVND) viruses [51]. These lesions are often particularly prominent in the mucosa of the proventriculus, ceca, and small and large intestine. They are markedly hemorrhagic and appear to result from necrosis of the intestinal wall or lymphoid tissues such as cecal tonsils and Peyer's patches. Generally, gross lesions are not observed in the central nervous system of birds infected with NDV, regardless of the pathotype [52]. Gross pathologic changes are not always present in the respiratory tract, but when observed they consist predominantly of mucosal hemorrhage and marked congestion of the trachea [53]. Air sacculitis may be present even after infection with relatively mild strains and thickening of the air sacs with catarrhal or caseous exudates is often observed in association with secondary bacterial infections [44].

Diagnosis:
Clinical diagnosis based on history, signs and lesions may establish a strong index of suspicion but the laboratory confirmation must be done. Hemagglutination and hemagglutination inhibition test, virus neutralization test, Enzyme linked immunesorbent assay, plaque neutralization test and reversetranscriptase polymerase chain reaction (RT-PCR) can be used for confirmation of the ND virus [54]. Now RT-PCR is the most exclusively used method to detect Avian influenza viruses (AIVs) and NDVs [9, 55,56]. RT-PCR assay is more sensitive, specific and less labor intensives as compare to other conventional methods used for lab diagnoses such as virus isolation, Immuno-Fluorescence Staining, Neuraminidase Inhibition and ELISA [57,58]. Using modern technologies, new diagnostic techniques are being developed for identification and differentiation of NDV strains [59]. Other molecular diagnostic tests like real time PCR and nucleotide sequence analysis are also important in viral disease diagnosis [58,60].

Isolation and Identification of Causative Agent
with Newcastle disease are as the follow: Fowl cholera, Direct Detection of Viral Antigens: Immunohistologic Highly pathogenic avian influenza, Laryngotracheitis, techniques offer a rapid method for the specific Fowl pox(diphtheritic form), Psittacosis(psittacine birds), demonstration of the presence of virus or viral antigens in Mycoplasmosis, Infectious bronchitis, Aspergillosis. organs or tissues. Immunofluorescence techniques for Also management errors such as deprivation of water, thin sections of trachea [61]. or impression smears [62] lack of or nutritionally deficient feed and poor ventilation. and an immunoperoxidase technique for thin sections In pet birds: Pacheco's parrot disease (psittacine birds), [63,64] have been reported and used in NDV infections.
salmonellosis, adenovirus, and other Paramyxoviruses. In Virus Isolation of NDV: Although molecular techniques, cholera and conformational abnormalities [71]. especially those developed to employ RT-PCR directly on samples from affected birds [65], mean that a positive Prevention and Control : The general approaches to the diagnosis at least can be obtained rapidly without virus control of Newcastle disease are hygiene and vaccination, isolation, it is still important that, for primary outbreaks this is always important, especially in the control of NCD especially, the virus is isolated for proper characterization in semi-intensive systems where birds are confined within and future work. a fenced yard or house. Hygiene includes measures such Culture System: Virulent ND viruses can be propagated personal hygiene of the farm staff. Vaccination in in many cell culture systems, and viruses of low virulence combination with appropriate hygiene measures, this can be induced to replicate in some of them. It is possible remains the most effective way of controlling NCD [72]. to use primary cell cultures or even cell lines for routine Vaccination against vND would result in immunity against isolation of NDV. The embryonated chicken egg, infection and replication of the virus. Realistically, ND however, represents an extremely sensitive and vaccination usually protects the bird from the more convenient vehicle for the propagation of NDV and is serious consequences of disease, but virus replication used almost universally in diagnosis. Embryonated and shedding may still occur [73,74]. chicken eggs should be obtained from a specific pathogen free (SPF) flock and incubated for 9-10 days at 37°C NCD Vaccines Are Available in Either "live" or "dead" before use. If SPF eggs cannot be obtained, eggs from a forms: Live vaccines are fragile and have very precise flock free of NDV antibodies should be used. NDV strains rules for use, requiring a cold chain up to the point of in eggs containing yolk antibodies can be propagated, but application to the bird. Their effectiveness is reduced if the virus titer is usually greatly reduced, and such eggs there are residual antibodies in the chickens. The immune should be avoided for diagnostic use.
response increases as the pathogenicity of the live Serologic Tests for Newcastle Disease Virus Antibodies: level of protection without serious reaction, vaccination Antibodies to NDV may be detected in poultry sera by a programs are needed that involve sequential use of variety of tests including single radial immunediffusion progressively more virulent viruses or live virus followed [66], single radial hemolysis [67], agar gel precipitin [68], by inactivated vaccine. Killed vaccines give good viral neutralization test (VN) in chick embryos [69], and immunity but require priming with a live vaccine for best plaque neutralization [44]. Sera from other species results, unless a natural infection has already served (including turkeys) may cause low-titer, nonspecific this purpose. In Ethiopia, vaccination has been reported agglutination of chicken RBCs, complicating the test.
as the only safeguard against endemic NCD. However, Such agglutination may be removed by adsorption with vaccines currently in use are mainly of benefit to chicken RBCs before testing. Although the HA and HI commercial poultry producers whose chickens are kept in tests are not greatly affected by minor changes in the large, single-age, confined flocks. Manufacturers produce methodology [70].
heat labile NCD vaccines in multidose vials, often Differential Diagnosis of Newcastle Disease: Differential (within19a 'cold chain') from manufacture until diagnosis is the process of differentiating Newcastle administration to the chickens. In contrast, village disease with other disease which share similar signs or chickens are raised in small, multi-age, free-range flocks symptoms. The disease which have similar clinical sign and large multi-dose vials of vaccine are inappropriate.
cormorants and other wild waterfowl: botulism, fowl as cleaning, disinfection, limiting access to wild birds, and vaccine increases [75]. Therefore, to obtain the desired containing 1,000 or 2,500 doses, which must be kept cold The cold chain is difficult to maintain under village virus will be shed in the ocular discharges from 4 to 7 conditions and purchase of commercial vaccines is a drain days. In some cases, mild, self-limiting influenza like on foreign exchange [76].
disease with fever and headache has also been reported Vaccines are being used to control and prevent ND.
in humans [33,83]. There is no evidence found to support Currently, many inactivated and live ND vaccines are human to human transmission but the potential for available around the world [77,78]. Chickens and turkeys human to bird transmission exists [83,85]. are immunized against New-castle disease. Live virus vaccines are administered by variety of routes and REFERENCES schedules from hatching till grow-out [79]. Pakistan.
Public Health Importance: Humans are among the many K. Kumanan, 2010. Molecular detection of Newcastle species that can be infected by NDV in addition to avian disease virus using Flinders Molecular detection of species. NDV may cause conjunctivitis in humans, when Newcastle disease virus using Flinders Tehnology a person has been exposed to large quantities of the virus Associates-PCR Tehnology Associates-PCR. J.