Date Published: December 2, 2018
Author(s): Muhammad Bashir Bello, Khatijah Mohd Yusoff, Aini Ideris, Mohd Hair-Bejo, Ben P. H. Peeters, Abdurrahman Hassan Jibril, Farouk Muhammad Tambuwal, Abdul Rahman Omar.
Newcastle disease (ND) is one of the most important avian diseases with considerable threat to the productivity of poultry all over the world. The disease is associated with severe respiratory, gastrointestinal, and neurological lesions in chicken leading to high mortality and several other production related losses. The aetiology of the disease is an avian paramyxovirus type-1 or Newcastle disease virus (NDV), whose isolates are serologically grouped into a single serotype but genetically classified into a total of 19 genotypes, owing to the continuous emergence and evolution of the virus. In Nigeria, molecular characterization of NDV is generally very scanty and majorly focuses on the amplification of the partial F gene for genotype assignment. However, with the introduction of the most objective NDV genotyping criteria which utilize complete fusion protein coding sequences in phylogenetic taxonomy, the enormous genetic diversity of the virus in Nigeria became very conspicuous. In this review, we examine the current ecological distribution of various NDV genotypes in Nigeria based on the available complete fusion protein nucleotide sequences (1662 bp) in the NCBI database. We then discuss the challenges of ND control as a result of the wide genetic distance between the currently circulating NDV isolates and the commonest vaccines used to combat the disease in the country. Finally, we suggest future directions in the war against the economically devastating ND in Nigeria.
Poultry production is globally threatened by a highly devastating disease of birds called Newcastle disease (ND). The disease was named after a place known as Newcastle Upon Tyne, in England where it was reported for the first time in 1926 . The disease was also reported around the same time in Java, Indonesia . Amazingly, its geographic distribution slowly expanded, leading to a well-established pandemic of the disease barely two decades after its novel emergence . Subsequently in the late 1960s, the second pandemic of the disease occurred with an incredibly high speed, taking only four years to spread throughout the world, probably due to extensive commercialization of poultry production and the improvement of air transport systems which facilitated the exchange of exotic birds into new areas . Although this pandemic was quickly placed under control with the then available ND vaccines, the third pandemic still occurred around the early 1980s among the racing pigeons [5, 6]. This particular pandemic proved to be difficult to control because of the nature of racing pigeon husbandry system. Eventually, the pandemic virus spilt over to the domesticated chicken and caused serious economic losses in the poultry subsector . The fourth pandemic, which started around the mid-1980s in the South-Eastern Asia, is currently believed to be on-going and has so far spread extensively to the Middle East, Europe, America, and Africa [8–11]. In Nigeria, the first official documentation of ND was in 1952 (Hill et al. 1953) and at present, the disease has been reported in all the ago-ecological zones of the country [12–15].
Although all NDV strains are classified under one serotype , their genetic diversity is enormous [36–39]. In the past, various schemes have been concurrently used to classify NDV based on their genetic information. The first classification system proposed by the Aldous group divides all the isolates into six lineages and 13 sublineages . An additional lineage and seven more sublineages were later proposed [41, 42]. The other scheme of NDV taxonomy proposed by Ballagi-Pordány et al.  and later substantiated by Czeglédi et al.  groups the NDV isolates into various genotypes and subgenotypes. Conflicts and confusion generated by these schemes of classification necessitated the need to develop unified criteria for NDV taxonomy. After analyzing the two systems extensively, Diel et al.  proposed the adoption of the genotype based classification not only because it is the most widely used, but also because it gives a stronger correlation between the intergenetic groups evolutionary distances and their phylogenetic relationships. Therefore, a unified nomenclature system was proposed for the then existing isolates and more comprehensive criteria for the assignment of newly emerged genotypes were proposed . According to the criteria, classification of a new genotype will be based on the phylogenetic topology using the complete, not partial F gene coding sequences. Furthermore, at least four isolates obtained from epidemiologically distinct events must form a phylogenetic cluster with a bootstrap value of nothing less than 60%. In addition, the isolates should have an average interpopulation evolutionary distance of ≥ 10. However, a mean evolutionary distance of 3-10% shall be used to designate a new subgenotype within a group .
Analysis of the complete F gene coding sequences (1662bp) for Nigerian strains of NDV available in the NCBI database reveals the occurrence of genetically distinct strains in various species of birds across the lengths and breadths of Nigeria (Table 2). Based on phylogenetic relationships and evolutionary distances, those isolates were grouped into class II genotypes I, VI, XIV, XVII, and XVIII. Except the genotype I isolates with GRQGRL amino acid motifs at positions 112-117 of the F gene, all other isolates considered in this study are predicted to be virulent in chicken based on the presence of multiple basic amino acid residues in their F cleavage sites (Table 1). Notably, among those virulent cleavage sites, the “RRQKRF” is the most diverse, being possessed by all the analyzed sequences except those from genotypes I and VIh. Furthermore, some strains from subgenotypes XVIIa, XIVb, and VIh display “RRRKRF” at their cleavage sites whereas only one isolate from subgenotype VIg, another one from subgenotype XVIIb, and four isolates from subgenotype VIh possess “KRQKRF”, “RRQRRF”, and “RRKKRF” cleavage sites, respectively. Interestingly, recent studies on amino acid composition of NDV F cleavage site revealed that strains with Q at the third position in the cleavage site are predicted to have an enhanced cell-cell spreading ability . Thus, in future development of vaccines based on indigenous NDV isolates in Nigeria, special consideration should be given to those isolates with Q at the third position of their F cleavage site.
Vaccination remains the most practical method of disease control in poultry and therefore plays a major role in strengthening the modern poultry industry [89, 90]. The ultimate goal of any vaccination program is the induction of sterilising immunity in the vaccinated host . However, this is hardly achievable in poultry , owing to numerous factors that may adversely affect the efficacy of vaccination. The fact that all NDV strains are grouped into one serotype  suggests that immunity developed against one strain should offer cross protection against challenge with any other strains. Unfortunately to date, outbreaks of ND are frequently reported among farms that have vaccinated using the available vaccines [32, 52, 53]. The cause of these disease outbreaks among the vaccinated birds is still controversial in the literature. While some researchers hold the view that the poor vaccine induced immunity is due to the suboptimal vaccine intake following its mass administration in poultry , others believe that the genetic variation between the vaccine and the circulating field strains might be the major factor responsible for the incomplete protective efficacy of the current vaccines [94, 95]. Although the currently used vaccines, when correctly administered, are known to fully protect birds against clinical disease and mortality [95, 96], they cannot block the replication of the virulent virus post challenge [44, 45]. Thus, the vaccinated birds may look apparently healthy but still excrete a large amount of the virulent virus, which can in turn cause disease among unprotected birds. Since it is an established fact that ND vaccines are more effective in reducing virus shedding when the vaccine strains are genetically closer to the challenge strain [57, 97], the evolutionary distance between the vaccine strains and the circulating field strain represents an important factor in effective disease control, since it explains the continuous occurrence of ND outbreaks despite the extensive poultry vaccination programs in the country.
The panacea for all these ND control challenges in Nigeria is the maintenance of strict biosecurity and the development of rationally designed vaccines based on the currently circulating isolates in the country. With the advent of reverse genetics technology that allows the recovery of recombinant NDV from their cloned cDNA , genotype-matched live attenuated vaccines can be easily generated. Since the complete genome sequence of some biologically well-characterized viruses in the country has already been obtained [33, 34], efforts should be intensified towards rescuing their attenuated counterparts by simply engineering their F cleavage site to encode monobasic amino acid residues instead of the poly basic motifs . By developing a reverse genetics system for one prevalent strain in the country, vaccine candidates against all the circulating strains can easily be obtained by F gene swapping in the full length infectious clone followed by the recovery of the chimeric viruses by reverse genetics techniques. Alternatively, recombinant viral vectors such as herpesvirus of turkey  (HVT) expressing surface glycoproteins (F and/or HN) of the circulating NDV can be developed as an effective genotype-matched vaccine against the prevailing genotypes in the country.
In summary, a comprehensive distribution of NDV genotypes in various regions of Nigeria has been provided. Apparently, multiple genetically distinct strains of NDV are cocirculating in some states of the federation, an important factor that may favour the emergence of novel virulent isolates in the country. In particular, apart from genotype VI isolates, all the virulent NDV genotypes prevalent in Nigeria have been isolated in Sokoto State between 2007 and 2011, making the State a potential hotspot of different NDV genotypes in Nigeria. It is interesting to know that genotype VII isolates responsible for the on-going fourth and the imminent fifth ND panzootic [102, 103] have not been reported in Nigeria despite their recent emergence in some African countries [104, 105]. Since these panzootic viruses have a high potential for international spread, there is a need to intensify disease surveillance activities and strengthen biosecurity barriers so as to avoid their introduction into the country. Finally, given the wide evolutionary divergence between the commonly used vaccines and the circulating NDV strains in the country, there is a need to revise the current ND control strategies in Nigeria. Genotype-matched vaccines with improved protective efficacy and virus shedding blocking ability should be designed to specifically target the currently circulating NDV genotypes in the country.