Recent breakthroughs have unveiled the many knowledge gaps in Clostridium perfringens-associated necrotic enteritis in chickens: the first International Conference on Necrotic Enteritis in Poultry

After decades as a scientifically neglected disease, necrotic enteritis (NE) has become an important focus for research by scientists armed with very powerful new technology and understanding. As agriculture moves away from the use of antibiotics to control endemic disease, scientists from numerous different disciplines can contribute their skills and collaborative efforts to controlling what has been described as a $6 billion disease. Finding alternatives to medically important antibiotics to control NE represents a considerable challenge to global broiler production but has unleashed a wave of creativity that was apparent at the first International Conference on Necrotic Enteritis in Poultry. The conference was held in Copenhagen in the summer of 2015, with Prof. K. Pedersen and Dr U. Lyhs as organizers. At this conference researchers and others involved in NE gave overviews of developments and raised provocative questions. The current Special Issue of Avian Pathology has compiled these overviews as short topical reviews, and has combined these with original papers on the disease. The intent is to help researchers and the poultry industry to have an up-to-date resource as well as to identify and engage with the knowledge gaps that still need solution. There are many. NE in chickens was first reported in the 1950s and subsequently in periodic episodes over time, depending on the world region. It has been clear that the use of antimicrobials and ionophorous coccidiostats have played a major role in keeping the disease under control for many years, well reviewed by Kaldhusdal et al. (2016) in this Conference issue. It is thus not surprising that a search in the biomedical literature database of PubMed, using the terms “Chicken, Clostridium perfringens”, shows an increasingly steep increase in the number of published papers starting from shortly before the ban on antimicrobial growth promoters (AGPs) in the European Union late in 2006 (Figure 1). Continuous genetic and management changes during the second half of the twentieth century that led to very high production performances, combined with AGP usage, thus caused a situation for 50 years in which there was no experience with antibiotic-free bird production. Intestinal health problems, including NE, emerged after the AGP ban. The disease is regarded as a typical production disease related to predisposing factors associated with the way the birds are raised, including the housing density, high energy diets and certain stresses, as discussed in the review paper of Moore (2016) in this issue. The example of broiler NE speculatively suggests that changing the “normal” phenotype of an animal can alter its susceptibility to specific diseases. The high production performance of food birds is important for providing the world population with reasonably priced animal protein but may be at the cost of endemic disease such as NE. The “epidemic” of NE in birds seems to be under control now because of the implementation of specific management factors (Tsiouris, 2016) and, again, the therapeutic use of antibiotics. To lower the antibiotic usage, there is a need to develop alternate strategies to control intestinal health problems. To be able to do this, a thorough knowledge of the interactions between the microbiota and the host and how this affects colonization with C. perfringens (and vice versa) can be essential. There are indeed specific microbiota changes correlated with NE, and the potential role of these changes is reviewed by Antonissen et al. (2016) in this issue. Development of strategies to control a disease requires thorough knowledge of the behaviour of the pathogen in the host and a clear understanding of the virulence factors associated with disease. Although the NetB toxin has been identified as the key toxin in NE in broilers, considerably more work is required to understand the detailed pathogenesis of NE. For epidemiological purposes and to be able to monitor the infection with virulent strains, markers need to be identified that easily detect and quantify levels of virulent C. perfringens strains. In addition, until now it has not yet been possible to identify subclinically affected birds without performing a necropsy and looking for macroscopic lesions. The identification of faecal markers associated with colonization by virulent strains or associated with macroscopic lesions might be of great value in targeting therapeutic interventions in a timely way. Although NetB has been identified as a key toxin involved in disease (Keyburn et al., 2008), this has still not led to the development of a vaccine for broilers (Mot et al., 2014). Several antigens in addition to NetB seem to be important in immunoprotection. Although vaccine development is one focus of NE research, it was one of the gaps at the Conference and an important area for further understanding. Apart from not understanding the basis of immunity to NE, and how effective immunity is, another challenge is the delivery of booster vaccines to broilers given the short life span of these birds. Breeder vaccines can be a solution but there is an important issue because of the decrease in maternal antibodies in