Preface
In the preface to the first edition, it was noted, with perhaps only a hint of irony, that paratuberculosis is ‘not a disease on which fast progress has been made'. This remains a truism, and during the past decade and a half since the first edition was written and published, much has changed, yet much remains the same.
To capture the state of knowledge, thought leaders in the field of paratuberculosis detail in the 23 chapters (condensed from 29 chapters) of this second edition, all the many improvements in the understanding of the epidemiology of the pathogen, the organism and its association with various hosts, as well as how to better diagnose infection and control disease. In so many ways, the progress is remarkable - yet much remains the same. Paratuberculosis is still stubbornly endemic across most of the world, and progress in control of the spread is dependent almost entirely on avoiding infection in the first instance through what might be considered largely as good husbandry practices that limit opportunities of transmission. Vaccines are still rarely used, not because they are entirely ineffective, but rather because they confound diagnosis of tuberculosis and the business case for their use remains unclear. Importantly as well, the long-hypothesized association of Mycobacterium avium subsp. paratuberculosis with Crohn's disease remains just that. However, there are several good reasons that this is just the right time to collectively take stock of what we have learnt and how far we have come; to begin to harmonize use of common terminology to facilitate better understanding; as well as to share perspectives on what might be achieved in the coming decades and how we might get there.In this new edition of the book we have reorganized some of the chapters to incorporate and place in context additional information that has come to light since the last edition.
With the focus being on new information, the chapter on the history of paratuberculosis has been omitted since the advances of the past two decades are implicit in the chapters in the new edition. With more researchers using whole genome sequencing, there is a plethora of new data on phylogenomics, epidemiology and strain diversity, and this information has been captured in Chapter 6 (Stevenson) rather than being distributed across chapters on the genome, on strain characterization and on comparative differences between strains. We have combined the first-edition chapters on experimental ruminant and small animal models. Likewise, the three chapters on control of paratuberculosis in Europe, the USA and Australia have been combined, together with new information from other countries, to provide a more balanced overview.Readers of the second edition will notice that to enable better harmonization and standardization, throughout the book, we have edited Mycobacterium avium subsp. paratuberculosis to MAP. This was done in the first edition, and we continue this approach, to avoid the unnecessary use of 50 characters in the place of three. The editors recognize that this is not a standardized abbreviation in microbial nomenclature, so we have not extended this to other organisms. Where the authors refer specifically to M. avium hominissuis, we have left this name as is; when referring to M. avium other than MAP, we have edited this to M. avium avium, in keeping with the latest recommended nomenclature (see Chapter 5, Turenne). Likewise, M. tuberculosis is not Mtb. Within MAP, there are different lineages that have been called strains by others. In some papers, these are called type I/II/III; in others, MAP-C and MAP-S. To harmonize across chapters, we have edited the usage to indicate that there is a C-lineage and an S-lineage, and these can be shortened to MAP-C and MAP-S (see Chapter 6, Stevenson, for more details on this). Similarly, when MAP causes infection and disease, different descriptive terms are used by different groups.
The word ‘latent’ appeared in several draft chapters, and it often was not clear whether this referred to an undiagnosed infection, immunological reactivity in the absence of clinical signs, a dormant bacteriological process or the interval between being infected and becoming infectious. The problems associated with the use of this term have been recently highlighted in the case of ‘latent TB’, and so we have tried to remove this word when the meaning was potentially ambiguous. We also encountered terms such as ‘silent’ and ‘subclinical’ infection, but the distinction between these entities was not always clear. We considered adopting throughout the book the recently proposed three-stage terminology (Whittington et al., BMC Veterinary Research, 2017, 13(1), 328): (i) subclinical infection, which is defined as MAP infection without demonstrable pathology in tissues; (ii) subclinical disease, which is defined as the presence of pathology in tissues without weight loss or diarrhoea; and (iii) clinical disease, which is defined as the presence of pathology + weight loss and/or diarrhoea. However, several authors have chosen to refer to four stages of disease, as has been classically done in the prior literature: silent, subclinical, clinical and advanced clinical. We decided to leave the four stages as written but encourage the field to consider ways to best harmonize the terminology regarding the progress of infection to disease. Related to this, some use Johne’s disease (JD) to describe all of these stages while others have used the term Johne’s disease to describe severe disease only. We have tried to use the term paratuberculosis throughout the book, and avoid the use of Johne’s disease, as it is arguably a subset of the overall process.The novel information on paratuberculosis, together with new technologies developed in the past decade, offer new opportunities and perspectives for the future. Areas of potential interest include using genomic comparisons to determine the age of MAP, the age of MAP-C divergence from MAP-S and the timing of introduction of MAP into regions and countries, in order to date the problem.
This has been performed for Mycobacterium tuberculosis and Mycobacterium leprae, and while this often corroborates pre-existing wisdom, there are occasional surprises, such as a pinnepid origin of human TB in pre-Columbian Peru. Other areas of potential interest are how one might differentiate infected but recovered or self-cured animals from those that are infectious or diseased, and how one might predict which infected animals are likely to shed and progress to clinical disease. For reasons not entirely clear, advances in understanding the immunology of host responses to MAP have somewhat lagged behind some of the more rapid advances in understanding the organism itself including diagnostics. Perhaps this is because of the lower-hanging fruit associated with technical advances in genomics and other omics fields. Another understudied area is the environment, particularly in terms of environmental transmission and survival of the organism. Plugging knowledge gaps in this area would better inform management and control.What is not here, and might present in the future, should the science so develop, includes new fundamental science (microbiome, epigenomics, microRNAs, organoid culture), and emergent translational tools in diagnostics (phage, point-of-care tests, sensor technologies, digital polymerase chain reaction (PCR)) and potentially treatment (probiotics, phage therapy). What is also not here and is much needed is fit-for-purpose interventions for better control of paratuberculosis in low and middle income countries where MAP is endemic, but traditional approaches to control (test and remove) are unfeasible due to socioeconomic considerations.
Finally, a word about standardization and why we wrote this book. As stated in the American Academy of Microbiology report on MAP (https://www.asmscience.org/content/report/colloquia/ colloquia.33), there is a lot we do not know, in part because the research is not sufficiently reproducible. There are numerous reasons for this conundrum.
For instance, MAP is a slow-growing organism that is difficult to enumerate. Borders block the flow of pathogens, constraining research opportunities. MAP infects different host species, with variable outcomes of infection, etc. Despite these differences, there is a lot that we do know, as articulated in the 23 chapters written by content experts, compiled here. For those coming into the MAP domain, for research or veterinary practice, we hope you can make use of this information, these methods, these current concepts, to fill the knowledge gaps. Work on MAP is slow and challenging enough; let's not have everyone start from zero, when there is a MAP research community that can offer its lessons, its reagents and its insights to those who wish to join. These were the intentions of our colleague Des Collins, who guided the first edition to completion and who provided generous and wise counsel to the three of us for this second edition. We hope this book serves its stated purpose.Marcel A. Behr Karen Stevenson Vivek Kapur January 2020
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