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Depending upon the involvement of etiological agent, the infectious respiratory diseases of small ruminants can be categorized as follows [9, 14]:bacterial: Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, enzootic pneumonia, and caseous lymphadenitis,viral: PPR, parainfluenza, caprine arthritis encephalitis virus, and bluetongue,fungal: fungal pneumonia,parasitic: nasal myiasis and verminous pneumonia,others: enzootic nasal tumors and ovine pulmonary adenomatosis (Jaagsiekte).
Manytimes due to environmental stress, immunosuppression, and deficient managemental practices, secondary invaders more severely affect the diseased individuals; moreover, mixed infections with multiple aetiology are also common phenomena [5, 8, 13, 15].
These conditions involve respiratory tract as primary target and lesions remain confined to either upper or lower respiratory tract [7, 16]. Thus, these diseases can be grouped as follows [5, 8, 14, 17].Diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, mainly remain confined to sinus, nostrils, and nasal cavity. Various tumors like nasal polyps (adenopapillomas), squamous cell carcinomas, adenocarcinomas, lymphosarcomas, and adenomas are common in upper respiratory tracts of sheep and goats. However, the incidence rate is very low and only sporadic cases are reported.Diseases of lower respiratory tract, namely, PPR, parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others which involve lungs and lesions, are observed in alveoli and bronchioles.
Depending upon the severity of the diseases and physical status of the infected animals, high morbidity and mortality can be recorded in animals of all age groups. These diseases alone or in combination with other associated conditions may have acute or chronic onset and are a significant cause of losses to the sheep industry [3, 10]. Thus, the respiratory diseases can also be classified on the basis of onset and duration of disease as mentioned below [3, 9, 14, 18]:acute: bluetongue, PPR, Pasteurellosis, and parainfluenza,chronic: mycoplasmosis, verminous pneumonia, nasal myiasis, and enzootic nasal tumors,progressive: Ovine progressive pneumonia, caprine arthritis encephalitis virus, caseous lymphadenitis, and pulmonary adenomatosis.
Small ruminants particularly sheep and goats contribute significantly to the economy of farmers in Mediterranean as well as African and Southeast Asian countries. These small ruminants are valuable assets because of their significant contribution to meat, milk, and wool production, and potential to replicate and grow rapidly. The great Indian leader and freedom fighter M. K. Gandhi “father of the nation” designated goats as “poor man's cow,” emphasizing the importance of small ruminants in poor countries. In India, sheep and goats play a vital role in the economy of poor, deprived, backward classes, and landless labours. To make this small ruminant based economy viable and sustainable, development of techniques for early and accurate diagnosis holds prime importance. Respiratory diseases of small ruminants are multifactorial and there are multiple etiological agents responsible for the respiratory disease complex. Out of them, bacterial diseases have drawn attention due to variable clinical manifestations, severity of diseases, and reemergence of strains resistant to a number of chemotherapeutic agents. However, sheep and goat suffer from numerous viral diseases, namely, foot-and-mouth disease, bluetongue disease, maedi-visna, orf, Tick-borne encephalomyelitis, peste des petits ruminants, sheep pox, and goat pox, as well as bacterial diseases, namely, blackleg, foot rot, caprine pleuropneumonia, contagious bovine pleuropneumonia, Pasteurellosis, mycoplasmosis, streptococcal infections, chlamydiosis, haemophilosis, Johne's disease, listeriosis, and fleece rot [3–10].
The respiratory diseases represent 5.6 per cent of all these diseases in small ruminants. Small ruminants are especially sensitive to respiratory infections, namely, viruses, bacteria, and fungi, mostly as a result of deficient management practices that make these animals more susceptible to infectious agents. The tendency of these animals to huddle and group rearing practices further predispose small ruminants to infectious and contagious diseases [6, 9]. In both sheep and goat flocks, respiratory diseases may be encountered affecting individuals or groups, resulting in poor live weight gain and high rate of mortality. This causes considerable financial losses to shepherds and goat keepers in the form of decreased meat, milk, and wool production along with reduced number of offspring. Adverse weather conditions leading to stress often contribute to onset and progression of such diseases. The condition becomes adverse when bacterial as well as viral infections are combined particularly under adverse weather conditions. Moreover, under stress, immunocompromised, pregnant, lactating, and older animals easily fall prey to respiratory habitats, namely, Streptococcus pneumoniae, Mannheimia haemolytica, Bordetella parapertussis, Mycoplasma species, Arcanobacterium pyogenes, and Pasteurella species [2, 4, 7–9, 12, 13]. Such infections pose a major obstacle to the intensive rearing of sheep and goat and diseases like PPR, bluetongue, and ovine pulmonary adenomatosis (Jaagsiekte) adversely affect international trade [2, 9, 10, 13], ultimately hampering the economy.
Considerable expertise has developed over many years among DAFM staff in Ireland regarding the investigation of suspect BSE cases. During this period, a questionnaire was informally and progressively developed by DAFM staff to guide the investigation of BSE, and particularly BARB, cases. The questionnaire, currently with 135 questions, is presented in online supplementary appendix 1. For ease of data collection, the questions are grouped by topics to aid data collection, including case animal details (Q1–25), herd details (Q26–41), parents (Q42–67), compliance with identification requirements (Q68–75), general farm management practices (Q76–92), feed (Q93–117), farm management practices when case animal was present on the farm (Q118–131) and history of on-farm deaths (Q132–135).
The BSE investigation questionnaire was developed to aid field-based data collection in Ireland. As part of the current study, we have adapted this questionnaire to maximise its usefulness as an investigative tool for suspect BSE cases. Specifically, drawing on current understanding of BSE and on experiences gained with BSE investigations in Ireland, we have developed an epidemiological framework to be used in conjunction with the BSE investigation questionnaire, focusing on (1) confirmation and discrimination; (2) estimating the date and location of exposure; and (3) determining the method/source of exposure (Box). At each step of the framework, we describe the tools available, information required and the relevant questions from the supplementary questionnaire. The steps to be taken during the investigation are guided by the type of BSE (classical or atypical) identified, as determined by OIE-approved discriminatory testing. If atypical H-type or L-type BSE is confirmed, the investigation does not progress beyond ‘1. Confirmation and discrimination’. If classical BSE is confirmed, the investigation continues to include ‘2. Estimating the date and location of exposure’ and ‘3. Determining the method/source of exposure’. Decisions with respect to ‘3. Determining the method/source of exposure’ should be made using a legal standard of proof of at least ‘on the balance of probabilities’ or ‘on the preponderance of the evidence’,41 42 after considering all data relevant to the biological plausibility of each alternative. The framework has been developed to be suitable for use during on-farm epidemiological investigations of suspect BSE cases.BOX :Epidemiological framework to investigate suspect BSE cases.*Confirmation and discriminationTools availableConfirmatory tests (OIE-approved immunoblot method) (see online supplementary appendix 2)Discriminatory tests (two-blot protocol)Clinical historyInformation requiredLaboratory confirmation of presence of BSE agent (Q1–2)Identification of BSE type (classical, atypical H-type or L-type) (no further investigation is conducted if atypical BSE is confirmed) (Q3–6)Description and timeline of clinical signs (Q7–Q11, Q2)Estimating the date and location of exposureTools availableBSE investigation questionnaire (see online supplementary appendix 1)National identification and movement databaseAdditional data gathering (personal interview, inspection of farm records)Information requiredDetails of case animal, including identification and movement history (Q12–Q14, Q15–Q18, Q19, Q20, Q21–Q28)Herd/farm details (Q29–Q31)Past BSE and scrapie history of farm (Q29, Q32, Q33)Likely infection window (encompassing the most likely period of infection of the case animal) (Q15, Q16, Q11)Progeny/cohort tracing (Q34, Q29, Q30)Determining the method/source of exposurePossible sources of exposure are:Maternal transmission (dam and progeny)Feedborne details and feed management/storageEnvironmental exposureIatrogenic transmissionTools availableEpidemiological investigations on index farm (the herd of residence of the case animal at the time of diagnosis) (and on previous farms if deemed necessary) (farm visit, interview, BSE investigation questionnaire (online supplementary appendix 1))Maps (other infected premises)Backward tracing information (animal movement, identification of cohorts and progeny)Additional data gathering (personal interview, farm records, feed company records, medicines, BSE status of parents/cohorts/progeny/disposal of carcases)Information requiredBSE status of parents of index case (Q35–Q38, Q39-Q64)Spatial relationship between index and other known infected premises (Q65–Q67, Q68, Q69)Location of index farm in relation to other features of potential interest (including neighbours, abattoirs, feed mills, roads, water courses, etc) (Q70–Q75, Q69)Source and storage of feeds and fertilisers (including milk replacer and proprietary calf feed) (Q76–Q100)On-farm animal movement during tracing window (progeny, cohorts and other movements) (Q29, Q101–Q103)Human and other movement during tracing window (Q104–Q108)Husbandry/medicinal practices (Q109–Q123)General farm management practices (Q124–Q135, Q104–Q108)The relevant questions in the associated BSE investigation questionnaire (online supplementary appendix 1) are included in brackets (in italics).*Suspect BSE case is defined in accordance with Article 3 of Regulation (EC) 999 of 2001.BSE, bovine spongiform encephalopathy; OIE, International Organisation for Animal Health.
This study describes the use of an epidemiological framework and associated BSE investigation questionnaire to structure the investigation of suspect BSE cases, detailing tools and information required to confirm and discriminate BSE, to estimate the date and location of exposure, and to determine the method/source of exposure. The framework and questionnaire provide a systematic approach to investigating suspect BSE cases, and subsequently confirmed classical BSE cases, based on the experience of the competent authorities in Ireland developed over the last 25 years. The epidemiological framework provided structure and focus to the BSE investigation questionnaire, noting that the latter has been used extensively to aid data collection during BSE investigations in Ireland.
Based on the results of our field investigation of the 2015 classical BSE case in Ireland, no source of exposure of the case animal to the BSE agent could be determined. Nonetheless, a number of tentative conclusions can be drawn in relation to this case, based on the results of the field investigation.
There is uncertainty as to whether maternal transmission of BSE from infected dam to offspring in bovines can occur.44 45 In this case, there was no evidence to support this hypothesis given that the dam of the index case never exhibited any clinical signs of BSE during her life and tested negative at healthy slaughter.
Although widely accepted as the main source of BSE prion transmission for cases of classical BSE, there was no evidence in this case to indicate that the feed supply chain was a contributory factor, or that the case animal had been fed with feed containing MBM. As well as carrying out a thorough investigation of the feed supply chain for the index herd, the investigation team evaluated the potential for contaminated feed to have been supplied to the farm. In 2009 and 2010, few BSE cases were detected in Ireland (9 in 2009, 2 in 2010) compared with a high of 333 in 2002. Also, comprehensive control measures had been put in place in 2009 and 2010, including active and passive surveillance, removal and destruction of dead-on-farm animals, effective rendering systems, and controls with regard to the potential for cross-contamination at mills. Feed imported into Ireland was also subject to routine inspection and testing, which did not identify any bone spicules. These controls led to a substantial reduction in the likelihood of contaminated feed acting as a source of the BSE agent. However, because of the passage of time, it was not possible to be certain that we obtained complete information on all possible sources of contamination of feed for the index herd. It has been shown that an animal can be infected by a very low oral dose of the BSE prion, with the attack rate and incubation period dependent on the dose.46 47 Findings in the UK have highlighted the possibility of persistence of traces of contaminated feed in on-farm feed stores and the need for special care in the cleaning and maintenance of feed bins and silos and other feed storage facilities.36 Consequently, inadvertent exposure to the BSE agent in residues of old particles of feed cannot be definitively ruled out.
Deposition of BSE prions in the environment may occur due to burial of carcases or through biosolids from water treatment plants processing infected animals.48 However, the risk of such transmission is extremely low, with no evidence to support environmental contamination as a relevant infection route.36 There was no evidence in our field investigation that the case animal was exposed to the BSE agent through an environmental source.
While there is evidence of iatrogenic transmission of the BSE prion,49 this investigation did not support the hypothesis that the case animal was exposed to the BSE agent via medicinal products or vaccines. All of the products used on the farm were routine medicinal products or vaccines and there was no evidence that they could contain BSE prion material. We had no reason to doubt the reliability of information obtained from farm records, from the herd owner and from the PVP.
The identification of BARB cases is not unprecedented, but continues to be challenging from an epidemiological perspective. The epidemiological framework and BSE investigation questionnaire overcome some of these challenges, in particular the use of methodology to facilitate data collection that is comprehensive and consistent. Further, the framework and questionnaire are underpinned by best available science. Nonetheless, several challenges remain that contribute to the difficulty in attributing cause to recent BSE cases. By its nature, a case study does not allow definite conclusions to be drawn on the source of disease. Further, the role of any specific putative source cannot be directly tested as no information is available on suitable controls. Finally, because of the passage of time between exposure and the development of clinical signs, there are inevitable information gaps that hamper attribution of the source of the BSE agent. Ireland’s 2015 BSE case was identified through existing surveillance mechanisms, and the investigation provided evidence that all BSE controls are operating as intended. Based on the investigation, no definitive source of infection with the BSE agent was identified.
Overall, the epidemiological framework and associated BSE investigation questionnaire provide structure, focus and detail to the field investigation of BSE cases in Ireland, and may be useful in other settings. We note that the main objective of the epidemiological framework is to hypothesise, or rule out, possible BSE sources on the balance of probabilities rather than beyond reasonable doubt. The framework provides an epidemiological logic to the assembly of evidence and allows the different steps of the investigation to be fully documented. The framework and associated questionnaire uses the best information available at the time of investigation of BSE cases. Given the rarity of BARB cases and uncertainty surrounding the source of infection for these cases, particularly as the interval between the implementation of the reinforced feed ban and the occurrence of new cases increases, it is essential that a comprehensive and thorough investigation of each new BARB case is carried out. It is hoped that the investigation procedure described here will be of benefit in that regard and that the information provided by the investigations will assist veterinary authorities in ensuring that the measures in place to eradicate BSE continue to be relevant, appropriate and fit for purpose.