Central Journal of Veterinary Medicine and Research Bringing Excellence in Open Access

Review Article *Corresponding author Abdinasir Yusuf Osman, Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, The Epidemiology and Universiti Malaysia Kelantan, Pengkalan Chepa 16100 Kota, Bharu, Kelantan, Malaysia, E-mail:

Pathophysiology of Caseous Submitted: 04 April 2018 Accepted: 19 April 2018 Lymphadenitis: A Review Published: 02 April 2018 ISSN: 2378-931X 1,2 1,3 Abdinasir Yusuf Osman *, Muhammad Luqman Nordin , Copyright 3 2 Arifah Abdul Kadir and Abdul Aziz Saharee © 2018 Dey et al. 1Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti OPEN ACCESS Malaysia Kelantan, Malaysia 2Department of Veterinary Clinical Studies, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Malaysia Keywords 3Department of Preclinical Studies, Faculty of Veterinary Medicine, Universiti Putra • C. pseudotuberculosis; Epidemiology; Malaysia, Malaysia Pathophysiology; Small ruminant

Abstract Caseous lymphadenitis is one of the most significant zoonotic diseases caused by C. pseudotuberculosis with enormous economic losses in animal industry worldwide. The global burden of its incidence in animal populations remains at an alarming rate. The impact of the disease is multidimensional in nature and not always well understood, therefore, significantly complicating effective policy response. The pathogenesis is complex and governed by several factors working together in synergistic manner. Information related to the epidemiology and pathophysiology is still scarce in the database and control programmes are rarely implemented. Therapy is based on wide spectrum with mysterious outcome as pre-existing vaccines appear not promising. Thus, understanding the biological behaviour of the disease becomes a fundamental issue. In this review, we highlight various key aspects of the disease with special reference to the epidemiology and the pathophysiology of the disease in and populations.

INTRODUCTION Corynebacterium pseudotuberculosis is a causative agent of differentiate between previously exposed animals and those still chronic in a number of different mammalian species, harboring the pathogen. and the coarse of infections consist of microbial adaptation The critical factors influencing the transmission dynamics the most significant of which is caseous lymphadenitis (CLA) or cheesy gland, a chronic granulomatous infectious disease of ofand economic change; developmenthost susceptibility; and land climate use; alteration; international changing trade; sheep and that is characterized by abscessation of one or ecosystem, demographic, and population including issues more lymph nodes. The organism was first isolated from a case of lymphangitis in a cow in 1888 by French bacteriologist Edward technology and industry; reduction in animal and public Nocard. Years later, however, another bacteriologist, Hugo von health services. Therefore, this review is conducted to provide Preisz, isolated analogous organism from a different case. CLA andmore discus comprehensive the importance and stimulating these aspects overview in controlling regarding of the is distributed globally and causes important economic losses for epidemiology and pathophysiology of caseous lymphadenitis, ovine and caprine breeders due to body wasting, subsequently disease.THE ORGANISM AND DISEASE HISTORY reduced meat, wool, milkC. pseudotuberculosis yields and segregation of affected animals, condemnation of downgraded of affected carcasses and mastitis,skins in abattoirsarthritis, orchitis, [1]. subcutaneous , commonly abortion, causes still microbe, the organism has come to be recognized as Bacillus birthCLA in and sheep prenatal and goats mortalities and, less and commonly, mastitis inpneumonia, and hepatitis,buffaloes pseudotuberculosisAs a result of various discoveries related to this th . The latter name has lasted until the end of [2]. In Malaysian small ruminants, the average prevalence of CLA Mycobacterium19 century and pseudotuberculosis was given in the assumption that there was was found to be 30% using a combined diagnostics tests [3] and a clinical similarity of lesions between caseous nodules and Numbers of serological modalities have been suggested 11.1% using conventional methods [4]. Corynebacterium and at the same. timeThrough renamed different to become names recognizedin different aseditions, Corynebacterium the organism ovis. was Since, placed the in the latter genus name of though these tests might be considered as a fundamental point to detect the evidence of CLA in animals [5-7]. Even indicated for specification and missed entirely the general for revealing of sub-clinically infected animals, most of them also be a host for the same agent, the species name, therefore, ability that may imply for other mammalian species which might suffer from low sensitivity, poor specificity and lack of ability to Cite this article: Osman AY, Nordin ML, Kadir AA, Saharee AA (2018) The Epidemiology and Pathophysiology of Caseous Lymphadenitis: A Review. J Vet Med Res 5(3): 1129. Dey et al. (2018) Email:

Central Bringing Excellence in Open Access had been changed back from ovis to the earlier designation of necrosis. In addition, mycolic acid induces degenerative pseudotuberculosis. From that time, the C. pseudotuberculosis has [14]. However, unlike the lethal effect of injection of similar that cause caseous lymphadenitis [8]. moleculeschanges and extracted death from in phagocytizing mycobacteria, leucocytes the cytotoxic (Batey, effect 1986) of C. formally become known as the officially recognized disagnation pseudotuberculosis GEOGRAPHICAL DISTRIBUTION [15]. Some authors have suggested that the mycolic acid coat The global distribution of caseous lymphadenitis is almost a enables C. pseudotuberculosis mycolic acid to is confined survive forto the extended site of injection periods mirror image of farmed small ruminants. The disease is generally within the environment, a feature common to other members of multicontinent and it has been reported to be widely prevalent in the actinomycete family. Corynebacterium pseudotuberculosis is , , , South and , and the Middle East [9]. CLA, in many of these countries, has been generally indeedIn naturalrelatively infections, resistant to the environmental waxy mycolic conditions acid coat [16]. of C. pseudotuberculosis provides the organism with mechanical, and economic losses and other health issues associated with animal considered as a devastating disease which is characterized by welfare in livestock. The infection of the disease, however, had present within lysosomes which in turn enables the bacterium to been observed predominantly in sheep and goats. survivepossibly phagocytosis biochemical, and protection to exist within from thethe hydrolytichost as a facultative enzymes The presence of close genotypic relationship, however, among intracellular parasite [17]. This capacity is likely to be essential C. pseudotuberculosis isolates ovine/goat origin from a various for the migration of the organism from the point of initial entry to the eventual site of lesion development. In addition, the toxic infections had a common source, and subsequently supporting nature of mycolic acid seems to contribute to abscess formation. thecountries assumption in the world that the[2], spreadmight be of sufficient the disease evidence followed that the exportation of sheep by colonial powers in 18th century [10]. demonstrated between the quantity of cell wall lipid produced New strict regulations, related to the presence of lesions in byIn different artificial isolates infections of C. ofpseudotuberculosis mice, a direct and relationship their ability was to imported carcasses were applied worldwide. Large scale studies produce chronic abscessation. on different aspects of the disease including pathogenesis and epidemiological - led to further series studies of control strategies HOST RESPONSE designated to reduce the remarkable CLA prevalence of that time The host cellular response to infection with organism and, therefore offered preventive ways for future studies. C. pseudotuberculosis pathological studies involving small ruminants particularly PATHOGENESIS VIRULENCE FACTORS sheep( challenged subcutaneously;) has not been vast numbersdescribed of in neutrophils detail. In A recent study in general has mainly focused on only two known few hours following infection. And within 24 h they began were found to infiltrate the site of inoculation within the first acids. Neither virulent strain nor plasmids of C. pseudotuberculosis to move to the local drainage lymph nodes. It was notably havevirulence yet factors been described. identified as Unlike phospholipase other pathogenic D (PLD) and organisms, mycolic reported that number of neutrophils began to decline after 3 the genome of this pathogen has yet to be fully sequenced. The days, while the numbers of macrophages at the inoculation site organism’s virulence mechanisms, therefore, remain poorly understood. The major virulence factor of C. pseudotuberculosis, developedincreased significantlywithin the cortical [18]. Thereafter, region of thea period node withinof generalized 24 h of virulence factors believed to promote bacterial dissemination inoculationinflammation these of the became lymph more node numerous was shown, after micro approximately however,by increasing is sovascular far considered permeability to following be phospholipase infection leading D. The to leakage of plasma from blood vessels and into the surrounding tissues, and from there into the lymphatic drainage [11]. This contained6 days, from clumps which ofpoint bacteria they began and cellular to enlarge debris and andcoalesce a high to effect may assist pathogenesis by favoring the lymphatic drainage proportionform more significant of eosinophils, purulent giving foci. a These characteristic early pyogranulomas green colour of C. pseudotuberculosis to the purulent material. In addition and concurrently with the

[12] while mutant strainsin tissue are unable fluid. toStudies cause have abscessation shown that of neutrophils declined while monocytes/macrophages became the the exotoxin (PLD) is necessary for establishment of the disease predominantcellular response cell type at the within site ofthe inoculation, infected node the [9]. infiltration The lesion of establishment of CLA might come from the observation that the the lymph nodes. Further evidence for the importance of PLD in became encapsulated shortly afterwards, resulting finally in a rich C. pseudotuberculosis of the . Once infection has become established, consideredcurrent vaccines the major are virulence produced factor from of formalin-inactivated CLA. PLD- gradualreduction expansion in the inflammatory of the lymph response node within may occur, the parenchyma depending culture supernatants in which PLD is on its location and whether or not it ruptures to discharge its Mycolic acid of does not produce a C. pseudotuberculosis contents. Lymph node enlargement is brought about through a protective capsule but has instead a waxy mycolic acid coat on process of repeated necrosis of the lesion capsule, followed by its the cell wall surface. This coat has well established cytotoxic reformation. Initially, pus within the abscesses is soft and semi properties, which play a major role in pathogenicity [13]. The subcutaneous injection into mice of mycolic acid extracted from solid and scattered clumps of bacteria may be observed within C. pseudotuberculosis fluid. However, over time this purulent material becomes more swelling, with congestion and a central area of haemorrhagic results in the production of a localized material, which cause it to become paler in color. Additionally, it. Small nodules of mineralization form within the purulent

J Vet Med Res 5(3): 1128 (2018) 2/7 Dey et al. (2018) Email:

Central Bringing Excellence in Open Access of C. pseudotuberculosis to chemical disinfectants that include lesions a lamellated appearance, which is often described as being calcium hypochlorite, formalin and cresol solution. Moreover, similarthese calcified to the cross-sectional foci tend to view form of in an concentric onion. This layers, “onion giving ring” the organism is also capable of surviving in commercial sheep dip presentation is characteristic in countries where the disease has solutions for 24h or more, a point of relevance to disease control [27]. beenEPIDEMIOLOGY endemic for a significant OF CLA period GLOBAL of time. PREVALENCE OF TRANSMISSION OF INFECTION CLA Most of recent public data base has given a considerable The disease is generally multicontinental and it has been C. pseudotuberculosis reported to be widely prevalent in the majority of the sheep contained with thick walled absences, are transferred from the rearing areas. However, only a few countries in this world has infectedattention toon thehow healthy this pathogen animal. ( In most cases, the ), infection commonly of relatively conducted epidemiological studies or research aimed animals, particularly small ruminants, with this microbe results at establishing disease prevalence rates where most of those in the formation of two form of abscesses; internal or external surveyed in Australia, the average prevalence of CLA in adult sheepstudies was were reported farm and 58% abattoir in 1973 based and 53% research. in1984 Among [14]. flocks In an abscesses. The latter one (the external form), also known as abattoir statistics was 54% of adult ewes and 3.4% of lambs cutaneous or superficial, form of CLA is characterized by the showed evidence of infection at meat inspection [14] whereas development of abscesses within the superficial lymph nodes surveys showed, particularly in western parts of Australia, of(Figure viable 1) bacteria or within in that the purulent subcutaneous discharge, tissue. estimated The rupture 10 and of that prevalence levels within the adult population to be as high 5superficial x 107, and abscesses, might subsequentlyhowever, releases result certainly in the contaminationhuge numbers6 of the immediate environment. Other animals in the same prevalence rate. This generally could be reasonably related to contaminated area may then be readily be exposed, either by theas 61%introduction [20]. Subsequentof a CLA vaccine surveys in 1983 reported [21] and steady its increasing declined direct physical contact with the affected animal, or indirectly via contaminated fomites. Moreover, the period of infection abattoir survey conducted by meat inspectors in New Zealand might last for a period of time due to the ability of the microbe acceptance within the farming community. In 1986-1987, an to survive in the environment for several weeks. According to previously published research in 19th century, the organisms may westernidentified parts, lesions suggested of CLA in that 7.1% the of averagethe adult disease sheep slaughtered prevalence amongstand 0.64% adult of lambs ewes [21].was asSurveys great asconducted 42.5% [22]. in USA, Similarly, particularly other this hypothetical theory seems to be of minor importance due to studies conducted in the Canadian province of Quebec, showed frequentbe recovered failure from of manythe faeces attempts of infected that have animals been [26]. carried However, out to isolate the organism from the soil in areas of endemic infection. amongst culled adult sheep [23]. Aerosol transmission of this organism has been postulated that the prevalence of clinical CLA ranged from 21% to 36% [22] and some studies proposed that animals with pulmonary Abattoir surveys from Alberta indicated that up to 5% of lesions might principally transfer the infection to the disease free mutton carcasses and 0.03% of lamb carcasses were condemned due to CLA, and that a further 8% of all carcasses were trimmed on epidemiological observations recorded in Australia, in which individuals within a flock [17]. This hypothesis is based principally sheep and goat farms in Southeastern parties particularly the stateto remove of Minas CLA Gerais lesions reportedly [24]. In indicated Brazil, surveys high prevalence conducted of the on Additionally,the seroprevalence the pathogenic of disease (CLA) organism increased (C. pseudotuberculosis) rapidly in groups disease where it was estimated to be 70.9% in sheep [25] and hasof sheep, been isolateddespite the from absence cases, tracheaof superficial of infected CLA lesions sheep, [26].with of sheep carcass condemnation in South African abattoirs [8] into the airways does indeed occur [22]. where78.9% lossesin goats of [23]. between CLA was0.24% also and identified 0.3% of as all the sheep leading carcasses cause pulmonary lesions confirming that discharge from lesions were attributed to CLA and substantial additional losses were Another type of CLA manifestation is visceral form, and it is incurred due to carcass trimming [8]. In Malaysia, a survey of farms reported that average disease prevalence to be around Caseous Lymphadenitis (CLA), conducted on small ruminant [3,4]. 30% using a two (AGPT and Elisa) combined diagnostics tests SURVIVAL It was reported that the organism is capable of surviving in the soil for several weeks, and therefore this might give a possible explanation that the period of infection might last for a period of time. According to previously published data in 19th century, the microbe may be recovered from the faces of infected animals for mode of transmission in the subsequent reviews. Until Figure 1 recently,[26], and therethen it are has few been research documented studies as potential about the significance resistance Distribution pattern of common swelling caused by caseous lymphadenitis (CLA).

J Vet Med Res 5(3): 1128 (2018) 3/7 Dey et al. (2018) Email:

Central Bringing Excellence in Open Access is still considered as a plague to the small ruminant production. individuals. The effected organs/tissues involved in this form To explore more about CLA in this country, much epidemiological often characterized by the formation of lesion within affected studies are certainly needed to be conducted on both farms and lymph nodes, and , although other tissues such as the abattoirs. liver,(Visceral the kidneysform) include or the mammarylymph nodes, glands primarily and less the frequently mediastinal the heart, the brain, the spinal cord, the testes, the uterus and the DISEASE DIAGNOSIS CLINICAL SIGNS joints may be included [28]. Some experimental infections of To diagnose the disease clinically, several basic C. pseudotuberculosis with different routes of administrations, procedures including case history, examination, hematological intratracheal administration of bacteria [29], intravenous route and biochemical analysis should be taken properly [4]. sub-cutaneous inoculation [9], have jointly shown that the most Ultrasonography and other diagnostic and technical tools must proportion of internal lesions were in the lungs and associated be given considerable values. Swellings of submandibular abscess thoracic lymph nodes. are among most frequently seen in cases associated with CLA

o inoculations of the organism, using sheep model, via intratracheal (Figure 2). However, the clinical parameters, in sheep, may show andDifferent intravaginal route routes infections of administration have been of bacteriacarried [30].out by In normalcoat, enlargement rates (temperature: of cutaneous 39.3 C; lymph frequency anodes breathing were commonrhythm: naturally observed animals, skin cuts which can appear during 28 bpm; cardiac rhythm: 100 ppm) [35]. Emaciation and poor common procedures, such as shearing, castration and ear tagging, are mainly believed to be the portal of entry of the microbe [31]. onlyin most if infection hospitalized of the CLA cutaneous cases. The lymph later nodeshad more progresses important to In cattle and buffaloes, C. pseudotuberculosis can be mechanically significance, because most of CLA cases can be diagnosed clinically natural mechanisms of infection with C. pseudotuberculosis are fistulation or, more rarely, visceral involvement leads to nottransmitted yet well understood. by houseflies and by other Diptera, though the hand, the hematological studies frequently revealed chronic anaemia,emaciation an (theincreasing so-called of acute thin ewephase syndrome). proteins and On decrease the other of ECONOMICAL EVALUATION OF THE DISEASE total proteins, particularly negative proteins such as albumin and cause of economic loss to the small ruminant industries globulin in blood stream. Based on urine biochemistry analysis, Caseous lymphadenitis (CLA) is recognized as a significant worldwide. Studies have shown that the disseminated visceral in sheep, proteinuria (100 mg/dl), pyuria (neutrophils) (>1000 form had much more economic losses due to extensive internal leucocytes/field40×)DIAGNOSTIC TOOLS and bacteriuria was observed [35]. abscesses [22]. Similarly, subclinical infections should also be taken into account because of their high probability to allow the A presumptive diagnosis of CLA is based on case history, organism to disseminate within and among herds [32]. Moreover, the characteristic greenish-yellow exudates that may have a lamellatedclinical examination appearance of superficially on the cut surface enlarged [27]. lymph Isolation nodes and Systemic infection by C. pseudotuberculosis is acknowledged to CLAbe detrimental can become to a thepublic productivity health problem of the asinfected it is a zoonosisanimal, but [33]. to C. pseudotuberculosis) from what extent is unclear. identification of the etiological agent ( oflesions the organismis necessary as for it wasconfirmation. considered Therefore, the gold the standard diagnostic in related to this disease has been extensively studied. The disease diagnosiscriteria of of CLA CLA. infections In the laboratory still remains, C. pseudotuberculosis culture and identification cultured has In led endemic to an estimated areas such loss as of Australia, $A12-$A15 where million financial per annum losses [32] to the meat industry. This is due both to carcasses losses and to the requirement for additional meat inspection and carcass from clinical samples may be identified from its enzymatic profile andSEROLOGICAL its ability to utilize TESTS various carbohydrate sources. data from 1992, it was estimated that CLA infection costs the Serological diagnostic tests for CLA are based on the detection Australiantrimming. Basedsheep onindustry disease an surveillanceapproximate and loss wool of $A17 production million per annum in lost wool production [7]. In North America CLA is explored as a method for controlling the disease by identifying andof a removing humoral infected response carrier to PLD animals exotoxin. in small Such ruminant tests have industry. been C. pseudotuberculosis beenregarded associated to be much with more so called significant ‘‘thin-ewe clinically. syndrome’’, There, the a visceralchronic emaciationform of infection of ewes, with occurring organism despite ( good appetite and in) hasthe given injections of serum from animals suspected of being infectedExperimental with C. pseudotuberculosis subjects (mice, rabbits. Thereafter, or guinea these pigs) animals were signs. Studies conducted in US indicated that CLA infection had an C. absence of significant parasitic infestation or specific clinical pseudotuberculosis culture supernatants. Reduction in the rate ofwere mortality then given of serum-treated lethal doses animals,of PLD toxin, as compared prepared with from that occureconomically due to significant the condemnation effect on culling of lamb rates carcasses and reproductive with CLA of controls, was considered to indicate passive protection by lesions,efficiency most in ewes commonly [34]. Inin thethe Middlesubmandibular East, the lympheconomic nodes. losses In serum antitoxin, and highly suggestive of C. pseudotuberculosis Egypt, it is estimated that CLA infections causes severe losses and infection. To facilitate in vitro serological screening, inclusion of

C. pseudotuberculosis antitoxin containing sera in the CAMP-inhibition test resulted in indicatescosts the themeat exact industry statistics approximately of CLA economic $ 1.76 loses,million the annually. disease exerted on staphylococcal b-lysin. This led to a new method In Malaysia, there is currently no official data available which neutralization of the inhibitory effect that

J Vet Med Res 5(3): 1128 (2018) 4/7 Dey et al. (2018) Email:

Central Bringing Excellence in Open Access

Figure 2 Corynebacterium pseudotuberculosis. Caseous lymphadenitis lesions in Boer cross doe from a farm located in Selangor region, Peninsular Malaysia; A) Mandibular abscess; B) Blood Agar culture showing colonies of surgical material before and after the procedure, and all of the sera from animals suspected of having CLA. This test has been disposable materials should be incinerated and buried, including useddesignated for disease the anti-haemolysin- diagnosis in sheep,inhibition goats (AHI) and test horses, for testing thus plastics and paper used to cover the area. avoiding the use of experimental animals [29]. Other tests used DISEASE CONTROL in the study on CLA include tube agglutination assays [36], prevention of CLA remains a matter of debate. However, indirect haemagglutination test (MT Shigidi, 1978) [37] and vaccinationGenerally, is the the primary most efficient means of strategy disease control for control in several and particulara double immunodifusionpromise. Other potential test. However, tests include the enzyme-linked a polymerase immunosorbent assay (ELISA) for use in diagnosis has shown infection, leading to a gradual decline in disease prevalence only whole blood ELISA [39]. incountries, some countries. whereby immunization is used to reduce the spread of chain reaction (PCR) method [38] and bovine interferon (IFN)-g TREATMENT Several vaccines have been developed to protect animals, in vitro sensitivity of C. pseudotuberculosis to but at the same time there is no currently available vaccine that penicillin, tetracyclines and cephalosporins [40], treatment with givesparticularly complete small protection ruminants against (sheep the disease. and goats) This againstis evidenced CLA, theseDespite drugs is the generally not effective as a result of several factors by a report from Australia which indicated that, despite the including the protective nature of the capsule, the formation of widespread use of a commercial CLA vaccine in that country the encapsulated abscess as well as the intercellularity of the since 1983, disease prevalence remained at approximately organism [41,42]. 20% in 2002 [33]. Serological diagnoses are of a value in those countries with low prevalence and with relaxation of borders. guarantee organism free from infected animals. Subsequently, These serological tests have been used as an alternative way of Prophylactic and therapeutic treatment, therefore, will not vaccination and offer a powerful means of controlling disease, infection. As a result of this, the most practical method of through the culling/segregation of infected animals. This controllingthese infected CLA flocksin small or ruminants individuals is to serve cull all as animals a reservoir with the of

approach, while potentially costly in the first instance, is a means palpable lesions [36]. byACKNOWLEDGMENT which CLA may be completely eradicated from affected flocks. infections particularly peripheral lymph nodes is often not Treatment of sheep and goat flocks suffering from CLA The author would like to acknowledge the support from located abscesses can be lanced or removed surgically. Abscesses the Ministry of Higher Education, Malaysia and The Islamic frequentlyjustifiable. recur, In valuable particularly breeding in sheep stock, and however, goats, after superficially draining or attempted surgical excision. Therefore, the infection repeats DevelopmentREFERENCES Bank, Saudi Arabia. itself through the life of the animal. If the abscess cannot be precisely located or in a position that is unfavorable for surgery, 1. Corynebacterium a prolonged course of antimicrobial treatment using lipophilic pseudotuberculosisPacheco LG, Pena RR, from Castro pure TL, cultures Dorella and FA, for Bahia rapid RC, detection Carminati of this R, drugs, such as one of the microlides at high dosage rates may be et al. Multiplex PCR assay for identification of effective. In horses, application of hot packs, surgical lancing and 2. pathogen in clinical samples. J Med Microbiol. 2007; 56: 480-486. genotyping of multinational ovine and caprine Corynebacterium pseudotuberculosisConnor KM, Fontaine MC, Rudge K, Baird GJ, Donachie W. Molecular flushing with antiseptics may be attempted for treatment of the avoids environmental contamination, with disinfection of the abscess. Drainage of the abscess should be done in a way that isolates using pulsed-field gel electrophoresis. Vet Res. 2007; 38: 613-623. J Vet Med Res 5(3): 1128 (2018) 5/7 Dey et al. (2018) Email:

Central Bringing Excellence in Open Access

3. KomalaTS, Ramlan M, Yeoh NN, Surayani AR, Sharifah Hamidah SM. Medical Journal. 1983. A survey of caseous lymphadenitis in small ruminant farms from two 22. disease prevalence, lesion distribution, and thoracic manifestations in Stoops SG, Renshaw HW, Thilsted JP. Ovine caseous lymphadenitis: districts in Perak, Malaysia-Kinta and Hilir Perak. Trop Biomed. 2008; a population of mature culled sheep from western United States. Am J 4. 25: 196-201. Osman AY, Jesse F, Saharee A. Sero-Prevalence of Caseous 23. VetSeyffert Res. N,1984; Guimar 45: ã557-561. Lymphadenitis Evaluated by Agar Gel Precipitation Test among es AS, Pacheco LG, Portela RW, Bastos BL, Dorella Small Ruminant Flocks in East Coast Economic Regions in Peninsular goat herds revealed by Corynebacterium pseudotuberculosis secreted FA, et al. High seroprevalence of caseous lymphadenitis in Brazilian 5. Malaysia. J Animal Vet Adv. 2012; 11: 3474-3480. Dercksen DP, Brinkhof JM, Dekker-Nooren T, Maanen K, Bode CF, 24. proteins-based ELISA. Res Vet Sci. 2010; 88: 50-55. Baird G, et al. A comparison of four serological tests for the diagnosis incidence of caseous lymphadenitis in Alberta sheep and assessment Stanford K, Brogden KA, McClelland LA, Kozub GC, Audibert F. The of caseous lymphadenitis in sheep and goats. Vet Microbiol. 2000; 75: of impact by vaccination with commercial and experimental vaccines. 167-175. detection of antibodies to Corynebacterium pseudotuberculosis in 6. Menzies PI, Muckle CA. The use of a microagglutination assay for the 25. CanGuimar J Vetã Res. 1998; 62: 38-43. 318. es A, Seyffert N, Bastos BL, Portela RWD, Meyer R, Carmo naturally infected sheep and goat flocks. Can J Vet Res. 1989; 53: 313- 7. Shigidi MT. An indirect haemagglutination test for the sero-diagnosis FB, et al. Caseous lymphadenitis in sheep flocks of the state of Minas Gerais, Brazil: prevalence and management surveys. Small Ruminant Research. 2009; 87: 86-91. 8. of C ovis infection in sheep. Corynebacterium Res Vet Sci. 1978; pseudotuberculosis 24: 57-60. and its The spread of Corynebacterium pseudotuberculosis infection to 26. Paton MW, Sutherland SS, Rose IR, Hart RA, Mercy AR, Ellis TM. 210.Baird GJ, Fontaine MC. role in ovine caseous lymphadenitis. J Comp Pathol. 2007; 137: 179- 27. unvaccinated and vaccinated sheep. Corynebacterium Aust Vet J. 1995; pseudotuberculosis 72: 266-269. 9. Research. 2008; Nairn ME, Robertson JP. Fontaine M, Baird G. Caseous lymphadenitis. Small Ruminant infection of sheep: role of skin lesions and dipping fluids. Aust Vet J. 10. 76: 42-48. 28. 1974; 50: 537-542. Hemisphere. 2000. In Proceedings of the Moredun Research Institute/ Animals. 1993; ScottishPaton MW.Agricultural Applying College the Workshop experience on Caseous of CLA Lymphadenitis in the Southern 3-15. Valli V, Parry B. Caseous lymphadenitis. Pathology of Domestic 29. 3: 238-240. 11. Carne H, Onon EO. Action of Corynebacterium ovis exotoxin on Brown C, Olander H. Caseous lymphadenitis of goats and sheep: a 30. review. Vet Bull. 1987; 57:12. 12. endothelial cells of blood vessels. Nature. 1978; 271: 246-248. infectionFontaine with MC, a Baird virulent G, ConnorUnited Kingdom KM, Rudge strain K, of SalesCorynebacterium J, Donachie CorynebacteriumSimmons CP, Dunstan pseudotuberculosis SJ, Tachedjian in Sheep. M, Krywult Infect Immun. J, Hodgson 1998; pseudotuberculosisW. Vaccination confers significant protection of sheep against AL, Strugnell RA. Vaccine Potential of Attenuated Mutants of 31. al‐Rawashdeh OF, al. ‐Vaccine.Qudah KM. 2006; Effect 24: of5986-5996. shearing on the incidence of 13. 66:Tashijian 474-479. JJ, Campbell SG. Interaction between caprine macrophages and corynebacterium pseudotuberculosis caseous lymphadenitis in Awassi sheep in Jordan. J Vet Med B Infect : an electron microscopic 32. Dis Vet Public Health. 2000; 47: 287-293. 14. study. Am J Vet Res. 1983; 44: 690-693. lymphadenitis and usage of caseous lymphadenitis vaccines in sheep Paton MW, Walker SB, Rose IR, Watt GF. Prevalence of caseous Batey RG. Pathogenesis of caseous lymphadenitis in sheep and goats. 15. AustHard Vet GC. J. 1986; Comparative 63: 269-272. toxic effect of the surface lipid of 33. flocks. Aust Vet J. 2003; 81: 91-95. Corynebacterium ovis on peritoneal macrophages. Infect Immun. et al. Corynebacterium pseudotuberculosis Join-Lambert OF, Ouache M, Canioni D, Beretti JL, Blanche S, Berche P, necrotizing lymphadenitis 1975; 12: 1439-1449. 34. in a twelve-year-old patient. Pediatric Infect Dis J. 2006; 25: 848-851.

16. 2002.West DM, Bruere AN, Ridler AL. The sheep: Health, disease & andRenshaw Moraxella HW, sppGraff from VP, Gatesinternal NL. abscesses Visceral caseousin emaciated lymphadenitis ewes. Am in J production: Veterinary Continuing Education, Massey University. thin ewe syndrome: isolation of Corynebacterium, Staphylococcus, 17. 35. Vet Res. 1979; 40: 1110-1114.ó ó Williamson LH. Caseous lymphadenitis in small ruminants. Vet Clin 18. é North Am Food Anim Pract. 2001; 17: 359-371. Ferrer LM, Lacasta D, Chac n G, Ramos J, Villa A, G mez P, et al. Clinical of the early phase during experimental Corynebacterium diagnosis of visceral caseous lymphadenitis in a Salz ewe. Small P pin M, Fontaine JJ, Pardon P, Marly J, Parodi AL. Histopathology pseudotuberculosis Ruminant Research. 2009; 87: 126-127. 134. node of sheep following injection of liver or killed Corynebacterium infection in lambs. Vet Microbiol. 1991; 29: 123- 36. ovisHusband AJ, Watson DL. Immunological events in the popliteal lymph 19. 105-112. into an afferent popliteal lymphatic duct. Res Vet Sci. 1977; 22: Middleton MJ, Epstein VM, Gregory GG. Caseous lymphadenitis on 37. Flinders Island: prevalence and management surveys. Aust Vet J. experimental Corynebacterium ovis 20. 1991;Al-Gaabary 68: 311-312. MH, Osman SA, Oreiby AF. Caseous lymphadenitis in sheep Shigidi MT. A comparison of five serological tests for the diagnosis of infection in sheep. Br Vet J. 1979; 38. 135: 172-177. and goats: clinical, epidemiological and preventive studies. Small Corynebacterium pseudotuberculosis isolates from 21. RuminantSeedik I, El Research. Timawy A, 2009; El Amarousi 87: 116-121. S, Zaki M, El Allawy T. Some studies Cetinkaya B, Karahan M, Atil E, Kalin R, De Baere T, Vaneechoutte M. Identification of sheep and goats by PCR. Vet Microbiol. 2002; 88: 75-83. on caseous lymphadenitis of sheep in Upper Egypt. Assiut Veterinary

J Vet Med Res 5(3): 1128 (2018) 6/7 Dey et al. (2018) Email:

Central Bringing Excellence in Open Access

39. to

Menziesof Corynebacterium PL, Hwang YT, pseudotuberculosis Prescott JF. Comparison infection of inan experimentallyinterferon-γ a phospholipase D enzyme-linked immunosorbent assay for diagnosis

40. Zhaoinfected HK, goats. Yonekawa Vet Microbiol. K, Takahashi 2004; T, Kikuchi100: 129-137. N, Hiramune T, Yanagawa R. Isolation of Corynebacterium pseudotuberculosis from the cervical

41. Ashfaqcanal of MK, clinically Campbell normal SG. sows. A survey Res Vetof caseous Sci.1993; lymphadenitis 55: 356-359. and its

etiology in goats in the United States. Veterinary medicine, small 42. animalIsmail A, clinician: Hamid Y. VM, Studies SAC,1979; on the 74: effect 1161. of some chemical disinfectants used in veterinary practice on Corynebacterium ovis Assoc. 1972. . J Egypt Vet Med

Cite this article Osman AY, Nordin ML, Kadir AA, Saharee AA (2018) The Epidemiology and Pathophysiology of Caseous Lymphadenitis: A Review. J Vet Med Res 5(3): 1129.

J Vet Med Res 5(3): 1128 (2018) 7/7