Histophilus somni Unique Features, Pathogenesis and Lesions Update

Ted Clark, DVM, MVSci, DACVP Prairie Diagnostic Services, University of Saskatchewan, Saskatoon, S7N 5B4, Canada

Abstract Classification, Factors and Special Features of H.somni Haemophilus somnus has recently been renamed Histophilus somni and it has been proposed this name Histophilus somni, Histophilus ovis and also includes Haemophilus agni and Histophilus ovis. Haemophilus agni are now considered to be the same The organism occurs in all management systems of the organism andH. somni is the only member of the genus cattle industry, but the most serious losses occur in beef Histophilus in the family. Microbiolo­ feedlots where co-mingling of cattle from numerous farms gists have never been happy with H. somni being clas­ occurs. The disease in feedlots most often manifests as sified as a Haemophilus genus member due to the lack the septicemic form and is known as the Histophilus of "X" and ''V" factors for in vitro growth. Recent phylo­ somni disease complex (HSDC), but pleuritis and bron­ genetic studies has resulted in the now accepted new chopneumonia are two other very common causes of dis­ name Histophilus somni based on sequence analysis of ease or death. Despite effective vaccines and antibiotics, the 165-rDNA and rpoB .1 sudden losses from 30 to 90 days after arrival at feedlots H. somni is a gram negative, nonmotile, pleomor­ 0 continue to occur in significant numbers, especially in phic and nonencapsulated bacterium with common sur­ "d ('[) certain geographical areas ofNorthAmerica and Europe. face antigens for all strains of the organism. Nonclinical ~ ~ There undoubtedly remains much to be learned about carriers make up 3.2 to 8.0% of cattle entering feedlots, (') (') predisposing factors to histophilosis and how this organ­ and the organism can be isolated from upper and lower ('[) en ism avoids natural body defense mechanisms. respiratory tracts and urogenital tracts, and most com­ en

monly from the preputial cavity of rams and bulls. The 8-:r:n Introduction organism is therefore a commensal in these sites. Simple q- isolation of the organism, therefore, does not necessar­ [ For nearly five decades Histophilus somni (recently ily confirm an etiologic diagnosis, and antibiotic therapy o· renamed from Haemophilus somnus) has been consid­ prior to death easily interferes with laboratory isola­ p ered as part of the bovine respiratory disease complex tion of the organism so do not rule it out based on simple (BRDC), as a cause of septicemia and its sequelae (the culture results. Therefore, as with Mycoplasma bovis, HSDC) and also a cause ofreproductive losses in cattle. typical histologic lesions and immunohistochemical Despite bacterins being available for many years and (IHC) demonstration of the organism relative to the le­ several antibiotics showing good in vitro sensitivity pat­ sions are very important to confirm the diagnosis. terns for H. somni, significant losses in beef cattle feed­ Many different strains of the organism with dif­ lots, cow-calf operations and dairy cattle continue to be ferent tissue tropisms and therefore a variety of dis­ highly significant problems in Canada, the United ease manifestations occurs, but in feedlot cattle the States, Germany, the United Kingdom, Switzerland and organism most commonly causes or a septi­ Israel. The organism also causes significant losses in cemia. Septicemic histophilosis in tissue can result in , bighorn sheep and bison. H. ovis and H. agni pleuritis, , thrombotic meningoencephalitis are common in Australia, New Zealand and Canadian (TME) or polyarthritis, and the septicemic forms are sheep flocks. Serum titres reach high levels in most referred to as the H. somni disease complex or HSDC. feedlot cattle 14 to 21 days after arrival but the organ­ Thoracolumbar myelitis, otitis media, laryngeal ism has many unique characteristics and virulence fac­ , conjunctivitis and retinal hemorrhages are also tors that allow it to not only colonize airways of the lung not uncommon feedlot cattle clinical or lesional mani­ parenchyma but also invade the bloodstream, which in . festations. turn results in a variety of clinical conditions and le­ A particularly unique feature of H. somni is its 4 5 sions at post mortem. , ability to invade into the bloodstream (likely via the

68 THE AABP PROCEEDINGS-VOL. 38 respiratory tract), even in the presence of high circu­ purative bronchopneumonia and myocarditis occur at lating antibody titers, and to avoid being killed despite the same time so the lung may be the source of the being phagocytosed by neutrophils, circulating mono­ organism for the myocarditis.3 cytes and tissue macrophages. This intracellular sur­ vival allows it to continue to replicate. This feature is Gross Post Mortem and Histopathologic Lesions due to immunoglobulin binding proteins (IgBPrs) on of Histophilosis the surface of the organism that prevents complement­ mediated destruction. Normally, in conjunction with I have had no experience with the lesions of H. organism-specific antibodies, this would result in ph­ somni placentitis, aborted fetuses, endometritis, vagini­ agocytosis and intracellular death, commonly referred tis, vulvitis, balanoposthitis, orchitis, seminal vesiculi­ to as opsonization. Also, outer membrane proteins tis or mastitis, but all of these are reported to occur in (OMPrs) have been demonstrated in virulent strains, both beef and dairy cattle. None of the above, except and rapid phase variation of these proteins result, in perhaps the disseminated lesions in multiple tissues of part, in the organism's avoidance of the normal host aborted fetuses, are considered part of the HSDC. defenses both within the bloodstream and after local­ The lesions of the HSDC are a result of a septice­ ization in tissues. mia and the hallmark histopathologic lesions, which may Unlike other Pasteurellaceae family members an or may not be seen as visible gross lesions, include fi­ exotoxin of H. somni has not been convincingly demon­ brinous thrombi, clumps of in or around small strated, but a lipooligosaccharide (LOS) has been clearly vessels and large numbers of neutrophils in these foci shown with H. somni. This LOS has been shown to be ofvasculitis. A vasculitis and "microabscesses" are there­ capable of undergoing structural and antigenic varia­ fore usually described and often, especially in the brain tion, and by so doing allows the organism to mimic host and meninges, the vasculitis is more specifically a throm­ antigens and thus evade immune mechanisms. The LOS bophlebitis since small veins and venules are clearly is also partially responsible for adherence of the organ­ involved. LOS-induced production ofTNF and IL-1 are ism to epithelial cells of airways and endothelial cells thought to play a role in the vasculitis lesions and im­ lining blood vessels. The lipid A content of LOS also mune complexes, and may be partially responsible for has an endotoxin-like effect on host tissues by inducing the vasculitis seen histologically. pro-inflammatory IL-1 and tumor necrosis factor (TNF) Reflecting the not-yet-totally understood and pe­ from macrophages. culiar tissue tropisms of different strains of H. somni, Lesions produced by the HSDC or septicemic form it is not uncommon to see gross lesions in only one or­ of H. somni requires that the organism first colonize gan or body system in the HSDC. The brain was the the respiratory tract tissues, then adhere to and dam­ first to have H.somni lesions described where it was age endothelial cells that line blood vessels. Once in­ named ITEME, but it is now recognized that 'embo­ travascular, the organism can evade host defenses as lism' per se does not occur so the disease is simply re­ mentioned above. In addition, as with Pseudomonas ferred to as thrombotic meningoencephalitis or TME. aeruginosa, virulent H. somni bacteria produce a One tissue where embolism might occur, however, is at sites of colonization which promotes epithe­ the spinal cord and cases of sudden onset posterior lial cell adherence and allows for bacterial inter-com­ paralysis can be due to H. somni embolic myelitis and munication, which is important for replication. can exist with or without concurrent brain involvement. Stressors such as transport, overcrowding, changes in A formalin fixative-immersed short segment of lum­ feed and adverse weather conditions appear to precipi­ bar spinal column removed with a handsaw is a useful tate disease outbreaks and damage to the mucociliary specimen to submit to a diagnostic lab in such cases. apparatus, especially of the lower respiratory tract The brain lesions are usually seen grossly as focal (lung), which promotes colonization of airway epithe­ brown to red lesions visible on the outer or cut sur­ lium. Several respiratory viruses commonly seen in faces of the brain, but if animals were treated with feedlots are significant contributors to initiating air­ antibiotics while sick, in our experience many cases way epithelial damage, but especially BRSV, PI3, BVD will be missed if multiple sections of brain are not ex­ and IBR. Depending on the strain of the organism, amined histopathologically. many of these lower respiratory H. somni infections The heart lesions are usually seen as a myocardi­ remain confined to the lung as a bronchopneumonia or tis and, except for a few cases thought to arise second­ invade into the vascular system as described above and ary to H. somni suppurative bronchopneumonia, are result in a septicemia. Less common cases of otitis thought to occur from a "silent" septicemia or bacter­ media, conjunctivitis and some cases of arthritis ap­ emia. Lesions are not usually seen concurrently in any pear to occur coexistent with or following several weeks other tissues. In the peracute to acute cases dark red of suppurative bronchopneumonia. Occasionally sup- hemorrhagic lesions may occur, especially in the left

SEPTEMBER, 2005 69 ventricle papillary muscles (very similar to Blackleg), nia. Typically seen is diffuse dark red and consolidated but more often chronic infarcted lesions are seen and cranial, middle, accessory and cranial portions of cau­ most often as sequestra in the papillary muscles of the dal lung lobes. The cut surfaces show variable amounts left ventricle. Sequestra are not true abscesses as they of purulent exudates in small airways, but unless M. are often described, but pale and dry central masses of haemolytica or Mycoplasma bovis are co-existent ar­ necrotic (infarcted) myocardium with outer zones of eas of necrosis or interlobular fibrin are not seen. A white fibrosis, although some may have intervening Pasteurella multocida bronchopneumonia looks iden­ zones of purulent material where the body is trying to tical to these H. somni bronchopneumonia cases in my rid itself of the central necrotic tissue (the process is opinion. Histologically and by IHC neutrophils and called sequestration). This is very similar to the se­ H. somni bacteria are within airway lumens and less questra that occur in Mycoplasma bovis in the lung. commonly in small patches of surrounding alveoli as Scattered smaller fibrotic (healed) foci may be present well. In the bronchioles the bacteria are mixed with throughout both ventricles, mural or vegetative en­ neutrophils, reflecting the organism's ability to be en­ docarditis may also be present, and sometimes sub­ gulfed by but not killed by neutrophils. It is also not acute to chronic fibrinous pericarditis co-exists along uncommon to have feedlot interstitial pneumonia with myocardial lesions. We have seen cases where an ("AIP") lesions in the caudal lung lobes and H. somni entire necrotic papillary muscle is suddenly pulled bronchopneumonia cranial-ventrally, and this combi­ away peracutely into the ventricle in the live animal nation of lung lesions is often referred to as "upstairs­ because of the chordae tendinae attachments of the downstairs" pneumonia. papillary muscles to the mitral valve leaflets. Feedlot In HSDC cases, if the larynx is routinely opened cattle that die of congestive heart failure due to H. at necropsy, bilateral tiny focal to large bilateral caseo­ somni myocarditis typically have passive congestion purulent ulcerative lesions of the vocal folds and/or of the lung characterized by heavy, non-collapsed lungs arytenoid cartilages and laryngeal mucosa are often with interlobular edema and a finely mottled hemor­ seen. A histologic and IHC workup will often show H. rhagic appearance throughout both pleural and cut somni in these lesions, but Mycoplasma bovis, Fusobac­ surfaces due to intra-alveolar hemorrhage. The cut terium necrophorum andArcanobacterium pyogenes may surfaces of these lungs, and especially in the caudal be present secondarily as well. Vasculitis due to H. lung lobes, will sometimes reveal round interlobular somni is often found histologically in the mildest laryn­ lymphatics distended with dark blood that is trying to geal cases, but usually in combination with septicemic exit the lung parenchyma. lesions in other organs or in cases of suppurative bron­ Currently, the most common manifestation of H. chopneumonia. somni in western Canada feedlots is acute fibrinous When a variety of other organs and tissues of sus­ pleuritis. These occur 30-90 days after arrival at the pect H. somni septicemic cases are examined grossly feedlot. Rarely are lesions seen in any other organ, and/or histologically, lesions are often found. Fibrinous even histologically. These animals usually are sudden arthritis is consistently found if looked for and the death cases, the parietal pleura on both sides of the amount of joint fibrin is much less than in Mycoplasma chest are covered in a thick sheet of fibrin and the lungs bovis cases in my opinion. Also all large joints will show are often remarkably collapsed. Abundant straw-col­ this fibrinous arthritis, unlike Mycoplasma bovis cases ored fluid is invariably present in the chest surround­ where only one or two joints are more commonly in­ ing both lungs. The cut surfaces of the lung either volved. Skeletal muscle, renal and intestinal vasculitis show simple compression collapse and congestion, or lesions are often found histologically, but severe and there may be yellow fibrin-distended interlobular obvious gross lesions of these tissues are occasionally septae, giving a "marbled" appearance to the cut sur­ seen as well. 2 faces. Airway exudates are not a feature of these cases, and in fact rarely can a pneumonic process be demon­ Conclusions strated at all, grossly or histologically. These marbled lungs with interlobular lymphatics plugged with fibrin Histophilus somni can cause a wide variety of clini­ and bacteria are easily confused with acute cal diseases and pathologic lesions and reliance on cul­ mannheimiosis cases. Histologically thrombolymphan­ tures alone, especially if there was antibiotic therapy, gitis is the hallmark lesion of both the visceral pleura commonly fails. There are many strains of the organ­ and the interlobular lesions, and organisms are easily ism that result in the different diseases, but pleuritis, demonstrated by IHC confined to the pleural and in­ the HSDC and its sequelae (TME, myocarditis, arthri­ terlobular lesions. tis, myelitis, laryngitis) and suppurative subacute to Pneumonic histophilosis is usually a subacute to chronic bronchopneumonia are by far the majority of chronic, cranial-ventral suppura ti ve bronchopneumo- cases seen in beef cattle feedlots.

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