Overview of Histophilosis

H somni is a gram-negative, nonmotile, nonsporeforming, nonencapsulated, pleomorphic coccobacillus that requires an enriched medium and a microaerophilic atmosphere for culture. Hemolysis on blood agar occurs within 48 hr due to an exotoxin produced by most disease-causing isolates. Pathogenic and nonpathogenic strains have been differentiated. The virulence of the organism may vary by region and age group.

H somni is considered a commensal of bovine mucous membranes. Pathogenic and nonpathogenic strains of H somni are found in the sheath and prepuce of males, the vagina of females, and in the nasal passages of both sexes. Nasal and urogenital secretions are believed to be sources of the organism. The organism may colonize the respiratory tract, presumably after inhalation, and gain access to the bloodstream via that route. Colonization of the male and female reproductive tracts may involve venereal spread.

Recently weaned calves are at higher risk of infection and death from histophilosis than are previously weaned older calves, yearlings, or mature animals. The risk of infection with H somni is highest early in the feeding period, with “high-risk” calves in confinement establishing peak titers to H somni at ~21–23 days after arrival. Although calves are generally exposed to H somni earlier in the feeding period, the average time on feed for calves that die of histophilosis has been reported to be 30–60 days. Sudden death due to peracute septicemia usually occurs within 21 days after arrival, although it may occur throughout the feeding period. Reproductive disease manifestations, including granular vulvovaginitis, abortion, and mastitis, can affect individual beef and dairy cattle or more of the herd.

Septicemia is likely required for most forms of histophilosis. Strains of H somni that cause disease adhere to the endothelium of vessels, resulting in contraction, exposure of collagen, platelet adhesion, and thrombus formation. The primary disease mechanism likely involves a thrombus, rather than a thromboembolism as once thought. Some bacterial strains may adhere to the endothelium in vessels of the pleura, myocardium, pericardium, synovium, or a variety of other tissues (eg, brain, larynx). Interruption of the blood supply in those areas results in the formation of an infarction with destruction of tissue and the formation of a necrotic sequestrum. The development of clinical signs is associated with the extent of organ system involvement. The susceptibility of individual animals and variations in the preference of strains of the organism for vessels in different tissues may be important in the development of the different forms of the disease, but these have not been extensively studied.

The apparent preference of H somni for different organ systems has defined the changing character of histophilosis. Initially, the disease presented primarily as an encephalitic syndrome that changed to one in which pleuritic and myocardial forms predominated. Anecdotal observations suggest that the organism may be changing again (eg, from a focal to a more generalized myocarditis). Recent microbiologic examinations of the organism have identified a variety of mechanisms that contribute to its diverse virulence and ability to withstand treatment.

Reproductive disease has not been associated with systemic infection; the inflammation appears to be more local, even though the pathogenesis in these situations is not well understood.

Sudden death is usually the first indication of H somni infection in a group of confined animals and is often mistaken by the stock attendants as evidence of a digestive tract upset such as bloat. A profound depression has been described as the most noticeable clinical sign of encephalitic histophilosis. Other findings are determined by the system(s) involved and may include rapid respiration, stiffness, muscle weakness, ataxia, lameness, and severe behavioral changes. Animals affected with pleuritic histophilosis are usually found dead without any treatment history; if alive, they may exhibit extreme dyspnea. Animals with myocarditis display very poor exercise tolerance and may collapse and die when movement to a handling facility is attempted. Animals with the encephalitic form and early depression rapidly proceed to recumbency, with occasional signs of hyperesthesia before death. Animals found dead and confirmed with H somni infection often have a history of treatment for undifferentiated fever or depression in the previous 14 days.

Closer individual examination usually reveals a febrile animal. Polypnea and/or dyspnea may be evident overtly and are easily confirmed by auscultation. Hypoxemia associated with a malfunctioning pulmonary or cardiovascular system can be easily confused with other clinical signs such as depression or even blindness. A sterile blood sample obtained from an untreated animal at this time tests positive for H somni in a high percentage of cases.

A definitive diagnosis is based on sampling and examination of affected tissues collected during a necropsy or clinical examination. A diagnosis at necropsy of “left heart failure” with a concomitant myocardial lesion or a carcass in which the thoracic space is filled with fluid and fibrin with little pneumonia is considered definitive for histophilosis. Historically, isolation of the organism from CSF, brain, blood, urine, joint fluid, or other sterile, internal organs or fluids has been used to confirm the diagnosis. Because H somni is a commensal of the mucous membranes of cattle, the bacterium should be isolated in predominant or pure culture from the respiratory or urogenital tract to be considered a significant etiologic agent. This may be difficult, because antimicrobial treatment often interferes with recovery of the organism. The characteristic histologic lesion is suppurative with heavy infiltrations of neutrophils in all tissues where localization of the bacteria occurs. Currently, the diagnosis is usually confirmed with molecular techniques such as immunohistochemical staining of H&E-stained; tissues or a fresh lesion swab subjected to a specific PCR test.

A major hindrance to successful treatment of individual histophilosis cases is the difficulty in identifying affected animals early in the course of disease because of its often rapidly fatal nature. Antimicrobial treatment is most effective in the early stages of disease. Florfenicol (20 mg/kg, IM, repeated in 48 hr, or 40 mg/kg, SC, once) may be the antimicrobial of choice if histophilosis is the tentative diagnosis in an individual animal.

Evidence supporting the use of prophylactic or metaphylactic treatment with a sustained-action antimicrobial or an oral antimicrobial supplement in the feed on arrival at the feedlot or in the face of occurring cases to reduce histophilosis mortality is scant. This contrasts with the evidence that H somni is susceptible in vitro to a wide range of antimicrobials, including florfenicol, tilmicosin, tulathromycin, tetracyclines, trimethoprim-sulfadoxine, fluoroquinolones, and ceftiofur. Historically, the precise mechanism by which the organism is able to avoid systemic antimicrobial blood levels has not been well understood. Recently, it has been postulated that as H somni proliferates, it forms biofilms that allow it to adhere to the endothelium and to withstand an otherwise adequate level of an antimicrobial.

Bacterins containing different strains of the organism have been used to immunize cattle against H somni. A favorable humoral response generated by a single immunization with a commercial vaccine has been shown to be improved when boosted with a second immunization. Calves initially immunized before “turn out” (estimated age to be 2 mo) will respond to a second immunization anamnestically on their arrival at the feedlot after weaning. Although protection with current bacterins and immunogens against histophilosis morbidity and mortality has been reported, the ability of immunization to consistently spare cattle from the disease is compromised when immunization and challenge occur at the same time (ie, arrival at the feedlot).