Infection by the bacterium Histophilus somni is common in North American cattle and sporadic in cattle at other locations worldwide. It is also a constituent pathogen of bovine respiratory disease complex. Infection can cause sudden death, lethargy, or a variety of clinical signs that depend on the system affected. Diagnosis is based on histological evaluation, bacterial isolation, and PCR assay. Because identification of infected animals is difficult early in the course of the disease, antimicrobial treatment might not be successful. Multivalent bacterins might help decrease morbidity and mortality rates. Further research is needed to understand H somni bacterin efficacy and possible interaction with other vaccine antigens.
Histophilosis, or Histophilus somni–associated disease, is common in North American cattle. It also has been reported to occur sporadically in beef and dairy cattle worldwide. H somni predominantly causes acute, often fatal, septicemia involving the respiratory, cardiovascular, musculoskeletal, or nervous systems, either singly or together in confined cattle.
The reproductive system is often affected without clinical signs or other systemic involvement; however, herd infertility has been reported to occur more frequently in infected herds, but H somni infection is probably uncommonly considered or pursued as a differential diagnosis.
Etiology and Transmission of Histophilosis
H somni is a gram-negative, nonmotile, non-spore-forming, nonencapsulated, pleomorphic coccobacillus that requires an enriched medium and a microaerophilic atmosphere for culture. Hemolysis on blood agar occurs within 48 hours because of an exotoxin produced by most disease-causing isolates. Pathogenic and nonpathogenic strains of H somni have been differentiated. Ongoing research has demonstrated that the virulence of the organism varies by region and age group infected, as well as by strain-specific capabilities to subvert bovine immunological mechanisms.
H somni is considered a commensal on bovine mucous membranes. Pathogenic and nonpathogenic strains can be isolated from the prepuce, vagina, and nasal passages. Genomic examination of such locations clearly reveals the presence of H somni in the microbiome.
Nasal and urogenital secretions are believed to transmit the organism. After it is inhaled, the organism can colonize the respiratory tract and enter the bloodstream. Venereal transmission can lead to colonization of both male and female reproductive tracts.
H somni and concurrent infection with bovine respiratory syncytial virus (BRSV) can have synergistic effects on the immune system. In one study, calves coinfected with BRSV and H somni had marked pulmonary lesions and consolidation; however, those inoculated with either pathogen individually did not (1).
BRSV infection can modulate the immune system such that type 2 helper-T-cell responses toward extracellular pathogens dominate. However, a type 1 helper-T-cell response is needed to resolve H somni infection, so in its absence, H somni can proliferate when type 2 helper-T-cell responses are induced by BRSV. BRSV also stimulates IgE antibody production against itself and other pathogens, and H somni–specific IgE is associated, paradoxically, with enhanced pathogenesis of the organism in sensitized cattle (2).
Epidemiology of Histophilosis
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 and disease with H somni is highest early in the feeding period; however, infection is typically later than with other respiratory bacteria, such as Mannheimia haemolytica.
High-risk calves in confinement establish peak titers to H somni at approximately 21–23 days after arriving at a feedlot. This timing suggests that infection frequently occurs as a result of exposure to infected resident cattle or that the transition of H somni from pathobiont to pathogen can manifest in stressed animals. Considerable evidence suggests that high titers do not confer protective immunity in all cases.
Although calves are generally exposed to H somni earlier in the feeding period, calves that die of histophilosis typically have been on feed for an average of 60 days. Sudden death due to peracute septicemia usually occurs within 21 days after arrival at the feedlot; death resulting from other clinical signs can occur throughout the feeding period.
Reproductive signs of histophilosis, including granular vulvovaginitis, abortion, and mastitis, can affect individual or multiple animals in both beef and dairy herds.
Pathogenesis of Histophilosis
Initially, septicemia is likely required for H somni to cause illness. 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 was once thought.
Some strains of H somni can adhere to the endothelium in vessels of the pleura, myocardium, pericardium, synovium, or a variety of other tissues (eg, brain, larynx). The result is interruption of the blood supply in those areas, followed by infarction, destruction of tissue, and formation of a necrotic sequestrum (see acute pan-myocarditis image).
Courtesy of Dr. Eugene D. Janzen.
The development of clinical signs of H somni infection depends on the extent of organ involvement. The susceptibility of individual animals and the preference of H somni strains for adhering to vessels in different tissues can be important in the development of different forms of the disease; however, these factors have not been studied extensively.
The apparent preference of H somni for infecting different organ systems has defined the changing character of histophilosis. Previously, the disease presented primarily as an encephalitic syndrome; however, it has changed to a syndrome in which pleuritic and myocardial forms now predominate. Anecdotal observations suggest that the disease might be changing again (eg, from a focal to a more generalized myocarditis).
Microbiological examinations of H somni have identified a variety of mechanisms that contribute to its diverse virulence and ability to resist treatment. Some mechanisms that promote virulence include lipopolysaccharide, antibody binding proteins, outer membrane proteins, histamine, biofilm formation, and quorum sensing. As described above, concomitant infection with BRSV can also enhance H somni pathogenesis (3).
Reproductive disease due to H somni has not been associated with systemic infection. Instead, H somni infection typically causes localized inflammation in the reproductive tract, even though the pathogenesis in these cases is not well understood.
Clinical Findings of Histophilosis
Sudden death is usually the first indication of H somni infection in a group of confined animals, and often it is mistaken by handlers as evidence of a digestive tract upset such as bloat. Treatment with antimicrobials can change the progression of the disease, resulting in more chronicity.
Profound lethargy has been described as the most noticeable clinical sign of encephalitic histophilosis. Other findings are determined by the system(s) involved and can include rapid respiration, stiffness, muscle weakness, ataxia, lameness, and profound behavior changes.
Animals affected with pleuritic histophilosis are usually found dead without any previous treatment; if alive, they can exhibit extreme dyspnea.
Animals with myocarditis display severe exercise intolerance and can collapse and die while being moved to a handling facility.
Animals with the encephalitic form of histophilosis and early lethargy rapidly become recumbent and occasionally show signs of hyperesthesia before death.
Animals found dead and confirmed with H somni infection often have a history of treatment for undifferentiated fever or lethargy in the previous 14 days.
Closer examination of an animal with histophilosis usually reveals fever. Overt tachypnea and/or dyspnea is easily confirmed by auscultation. Hypoxemia associated with pulmonary or cardiovascular involvement can be easily misinterpreted as neurological in origin, along with other clinical CNS signs, such as ataxia, lethargy, 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.
Because the clinical presentation of histophilosis can be severe and peracute, humane euthanasia is often deemed appropriate before an extensive clinical workup can be performed.
Lesions
Feedlot cattle, or even calves on range, that die of suspected histophilosis should be examined at necropsy. Postmortem findings can include the following:
fibrinous pleuritis with or without bronchopneumonia
a focal myocardial lesion (often in the papillary muscle of the left ventricle)
fibrinous pericarditis
bronchopneumonia
polyarthritis
fibrinous laryngitis
Less common gross postmortem lesions of histophilosis include polyserositis, fibrinous gonitis, and fibrinopurulent meningitis. Probably the most common lesion in feedlot cattle is acute left-sided heart failure, grossly visible as a distinctive myocardial discoloration that is often restricted to the papillary muscle. Pulmonary congestion and edema may also be evident as a result of left-sided heart failure (see acute left-sided heart failure image).
Courtesy of Dr. Eugene D. Janzen.
In animals that survive long enough for pathology to progress, the fibrinous portion of lesions becomes fibrotic, and infarctions become surrounded by scar tissue. Both cardiac and laryngeal lesions can liquefy, wall off, and become abscessed. This process often is associated with the formation of a marked necrotic sequestrum in the papillary muscle (see myocardial necrotic sequestrum image).
Courtesy of Dr. Eugene D. Janzen.
Proliferative endocarditis is another grossly visible pathological process resulting in left-sided heart failure due to H somni infection.
Reproductive tract lesions resulting from H somni infection can include suppurative vaginitis, cervicitis, orchitis, and endometritis; however, these findings are rarely documented, because they are not life-threatening. Necropsy is rarely requested for signs of infertility.
Diagnosis of Histophilosis
Gross lesions
Bacterial culture
PCR assay
A definitive diagnosis of histophilosis is based on sampling and examination of affected tissues collected during necropsy or clinical examination. A diagnosis at necropsy of left-sided heart failure with a concomitant myocardial lesion, or a carcass in which there is fibrinous pleural effusion with little pneumonia, is considered definitive for histophilosis.
Historically, isolation of H somni from CSF, brain, blood, urine, joint fluid, or other sterile, internal organs or fluids has confirmed the diagnosis of histophilosis. Because H somni is a commensal on bovine mucous membranes, it should be isolated in predominant or pure culture from the respiratory or urogenital tract to be implicated as an important etiological agent. Such isolation can be difficult, because antimicrobial treatment often interferes with recovery of the organism.
The characteristic early histological lesion of histophilosis is suppurative, with heavy neutrophilic infiltration in all tissues where the bacteria are localized. H somnican be visible in the lesion.
Currently, the diagnosis of histophilosis is usually confirmed with molecular techniques such as immunohistochemical examination of H&E-stained tissues or specific PCR testing of a fresh lesion swab.
Treatment and Prevention of Histophilosis
Florfenicol and other antimicrobials, administered early in the course of disease
Univalent and multivalent bacterins
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 progression. Antimicrobial treatment is most effective in the early stages of disease.
Florfenicol (20 mg/kg, IM, in the neck only, repeated in 48 hours; or 40 mg/kg, SC, once) is the antimicrobial of choice if histophilosis is the presumptive diagnosis in an individual animal. Florfenicol should not be administered to calves intended for veal.
Evidence is scant to support the use of prophylactic or metaphylactic antimicrobials on arrival at the feedlot or in the face of occurring histophilosis cases. Although H somni is susceptible to a wide range of antimicrobials in vitro, metaphylaxis may not be as effective for control of this bacterium as it is for other bacteria (eg, M haemolytica, Pasteurella multocida). Metaphylaxis is a highly effective management strategy for controlling bovine respiratory disease complex in high-risk animals.
The precise mechanism by which H somni is able to avoid systemic blood concentrations of antimicrobials is not well understood. It has been postulated that as H somni proliferates, it forms biofilms that enable it to adhere to endothelia and to withstand the effects of an otherwise effective antimicrobial concentration.
Bacterins containing different strains of H somni have been used to immunize cattle against the bacterium. Currently, many multivalent clostridial bacterins also are available with an H somni fraction.
A favorable humoral response generated by a single immunization with a commercial vaccine can be improved when boosted with a second immunization. Calves initially immunized before turnout (at approximately 2 months old) respond to a second immunization anamnestically at preweaning processing or on their arrival at the feedlot after weaning. bovine
Current bacterins and immunogens against histophilosis have been reported to provide some protection against disease and death. However, the ability of immunization to consistently spare cattle from the disease is compromised when immunization and challenge occur at the same time (ie, upon arrival at the feedlot), when poor immunization develops because of stress, or when the natural challenge exceeds the extent of immunization. In addition, reports have suggested that the same process of biofilm production by the fulminating bacteria that protects them from antimicrobials can also prevent immunoglobulins from reaching the organism (4).
Zoonotic Risk of Histophilosis
Histophilosis is not a known zoonotic disease.
Key Points
Infection with Histophilus somni is common among cattle in North America and sporadic in other areas worldwide.
In young cattle, sudden death is often the first sign of H somni infection.
Antimicrobial treatment is often unsuccessful, because the disease progresses rapidly.
Monovalent or multivalent bacterins can help immunize cattle against H somni; however, their efficacy is affected by timing and host-specific factors.
For More Information
Corbeil LB. Host immune response to Histophilus somni. In: Inzana TJ, ed. Histophilus somni: Biology, Molecular Basis of Pathogenesis, and Host Immunity. Springer, Cham; 2015:109-129. Current Topics in Microbiology and Immunology; vol 396. doi:10.1007/82_2015_5012
References
Gershwin LJ, Berghaus LJ, Arnold K, Anderson ML, Corbeil LB. Immune mechanisms of pathogenetic synergy in concurrent bovine pulmonary infection with Haemophilus somnus and venire respiratory syncytial virus. Vet Immunol Immunopathol. 2005;107(1-2):119-130. doi:10.1016/j.vetimm.2005.04.004
Corbeil LB. Histophilus somni host-parasite relationships. Anim Health Res Rev. 2007;8:151-160. doi:10.1017/S1466252307001417
Corbeil LB. Host immune response to Histophilus somni. In: Inzana TJ, ed. Histophilus somni: Biology, Molecular Basis of Pathogenesis, and Host Immunity. Springer, Cham; 2015:109-129. Current Topics in Microbiology and Immunology; vol 396. doi:10.1007/82_2015_5012
Sandal I, Hong W, Edward Swords W, Inzana, TJ. Characterization and comparison of biofilm development by pathogenic and commensal isolates of Histophilus somni. J Bacteriol. 2007;189(22):8179-8185. doi:10.1128/JB.00479-07
