Epidemiology, predisposing factor and transmission route 

H. somni can be considered as a global problem for dairy and beef cattle farming, as it has been reported in many countries worldwide, affecting preferentially young animals, from one week of age to 10 months, although the greatest number of cases are found from 4 to 10 months (Schiavon et al., 2008).  

H. somni manifests its pathogenicity especially in newly arrived intensively reared beef cattle, but affects also, albeit less frequently, dairy calves, grazing heifers or dairy cattle (Schiavon et al., 2008). Indeed, in intensive beef cattle farming, predisposing factors such as commingling or transport, can  facilitate the spread of H. somni, as well as other pathogens involved in the BRD complex, due to a stress-related immunosuppression (Sgoifo Rossi et al., 2022; Siddaramppa et al., 2004). Disease occurs year–round, but, most clinical cases occur between October and January, due to abrupt changes in the temperature as well as to extremely low temperature (O’Toole et al., 2016; Orr et al., 1992).  

Transmission of the infection occurs through secretions from the respiratory system, such as cough and, in some cases, nasal mucus, especially in intensively reared beef cattle. Cough is the more effective vehicle of infection, considering that the bacterium usually colonizes and exert his pathological effects in the lower respiratory airways (Gogolewski et al. 1989; Perez et al., 2010).  

Virulence factors 

Even when there is still a lack of knowledge about the precise mechanisms which lead to the triggering of pathological symptoms, several virulence factors/mechanisms have been identified in H. somni that can explain its ability to cause all the various pathologies to which it is related, as well as to escape the immune defences.  

H. somni can colonize the surface of the mucous membranes and attaches to bovine endothelial cells (BECs) (Perez et al., 2010). Also, the capacity to form biofilm is involved in the ability to adhere to the mucosal surface (Sandal et al., 2009).  

As other Gram-negative bacteria, H. somni expresses a variety of structures on the outer leaflet of the outer membrane, such as lipo-oligosaccharides (LOS) (Siddaramppa et al., 2004), which provides critical protection to the bacterium against host defenses, may act as an adhesin, and, is an endotoxin that cause inflammation (Inzana et al., 2015).  

LOS of H. somni can undergo to several modifications that led to an increased variability and continuous changing in the antigen expression by the bacterium, that allows it to escape the host immune defences. 

H. somni is able to inhibit the killing ability of the neutrophils once engulfed (Perez et al., 2010). and survive inside the neutrophils, escaping also the other host defences. It would contribute to the invasion of other tissues and also to the establishment of chronic and multisystemic infections (Perez et al., 2010; Siddaramppa et al., 2004).  

Biofilm 

It was demonstrated that H. somni is able to form a biofilm both in vitro and in vivo, in his natural host (Sandal et al., 2007; Sandal et al., 2009). Moreover, the biofilm created by H. somni can be used also by other pathogens, such as Pasteurella multocida, to persist in the host and escape immune defences, especially during chronic BRD (Petruzzi et al., 2020).  

Clinical diseases 

The pathological picture attributable to H. somni is complex and includes neurological, respiratory, cardiac pathologies, arthritis and also symptoms affecting the reproductive system (Siddaramppa et al., 2004). The original disease manifestation associated with H. somni was thrombotic meningoencephalitis-myelitis (TME). However, nowadays, there is a predominance of manifestations affecting the respiratory system and myocardium (Schiavon et al., 2008, Orr et al., 1992). Sometimes, two or more symptomatology related to H. somni can occur contemporaneously (O’Toole et al., 2016).  

Clinical diseases associated with H. somni occurred either in peracute, acute, subacute and chronic forms. The neurological forms are usually peracute or acute while the respiratory and cardiac ones are usually subacute or chronical, even if those pathologies can lead to death (Perez et al., 2010, O’Toole et al., 2016).  

Thrombotic meningoencephalitis-myelitis (TME) 

TME affect primarily fattening beef cattle, between 6 to 12 months and, to a lesser extent, dairy calves (Francoz et al., 2015; O’Toole et al., 2016). H. somni, in the case of TME, does not behave like a contagious disease even if, during an outbreak, different cases can occur in the herd (O’Toole et al., 2016).  

Clinical signs and symptoms are typical of acute meningoencephalitis with lateral recumbency, depression, anorexia, excitement, irritability, fever, head tilt, nystagmus, strabismus, blindness, coma, convulsions and sudden death (De Lahunta et al., 2008; Perez et al., 2010; O’Toole et al., 2016). One of the typical signs of TME is the presence of closed or semi closed eyes, that gives rise to the common phrase of “sleeper syndrome” and to the denomination “somni” (O’Toole et al., 2016).  

Classical lesions of TME, such as multifocal haemorrhages with necrosis and fibrinopurulent meningitis, can be found in the brain or in the spinal cord (Stephens et al., 1981; Clark et al., 2005; O’Toole et al, 2016). The cerebrospinal fluid is cloudy and blood-tinged (Nietfeld et al., 2012; O’Toole et al., 2016).  

Bovine Respiratory Disease 

The incidence of pulmonary disease associated to H. somni is gaining interest in the last years, becoming the most frequent and impactful form of histophilosis in beef cattle farming (Perez et al., 2010; O’Toole et al., 2016). Indeed, H. somni is a component of the BRD complex. Often, the symptomatology is driven by  more than one single pathogen, with commensal pathogens such as H. somni acquiring virulence characteristics after the first action of other pathogens (Woolums et al., 2015; Lin et al., 2016). Nevertheless, H. somni can also cause BRD alone (O’Toole et al., 2016).  

Pulmonary forms are frequent in intensively reared beef cattle and especially in the most critical phases, where the stress-related immunosuppression is more frequent, peaking within the first 2 weeks after the arrival (O’Toole et al., 2016 Sgoifo Rossi et al., 2013). Moreover, pneumonia caused by H. somni can represent the first step of a complex of diseases, that due to septicaemia, can lead to the other pathologies related to histophilosis, such as myocarditis (Clark et al., 2005).  

Clinical signs and symptoms are those typical of BRD: tachypnoea, fever, cough, nasal discharge, depression and anorexia. Anatomopathological lesions are more frequent in the case of acute pneumonia and can develop mainly in three principal forms: anteroventral fibrinosuppurative bronchopneumonia, fibrinosuppurative bronchopneumonia associated with pleuritis and interstitial pneumonia (O’Toole et al., 2016).  

These lobular lesions are bilateral and affect cranial–ventral portions of the lungs. Affected parenchyma is consolidated and grey to red-grey, with intraluminal exudate in small airways. Also, multiple small abscesses can be detected in the bronchioles. Mediastinal and tracheobronchial lymph nodes can be mildly edematous (O’Toole et al., 2016).  

Conversely, interstitial pneumonia, that is caused mainly by septicaemia and endotoxemia, is characterized by intra-alveolar edema and haemorrhage, with heavy and red lungs due to edema (Caswell and Williams et al., 2007).  

Myocarditis  

The incidence of the myocardial form has also increased in recent years, even when it is considered rare and sporadic. It affects mainly intensively reared fattening beef cattle, occurring on average sixty days after the arrival and, often, as a follow up of a pulmonary symptomatology (Gagea et al., 2006).  

The anatomical cardiac lesions associated with H. somni are myocardial infarction, myocarditis and fibrinous pericarditis (Schiavon et al., 2008; O’Tool et al., 2016). Usually, those lesions are located in the left ventricular myocardium and affect one or both of its papillary muscles (O’Toole et al., 2016). Signs of acute forms include areas of 1-3 cm of purple haemorrhage, while subacute and chronic lesions are fibrotic and characterized by apoptosis and necrosis of the endothelium and of the cardiocytes (O’Toole et al. 2016).  

Other 

In addition, even with a lower incidence and spread, infection with H. somni can result in cattle, in reproductive failure, abortion (Chladek, 1975), infertility (Kwiecien and Little, 1991), arthritis (Pritchard et al., 1979) and mastitis (Hazlett et al., 1985) with varying degrees of frequency and severity (Siddaramppa et al., 2004; Perez et al., 2010).  

Treatment and prevention  

The treatment of symptomatic diseases caused by H. somni is hard due to the difficulty in intervening promptly at the onset of the first symptoms, as it is often rapidly fatal, and presents similar symptoms caused by other pathogens. In any case the efficacy of the treatment is still scant and vague, even if it has a good susceptibility toward many antimicrobials in vitro, (Goldspink et al., 2015).the results in vivo showed that the efficacy is low, variable, and scant.  

The mechanisms of protective immunity against H. somni are still not so well understood, but antibodies are likely to be an important part of the protection system, and vaccination is thus used as the primary way to counteract H. somni (Corbeil et al., 2016).  

Attempts have been made for decades to control H. somni infection by vaccination (Humphrey and Stephens 1983). Various preparations of formalin-killed commercial bacterins for prophylaxis against H. somni diseases are available from major pharmaceutical companies. Commercial vaccines for H. somni include killed cells or outer membrane proteins that have helped prevent infectious thrombotic meningoencephalitis and pneumonia caused by H. somni. Particularly in Europe there is only one inactivated vaccine available containing H. somni in combination with Mannheimia haemolytica leukotoxoid. 

Conclusion  

H. somni has been reported in many countries and can be considered a worldwide problem, impacting efficiency and profitability of both dairy and beef cattle farming. 

It is an important component of the BRD complex and, although a H. somni infection can cause different clinical presentations, the pulmonary disease is the most frequent and impactful form of histophilosis, affecting mainly young animals due to a stress-related immunosuppression. 

Antibiotic treatment seems to have scare success under field conditions, making prevention the best approach to control the disease. Since antibodies are the main protective and counteracting mechanism to cope with H. somni, vaccination is the best way to protect cattle from the disease. 

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