Mannheimia haemolytica infections

International Common Names

• English: bovine pneumonic mannheimiosis; bovine respiratory disease; calf pneumonia; enzootic calf pneumonia; ewe mastitis; mannheimia haemolytica pneumonia, shipping fever, pasteurellosis; mannheimia haemolytica-like organism associated with diarrhea in swine; Mannheimia mastitis; mannheimia mastitis in goats; mannheimia mastitis in sheep; Mannheimia pleuritis; Mannheimia pneumonia; mannheimia pneumonia, shipping fever, pasteurellosis; mannheimia, pasteurella mastitis in cattle; mannheimia, pasteurella pneumonia of sheep and goats; mannheimia, pasteurella pneumonia, septicemia, of sheep and goats; mannheimiosis; mastitis; mastitis in ewes due to miscellaneous bacteria; necrotizing pleuropneumonia in pigs; otitis media, externa, interna, middle and inner ear infections; Pasteurella haemolytica infections; Pasteurella mastitis; Pasteurella pleuritis; pasteurella, mannheimia, pneumonia, pleuritis, in swine; pasteurellosis; pasteurellosis in cattle; pasteurellosis of sheep and goats; pasteurellosis of swine; pneumonic pasteurellosis; septicemic pasteurellosis; septicemic pasteurellosis of cattle; septicemic pasteurellosis of sheep; septicemic pasteurellosis of swine; shipping fever; shipping fever pneumonia; stockyard pneumonia; summer mastitis; summer mastitis in cattle; systemic pasteurellosis; transit fever
• French: mannheimiose

Local Common Names

• Italy: pasteurellosi

English acronym

• BRD

Mannheimia haemolytica

Mannheimia haemolytica (from Greek haima - blood, lyt – adverb form of verb lyo - dissolve, and adjectival suffix – ikos latinized in – ica) is a Gram-negative bacterium which produces a weak haemolytic phenotype on sheep blood agar plates. This microorganism corresponds to Pasteurella haemolytica biogroup 1 which in 1999 was renamed as Mannheimia, in tribute to Walter Mannheim, a German microbiologist who studied the taxonomy of the family Pasteurellaceae (Angen et al., 1999).

M. haemolytica is an important cause of bacterial respiratory mortality in cattle, sheep and goats; moreover, it is responsible for mastitis in ewes and camels, and rarely for abortion in cattle. It also causes a rare respiratory disease in pigs associated with Actinobacillus pleuropneumoniae, and it has been isolated from some wild and domesticated birds (Odugbo et al., 2004; Blackall et al., 2002; Christensen et al., 2003; Dewani et al., 2002; Frank, 1998; Martino, 2000; Oladele et al., 1999).

Healthy animals carry M. haemolytica as a nasal and nasopharyngeal commensal without developing clinical signs. However, when cattle (particularly younger animals) are stressed (for example in transportation from pastured herds to feedlots), and/or become infected with respiratory viruses, M. haemolytica replicates and is inhaled into the lower respiratory tract where it causes great damage. In addition, other opportunistic bacteria such as Pasteurella multocida, Histophilus somni, or Trueperella pyogenes (formerly Arcanobacterium pyogenes) can also take advantage of the damage done to the respiratory tissue. The interaction between the various pathogens can cause respiratory disease, which as a result is often referred to as bovine respiratory disease complex.

In particular, M. haemolytica is the principal microorganism responsible for bovine pneumonic pasteurellosis (older name) or mannheimiosis, also known as shipping fever. This respiratory disease is an economically significant disease in cattle, accounting for about 30% of total cattle deaths in the world; it is associated with an annual economic loss of over US $1 billion in North America alone (Miles, 2009; Frank, 1998).

There are several pathogenicity factors associated with M. haemolytica: fimbriae, capsule, lipopolysaccharide, leukotoxin, etc. It causes several clinical signs in domestic and wild animals: fever, cough, nasal discharge, weight loss, etc. (Alley, 2002; Kanwar et al., 1998; Alhendi, 2000; Ali and Youssef, 2003; Frank, 1998; Catry et al., 2002).

Antimicrobials such as tilmicosin, tildipirosin, danofloxacin, oxytetracycline, amoxicillin and clavulanic acid are used against the bacterium (Aslan et al., 2002; Christodoulopoulos et al., 2002; Frank et al., 2002; Hurd, 1999; Amrine et al., 2014; Lubbers and Turnidge, 2015) and vaccination to reduce the incidence of respiratory disease is widespread (Auad et al., 2001; Choe et al., 2000; Cusack, 2004; Hay et al., 2016).

Although M. haemolytica is not normally an important zoonotic agent, it can cause serious disease in human infants and immunocompromised adults; it has been demonstrated in septicaemia of infants and in adults with heart disease (Punpanich and Srijuntongsiri, 2012; Takeda et al., 2003).

There is a separate datasheet on the sheep disease atypical non-progressive proliferative pneumonia, to which M. haemolytica can be a contributory cause.

blood and circulatory system diseases of large ruminants
blood and circulatory system diseases of pigs
blood and circulatory system diseases of small ruminants
digestive diseases of pigs
mammary gland diseases of large ruminants
mammary gland diseases of pigs
mammary gland diseases of small ruminants
multisystemic diseases of large ruminants
multisystemic diseases of pigs
multisystemic diseases of poultry
multisystemic diseases of small ruminants
reproductive diseases of poultry
respiratory diseases of large ruminants
respiratory diseases of pigs
respiratory diseases of poultry
respiratory diseases of small ruminants

In bovine mannheimiosis, the hallmark histopathological feature of the disease is alveoli filled with fibrin interspersed with neutrophils and macrophages.  Larger airways are often spared inflammatory changes unless there are complicating bacteria or viruses. Interlobular septa are expanded due to fibrin-rich edema with lymphatic thrombi and a mild leukocyte infiltrate. In addition, fibrin is present on the pleural surface, and the mesothelium is denuded or hypertrophied.  Lymphocytes, neutrophils and macrophages may infiltrate the subpleura.  Within a few days, thrombosis of vessels with coagulation necrosis of entire or nearly entire lobules is noted (Caswell and Williams, 2007).

Septicemic bovine mannheimiosis is rare and usually occurs terminally in cattle that have severe pneumonia (Mahu et al., 2015; Odendaal and Henton, 1995).  M. haemolytica septicemia has also been associated with dairy cattle with naturally occurring coliform mastitis (Wenz et al., 2001). In the case of sheep with septicemia, the older literature can be unclear in that many of the cases of Pasteurella haemolytica septicemia were likely what is now Bibersteinia trehalosi; however, M. haemolytica can cause septicemia in lambs that are <3 months old (Caswell and Williams, 2007; Mackie et al., 1995). M. haemolytica has also been demonstrated in septicemia of human infants or in people with heart disease (Punpanich and Srijuntongsiri, 2012; Takeda et al., 2003).

In the pathology of domestic and Bighorn sheep and goat lungs, lesions consist of large areas of cranioventral haemorrhagic to suppurative to fibrinosuppurative bronchopneumonia that may have fibrin on the pleural surface (Caswell and Williams, 2007). Septicaemia of lambs causes sero-haemorrhagic effusions, and haemorrhages in the serosal membranes, epicardium and lungs, particularly in the peripheric lobes. The abomasal space and some intestinal tracts show a catarrhal-haemorrhagic inflammation. There is also obvious serofibrinous pleuritis and pericarditis (Caswell and Williams, 2007).

In camels, the major postmortem lesions are hydrothorax, adhesion of the lung to the thorax, emphysema, hydropericardium and fibrinous pericarditis (Seddek, 2002).

The pathogenesis of infections by Mannheimia haemolytica is not well understood. After colonization of the upper respiratory tract, the microorganism colonizes the lower respiratory tract and finally enters the alveolar spaces (Singh et al., 2011b). At these sites, there is a strong influx of neutrophils, which is associated with alveolar epithelial damage and necrosis, which results in increased vascular permeability, leading to alveolar flooding and pulmonary dysfunction. M. haemolytica lipopolysaccharide is probably involved in the initial increased vascular permeability and activation of macrophages (Singh et al., 2011a; Singh et al., 2012; Whiteley et al., 1990).

Neutrophils cause lung damage by release of elastase, myeloperoxidase and reactive oxygen intermediates, which cause structural degradation of lung tissue (Malazdrewich et al., 2004). Lung damage due to release of neutrophil hydrolytic enzymes is enhanced by the membrane effects of leukotoxin on neutrophils (Czuprynski, 2009; Lo, 2001). In addition, neutrophils can secrete cytokines, which can amplify and sustain the inflammatory response in the lung, resulting in lung pathology associated with disease. The inflammatory cytokines tumor necrosis factor α (TNF-α), IL-1β and IL-8 play a pivotal role in the initiation of the interactions between cytokines, leukocytes, vascular endothelium, cellular adhesion molecules and soluble chemotactic factors (Singh et al., 2011b). Studies indicate that bovine IL-8 is a chemoattractant for neutrophils and plays a key role in the genesis of lung injury associated with bovine pneumonic mannheimiosis (Malazdrewich et al., 2001; Caswell et al., 2001).

Pneumonic mannheimiosis is characterized in feedlot cattle by acute fibrinopurulent pleuropneumonia. Morbidity is due to substantial weight loss, obstruction of bronchioles due to fibrinous exudate, accumulation of macrophages and fibrin in the alveoli, and subsequent thrombosis and lymphatic vessel distention. The disease can rapidly progress to fatality (Apley, 2006) .

In ovine mastitis, the nursing lamb is suspected of both introducing the agent and providing the mechanical trauma needed for the development of clinical disease, which is characterized by severe, usually unilateral, necrotizing inflammation of the mammary gland (‘blue bag’) (Dewani et al., 2002, Scott and Jones, 1998). M. haemolytica adheres to mammary epithelial cells, which is considered critical for colonization. A study in vitro (Vilela et al., 2004) has demonstrated that adherence and internalization mechanisms may be present in the onset of mastitis caused by M. haemolytica. These mechanisms may be an important feature of the development of mastitis, allowing bacteria to survive and persist in the mammary gland.

Septicaemia of sheep due to M. haemolytica and the closely related Bibersteinia trehalosi takes two forms. M. haemolytica most often occurs in lambs less than 3 months old, involving severe pleuritis, synovitis, and pericarditis. B. trehalosi most often occurs in lambs of 5-12 months of age and is acute or peracute; outbreaks of disease often coincide with a change in diet or other stress. It is postulated that microorganisms already present in the tonsils multiply and invade the adjacent tissues of the alimentary tract. Microorganisms enter the bloodstream as emboli and lodge in the capillary beds of the lung, liver and spleen. Rapid multiplication of M. haemolytica in these tissues leads to death (Lopez and Martinson, 2017).

In adult camels, M. haemolytica has been isolated from pneumonic lungs and from cases of chronic, suppurative mastitis (Woubit et al., 2001; Alhendi, 2000; El Jakee, 1998). In addition, M. haemolytica has been isolated from laryngeal abscesses in alpaca crias (Dwan et al., 2008).

Mannheimia haemolytica is a commensal of the nasopharynx of cattle and sheep, but it can act as a primary pathogen in septicaemia of lambs or in bronchopneumonia of calves and cattle (Taylor et al., 2010a, b).

Many ruminant species carry M. haemolytica as a commensal in the nasopharynx and tonsils (cattle, sheep, goat, buffaloes, etc.), but it causes disease in only a few species. Sheep and goats are most often affected, followed by cattle and buffaloes, in which it is often possible to observe diseases associated with stress of transportation (shipping fever), sometimes associated with Pasteurella multocida, Mycoplasma bovis, and Histophilus somni infections and viral agents (such as parainfluenza-3 virus, bovine respiratory syncytial virus, bovine viral diarrhea virus, or bovine herpesvirus-1) (Taylor et al., 2010a). In other species, such as camelids, wild and domesticated birds, etc., the bacterium is isolated less frequently and is generally associated with viral and mycoplasmal infections, or mixed infections with other bacteria (Kanwar et al., 1998; Mackie et al., 1995; Martin et al., 1998; Khan and Khan, 1997; Martrenchar et al., 1995; O’Connor et al., 2001; Oladele et al., 1999; Ward et al., 1999). Some further information on predisposing factors in different species is provided in the 'Hosts/species affected' section.

Calves, lambs, and kids develop nasal colonization at a young age via direct transmission from the dam via nasal secretions or droplets, by transmission from one young animal to another, or through fomites. M. haemolytica and P. multocida have been isolated from the nasal passages of some dairy calves as early as 24-36 hours after birth (Step et al., 2005). Epidemiological studies in several states of the USA have attempted to identify risk factors for morbidity and mortality both at the individual calf and herd levels. Approximately 40-80% of all diseases of cattle in various countries involve the respiratory system, and bovine respiratory disease complex is the most important problem; it involves three clinical syndromes, of which shipping fever and pneumonic mannheimiosis are due to M. haemolytica (Hay et al., 2014; Hay et al., 2016; Murray et al., 2016; Murray et al., 2017; Sivula et al., 1996).

In Africa, especially in Ethiopia, bronchopneumonia, mainly attributed to M. haemolytica, causes both morbidity (18.6%) and mortality (10.6%) in sheep and goats. In this environment the highest percentage of bacterial isolation was recorded from September to November (Sisay and Zerihun, 2003).

In experiments, the survival of M. haemolytica was 1 h on a wooden plank and 24 h in straw maintained at 20°C. Nevertheless, relative humidity and cold weather increase its survival, which can reach 48 h at 4°C, 3 days in milk or in water at 20 °C, 7 days in water at 4°C and 8 days in milk at 4°C (Euzeby, 1999).

In the USA, pneumonia caused by M. haemolytica is the main cause of economic losses in the breeding of calves. The same condition is also observed in Europe (Fels-Klerx et al., 2002). In addition, M. haemolytica is the second commonest agent causing mastitis in goats in Europe and is one of the main aetiological agents of this disease in USA. Gelasakis et al. (2015) report that sheep mastitis due to M. haemolytica and Staphylococcus aureus causes substantial economic and disease losses to the sheep industry

Financial losses that result from calf pneumonia occur due to death, treatment cost and decreased lifetime productivity (and possibly a lower grade of meat in cattle treated multiple times for the disease). Michigan dairy producers estimated that respiratory disease in calves cost them US $14.71 per calf/year (Kaneene and Hurd, 1990) while producers in California estimated that calf respiratory disease cost them US $9 per calf/year (Sischo et al., 1990). The economic loss is over US $1 billion in North American beef and dairy cattle (Miles, 2009) (Griffin, 1997).

A study in two dairies in Mexico (Pijoan and Chavez, 2003) evaluated direct and indirect costs of losses due to pneumonia. Direct costs included fatalities, discards and treatment. Indirect costs included vaccination and preventive treatment. The range varied from US $52.78 per calf to US $24.72 per calf.

In free ranging North American Bighorn sheep (Ovis canadensis), M. haemolytica (and also Bibersteinia trehalosi) cause severe pneumonia in all age groups (Besser et al., 2013). These bacteria have been largely responsible for the large decline in the Bighorn sheep population.

Because respiratory disease is the major cause of economic losses in the beef cattle industry and M. haemolytica is such a major cause of bovine pneumonia, antibiotics are used in large amounts to control the pneumonia (Rice et al., 2007).  This practice has led to concern that high antibiotic use in meat and dairy cattle can lead to antimicrobial resistance in human pathogens (Oliver et al., 2011).

Although M. haemolytica is not normally an important zoonotic agent, it can cause serious disease in human infants and immunocompromised adults; it has been demonstrated in septicaemia of infants and in adults with heart disease (Punpanich and Srijuntongsiri, 2012; Takeda et al., 2003).

Mannheimia haemolytica is not normally an important zoonotic agent, but it can cause serious disease in infants and immunocompromised adults; it has been demonstrated in septicaemia of infants and in adults with heart disease (Punpanich and Srijuntongsiri, 2012; Takeda et al., 2003).

Heat treatment of milk (pasteurization or ultra-high temperature treatment) allows elimination of M. haemolytica and assures milk safety. However, in countries where milk is consumed untreated and the microorganism is widely spread, risk of infection could be high.

Mass medication of livestock used in treatment and prevention of bovine respiratory disease increases the risk of unwanted drug residues in meat and milk intended for human consumption.

At present, treatment of bovine pneumonic mannheimiosis is based almost exclusively on systemic antibiotic therapy. In fact, there are many antibiotics that are used for treatment, often both in calves and in lambs. Examples are oxytetracycline, danofloxacin, enrofloxacin, marbofloxacin, tilmicosin, tildipirosin, amoxicillin plus clavulanic acid, talaromycin and florfenicol, with a dosage ranging from 6 mg/kg to 20 mg/kg (Apley, 2006; Aslan et al., 2002; Christodoulopoulos et al., 2002; Cusack, 2004; Frank et al., 2002; Hurd, 1999; Rowan et al., 2004; Sarasola et al., 2002; Schwan, 1998; Thomas et al., 2001; Traeder and Grothues, 2004).

Furthermore, metaphylactic administration of long-acting antibiotics (such as oxytetracycline, tilmicosin, enrofloxacin, or tildipirosin) to calves on arrival at the feedlot has become a common preventive measure. This procedure reduces morbidity and mortality during the early feeding period in calves (Malazdrewich et al., 2004).

The bovine strains are more resistant than ovine strains to several antibiotics: ampicillin, streptomycin, neomycin, gentamicin, tetracycline, chloramphenicol, etc. (Euzeby, 1999, Singer et al., 1998).

The resistance to ampicillin is due to plasmids that code for a β-lactamase named ROB-1, the resistance to chloramphenicol is due to the synthesis of an acetyltransferase III coded by a plasmid that can also act on florfenicol. A chromosomal gene encodes for resistance to sulfonamides (Euzeby, 1999).

Current evidence indicates that widespread use of antibiotics may have contributed to the emergence of multiple antibiotic-resistant strains of M. haemolytica (Malazdrewich et al., 2004; Euzeby, 1999). Mass medication of cattle with antibiotics also promotes the transfer of antibiotic resistance genes from animal pathogens to human bacterial pathogens. Other approaches to bovine mannheimiosis, such as improved vaccines and immunostimulants, are therefore being researched as alternatives to antibiotic mass medication.