Review on Bovine Pneumonic Pasteurellosis

Review Article

Austin J Infect Dis. 2023; 10(4): 1092.

Review on Bovine Pneumonic Pasteurellosis

Mathewos Belina Woyessa¹; Abdi Ahmed Umer²*

¹Jimma University College of Agriculture and Veterinary Medicine, Jimma, Ethiopia

²Animal Health Institute (AHI), Microbiology Research Laboratory, Sebeta, Ethiopia

*Corresponding author: Abdi Ahmed Umer Animal Health Institute (AHI), Microbiology Research Laboratory, P.O. Box 04, Sebeta, Ethiopia. Email: abdivet2014@gmail.com

Received: October 18, 2023 Accepted: November 17, 2023 Published: November 24, 2023

Abstract

Bovine pneumonic pasteurellosis is an economically important disease of cattle mainly in feedlot industry; and is characterized clinically by acute bronchopneumonia with toxemia. The bacteria have many virulence factors like capsule, fimbriae, endotoxin and leukotoxin. The disease is mostly associated with stress factors as the bacteria are commensals in the upper respiratory tract. The most common predisposing factors that expose cattle to bovine pneumonic pasteurellosis are transportation, the presence of concurrent bacterial, viral and parasitic disease, overstocking, any mass veterinary and animal husbandry practices like mass vaccination, prophylactic treatment, castration, docking, dehorning etc. Suddenly change of macro and micro climatic conditions, starvation and water deprivation of cattle can also expose the cattle to pneumonic pasteurellosis. Because they are stress factors that reduce the immune status of animals; as the result the commensal organism becomes pathogenic to stressed cattle and cause bovine pneumonic pasteurellosis. Bovine pneumonic pasteurellosis can be diagnosed by considering the epidemiology, clinical signs and the necropsy findings. However, confirmatory diagnose of bovine pneumonic pasteurellosis is done by isolation and identification of the causative agent from clinical specimens. Bovine pneumonic pasteurellosis must be differentiated from CBPP; Infectious Bovine Rhinotrachitis (IBRT), lung worms that have almost similar clinical findings. Treatment of the disease is effective in the early stage of the disease by using different antimicrobial drugs. However, the bacteria have many antimicrobial resistance factors and resistant to many antimicrobial drugs. The disease can be prevented and controlled by reducing stress factors, by improving management, by using antimicrobial drugs in their prophylactic treatment and using effective vaccines. But the presence of many serotypes and antimicrobial resistance factors of the organism make the disease difficult to prevent and control. So that reducing stress factors, performing qualitative antibiogram and using efficient vaccine which contains the major serotypes of Mannheimia haemolytica are crucial to control the disease.

Keywords: Bovine pneumonic pasteurellosis; Mannheimia haemolytica; Serotype; Stress; Virulence

Introduction

Animal production has been considered as the main component of agricultural development in most parts of sub-Saharan Africa. Ethiopia is known for its high livestock population, being the first in Africa and tenth in the world. The countries most recent estimates of its livestock population about 44.3 million heads of cattle, 23.6 million sheep and 23.3 million goats [1]. Despite the large number of livestock in Ethiopia the sector is characterized by low productivity and, hence, income derived from this sector of agriculture’s could not impart significant role in the development of the country’s economy. The low productivity is attributed to the low genetic potential of indigenous cattle, poor nutrition and reproductive performance, inadequate management, high disease incidence and parasite burden. These illnesses have a variety of effects on the productivity and fertility of herds, including losses from mortality and morbidity, weight loss, slowed growth and a decline in physical strength.

Due to environmental factors such as high temperatures and humidity, topography that is sloppy and vulnerable to flooding, stress factors, and drought that are frequent in these areas, there are many livestock health issues in tropical areas. As a result, there is a limited supply of feed and little vegetation coverage; additionally, there is a lack of knowledge about animal health services [2]. According to [3], organized research that can clarify major animal health problems is a key issue for further study of epidemiological study on the diseases of livestock. However, knowing the type and extent of the major health problems is very important for livestock owners, veterinarians, and researchers and can assist in the development of herd health strategies and the selections of potential interventions.

Infections of the respiratory system are frequently seen in a variety of domestic and farming animal species. The most prevalent instance, with a high incidence in ruminant animals, is pneumonic pasteurellosis, also referred to as respiratory mannheimiosis. Bovine Respiratory Disease (BRD) is the illness that causes the greatest morbidity and mortality in calf populations. It is known that two members of the Pasteurellaceae family, Mannheimia haemolytica and Pasteurella multocida, function as opportunistic pathogens in the BRD complex [4]. It is commonly known that pneumonic pasteurellosis is the leading cause of death in feedlot animals, with the illness being the reason for about 30% of all cattle deaths globally. More than one billion dollars are lost annually in the beef cattle business in North America alone as a result of the disease, which has a significant global economic impact [5]. Additionally, a considerable sum of money was lost virtually year for projects to improve farm management, animal husbandry, chemoprophylaxis, treatment, and vaccination. Therefore, the goals of this review are to understand the causes, epidemiology, and methods of preventing and controlling bovine pneumonic pasteurollosis.

Bovine Pneumonic Pasteurollosis

Pneumonic pasteurellosis (locally called “Fura” and “Gororsa” in Afan Oromo) and is one of the most important economical diseases in cattle. It is a multi - factorial respiratory disease of cattle that mainly affects calves. Bovine pneumonic pasteurellosis was first described in the United States in 1915 and in the United Kingdom in 1925. Bacteria belonging to the family Pasteurellaceae are involved. The bacteria are part of the normal microflora in the upper respiratory tract making the disease difficult to prevent [6].

Etiology

Mannheimia haemolytica biotype A, serotype 1 is considered to be the most common cause of the bovine pneumonic pasteurellosis. However, in some cases, other biotype strains have been isolated from cases of pneumonic pasteurellosis in cattle; that is why Pasteurella multocida is isolated in a few cases occasionally. Other pathogens like viruses or mycoplasmas may act synergistically with Mannheimia haemolytica. Mannheimia haemolytica, serotype 1 is the bacterium which is the most frequently isolated organism from the lungs of cattle with BRD; but Haemophilus somni is being increasingly recognized as an important pathogen in BRD; these bacteria are normal inhabitants of the nasopharynx of cattle. However, when pulmonary abscessation occurs, generally in association with chronic pneumonia, Arcanobacterium pyogenes is frequently isolated [3].

Under normal conditions, M. haemolytica remains confined to the upper respiratory tract, in particular the tonsillar crypts, and are difficult to culture from healthy cattle. After stress or viral infection, the replication rate of M. haemolytica in the upper respiratory tract increases rapidly. The increased bacterial growth rate in the upper respiratory tract, followed by inhalation and colonization of the lungs, may occur because of suppression of the host's defense mechanism related to environmental stressors or viral infections. It is during this log phase of growth of the organism in the lungs that virulence factors are elaborated by M. haemolytica, such as an exotoxin that has been referred to as leukotoxin. Haemophilus somni may invade the lung and cause pneumonia after damage to the respiratory defenses. This organism is capable of systemic spread from the lung to the brain, myocardium, synovial, and pleural and pericardial surfaces; often, death can occur later in the feeding period (40–60 days after arrival) from involvement of these additional organ systems [3].

Classification of Mannheimia haemolytica Based on its Biotypes and Serotypes

Organisms belonging to the bacterial family Pasteurellaceae are ubiquitously present in the respiratory, alimentary and reproductive tracts of different avian, mammalian, reptilian, and likely amphibian hosts.

Members of this family are small (0.2 - 2μm), Gram-negative, non-motile, facultatively anaerobic coccobacilli or rods. In addition they are, with few exceptions, fermentative and oxidase and catalase positive. Growth on artificial media is enhanced by the addition of serum or blood on which they appear after 24 hours of incubation as round, grayish colonies of moderate size [7].

During the last two decades, the combination of 16S r - RNA sequencing and other molecular techniques [8], has led to several new genera and over 58 formally recognized species and 25 unnamed taxa within the family Pasteurellaceae [9]. The most substantial reclassification in relation to bovine diseases was the redesignation of organisms formerly known as Pasteurella haemolytica into the new genus Mannheimia, with Mannheimia haemolytica as the type species besides. Organisms previously identified as Pasteurella haemolytica have earlier been categorized into 3 biotypes (sugar fermentation pattern of trehalose (T) and arabinose (A)), 12 biogroups (extended phenotyping including fermentation patterns of sugars and glycosides), and 17 serotypes (surface antigens) [10].

Despite this, strains formerly designated as Pasteurella haemolytica biotype T (fermenting trehalose) were redefined in 1990 and are currently still referred to us Pasteurellatrehalosi [11]. Remarkably confusing, two of the most detailed studied serotypes of M. haemolytica sensu latu (s.l.), i.e. A1 and A6, do not ferment arabinose although the original affiliation (“A”) was based on this characteristic and this typing is currently still used in vaccination leaflets. Species specific allocation of M. haemolytica [12] requires additional tests compared to the identification of Pasteurella haemolytica [13], but routine laboratory diagnosis and many peer reviewed manuscripts still regard these two as synonyms. Mannheimia (unless otherwise specified, e.g. M. haemolytica serotype A1), or where M. haemolytica was used as synonym for Pasteurella haemolytica. Although for several groups of Pasteurellaceae, host range and disease manifestations are not constant, the host animal species is indicative for routine bacterial identification [14]. In spite of the molecular advances, morphology and restricted phenotyping are routinely used for primary identification of Pasteurellaceae. Mostly, the primary identification of M. haemolytica is based on the isolation of round grayish colonies of moderate size with a small pronounced surrounding zone of haemolysis after 24 hrs of aerobic incubation on sheep blood agar. M. haemolytica does not produce indole and tolerates bile salts. P. multocida typically grows as mucoid confluent colonies, and in routine diagnostic bacteriology it is distinguished from M. haemolytica by production of indole from tryptophan, and by lack of haemolysis. A typical sweetish odour can be present ; whereas the habitat and the clinical relevance of M. haemolytica is predominantly restricted to ruminants, and more particularly cattle [7].

Historically, serotype A1 has been the predominant strain associated with pneumonic pasteurellosis but results of recent U.S survey reaffirmed that fact, including that serotype A1 accounted for approximately 60% of the total isolates recovered from pneumonic bovine lungs, where as serotype A 6 was isolated from 26% and serotype A 2 from 7%. The remaining 7% was composed of serotype A 9, A 11 or untypable strains bovine respiratory disease is multifactorial, involving environmental factors and concurrent infections with viruses (infectious bovine rhinotracheitis, bovine viral diarrhea [15]. The five current species in genus Mannheimia are Mannheimia haemolytica, Mannheimia grannulomatis, Mannheimia glucosidal, Mannheimia gramulo and Mannheimia varigena [16].

Geographical Distribution

Pneumonic pasteurellosis epidemiology is a common disease of cattle in all over the world including Europe, North America and Asia etc. In Canada and the United States the disease occurs most commonly in beef calves after weaning in the fall of the year and is the most important disease in cattle that has been recently introduced into feed lots. It also occurs in Africa including Ethiopia [17].

Occurrence

Pneumonic pasteurellosis is common in all farm animals including domestic and wild species of mammals and birds. Pasteurella and Mannheimia have an extremely broad spectrum of animal hosts. Many apparently healthy mammals and birds can harbor Pasteurella and Mannheimia organisms in upper respiratory tract and mouth; and according to the most accepted hypothesis, pasteurellosis is a disease of weakened animals that are subjected to stress and poor hygienic conditions. In animals with lowered resistance, Pasteurella/ Mannheimia harbored trachea and become pathogenic for their host [18].

Risk Factors

The disease occurs most commonly in young growing cattle from 6 months up to 2 years of age although all age groups are susceptible. While, the disease happens in young beef cattle soon after introduction to feedlot, it is uncommon in dairy herds, calves which originate from many different farms and mixed at the market are at high risk of infection. Beef calves may develop the disease before weaning if they are subjected to the stress of early snow storm in the late fall. The disease occurs commonly in outbreaks 7 - 10 days after cattle have arrived in the feedlot following stressful transportations of calves which are not immune to the disease [20].

The Bruce country beef cattle project in Canada identified some of the epidemiological factors associated with mortality in cattle shipped from Western Canada to small feedlots over a period of 3 successive years. Mixing of calves from different sources at auction markets was associated with increased risk of fatal fibrinous pneumonia in calves moved to feedlots in Canada. The role of stress as an epidemiological determinant in shipping fever pneumonia. Transportation and handling to mimic stress followed by an aerosol infection by M .haemolytica did not result in significant lesion of pneumonia but did mark the animals susceptible to bovine herpes virus. The transpiration and assembling of yearling in beef calves can result in an increase in the levels of plasma fibrinogen which is an induction of some stress. Deprivation of feed and water followed by confinement in unfamiliar surroundings also results in an increase in fibrinogen. The response of the animals was also dependent up on the previous environment and management applied to them before assembly and transportation. Experimentally, subjecting yearling bulls to a treated mill exercise makes them more susceptible to experimental pneumonia than bull which is not exercised [20].

The frequency of isolation of Pasteurella and Mannheimia spp. from the nasal passage of normal health unstressed calves is low but increases as the animals are moved to an auction market and then to a feedlot. The isolation rate of M. haemolytica biotype A serotype 1 in the nasal cavity and trachea can be low in beef calves from a closed herd that is maintained on range pastures, and serum antibody levels are also low, over time but there may be an increase in the frequency of isolation of the bacteria from healthy calves which were moved to pens held in low population densities and maintained under low stress conditions.

In some cases serotype 2 predominates while the calves are on the range pastures but serotype 1 predominates when the calves are in the feedlot and affected with pneumonia. There are relationships between the number of bacteria in the nasopharynx and the ambient temperature and humidity. In calves kept at a constant temperature of 160C (600F), the bacterial populations in the nasopharynx where at a minimum between 65 and 75% of relative humidity but tended to rest at humidity outside the range. The possibility might be infection with several different viruses and mycoplasmas that may predispose to pneumonic pasteurellosis [21].

Predisposing Factors

The multifactorial character of bovine pasteurellosis relates to predisposing factors of viral infections and the different bacterial and parasitic agents are involved. Predisposing factors are severe climate change and stress due to overcrowding and transport which are typically found in feedlots and veal calf industry. Following transport, the disease is also known as “shipping fever”. Generally speaking, both predisposing factors and concurrent viral, bacterial infections and parasitic diseases are capable of inducing impairment of pulmonary defenses which allow secondary infections mostly by opportunistic pathogenic of Pasteurellaceae [23].

Mode of Transmition

Transmission occurs by inhalation of infected droplets coughed up or exhaled by infected animals which may be clinical cases or recovered carriers in which the infection persists in the upper respiratory tract. Mannheimia haemolytica and Pasteurella multocida are highly susceptible to environmental influences and it is unlikely mediated contagion is an important factor in the spread of disease. When conditions are optimum, particularly when cattle are closely confined in inadequately ventilated barns over crowded in trucks or trains or held lots, disease spread very quickly and affects a high proportion within 48 hours [24].

Pathogenesis

The pathogenesis of pneumonic pasteurellosis remained a subject of considerable speculation and controversy due to the complex nature of the disease and lack of consistency. Pneumonic pasteurellosis is a secondary bacterial complication of a previous infection of the respiratory system [25]. However, the sequential development of the pulmonary lesions is highly mediated by complex interactions between the naturally existing causative organism in the upper respiratory tract, the immunological status of the animal and the role of predisposing factors in the initiation of infection. In either situation, the disease is essentially triggered by sudden exposure to a stressful condition or by initial infection with certain respiratory viruses, mycoplasmas or bacteria. Stress or viral infection would eventually impair the local pulmonary defense mechanisms by causing deleterious effects on the ciliating cells and mucous coating of the trachea, bronchi and bronchioles. The causative bacteria from the nasopharynx will then reach the ventral bronchi, bronchioles and alveoli by gravitational drainage along the tracheal floor and there become deeply introduced into the lung tissue. Endotoxin produced by rapid growth and multiplication of the bacteria in infected lobules will cause extensive intravascular thrombosis of pulmonary veins, capillaries and lymphatics. These vascular disturbances eventually result in focal ischaemic necrosis of the pulmonary parenchyma accompanied by severe inflammatory reaction dominated by fibrinous exudates [26].

Virulence Factors of Mannheimia haemolytica: The virulence factors of Mannheimia haemolytica include fimbriae, polysaccharide capsule, outer membrane proteins, endotoxin (lipopolysaccharide), and leukotoxin. The severity of lesions, depends on the rate and extent of bacterial proliferation and the amount of endotoxin released, which in turn depends on the virulence of the bacterial strain and the degree to which the defenses of the host are impaired. These factors are generally designated as virulence factors and constitute parts of the surface components of the bacterial cell and cellular products. Virulence factors are, in fact, capable of promoting adhesion, colonization and proliferation of the organism within the animal tissues. In other words, virulence factors are actively involved in conversion of the organism from commensals into pathogen. The roles of virulence factors in the pathogenicity of M. haemolytica have been extensively investigated [27].

Bacterial Capsule

The cell capsule constitutes an important virulence factor which plays vital roles in the pathogenicity of pathogenic bacteria and establishment of infection. The virulence mechanism of the cell capsule is mostly attributed to its ability to protect the invading organism against cellular and humoral defense mechanisms of the host. The capsular materials of M. haemolytica and other Pasteurella species were identified as polysaccharide and are basic structures produced during the logarithmic phase of growth of the bacteria. Each serotype of M.haemolytica produces a characteristic polysaccharide capsule in order to avoid phagocytosis by macrophages and polymorphonuclear leukocytes and to protect the organism against complement mediated destruction of the outer membrane in serum. The capsular material of M. haemolytica can also interact with the pulmonary surfactant and thereby facilitates the adhesion of the invading organism to the respiratory tract epithelium of susceptible animals [28].

Fimbriae

Fimbriae are smaller appendages present in the surface of many Gram negative bacteria. They are specific surface structures of the bacterial cell wall which permit or enhance adherence to and colonization of the target epithelium of the susceptible animals. Fimbriae are present in various strains of Pasteurella and Mannheimia species. Two types of fimbriae have been detected in serotype 1 of M. haemolytica. One of them is large and rigid; measuring 12 nm in width and the other is smaller, flexible and measures only 5 nm. The large rigid fimbriae are composed of 35 KDa subunits and proved to be highly immunogenic. The two types of fimbriae produced by M. haemolytica are both capable of enhancing mucosal attachment of the organism and colonization of the lower respiratory tract epithelium of cattle and sheep. Successful colonization will thus enable considerable increase in the number of bacteria seeded in the lung tissue beyond the level that normal lung capacity could efficiently resolve [29].

Endotoxin

Similarly to all other Gram negative bacteria, the cell wall of M. haemolytica contains a lipopolysaccharide (LPS) endotoxin. This endotoxin is one of the most important virulence factors involved in the pathogenesis of bovine pneumonic pasteurellosis. It has been shown that serotypes 2 and 8 of M. haemolytica possess a rough LPS while the other 14 serotypes have characteristic smooth LPS. Experimental evidence indicated that M. haemolytica endotoxin is directly toxic to endothelial cells and capable of altering leukocyte functions and causing lysis of blood platelets. Further subsequent investigations in calves also revealed a number of physiological effects of the purified LPS similar to those produced by chemical mediators such as thromboxane A2, prostaglandins, serotonin, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). All these previously mentioned mediators were known to be responsible for the clinical signs associated with endotoxic shock [30].

Leukotoxin

The leukotoxin is a102 KDa protein secreted at the logarithmic phase of growth of the bacteria and also considered as a main weapon or virulence factor for M. haemolytica. In fact, the leukotoxin is pore forming cytolysin which can produce several biological effects on leukocytes and blood platelets of ruminants. The most susceptible cells are bovine macrophages, neutrophils from most ruminant species. Lymphocytes and cultured lymphoma cells of ruminants are also susceptible to leukotoxin. At low concentration, leukotoxin impairs phagocytosis and lymphocyte proliferation while at higher concentration it has a cytotoxic effect resulting in cell death due to lysis. The lysis of cells is attributed to the formation of transmembrane pores in the target cell, and thereby allowing the movement of potassium, sodium and calcium ions through transmembrane gradients [31].

Leukotoxin also causes stimulation of polymorphonuclear leukocytes and activation of macrophages with consequent release of proinflammatory cytokines such as interleukin - 1 (IL - 1), interleukin - 8 (IL - 8), leukotrienes and tumour necrosis factor - a (TNF - a). Their action would further lead to the release of H2O2 which, in turn, is converted into hydroxyl radicals by alveolar endothelial cells. The free hydroxyl radicals cause considerable damage and necrosis of the pulmonary alveolar epithelium resulting in accumulation of oedema fluid and fibrin inside alveoli and interstitial spaces. The leukotoxin and enzymes released following cytolysis are both chemotactic for various types of inflammatory cells causing more damage to the lung tissue due to increased cell recruitment into the area. Furthermore, M. haemolytica leukotoxin was found to induce “in vitro” morphological alterations in calves’ neutrophils similar to those produced by the viable infective organism during the natural course of the disease in the living animal. The effect of leukotoxin and O-sialoglycoproteins produced by M. haemolytica A1 on bovine platelets activation was results in bovine blood platelets adhesion was considerably enhanced by both bacterial products. These two bacterial proteins could directly interact with bovine platelets to initiate platelet aggregation and fibrin formation in the alveolar tissue of the affected lungs [32].

Diagnosis

Clinical symptom

Clinical signs of pneumonic respiratory bacterial in cattle like depression and fever (104°F – 106°F (40°–41°C])), without any signs attributable to other body systems are the classic components of a case definition for early cases of BRD. Serous to mucopurulent nasal discharge; moist cough; and a rapid, shallow respiratory rate. Auscultation of the cranio ventral lung field reveals increased bronchial sounds, crackles, and wheezes. In severe cases, pleurisy may develop, characterized by an irregular breathing pattern and grunting on expiration. The animal will become unthrifty in appearance if the pneumonia becomes chronic, which is usually associated with formation of pulmonary abscesses [33]. Acute toxemic bronchopneumonia is characterized by moderate dyspnea, fever, and increased breathing sounds over ventral aspects of lungs. Moist crackles, coughing, pluritis, leucopenia and neutropenia are the main clinical signs and clinical pathology of bovine pneumonic pasteurellosis in severe cases. The disease usually develops in cattle within 10 to 14 days after they have been stressed. Sudden deaths without any previous warning signs may be seen in peracute form of the disease. Many calves are in the sign of an outbreak in which many claves are obviously affected and some are in the incubation stages of the disease. Viewed from a distance affected cattle are usually depressed and the respirations are shallow and rapid. There is a weak protective cough which may become more pronounced and frequent if they are urged to walk. Animals which have been ill for a few days will appear gaunt in the abdomen because of anorexia. A mucopurulent nasal discharge, crusty nose and an ocular discharge are common. Although affected cattle are anorexia they may continue to drink maintenance amount of water which may be useful in mass medication of the water supplies. Mucopurulent nasal discharge, crusty nose and ocular discharge are common and apparently health cattle may have temperature of 40°C - 41°C. In the early stages, loud breath sounds (bronchial tones) are audible over the anterior ventral parts of the lungs and as the disease progresses the breath sounds become launder and extend over a greater area and abnormal lung sounds like crackles and wheezes can be audible in few days; and rubs may be audible and in severe cases dyspnea is marked [34].