Vaccination against staphylococcal mastitis

Extract

Sir:- Immunisation with staphylococcal vaccines is a potential means of increasing the resistance to bacterial invasion of the udder. However, the development of an effective vaccine for control of staphylococcal mastitis in ruminants has proved to be an elusive goal. There have been numerous attempts to develop vaccines against coagulase-positive Staphylococcus aureus mastitis, but very few attempts to develop vaccines using coagulase-negative staphylococci. Development of a vaccine against coagulase-negative staphylococci may help control the sub-clinical mastitis caused by these organisms and assist in the search for an effective vaccine against mastitis caused by the more pathogenic coagulase-positive S. aureus.We describe here an experiment in which ewes were immunised with live coagulase-negative staphylococcal vaccine and challenged during lactation by intramammary infusion of a homologous strain.     

Immunology of experimental staphylococcal mastitis in mice

Anti-staphylococcal serum, inoculated intramammarily, significantly reduced the number of bacteria recovered from mammary glands in which staphylococcal mastitis had been induced. In addition, there was an alleviation of some of the pathological clinical signs following the immune-serum treatment. Intramammary inoculated normal serum and systemically inoculated immune serum failed to elicit any protection.

The role of cell-mediated immunity in relation to staphylococcal mastitis was not clearly established.     

金黄色葡萄球菌诱发小鼠乳腺炎模型的建立

近年来,国内外开始选用小鼠建立乳腺炎病理模型,成功解决了使用奶牛或奶山羊等动物成本太高或操作不便以及无法进行标准化管理的问题[1-2].但其在诱发小鼠乳腺炎的操作中对小鼠乳腺组织易造成人为的损伤,不能真实模拟奶牛乳腺炎的自然发病机制[3].本试验用乳腺炎病牛奶样中分离到的金黄色葡萄球菌人工诱发小鼠乳腺炎,成功建立了小鼠乳腺炎模型,为研究乳腺的免疫学、病理学、药动学、药效学和临床治疗等提供了试验平台,报道如下.     

Pharmacokinetic-pharmacodynamic model for spiramycin in staphylococcal mastitis

Simultaneous pharmacokinetic-pharmacodynamic (PK/PD) modelling for spiramycin in staphylococcal infections of the mammary gland of cows was used to predict the efficacy of spiramycin. A differential equation derived from the Zhi model was fitted to an in vitro killing curve and post-antibiotic effect determination. A seven-compartment PK model, in which 4 compartments representing each quarter of the mammary gland which was considered to be the effect compartment, was included. The PD model linked to the PK model was able to describe the in vivo spiramycin effect against Staphylococcus aureus . The parameters calculated from in vitro data predicted a rapid decrease for the first 12-24 h, and regrowth within 72 h following the treatment, whereas in vivo the bacterial effect was much less after 24 h than that predicted by the in vitro data. PK/PD modelling permitted the simulation of various doses to optimize the efficacy of the antibiotic, taking into account such dynamic parameters as bacterial growth rate constant, bacterial killing rate constant and the Michaelis-Menten type saturation constant. An optimal dosage regimen of 20 000 IU/kg per day for 3 days was predicted for the treatment of Staphylococcus aureus mastitis.     

Vaccination against experimental staphylococcal mastitis in ewes

Experiments were carried out in ewes using a new vaccine developed for the prevention of mastitis caused by Staphylococcus aureus. The vaccine comprised three major components: (i) killed S aureus cells which had been cultured to induce synthesis of pseudocapsule; (ii) toxoided staphylococcal beta haemolysin and (iii) the adjuvant dextran sulphate. Ewes systemically vaccinated twice during pregnancy developed significantly elevated circulating levels of IgG1 and IgG2 anti-pseudocapsule antibody, as well as increased serum titres of anti-beta haemolysin. Five different strains of S aureus were used to challenge both vaccinated and control ewes by the intramammary route during the ensuing lactation. The incidence of acute gangrenous mastitis and nonacute, clinical mastitis was significantly lower in vaccinated than in control groups after challenge with each strain. Vaccinated ewes produced significantly more milk than control ewes after challenge with four of the five strains of S aureus.     

Aspects of the epidemiology of bovine staphylococcal mastitis

Abstract

Strains of Staphylococcus aureus which are not susceptible to many antibiotics are now generally regarded as the most important pathogens in bovine mastitis. More effective methods for controlling the disease must, therefore, take into account recent advances in our knowledge of the epidemiology of the disease. These include information about the principal habitats of S. aureus in the host, the minimal numbers of organisms that may establish new udder infections, which animals act as reservoirs of infection in herds, and the transmission of infection in lactating and non-lactating cows. Such matters are discussed in relation to the application of mastitis control measures involving herd management, hygiene, antibiotic therapy, culling and milking machine maintenance.     

Vaccination against experimental staphylococcal mastitis in dairy heifers

Vaccination-challenge experiments were carried out with dairy heifers using new, killed cell-toxoid-adjuvant Staphylococcus aureus vaccines. The organisms in the vaccines were cultured under conditions which simulated in vivo growth and induced expression of a pseudocapsule. Dextran sulphate which promotes synthesis of IgG2 antibody was included in the vaccines as the primary adjuvant. Vaccinated heifers developed very high levels of both IgG1 and IgG2 anti-pseudocapsule antibody in serum, however, titres of neutralising antibody against toxoided haemolysins were generally low. Vaccinated and unvaccinated control heifers were challenged by intramammary infusion of three virulent strains of S aureus in four experiments. Vaccinated heifers were more resistant to clinical mastitis following challenge than were controls, and the vaccinates had significantly greater milk production than controls following challenge. The most promising vaccine had dextran sulphate combined with mineral oil as the adjuvant injected intramuscularly.     

Intramuscular treatment of subclinical staphylococcal mastitis in lactating cows with penicillin G, methicillin and their esters

The relationship between antibiotic milk concentrations and bacteriological efficacy was investigated in groups of lactating cows with subclinical mastitis due to either penicillin G-sensitive or penicillin G-resistant Staphylococcus aureus. Treatments consisted of the intramuscular injection of procaine penicillin G, or its weak base ester penethamate hydriodide, and sodium methicillin, or its weak base ester tamethicillin. Antibiotics were administered once daily for 2 or 4 days at accepted dosages. After four daily, treatments with procaine penicillin G and penethamate hydriodide, infections were eliminated from 56.5% and 68.8%, respectively, of quarters infected with penicillin G-sensitive staphylococci, and from 14.3% and 7.7%, respectively, of quarters infected with penicillin G-resistant staphylococci. After four daily treatments with sodium methicillin and tamethicillin, infections were eliminated from 32.4% and 48.6%, respectively, of quarters infected with penicillin G-resistant staphylococci. The better efficacy of penethamate hydriodide and tamethicillin was considered to be linked to the higher milk drug concentrations obtained with these drugs as opposed to the lower concentrations measured in the milk after treatment with the parent drugs. Cure rates were generally higher after treatment for 4 days than after the 2-day course of therapy. Treatment efficacy decreased progressively with increasing age of the cows. Intramuscular treatment of subclinical staphylococcal mastitis in lactating cows can serve as a useful model for screening existing and new antibacterial agents and drug products intended for the parenteral treatment of clinical staphylococcal mastitis.     

The effect of incorporation of cloxacillin in liposomes on treatment of experimental staphylococcal mastitis in mice

The effect of incorporation of cloxacillin in liposomes on the treatment of staphylococcal mastitis was assessed bacteriologically 18 h after treatment of experimental infections in mice caused by two strains of Staphylococcus aureus. Intramammary treatments were cloxacillin incorporated in liposomes, cloxacillin in combination with liposomes, empty liposomes, cloxacillin in saline and saline alone. In none of the experiments did entrapment of cloxacillin within liposomes enhance its antibacterial effects. Electron microscopic studies demonstrated the presence of liposomes in neutrophils which also contained staphylococci. The results support the hypothesis that intracellular staphylococci are metabolically dormant and therefore not susceptible to the action of inhibitors of cell wall synthesis such as cloxacillin.     

Production of staphylococcal enterotoxins and TSST-1 by coagulase negative staphylococci isolated from ruminant mastitis.

The production of staphylococcal enterotoxins (SE) and toxic shock syndrome toxin-1 by 40 coagulase negative staphylococci isolated from sheep, goat and cow mastitis was studied. Both ELISA double sandwich and Western blot were used to detect the production of these toxins. Only two strains of S. xylosus were enterotoxigenic, producing SEC. TSST-1 was seen to be produced by 5 strains of S. xylosus, 1 S. sciuri and 2 S. epidermidis. Results obtained by ELISA and by Western blot agreed in all cases except in one strain of S. epidermidis which was only positive using ELISA.