Efficacy of doxycycline in feed for the control of pneumonia caused by Pasteurella multocida and Mycoplasma hyopneumoniae in fattening pigs

A multicentre, controlled, randomised and blinded study was carried out in three French pig herds to assess the efficacy of doxycycline administered in the feed for the control of pneumonia. About 20 per cent of 363 pigs from the three fattening units were diseased at the start of the study. Pneumonic lesions were found on pigs examined postmortem and Pasteurella multocida was isolated from the lungs of pigs in all the herds. Mycoplasma hyopneumoniae infection was confirmed either by detection in pneumonic lungs or by seroconversion in pigs sampled three weeks apart. P multocida, Bordetella bronchiseptica and Actinobacillus pleuropneumoniae were isolated from 64 per cent, 50 per cent and 2 per cent, respectively, of 148 nasal swabs. The following variables were significantly different between the treated and untreated groups (P < or = 0.001): the incidence of diseased pigs during the three weeks from the start of treatment (8.1 per cent in treated group v 35.4 per cent in control group), mean daily weight gain over the same period (934 g/day in the treated group v 834 g/day in the control group) and the cure rate of pigs which were diseased at the start of treatment (73.5 per cent in treated group v 35.3 per cent in control group). These data demonstrate that an average dose of 11 mg doxycycline/kg bodyweight per day in feed for eight days was effective in controlling pneumonia due to P multocida and M hyopneumoniae in these fattening pigs.     

Lysogeny in Pasteurella multocida]

Studied was the possibility of lysis-producing factors (the phenomenon of lysogeny) with 59 strains of Pastuerella multocida isolated in Bulgaria, Cuba, and Czechoslovakia. It was found that eleven of them were lysogenic in terms that a total of 12 bacteriophage strains were isolated from them; one of them yielded 2 phages. Established were three different indicator strains of Pasteurella multocida-97, SHD, and R-II--by means of which 3 different groups of P. multocida phages were isolated. The latter were stabilized and allowed to multiply up to 10(11) phage particles per 1 cc through continuous passaging, and they could be be stored at + 4 degrees C. In accordance with the host strain for multiplying the isolated P. multocida phages were divided into three different groups: phages 3, 4, 5, 6, 22, and Sl fell into group II, and phages 1075 and S-2--to group III.     

Two-color hybridization assay for simultaneous detection of Bordetella bronchiseptica and toxigenic Pasteurella multocida from swine

Bordetella bronchiseptica and toxigenic Pasteurella multocida are the etiologic agents of swine atrophic rhinitis. Methods currently used for their identification are time-consuming and suffer from a lack of sensitivity. We describe a colony lift-hybridization assay for detection of B. bronchiseptica and toxigenic P. multocida that can be performed with a single colony lift derived from a primary isolation plate without the need for pure subcultures of suspect bacteria. Membranes are hybridized simultaneously to probes derived from the B. bronchiseptica alcA gene and the P. multocida toxA gene. A multicolor development procedure permits sequential detection of bound probes. The assay was tested with 84 primary isolation plates generated from nasal swabs from swine with clinical signs of atrophic rhinitis. Comparison of the results from the colony lift-hybridization assay with those from conventional testing, based on a combination of colony morphology, biochemical reactions, mouse lethality, and enzyme-linked immunosorbent assay, indicated that the colony lift assay has superior sensitivity and comparable specificity. This technique has wide application for diagnostic and experimental studies.     

Pasteurella multocida septicaemia in Milroy''s disease

Diaziquone (AZQ) is a lipid soluble alkylating agent which was designed for increased CNS penetration. Its principle toxicity is myelosuppression. We conducted a phase I trial using AZQ in combination with GM-CSF to determine if the maximal tolerate dose (MTD) of AZQ could be escalated. Using GM-CSF on a standard schedule, we were unable to escalate the previously determined MTD of diaziquone with the use of this colony stimulating factor.     

Pasteurella multocida tonsillitis: case report and review

Pasteurella multocida is frequently part of the normal flora of the nasopharynx and digestive tract of several wild and domestic animals. Although P. multocida can produce a variety of upper and lower respiratory tract infections, only four previous cases of tonsillitis caused by this organism have been reported. We present a case of pasteurella tonsillitis in a 30-year-old female who was exposed through her cat, which manifested upper respiratory symptoms.     

Pasteurella multocida meningitis in a two-day old neonate

A normal full-term baby boy, born by vaginal delivery, became ill on day 2 with fever and failure to feed. CSF examination revealed 260 x 10(6)/l leucocytes, mainly mononuclears, protein 2 g/l and glucose zero. Pasteurella multocida was isolated in pure culture from the baby's CSF, blood and umbilicus and from the mother's vagina. The baby was treated with i.v. penicillin for 7 weeks. Progress was complicated by mild hydrocephalus, which resolved, and prolonged low grade fever. Recovery was complete, without neurological sequelae. This case illustrates that P. multocida can infect the vagina where it presents a hazard to a newborn infant delivered vaginally. Early diagnosis is critical, intravenous high dose penicillin being the treatment of choice.     

Intrastrain variation of lipopolysaccharide of Pasteurella multocida in turkeys

The nuclear enzyme DNA topoisomerase II (topo II) is the target of important antitumor agents such as etoposide. Recent work has classified topo II targeting drugs into either topo II poisons that act by stabilizing enzyme-DNA cleavable complexes leading to DNA breaks, or topo II catalytic inhibitors that act at stages in the catalytic cycle of the enzyme where both DNA strands are intact and, therefore, do not cause DNA breaks. Accordingly, catalytic inhibitors are known to abrogate DNA damage and cytotoxicity caused by topo II poisons. In this commentary, we have focused on the possibilities of enabling high-dose therapy with the topo II poison etoposide by protection of normal tissue with catalytic inhibitors, analogous to folinic acid rescue in high-dose methotrexate treatment. Thus, we have demonstrated recently that (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF-187) enabled a 3- to 4-fold dose escalation of etoposide in mice. Two high-dose etoposide models are described, namely use of the weak base chloroquine in tumors with acidic extracellular pH and targeting of CNS tumors with protection of normal tissue by the bisdioxopiperazine ICRF-187. In conclusion, high supralethal doses of topo II poisons in combination with catalytic inhibitor protection form a new strategy to improve the antitumor selectivity of etoposide and other topo II poisons. Such an approach may be used to overcome problems with drug resistance and drug penetration.     

Three cases of Pasteurella multocida infection in the respiratory tract

Pasteurella multocida (P. multocida) is well recognized as "normal flora" in the upper respiratory tract of cats, dogs and other animals. Recently, various infections due to P. multocida in human have been noted as pulmonary infections in the patients with chronic pulmonary diseases as well as skin abscesses or septicemia after an animal bite or scratch. We report here three cases of respiratory tract infections caused by P. multocida. The first two patients had acute exacerbation of bronchiectasis caused by P. multocida and the other patients with pulmonary emphysema developed pneumonia. These three patients improved by antibiotic therapy. In Japan, P. multocida respiratory tract infection is rare, but it may become more common in the future. Therefore, it seems to be important to take this pathogen into consideration in the management of chronic lung disease.     

Identification of a novel adhesin-like glycoprotein from Mycoplasma hyopneumoniae

A Ca2+-activated (ICl,Ca) and a swelling-activated anion current (ICl,vol) were investigated in Ehrlich ascites tumor cells using the whole cell patch clamp technique. Large, outwardly rectifying currents were activated by an increase in the free intracellular calcium concentration ([Ca2+]i), or by hypotonic exposure of the cells, respectively. The reversal potential of both currents was dependent on the extracellular Cl- concentration. ICl,Ca current density increased with increasing [Ca2+]i, and this current was abolished by lowering [Ca2+]i to <1 nm using 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA). In contrast, activation of ICl,vol did not require an increase in [Ca2+]i. The kinetics of ICl,Ca and ICl,vol were different: at depolarized potentials, ICl,Ca as activated in a [Ca2+]i- and voltage-dependent manner, while at hyperpolarized potentials, the current was deactivated. In contrast, ICl,vol exhibited time- and voltage-dependent deactivation at depolarized potentials and reactivation at hyperpolarized potentials. The deactivation of ICl, vol was dependent on the extracellular Mg2+ concentration. The anion permeability sequence for both currents was I- > Cl- > gluconate. ICl,Ca was inhibited by niflumic acid (100 micron), 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, 100 micron) and 4, 4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS, 100 micron), niflumic acid being the most potent inhibitor. In contrast, ICl,vol was unaffected by niflumic acid (100 micron), but abolished by tamoxifen (10 micron). Thus, in Ehrlich cells, separate chloride currents, ICl,Ca and ICl,vol, are activated by an increase in [Ca2+]i and by cell swelling, respectively.     

Mycoplasma hyopneumoniae potentiation of porcine reproductive and respiratory syndrome virus-induced pneumonia

An experimental model that demonstrates a mycoplasma species acting to potentiate a viral pneumonia was developed. Mycoplasma hyopneumoniae, which produces a chronic, lymphohistiocytic bronchopneumonia in pigs, was found to potentiate the severity and the duration of a virus-induced pneumonia in pigs. Pigs were inoculated with M. hyopneumoniae 21 days prior to, simultaneously with, or 10 days after inoculation with porcine reproductive and respiratory syndrome virus (PRRSV), which induces an acute interstitial pneumonia in pigs. PRRSV-induced clinical respiratory disease and macroscopic and microscopic pneumonic lesions were more severe and persistent in M. hyopneumoniae-infected pigs. At 28 or 38 days after PRRSV inoculation, M. hyopneumoniae-infected pigs still exhibited lesions typical of PRRSV-induced pneumonia, whereas the lungs of pigs which had received only PRRSV were essentially normal. On the basis of macroscopic lung lesions, it appears that PRRSV infection did not influence the severity of M. hyopneumoniae infection, although microscopic lesions typical of M. hyopneumoniae were more severe in PRRSV-infected pigs. These results indicate that M. hyopneumoniae infection potentiates PRRSV-induced disease and lesions. Most importantly, M. hyopneumoniae-infected pigs with minimal to nondetectable mycoplasmal pneumonia lesions manifested significantly increased PRRSV-induced pneumonia lesions compared to pigs infected with PRRSV only. This discovery is important with respect to the control of respiratory disease in pigs and has implications in elucidating the potential contribution of mycoplasmas in the pathogenesis of viral infections of other species, including humans.     

The capsule biosynthetic locus of Pasteurella multocida A:1

OBJECTIVES: The purpose of this study was to investigate the progression of autonomic dysfunction in patients with Duchenne-type progressive muscular dystrophy (DMD) over time by using heart rate variability. BACKGROUND: Although previous studies suggest the presence of autonomic dysfunction in patients with DMD, the precise cause is not known. On the other hand, it is well known that analysis of heart rate variability provides a useful, noninvasive means of quantifying autonomic activity. High frequency power is determined predominantly by the parasympathetic nervous system, whereas low frequency power is determined by both the parasympathetic and sympathetic nervous systems. METHODS AND RESULTS: Frequency and time domain analyses of heart rate variability during ambulatory electrocardiographic monitoring were performed in 17 patients with DMD over a 9-year period. At the time of entry, the mean patient age was 11 years and the mean Swinyard-Deaver stage was 4. In the first year, high frequency power was significantly lower and the ratio of low frequency to high frequency was significantly higher in patients with DMD than in the normal control subjects. These differences become significantly greater as the disease progressed. At the time of entry, low and high frequency powers increased at night in both groups. However, over time, high and low frequency powers at night tended to decrease. All of the time domain parameters were significantly lower in the patients with DMD at all time points compared with the normal control subjects. CONCLUSIONS: We concluded that DMD patients have either a decrease in parasympathetic activity, an increase in sympathetic activity, or both as their disease progresses.     

Effects of the major Pasteurella multocida porin on bovine neutrophils

OBJECTIVE: To evaluate in vitro effect of the major fraction of outer membrane proteins of Pasteurella multocida with porin-like activities on some biological functions of bovine neutrophils. ANIMALS: Neutrophils from 5 adult cattle. PROCEDURE: Variations in such biological processes as actin polymerization and chemotaxis and evaluation of hydrogen peroxide attributable to variable concentrations of P multocida were recorded and compared. Data were obtained, using the porin and lipopolysaccharide (LPS) isolated from a strain of P multocida cultivated in brain-heart infusion (BHI) broth. Various concentrations of porin and LPS were analyzed to evaluate changes in functional activation and microbicidal activity of bovine neutrophils. RESULTS: The 37.5-kd major polypeptide of the outer membrane of P multocida was isolated. Presence of this porin was significantly correlated with variations of some biological functions of bovine neutrophils. These immunocompetent cells had a concentration-dependent increase in actin polymerization and chemotactic activity. A concentration-dependent variation in the oxidative burst also was observed. CONCLUSIONS: The porins of gram-negative bacteria affect several biological functions of cells involved in the immune response as well as in inflammation. Significant correlation of results of in vitro experiments also was identified between porin and LPS effect. Pretreatment of bovine neutrophils with various concentrations of porin always caused a concentration-dependent increase in examined biological activities.     

Pasteurella multocida infection involving cranial air spaces in White Leghorn chickens

OBJECTIVE: We retrospectively reviewed five pathologically proven cases of diffuse cavernous hemangioma of the rectosigmoid colon to define the MR imaging features of this entity. CONCLUSION: Diffuse cavernous hemangioma of the rectosigmoid colon is revealed as rectosigmoid wall thickening with high signal intensity on T2-weighted MR images. Such wall thickening is associated with abnormal perirectal fat. The extent of bowel involvement and extrarectal locations are well shown on T2-weighted MR images.     

Adaptive acquisition of novobiocin resistance in Pasteurella multocida strains of avian origin

Naturally occurring strains of Pasteurella multocida are atypically susceptible to hydrophobic antibiotics such as novobiocin, despite their Gram-negative cell envelope ultrastructure. Four strains adaptively resistant to 1000 micrograms/ml of novobiocin were obtained by sequentially subculturing cell surface hydrophobic variants of avian origin in the presence of increasing antibiotic concentrations. Adaptive novobiocin resistance was accompanied in all cases by the concomitant acquisition of resistance to coumermycin, a hydrophobic antibiotic possessing the same mechanism of action, but not to the functionally disparate hydrophobic antibiotic rifamycin. The acquisition of resistance was not accompanied by alterations in the lipid composition of the cell envelope. Subsequent growth of adaptively resistant strains in the absence of novobiocin did not result in the restoration of susceptibility to either novobiocin or coumermycin. Acquisition of adaptive resistance in encapsulated parental strains resulted in an inability to synthesize capsular material and enhanced cell surface hydrophobicity; however, parental encapsulation and decreased cell surface hydrophobicity were restored upon removal of novobiocin. These data suggest that acquisition of adaptive resistance to novobiocin conferred in this manner is the result of a stable genetic event affecting the mechanistic target of both novobiocin and coumermycin rather than a physiological adaptation involving outer membrane impermeability.