- Parenteral Administration of Capsule Depolymerase EnvD Prevents Lethal Inhalation Anthrax Infection. [Journal Article]
- AAAntimicrob Agents Chemother 2015; 59(12):7687-92
- Left untreated, inhalation anthrax is usually fatal. Vegetative forms of Bacillus anthracis survive in blood and tissues during infection due to elaboration of a protective poly-γ-D-glutamic acid (PD…
Left untreated, inhalation anthrax is usually fatal. Vegetative forms of Bacillus anthracis survive in blood and tissues during infection due to elaboration of a protective poly-γ-D-glutamic acid (PDGA) capsule that permits uncontrolled bacterial growth in vivo, eventually leading to overwhelming bacillosis and death. As a measure to counter threats from multidrug-resistant strains, we are evaluating the prophylactic and therapeutic potential of the PDGA depolymerase EnvD, a stable and potent enzyme which rapidly and selectively removes the capsule from the surface of vegetative cells. Repeated intravenous administration of 10 mg/kg recombinant EnvD (rEnvD) to mice infected with lethal doses of B. anthracis Ames spores by inhalation prevented the emergence of symptoms of anthrax and death; all animals survived the 5-day treatment period, and 70% survived to the end of the 14-day observation period. In contrast to results in sham-treated animals, the lungs and spleen of rEnvD-dosed animals were free of gross pathological changes. We conclude that rEnvD has potential as an agent to prevent the emergence of inhalation anthrax in infected animals and is likely to be effective against drug-resistant forms of the pathogen.
- Research on tuberculosis: 75 years of IBIT contributions. [Historical Article]
- BJBraz J Infect Dis 2013 Mar-Apr; 17(2):205-10
- In 1937, the foundation year of the Brazilian Institute for Tuberculosis Research, three questions persisted in the researchers' mind: "What is the real value of BCG? How to solve the problem of the …
In 1937, the foundation year of the Brazilian Institute for Tuberculosis Research, three questions persisted in the researchers' mind: "What is the real value of BCG? How to solve the problem of the chest register of large communities? When will we have a specific drug for the treatment of tuberculosis?" Along with this line of thought, the author presents a list of the Institute's main contributions, by pointing out the following topics: different diagnoses between pulmonary tuberculosis and pulmonary schistosomiasis; innocuity of iodine salts in pulmonary tuberculosis; relative value of Weltmann and Takata-Ara's reactions, and of blood and lipase rates in bacillosis; the value of the bacteriologic diagnosis (method of precipitation, standardization of drug sensitivity tests; identification of non-pathogenetic germs not only in the sputum but also in gastric Broncho-Alveolar Lavage, playing an important role in the infection tropics; probable protective role of BCG in tuberculin positive individuals; increase in awareness of the value of tuberculin; comparative studies of several types of tuberculin; clinical and epidemiological importance of nontoxic drugs; tuberculin surveys in Salvador and Feira de Santana cities; proposed classification of clinical forms of pulmonary tuberculosis; increase in the value of selective miniature chest radiography; standardization of radiological shadows; and tests on the therapeutic value of the drugs. To SILVEIRA, IBIT'S contribution can be summarized in eight points: importance of bacteriology in the diagnosis and therapeutic procedures; increase in the value of tuberculin tests; selective miniature chest radiography; possibility of replacing the hospital by an ambulatory care center; BCG vaccination; wide and general indispensability of a well-done and well-balanced therapeutic scheme; simplified treatment; progressive shortening of the treatment program; no over optimism about the first victories in the bacilli therapy.
- Integration of pharmacokinetic and pharmacodynamic indices of marbofloxacin in turkeys. [Journal Article]
- AAAntimicrob Agents Chemother 2006; 50(11):3779-85
- Fluoroquinolones are extensively used in the treatment of systemic bacterial infections in poultry, including systemic Escherichia coli bacillosis, which is a common disease in turkey flocks. Marbofl…
Fluoroquinolones are extensively used in the treatment of systemic bacterial infections in poultry, including systemic Escherichia coli bacillosis, which is a common disease in turkey flocks. Marbofloxacin has been licensed for use in various mammalian species, but not as yet for turkeys, although its kinetic properties distinguish it from other fluoroquinolones. For example, the longer half-life of marbofloxacin in many animal species has been appreciated in veterinary practice. It is generally accepted that, for fluoroquinolones, the optimal dose should be estimated on the basis of the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the drug under consideration. Knowledge of these specific data for the target animal species allows the establishment of an integrated PK-PD model that is of high predictive value. In the present study, the antibacterial efficacy (PD indices) against a field isolate of Escherichia coli O78/K80 was investigated ex vivo following oral and intravenous administration of marbofloxacin to turkeys (breed BUT 9; six animals per group) at a dose of 2 mg/kg of body weight (BW). At the same time, the serum concentrations of marbofloxacin were measured at different time intervals by a standardized high-performance liquid chromatography method, allowing the calculation of the most relevant kinetic parameters (PK parameters). The in vitro serum inhibitory activity of marbofloxacin against the selected E. coli strain, O78/K80, was 0.5 mug/ml in the blood serum of turkeys, and the ratio of the maximum concentration of the drug in serum to the serum inhibitory activity was 1.34. The lowest ratio of the measured serum concentration multiplied by the incubation period of 24 h to the serum inhibitory activity required for bacterial elimination was lower than the ratio of the area under the serum concentration-time curve (AUC) to the serum inhibitory activity. These first results suggested that the recommended dose of 2 mg/kg BW of marbofloxacin is sufficient to achieve a therapeutic effect in diseased animals. However, considering the risk of resistance induction, the applied dose should be equal to an AUC/MIC of >125, the generally recommended dose for all fluoroquinolones. According to the PK-PD results presented here, a dose of 3.0 to 12.0 mg/kg BW per day would be needed to meet this criterion. In conclusion, the results of the present study provide the rationale for an optimal dose regimen for marbofloxacin in turkeys and hence should form the basis for dose selection in forthcoming clinical trials.
- Perspectives on Shiga-like Toxin Infections in Argentina †. [Journal Article]
- JFJ Food Prot 1997; 60(11):1458-1462
- Argentina has the highest frequency of hemolytic uremic syndrome (HUS) in the world (300 cases/year). The risk of HUS in children from 6 to 48 months old is approximately 22/100,000 in Buenos Aires. …
Argentina has the highest frequency of hemolytic uremic syndrome (HUS) in the world (300 cases/year). The risk of HUS in children from 6 to 48 months old is approximately 22/100,000 in Buenos Aires. In Argentina, HUS is the most frequent cause of acute renal damage and the second cause of chronic renal injury in children. We have shown that during the spring/summer season, the incidence of Shiga-like toxin (SLT)-associated bloody diarrhea in children less than 5 years old is 30 to 39%. The risk of HUS in SLT-associated bloody diarrhea is about 4 to 5%; 14% of children with SLT diarrhea developed incomplete HUS. Household contacts of children with HUS are commonly colonized with SLT-producing Escherichia coli (39%), and seroconversion occurs in 42% of these. No evidence of free fecal SLTs was observed in healthy children. In Argentina E. coli serotype O157:H7 has been associated with only 2 to 18% of HUS patients and in 4.5 to 7% of children with bloody diarrhea. Other serotypes were also recognized. About 20% of Argentine children start to eat meat at 5 months old, and 80% of them have meat in their diets at least three times a week. Eighty percent of the meat consumed is undercooked. Few data about the incidence of SLT-producing E. coli in cows in our country are available. E. coli O157:H7 was isolated in only 7.7% of calves aged 1 to 3 weeks with E. coli bacillosis from different farms in Argentina. Preliminary data show that SLT-producing E. coli were also present in stools from healthy animals and in fresh retail ground beef, determined by polymerase chain reaction.
- [Biochemical diagnosis of the presence of poisoning by Bacillus thuringiensis serotype "H3a,3b" in two lepidopterans]. [Journal Article]
- CJCan J Microbiol 1989; 35(4):444-9
- A detailed biochemical analysis has shown that during larval development on artificial medium, the amounts of K+, Na+, and Ca2+ in the hemolymph of healthy Choristoneura fumiferana varied from 85 to …
A detailed biochemical analysis has shown that during larval development on artificial medium, the amounts of K+, Na+, and Ca2+ in the hemolymph of healthy Choristoneura fumiferana varied from 85 to 110 mg/100 mL, 29 to 33 mg/100 mL, and 4.8 to 7.3 mg/100 mL, respectively. Similar results were obtained with Malacosoma disstria. Intoxication by Bacillus thuringiensis "H3a,3b" (B. t.) considerably modified the amounts of the cations. Thus, after 4 h, the quantity of K+ in M. disstria increased from 99 to 229 mg/100 mL and Na+ from 26.5 to 50.3 mg/100 mL while that of Ca2+ decreased from 5.8 to 1.2 mg/100 mL. Similar results were observed with C. fumiferana, but these variations occurred after 2 to 4 days of B. t. intoxication. The variations detected during the bacillosis, with respect to the cationic composition of the insect hemolymph, are rapidly detectable, well before light microscope observation can confirm the presence of this intoxication. Aspartate aminotransferase, alanine aminotransferase, alpha-hydroxybutyrate dehydrogenase, and isocitrate dehydrogenase activity fluctuated very slightly in the hemolymph of either healthy or bacillosed larvae of the two insects under study. These results suggest that it is possible to diagnose biochemically the presence of a B. t. intoxication in lepidopteran forest pests following treatments by this biological insecticide for their control.
- Coli-bacillosis in chicks in Saudi Arabia. [Journal Article]
- TATrop Anim Health Prod 1980; 12(1):15-6
- [Pathology and pathogenesis of coli dysentery and coli diarrhea in suckling piglets. 2. Studies on the experimental induction of disease through the intragastric administration of coli-enterotoxin]. [Journal Article]
- AEArch Exp Veterinarmed 1976; 30(5):709-25
- Fractionated intragastric application of a crude enterotoxin of Escherichia coli O 149:K91 (B) K88 (L) was part of experimental intoxication of 88 nursed piglets, aged between one and three days. The…
Fractionated intragastric application of a crude enterotoxin of Escherichia coli O 149:K91 (B) K88 (L) was part of experimental intoxication of 88 nursed piglets, aged between one and three days. The experiment was based on culture filtrate supernatant which had produced positive enterotoxic effect in an intestinal ligature test of swine and rabbit. The results were compared with 50 controls, piglets of the same age with intragastric administration of physiological salt solution. The experiment gave pronounced aquaeous diarrhoea (100 per cent) accoumpanied by exsiccosis, weight loss, rough hair, greyish discoloration of the skin, and other manifestations. The mortality was nine per cent. The clinical and pathomorphological picture of the enterotoxin syndrome was in close agreement with spontaneous coli-bacillosis of nursed piglets. Enterotoxin-caused diarrhoea occurred, with the gastro-intestinal mucous membrane remaining morphologically intact. This intoxication method has proved to be a safe model for experimental induction of coli-bacillosis, and it is likely to be suitable for vaccine testing. It can be used, as well, as a simple qualitative enterotoxin test. Additional issues relating to the pathology and pathogenesis of the coli-enterotoxin syndrome of piglets are discussed.
- [Pathology and pathogenesis of coli dysentery and coli diarrhea in suckling piglets. 1. Studies on the pathomorphology of the gastrointestinal tract in coli dysentery as well as coli diarrhea in the suckling piglet]. [Journal Article]
- AEArch Exp Veterinarmed 1976; 30(5):687-708
- The following findings were obtained from histomorphological examination of 45 piglets with coli-bacillosis (with serotypical Escherichia coli detected) and ten piglets with coli-diarrhoea (with non-…
The following findings were obtained from histomorphological examination of 45 piglets with coli-bacillosis (with serotypical Escherichia coli detected) and ten piglets with coli-diarrhoea (with non-serotypical E. coli detected): Diarrhoea accompanying either disease was not attributable to catarrhal or haemorrhagic gastro-enteritis. The mucous membrane of the gastro-insestinal tract remained histomorphologically intact in either disease. No change was recorded particularly from villous or surface epithelia and glandular epithelium, and the villous structure was not basically altered. Different degrees of hyper aemia of the gastro-intestinal mucous membrane and moderate oedematisation of the villous stroma were irregular findings. Adhesion of enteropathogenic E. coli to mucous membrane surface was observed but rarely and did not exhibit any visible relationship with the incidence in E. coli of L-antigen K88. In coli-bacillosis and coli-diarrhoea both the diarrhoea and morphological situation of the gastro-bacillosis tract were in conformity with the cholera-type "intestinal noninflammatory secretory diarrhoea" as caused by enterotoxins. Other issues relating to pathology and diagnosis are also discussed.
- [Problems of resistance (author's transl)]. [Journal Article]
- TDTijdschr Diergeneeskd 1975 Mar 01; 100(5):270-3
- The results of sensitivity tests performed during the period from 1970 up to 1973 inclusive are compared with those obtained in pervious years. This showed that resistance to penicillin had increased…
The results of sensitivity tests performed during the period from 1970 up to 1973 inclusive are compared with those obtained in pervious years. This showed that resistance to penicillin had increased in staphylococci causing bovine mastitis. During each single year, however, there was a decrease. S. typhimurium isolated from cattle showed increased resistance to chloramphenicol, neomycin and ampicillin; S. dublin showed an increase in resistance to chloramphenicol. E. coli isolated from calves with coli-bacillosis had become less sensitive to all the antibiotics studied. Pathogenic strains of E. coli isolated from swine also showed increased resistance, among others to tetracycline, neomycin and ampicillin. The danger constituted by this development and the factthat comparison with the results obtained by other presents difficulties in some cases are stressed.
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- Enteropathogenicity of Escherichia coli. I. Evaluation of mouse intestinal loops. [Journal Article]
- IIInfect Immun 1971; 4(4):473-8
- A ligated mouse intestinal loop assay has been introduced to evaluate the enteropathogenicity of strains of Escherichia coli. When inoculated as whole cultures, 19 (34%) of 55 strains isolated from d…
A ligated mouse intestinal loop assay has been introduced to evaluate the enteropathogenicity of strains of Escherichia coli. When inoculated as whole cultures, 19 (34%) of 55 strains isolated from diarrheic infants, each of 4 strains associated with diarrhea in human adults, and 5 of 7 strains associated with porcine coli bacillosis were found capable of causing fluid accumulation in this model. In contrast, only 1 of 28 strains isolated from normal individuals was positive in this test. Sterile concentrated filtrates of positive strains cultivated in Brain Heart Infusion broth or syncase broth were also positive, whereas filtrates of negative strains did not cause fluid accumulation. All of the strains associated with diarrhea in human adults and 16 of the 19 positive strains from diarrheic children were also found capable of causing hemagglutination of chicken erythrocytes in a slide test used to evaluate the "adhesiveness" of the bacteria, a property which may enable them to stick in the small bowel and avoid the normally efficient peristaltic clearance mechanism. Few of the nonenteropathogenic strains were positive in this test. The slide hemagglutination test may be a useful, rapid means of screening potentially enteropathic E. coli strains and merits further evaluation and study. Although not ideal, the mouse intestinal loop model offers some advantages over the rabbit ileal loop assay.