Acute Systemic Infection Research Articles

Hypothalamic mechanisms of pain modulatory actions of cytokines and prostaglandin E2.

A decrease and subsequent increase in nociceptive threshold in the whole body are clinical symptoms frequently observed during the course of acute systemic infection. These biphasic changes in nociceptive reactivity are brought about by central signal substances induced by peripheral inflammatory messages. Systemic administration of lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta), an experimental model of acute infection, may mimic the biphasic changes in nociception, hyperalgesia at small doses of LPS, and IL-1 beta and analgesia at larger doses. Our behavioral and electrophysiological studies have revealed that IL-1 beta in the brain induces hyperalgesia through the actions of prostaglandin E2 (PGE2) on EP3 receptors in the preoptic area and its neighboring basal forebrain, whereas the IL-1 beta-induced analgesia is produced by the actions of PGE2 on EP1 receptors in the ventromedial hypothalamus. An intravenous injection of LPS (10-100 micrograms/kg) produced hyperalgesia only during the period before fever develops and was abolished by microinjection of NS-398 (an inhibitor of cyclooxygenase 2) into the preoptic area, but not into the other areas in the hypothalamus. The hyperalgesia induced by the cytokines PGE2 and LPS may explain the systemic hyperalgesia clinically observed in the early phase of infectious diseases, which probably warns the organisms of infection before the full development of sickness symptoms. The switching of nociception from hyperalgesia to analgesia accompanied by sickness symptoms may reflect changes in the host's strategy for fighting microbial invasion as the disease progresses.

Immunity against Escherichia coli Infection in Chickens Assessed by Viable Bacterial Counts in Internal Organs

Septicemic strains of Escherichia coli cause systemic infection in chickens after the intra-airsac inoculation. We have investigated whether levels of immunity can be determined by the viable organism count in the internal organs of infected birds. The intra-airsac inoculation of O1:K1 strain caused acute systemic infection in 6 hr. The viable count was highest in the lung followed by the liver, spleen, and blood. The count was significantly (P < 0.05) lower in the liver or spleen of vaccinated birds at 6, 12, or 24 hr after inoculation than in controls. Vaccines containing various adjuvants were tested in this system, and three oil-based adjuvants demonstrated significant (P < 0.05) immunity, whereas an alum-precipitated vaccine or one without an adjuvant failed to do so compared with nonvaccinated controls. An oil-adjuvanted vaccine showed some deterioration in its immunogenicity after prolonged storage or heating at 100 C. The acute phase response induced by intravenous injection of killed O1: K1 cells or lipopolysaccharide purified from Salmonella typhimurium in aqueous suspension induced significant immunity against the E. coli infection. These results indicate that the method referred to as "in vivo viable count method" produces quantitative results in a reproducible manner and suggest that it may be used as an alternative method to mortality measurement.

Role of the individual interferon systems and specific immunity in mice in controlling systemic dissemination of attenuated pseudorabies virus infection.

The importance of each of the two interferon (IFN) systems in impeding herpesvirus replication and in stimulating virus-specific lymphocytes to control an acute systemic infection is not completely understood. To further our knowledge, pseudorabies virus, attenuated by deletion of the glycoprotein E gene to impair its neurovirulence and by deletion of the thymidine kinase gene (gE-TK-PRV), was used to infect wild-type 129Sv/Ev and congenic mice with immune system-associated genetic deficiencies. Mice with mature B and T lymphocytes but lacking either one or both functional receptors for members of each of the two IFN families were infected with gE-TK-PRV. At 3 and 7 but not 14 days after infection, replicating gE-TK-PRV could be isolated only from livers or spleens of mice lacking the receptors for both IFN families, and these mice survived the infection. Therefore, functional IFN receptors were not required to induce a protective immune response against an acute infection with gE-TK-PRV. Furthermore, PRV-specific antibodies of all immunoglobulin G isotypes were produced in these mice. Mice without mature B and T lymphocytes and lacking either one or both functional receptors for members of each of the two IFN families were also infected with gE-TK-PRV. Three days after infection, replicating virus could be isolated only from mice lacking both mature B and T lymphocytes and functional IFN receptors, and these mice were not able to clear the virus. We present evidence that mice with an intact gamma IFN system but without mature B and T cells were able to prevent systemic dissemination of gE-TK-PRV.

Bacteriological activity of trovafloxacin, a new quinolone, against respiratory tract pathogens.

The use of established fluoroquinolones, such as ciprofloxacin and ofloxacin, as empirical therapy for the treatment of moderate-to-severe respiratory tract infections is limited by their poor activity against gram-positive and atypical pathogens. Data from in vitro susceptibility studies and in vivo animal protection models suggest that the new fluoroquinolone, trovafloxacin, compared with ciprofloxacin and ofloxacin offers equivalent activity against gram-negative pathogens and improved activity against gram-positive pathogens. In particular, susceptibility data indicate that trovafloxacin is at least 16-fold more potent than either ciprofloxacin or ofloxacin against penicillin-susceptible and penicillin-resistant strains of Streptococcus pneumoniae. Other susceptible pathogens include Streptococcus pyogenes, vancomycin-susceptible Enterococcus faecalis and the atypical respiratory pathogens Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae. In vivo studies involving models of protection against acute systemic infection and pneumococcal pneumonia in mice, and Legionnaires' disease in guinea pigs, indicate that the antibacterial spectrum observed for trovafloxacin in vitro extends to the in vivo setting. Together, these findings suggest that trovafloxacin may offer clinical efficacy against respiratory pathogens superior to that of ciprofloxacin and of ofloxacin, and may find a useful role as empiric therapy in both the community and hospital setting.

Mucosally transmitted feline immunodeficiency virus induces a CD8+ antiviral response that correlates with reduction of cell-associated virus.

Intravaginal inoculation of cats with feline immunodeficiency virus (FIV) results in acute systemic infection accompanied by a strong CD8+ immune response that inhibits viral replication. CD8+ anti-FIV activity, revealed by increased FIV replication in peripheral blood mononuclear cells (PBMC) depleted of CD8+ lymphocytes, was detected by 6 weeks after inoculation and correlated with reduced PBMC-associated virus at 12, 16, and 32 weeks after inoculation. Some cats with strong CD8+ anti-FIV activity during acute infection did not seroconvert and yielded no evidence of FIV infection at later times. These data suggest that CD8+ immunity may play a major role in eliminating virus during primary transmucosal FIV infection and may down-regulate viral replication during asymptomatic infection.

Intraocular Pressure Changes in Nephropathia Epidemica: A Prospective Study of 37 Patients with Acute Systemic Puumala Virus Infection

Background: Nephropathia epidemica is a zoonose in the group of hemorrhagic fevers with renal syndrome and is caused by Puumala virus in Hantavirusgenus. The purpose of this study is to find out how the intraocular pressure (IOP) is affected by the acute phase of this disease and how it relates to the previous case reports on angle-closure glaucoma attacks.Patients and Methods: The prospective study documents IOP and anterior chamber depth measurements in 37 patients during the winter epidemic of nephropathia epidemica from 1992 to 1.993. Ocular examinations were performed during the acute systemic infection and after clinical recovery.Results: The IOP was lower and the anterior chamber shallower in the acute phase than after the clinical recovery of nephropathic epidemica. The mean differences in IOP were 1.8 mmHg in the right eye and 1.9 mmHg in the left (P < 0.001) and the mean differences in the anterior chamber depth were 0.22 mm in the right eye and 0.20 mm in the left (P < 0.001). No acute angle-closure attacks with highly elevated IOP were encountered in this study. The mean IOP did not rise higher than 14.3 mmHg in both eyes after the clinical recovery of systemic infection.Conclusion: In contradistinction to earlier assumptions, Puumala virus infection decreases the IOP. Shallowing of anterior chamber and narrowing of the anterior chamber angle in the acute phase of nephropathia epidemica did not lead to angle-closure attacks in this series.

A Superantigen as Virulence Factor in an Acute Bacterial Infection

This study addresses the role of a bacterial superantigen as a potential virulence factor during an acute systemic infection. BALB/c mice were intravenously infected with a recombinant Staphylococcus aureus strain capable of producing plasmid-encoded staphylococcal enterotoxin B (SEB) or with the SEB plasmid-deficient parental strain. Infection with SEB-producing bacteria resulted in an initial expansion and subsequent decrease of circulating V beta 8+ T lymphocytes. This numeric decrease was accompanied by a SEB-specific state of hyporesponsiveness of splenic T cells. In parallel with SEB-triggered unresponsiveness of a large proportion of T lymphocytes, a weakening of the overall T cell responsiveness towards the invading bacteria was found. Furthermore, the production of SEB altered the kinetics of bacterial clearance: Animals infected with the SEB-producing variant showed a significantly elevated bacterial burden and could less efficiently clear the bacteria. However, the overall effect of SEB production on the course of bacterial infection was surprisingly weak, suggesting that the superantigen was only a minor virulence factor for the bacterium.

Anemia of Acute Focal Infection in Children in the Area of Riyadh

Chronic or acute systemic bacterial infection is usually associated with anemia. This study shows that anemia can also be associated with acute focal infections which are usually treated in outpati...

Vaccine‐associated Canine Distemper Infection in a Litter of African Hunting Dogs (Lycaon pictus)

Four, 57 days old, African hunting dog puppies (Lycaon pictus) from one litter died within three weeks following vaccination with modified-live canine distemper virus (CDV) and killed canine adenovirus type 1, canine parvovirus and Leptospira icterohemorrhagiae and canicola. 18 days post vaccination, the animals developed neurologic disease characterized by episodes of grand mal seizures and circling. Macroscopic, histological and immunohistochemical studies revealed acute systemic CDV infection with acute encephalopathy. Virus isolation attempts using primary dog kidney cells, lung macrophages and Vero cells were negative. Therefore, the question whether the infection was the result of vaccination or natural infection remains open. The benefits and risks regarding the use of modified-live CDV vaccines and killed canine distemper vaccines in exotic carnivores are briefly discussed.

Contribution of granulocytes and monocytes to resistance against experimental disseminated Candida albicans infection.

The aim of the present study was to investigate the contribution of granulocytes and monocytes to resistance against an acute systemic candidal infection in mice. To this end granulocytopenia and monocytopenia were induced by irradiation or treatment with cyclophosphamide, and monocytopenia was obtained by treatment with VP-16. After intravenous injection of 1 X 10(4) Candida albicans into mice irradiated with 8 GY, the number of Candida albicans cultured from the kidneys, expressed as the geometric mean of the number of CFU/g tissue, was 5.4 X 10(4), 7.1 X 10(6) and 5.8 X 10(7) on days 1, 3 and 5 of infection respectively (p less than 0.001 compared to normal mice). The number of Candida albicans cultured from the liver and spleen was also significantly higher for irradiated animals than for normal mice (p less than 0.001). For cyclophosphamide-treated mice the number of organisms in the kidney (1.7 X 10(4) CFU/g on day 1, 1.9 X 10(6) on day 3 and 3.8 X 10(6) on day 5 of infection) and spleen was significantly higher (p at least less than 0.02) than for normal mice after injection of 1 X 10(3) Candida albicans. Monocytopenia induced by VP-16 did not result in an increase in the number of Candida albicans cultured from the kidney or spleen after infection. From these studies it is concluded that granulocytes and not monocytes or exudate macrophages play an important role in resistance against Candida albicans during the first five days of a systemic infection.

A Non-capsid Protein Associated with Unencapsidated Virus RNA in Barley Infected with Barley Stripe Mosaic Virus

Summary Barley tissue with an acute systemic infection of barley stripe mosaic virus contained a large amount of unencapsidated virus RNA which was stable in extracts made in ribosome isolation buffer. The virus RNA in ribosome preparations sedimented in a broad band at 80S to 100S in sucrose gradients, which is less than the virion sedimentation rate of 180S to 200S. A protein of apparent M r 60000, which sedimented with the virus RNA, was present in ribosome extracts from infected plants but absent from those from uninfected plants. The protein is probably a virus protein because its apparent molecular weight varied slightly with the strain of virus. The structure containing the M r 60000 protein did not sediment in sucrose gradients in a compact zone as would be expected for a particle of uniform size. The M r 60000 protein was present at a concentration equal to or slightly higher (up to 400 µg/g leaf tissue) than the unencapsidated virus RNA (up to 300 µg/g leaf tissue). Sedimentation results support the conclusion that the virus RNA and the M r 60000 protein were combined in polydispersed nucleoprotein particles which may or may not have been attached to ribosomes or ribosome subunits. The M r 60000 protein was not serologically related to the capsid protein. Gold-labelled antibodies to the M r 60000 protein stained the cytoplasm in thin sections of infected cells but not that of uninfected cells. However, no distinct immunogold-labelled particle could be identified as the presumed nucleoprotein.

Enhancement of resistance to Escherichia coli infection in mice by dihydroheptaprenol, a synthetic polyprenol derivative.

The effect of a chemically synthesized polyprenol derivative, dihydroheptaprenol (DHP), on the nonspecific resistance of mice to infection with Escherichia coli was investigated. Mice that had been injected intramuscularly with 100 mg of DHP per kg of body weight, prepared as a microemulsion with lecithin, 1 to 4 days before infection showed enhanced resistance to subcutaneous (s.c.) infection with E. coli. When DHP-injected mice were inoculated s.c. with 3 X 10(8) E. coli, which induces fatal acute systemic infection in normal mice, propagation of bacteria in the blood, liver, and spleen was significantly inhibited. Enhanced resistance of athymic (nude) mice to E. coli infection was also induced by DHP. DHP markedly stimulated the generation of peripheral blood neutrophils, significantly enhanced clearance of E. coli from the bloodstream, and activated neutrophils and peritoneal macrophages for H2O2 generation. DHP restored the resistance to E. coli infection in cyclophosphamide-treated mice over the normal level. Furthermore, DHP shortened the period of the recovery of neutrophils and also enhanced clearance of E. coli from the bloodstream in cyclophosphamide-treated mice. DHP was nontoxic for mice and rats (400 mg/kg intramuscularly and 800 mg/kg s.c.) and nonpyrogenic at a dose of 30 mg/kg when administered intravenously to rabbits. These results suggest that the mechanism of action of DHP for enhancing resistance in mice may be, at least in part, its ability to stimulate the generation of potent neutrophils and to activate macrophages in the reticuloendothelial system.

Appraisal of the suitability of a disease model of acute salmonellosis in calves for chemotherapeutic studies

When young calves were dosed orally with 10(10) organisms of a culture of Salmonella dublin, typical symptoms of acute salmonellosis followed with a death rate of 86 per cent. Peak mortality occurred six days after infection. As a result of a statistical appraisal of the consistency of mortality in groups of untreated calves a model is proposed for the therapeutic evaluation of antibacterial compounds, which compares the number of survivors in groups of seven or eight calves with a minimum of four needed for significant indication of efficacy. Bacteriological and pathological investigations showed that the experimental disease was initially an acute systemic infection followed by severe enteritis. Measurements of plasma concentrations of enzymes and other constituents did not achieve the desired objective of establishing a method of quantitative evaluation of the clinical status of individual animals, although some changes occurred which were consistent with the pathology of the disease and suggested possible mechanisms by which jaundice occurred.

Persistent Viral Infections as Models for Research in Virus Chemotherapy

Publisher SummaryThe acute systemic virus infection is commonly used as an experimental model in chemotherapy research despite the fact that the chance for an effective chemotherapy of acute virus infections is small. In most acute infections, virus multiplication is well advanced before the disease is expressed and treatment will, in many cases, come too late. However, control by chemotherapy might be promising for persistent virus infections, where, owing to the slow progression of the disease, sufficient time for treatment is available. Although there are various ways in which viruses can persist in their hosts, comparative studies in vitro and in vivo reveal common features that shall be briefly reviewed. Animal models with persistent virus infections are usually difficult to experiment with because of the varying length of the incubation period brought about by the complex relationship among virus replication, immune reactions, and disease.

Altered absorption and regulation of iron in chicks with acute Salmonella gallinarum infection

Chicks aged 15 days were infected orally with Salmonella gallinarum. During the six-day period immediately following infection the absorption of 59Fe from the gut fell progressively to be eventually about half that in noninfected chicks. This reduced uptake was accompanied by a shift in the distribution of the 59Fe absorbed, more occurring in the spleen and less in the liver and blood. During the eight-day period that immediately followed infection in another experiment, serum iron concentration on day 4 and 6 in infected chicks was significantly lower than that in noninfected birds. In the infected chicks also the transferrin saturation was significantly lower and the unsaturated ironbinding capacity higher, on days 4, 6, and 8 after infection. These findings show that there is a major disturbance in iron regulation in acute systemic bacterial infection in the immature fowl and suggest that the mild anaemia which occurs in chicks during acute S gallinarum infection a shortage of iron in the body.

Murine gastrointestinal tract as a portal of entry in experimental Pseudomonas aeruginosa infections.

Peroral administration of viable Pseudomonas aeruginosa into the stomach of mice resulted in an acute systemic infection, with death occurring within 72 h. One strain, ATCC 19660, a non-encapsulated form of P. aeruginosa, had a median lethal dose of 5.3 X 10(6) colony-forming units, whereas two encapsulated strains, ATCC 17933 and 17934, had median lethal dose values of 5.0 x 10(7) and 5.6 x 10(7) colony-forming units, respectively. Each strain required fewer organisms to establish a lethal infection via the stomach than by intravenous or intraperitoneal routes. The non-encapsulated strain, ATCC 19660, did not cause any diarrhea in the infected animals, whereas the two encapsulated strains, although less virulent, caused diarrhea when administered perorally. No signs of necrosis were noted within the gastrointestinal tract; however, hematogenous spread of the organism resulted in a vasculitis associated with the pulmonary vessels and bacterial invasion of the renal tissues. Treatment of animals with antineoplastic drugs 24 h before or simultaneously with peroral challenge resulted in an increased susceptibility to infection.

Staphylococcal infection and toxoplasmosis in a young harbor seal.

Generalized subcutaneous abscessation followed by acute systemic infection occurred in a young male harbor seal (Phoca vitulina richardii). Clinically, infection was manifested by malaise, progressive weight loss, labored respiration, intermittant vomitation, and mucohemorrhagic diarrhea. A coagulase-positive Staphylococcus aureus was isolated from the subcutaneous abscesses, and specimens of lung, liver, small intestine, and kidney. Microscopically, cysts and trophozoites of Toxoplasma gondii were found in, or adjacent to, foci of necrosis present throughout the liver parenchyma.

Changes in plasma protein-bound carbohydrates and glycoprotein patterns during infection, inflammation and starvation.

SummaryLocalized inflammation and acute systemic infection in the rat produced similar alterations in plasma protein-bound carbohydrates and glycoproteins, characterized by: (a) increased total plasma protein-bound carbohydrates, including protein-bound hexose, hexosamine and sialic acid; (b) increased α1, α2 and β glycoglobulin fractions. Moreover, these changes occur despite severe starvation; therefore, they appear to be independent of nutritional intake. Similar changes were produced when an extract from stimulated leukocytes was administered to normal rats. This suggests that changes in protein-bound carbohydrates and glycoproteins during inflammation and infection may have been mediated by an endogenous humoral factor(s).

Carbenicillin indanyl sodium, an orally active derivative of carbenicillin.

Carbenicillin indanyl sodium, an orally active derivative of carbenicillin, is active against a broad spectrum of bacterial species. Although the ester has in vitro antimicrobial activity per se when evaluated in Brain Heart Infusion broth, the in vivo antibacterial activity seen in mice and rats reflects primarily the efficient hydrolysis of the ester to carbenicillin. With an acute systemic infection in mice as a test system, orally administered carbenicillin indanyl sodium protected mice against lethal infections produced by Escherichia coli, Salmonella choleraesuis, Pasteurella multocida, Proteus vulgaris, Staphylococcus aureus, and Streptococcus pyogenes. The dose that protected 50% of the animals against each of these infections was comparable to that of parenteral carbenicillin. Against experimental urinary-tract disease in rats produced by E. coli, P. vulgaris, and Pseudomonas aeruginosa, it was again observed that carbenicillin indanyl sodium provided activity comparable to that of parenterally administered carbenicillin.

Parotitis after diuretic therapy.

FEW diseases illustrate the prophylactic benefit of current fluid-balance concepts as well as that of acute suppurative parotitis. As recently as ten years ago, suppurative parotitis occurred by and large as a complication either of an acute systemic infection or of the postoperative state1 — hence the name "surgical parotitis." That the infection for the most part arises from a retrograde invasion of the gland by oral bacteria has been supported by bacteriologic and other studies over the past fifty years,2 , 3 the most necessary prerequisite appearing to consist of dehydration and a reduced flow of saliva from the gland. It . . .