Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009450 (infectious diseases)
 83,438 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infectious disease processes follow the initial steps of adherence of the organism to host tissues and subsequent colonization of the target tissues that can occur through specific adhesion-receptor systems. Bordetella pertussis, the human pathogen that causes whooping cough, has evolved a genetically controlled system whereby adhesins are expressed when they enter the human host. Two adhesins, filamentous hemagglutinin (FHA) and pertactin, mediate the adherence of the bacterium to eukaryotic cells through varied attachment mechanisms, including lectin-like binding sites that interact with sulfated sugars on cell surface glycoconjugates and the ARG-GLY-ASP binding sequence, which recognizes a family of integrins found on the cell surface. The differential expression of relevant receptors by various eukaryotic cells likely plays a role in the pathogenesis and immune response to the bacterium by the host, directing the organism to specific cell types and to specific tissue sites. Substantial evidence exists that the B. pertussis adhesins, FHA and pertactin, elicit immune responses that are protective in animal models for the disease, including serum antibody production and local immune responses in the respiratory tract following nasal administration of encapsulated antigens. Both of these adhesins are components of new acellular pertussis vaccines that have proven safe and highly effective for prevention of serious disease in infants.
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PMID:Pertussis antigens that abrogate bacterial adherence and elicit immunity. 887 33

New prophylactic or treatment options are available for a number of infectious diseases that may be transmitted in the health care setting. Infectious diseases that can now be prevented by vaccination of the employee include hepatitis A, pertussis, hepatitis B, and primary varicella. New prophylactic or treatment regimens are available for Neisseria meningitidis, Streptococcus pyogenes, and Bordetella pertussis; treatment of multidrug-resistant tuberculosis is also discussed. Finally, management of the HIV-infected health care worker is reviewed.
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PMID:Frontiers of occupational health. New vaccines, new prophylactic regimens, and management of the HIV-infected worker. 918 49

Infecto-contagious diseases in the twenty-first century with respect to precedent will see themselves deprived of smallpox, dracunculiasis and very probably of paralyzing poliomyelitis. Vaccination-preventable diseases, such as measles, whooping cough, diphtheria, tetanus, rabies, some forms of meningitis, yellow fever and episodes of disseminated tuberculosis will greatly diminish in their rates of morbi-lethality; the elimination of some, and the eradication of measles, are expected. Other diseases such as diarrhea (including cholera), geo-helminthiasis, some severe respiratory tract infections and the majority of vector-transmitted infectious diseases will decrease due to improvements in potable water services, drainage, sanitary food control, living quarters, and individual and community anti-vector action. Leprosy, onchocerciasis and several parasitoses will be controlled by the available antimicrobial drugs. Infectious diseases will continue to be an important health problem due to: Reduction in the immunocompetence resulting from the aging of the population, chemotherapies necessary for neoplasms, and autoimmune pathology and the survival of persons with primary immunodeficiencies; lifestyles prone to infectious pathology, such as mega-city urbanization, children in day care centers, industrialized foods, intravenous drug addiction, sexual liberation, global commerce, and tourism; antibiotic-multiresistant microbial flora; environmental disturbances as a result of global warming, deforestation, the settling of virgin areas, dams, the large-scale use of pesticides, fertilizers and antimicrobials, and natural/social disasters generators of poverty, violence and deprivation will result in emergence or re-emergence of infectious diseases already controlled in the past.
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PMID:Infectious diseases in the 21st century. 920 2

Pertussis toxin from Bordetella pertussis is one of the ADP-ribosylating toxins which are the cytotoxic agents of several infectious diseases. Transition state analogues of these enzymes are expected to be potent inhibitors and may be useful in therapy. Pertussis toxin catalyzes the ADP-ribosylation of a cysteine in the synthetic peptide alphai3C20, corresponding to the C-terminal 20 amino acids of the alpha-subunits of the G-protein Gi3. A family of kinetic isotope effects was determined for the ADP-ribosylation reaction, using 3H-, 14C- and 15N-labeled NAD+ as substrates. Primary kinetic isotope effects were 1.050 +/- 0.006 for [1'N-14C] and 1.021 +/- 0.002 for [1N-15N], the double primary effect of [1'N-14C,1N-15N] was 1.064 +/- 0.002. Secondary kinetic isotope effects were 1.208 +/- 0.014 for [1'N-3H], 1.104 +/- 0.010 for [2'N-3H], 0.989 +/- 0.001 for [4'N-3H], and 1.014 +/- 0.002 for [5'N-3H]. Isotope trapping experiments yielded a commitment factor of 0.01, demonstrating that the observed isotope effects are near intrinsic. Solvent D2O kinetic isotope effects are inverse, consistent with deprotonation of the attacking Cys prior to transition state formation. The transition state structure was determined by a normal mode bond vibrational analysis. The transition state is characterized by a nicotinamide leaving group bond order of 0.14, corresponding to a bond length of 2.06 A. The incoming thiolate nucleophile has a bond order of 0.11, corresponding to 2.47 A. The ribose ring has strong oxocarbenium ion character. Pertussis toxin also catalyzes the slow hydrolysis of NAD+ in the absence of peptides. Comparison of the transition states for NAD+ hydrolysis and for ADP-ribosylation of peptide alphai3C20 indicates that the sulfur nucleophile from the peptide Cys participates more actively as a nucleophile in the reaction than does water in the hydrolytic reaction. Participation of the thiolate anion at the transition state provides partial neutralization of the cationic charge which normally develops at the transition states of N-ribohydrolases and transferases. Thus, the presence of the peptide provides increased SN2 character in a loose transition state which retains oxocarbenium character in the ribose.
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PMID:Pertussis toxin: transition state analysis for ADP-ribosylation of G-protein peptide alphai3C20. 920 66

Infection with Bordetella pertussis continues to result in widespread morbidity and mortality. Although whole cell pertussis vaccines are effective in controlling pertussis, concerns relating to adverse effects following vaccination have led to the development of a new generation of pertussis vaccines. Acellular pertussis vaccines have decreased endotoxin content and are less reactogenic than whole cell vaccines. The composition of acellular pertussis vaccines varies, resulting in differing immunogenicity. Recent studies have demonstrated that these vaccines, in general, have an efficacy similar to that of whole cell vaccines. The development of acellular pertussis vaccines is an advance that should result in less discomfort from vaccination and the potential for increased vaccine usage, resulting in the possible elimination of this disease.
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PMID:An overview of the status of acellular pertussis vaccines in practice. 925 78

Using a mouse model of Bordetella pertussis infection, we have analyzed the role of gamma interferon (IFN-gamma) in bacterial clearance from the respiratory tract. Adult BALB/c mice began to clear a respiratory infection within 3 weeks postinfection, with complete resolution of infection 6 to 8 weeks postinfection. In contrast, neither adult SCID mice (which lack mature B and T lymphocytes) nor adult nude mice (which lack mature T lymphocytes) controlled B. pertussis infection, and both strains died within 3 to 5 weeks postinfection. Short-term T-cell lines generated from the draining lymph nodes of the lungs of infected BALB/c mice were found to be CD4+ and produced IFN-gamma but no detectable interleukin-4. Analyses of IFN-gamma mRNA induction in the lungs of mice following B. pertussis infection showed that in both BALB/c and C57BL/6 mice, IFN-gamma mRNA levels increased sharply by 1 week postinfection and then subsequently declined. Further exploration of a potential role for IFN-gamma demonstrated that infection of adult BALB/c mice depleted of IFN-gamma in vivo with anti-IFN-gamma monoclonal antibodies resulted in greater numbers of bacteria recovered from the lungs than in infected, control BALB/c mice, although IFN-gamma-depleted mice could subsequently clear the infection. Infection of mice which have a disrupted IFN-gamma gene resulted in bacterial clearance with a time course similar to those seen with IFN-gamma-depleted mice. These results indicate that IFN-gamma plays a role in controlling B. pertussis infection.
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PMID:Role of gamma interferon in natural clearance of Bordetella pertussis infection. 939 74

The number of whooping cough notifications has declined in recent years, as vaccine coverage has recovered from the low levels seen in the 1970s and 1980s. Notification of infectious disease is often incomplete, and this study aimed to estimate the extent to which whooping cough is undernotified. We included all cases of whooping cough occurring in the North West Region between 1 April 1994 and 31 December 1996, identified by notification, hospital admission data, or laboratory reports. By combining the three sources, 1239 cases were identified, 69.6% of which were notified. The notification rate was 29.6% (131/442) for cases admitted to hospital and 45.6% (78/170) for laboratory reported cases. Completeness of notification was estimated to be 35.7% (863/2420; 95% confidence interval 30.3-43.4%) using the capture-recapture method. The study confirms that notification of whooping cough is incomplete and suggests that two thirds of cases are not notified.
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PMID:Whooping cough surveillance in the north west of England. 964 26

Between 1 November 1993 and 31 October 1996, admissions to paediatric departments for Bordetella pertussis complications were reported to a nationwide, hospital-based active surveillance system. The case definition included pertussis complicated by pneumonia, apnoea requiring assisted ventilation, seizures, encephalopathy or a combination of these. Two hundred sixteen cases of pertussis complications were registered. 57.4% of them were in infants, 50.9% of them less than 6 months old. There were five deaths, three previously healthy children died. At the time of hospital admission, 106 cases would have been eligible for at least three doses of pertussis vaccine, only four (3.8%) had received the recommended number of immunisations. From the second quarter of 1995, the reported number of cases declined. The decrease coincides with an improvement of pertussis vaccination coverage between 1992 and 1995 due to an increased use of acellular vaccines. The reduction of complicated pertussis was observed even in age-groups too young for the recommended vaccinations. The observed decrease could be due to the increase in vaccination coverage with interruption of the chain of transmission to the younger age-groups, to a cyclic decrease in pertussis cases, or to a combination of both. Continued surveillance will provide information on the epidemiological trend of hospitalisations for pertussis complications in the first European country to have introduced vaccination with acellular vaccines on a large scale.
Infection
PMID:Pertussis complications in Germany--3 years of hospital-based surveillance during the introduction of acellular vaccines. 971 80

A drug susceptibility test of the combination drug TAZ/PIPC, which consists of a newly developed beta-lactamase inhibitor, tazobactam (TAZ), and one of penicillin antibiotics, piperacillin (PIPC), with combination ratio of 1:4 in potency, was conducted with stock strains and clinical isolates. The clinical efficacy and safety of its injection was also evaluated in children with a variety of infectious diseases. The results were as follows: 1. In susceptibility test, 114 strains from 4 species of stock strains were treated with 8 drugs, that is, TAZ/PIPC, PIPC, penicillin G (PCG), ampicillin (ABPC), cefotiam (CTM), cefotaxime (CTX), ceftazidime (CAZ), and sulbactam/cefoperazone (SBT/CPZ). Of three clinically isolated species from patients, Staphylococcus aureus (S. aureus) was treated with TAZ/PIPC, PIPC, methicillin (DMPPC), CTM, CTX, and SBT/CPZ, and the others were treated with the same drugs except for DMPPC. The MICs were measured for these bacterial strains inoculated at the concentration of 10(6) CFU/ml. The MIC90 values of TAZ/PIPC against 45 strains of Streptococcus pyogenes (S. pyogenes), one of the stock cultures of Gram-positive cocci, were 0.05 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. The MICs of TAZ/PIPC for 28 strains of Streptococcus agalactiae (S. agalactiae) were 0.39 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. As for Gram-negative bacilli, the MIC90 of TAZ/PIPC against 10 strains of Bordetella pertussis (B. pertussis) were 0.10 microgram/ml and similar to those of PIPC. The MIC90 of TAZ/PIPC against 31 strains of Haemophilus influenzae (H. influenzae) were 0.05 microgram/ml and similar to those of PIPC, CTX, and SBT/CPZ. Regarding Gram-positive cocci isolated from patients received this combination drug, the MIC90 of TAZ/PIPC against 2 strains of S. aureus, a non beta-lactamase producing strain and a low-beta-lactamase producing strain, were 0.78 microgram/ml and 3.1 micrograms/ml, respectively; the former value was similar to those of PIPC, DMPPC, CTM, and CTX, and the latter was similar to those of PIPC, DMPPC, CTX, and SBT/CPZ. Of 4 strains of Streptococcus pneumoniae, 2 strains were inhibited at 0.05 microgram/ml, and the others at 1.56 micrograms/ml; both values were similar to those of PIPC, SBT/CPZ. As for Gram-negative bacilli, 6 of 7 strains of H. influenzae did not produce beta-lactamase and 1 strain was a high producer. The MICs of TAZ/PIPC against beta-lactamase nonproducing strains were < or = 0.025 microgram/ml in 5 strains and 0.39 microgram/ml in 1 strain, and the values were similar to those of PIPC and SBT/CPZ. While the MIC of TAZ/PIPC against the high beta-lactamase producing strain was 0.78 microgram/ml; similar to that of SBT/CPZ and smaller than that of PIPC. 2. The results of clinical effects on 7 diseases in 33 cases were as follows: TAZ/PIPC was clinically judged "excellent" in 17 (51.5%); good in 14 (42.4%); fair in 2 (6.1%). No case with no response was seen in this study, and the total efficacy rate of "excellent" and "good" was 93.9%. 3. Bacteriological effects were evaluated in 17 strains of 4 species, and all of them were eradicated. 4. Adverse reactions were judged in 35, which consisted of 33 in which the clinical effects were evaluated and 2 dropped from this study. Of these cases, diarrhea was observed in 4 (11.4%). 5. Laboratory tests revealed an increase in platelets in 1 of 32 cases (3.1%), and eosinophilia in 2 of 29 cases (6.9%). Biochemical profile showed an increase in GPT alone and abnormal increases in both GOT and GPT in 1 each out of 21 cases.
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PMID:[Basic and clinical studies on tazobactam/piperacillin in pediatric field]. 975 31

Among the 315 protein toxins elicited by gram positive and gram negative bacteria so far characterized, about 50 toxins are currently considered as totally or partially, responsible of the pathological manifestations and/or lethality resulting from host infection or intoxication (contaminated food) by relevant toxinogenic bacteria. A certain number of criteria are required for the assessment of indisputable involvement of a toxin or an array of toxins (from the same bacteria) in infectious diseases: 1) The bacterial microorganism clearly identified as the pathogenic agent of the disease produces component(s) considered as toxin(s); 2) The administration to appropriate animal(s) of the toxin(s) separated from the relevant bacteria or produced by genetic engineering from a heterologous tox+ recombinant bacterial strain produces symptoms and pathophysiological disorders that mimic those observed in the natural disease or at least those elicited in experimental animals by the cognate toxin-producing bacteria; 3) The in vitro incubation of the isolated toxin(s) with appropriate animal organs, tissues or cells elicits certain pathophysiological, biochemical or metabolic manifestions observed in the host infected with the relevant toxinogenic bacteria; 4) Toxin concentration in the organism of the host infected by the toxinogenic bacteria should be compatible with the characteristics of the relevant disease. The toxins of pathogenic interest exhibit a variety of effects in bacterial diseases. Bacteria that colonize a wound or mucosal surface but do not invade target cells can produce toxins that act locally or enter the bloodstream and attack internal organs (e.g. Corynebacterium diphtheriae, Vibrio cholerae, ...). Bacteria growing in a wound can produce toxins that destroy host tissue and kill phagocytes in the immediate vicinity of the bacteria, thus facilitating bacterial growth and spread. On the basis of the above mentioned criteria, the following bacterial diseases among many others are toxin-associated (toxinoses): diphtheria, tetanus, botulism, whooping cough, diarrhea, bloody diarrhea, hemolytic uremic syndrome, cholera, scarlet fever, toxic shock syndrome, gas gangrene, B. fragilis diarrhea, anthrax, pseudomembranous colitis.
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PMID:[Implications of bacterial protein toxins in infectious and food-borne diseases]. 975 85


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