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R Lagos

Publications and source records attributed to R Lagos.

At least 37 records · Page 2Linked to original sources
PubMed1998

The introduction of routine Haemophilus influenzae type b conjugate vaccine in Chile: a framework for evaluating new vaccines in newly industrializing countries.

OBJECTIVE: To determine the burden of Haemophilus influenzae type b (Hib) disease, the safety and immunogenicity of Hib conjugate vaccine, the practicality of combining Hib conjugate and diphtheria-tetanus-pertussis vaccines and the effectiveness of routine vaccination. STUDY DESIGNS: A series of studies were carried out involving infants and children in Santiago, Chile. The study designs included retrospective surveillance, cost-benefit analysis, randomized placebo-controlled trials of safety and immunogenicity and a Phase IV postlicensure evaluation of vaccine effectiveness. RESULTS: The studies included in this stepwise process showed that Hib invasive disease was a significant public health problem with a substantial economic burden; that combining Hib conjugate and diphtheria-tetanus-pertussis vaccines was practical, safe and elicited a strong immunologic response; and that the combined formulation afforded a high level of protection against invasive Hib disease (90% effectiveness). CONCLUSIONS: In July, 1996, Chile became only the third newly industrializing country to introduce routine Hib conjugate vaccination. New vaccines, such as Hib conjugates, will be more expensive than existing ones. The stepwise process used in Chile may serve as an example for the evaluation of new vaccines in nonindustrialized countries.

Child, Preschool↗
PubMed1998

[Antimicrobial multiresistance of Shigella sp strains in a semi rural community of northern Santiago].

UNLABELLED: Appropriate antimicrobial therapy shortens the duration of Shigellosis and significantly reduces the risk of transmission. Shigella strains resistant to common antimicrobials have increased during the past years, determining the need for a periodic surveillance, to guide effective therapy. AIM: To report the results of a surveillance program in a rural community near Santiago (Colina), for Shigella infections. MATERIAL AND METHODS: Between 1995 and 1997, stool samples from 3,534 episodes of diarrhoea, that occurred in Colina, were obtained. Two hundred twenty six Shigella strains were isolated and studied for susceptibility to ampicilin (AM), amoxicillin/clavulanic acid (AMC), cotrimoxazole (STX), chloramphenicol (CAF), tetracycline (TET), furazolidine (FU), ciprofloxacine (CIPR), nalidixic acid (AC NAL), gentamycin (GENT) and cefotaxime (CFTX). RESULTS: Shigella flexnerii represented 134 of 226 Shigella strains isolated. All strains were susceptible to CIPR, AC NAL, GENT and CFTX. Yearly variation of resistance patterns to other antimicrobials were observed for these strains. Resistance to AM varied from 56 to 76%, to AMC from 25 to 56%, to STX from 21 to 47%, to CAF from 36 to 69%, to TET from 44 to 78% and to FU from 9 to 18%. Overall resistance was higher during 1997. All 85 strains of S sonnei were susceptible to CIPR, AC NAL and CFTX. Resistance throughout the years varied from 56 to 88% for AM, from 0 to 28% for AMC, from 44 to 53% for STX, from 11 to 40% for CAF, from 11 to 42% for TET and from 5 to 11% for FU. Overall resistance was also higher during 1997, except for AM and STX. Seven S hoydii strains were isolated, only during 1995. All seven were resistant to AM and TET and none were resistant to FU, CIPR, AC NAL and CFTX. Two strain was resistant to AMC, STX and CAF. CONCLUSIONS: Antimicrobial resistance patterns of Shigella sp isolated in Colina have increased from 1995 to 1997, specially for commonly used antimicrobials. Resistance remains low for furazolidine and all strains remain susceptible to quinolones.

Child, Preschool↗
PubMed1997

Factors associated with superior antibody responses to a single dose of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine administered to Chilean infants at 2 months of age.

The anticapsular antibody response of Chilean infants to a single dose of Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate, vaccine is substantially higher than that observed among infants of similar age from the USA. Comparison of selected demographic and environmental factors indicates that low maternal education and a greater number of persons in the home are significantly associated with the superior responder phenotype. High anticapsular antibody responses were associated with high antibody responses to tetanus toxoid, the carrier protein in this conjugate, but not to diphtheria toxoid. These data suggest that environmental factors may enhance the magnitude of the primary antibody response to PRP-T vaccine.

Antibodies, Bacterial↗
PubMed1997

Cloning and expression in Escherichia coli of genetic determinants for production of and immunity to microcin E492 from Klebsiella pneumoniae.

Microcin E492 is a polypeptide antibiotic that is produced and excreted by Klebsiella pneumoniae RYC492. The genetic determinants for microcin synthesis and immunity were cloned in Escherichia coli VCS257 into the cosmid vector pHC79, starting from total DNA of K. pneumoniae RYC492. The microcin E492 expressed in E. coli had the same properties as that of K. pneumoniae, i.e., the same molecular weight, the ability to form ionic channels in planar phospholipid bilayers, and essentially identical biological properties. Microcin E492 expression in E. coli, like that in K. pneumoniae, was mainly in the exponential phase of growth, declining in the stationary phase. The immunity determinant was subcloned into the same vector, and its expression was found to disappear in the stationary phase. This phenomenon is not dependent on rpoS, the stationary-phase sigma factor.

Anti-Bacterial Agents↗
PubMed1996

The activity of microcin E492 from Klebsiella pneumoniae is regulated by a microcin antagonist.

Microcin E492 is a polypeptide antibiotic that is produced and excreted by Klebsiella pneumoniae. Different growth conditions of the producer strain affect microcin activity. The production of a microcin antagonist is responsible for the changes in microcin activity. The microcin antagonist is induced when cells are iron-deprived, resulting in a low microcin activity. The microcin antagonist was purified using a procedure developed for the isolation of a catechol-type siderophore, and its activity was titrated using purified microcin. The inhibitory effect of the microcin antagonist is not observed when this compound is forming a complex with iron. The same inhibitory effect on microcin activity was obtained using purified enterochelin from Escherichia coli. The microcin antagonist was identified as enterochelin through thin-layer chromatography.

Anti-Bacterial Agents↗
PubMed1996

No adverse impact on protection against pertussis from combined administration of Haemophilus influenza type b conjugate and diphtheria-tetanus toxoid-pertussis vaccines in the same syringe.

To assess whether combining a Haemophilus influenzae type b conjugate vaccine (PRP-T) and diphtheria-tetanus toxoid-pertussis (DTP) vaccine in a single syringe would impact adversely the antibody response and clinical protection conferred by pertussis vaccine, surveillance and a nested serosurvey were conducted among infants in a large-scale evaluation of PRP-T in Santiago. Infants received either combined PRP-T/DTP or DTP only at 2, 4, and 6 months of age. At 8 months, pertussis agglutinin, anti-pertussis toxin, and anti-filamentous hemagglutinin antibody levels in the PRP-T/DTP (137.7, 23.1, and 12.2, respectively) and DTP (142.9, 20.6, and 13.0, respectively) groups were comparable. The incidence of pertussis was similar among infants assigned to health centers administering combined PRP-T/DTP and those administering DTP alone (13.1 vs. 12.2 cases/10(5) child-years). Combined PRP-T/DTP vaccine did not diminish protection against pertussis.

Agglutination Tests↗
PubMed1996

Large scale, postlicensure, selective vaccination of Chilean infants with PRP-T conjugate vaccine: practicality and effectiveness in preventing invasive Haemophilus influenzae type b infections.

BACKGROUND: Haemophilus influenzae type b (Hib) conjugate vaccines have demonstrated an impressive impact in diminishing Hib disease in industrialized countries. However, their high cost prompts nonindustrialized countries to corroborate their effectiveness under local conditions before considering their programmatic implementation. Such a postlicensure evaluation of vaccine effectiveness was undertaken in Chile. METHODS: After its licensure in Chile polyribosylribitol phosphate-tetanus toxoid protein conjugate vaccine (PRP-T), combined with diphtheria-tetanus-pertussis vaccine, was introduced into the Expanded Program on Immunization schedules in 36 health centers throughout metropolitan Santiago for 12 months, whereas 35 similar health centers administered only diphtheria-tetanus toxoid-pertussis vaccine. Bacteriologic surveillance data for invasive Hib cases collected over the ensuing 30 months were analyzed. RESULTS: In an intent-to-vaccinate (effectiveness) analysis, PRP-T provided 90.2% protection (95% confidence interval, 74.5 to 100%) against invasive Hib disease (40 vs. 4 cases, P < 0.001). Vaccine effectiveness was 91.3% against meningitis (22 vs. 2 cases) and 80% against pneumonia and empyema (10 vs. 2 cases, P = 0.039). Vaccine efficacy among infants who received all three doses of PRP-T was 91.7% (95% confidence interval, 64.8 to 100%). CONCLUSIONS: Programmatic use of Hib conjugate vaccine administered in combination with diphtheria-tetanus-pertussis vaccine constitutes a highly effective and practical intervention in Chile, a newly industrializing country.

Bacterial Capsules↗
PubMed1996

Recovery of soluble protein after expression in Escherichia coli depends on cellular disruption conditions.

Proteins overproduced in Escherichia coli are frequently recovered from bacterial extracts as insoluble material. The influence of different cell disruption procedures on the recovery of soluble protein, after recombinant protein expression in E. coli, was assessed using two beta-tubulin derivatives. Nonionic detergents such as Triton X-100 and Nonidet P-40 promote aggregation when present in the lysis buffer. The effect of Triton X-100 is reversed by the addition of 1 M NaCl in the lysis buffer indicating that the recombinant protein aggregation is probably caused by interactions with membrane proteins. The importance of the cellular disruption method on the recovery of potentially soluble recombinant proteins is discussed.

Escherichia coli↗
PubMed1996

[Bacterial urovirulence factors and their association with functional and anatomical abnormalities and recurrence of urinary tract infections in children].

BACKGROUND: Urinary tract infections in children are associated with functional and anatomical abnormalities of the urinary tract, they tend to recur and can cause permanent kidney damage. AIM: To study in children with urinary tract infections, microbiological factors associated to recurrence, functional and anatomical abnormalities of the urinary tract. PATIENTS AND METHODS: A prospective sample of children was incorporated into a follow-up protocol after their first episode of bacteriologically-demonstrated urinary tract infection. In all patients an abdominal ultrasound examination and a mictional urethrocystography were done and the presence of fimbriae was studied in isolated strains of Escherichia coli. RESULTS: Two hundred fifteen cases bad an adequate adherence to the study protocol, 190 caused by E coli. Fimbriated E coli strains were isolated with greater frequency from children with pyelonephritis than from those with a low urinary tract infection (50 and 28% respectively). The absence of fimbriae in E coli strains was associated with a higher risk of recurrent infections (odds ratio = 3, confidence intervals = 2-9.2) and an abnormal urethrocystography (odds ratio = 3, confidence intervals = 1.1-10.2). CONCLUSIONS: These data are consistent with foreign reports and support the need to study adhesins in E coli strains isolated from children with urinary tract infections.

Bacterial Infections↗
PubMed1995

Tubulin-tyrosine ligase catalyzes covalent binding of 3-fluoro-tyrosine to tubulin: kinetic and [19F]NMR studies.

The use of 3-fluoro-tyrosine as an alternative substrate for the enzyme tubulin:tyrosine ligase which catalyzes the incorporation of tyrosine into the alpha-tubulin subunit was investigated. The incorporation of tyrosine into tubulin was inhibited competitively by 3-fluoro-tyrosine with an apparent Ki of approximately 25 microM. The affinity for this analog was similar to that of tyrosine, confirming that the hydrogen at position 3 of the aromatic ring is not essential for the reaction catalyzed by TTLase. The incorporation of 3-fluoro-tyrosine into the C-terminus of the alpha-tubulin subunit was demonstrated through [19F]NMR spectroscopy. The 3-fluoro-tyrosine signal at -58.6 ppm (trifluoroacetic acid as external standard), with a bandwidth of 24.7 Hz presented a chemical shift of 0.75 ppm upfield and an enlargement in the bandwidth (30.5 Hz) when incorporated into tubulin. These results strongly suggest that this amino acid is exposed to the solvent in tubulin. Tubulin covalently labeled with 3-fluoro-tyrosine was competent to polymerize into microtubules. The use of fluorinated tubulin in [19F]NMR spectroscopy for studying questions concerning protein conformation and interactions will be discussed.

Animals↗
PubMed1995

Attenuated live cholera vaccine strain CVD 103-HgR elicits significantly higher serum vibriocidal antibody titers in persons of blood group O.

Persons of blood group O are at increased risk of developing cholera gravis. In a randomized, placebo-controlled, double-blind safety-immunogenicity trial of live oral cholera vaccine CVD 103-HgR in 5- to 9-year-old Chilean children, vibriocidal antibody seroconversion (74% overall) did not differ by blood group. However, the reciprocal geometric mean titer (GMT) in blood group O vaccines (GMT = 486) was higher than that in non-O vaccines (GMT = 179) (P < 0.02).

ABO Blood-Group System↗
PubMed1993

Cost-benefit analysis for the use of Haemophilus influenzae type b conjugate vaccine in Santiago, Chile.

Cost-benefit analyses can be integral to the evaluation of interventions in developing countries. The authors compare the potential benefits to the Chilean Ministry of Health, in terms of treatment costs averted, by prevention of Haemophilus influenzae type b (HIB) invasive disease, with the costs of adding HIB conjugate vaccine to the diphtheria-tetanus-pertussis (DTP) immunization routinely administered to infants. In their basecase model, over a 10-year period (1991-2000), vaccination against HIB will prevent 1,229 cases of HIB invasive disease, including 713 cases of meningitis, 107 of whom would suffer severe, long-term sequelae, and between 29 and 116 deaths. Assuming a cost of US$1 for a full three-dose regimen of vaccine, the benefit/cost ratio of 1.66, with a net discounted savings of over $403,225, illustrates that HIB vaccine can be cost-beneficial. Sensitivity analyses which alter each of the variables in the analysis indicate that if the true incidence of HIB disease is twice the published rate, then three doses of vaccine remains cost-beneficial at US#3.

Bacterial Vaccines↗
PubMed1993

Interaction between the C-terminal peptides of tubulin and tubulin S detected with the fluorescent probe 4',6-diamidino-2-phenylindole.

The digestion of tubulin with subtilisin and the reassociation of the digestion products was followed by means of the fluorescent probe 4',6-diamidino-2-phenylindole (DAPI). The fluorescence spectra of DAPI bound to chicken brain tubulin and to the main products of tubulin digested with subtilisin-agarose (tubulin S and C-terminal peptides) were analyzed. The corrected emission spectrum of DAPI in the presence of tubulin showed an enhancement of fluorescence intensity with a maximum at 452 nm. The digestion reaction was followed by the diminution of the area of DAPI-tubulin emission spectra, which showed biphasic pseudo-first-order kinetics. The values for the rate constants were 1.2 x 10(-2) min-1 and 3.5 x 10(-2) min-1 for the alpha and beta subunits, respectively, and were similar to those determined from the undigested subunits using polyacrylamide gel electrophoresis. Tubulin S and the C-terminal peptides were purified by means of a Bio-Gel P-60 column. The C-terminal peptides obtained from this column were analyzed by urea-sodium dodecyl sulfate polyacrylamide gel electrophoresis, and an apparent molecular weight around 3000 was determined. The corrected emission spectrum of DAPI in the presence of tubulin S showed a maximum shifted to 460 nm and a lower enhancement of fluorescence than the emission spectrum of the DAPI-tubulin complex. Titration of purified tubulin S with the C-terminal peptides of tubulin showed, after the addition of DAPI, an increase in the fluorescence intensity at 460 nm with a saturation function dependent on the concentration of peptides added. On the other hand, the emission spectrum of DAPI in the presence of the C-terminal peptides was unchanged from that of free DAPI in the solution. From these results we propose that the DAPI binding site is located on tubulin S and that the C-terminal peptides interact with tubulin S after digestion with subtilisin.

Fluorescent Dyes↗
PubMed1993

Microcin E492 forms ion channels in phospholipid bilayer membrane.

Microcin E492, a polypeptide antibiotic, has been shown to have an M(r) of 6,000 by urea-SDS-polyacrylamide gel electrophoresis of the fluorescently labelled compound. It is known that the bactericidal action of microcin involves a loss of the transmembrane potential. In this study we show that microcin forms cation-selective channels in planar phospholipid bilayers. The channels have two main conductance states the current-voltage curves of which rectify. The reversal potentials measured under biionic conditions indicate a permeability sequence of NH4+ > K+ = Rb+ = Cs+ > Na+ = Na+ = Li+ > Tris+. The results suggest that membrane potential dissipation induced by microcin is a consequence of the formation of pores in the bacterial membrane.

Anti-Bacterial Agents↗
PubMed1993

The binding of terbium ions to tubulin induces ring formation.

The intrinsic fluorescence excitation and emission spectra of chicken brain tubulin showed the characteristic tryptophan fluorescence. The emission spectrum of Tb3+ in the presence of tubulin and GTP excited at 295 nm, showed four peaks, with the maxima at 490, 545, and 586 nm and a minor peak around 620 nm. Titration of tubulin with Tb3+ was followed by the increment in luminescence at 545 nm and showed a sigmoidal curve where the initial lag interval and the maximal luminescence intensity depended on tubulin concentration. The presence of Mg2+, Co2+, and Zn2+ diminished both the sigmoidicity of the curve and the maximal luminescence intensity. Titration of tubulin with Tb3+ also produced a sigmoidal increase in turbidity, which was shifted to the left with respect to the luminescence curve. The dependence of turbidity on the wavelength of the Tb(3+)-induced polymers revealed that the large structures formed were not microtubules. Electron microscopy of the aggregates induced by Tb3+ showed mainly a lattice of double rings with side-by-side contacts. These results indicate that Tb3+ induces principally double ring formation and that these rings (33 +/- 2 nm external diameter) aggregate in large-ordered arrays. The luminescence of Tb3+ seems to be induced mainly by the aggregation of rings.

Animals↗
PubMed1993

Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine does not depress serologic responses to diphtheria, tetanus or pertussis antigens when coadministered in the same syringe with diphtheria-tetanus-pertussis vaccine at two, four and six months of age.

The safety and immunogenicity of a vaccine against Haemophilus influenzae type b consisting of purified polyribosylribitol phosphate conjugated to tetanus toxoid (PRP-T) were evaluated in 277 Chilean infants who were randomly assigned to one of three treatment groups: Group A, PRP-T mixed with diphtheria-tetanus-pertussis (DTP) vaccine in a single syringe and given as a single inoculation in one arm and placebo in the other arm; Group B, PRP-T given in one arm and DTP in the other arm; Group C, DTP given in one arm and placebo in the other. Infants were immunized at 2, 4 and 6 months of age and examined daily for 4 days after each immunization. Serum PRP antibodies; tetanus, diphtheria and pertussis antitoxin; pertussis agglutinins; and antibodies to Bordetella pertussis filamentous hemagglutinin were measured at baseline and 2 months after each dose. PRP-T was well-tolerated. After three doses of PRP-T vaccine 100% of infants attained PRP antibody concentrations > or = 0.15 micrograms/ml and 96 to 99% achieved high anti-PRP concentrations (> or = 1.0 micrograms/ml). The post-third dose anti-PRP geometric mean titer was high (6.94 micrograms/ml) in infants who were given PRP-T combined with DTP, although it was somewhat lower than the geometric mean titer of the group who received PRP-T in a separate arm (9.93 micrograms/ml) (P not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗
PubMed1993

[Benzathine penicillin G and miocamycin in the treatment of children with streptococcal pharyngitis: a controlled therapeutic trial].

The aim of this study was to compare the clinical and bacteriologic effectiveness of miocamycin (Miocamin, Merck) as compared to benzathine penicillin G in the treatment of streptococcal pharyngitis. One hundred forty nine patients (aged 2 to 15 years) with culture proven Group A streptococcal pharyngitis were randomly assigned to receive miocamycin (15 mg/kg/day bid per os) or one injection of 600,000 or 1,200,000 units of benzathine penicillin G. The clinical response was similar in both groups, in terms of fever duration (16 +/- 14 hours with miocamycin vs 13 +/- 13 hours with penicillin) and normalization of appetite (87.7% of children with miocamycin vs 95.8% of children with penicillin after three days). Bacteriologic eradication of streptococcus was achieved in 66% of children treated with penicillin and 32% of those treated with miocamycin (p < 0.001). We conclude that a single benzathine penicillin is more effective eradicating streptococcus pyogenes than miocamycin in children with streptococcal pharyngitis.

Child↗