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T V Murphy

Publications and source records attributed to T V Murphy.

At least 19 recordsLinked to original sources
PubMed1998

Invasive pneumococcal disease in Dallas County, Texas: results from population-based surveillance in 1995.

We studied the epidemiology of invasive disease caused by Streptococcus pneumoniae in 1995 among 1.9 million residents of Dallas County, Texas. The sociodemographic characteristics and chronic medical conditions of 432 patients were identified through active, population-based surveillance and review of medical records. The incidence of disease was 22 cases per 100,000 person-years and was highest for children < 2 years of age (136 cases per 100,000 person-years) and for adults > or = 65 years of age (80 cases per 100,000 person-years). Twenty percent of isolates were nonsusceptible to penicillin; the highest rates of resistance were among the youngest and oldest age groups (28% and 22% of isolates, respectively). An increased incidence of disease was associated with low income (42 cases per 100,000 person-years) and black race (39 cases per 100,000 person-years). The frequency of most chronic medical conditions increased with age; smoking, heavy alcohol use, and infection due to human immunodeficiency virus were most common between 30 and 64 years of age. Of otherwise healthy patients 30-64 years of age, 47% were current smokers, an association requiring further investigation. Characterizing groups at risk for invasive pneumococcal disease could aid in the development of prevention programs and increase the benefits from wide use of effective vaccines.

Adolescent↗
PubMed1998

Methicillin-resistant Staphylococcus aureus in two child care centers.

Methicillin-resistant Staphylococcus aureus (MRSA) has not been studied in child care centers. The prevalence of MRSA colonization was determined at two centers with an index patient. Two (3%) of 61 children at center X had MRSA; strains from both children and the index illness were pulsed-field gel electrophoresis type B. Nine (24%) of 40 children at center Y had MRSA; strains from 5 children and the index illness were type B, and strains from 4 children were type A. Ten of 11 colonized children were in classes with 2- and 3-year-old children. Colonization with MRSA was not associated with health care contact by subjects or by members of their households. MRSA in child day care centers indicates accelerated spread of MRSA in the community.

Child↗
PubMed1998

17Beta-oestradiol enhances nitric oxide synthase activity in endothelium-denuded rat aorta.

1. It has been suggested that oestrogen-produced vasodilatation is due to induction of endothelial nitric oxide synthase (NOS), but there are many reports of direct effects on vascular smooth muscle. In the present study, these processes were investigated in rat aorta isolated from ovariectomized rats. 2. Short-term treatment (10 min) with 17beta-oestradiol (10 micromol/L) produced a small attenuation of the phenylephrine (PE)-induced constriction, which was unaffected by the nitric oxide synthase inhibitor L-N5(-1-iminoethyl)ornithine (NIO; 100 micromol/L). Long-term treatment (6 h) with 17beta-oestradiol (10 micromol/L) did not affect acetylcholine-mediated vasorelaxation in endothelium-intact aortic rings, but did attenuate PE-induced constriction. This attenuation was also observed in endothelium-denuded preparations after 17beta-oestradiol (10 micromol/L for 6 h) and was far greater than the acute effect of 17beta-oestradiol (10 micromol/L). 3. The attenuation produced by 17beta-oestradiol (10 micromol/L for 6 h) was significantly inhibited by concomitant treatment with cycloheximide (1 micromol/L), suggesting that protein synthesis was involved. NIO (100 micromol/L) also attenuated the effect, which suggests that the anti-constrictor effect of 17beta-oestradiol occurs through the increased production of nitric oxide (NO). 17Beta-oestradiol increased NO production, as assessed by the conversion of [3H]-arginine to [3H]-citrulline in rat aorta. These effects were prevented by cycloheximide and NIO. The anti-constrictor effect of oestrogen was blocked by the oestrogen receptor antagonist ICI 182 780 (100 nmol/L). 4. Western blotting using an antibody specific for inducible nitric oxide synthase (NOS) revealed that 17beta-oestradiol (10 micromol/L for 24 h) treatment induced the formation of inducible NOS protein in the aorta, an effect blocked by cycloheximide. The results indicate that 17beta-oestradiol can attenuate the vasoconstrictor effect of PE by a specific receptor-mediated process that involves induction of inducible NOS.

Acetylcholine↗
PubMed1997

Noradrenaline release and the effect of endogenous activation of the phospholipase C/protein kinase C signalling pathway in rat atria.

1. It has been proposed that protein kinase C (PKC) in sympathetic nerves is activated during action-potential evoked release of noradrenaline and helps maintain transmitter output. We studied this phenomenon further in rat atria radiolabelled with [3H]-noradrenaline. 2. Noradrenaline release was elevated by continuous electrical stimulation of the atria for 10 min at either 5 or 10 Hz. Two inhibitors of PKC, polymyxin B (21 microM) and Ro 318220 (3 microM), markedly inhibited the release of noradrenaline but only at the higher stimulation frequency. 3. Further experiments were conducted with 10 Hz stimulation but for shorter train durations. In this case polymyxin B inhibited noradrenaline release during a 10 or 15 s train of impulses but not during a 5 s train. This suggests that PKC effects are induced during the stimulation train by some process. 4. The diacylglycerol kinase inhibitor R59949 (10 microM), which prevents the breakdown of diacylglycerol, enhanced noradrenaline release elicited by stimulation at 10 Hz for 10 or 15 s. This effect was not seen if polymyxin B was present and suggests that diacylglycerol is the endogenous activator of PKC. 5. The source of the diacylglycerol may be through phospholipase C pathways, since the phospholipase C inhibitor U73122 (3 microM) inhibited noradrenaline release at 10 Hz for 10 s and the effect was not seen if polymyxin B was also present. 6. It is unlikely that phospholipase D is the source of diacylglycerol. Although the phospholipase D inhibitor wortmannin (1 microM) inhibited noradrenaline release, this effect was still observed in the presence of polymyxin B. Furthermore ethanol, which inhibits diacylglycerol formation by phospholipase D, had no effect on noradrenaline release. 7. We therefore suggest that during a train of high frequency pulses phospholipase C is activated and this results in the production of diacylglycerol which in turn activates PKC. This enables the neurones to maintain transmitter release at a high level.

Androstadienes↗
PubMed1997

Factors associated with unnecessary immunization given to children.

OBJECTIVE: To determine the factors associated with unnecessary immunization during the pre-school years. METHODS: Children were selected from birth certificates and their parents were interviewed to identify all immunizations to 72 months of age. The immunizations were verified. RESULTS: Of 187 children studied 34 (18%) received unnecessary immunization. Unnecessary immunization was strongly associated with ever receiving immunization in a large system of public clinics (designated "Public A") (33%) compared with other providers (5%) (P < 0.00001). Among children immunized in Public A, unnecessary immunization was associated with the parent having an incomplete or no copy of the child's immunization record (P = 0.007) and with not being up to date for immunizations at 24 months of age (P = 0.04). Complete documentation of immunizations either in the Public. A record or in the parent's copy of the record was associated with a 4% rate of unnecessary immunization; incomplete or no documentation in both the Public A and the parent's record was associated with a 45% rate of unnecessary immunization (P = 0.001). CONCLUSIONS: Access to a complete immunization record, be it the provider's, the parent's or ideally both, decreases substantially a child's risk of unnecessary immunization.

Analysis of Variance↗
PubMed1997

Protein kinase C and transmitter release.

1. Protein kinase C (PKC) is an important second messenger-activated enzyme. In noradrenergic nerves it appears to be tonically activated by diacylglycerol (DAG) to facilitate transmitter release and the steps in this involve activation of phospholipase C, generation of DAG and activation of PKC. It is suggested that the subsequent facilitation of transmitter release is due to the phosphorylation of proteins involved in the release process distal to Ca2+ entry, presumably those involved in vesicle dynamics. 2. There are differences between central noradrenergic neurons and sympathetic nerves. In central neurons PKC appears to be tonically active and its inhibition results in a decrease in noradrenaline release under most, if not all, conditions. 3. In sympathetic nerves PKC inhibitors only decrease transmitter release during high-frequency stimulation and not during low-frequency stimulation. At high frequency there is a gradual increase in the effect of PKC inhibitors on transmitter release during the first 15 s of a stimulation train. It is suggested that this is due to a progressive rise in intracellular Ca2+ and a consequent activation of PKC. 4. Activation of PKC by phorbol esters produces a large enhancement in action potential-evoked noradrenaline release in both the central nervous system and in peripheral tissues. The structural requirements of the phorbol esters for maximal effect suggest that the phorbol esters must access the interior of the nerve terminal to activate PKC and the neural membrane acts as a barrier for highly lipophilic phorbol esters, thereby reducing their activity. Activation of PKC represents one of the most powerful ways to enhance transmitter release and may have therapeutic potential.

Animals↗
PubMed1995

Specific accumulation of inositol 1,4,5-trisphosphate in rabbit basilar artery in response to noradrenaline but not 5-hydroxytryptamine.

This study examined the ability of 5-hydroxytryptamine and noradrenaline to stimulate inositol 1,4,5-trisphosphate (IP3) mass accumulation in segments of the rabbit basilar artery. 5-Hydroxytryptamine (5-HT, 100 microM) failed to stimulate any significant accumulation of IP3 during the 5 min period following its application. In the presence of prazosin, 5-HT (300 microM) caused a rapid, transient decrease in IP3 accumulation which was significant after 5 s but had increased to pre-stimulation levels within 15 s. In contrast, noradrenaline (10 microM) stimulated a rapid, transient accumulation of IP3 which was significant after 5 s but had declined to basal levels after 60 s. In basilar artery segments bathed in Krebs solution containing 25.7 mM K+ (normal concentration 5.7 mM), the basal IP3 concentration was significantly elevated. The IP3 accumulation stimulated by either 5-HT or raised K+ was not reduced by the presence of the alpha 1-adrenoceptor antagonist, prazosin (0.1 microM). In the presence of raised K+, 5-hydroxytryptamine caused a rapid, transient inhibition of the K(+)-induced IP3 accumulation, which was maximal after 5 s but had increased to pre-stimulation levels within 30 s in the continued presence of 5-hydroxytryptamine. Noradrenaline did not affect the IP3 accumulation induced by raised extracellular [K+]. These results provide further evidence that IP3 is not involved in 5-hydroxytryptamine-induced smooth muscle contraction in the rabbit basilar artery, but support a role for this second messenger in the contraction induced in response to noradrenaline.

Animals↗
PubMed1995

Characterisation of inositol 1,4,5-trisphosphate binding sites in rabbit aortic smooth muscle.

The present study investigated the characteristics of D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) binding sites in crude membrane preparations of rabbit aortic smooth muscle. A particular aim was to demonstrate if increases in cytoplasmic cyclic guanosine 3':5' monophosphate (cGMP), which mediates the effect of nitrovasodilators, may cause smooth muscle relaxation in part by the displacement of Ins(1,4,5)P3 binding. Negligible Ins(1,4,5)P3 binding was observed at pH < 7, while maximum binding occurred over the pH range 8-9. Saturation analysis of isotopic dilution binding data revealed an apparently homogenous population of Ins(1,4,5)P3 binding sites with a KD of 4.02 +/- 0.53 nM and a Bmax of 27.7 +/- 4.6 fmol/mg protein. Heparin, an Ins(1,4,5)P3 receptor antagonist, inhibited binding with an IC50 of 11.43 +/- 2.81 micrograms/ml. The ability of other polyphosphate compounds to inhibit Ins(1,4,5)P3 binding in this preparation was also examined. D-myo-Inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), adenosine 5'-triphosphate (ATP) and guanosine 5'-triphosphate (GTP) inhibited Ins(1,4,5)P3 binding, although each was significantly less potent that Ins(1,4,5)P3. In contrast, cyclic guanosine 3':5' monophosphate (cGMP) did not significantly alter Ins(1,4,5)P3 binding in rabbit aortic smooth muscle. This observation suggests that competitive inhibition of Ins(1,4,5)P3 receptor binding is not an important consideration in cGMP-mediated vascular smooth muscle cell relaxation.

Adenine Nucleotides↗
PubMed1995

Pediatric clinical clerkships are associated with an excess risk of acute infection.

OBJECTIVE: To determine the incidence of acute respiratory and gastrointestinal tract illness and associated absence by third-year medical students during pediatric and nonpediatric (control) clinical clerkships. DESIGN: A self-administered questionnaire was completed by students after the first 4 weeks of two pediatric clerkships (inpatient and outpatient) and two non-pediatric clerkships (obstetrics-gynecology and psychiatry). Information was obtained on the symptoms of acute respiratory and gastrointestinal tract illness and related absences. ANALYSIS: Results from each student's pediatric clerkship were compared with the results from the same student's control clerkship by means of matched-pair analysis. SUBJECTS: Students who made up the junior class at the University of Texas Southwestern Medical School at Dallas, July 1, 1990, to June 30, 1991. RESULTS: Of 177 students (77%) who completed questionnaires after one pediatric and one control clerkship, 108 students (61%) had had an acute illness while on pediatric clerkships in contrast to 69 students (39%) on control clerkships (odds ratio, 3.3; 95% confidence interval, 2.0 to 5.4; P < .001). More students were absent for illness during pediatric than control clerkships (23 [13%] vs nine [5%], respectively; odds ratio, 2.7; 95% confidence interval, 1.2 to 6.2; P = .02). The higher risk of illness during pediatric clerkships was not related to the order of the pediatric or control clerkship, the order of inpatient and outpatient pediatrics, or the season of the year. CONCLUSION: Pediatric clinical clerkships in the third year of medical school were associated with excess morbidity from acute infectious illness. Studies are needed to determine whether emphasizing infection control practices decrease this morbidity and any resulting nosocomial spread to patients.

Absenteeism↗
PubMed1995

Estimating immunization coverage from school-based childhood immunization records.

To determine the accuracy of school-based childhood immunization records and to describe the effects of their use on estimates of community-wide immunization coverage, we verified the immunizations to 72 months of age for children born in 1986 to residents in Dallas County, TX, and in Minnesota. Verified immunizations were compared with those documented in the school record. Major transcription errors accounted for fewer than 1% of discrepancies between school and provider records. For 99 subjects with 987 verified immunizations in Minnesota, age-appropriate immunization coverage estimated from the school records was within two percent of actual coverage. For 86 subjects with 981 verified immunizations in Dallas County, age-appropriate immunization coverage from the school records underestimated actual coverage by as much as 21%. The primary factor explaining the underestimate in Dallas was incomplete school immunization records for 33 (38%) subjects and 126 (13%) immunizations. Selective recording of immunizations related to the minimum state requirements in Texas contributed to incomplete school records in Dallas County. Verification of the completeness of records selected to estimate immunization coverage is essential if the estimates are used to monitor trends or to make public policy decisions.

Child↗
PubMed1994

Phorbol esters impair endothelium-dependent and independent relaxation in rat aortic rings.

1. This study examined the ability of various nitro-vasodilators, 8-bromo cyclic guanosine 3':5' monophosphate (8-BrcGMP) and forskolin to relax rings of rat thoracic aorta pre-contracted with either noradrenaline (0.1 microM) or the protein kinase C activators, phorbol 12,13-dibutyrate (PDB, 0.1 microM) or phorbol 12-myristate 13-acetate (PMA, 0.5 microM). 2. In noradrenaline pre-contracted rings, acetylcholine (10 nM-10 microM), sodium nitroprusside (1 nM-0.5 microM), the calcium ionophore A23187 (10 nM-10 microM) and 8-BrcGMP (10 mM) totally reversed the smooth muscle contraction. In PDB-contracted aortic rings acetylcholine, sodium nitroprusside and 8-BrcGMP-induced relaxation was reduced compared to that in noradrenaline-contracted aortic rings, but A23187 and forskolin-induced relaxations were unaffected. Both acetylcholine and A23187-induced relaxations in PDB-contracted rings were abolished in the presence of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine (NOLA, 100 microM). 3. Acetylcholine and sodium nitroprusside were even less potent in their ability to relax PMA-contracted aortic rings compared with noradrenaline and PDB-contracted rings. A23187-induced relaxation was also inhibited in PMA-contracted rings. 4. These results show that protein kinase C activation reduces the ability of agents which liberate nitric oxide to induce smooth muscle relaxation, and also inhibits the biochemical pathways which are subsequently activated by nitric oxide and lead to vascular smooth muscle relaxation.

Acetylcholine↗
PubMed1994

Importance of inositol (1,4,5)-trisphosphate, intracellular Ca2+ release and myofilament Ca2+ sensitization in 5-hydroxytryptamine-evoked contraction of rabbit mesenteric artery.

1. Small strips from third-order branches of rabbit mesenteric artery (approximately 150-200 microM wide) contracted in response to noradrenaline (10 microM) or 5-hydroxytryptamine (5-HT; 10 microM) in oxygenated Krebs solution containing 2.5 mM Ca2+. In a Ca(2+)-free mock intracellular solution (0 Ca2+ plus 0.2 mM EGTA), noradrenaline (10 microM) and caffeine (10 mM) induced only a single, transient contraction in artery strips, while 5-HT (10 microM) failed to induce any response. 2. In strips of mesenteric artery which had been permeabilized with Staphylococcus alpha-toxin and bathed in Ca(2+)-free mock intracellular solution, noradrenaline (10 microM), caffeine (10 mM) and D-myo-inositol (1,4,5)-trisphosphate (IP3, 100 microM), but not 5-HT (10 or 100 microM) induced a transient contraction. In contrast to the non-permeabilized strips, contractions to noradrenaline, caffeine and IP3 were restored by prior incubation (10 min) in solution containing 0.08 microM Ca2+. The contractions to noradrenaline and IP3 in permeabilized muscle strips required the presence of 100 microM guanosine 5'-triphosphate (GTP), although in the absence of Ca2+. GTP alone did not induce contraction. 3. Exposure of permeabilized mesenteric artery strips to IP3 significantly reduced the subsequent contractile responses to caffeine. Contractile responses to caffeine and IP3 were abolished by the Ca(2+)-ATPase inhibitor, thapsigargin (1 microM). 4. Ca2+ (0.1-10 microM) induced concentration-dependent contraction in permeabilized artery strips. In strips which were submaximally contracted with 0.5 microM Ca2+/100 microM GTP, the subsequent addition of 5-HT (10 microM) stimulated further contraction. The protein kinase C inhibitor, H-7 (1 microM) abolished the 5-HT/GTP-induced contraction, but did not alter the contraction to Ca2+. 5. In non-permeabilized, endothelium-denuded segments of rabbit mesenteric artery bathed in Ca2+-replete Krebs solution, noradrenaline (10 microM) stimulated a rapid, transient accumulation of IP3. 5-HT(100 microM) failed to stimulate IP3 accumulation during exposure periods of up to 5 min. 5-HT (100 microM)did stimulate IP3 accumulation if the external K+ concentration was raised (to around 25 mM). This concentration of K+ alone did not stimulate IP3 production and the 5-HT-stimulated IP3 accumulation in the presence of elevated extracellular [K+] was abolished by the alpha l-adrenoceptor antagonist, prazosin(O.1 microM).6. These results suggest that intracellular Ca2+ release does not play an important role in 5-HT-induced smooth muscle contraction in the rabbit mesenteric artery. This is despite the fact that a significant intracellular Ca2+ pool is present in these cells, which can be discharged by either noradrenaline or IP3.However, 5-HT did stimulate smooth muscle contraction in the presence of raised intracellular calcium,suggesting that a component of the contraction to 5-HT will reflect an increase in myofilament Ca2+sensitivity, possibly due to the activation of protein kinase C.

Actin Cytoskeleton↗
PubMed1993

Declining incidence of Haemophilus influenzae type b disease since introduction of vaccination.

OBJECTIVE: To determine the incidence of invasive Haemophilus influenzae type b disease in children living in Minnesota and Dallas County, Texas, before and since introduction of plain polysaccharide vaccine in 1985, and conjugate vaccine in 1988. Initially, use of these vaccines was limited to infants 18 months of age and older. DESIGN: Identification of culture-proven cases of H influenzae type b disease was through systems of active, laboratory-based surveillance. The mean incidence of disease (cases observed/100,000 child-years) for 1983 and 1984 served as a baseline for comparison with subsequent years through 1991. PARTICIPANTS: Children less than 5 years of age in Minnesota and Dallas County, Texas. Overall, there were 2557 confirmed age-eligible cases of invasive H influenzae type b disease from 1983 through 1991. RESULTS: Between the 1983-1984 baseline and 1991, the incidence of H influenzae type b disease decreased 85% in Minnesota and 92% in Dallas. Notably, declines in incidence were observed in children in the age group being vaccinated as well as in infants younger than 18 months of age prior to introduction of vaccination. CONCLUSION: In two widely separated areas of the United States, a profound decrease in the incidence of H influenzae type b disease has occurred. The data suggest that vaccination may be protecting against disease, as well as decreasing the spread of infection to unvaccinated infants.

Bacterial Capsules↗
PubMed1993

Decreased Haemophilus colonization in children vaccinated with Haemophilus influenzae type b conjugate vaccine.

OBJECTIVE: The incidence of invasive Haemophilus disease has unexpectedly decreased in unvaccinated children since the introduction of conjugate vaccine in the United States. The purpose of this study was to determine whether conjugate vaccination decreases colonization with Haemophilus influenzae type b. DESIGN: This study was a prospective, bimonthly survey of pharyngeal colonization with H. influenzae type b in children attending day care from October 1987 through September 1989. Vaccination status was determined from the medical record. SUBJECTS: We obtained 1188 pharyngeal cultures from 283 healthy children, 18 to 59 months of age; 51 children had received unconjugated polysaccharide vaccine (PRP), and 89 had received conjugate vaccine (94% PRP-diphtheria toxoid). MEASUREMENTS AND RESULTS: Multivariate analysis was used to test the possibility of an association between vaccination status and the rate of colonization with H. influenzae type b. Among children known to be exposed to at least one child with a positive culture result, the efficacy of conjugate vaccination to prevent H. influenzae type b colonization in an unmatched analysis was 64% (95% confidence interval: 5%, 86%; p = 0.02) and in a matched analysis 81% (95% confidence interval: 7%, 96%; p = 0.02). No effect on colonization was found with PRP vaccination. CONCLUSIONS: Conjugate vaccination decreases H. influenzae type b pharyngeal colonization and thereby may decrease transmission of this agent among healthy children.

Bacterial Proteins↗
PubMed1993

Induction of immunologic memory in infants primed with Haemophilus influenzae type b conjugate vaccines.

The ability of different Haemophilus influenzae type b conjugate vaccines to induce immunologic memory was compared in 381 infants who were vaccinated with one of three conjugate vaccines beginning at 2 months of age. All infants were vaccinated with unconjugated type b capsular polysaccharide, polyribosylribitol phosphate (PRP), at 12 months. In each group, high antibody responses were detected by 6-9 days after vaccination. One month after receiving PRP, infants primed with PRP conjugated to the outer membrane protein of Neisseria meningitidis or PRP oligomers conjugated to the cross-reactive mutant diphtheria protein, CRM197, had twofold higher total anti-PRP antibody concentrations than did infants primed with PRP conjugated to tetanus toxoid (P < .005). After the conjugate and the PRP boost, notable differences were present among vaccine groups with respect to the magnitude of the IgG anti-PRP antibody concentrations and light chain variable region usage as determined by idiotypic analysis. Thus, each of the conjugate vaccines primed infants for the ability to evoke memory antibody responses to PRP, but qualitative and quantitative differences in priming induced by different vaccines may affect their ability to confer protection against disease.

Bacterial Outer Membrane Proteins↗
PubMed1992

Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants.

OBJECTIVE: To compare the immunogenicity of three Haemophilus influenzae type b (Hib) conjugate vaccines in infants residing in different geographic areas. DESIGN: A multicenter, randomized immunogenicity trial with sera assayed in one laboratory without knowledge of vaccine brand status. In Minneapolis and Dallas, infants were vaccinated at 2, 4, and 6 months of age; in St. Louis, infants were vaccinated at 2 and 4 months of age. SUBJECTS: A convenience sample of 458 infants recruited largely from private pediatric practices. MEASUREMENTS AND RESULTS: At each of the study sites, the respective trends between the anticapsular antibody responses of the infants assigned to the different conjugate vaccine groups were similar. After one or two doses, Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis (PRP-OMP) was more immunogenic than Hib polysaccharide-tetanus toxoid conjugate (PRP-T), or Hib oligomers conjugated to the mutant diphtheria toxin CRM197 (HbOC) (p less than 0.001). After two doses, PRP-T was more immunogenic than HbOC (p less than or equal to 0.001). After three doses there was no significant difference in the geometric mean antibody concentrations of the three groups, and 88% to 97% of the infants had greater than 1.0 microgram/ml of antibody. The HbOC vaccine elicited a 10-fold lower antibody response after two doses (0.45 micrograms/ml vs 5.9 micrograms/ml) and a threefold lower antibody response after three doses (6.3 micrograms/ml vs 22.9 micrograms/ml) than observed by us previously with a prelicensure lot of this vaccine (p less than 0.001). Because of these low responses, the infants in St. Louis who received two doses of HbOC were revaccinated with unconjugated PRP at a mean age of 8.9 months. This group was immunologically primed, as evidenced by a 10-fold increase in geometric mean antibody concentration after vaccination at an age when unprimed infants do not normally respond to this vaccine. CONCLUSIONS: In infants in three geographic regions, PRP-OMP elicited earlier acquisition of serum antibody than the other two conjugate vaccines; however, after three doses the antibody concentrations of the three groups were not significantly different. The reason for the markedly lower immunogenicity of HbOC vaccine than reported previously is unknown.

Age Factors↗