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Biomedical subjects

G Hogg

Publications and source records attributed to G Hogg.

At least 19 recordsLinked to original sources

A combined liquid Hib (PRP-OMPC), hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine: controlled studies of immunogenicity and reactogenicity.

We evaluated the immunogenicity and reactogenicity of a new liquid pentavalent combination vaccine, which incorporates a diphtheria, tetanus and whole-cell pertussis vaccine (DTP) with Hib (PRP-OMPC) and hepatitis B vaccine (HB), in a series of three studies involving 2156 infants. The vaccination schedule was 2, 4, 6 and 18 months for all studies. In addition, subjects in the third study also received a dose of monovalent hepatitis B vaccine at birth. The principal study was a randomised double blind trial of two separate, but concurrently administered vaccines in each of three groups: pentavalent vaccine [DTP-Hib-HB] plus placebo (Group A, n=619); quadrivalent vaccine [DTP-HB] plus Hib vaccine (Group B, n=620); and bivalent vaccine [Hib-HB] plus DTP (Group C, n=226). The second study (Group D, n=231) was an open trial of three separate, but concurrently administered licensed control vaccines (DTP, Hib and HB). The third study (Group E, n=460) administered a dose of monovalent hepatitis B vaccine at birth followed by pentavalent vaccine as for Group A. Subjects were bled prior to the 2- and 18-month vaccinations, and a month after the 6- and 18-month vaccinations. A diary card was used to record subject temperatures and other systemic and local clinical signs for 7 days after each vaccination. The pentavalent vaccine, whether or not preceded by a birth dose of hepatitis B vaccine, was generally well tolerated at all administration times, and had a reactogenicity profile similar to that observed for licensed vaccine controls. Diphtheria and tetanus antibody levels were substantially above protective levels in all study groups. The anti-HBs responses (% > or = 10 mIU/ml) following the 6-month dose of vaccines were, respectively, for Groups A-E: 83.2, 91.7, 96.5, 98.8 and 93.9%, and following the 18-month doses: 87.9, 97.5, 98.8, 98.8 and 92.8%. Anti-PRP responses (% > or = 1.0 microg/ml) following the 6-month dose for Groups A-D were 86.0, 90.5, 91.2, and 74.4%, and after the 18-month dose for Groups A-E were 97.3, 98.3, 98.1, 97.0, and 99.5%. Consistently higher geometric mean titres (GMTs) for pertussis antibodies to agglutinogens (Agg2, Agg3) and pertactin were recorded for the pentavalent vaccine compared to the licensed control vaccine, though they were somewhat lower for pertussigen (PT). Except for the hepatitis B response, antibody responses induced by the pentavalent vaccine to all antigens with a schedule commencing at 2 months of age and completed at 18 months were equivalent to responses to the same antigens induced by the separate, but concurrently administered licensed control vaccines. A regimen of a birth dose of hepatitis B vaccine followed by pentavalent vaccine at 2, 4, 6 and 18 months was not countered by any clinically significant decrease in seroresponses.

Age Factors↗

The impact of diagnosis by legionella urinary antigen test on the epidemiology and outcomes of Legionnaires' disease.

Legionnaires' disease is an uncommon but important cause of life-threatening community-acquired or nosocomial pneumonia. The urinary antigen enzyme immunoassay test, used in Victoria since 1995, now accounts for the majority of initial laboratory notifications (81% in 1999). We review the impact of the test on the disease epidemiology and the public health investigative process. We focus on the major subgroup of cases due to Legionella pneumophila serogroup 1, comparing delays until notification and mortality for urinary antigen detected cases with culture detected cases. The urinary antigen test facilitates a 5-day reduction for the delay between onset of illness and notification. We observed that there was minimal clinical heterogeneity of urinary antigen detected cases whether they were subsequently culture confirmed or not. We encourage clinician use of the urinary antigen test in cases of community-acquired pneumonia where Legionnaires' disease is a possible diagnosis, in conjunction with culture of clinical specimens.

Adult↗

Surveillance of antibiotic resistance in invasive isolates of Neisseria meningitidis in Australia 1994-1999.

A total of 1434 strains of Neisseria meningitidis isolated from cases of invasive meningococcal disease (IMD) in Australia between 1994 and 1999 were examined by standard methods for susceptibility to antibiotics used for treatment and prophylaxis. The proportion of isolates fully susceptible to penicillin decreased from 45% in 1994 to 26% in 1999 (P<0.001). All the other isolates were less sensitive to penicillin except for two meningococci with a penicillin MIC of 1 mg/l. The geometric mean penicillin MIC increased from 0.045 to 0.065 mg/l from 1994 to 1999. There was no significant difference in the geometric mean penicillin MICs of serogroup B and serogroup C meningococci. Penicillin susceptibility was significantly associated with a poorer outcome. Isolates from survivors of IMD had a higher geometric mean penicillin MIC (0.06 mg/l) than those from fatal cases (0.048 mg/l) (P< 0.001). This suggests that factors other than the decrease in susceptibility to penicillin observed were more relevant to outcome in IMD. All isolates were fully susceptible to ceftriaxone. Rifampicin resistance was infrequent (eight isolates in 6 years) and sporadic. A single isolate had decreased quinolone susceptibility. Despite the significant shift in susceptibility to penicillin recorded, this group of antibiotics remains a suitable treatment for IMD in Australia.

4-Quinolones↗

An outbreak of serogroup C meningococcal disease associated with a secondary school.

An outbreak of 3 cases of invasive meningococcal disease occurred in a secondary school on 2 campuses in Victoria. Despite having only one isolate (a C.2a:nst strain), meningococcal DNA was identified by polymerase chain reaction (PCR) in early culture-negative blood specimens of the other 2 cases. Both were subsequently shown by PCR to be capsule serogroup C by PCR. An committee was formed to manage the response to the outbreak. Chemoprophylaxis was offered to family and children who had been in close contact with the cases. As one strain had been confirmed as being of a vaccine-preventable group, vaccination was offered to the whole school community as well as the families of cases. The direct costs of the outbreak to public health, which would have been identical whatever the causative serogroup, was $8,178. Vaccine charges accounted for most of the additional $56,941 cost of vaccinating the target group of 1600 students, staff, and families. No further cases have been associated with this outbreak.

Child↗

Legionnaires' disease outbreak: Victoria's largest identified outbreak.

This paper describes and analyses some aspects of an outbreak of Legionnaires' disease in Victoria, commencing in late October 1998. In all, 18 cases caused by Legionella pneumophila serogroup 1 were notified within 10 days making this the largest outbreak in Victoria reported to that date. All cases had epidemiological links to an industrial estate in a northern Melbourne suburb. Extensive environmental sampling revealed Legionella bacteria in five cooling towers. Molecular sub-typing techniques were used to compare clinical and environmental isolates. Isolates from one tower had a pulsed-field gel electrophoresis pattern that was indistinguishable from clinical isolates from eight cases. Control of outbreaks caused by Legionella bacteria requires rapid, coordinated responses to linked cases of disease. The Legionella urinary antigen test facilitated a rapid public health response, and culture and molecular sub-typing of clinical specimens assisted in developing epidemiological links.

Adult↗

Outcome of a screening program for vancomycin-resistant enterococci in a hospital in Victoria.

OBJECTIVE: To screen for faecal colonisation with vancomycin-resistant enterococci (VRE) among potentially at-risk patients. DESIGN: Infection control screening program. SETTING: Monash Medical Centre (a tertiary care hospital), Melbourne, Victoria, in the seven months from June 1997. PATIENTS: Patients in the Renal, Oncology and Intensive Care (ICU) Units. MAIN OUTCOME MEASURES: Presence of VRE in a rectal swab or faecal specimen taken at admission and at regular intervals during inpatient stay; presence of vancomycin-resistance genes (vanA, vanB and vanC) assessed by polymerase chain reaction (PCR); genetic clonality of isolates assessed by pulsed-field gel electrophoresis (PFGE). RESULTS: 574 patients (356 renal, 134 ICU and 84 oncology) were screened; 12 were colonised with VRE--nine renal inpatients, two having peritoneal dialysis or incentre haemodialysis, and one ICU patient. Nine isolates were Enterococcus faecalis (seven positive for vanB and two negative for all three resistance genes) and three were Enterococcus faecium (all positive for vanB). Eight were high-level gentamicin resistant. PFGE suggested genetic clonality between the index isolate and five other isolates from renal patients. No specific clinical practice was associated with VRE colonisation. Attempts to clear rectal carriage with oral ampicillin/amoxycillin or bacitracin were of limited success. Although antibiotic prescribing in the Renal Unit was generally consistent with defined protocols, use of vancomycin and third-generation cephalosporins has been further restricted. CONCLUSIONS: Renal inpatients in our institution appear most at risk of VRE colonisation (4.6% overall) and therefore of VRE infection. Routine screening, especially of potentially high-risk patients, should be considered in major Australian hospitals.

Adult↗

Implications of endotracheal tube biofilm for ventilator-associated pneumonia.

OBJECTIVE: To determine the relationship between, and antibiotic resistance of, endotracheal tube (ET) biofilm and pulmonary pathogens in ventilator-associated pneumonia (VAP). SETTING: General intensive care units in two university teaching hospitals. DESIGN: The microbiology of ET biofilm and tracheal samples from patients with and without VAP were compared. For individual patients, matching pairs of pathogens were confirmed as identical and characterised for antibiotic susceptibility. PATIENTS: 40 intensive care unit patients - 20 with VAP, 20 without VAP as control. The duration of intubation (median and range) was 6.5 days (3-17) and 5 days (2-10), respectively. MEASUREMENTS AND RESULTS: Samples of tracheal secretions were taken during ventilation for bacteriological culture. Following extubation, ETs were examined for the presence of biofilm. Isolates of high pathogenic potential included Staphylococcus aureus, enterococci, Enterobacteriaceae, pseudomonads and Candida spp. Where the same microorganism was found on tracheal and ET samples by phenotyping, these were confirmed as identical by genotyping and characterised for antibiotic susceptibility in both the free floating and biofilm forms. Seventy per cent of patients with VAP had identical pathogens isolated from both ET biofilm and tracheal secretions. No pairing of pathogens was observed in control patients (p < 0.005). Susceptibility data for these pairs show that the ET acts as a reservoir for infecting microorganisms which exhibit significantly greater antibiotic resistance than their tracheal counterparts. CONCLUSION: This investigation provides further evidence for the role of ET biofilm in VAP. The difficulty in eradicating an established microbial biofilm using antibiotics implies that increased attention must be directed towards modification of the ET to prevent or substantially reduce biofilm formation.

Adolescent↗

Safety and pharmacokinetics of an intramuscular monoclonal antibody (SB 209763) against respiratory syncytial virus (RSV) in infants and young children at risk for severe RSV disease.

We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized monoclonal antibody against a respiratory syncytial virus (RSV) fusion protein (SB 209763) to evaluate its safety, pharmacokinetics, and fusion inhibition and neutralization titers. Forty-three infants who were either delivered prematurely (</=35 weeks' gestation) or exhibited bronchopulmonary dysplasia were administered either single or repeat (two doses, 8 weeks apart) intramuscular injections of SB 209763 at a concentration of 0.25, 1.25, 5.0, or 10.0 mg/kg or of a placebo. Four of 229 adverse events were considered related to the study drug, including purpura (n = 3) and thrombocytosis (n = 1). No subject developed a detectable level of anti-SB 209763 antibody. Approximately 1 week after administration of the second dose of SB 209763 at 10 mg/kg, the mean plasma concentration (n = 9) was 68.5 micrograms/ml. The terminal half-life (T1/2) determined by noncompartmental analysis ranged from 22 to 50 days. The population pharmacokinetics for SB 209763 following intramuscular administration was appropriately described by a one-compartment model with first-order input and elimination. Higher values for clearance and volume of distribution at steady state were observed for younger patients, with values decreasing to 0.143 (ml/h)/kg and 161 mL/kg, respectively, by a mean age of 298 days (approximately 10 months). The mean T1/2 of SB 209763 for the study population was 32.5 days. No other factor (dose, weight, gender, race, premature birth, or bronchopulmonary dysplasia) was observed to alter the population pharmacokinetics of SB 209763 in this study of infants and young children. The mean neutralization titer on day 6 was 286, and the mean fusion inhibition titer was 36. At least 57% of subjects dosed at 1.25 to 10.0 mg of SB 209763 per kg of body weight who were seronegative at baseline experienced a fourfold or greater increase in fusion inhibition titer. Nine RSV infections were documented during the 16-week course of the study; the numbers of RSV infections were similar for the different regimens, including the placebo. The doses of SB 209763 studied may have been insufficient to confer protection against RSV lower respiratory tract disease; these results suggest that additional trials using higher doses of monoclonal antibody for immunoprophylaxis should be considered.

Antibodies, Monoclonal↗

Vulvovaginitis: clinical features, aetiology, and microbiology of the genital tract.

AIM: To clarify the contribution of clinical and environmental factors and infection to the aetiology of vulvovaginitis in premenarchal girls, and to determine clinical indicators of an infectious cause. DESIGN: It was necessary first to define normal vaginal flora. Cases were 50 premenarchal girls > 2 years old with symptoms of vulvovaginitis; 50 controls were recruited from girls in the same age group undergoing minor or elective surgery. RESULTS: Interview questionnaire showed no difference between cases and controls in regards to hygiene practices, exposure to specific irritants, or history of possible sexual abuse. Normal vaginal flora was similar to that described in previous studies, with the exception of organisms likely to be associated with sexual activity. 80% of cases had no evidence of an infectious cause. In the 10 cases in whom an infectious cause was found, there was significantly more visible discharge and distinct redness of the genital area on examination compared with other cases. CONCLUSIONS: The findings suggest that vulvovaginitis in this age group is not usually infectious or necessarily related to poor hygiene, specific irritants or sexual abuse, although any of these can present with genital irritation. The possibility of sexual abuse should always be considered when a child presents with genital symptoms, but our data indicate it is not a common contributing factor. Infection is generally associated with vaginal discharge and moderate or severe inflammation.

Adolescent↗

A combined liquid Hib (PRP-OMP), hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine: uncontrolled preliminary clinical trial of immunogenicity and reactogenicity.

We have conducted a preliminary uncontrolled clinical trial of the immunogenicity and reactogenicity of a new fully liquid pentavalent combination vaccination which incorporates a diphtheria, tetanus and whole-cell pertussis vaccine with Hib (PRP-OMP) and hepatitis B vaccines. Forty-five infants received three doses of the pentavalent vaccination at 2, 4, and 6 months of age, and then a fourth dose at 18 months of age. Subjects were bled prior to each vaccination, and a month after the third and fourth vaccinations. A 7-day diary card was used to record subject temperatures and other systemic and local clinical signs after each vaccination. After the third dose, 98% of subjects had anti-PRP titres above 1 microgram ml-1 (95%ci 88%, 100%). Following boosting, the geometric mean titre (GMT) rose a mean 27-fold (95%ci 19-fold, 38-fold) to 33 micrograms ml-1, and all subjects' titres (lower bound of 95%ci 92%) exceeded 1 microgram ml-1. For hepatitis B antibody, there was a GMT of 100 mIU ml-1 after the third dose, and 86% of infants (95%ci 73%, 95%) had antibody levels > or = 10 mIU ml-1. After the fourth dose, there was a mean 77-fold boost (95%ci 48-fold, 130-fold) to a GMT of 860 mIU ml-1 and 95% (95%ci 84%, 99%) of subjects had titres > or = 10 mIU ml-1. Diphtheria, tetanus, and pertussis antibody levels were all at acceptable levels after the first three doses and again after the fourth vaccination. The pentavalent vaccine was well tolerated at all administration times, and had a minor reactogenicity profile similar to DTPw alone as reported in previous studies. This study has provided preliminary evidence for both the safety and immunogenicity of the pentavalent vaccine given as a course at 2, 4, 6 and 18 months.

Antibodies, Bacterial↗

Immunogenicity and reactogenicity associated with an 18-month booster dose of a new diphtheria-tetanus-whole cell pertussis vaccine.

OBJECTIVE: To establish safety and immunogenicity of a reformulated whole cell pertussis based diphtheria-tetanus-pertussis vaccine (DTPw) at the 18-month booster stage following a 2, 4, and 6-month primary immunization course. METHOD: Open trial in suburban Melbourne in 100 healthy children initially recruited through maternal and child health centres. Thirty-five subjects were bled prior to vaccination, and 4-6 weeks after vaccination. A 7-day diary card was used to record subject temperatures and other systemic and local clinical signs. RESULTS: The increase in antibody geometric mean titres (GMT) after boosting was 19.5-fold (95%ci 14.2, 27.2) for tetanus and 26.5-fold (95%ci 16.6, 42.4) for diphtheria. Pertussis antibody GMTs also all showed substantial increases following the booster, with mean fold changes in titre ranging from 7.3 (Agg2) to 31.3 (Fha). Seventeen percent of subjects (95%ci 10%, 26%) experienced axillary temperatures > or = 38 degrees C during the 24-h period following vaccination. Low rates of significant (> 25 mm) injection site redness (13%) and swelling (8%) were recorded at 24 h postvaccination. CONCLUSION: This vaccine was well tolerated by children at 18 months of age, and showed substantial boosting of antibody to all components.

Diphtheria-Tetanus-Pertussis Vaccine↗

Primary course immunogenicity and reactogenicity of a new diphtheria-tetanus-whole cell pertussis vaccine (DTPw).

OBJECTIVE: To establish safety, immunogenicity, and batch stability of a reformulated whole cell pertussis based diphtheriatetanus-whole cell pertussis (DTP) vaccine (nDTPw) compared to the currently marketed Australian DTPw vaccine (Triple Antigen) in a three dose 2, 4 and 6 month primary immunization course. Reformulation was necessary to make the DTPw vaccine suitable for combination with hepatitis B and Haemophilus influenzae b vaccines. METHODS: Double blind randomized controlled trial in suburban Melbourne in 812 healthy infants recruited through maternal and child health centres, of whom 208 received Triple Antigen and 604 received nDTPw. RESULTS: Results for both reactogenicity and immunogenicity were similar and were not significantly different for the three batches of nDTPw. No new, serious, or unexpected adverse effect was recorded. Nearly twice as many nDTPw infants experienced no general reaction to the third dose (18%) compared to Triple Antigen (11%, P = 0.06). An elevated temperature (> or = 38 degrees C axillary) occurred in about three out of 10 babies overall, with rates being slightly higher for both vaccines after the second vaccination. Local reaction rates were significantly less common for nDTPw on days 2 and 3 following each of the three vaccinations. After dose three, 30% of nDTPw subjects experienced no local reaction compared to 20% of Triple Antigen subjects (P = 0.015, 95% Cl on difference 2%, 19%). Swelling after doses one and three occurred in 30% and 24% of Triple Antigen subjects, compared to 23% (P = 0.07, 95% Cl diff 0%, 13%) and 14% (P = 0.017, 95% Cl diff 2%, 17%) of nDTPw subjects. Tenderness after doses two and three occurred in 80%, and 78% of Triple Antigen subjects, compared to 71% (P = 0.04, 95% Cl diff 1%, 17%) and 68% (P = 0.025, 95% Cl diff 2%, 19%) of nDTPw subjects. There was a significantly higher post immunization diphtheria antitoxin GMT (2.73 IU/mL) for Triple Antigen compared to nDTPw (1.89 IU/mL; P = 0.02), although no subject in either vaccine group had a tetanus or diphtheria antibody titre less than six times the protective level of 0.01 IU/mL following immunization. The nDTPw post immunization GMTs were significantly higher for Agg2, Fha, and pertactin compared to Triple Antigen geometric mean titres (GMTs). CONCLUSION: nDTPw is a safe and immunogenic vaccine when compared to Triple Antigen. The reformulated vaccine is an acceptable replacement for the currently marketed formulation, and for evaluation as a component of future combination vaccines.

Antibody Formation↗

Antibodies to diphtheria, tetanus and pertussis in infants before and after immunization with DTP (Triple Antigen) vaccine.

OBJECTIVE: To determine antibody levels to the Australian manufactured combined diphtheria, tetanus and pertussis (DTP) vaccine (Triple Antigen, CSL Ltd) in infants before and after their primary immunization course. METHODOLOGY: Serosurvey (antibody prevalence study) in two groups: infants aged 5-9 weeks who had not received any immunizations (n = 25), and infants aged 7-10 months who had received two (n = 25) or three immunizations (n = 57) with DTP, sampled from infants attending the Royal Children's Hospital, Melbourne, either as inpatients or outpatients between February and April 1993. The immunization history for each infant was determined from hospital records, the parent-held child health record, or the local council or family doctor who immunized the infant. RESULTS: Enzyme immunoassay (EIA) of antibodies to diphtheria and tetanus showed all infants to have adequate protective levels after two or three vaccinations (> or = 0.01 IU/mL). All subjects who had received all three DTP vaccinations had detectable antibody to at least one pertussis antigen. Antibodies to the pertussis antigens filamentous haemagglutinin and pertussigen (pertussis toxin) were comparable to levels determined for whole cell pertussis vaccines used elsewhere in the world. EIA-determined antibodies to pertussis agglutinogen type 2 and agglutinogen type 3 showed substantially higher geometric mean titres when results for pre-immunization and post-immunization subjects were compared. CONCLUSIONS: These data show that the Australian manufactured DTP vaccine has immunogenic properties similar to those of vaccines used elsewhere, and that antibody concentrations following immunization are at levels consistent with efficacy.

Analysis of Variance↗

Acyclovir for the prevention and treatment of varicella zoster in children, adolescents and pregnancy.

Varicella causes a mild, self-limiting childhood disease that may reactivate years later as shingles. In immunocompromised patients with altered cell mediated immunity, and rarely in healthy individuals, varicella results in a life-threatening infection. The antiviral drug, acyclovir, substantially reduces the mortality and risk of severe disease in these groups of patients. Early commencement of acyclovir is recommended for children with both varicella and altered cell mediated immunity, newborns during the first 2 weeks of life, preterm infants in the neonatal nursery, and severe varicella or shingles (including ocular zoster) in any patient, as well as during pregnancy. Acyclovir may be considered in children with serious cardiopulmonary disease or chronic skin disorders where varicella may exacerbate the underlying disease or increase the risk of secondary bacterial sepsis. Acyclovir, however, is not recommended for healthy individuals without severe disease, as a prophylactic agent against varicella, for asthmatics receiving aerosolized or low-dose oral steroids and/or as treatment of the post-varicella syndromes. When acyclovir is prescribed it should be given intravenously to those with severe disease, those at risk of dissemination and in children younger than 2 years of age.

Acyclovir↗

Increasing severity of invasive group A streptococcal disease in Australia: clinical and molecular epidemiological features and identification of a new virulent M-nontypeable clone.

We conducted a 12-year review of all cases of group A streptococcal (GAS) bacteremia that were seen at Royal Children's Hospital in Melbourne, Australia, from 1982 through 1993. Forty-two cases were identified. There was a trend towards increased incidence of infections, as well as a clear increase in their severity, during the study period; more previously healthy children were affected during the last 6 years of the study (80% of cases) than during the first 6 years (47% of cases), and more complications occurred during the latter period than during the former (40% vs. 20%, respectively, with an 88% complication rate over the last 12 months). Seventy-four GAS isolates (41 invasive, 23 noninvasive, and 10 indeterminate) were analyzed. An M type 1 clone that was positive for the pyrogenic exotoxin A gene (speA) and that has been found to cause invasive disease in the Northern Hemisphere was most frequent among invasive isolates. Molecular typing also identified a genetically distinct strain that was virulent, mucoid, and M nontypable. Invasive GAS disease in Melbourne has become increasingly aggressive. Newer typing methods should be used in conjunction with traditional serotyping in order to maintain epidemiological surveillance of virulent strains.

Adolescent↗

Slim pickings.

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Community Participation↗