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ABSTRACT: 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.
Epidemiology and Infection 11/2001; 127(2):275-80. · 2.84 Impact Factor
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ABSTRACT: To describe the epidemiological and microbiological characteristics and notification patterns of invasive meningococcal disease (IMD) in Victoria between 1990 and 1999.
Cases of IMD occurring between 1990 and 1995 identified in any of three databases were combined, matching where possible. Statistical modelling provided estimates of cases missing from all datasets. Notification sources for 1999 and 2000 cases were identified. Cases identified from notification and laboratory results provided the data to describe IMD epidemiology between 1990 and 1999.
Between 1990 and 1995, 479 cases of IMD were identified. Three individual datasets each identified between 62 and 82% of cases and 47% of cases were identified in all three datasets. Statistical modelling estimated that between 37 and 83 additional cases were not identified by any dataset. Serogroup B and C strains caused 63 and 33% of culture-positive cases, respectively, with a substantial rise in serogroup C cases in 1999. Epidemiological characteristics remained relatively constant between 1990 and 1998, but an increase in patient age was seen in cases with serogroup C disease in 1999. In addition to three clonal strains seen elsewhere, an additional strain was identified that was unique to Victoria. Since January 1999, only 72% of notifications have come from treating doctors.
Meningococcal disease is of increasing public health significance in Victoria. Laboratory enhanced notification has improved case identification and detailed microbiological information has improved our understanding of the changing epidemiology of this disease. Collaboration with laboratories and other agencies, active investigation of putative cases and microbiological monitoring are important elements in supporting public health decisions about the control of IMD.
Journal of Paediatrics and Child Health 11/2001; 37(5):S7-12. · 1.28 Impact Factor
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ABSTRACT: 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.
Communicable diseases intelligence 09/2001; 25(3):121-5.
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ABSTRACT: 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.
Vaccine 03/2001; 19(15-16):2127-37. · 3.77 Impact Factor
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ABSTRACT: 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.
Communicable diseases intelligence 08/2000; 24(7):199-202.
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ABSTRACT: To screen for faecal colonisation with vancomycin-resistant enterococci (VRE) among potentially at-risk patients.
Infection control screening program.
Monash Medical Centre (a tertiary care hospital), Melbourne, Victoria, in the seven months from June 1997.
Patients in the Renal, Oncology and Intensive Care (ICU) Units.
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).
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.
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.
The Medical journal of Australia 09/1999; 171(3):133-6. · 2.81 Impact Factor
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Vaccine 08/1999; 17 Suppl 1:S119-21. · 3.77 Impact Factor
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ABSTRACT: 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.
Vaccine 01/1999; 16(20):2085-9. · 3.77 Impact Factor
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ABSTRACT: 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.
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.
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.
This vaccine was well tolerated by children at 18 months of age, and showed substantial boosting of antibody to all components.
Journal of Paediatrics and Child Health 08/1998; 34(4):346-8. · 1.28 Impact Factor
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ABSTRACT: 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.
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 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).
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.
Journal of Paediatrics and Child Health 10/1997; 33(5):413-7. · 1.28 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Journal of Paediatrics and Child Health 10/1996; 32(5):378-81. · 1.28 Impact Factor
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ABSTRACT: Mucormycosis is an opportunistic infection that has been mainly described in adults with preexisting disease affecting immune status, eg, diabetes, leukemia, lymphoma, and renal failure on peritoneal dialysis. Few cases have been described in neonates. The presentation of mucormycosis as a cause of neonatal necrotizing enterocolitis is an unusual phenomenon. Three fatal cases of mucormycosis of the gut in premature infants in the period 1990 to 1991 are described. It is not clear whether this should be considered a separate disease or a variant of necrotizing enterocolitis. All three patients died soon after laparotomy from septic shock and the histological diagnosis of mucormycosis was made too late for effective chemotherapy.
Journal of Pediatric Surgery 07/1992; 27(6):737-40. · 1.45 Impact Factor