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Biomedical subjects

G L Gilbert

Publications and source records attributed to G L Gilbert.

At least 19 recordsLinked to original sources

Population-based seroprevalence of Neisseria meningitidis serogroup C capsular antibody before the introduction of conjugate vaccine, in Australia.

Neisseria meningitidis serogroup C (NMC) conjugate vaccine was introduced, in Australia, in 2003. Our aims were to determine pre-immunisation IgG NMC seroprevalence and evaluate an enzyme-linked immunosorbent assay (ELISA), previously validated against the serum bactericidal assay (SBA). 2409 sera, collected in 2002, from subjects aged 2-34 years, were tested. The geometric mean concentration (GMC) of NMC anticapsular IgG was 0.38 U/mL in subjects under 19 years and it increased to 0.67 U/mL for those aged 30-34 years. Variation in GMC correlated with reported NMC disease incidence and was higher in males than females (0.52 U/mL versus 0.41 U/mL; p=0.005). The ELISA appears suitable for serosurveillance but the IgG level that correlates with protection needs further investigation. Serosurveys will be repeated to monitor the impact of vaccination.

Adolescent↗

Evaluation of two enzyme immunoassays for detection of immunoglobulin G antibodies to mumps virus.

To determine suitability for national serosurveys, we compared two commercial enzyme-linked immunosorbent assays (ELISAs) for mumps antibody, Enzygnost Anti-Parotitis-Virus/IgG (which uses a whole-virus antigen) and Microimmune Mumps IgG Screen ELISA (which uses a recombinant nucleoprotein antigen), by testing 1,915 opportunistically collected sera submitted to diagnostic laboratories across Australia in 1997 to 1998. The proportion of positive results increased with age in both ELISAs but was significantly higher with the Microimmune than with the Enzygnost ELISA overall (88% versus 63%; P < 0.01) and in all age groups. However, the proportion of equivocal results was significantly higher with the Enzygnost than with the Microimmune ELISA (9% versus 4%; P < 0.01). Of the 572 sera with discrepant or equivocal results, 508 had sufficient sample remaining to perform the neutralization test (NT). A proportion with concordant results in both ELISAs were also tested by the NT. For sera with discrepant results, there was significantly better agreement between the NT and Microimmune than between the NT and Enzygnost (310/444 [70%] versus 135/348 [39%]; P < 0.01). Of 64 sera with equivocal Microimmune results, 45 (70%) were positive in the NT compared with 140 of 160 (88%) equivocal Enzygnost results (P < 0.01). Compared with the NT, the Microimmune ELISA is more sensitive (96% versus 80%) but apparently less specific (36% versus 85%) than the Enzygnost ELISA. However, this is likely to be due to the generally lower sensitivity of the NT, since the Microimmune results reflect expected seroprevalence, based on vaccine uptake in the age groups studied. We conclude that the Microimmune ELISA is a more appropriate assay than the Enzygnost ELISA for estimation of mumps seroprevalence.

Adolescent↗

Sensitivity of human gamma interferon assay and tuberculin skin testing for detecting infection with Mycobacterium tuberculosis in patients with culture positive tuberculosis.

SETTING: Nine university-affiliated chest clinics in Australia. OBJECTIVE: To evaluate the sensitivity of a whole blood human gamma-interferon assay (HGIA, QuantiFERON-TB) for specific T lymphocyte responses and Tuberculin skin testing (TST) for the detection of Mycobacterium tuberculosis infection in subjects with culture-proven M. tuberculosis disease (TBCP). DESIGN: Prospective testing of 129 patients with recent TBCP and 100 patients with non-tuberculosis lung disease (NTBLD). RESULTS: Using a defined level of specific IFN-gamma production and TST 10mm as positive cut-offs, the sensitivity of HGIA was 81% compared to 89% for TST (p=0.06). When positive responses in both TST and HGIA were combined, 96% of TB patients were detected. For the NTBLD group, 43% of whom were born overseas, 73% were negative for both the HGIA and TST. Prior immunization with M. bovis (bacille Calmette-Guerin) (BCG) or the type of TB had no effect on the sensitivities of the assays. For those treated for <2 months, the sensitivities for both assays were 84%, but for those treated for >2 months the sensitivity of TST (90%) tended to be higher than for HGIA (81%) (p=0.07). The distribution of TST results in TB patients showed a broad peak between 10 and 25 mm, while the results in the HGIA were bimodal in both TB and NTBLD patients. CONCLUSION: HGIA may prove an alternative to skin testing for detecting M. tuberculosis infection in certain settings.

Adult↗

A boarding school outbreak of pertussis in adolescents: value of laboratory diagnostic methods.

Culture for Bordetella pertussis (B. pertussis) is the traditional gold standard for laboratory diagnosis of pertussis but is insensitive, especially later in the course of illness and in vaccinated persons. Interpretation of serology is limited by the lack of an appropriate reference standard. An outbreak of pertussis in a crowded boarding-school dormitory allowed evaluation of laboratory correlates of infection. Questionnaires, serum samples and throat swabs were collected from members of the exposed group. Serum samples from unexposed controls of a similar age group were used for comparison. B. pertussis PCR was performed on throat swabs, and sera were tested for IgA antibodies against whole-cell (WC) B. pertussis antigen and IgG antibodies to pertussis toxin (PT). The Centers for Disease Control and Prevention definition for pertussis was used to define clinical cases. We evaluated the use of a previously published cut-off for PT IgG of 125 EIA units (EU)/ml. Completed questionnaires were obtained from 115 students, of whom 85 (74%) reported coughing symptoms, including 32 (28%) who met the clinical case definition for pertussis. B. pertussis was detected by PCR in 17 (15%) and WC IgA in 22 (19%) students; neither correlated with symptoms, but dormitory of residence strongly predicted PCR status. The mean PT IgG geometric mean concentration, in this situation of high pertussis exposure, correlated with severity of symptoms and was significantly higher in both symptomatic and asymptomatic children exposed during the outbreak (P < 0.001) than in control children. A cut-off for PT IgG of 125 EU/ml was too high in an outbreak situation to be sensitive enough to identify pertussis cases. A case of pertussis in a crowded boarding-school dormitory resulted rapidly in an outbreak. Serology and PCR were useful in identifying the outbreak and commencing disease control measures. The use of serology has mostly been evaluated in community serosurveys, where it is not possible to determine if immunity reflects vaccination, asymptomatic disease or symptomatic disease. This outbreak gave us the opportunity to evaluate the value of serology and PCR in the presence of confirmed exposure to pertussis.

Adolescent↗

Antibiotics for ureaplasma in the vagina in pregnancy.

BACKGROUND: Preterm birth is a significant obstetric problem in high-income countries. Genital infection including ureaplasmas are suspected of playing a role in preterm birth and preterm rupture of the membranes. Antibiotics are used to treat women with preterm prelabour rupture of the membranes and results in prolongation of pregnancy and lowers the risks of maternal and neonatal infection. However, antibiotics may be beneficial earlier in pregnancy to eradicate potentially causative agents. OBJECTIVES: The objective of this review is to assess whether antibiotic treatment of pregnant women with ureaplasma in the vagina reduces the incidence of preterm birth and other adverse pregnancy outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (April 2003). SELECTION CRITERIA: All randomised controlled trials that compared any antibiotic regimen with placebo or no treatment in pregnant women with ureaplasma detected in the vagina. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed eligibility and trial quality and extracted data. MAIN RESULTS: One trial involving 1071 women was included. Of these, 644 randomly received antibiotic treatment (174 erythromycin estolate, 224 erythromycin sterate, and 246 clindamycin hydrochloride) and 427 received placebo. This trial did not report data on preterm birth. Incidence of low birthweight less than 2500 grams was only evaluated for erythromycin (combined) (n = 398 ) compared to placebo (n = 427) and there was no statistically significant difference between those treated and those not treated (relative risk (RR) 0.70, 95% confidence interval (CI) 0.46 to 1.07). In regards to side-effects sufficient to stop treatment, data were available for all women, and there were no statistically significant differences between any antibiotic (combined) and the placebo group (RR 1.25, 95% CI 0.85 to 1.85). REVIEWER'S CONCLUSIONS: There is insufficient evidence to show whether giving antibiotics to women with ureaplasma in the vagina will prevent preterm birth.

Anti-Bacterial Agents↗

Temporal trends in circulating Bordetella pertussis strains in Australia.

Australia experienced a resurgence of pertussis in the 1990s despite improved vaccine coverage. Although much of the increase was attributable to increased detection of cases in older persons with waning immunity by serology, vaccine changes or alterations in circulating Bordetella pertussis strains may also have contributed. We determined the frequency of variants of B. pertussis pertactin (prn), and pertussis toxin subunit 1 (ptxS1) genes, restriction fragment length polymorphism (RFLP) types and fimbrial serotypes prevalent in Australia prior to, and during the 1990s. Ampoules of the whole-cell vaccine in use prior to 1999 and 84 B. pertussis isolates stored between 1967 and 1998 by laboratories around Australia were analysed. One pertactin allele, Prn3, not detected before 1985, was found in 24 out of 57 (42%) isolates between 1989 and 1998 (P<0.0001). PtxS1A was found in all isolates. IS1002 type 29, found in 17 out of 31 (55%) isolates tested, was the predominant RFLP type. The only difference in fimbrial serotype distribution between the time-periods was an increase in serotype 3 (P=0.054). The whole-cell vaccine contained only the alleles prn1 and ptxS1A. Antigenic shift in B. pertussis may have contributed to the re-emergence of pertussis in Australia. Monitoring these trends will be important as acellular vaccines are introduced and changes are made to pertussis vaccine schedules.

Bacteremia↗

A large outbreak of influenza A and B on a cruise ship causing widespread morbidity.

In September 2000 an outbreak of influenza-like illness was reported on a cruise ship sailing between Sydney and Noumea with over 1,100 passengers and 400 crew on board. Laboratory testing of passengers and crew indicated that both influenza A and B had been circulating on the ship. The cruise coincided with the peak influenza period in Sydney. Morbidity was high with 40 passengers hospitalized, two of whom died. A questionnaire was sent to passengers 3 weeks after the cruise and 836 of 1,119 (75%) responded. A total of 310 passengers (37%) reported suffering from an influenza-like illness (defined as cough, fever, myalgia and weakness) and 528 (63%) had seen a doctor for illness related to the cruise. One-third of passengers reported receipt of influenza vaccination in 2000; however neither their rates of influenza-like illness nor hospitalization were significantly different from those in unvaccinated passengers. A case-control study also found no significant protective effect of influenza vaccination. With the increasing popularity of cruise vacations, such outbreaks are likely to affect increasing numbers of people. Whilst influenza vaccination of passengers and crew may afford some protection, uptake and effectiveness may not be sufficient to prevent outbreaks. Surveillance systems and early intervention measures, such as antiviral therapies, should be considered to detect and control such outbreaks.

Adult↗

The seroepidemiology and transmission dynamics of varicella in Australia.

To enhance our understanding of the epidemiology and transmission dynamics of varicella in the pre-vaccine era we performed a serosurvey using opportunistically collected sera submitted to diagnostic laboratories across Australia during 1997-1999. A representative sample by state and sex of 2027 sera from persons aged 1-49 years was tested using an enzyme immunoassay method. The average age of infection and age-specific forces of infection (the probability that a susceptible individual acquires infection) were calculated using published methodologies. Seropositivity increased with age, with 83% of sera positive by ages 10-14 years. The highest force of infection was in the 5-9 years age group (0.195 per susceptible year) followed by the 0-4 years age group (0.139 per susceptible year) and the average age of infection was 8.15 years. These results provide valuable baseline information to measure the impact of vaccination and indicate that vaccination should be aimed at children less than 5 years of age, although further modelling using the serosurvey data is warranted.

Adolescent↗

A mathematical model to measure the impact of the Measles Control Campaign on the potential for measles transmission in Australia.

BACKGROUND: The aims of this study were to determine the impact of the Australian Measles Control Campaign (MCC) on the transmission dynamics of measles by calculating the reproductive number (R) before and after the MCC, and to predict measles control in Australia in the future. METHODS: A national serosurvey was conducted before and after the MCC. Sera were tested for anti-measles IgG using enzyme immunoassay (EIA). A mathematical model, using serosurvey results and vaccine coverage estimates, was used to calculate the change in R after the MCC. RESULTS: The values of R calculated before and after the MCC were 0.90 and 0.57. At vaccine coverage levels indicated by the Australian Childhood Immunisation Register (ACIR), the value of R will exceed 1 (the epidemic threshold) in 2007-2008 nationally, and sooner in some regions of Australia. Coverage of at least 84% with two doses of MMR is required to sustain measles control. CONCLUSIONS: The Australian MCC had a significant impact on the transmission dynamics of measles. However, current vaccine coverage levels may result in indigenous measles transmission by 2007. Sustained efforts are required to improve coverage with two doses of MMR and to ensure elimination of indigenous measles transmission.

Adolescent↗

Treat or test first? Decision analysis of empirical antiviral treatment of influenza virus infection versus treatment based on rapid test results.

BACKGROUND: neuraminidase (NA) inhibitors have recently become available for treatment of influenza. Rapid antigen detection assays at 'point-of-care' may improve the accuracy of clinical diagnosis, but the value of these techniques in assisting with the appropriate use of antivirals remains controversial. OBJECTIVE: to compare the diagnostic utilities of two management strategies for influenza, empirical antiviral therapy versus therapy based on a positive rapid test result in pre-epidemic and epidemic periods. STUDY DESIGN: a threshold decision analytic model was designed to compare these competing strategies and sensitivity analysis performed to examine the impact of diagnostic variables on the expected utility of the decision with a range of prior probabilities of infection between 1 and 50%. RESULTS: on the basis of the calculated sensitivity (77%) and specificity (95%) of a point-of-care test for influenza, pre-treatment testing was preferred and cost-effective in non-epidemic stage of the influenza cycle. The alternative strategy of empirical treatment produces a higher utility value during epidemics, but may result in overuse of antivirals for low-risk populations. The two strategies had equivalent efficacy when the probability of influenza was 42%. CONCLUSIONS: Patients with flu-like illness, who present outside the influenza outbreak and are considered to be at low risk for influenza-related complications, should be tested to confirm the diagnosis before starting antiviral treatment with a NA inhibitor. The most important variables in the model were the accuracy of the clinical diagnosis and the pre-test probability of influenza. A threshold probability of influenza of 42% would dictate changing from the rapid testing strategy to a 'treat regardless' strategy.

Antiviral Agents↗

Serological diagnosis of pertussis: evaluation of IgA against whole cell and specific Bordetella pertussis antigens as markers of recent infection.

In Australia, notification of pertussis cases in older children or adults has increased significantly in recent years. In most cases, laboratory diagnosis is based only on a positive serological test for IgA antibody against whole cell Bordetella pertussis. During a 3-month period, 318 consecutive sera submitted for diagnosis of pertussis were tested for IgA antibody against whole cell (WC) sonicated B. pertussis, pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN). Results of one or more of these tests were positive in sera from 175 subjects and clinical information was obtained by telephone interview from 90 subjects. Using a clinical case definition as the reference standard, the sensitivities of the four IgA assays were variable but quite low (24-64%), but the specificities were high (93-98%). For diagnosis of pertussis in subjects with a compatible clinical illness, these and other findings support the use of serological testing for IgA antibody.

Adolescent↗

Epidemiology and predictive values of risk factors for neonatal group B streptococcal sepsis.

OBJECTIVES: To determine the incidence of and factors affecting risk factors for neonatal group B streptococcal (GBS) sepsis and their predictive values for intrapartum GBS carriage; to calculate the proportions of women eligible for intrapartum antibiotic prophylaxis (IAP) using different selection protocols. DESIGN: Cohort study. SETTING: Antenatal clinics and labour wards of a community hospital and a tertiary referral centre in western Sydney POPULATION: Women attending antenatal clinics during the study periods were invited to participate. METHODS: Approximately 500 women attending antenatal clinics were screened for GBS carriage at 26-32 weeks gestation and at delivery, using several screening methods. Clinical risk factors for neonatal sepsis were recorded during labour. MAIN OUTCOME MEASURES: Incidence of antenatal anovaginal GBS carriage and clinical risk factors during labour, their predictive values for intra-partum GBS carriage and their relationship, if any, to demographic and obstetric factors. RESULTS: Antenatal and intra-partum GBS carriage rates were similar but varied from 18% to 27%, depending on screening methods. The best positive and negative predictive values of antenatal GBS culture, for intra-partum carriage, were 69% (95% confidence interval (CI) 64-74) and 92% (95% CI 50-94) respectively Clinical risk factors occurred in similar proportions of GBS carriers and non-carriers. CONCLUSIONS: Neither early antenatal screening nor clinical risk factors are reliable predictors of intra-partum GBS carriage. Intra-partum antibiotic prophylaxis based on GBS carriage or risk factors when carrier status is unknown would involve approximately 35% of women, compared with approximately 16% if based on risk factors only Both strategies would prevent similar proportions of neonatal deaths from GBS sepsis. Compliance with a preventive protocol is the most likely determinant of its overall effectiveness.

Adult↗

The Australian Measles Control Campaign, 1998.

The 1998 Australian Measles Control Campaign had as its aim improved immunization coverage among children aged 1-12 years and, in the longer term, prevention of measles epidemics. The campaign included mass school-based measles-mumps-rubella vaccination of children aged 5-12 years and a catch-up programme for preschool children. More than 1.33 million children aged 5-12 years were vaccinated at school: serological monitoring showed that 94% of such children were protected after the campaign, whereas only 84% had been protected previously. Among preschool children aged 1-3.5 years the corresponding levels of protection were 89% and 82%. During the six months following the campaign there was a marked reduction in the number of measles cases among children in targeted age groups.

Adolescent↗

Hepatitis A epidemiology in Australia: national seroprevalence and notifications.

OBJECTIVES: To determine hepatitis A seroprevalence and notification rates in Australia in order to inform vaccination policy. DESIGN: Seroprevalence was determined by cross-sectional survey of opportunistically collected sera; notifications were extracted from the National Notifiable Diseases Surveillance System. PARTICIPANTS: 3,043 serum samples collected in 1998 were obtained from 46 laboratories around Australia. Sample size in each age group was based on expected seroprevalence, and States and Territories were sampled proportionally to their population size. Males and females were equally represented. Notifications were extracted for cases with onset between 1 January 1991 and 31 December 1998. MAIN OUTCOME MEASURES: Seroprevalence and notifications were analysed by age, sex and State/Territory. RESULTS: 41.1% of serum samples were seropositive for hepatitis A (95% CI, 39.4%-42.9%) (population-weighted seroprevalence, 38.3%). Seroprevalence was significantly associated with increasing age (P<0.001), but did not differ between the sexes (male:female ratio, 1.04:1; 95% CI, 0.95-1.14). However, significantly more notifications were recorded for males than females (male:female ratio, 1.65:1; 95% CI, 1.60-1.70). The Northern Territory had the highest seroprevalence (68.8%; 95% CI, 52.7%-84.8%) and annual notification rates (48.7 per 100,000 population; 95% CI, 45.0-52.4 per 100,000). CONCLUSIONS: These data show that about half the Australian population has not been exposed to hepatitis A and is therefore susceptible to infection. However, any decision on national routine childhood hepatitis A vaccination requires a cost-benefit analysis. Routine vaccination of high-incidence communities remains controversial.

Adolescent↗

Antibiotic therapy of ventilator-associated pneumonia--a reappraisal of rationale in the era of bacterial resistance.

Ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection in intensive care units (ICU). Resistance patterns seen in ICUs suggest that prescribing recommendations should be reappraised to limit practices engendering resistance to large families of antibiotics. Despite concern surrounding the use of antibiotics in the management of VAP, there is limited evidence to assist the clinician in making decisions about the indications for such therapy, the selection of the correct antibiotic(s), the timing of initiation of therapy and its duration. The high amount of antibiotic use, in combination with the low grade colonisation of patients with multi-resistant pathogens at the time of admission, turns the ICU into an environment where antibiotic policy is likely to have an effect on the resistance problem. Opinions are changing as to the validity of invasive techniques in guiding prescribing decisions. Invasive and semi-invasive diagnostic testing increases physician confidence in the diagnosis and management of VAP and helps to limit or discontinue antibiotic treatment.

Anti-Bacterial Agents↗

Impact of the Australian Measles Control Campaign on immunity to measles and rubella.

To evaluate the impact of the 1998 Australian Measles Control Campaign on immunity to measles and rubella, 4400 opportunistically-collected sera, submitted to diagnostic laboratories across Australia from subjects aged 1-49 years, and 3000 from subjects aged 1-18 years, were tested before and after the campaign, respectively. The proportion of individuals aged 1-18 years who were immune to measles rose from 85% before, to 90% after, the campaign (P < 0.001). The greatest increase was in preschool (7%, P < 0.001) and primary school (10%, P < 0.001) children, who were actively targeted by the campaign. Rubella immunity in 1-18 year-olds rose from 83% to 91% (P < 0.0001), again with significant increases in preschool (4%, P = 0.002) and primary school (16%, P < 0.001) children. 94% of individuals aged 19-49 years were immune to rubella. These serosurveys confirm other evidence of the effectiveness of the Australian Measles Control Campaign and demonstrate the value of serosurveillance using opportunistically collected sera.

Adolescent↗