Quantifying differences in the epidemic curves from three influenza surveillance systems: a nonlinear regression analysis.

Influenza surveillance enables systematic collection of data on spatially and demographically heterogeneous epidemics. Different data collection mechanisms record different aspects of the underlying epidemic with varying bias and noise. We aimed to characterize key differences in weekly incidence data from three influenza surveillance systems in Melbourne, Australia, from 2009 to 2012: laboratory-confirmed influenza notified to the Victorian Department of Health, influenza-like illness (ILI) reported through the Victorian General Practice Sentinel Surveillance scheme, and ILI cases presenting to the Melbourne Medical Deputising Service. Using nonlinear regression, we found that after adjusting for the effects of geographical region and age group, characteristics of the epidemic curve (including season length, timing of peak incidence and constant baseline activity) varied across the systems. We conclude that unmeasured factors endogenous to each surveillance system cause differences in the disease patterns recorded. Future research, particularly data synthesis studies, could benefit from accounting for these differences.

Decreased varicella and increased herpes zoster incidence at a sentinel medical deputising service in a setting of increasing varicella vaccine coverage in Victoria, Australia, 1998 to 2012.

We performed an ecological study using sentinel consultation data from a medical deputising service to assess the impact of increasing coverage with childhood varicella vaccine on the incidence risk of varicella and zoster in the population served by the deputising service in Victoria, Australia from 1998 to 2012. Following a successful vaccination programme, the incidence of varicella in Australia was modelled to decrease and the incidence of zoster to increase, based on a theoretical decrease in boosting of zoster immunity following a decrease in wild varicella virus circulation due to vaccination. Incidence risks (consultation proportions for varicella and zoster) were directly age-standardised to the Melbourne population in 2000, when varicella vaccine was first available. Age-standardised varicella incidence risk peaked in 2000 and halved by 2012. Age-standardised zoster incidence risk remained constant from 1998 to 2002, but had almost doubled by 2012. The increase in zoster consultations largely reflected increases in people younger than 50 years-old. Although causality cannot be inferred from ecological studies, it is generally agreed that the decrease in varicella incidence is due to increasing varicella vaccine coverage. The possible indirect effect of the vaccine on zoster incidence is less clear and ongoing monitoring of zoster is required.

Moderate influenza vaccine effectiveness in Victoria, Australia, 2011.

We used a sentinel general practitioner (GP) network to conduct surveillance for laboratory-confirmed influenza amongst patients presenting with influenza-like illness (ILI) in Victoria, Australia in 2011. The test negative variation of the case control study design was used to estimate effectiveness for seasonal trivalent influenza vaccine. Cases and controls were ILI patients that tested positive and negative for influenza, respectively. Vaccination status was recorded by GPs and vaccine effectiveness (VE) was calculated as (1-adjusted odds ratio)x100%. There were 529 patients included in the study, of which 29% were influenza positive. Twelve percent of study participants were reported as vaccinated, 6% of cases and 15% of controls. Adjusted VE against all influenza was 56%, but not statistically significant. There was generally little variation in VE estimates when stratified by virus type and subtype, which is consistent with good matches between circulating strains and the vaccine strains. The VE was higher among adults of working age than among children.

Seasonal influenza vaccine effectiveness estimates: Development of a parsimonious case test negative model using a causal approach.

BACKGROUND: Influenza vaccine effectiveness (VE) is increasingly estimated using the case-test negative study design. Cases have a symptom complex consistent with influenza and test positive for influenza, while non-cases have the same symptom complex but test negative. We aimed to determine a parsimonious logistic regression model for this study design when applied to patients in the community. METHODS: To determine the minimum covariate set required, we used a previously published systematic review to find covariates and restriction criteria commonly included in case-test negative logistic regression models. Covariates were assessed for inclusion using a directed acyclic graph. We used data from the Victorian Influenza Sentinel Practice Network from 2007 to 2013, excluding the pandemic year of 2009, to test the model. VE was estimated as (1-adjusted OR) * 100%. Changes in model fit from addition of specified covariates were examined. Restriction criteria were examined using change in VE estimate. VE was estimated for each year, all years aggregated, and for influenza type and sub-type. RESULTS: Using publicly available software, the directed acyclic graph indicated that covariates specifying age, time within the influenza season, immunocompromising comorbid conditions and year or study site, where applicable, were required for closure. The inclusion of sex was not required. Inclusions and exclusions were validated when testing the variables (when collected) with our data. Restriction by time between onset and swab was supported by the data. VE for all years aggregated was estimated as 53% (95%CI 38, 64). VE was estimated as 42% (95%CI 19, 59) for H3N2, 75% (95%CI 51, 88) for H1N1pdm09 and 63% (95%CI 38, 79) for influenza B. CONCLUSION: Theoretical covariates specified by the directed acyclic graph were validated when tested against surveillance data. A parsimonious model using the case test negative design allows regular estimates of VE and aggregated estimates by year.

Verification of measles elimination in Australia: Application of World Health Organization regional guidelines.

BACKGROUND: The World Health Organization (WHO) Western Pacific Region (WPR) Guidelines on verification of measles elimination were established in 2012. This article outlines Australia's approach to addressing the guideline's five lines of evidence, which led to formal verification of elimination by the WHO Regional Verification Commission (RVC) in March 2014. METHODS: The criteria were addressed using national measles notifications, data from selected laboratories, the national childhood immunization register, and three national serosurveys (1998/1999, 2002, 2007). RESULTS: Australia met or exceeded all indicator targets with either national or sentinel data. Laboratory and epidemiological surveillance were of high quality, with 85% of cases documented as imported/import-related (target 80%); coverage with the first dose of measles vaccine was close to 94% in 2008-2012 and second dose coverage increased to 91% in 2012 (target >95%). There is ongoing commitment by the Australian Government to increase immunization coverage, and the absence of sustained transmission of any single measles genotype was demonstrated. CONCLUSIONS: This is the first documentation of the successful application of the WPR RVC guidelines. The indicators afford some flexibility but appear to provide appropriate rigor to judge achievement of measles elimination. Our experience could assist other countries seeking to verify their elimination status.

Incidence of IDDM in Western Australia in children aged 0-14 yr from 1985 to 1989.

OBJECTIVE: To document the incidence of insulin-dependent diabetes mellitus (IDDM) in Western Australia in children aged 0-14 yr between 1985 and 1989 and to test for differences in incidence by year of diagnosis, age of diagnosis, and sex. RESEARCH DESIGN AND METHODS: A population-based register that used a primary source of case ascertainment (diabetes clinics at teaching hospitals and direct approach to general practitioners and general physicians) and a secondary source (Western Australian Hospital Morbidity Data System) established numerator data. Denominator data were obtained from the Australian Bureau of Statistics. RESULTS: From 1985 to 1989 inclusive, 235 children in the 0- to 14-yr age-group were diagnosed with IDDM in Western Australia. Case ascertainment was estimated at 99% complete. The mean age-adjusted (developed-world population) annual incidence of IDDM was 13.2 per 100,000 person-yr and there was no evidence of an increasing incidence over the 5 yr. However, girls were more likely than boys to be diagnosed with IDDM in this period (P = 0.006). CONCLUSIONS: The incidence of IDDM in Western Australia is in the middle range of IDDM incidence in countries throughout the world. The unexpected finding of an increased incidence of IDDM in girls compared with boys needs to be confirmed in a future study.

A serosurvey evaluation of the school-based measles 'catch-up' immunisation campaign in Victorian school-aged children.

OBJECTIVE: To determine the proportion of Victorian primary school students protected against measles infection one year after the completion of the measles 'catch-up' immunisation campaign of 1998 and to compare this with the proportion of year 9 and 10 (aged 14-16 years) students. DESIGN & SETTING: Three-stage random cluster survey in Victorian primary and secondary schools. MAIN OUTCOME MEASURES: Proportion of primary and year 9 and 10 secondary school students protected against measles infection one year after the completion of the mass 'catch-up' immunisation campaign. SECONDARY OUTCOMES: the proportion of both primary and year 9 and 10 secondary school students protected against both mumps and rubella. RESULTS: Of 1,037 Victorian primary and 2,357 years 9 and 10 secondary school students invited to participate in this study, 403 (39%) and 752 (32%) respectively provided a blood specimen for serological testing for antibodies against measles, mumps and rubella. 94.8% (95% confidence interval, 91.5, 96.9) of primary school and 93.1% (90.9, 94.8) of year 9 and 10 students were protected against measles infection. CONCLUSION: One year after the completion of the school-based measles 'catch-up' immunisation campaign the level of protection in Victorian primary school aged students is sufficient to prevent the continuing circulation of measles virus within this age group. The proportion of year 9 and 10 secondary school students protected against measles is also probably sufficient to prevent continuing circulation of wild type virus in Victoria, even though this age group was not specifically targeted by the 'catch-up' campaign.

Properties and partial genetic characterization of Nepean phage and other lytic phages of Brucella species.

Nepean (Np), a new brucellaphage, was associated with atypical Brucella abortus strains from Ontario cattle. Carriage of Np was associated with loss of smooth lipopolysaccharide, changes in some protein bands in acrylamide gel electrophoresis profiles, increased susceptibility to colistin, and increased resistance to ultraviolet killing. Nepean (Np) was compared with brucellaphages Tb, Fi, Wb, Iz and R/C. All were morphologically identical, with icosahedral capsids (50-65 nm diameter) and short tails (15-25 nm long), but Np had a more restricted host range, replicating only in smooth strains of B. abortus. All six brucellaphages were generally similar in resistance to chemical and physical agents. Brucellaphage DNA was double stranded and unmethylated; its molecular size was 38 kilobase pairs. The DNAs of Tb, Fi, Wb, Iz and R/C could not be differentiated by restriction endonuclease digest profiles produced by BgII, EcoRI, HindIII or PvuII. Nepean (Np) DNA was very similar to that of the other brucellaphages, but with every enzyme used its profile differed in the number and/or position of at least one fragment. However, there was complete cross-hybridization of Tb and Np DNAs. Hybridization techniques failed to detect Brucella DNA in Dp or Tb phages, or phage DNA in Brucella cells. Extrachromosomal plasmid DNA was not detected.

The immunological response of llamas (Lama glama) following experimental infection with Mycobacterium bovis.

Llamas were experimentally infected with Mycobacterium bovis in order to evaluate the axillary skin test and the ELISA as diagnostic procedures for tuberculosis in llamas (Lama glama). Six llamas were given a single intratracheal challenge with 1 of 2 doses of a recent field isolate of M. bovis and 2 llamas were left as noninfected controls. This resulted in a progressive disease in some animals with 1 mortality as early as 68 d post-infection (PI). The tuberculin skin test, at the axillary site, was positive in 4 of 5 infected llamas at 80 d PI. At 143 d PI, all 3 surviving lamas were positive, including the one which had not responded at 80 d PI. The application of skin and serological tests throughout the course of this experiment adds support for the need to further evaluate the skin test and its anamnestic effect on serodiagnosis since serological responses were generally not observed in the absence of skin testing or antibiotic treatment. The wide variation in M. bovis antigens recognized by the serological response would indicate that a diagnostic panel should include multiple antigens such as MPB70 and lipoarabinomannan (LAM). While skin testing or serology alone may be of limited value to diagnose tuberculosis in llamas, together they may offer an enhanced potential for immunodiagnosis of tuberculosis.

Fifth disease in a small rural community. What are the consequences?

OBJECTIVE: To characterise the implications of an outbreak of human parvovirus in a small community. METHOD: A community survey was conducted over a period of 18 months in a small rural town in Western Australia with a population of approximately 4300 people. Outbreak cases were assessed by the single general practice in the town. Notification of the survey was placed in both the schools and by advertisement in the local paper. Survey questionnaires distributed to community members were returned on a voluntary basis. After 12 months repeat surveys were sent to all adults who had responded to the initial survey. RESULTS: Eighty-eight definite and 14 equivocal cases were identified as part of the outbreak, which occurred between late July 1994 and February 1995. Serological testing which confirmed human parvovirus B19 infection was available for 29% of cases. The highest attack rate was in the 5-9 year age group. One-third of cases were adults and 9% of them developed symptoms lasting longer than 6 months. Transient anaemia almost certainly due to parvovirus infection was identified in one adult women during the course of the outbreak. No pregnant woman suffered any adverse fetal outcome as a result of human parvovirus infection. CONCLUSION: In an outbreak of parvovirus, children will be most commonly affected although adults can develop polyarthralgia/arthritis which may persist for several months and some may suffer transient anaemia. Pregnant women are potentially at risk of the development of fetal hydrops and fetal death, but advice to them can be based on the estimate of a less than 1% risk of adverse fetal outcome due to parvovirus infection.

Hospitalized community-acquired pneumonia in the elderly: an Australian case-cohort study.

This study describes the epidemiology of community-acquired pneumonia (CAP) in elderly Australians for the first time. Using a case-cohort design, cases with CAP were in-patients aged > or = 65 years with ICD-10-AM codes J10-J18 admitted over 2 years to two tertiary hospitals. The cohort sample was randomly selected from all hospital discharges, frequency-matched to cases by month. Logistic regression was used to estimate risk ratios for factors predicting CAP or associated mortality. A total of 4772 in-patients were studied. There were 1952 cases with CAP that represented 4% of all elderly admissions: mean length of stay was 9.0 days and 30-day mortality was 18%. Excluding chest radiograph, 520/1864 (28%) cases had no investigations performed. The strongest predictors of CAP were previous pneumonia, history of other respiratory disease, and aspiration. Intensive-care-unit admission, renal disease and increasing age were the strongest predictors of mortality, while influenza vaccination conferred protection. Hospitalization with CAP in the elderly is common, frequently fatal and a considerable burden to the Australian community. Investigation is ad hoc and management empirical. Influenza vaccination is associated with reduced mortality. Patient characteristics can predict risk of CAP and subsequent mortality.

Varicella infection--evidence for peak activity in summer months.

This study aimed to identify seasonal variations in the presentation of primary varicella infection in susceptible patients in Victoria (a temperate region in south-east Australia) by analysing Victorian hospital admissions data and medical locum service data from the years preceding the introduction of a universally offered vaccination, complemented by available surveillance data from the neighbouring state, of South Australia. Contrary to the conventional assumption, which is based on observations in temperate regions elsewhere in the world, we found no consistent evidence of seasonal peaks during late winter and early spring for varicella infection in Victoria. This finding may have implications for prevention in temperate regions elsewhere in the world wherever estimations of local seasonal trends have been based on international experiences.

ICD-10 codes are a valid tool for identification of pneumonia in hospitalized patients aged > or = 65 years.

This study examines the validity of using ICD-10 codes to identify hospitalized pneumonia cases. Using a case-cohort design, subjects were randomly selected from monthly cohorts of patients aged > or = 65 years discharged from April 2000 to March 2002 from two large tertiary Australian hospitals. Cases had ICD-10-AM codes J10-J18 (pneumonia); the cohort sample was randomly selected from all discharges, frequency matched to cases by month. Codes were validated against three comparators: medical record notation of pneumonia, chest radiograph (CXR) report and both. Notation of pneumonia was determined for 5098/5101 eligible patients, and CXR reports reviewed for 3349/3464 (97%) patients with a CXR. Coding performed best against notation of pneumonia: kappa 0.95, sensitivity 97.8% (95% CI 97.1-98.3), specificity 96.9% (95% CI 96.2-97.5), positive predictive value (PPV) 96.2% (95% CI 95.4-97.0) and negative predictive value (NPV) 98.2% (95% CI 97.6-98.6). When medical record notation of pneumonia is used as the standard, ICD-10 codes are a valid method for retrospective ascertainment of hospitalized pneumonia cases and appear superior to use of complexes of symptoms and signs, or radiology reports.

Ear disease in three aboriginal communities in Western Australia.

Surveys of ear disease amongst Aboriginal people in two isolated bush communities (Wiluna and La Grange) and one urban community (Kwinana) in Western Australia were undertaken in 1988 or 1989. The age-adjusted prevalence odds ratio (relative risk) of perforations of the tympanic membrane for Wiluna compared with Kwinana was 5.0 (95% confidence interval [CI] 2.7-12.2) and 6.8 (95% CI 3.5-13.9) for La Grange compared with Kwinana. The relative risk of mild hearing loss, in comparison with Kwinana, was 2.5 (95% CI 1.5-4.3) for Wiluna and 3.2 (95% CI 2.0-5.0) for La Grange. There was no significant difference in the relative risk of moderate or severe hearing loss or impedance pattern B, usually interpreted as "glue ear", in any of the three communities. Overall, the urban Aboriginal community had less ear disease and hearing loss than either of the isolated bush communities, but even this community did not approach the much lower levels of prevalence in Australia as a whole.

Superior vena caval thrombosis in a child: an uncommon presentation of idiopathic dilated cardiomyopathy.

A nine year old girl who presented with a thrombosis of the right internal jugular vein and superior vena cava was found to be in cardiac failure and to have a dilated cardiomyopathy. After transient improvement she deteriorated and was accepted for cardiac transplantation. Following transplantation her condition has been much improved.

Measuring the HIV epidemic: the Western Australian experience.

Previous discussion about sources of error in measuring the human immunodeficiency virus (HIV) epidemic has tended to emphasise errors which underestimated the number of HIV infected persons. Data are provided from Western Australia illustrating potential errors which may result in overestimating the size of the epidemic. Duplication of persons notified in more than one State and multiple notifications by doctors and laboratories of single cases may give rise to substantial errors in over-estimation.