Measuring school level attributable risk to support school-based HPV vaccination programs.

BACKGROUND: In Australia in 2017, 89% of 15-year-old females and 86% of 15-year-old males had received at least one dose of the HPV vaccine. However, considerable variation in HPV vaccination initiation (dose one) across schools remains. It is important to understand the school-level characteristics most strongly associated with low initiation and their contribution to the overall between-school variation. METHODS: A population-based ecological analysis was conducted using school-level data for 2016 on all adolescent students eligible for HPV vaccination in three Australian jurisdictions. We conducted logistic regression to determine school-level factors associated with lower HPV vaccination initiation (< 75% dose 1 uptake) and estimated the population attributable risk (PAR) and the proportion of schools with the factor (school-level prevalence). RESULTS: The factors most strongly associated with lower initiation, and their prevalence were; small schools (OR = 9.3, 95%CI = 6.1-14.1; 33% of schools), special education schools (OR = 5.6,95%CI = 3.7-8.5; 8% of schools), higher Indigenous enrolments (OR = 2.7,95% CI:1.9-3.7; 31% of schools), lower attendance rates (OR = 2.6,95%CI = 1.7-3.7; 35% of schools), remote location (OR = 2.6,95%CI = 1.6-4.3; 6% of schools,) and lower socioeconomic area (OR = 1.8,95% CI = 1.3-2.5; 33% of schools). The highest PARs were small schools (PAR = 79%, 95%CI:76-82), higher Indigenous enrolments (PAR = 38%, 95%CI: 31-44) and lower attendance rate (PAR = 37%, 95%CI: 29-46). CONCLUSION: This analysis suggests that initiatives to support schools that are smaller, with a higher proportion of Indigenous adolescents and lower attendance rates may contribute most to reducing the variation of HPV vaccination uptake observed at a school-level in these jurisdictions. Estimating population-level coverage at the school-level is useful to guide policy and prioritise resourcing to support school-based vaccination programs.

Post-pandemic influenza A/H1N1pdm09 is associated with more severe outcomes than A/H3N2 and other respiratory viruses in adult hospitalisations.

This study compares the frequency and severity of influenza A/H1N1pdm09 (A/H1), influenza A/H3N2 (A/H3) and other respiratory virus infections in hospitalised patients. Data from 17 332 adult hospitalised patients admitted to Sir Charles Gairdner Hospital, Perth, Western Australia, with a respiratory illness between 2012 and 2015 were linked with data containing reverse transcription polymerase chain reaction results for respiratory viruses including A/H1, A/H3, influenza B, human metapneumovirus, respiratory syncytial virus and parainfluenza. Of these, 1753 (10.1%) had test results. Multivariable regression analyses were conducted to compare the viruses for clinical outcomes including ICU admission, ventilation, pneumonia, length of stay and death. Patients with A/H1 were more likely to experience severe outcomes such as ICU admission (OR 2.5, 95% CI 1.2-5.5, P = 0.016), pneumonia (OR 3.0, 95% CI 1.6-5.7, P < 0.001) and lower risk of discharge from hospital (indicating longer lengths of hospitalisation; HR 0.64 95% CI 0.47-0.88, P = 0.005), than patients with A/H3. Patients with a non-influenza respiratory virus were less likely to experience severe clinical outcomes than patients with A/H1, however, had similar likelihood when compared to patients with A/H3. Patients hospitalised with A/H1 had higher odds of severe outcomes than patients with A/H3 or other respiratory viruses. Knowledge of circulating influenza strains is important for healthcare preparedness.

Long-term outcomes of Murray Valley encephalitis cases in Western Australia: what have we learnt?

BACKGROUND: Murray Valley encephalitis virus (MVEV) is a mosquito-borne flavivirus that causes encephalitis in some cases of infection. It is endemic in Northern Australia and cases occasionally occur in South Eastern Australia. The long-term sequelae of MVEV infection have not previously been well described. AIM: To investigate the long-term sequelae of MVEV infection. METHODS: This was a descriptive case series of all clinical MVEV infections using data linkage and standard surveys. Hospital admissions, emergency department, psychiatric outpatients and mortality data were obtained. We attempted to follow-up all 53 cases of MVEV clinical infection that occurred in Western Australia from 1978 to 2011 inclusive. Two cases opted out of the study. RESULTS: We followed-up 39 surviving cases. Seven of the nine with paralysis or paresis were under 5 years and they fared worse than other patients, requiring lengthy hospitalisation (median duration 133 days). Two died due to complications of quadriplegia following a total of 691 days in hospital. Nine surviving patients, including two with non-encephalitic illness, required care for depression and other psychiatric conditions following MVEV infection. Two patients who were discharged with neurological sequelae had no further documented hospital occasions of service but reported ongoing challenges with cognitive dysfunction and inability to work. CONCLUSIONS: This is the first study of long-term outcomes of Murray Valley encephalitis that included cases with no obvious sequelae at discharge. In spite of the small numbers involved, the study demonstrated the significant medical and social burden due to MVEV in Australia.

Differences in school factors associated with adolescent HPV vaccination initiation and completion coverage in three Australian states.

BACKGROUND: Schools are the primary setting for the delivery of adolescent HPV vaccination in Australia. Although this strategy has achieved generally high vaccination coverage, gaps persist for reasons that are mostly unknown. This study sought to identify school-level correlates of low vaccination course initiation and completion in New South Wales, Tasmania, and Western Australia to inform initiatives to increase uptake. METHODS: Initiation was defined as the number of first doses given in a school in 2016 divided by vaccine-eligible student enrolments. Completion was the number of third doses given in a school in 2015-2016 divided by the number of first doses. Low initiation and completion were defined as coverage ≤ 25thpercentile of all reporting schools. We investigated correlations between covariates using Spearman's rank correlation coefficients. Due to multicollinearity, we used univariable logistic regression to investigate associations between school characteristics and low coverage. RESULTS: Median initiation was 84.7% (IQR: 75.0%-90.4%) across 1,286 schools and median completion was 93.8% (IQR: 86.0%-97.3%) across 1,295 schools. There were strong correlations between a number of school characteristics, particularly higher Indigenous student enrolments and lower attendance, increasing remoteness, higher postcode socioeconomic disadvantage, and smaller school size. Characteristics most strongly associated with low initiation in univariate analyses were small school size, location in Tasmania, and schools catering for special educational needs. Low completion was most strongly associated with schools in Tasmania and Western Australia, remote location, small size, high proportion of Indigenous student enrolments, and low attendance rates. CONCLUSION: This study provides indicative evidence that characteristics of schools and school populations are associated with the likelihood of low initiation and completion of the HPV vaccination course. The findings will guide further research and help target initiatives to improve vaccination uptake in schools with profiles associated with lower coverage.

A morbillivirus that caused fatal disease in horses and humans.

A morbillivirus has been isolated and added to an increasing list of emerging viral diseases. This virus caused an outbreak of fatal respiratory disease in horses and humans. Genetic analyses show it to be only distantly related to the classic morbilliviruses rinderpest, measles, and canine distemper. When seen by electron microscopy, viruses had 10- and 18-nanometer surface projections that gave them a "double-fringed" appearance. The virus induced syncytia that developed in the endothelium of blood vessels, particularly the lungs.

Global climate change: time to mainstream health risks and their prevention on the medical research and policy agenda.

Climate change is unequivocal. The fourth assessment report of the Intergovermental Panel on Climate Change has recently projected that global average surface temperature will increase by 1.1 to 6.4 degrees C by 2100. Anthropogenic warming during the twenty-first century would be much greater than that observed in the twentieth century. Most of the warming observed over the last six decades is attributable to human activities. Climate change is already affecting, and will increasingly have profound effects on human health and well-being. Therefore, there is an urgent need for societies to take both preemptive and adaptive actions to protect human populations from adverse health consequences of climate change. It is time to mainstream health risks and their prevention in relation to the effects of climate change on the medical research and policy agenda.

Nosocomial methicillin-resistant Staphylococcus aureus bacteremia: is it any worse than nosocomial methicillin-sensitive Staphylococcus aureus bacteremia?

OBJECTIVE: To determine the comparative virulence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S aureus (MSSA) by consideration of predisposing factors and outcomes in patients infected with these organisms in the healthcare setting. DESIGN: Analysis of an historical cohort of 504 bacteremic patients (316 MSSA and 188 MRSA), examining factors associated with mortality. SETTING: A 916-bed, university-affiliated, tertiary referral hospital. RESULTS: Risk factors for the development of MRSA include male gender, admission due to trauma, immunosuppression, presence of a central vascular line or an indwelling urinary catheter, and a past history of MRSA infection. Overall mortality was 22%. Death due to bacteremia was significantly greater in the MRSA group (risk ratio, 1.68; P<.05), although these patients were not found to be more likely to die due to underlying disease during treatment of bacteremia. In those patients who recovered from bacteremia, no significant differences for the outcome of death could be determined between the MRSA and MSSA groups. CONCLUSIONS: There is a general consensus in the published literature that MRSA bacteremia is more likely to be associated with death, and we confirm this conclusion. However, in contrast to other studies, our MRSA cohort does not appear to be more at risk of death due to underlying disease during treatment for bacteremia. Similarly, the general consensus that MRSA patients have an increased overall mortality was not confirmed in our study. Differences in comorbidities of patients may provide some explanation of these conflicting results, while an alternate explanation is that MRSA strains are more virulent than MSSA in some centers. Perhaps the most plausible explanation is that treatment is provided earlier and in a more aggressive fashion in some centers, leading to an overall lower mortality rate in all staphylococcal bacteremias in these institutions.

Human papillomavirus type 16 E6, E7 and L1 and type 18 E7 proteins produced by recombinant baculoviruses.

Proteins derived from the E6, E7 and L1 ORFs of HPV16 and the E7 ORF of HPV18 were produced in insect cells using a baculovirus expression system. HPV ORFs were inserted into baculovirus transfer vectors pAcYM1 or pVL1393/2, and recombinant baculoviruses isolated using a combination of limiting dilution and plaque assay. Using HPV-specific antisera and monoclonal antibodies HPV proteins were identified in lysates of Spodoptera frugiperda (Sf-21) cells infected with HPV-recombinant baculovirus. Immunoreactive HPV16 E7 protein produced in Sf-21 cells had an apparent M(r) of 19 kDa, larger than that predicted from the amino acid sequence, and similar to that of native HPV16 E7 protein in HeLa and CaSki cells. The apparent M(r) of recombinant HPV18-E7, HPV16-L1 and HPV16-E6 proteins was equivalent to the M(r) values predicted from the amino acid sequence. Thermostability studies revealed that the half-life of HPV16-E7 protein in Sf-21 cell lysate was approx. 20 h at 4 degrees C, 2 h at 22 degrees C, and less than 30 min at 37 degrees C. HPV16 L1, HPV16 E7 and HPV18 E7 proteins were predominantly localised in the nucleus of recombinant baculovirus-infected Sf-21 cells, whereas recombinant HPV 16 E6 protein was localised in both the cytoplasm and nucleus of infected insect cells. Northern blot analysis of RNA derived from insect cells infected with vAc16E6E7, a recombinant baculovirus containing both HPV16 E6 and E7 ORF's, revealed the presence of only E6 ORF transcripts, suggesting that the splicing of RNA products derived from the E6 and E7 ORF's, as observed in cervical cancer-derived cell lines, is not performed in insect cells. Baculovirus-derived HPV proteins have similar biological properties to the native proteins and should be suitable for studies on the immunology of HPV.

An ELISA capture assay for the E7 transforming proteins of HPV16 and HPV18.

ELISA capture assays were established for the E7 transforming proteins of HPV16 and HPV18, based on a range of previously characterised polyclonal and monoclonal antibodies. No cross-reactivity was observed in the ELISAs between HPV18 E7 and HPV16 E7. Immunoreactive E7 protein (iE7) was measured in a series of HPV-transformed cell lines, and ranged from 0.6 to 17.7 ng iE7/mg cell protein. iE7 was labile at 22 degrees C (t1/2 = 37 min) but relatively more stable at 4 degrees C (t1/2 = 210 min). HPV16 E7 protein at concentrations from 0.10 to 0.69 ng iE7/mg cell protein was detected in 5 of 13 smears from women with abnormal cervical cytology. Assay of E7 protein may play a role in the detection of HPV-induced cervical lesions with malignant potential.

Post-discharge surveillance: can patients reliably diagnose surgical wound infections?

Post-discharge surgical wound infection surveillance is an important part of many infection control programs. It is frequently undertaken by patient self-assessment, prompted either by a telephone or postal questionnaire. To assess the reliability of this method, 290 patients were followed for six weeks postoperatively. Their wounds were photographed and also covertly assessed for signs of infection by two experienced infection control nurses (ICNs). Patients also responded to a postal questionnaire seeking evidence of infection at both week four and week six post-surgery. Correlation between the patient's assessment of their wound and the ICNs diagnosis was poor (r = 0.37) with a low positive predictive value (28.7%), although negative predictive value was high (98.2%). Assessment of photos for signs of infection by two experienced clinicians also correlated poorly with the ICNs diagnosis of infection (r = 0.54). The patient's recall of prescription of an antibiotic by their general practitioner (GP) for wound infection during the postoperative period correlated best with the ICNs diagnosis (r = 0.76). This latter measure, particularly when confirmed by the GP in those patients reporting an infection, appears to provide the most valid and resource efficient marker of post-discharge surgical wound infection.

Transmissibility from horses to humans of a novel paramyxovirus, equine morbillivirus (EMV).

OBJECTIVES: Determination of potential infectivity of a new paramyxovirus equine morbillivirus (EMV) from horses to humans and humans to humans as a result of two outbreaks in Queensland which involved 23 horses and three humans. METHODS: Seroepidemiological testing using neutralizing and immunofluorescing antibodies on people with variable levels of exposure to infected horses and humans. RESULTS: All serological testing on a total of 298 individual contacts was negative. CONCLUSIONS: While the three human cases of EMV were probably infected as a result of very close contact with horses, these data suggest that infectivity from horses or humans is very low.

Incidence and prevalence of hepatitis C among clients of a Brisbane methadone clinic: factors influencing hepatitis C serostatus.

The objective of this study was to describe the incidence and prevalence of hepatitis C infection among clients of a methadone program in Queensland. The clinical notes of clients receiving methadone for treatment of opiate dependence who first registered at the clinic after 1989 were perused for information about their serological status for hepatitis C and hepatitis B infections during a six-week period in 1994. We followed hepatitis C negative clients until August-September 1995. At study entry, 69 per cent of the clients were recorded as being hepatitis C positive. Of those who were negative, the seroconversion rate was 11 per 100 person-years. The high incidence and prevalence of hepatitis C among methadone clients emphasises the need for effective early intervention strategies to prevent the transmission of hepatitis C among injecting drug users.

Reported prevalence of hepatitis C among clients of needle exchanges in southeast Queensland.

The aim of the study was to estimate the prevalence of hepatitis C infection among attenders of several high-volume needle exchanges in southeast Queensland, and to compare the prevalences among the needle exchanges. Clients at four needle exchanges were surveyed over a five-day period by means of a self-administered questionnaire. A high proportion of respondents (76 per cent) reported having been tested for hepatitis C antibodies and the overall prevalence of reported hepatitis C infection was 34 per cent. Thirty-one per cent of the respondents were amphetamine injectors, among whom there was a lower prevalence of reported hepatitis C infection than among opioid injectors (odds ratio 0.18, P < 0.01). There were some differences in the respondents' characteristics and in hepatitis C prevalence between different needle exchanges. The reported prevalence of HIV infection was 2 per cent. This study highlights the importance of surveying a range of needle exchanges to obtain a representative sample of needle-exchange clients overall. The low prevalence of hepatitis C in some groups of injecting drug users suggests that it is possible to prevent hepatitis C transmission among injecting drug users, and points to the opportunity for aiming hepatitis C prevention strategies at these groups.

Investigation of notifications of hepatitis C in 1994: the experience of three health departments.

Laboratories must notify health departments of cases of hepatitis C in Queensland, the Northern Territory (NT) and the Australian Capital Territory (ACT). Our objectives were to estimate the minimum proportion of notified cases of hepatitis C that were recent infections and to determine the risk factors for infection of the notified cases. We conducted a retrospective investigation of all eligible notifications received at the health departments in Queensland, the Northern Territory and the Australian Capital Territory. Of the 963 notifications about which information was received, 16 per cent were repeat notifications. These were excluded from further analysis. In Queensland, 7 per cent, and in both NT and ACT, 3 per cent of the notifications were considered to be recent infections. The most common risk factor reported for both recent and all other hepatitis C cases was a history of injecting drug use, although the proportion of cases with that history was different in NT from ACT and Queensland. Cases were tested because of screening programs: for drugs and alcohol, in sexually transmitted diseases clinics and prison; and because of clinical indications such as a risk factor, symptoms, or results of liver function tests. Another common reason for testing was a request from a patient. A significant proportion of recorded notifications was repeat notifications. Most notifications were of patients who had become infected more than 12 months ago and the most common risk factor was injecting drug use. There was not a high proportion of cases with unknown risk factors.

Onshore catering increases the risk of diarrhoeal illness amongst cruise ship passengers.

Of 134 Queensland passengers on a cruise, 91 (67.9%) people reported various illnesses including 41 (30.6%) who reported diarrhoeal symptoms. Queensland passengers who ate while onshore at non-Australian ports were significantly more at risk of developing diarrhoeal symptoms than those who did not. Passengers were particularly at risk when they ate onshore while undertaking a tour compared with those who did not undertake this tour. Travellers should be warned of the possibility of contracting diarrhoeal illness from onshore catering.

Male partners of women with genital human papillomavirus infection. An assessment of colposcopic abnormalities by histological examination and human papillomavirus hybridization.

Men whose female sexual partners showed histological evidence of human papillomavirus infection were examined. Human papillomavirus DNA was identified in 29 of 35 biopsy samples of colposcopically-identified penile lesions. Human papillomavirus strains that were related to human papillomavirus genotypes 6/11 were observed most commonly (seven of eight patients) in the partners of patients with warty atypia or condylomata, while human papillomavirus strains that were related to human papillomavirus genotypes 16/18 were most-commonly (eight of 15 patients) observed in tissue from the partners of patients with cervical intraepithelial neoplasia. Measurement of human papillomavirus DNA in lesions by the filter in-situ hybridization technique more-frequently indicated human papillomavirus infection (29 of 35 lesions) than did conventional histopathological assessment (21 of 35 lesions) in this "high-risk" group. We conclude that colposcopically-identifiable lesions in male sexual partners are likely to contain human papillomavirus DNA, even if is no definite histological evidence of human papillomavirus infection is present, and that such lesions frequently contain strains of human papillomavirus that have been associated with the development of anogenital carcinoma.

Enhanced surveillance for meningococcal disease in Queensland in 1999.

Enhanced surveillance of invasive meningococcal disease commenced in Queensland in 1999. There were 93 cases, an incidence of 2.8/100,000 population. Most (87%) cases were laboratory confirmed, but 12 per cent were probable cases without laboratory confirmation. The highest age-specific attack rates were in the under 1, 1 to 4 and 15 to 24 year age groups. Most of the serologically characterised isolates were group B (70%), followed by group C (24%). There were 12 deaths, resulting in a case fatality rate of 13 per cent. Those who died were more likely to have group C than group B disease (OR 5.04, CI 1.05-25.14). Only 14 per cent of cases that saw a general practitioner (GP) prior to hospitalization received parenteral antibiotics, 23 per cent of the 35 cases referred to hospital by a GP received pre-hospital parenteral antibiotics and 33 per cent of cases were notified to health authorities within 24 hours of hospital admission. Thirty per cent were notified two or more days after hospitalization, delaying the start of public health action. Enhanced surveillance has demonstrated a need to promote the use of pre-hospital parenteral antibiotics by GPs and a need to encourage more timely reporting of cases to health authorities.

An outbreak of measles in a rural Queensland town in 1997; an opportunity to assess vaccine effectiveness.

This report describes a measles outbreak in a rural town in south-east Queensland and presents the results of a vaccine effectiveness (VE) study performed during this outbreak. It is important to assess the effectiveness of a vaccine in an outbreak to determine if the outbreak is due to failure of the vaccine or failure to vaccinate. There were 44 cases of measles amongst local residents, which represents a notification rate of 396.7 per 100,000 population. Case investigations identified a group of people who had been exposed to measles at a seminar. The attack rate for the seminar cohort was 18% (11/61). This presented an opportunity to conduct a VE study using data about children aged less than 16 years who attended the seminar. In this cohort of 23 attendees, all 7 children who had not received any measles vaccinations became cases whilst the 6 who were fully vaccinated for their age according to NHMRC guidelines were protected from measles illness. Although there were insufficient fully vaccinated cohort members to reliably estimate VE for this group, the vaccine was 84.6% (95% CI: 15.0-99.7%) effective for those who had received at least one validated dose of vaccine. Despite the sample size limitations, the results support the view that failure to vaccinate rather than vaccine failure contributed to the high infection rate in the seminar cohort.

Preferential expansion and activation of V beta 5+ CD4+ T cells in murine acquired immunodeficiency syndrome.

Infection of B6 mice with LP-BM5 MuLV results in a syndrome characterized by progressive and profound immunodeficiency, termed murine acquired immunodeficiency syndrome (MAIDS). In this report we show that preferential expansion and activation of V beta 5+ CD4+ spleen cells occurs early in the course of disease, which then progresses to more widespread polyclonal activation of CD4+ T cells. V beta 5 expansion occurs only on infection with MAIDS-associated MuLV and is not observed after infection with other MuLV. The possible role of V beta 5 activation and expansion as a necessary early step in the pathogenesis of MAIDS is discussed.