Quantifying effects of wild dogs, domestic dogs and humans on the spread of rabies in Australia

Rabies is a preventable viral zoonosis that causes inflammation of the brain, and eventually death, in infected mammals. With few exceptions, including Australia, terrestrial rabies can be found worldwide. More than 55,000 deaths from rabies infection are reported annually; these are mainly in Asia and Africa where the primary reservoir is the domestic dog. Despite ongoing control efforts in Indonesia, canine rabies remains a disease of critical concern there. Although rabies is not endemic in Australia, at less than 300km away in Indonesia, a rabies incursion is a likely and imminent threat. To improve preparedness for a canine rabies outbreak in Australia, I collected data on a number of extant dog populations in northern and eastern Australia. I used a range of methods including self-administered questionnaires, GPS telemetry collars, camera trapping and mark-recapture studies. Using my own data and parameters collected from the wider literature, I developed state-transition models to determine how rabies could spread through these dog populations. Finally, I used these same models to evaluate a range of control strategies, including dog removal and vaccination, to identify the most effective options for reducing impacts in Australian communities following a rabies incursion. Model outputs suggested that rabies will progress differently within functionally different dog populations present within Australia. Restrained domestic dogs posed limited risk for rabies transmission, because interactions with other dogs were limited and generally supervised by owners. Free-roaming domestic and hunting dogs will likely play an important role in rabies transmission in some situations only, primarily based on their ability to roam, access to other free-roaming dogs and their interactions within and between dog groups. Wild dogs (including dingoes) proved the most critical type of dog for rabies spread and maintenance in Australia, because they are widely distributed, often in high abundance, roam over large distances and frequently interact. I found that time to detection for rabies in wild dogs will likely be lengthy, probably due to low infection rates prior to an epidemic and limited contact with humans, relative to the other categories of dog that I studied. Further, the capacity of authorities to implement effective control strategies for wild dogs will likely be restricted because of limited access to individual animals. The economic costs of controlling a rabies outbreak involving wild dogs will be substantial and likely equivalent to the costs for extensive aerially-based wild dog control that are currently used in some areas of Australia (~Aus$34 km-2). Australia’s current plans to address rabies incursions, which were developed in the 1990s are clearly outdated. My findings reveal that revision of these plans, taking specific account of relevant differences between restrained domestic dogs, free-roaming domestic dogs and extensive wild dog populations is necessary to ensure that Australia is adequately prepared for the arrival of canine rabies

Two-year follow-up of infant and maternal outcomes after planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial

OBJECTIVE: We evaluated the best time to initiate delivery in late preterm pre-eclampsia in order to optimise long-term infant and maternal outcomes. DESIGN: Parallel-group, non-masked, randomised controlled trial SETTING: 46 UK maternity units POPULATION: Women with pre-eclampsia between 34+0 and 36+6 weeks' gestation, without severe disease, were randomised to planned delivery or expectant management. PRIMARY LONG-TERM OUTCOME: Infant neurodevelopmental outcome at 2 years of age, using the PARCA-R (Parent Report of Children's Abilities-Revised) composite score. RESULTS: Between Sept 29, 2014, and Dec 10, 2018, 901 women were enrolled in the trial, with 450 allocated to planned delivery and 451 to expectant management. At 2-year follow-up, the intention-to-treat analysis population included 276 women (290 infants) allocated to planned delivery and 251 women (256 infants) to expectant management. The mean composite standardised PARCA-R scores were 89.5 (standard deviation (SD) 18.2) in the planned delivery group and 91.9 (SD 18.4) in the expectant management group, with an adjusted mean difference of -2.4 (95% CI -5.4 to 0.5) points. CONCLUSION: In infants of women with late preterm pre-eclampsia, average neurodevelopmental assessment at 2 years lies within the normal range, regardless of whether planned delivery or expectant management is pursued. Because of lower than anticipated follow-up, there was limited power to demonstrate these scores were not different, but the small between-group difference in PARCA-R scores is unlikely to be clinically important

Repeat Placental Growth Factor-Based Testing in Women with Suspected Preterm Preeclampsia:A Stratified Analysis of the PARROT-2 Trial

BACKGROUND: PlGF (placental growth factor)-based testing reduces severe maternal adverse outcomes. Repeat PlGF-based testing is not associated with improved perinatal or maternal outcomes. This planned secondary analysis aimed to determine whether there is a subgroup of women who benefit from repeat testing. METHODS: Pregnant individuals with suspected preterm preeclampsia were randomized to repeat revealed PlGF-based testing, compared with usual care where testing was concealed. Perinatal and maternal outcomes were stratified by trial group, by initial PlGF-based test result, and by PlGF-based test type (PlGF or sFlt-1 [soluble fms-like tyrosine kinase-1]/PlGF ratio). RESULTS: A total of 1252 pregnant individuals were included. Abnormal initial PlGF-based test identified a more severe phenotype of preeclampsia, at increased risk of adverse maternal and perinatal outcomes. Repeat testing was not significantly associated with clinical benefit in women with abnormal initial results. Of women with a normal initial result, 20% developed preeclampsia, with the majority at least 3 to 4 weeks after initial presentation. Repeat test results were more likely to change from normal to abnormal in symptomatic women (112/415; 27%) compared with asymptomatic women (163/890; 18%). A higher proportion of symptomatic women who changed from normal to abnormal were diagnosed with preeclampsia, compared with asymptomatic women. CONCLUSIONS: Our results do not demonstrate evidence of the clinical benefit of repeating PlGF-based testing if the initial result is abnormal. Judicious use of repeat PlGF-based testing to stratify risk may be considered at least 2 weeks after a normal initial test result, particularly in women who have symptoms or signs of preeclampsia. REGISTRATION: URL: https://www.isrctn.com/ISRCTN85912420; Unique identifier: ISRCTN85912420.</p

Distribution of health literacy strengths and weaknesses across socio-demographic groups: a cross-sectional survey using the Health Literacy Questionnaire (HLQ)

BACKGROUND: Recent advances in the measurement of health literacy allow description of a broad range of personal and social dimensions of the concept. Identifying differences in patterns of health literacy between population sub-groups will increase understanding of how health literacy contributes to health inequities and inform intervention development. The aim of this study was to use a multi-dimensional measurement tool to describe the health literacy of adults in urban and rural Victoria, Australia. METHODS: Data were collected from clients (n = 813) of 8 health and community care organisations, using the Health Literacy Questionnaire (HLQ). Demographic and health service data were also collected. Data were analysed using descriptive statistics. Effect sizes (ES) for standardised differences in means were used to describe the magnitude of difference between demographic sub-groups. RESULTS: Mean age of respondents was 72.1 (range 19-99) years. Females comprised 63% of the sample, 48% had not completed secondary education, and 96% reported at least one existing health condition. Small to large ES were seen for mean differences in HLQ scales between most demographic groups. Compared with participants who spoke English at home, those not speaking English at home had much lower scores for most HLQ scales including the scales 'Understanding health information well enough to know what to do' (ES -1.09 [95% confidence interval (CI) -1.33 to -0.84]), 'Ability to actively engage with healthcare providers' (ES -1.00 [95% CI -1.24, -0.75]), and 'Navigating the healthcare system' (ES -0.72 [95% CI -0.97, -0.48]). Similar patterns and ES were seen for participants born overseas compared with those born in Australia. Smaller ES were seen for sex, age group, private health insurance status, number of chronic conditions, and living alone. CONCLUSIONS: This study has revealed some large health literacy differences across nine domains of health literacy in adults using health services in Victoria. These findings provide insights into the relationship between health literacy and socioeconomic position in vulnerable groups and, given the focus of the HLQ, provide guidance for the development of equitable interventions

Two-year follow-up of infant and maternal outcomes after planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): A randomised controlled trial

ObjectiveWe evaluated the best time to initiate delivery in late preterm pre-eclampsia in order to optimise long-term infant and maternal outcomes.DesignParallel-group, non-masked, randomised controlled trial.SettingForty-six maternity units in the UK.PopulationWomen with pre-eclampsia between 34+0 and 36+6 weeks of gestation, without severe disease, were randomised to planned delivery or expectant management.Main outcome measuresInfant neurodevelopmental outcome at 2 years of age, using the Parent Report of Children’s Abilities – Revised (PARCA-R) composite score.ResultsBetween 29 September 2014 and 10 December 2018, 901 women were enrolled in the trial, with 450 women allocated to planned delivery and 451 women allocated to expectant management. At the 2-year follow-up, the intention-to-treat analysis population included 276 women (290 infants) allocated to planned delivery and 251 women (256 infants) allocated to expectant management. The mean composite standardised PARCA-R scores were 89.5 (SD 18.2) in the planned delivery group and 91.9 (SD 18.4) in the expectant management group, with an adjusted mean difference of −2.4 points (95% CI −5.4 to 0.5 points).ConclusionsIn infants of women with late preterm pre-eclampsia, the average neurodevelopmental assessment at 2 years lies within the normal range, regardless of whether planned delivery or expectant management was pursued. With the lower than anticipated follow-up rate there was limited power to demonstrate that these scores did not differ, but the small between-group difference in PARCA-R scores is unlikely to be clinically important

Repeat placental growth factor-based testing in women with suspected preterm pre-eclampsia (PARROT-2): a multicentre, parallel-group, superiority, randomised controlled trial.

BackgroundPlacental growth factor (PlGF)-based testing has high diagnostic accuracy for predicting pre-eclampsia needing delivery, significantly reducing time to diagnosis and severe maternal adverse outcomes. The clinical benefit of repeat PlGF-based testing is unclear. We aimed to determine whether repeat PlGF-based testing (using a clinical management algorithm and nationally recommended thresholds) reduces adverse perinatal outcomes in pregnant individuals with suspected preterm pre-eclampsia.MethodsIn this multicentre, parallel-group, superiority, randomised controlled trial, done in 22 maternity units across England, Scotland, and Wales, we recruited women aged 18 years or older with suspected pre-eclampsia between 22 weeks and 0 days of gestation and 35 weeks and 6 days of gestation. Women were randomly assigned (1:1) to revealed repeat PlGF-based testing or concealed repeat testing with usual care. The intervention was not masked to women or partners, or clinicians or data collectors, due to the nature of the trial. The trial statistician was masked to intervention allocation. The primary outcome was a perinatal composite of stillbirth, early neonatal death, or neonatal unit admission. The primary analysis was by the intention-to-treat principle, with a per-protocol analysis restricted to women managed according to their allocation group. The trial was prospectively registered with the ISRCTN registry, ISRCTN 85912420.FindingsBetween Dec 17, 2019, and Sept 30, 2022, 1253 pregnant women were recruited and randomly assigned treatment; one patient was excluded due to randomisation error. 625 women were allocated to revealed repeat PlGF-based testing and 627 women were allocated to usual care with concealed repeat PlGF-based testing (mean age 32·3 [SD 5·7] years; 879 [70%] white). One woman in the concealed repeat PlGF-based testing group was lost to follow-up. There was no significant difference in the primary perinatal composite outcome between the revealed repeat PlGF-based testing group (195 [31·2%]) of 625 women) compared with the concealed repeat PlGF-based testing group (174 [27·8%] of 626 women; relative risk 1·21 [95% CI 0·95-1·33]; p=0·18). The results from the per-protocol analysis were similar. There were four serious adverse events in the revealed repeat PlGF-based testing group and six in the concealed repeat PlGF-based testing group; all serious adverse events were deemed unrelated to the intervention by the site principal investigators and chief investigator.InterpretationRepeat PlGF-based testing in pregnant women with suspected pre-eclampsia was not associated with improved perinatal outcomes. In a high-income setting with a low prevalence of adverse outcomes, universal, routine repeat PlGF-based testing of all individuals with suspected pre-eclampsia is not recommended.FundingTommy's Charity, Jon Moulton Charitable Trust, and National Institute for Health and Care Research Guy's and St Thomas' Biomedical Research Centre

Repeat Placental Growth Factor-Based Testing in Women With Suspected Preterm Preeclampsia: A Stratified Analysis of the PARROT-2 Trial

BACKGROUND: PlGF (placental growth factor)-based testing reduces severe maternal adverse outcomes. Repeat PlGF-based testing is not associated with improved perinatal or maternal outcomes. This planned secondary analysis aimed to determine whether there is a subgroup of women who benefit from repeat testing. METHODS: Pregnant individuals with suspected preterm preeclampsia were randomized to repeat revealed PlGF-based testing, compared with usual care where testing was concealed. Perinatal and maternal outcomes were stratified by trial group, by initial PlGF-based test result, and by PlGF-based test type (PlGF or sFlt-1 [soluble fms-like tyrosine kinase-1]/PlGF ratio). RESULTS: A total of 1252 pregnant individuals were included. Abnormal initial PlGF-based test identified a more severe phenotype of preeclampsia, at increased risk of adverse maternal and perinatal outcomes. Repeat testing was not significantly associated with clinical benefit in women with abnormal initial results. Of women with a normal initial result, 20% developed preeclampsia, with the majority at least 3 to 4 weeks after initial presentation. Repeat test results were more likely to change from normal to abnormal in symptomatic women (112/415; 27%) compared with asymptomatic women (163/890; 18%). A higher proportion of symptomatic women who changed from normal to abnormal were diagnosed with preeclampsia, compared with asymptomatic women. CONCLUSIONS: Our results do not demonstrate evidence of the clinical benefit of repeating PlGF-based testing if the initial result is abnormal. Judicious use of repeat PlGF-based testing to stratify risk may be considered at least 2 weeks after a normal initial test result, particularly in women who have symptoms or signs of preeclampsia. REGISTRATION: URL: XXX; Unique identifier: ISRCTN85912420

Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: In women with late preterm pre-eclampsia, the optimal time to initiate delivery is unclear because limitation of maternal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of neonatal or infant outcomes, compared with expectant management (usual care) in women with late preterm pre-eclampsia. Methods: In this parallel-group, non-masked, multicentre, randomised controlled trial done in 46 maternity units across England and Wales, we compared planned delivery versus expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia from 34 to less than 37 weeks' gestation and a singleton or dichorionic diamniotic twin pregnancy. The co-primary maternal outcome was a composite of maternal morbidity or recorded systolic blood pressure of at least 160 mm Hg with a superiority hypothesis. The co-primary perinatal outcome was a composite of perinatal deaths or neonatal unit admission up to infant hospital discharge with a non-inferiority hypothesis (non-inferiority margin of 10% difference in incidence). Analyses were by intention to treat, together with a per-protocol analysis for the perinatal outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN01879376. The trial is closed to recruitment but follow-up is ongoing. Findings: Between Sept 29, 2014, and Dec 10, 2018, 901 women were recruited. 450 women (448 women and 471 infants analysed) were allocated to planned delivery and 451 women (451 women and 475 infants analysed) to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group (289 [65%] women) compared with the expectant management group (338 [75%] women; adjusted relative risk 0·86, 95% CI 0·79–0·94; p=0·0005). The incidence of the co-primary perinatal outcome by intention to treat was significantly higher in the planned delivery group (196 [42%] infants) compared with the expectant management group (159 [34%] infants; 1·26, 1·08–1·47; p=0·0034). The results from the per-protocol analysis were similar. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group. Interpretation: There is strong evidence to suggest that planned delivery reduces maternal morbidity and severe hypertension compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater neonatal morbidity. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery. Funding: National Institute for Health Research Health Technology Assessment Programme