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Extended Model Semantics and Forgetting in Dynamic Epistemic Logic

Fri, 01 Jan 2021 00:00:00 GMT

Eckhardt, Timo 2021 Extended Model Semantics and Forgetting in Dynamic Epistemic Logic In this thesis I investigate the idea of modeling epistemic updates as static modal operators. I discuss Extended Model Semantics for Dynamic Epistemic Logics, specifically Action Model Logic with postconditions. I argue that we get a better and more versatile framework for epistemic actions than with the standard update semantics. This comes from the use of normality conditions which act like frame conditions for the modal relationships corresponding to actions. By defining those we pin-point the exact type of actions we are trying to model and so they give us an easy option to change our actions by simply adding, removing, or changing normality conditions. Extended models will be used to develop new axiomatic systems. These axioms are non-reductive, i.e. do not simply reduce the truth of dynamic formulas down to the truth of corresponding static epistemic formulas, in nature and therefore allow for a better categorization of epistemic actions mirroring the normality conditions from which they are derived. These axioms will also be used to develop Display Logic proof systems for all logics discussed in the thesis. These are then analyzed and shown to be sound and complete and allow for cut-elimination. This has a twofold purpose: It shows the usefulness of normality conditions and the corresponding axioms and it also helps us add to the toolbox of Display Logic as a proof system for modal logic. I also develop logics of forgetting that allow for modelling of the forgetting of positive epistemic formulas in multi-agent epistemic logic. I also discuss and develop extensions that allow for considering epistemic entrenchment of formulas and the forgetting of negative epistemic formulas and so all epistemic formulas. Additionally, extended semantics for the different logics of forgetting are developed with corresponding non-reductive axioms and, as already mentioned, display calculi. © 2021 Timo Eckhardt PhD thesis

Malaria: global challenges for malaria eradication

Tue, 01 Mar 2016 00:00:00 GMT

Brown, G; Rogerson, S 2016-03-01 Malaria: global challenges for malaria eradication The enormous decline in the annual morbidity and mortality from malaria is the spectacular global public health success of the past decade. This achievement results largely from increased finance for investment in measures known to prevent malaria: bednets treated with long-lasting insecticides, chemoprophylaxis, and rapid access to effective treatment. Such has been the success of these measures that plans are being put in place to achieve the vision of a malaria-free world within the next three decades. Large financial and political commitments and ongoing research will be required to maintain the gains, overcome known and unknown challenges such as drug and insecticide resistance, and to achieve those goals. Effective vaccines or methods for reducing mosquito vectorial capacity would add enormously to the chance of achieving this goal. The aim of this article is to summarise the current status of malaria control, the recent research successes, the challenges being addressed, and the plan for progress to elimination of malaria in the longer term. Journal Article

Safety, tolerability and pharmacokinetic properties of coadministered azithromycin and piperaquine in pregnant Papua New Guinean women

Fri, 01 Jul 2016 00:00:00 GMT

Moore, BR; Benjamin, JM; Auyeung, SO; Salman, S; Yadi, G; Griffin, S; Page-Sharp, M; Batty, KT; Siba, PM; Mueller, I; Rogerson, SJ; Davis, TME 2016-07-01 Safety, tolerability and pharmacokinetic properties of coadministered azithromycin and piperaquine in pregnant Papua New Guinean women AIMS: The aim of the present study was to investigate the safety, tolerability and pharmacokinetics of coadministered azithromycin (AZI) and piperaquine (PQ) for treating malaria in pregnant Papua New Guinean women. METHODS: Thirty pregnant women (median age 22 years; 16-32 weeks' gestation) were given three daily doses of 1 g AZI plus 960 mg PQ tetraphosphate with detailed monitoring/blood sampling over 42 days. Plasma AZI and PQ were assayed using liquid chromatography-mass spectrometry and high-performance liquid chromatography, respectively. Pharmacokinetic analysis was by population-based compartmental models. RESULTS: The treatment was well tolerated. The median (interquartile range) increase in the rate-corrected electrocardiographic QT interval 4 h postdose [12 (6-26) ms(0) (.5) ] was similar to that found in previous studies of AZI given in pregnancy with other partner drugs. Six women with asymptomatic malaria cleared their parasitaemias within 72 h. Two apararasitaemic women developed late uncomplicated Plasmodium falciparum infections on Days 42 and 83. Compared with previous pregnancy studies, the area under the concentration-time curve (AUC0-∞ ) for PQ [38818 (24354-52299) μg h l(-1) ] was similar to published values but there was a 52% increase in relative bioavailability with each dose. The AUC0-∞ for AZI [46799 (43526-49462) μg h l(-1) ] was at least as high as reported for higher-dose regimens, suggesting saturable absorption and/or concentration-dependent tissue uptake and clearance from the central compartment. CONCLUSIONS: AZI-PQ appears to be well tolerated and safe in pregnancy. Based on the present/other data, total AZI doses higher than 3 g for the treatment and prevention of malaria may be unnecessary in pregnant women, while clearance of parasitaemia could improve the relative bioavailability of PQ. Journal Article

Prevention and control of malaria in pregnancy - new threats, new opportunities?

Sat, 01 Apr 2017 00:00:00 GMT

Rogerson, SJ; Unger, HW 2017-04-01 Prevention and control of malaria in pregnancy - new threats, new opportunities? INTRODUCTION: Over 100 million women and their babies are at risk of malaria in pregnancy each year. Malaria prevention in pregnancy relies on long-lasting insecticidal nets (LLINs), and, in Africa, intermittent preventive treatment in pregnancy (IPTp). Increasing resistance of malaria parasites to sulfadoxine-pyrimethamine, the only drug endorsed for IPTp, and increasing mosquito resistance to pyrethroids used in LLINs, threaten the efficacy of these proven strategies, while operational challenges restrict their implementation in areas of great need. Areas Covered: This review summarizes strategies for malaria prevention in pregnancy (both currently used and those undergoing preclinical and clinical evaluation), primarily drawing on publications and study protocols from the last decade. Challenges associated with each strategy are discussed, including the particular problem of HIV and malaria in pregnancy, and areas of further research are highlighted. Expert Commentary: Alternative drugs for IPTp are needed. Dihydroartemisinin-piperaquine is particularly promising, but requires further evaluation, and might contribute to artemisinin resistance. Intermittent screening and treatment in pregnancy (ISTp) is an alternative to IPTp that could reduce unnecessary antenatal drug exposure and resistance risk, but it is not recommended with current, insensitive screening tests. Optimal strategies for areas of low or declining malaria transmission remain to be determined. Journal Article

Optimal Antimalarial Dose Regimens for Sulfadoxine-Pyrimethamine with or without Azithromycin in Pregnancy Based on Population Pharmacokinetic Modeling

Mon, 01 May 2017 00:00:00 GMT

Salman, S; Baiwog, F; Page-Sharp, M; Griffin, S; Karunajeewa, HA; Mueller, I; Rogerson, SJ; Siba, PM; Ilett, KF; Davis, TME 2017-05-01 Optimal Antimalarial Dose Regimens for Sulfadoxine-Pyrimethamine with or without Azithromycin in Pregnancy Based on Population Pharmacokinetic Modeling Optimal dosing of sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment in pregnancy remains to be established, particularly when coadministered with azithromycin (AZI). To further characterize SP pharmacokinetics in pregnancy, plasma concentration-time data from 45 nonpregnant and 45 pregnant women treated with SP-AZI (n = 15 in each group) and SP-chloroquine (n = 30 in each group) were analyzed. Population nonlinear mixed-effect pharmacokinetic models were developed for pyrimethamine (PYR), sulfadoxine (SDOX), and N-acetylsulfadoxine (the SDOX metabolite NASDOX), and potential covariates were included. Pregnancy increased the relative clearance (CL/F) of PYR, SDOX, and NASDOX by 48, 29, and 70%, respectively, as well as the relative volumes of distribution (V/F) of PYR (46 and 99%) and NASDOX (46%). Coadministration of AZI resulted in a greater increase in PYR CL/F (80%) and also increased NASDOX V/F by 76%. Apparent differences between these results and those of published studies of SP disposition may reflect key differences in study design, including the use of an early postpartum follow-up study rather than a nonpregnant comparator group. Simulations based on the final population model demonstrated that, compared to conventional single-dose SP in nonpregnant women, two such doses given 24 h apart should ensure that pregnant women have similar drug exposure, while three daily SP doses may be required if SP is given with AZI. The results of past and ongoing trials using recommended adult SP doses with or without AZI in pregnant women may need to be interpreted in light of these findings and consideration given to using increased doses in future trials. Journal Article

Optimal antimalarial dose regimens for chloroquine in pregnancy based on population pharmacokinetic modelling

Sun, 01 Oct 2017 00:00:00 GMT

Salman, S; Baiwog, F; Page-Sharp, M; Kose, K; Karunajeewa, HA; Mueller, I; Rogerson, SJ; Siba, PM; Ilett, KF; Davis, TME 2017-10-01 Optimal antimalarial dose regimens for chloroquine in pregnancy based on population pharmacokinetic modelling Despite extensive use and accumulated evidence of safety, there have been few pharmacokinetic studies from which appropriate chloroquine (CQ) dosing regimens could be developed specifically for pregnant women. Such optimised CQ-based regimens, used as treatment for acute malaria or as intermittent preventive treatment in pregnancy (IPTp), may have a valuable role if parasite CQ sensitivity returns following reduced drug pressure. In this study, population pharmacokinetic/pharmacodynamic modelling was used to simultaneously analyse plasma concentration-time data for CQ and its active metabolite desethylchloroquine (DCQ) in 44 non-pregnant and 45 pregnant Papua New Guinean women treated with CQ and sulfadoxine/pyrimethamine or azithromycin (AZM). Pregnancy was associated with 16% and 49% increases in CQ and DCQ clearance, respectively, as well as a 24% reduction in CQ relative bioavailability. Clearance of DCQ was 22% lower in those who received AZM in both groups. Simulations based on the final multicompartmental model demonstrated that a 33% CQ dose increase may be suitable for acute treatment for malaria in pregnancy as it resulted in equivalent exposure to that in non-pregnant women receiving recommended doses, whilst a double dose would likely be required for an effective duration of post-treatment prophylaxis when used as IPTp especially in areas of CQ resistance. The impact of co-administered AZM was clinically insignificant in simulations. The results of past/ongoing trials employing recommended adult doses of CQ-based regimens in pregnant women should be interpreted in light of these findings, and consideration should be given to using increased doses in future trials. Journal Article

Linking EPCR-Binding PfEMP1 to Brain Swelling in Pediatric Cerebral Malaria

Wed, 08 Nov 2017 00:00:00 GMT

Kessler, A; Dankwa, S; Bernabeu, M; Harawa, V; Danziger, SA; Duffy, F; Kampondeni, SD; Potchen, MJ; Dambrauskas, N; Vigdorovich, V; Oliver, BG; Hochman, SE; Mowrey, WB; MacCormick, IJC; Mandala, WL; Rogerson, SJ; Sather, DN; Aitchison, JD; Taylor, TE; Seydel, KB; Smith, JD; Kim, K 2017-11-08 Linking EPCR-Binding PfEMP1 to Brain Swelling in Pediatric Cerebral Malaria Brain swelling is a major predictor of mortality in pediatric cerebral malaria (CM). However, the mechanisms leading to swelling remain poorly defined. Here, we combined neuroimaging, parasite transcript profiling, and laboratory blood profiles to develop machine-learning models of malarial retinopathy and brain swelling. We found that parasite var transcripts encoding endothelial protein C receptor (EPCR)-binding domains, in combination with high parasite biomass and low platelet levels, are strong indicators of CM cases with malarial retinopathy. Swelling cases presented low platelet levels and increased transcript abundance of parasite PfEMP1 DC8 and group A EPCR-binding domains. Remarkably, the dominant transcript in 50% of swelling cases encoded PfEMP1 group A CIDRα1.7 domains. Furthermore, a recombinant CIDRα1.7 domain from a pediatric CM brain autopsy inhibited the barrier-protective properties of EPCR in human brain endothelial cells in vitro. Together, these findings suggest a detrimental role for EPCR-binding CIDRα1 domains in brain swelling. Journal Article

Intermittent Preventive Therapy in Pregnancy and Incidence of Low Birth Weight in Malaria-Endemic Countries

Thu, 01 Mar 2018 00:00:00 GMT

Cates, JE; Westreich, D; Unger, HW; Bauserman, M; Adair, L; Cole, SR; Meshnick, S; Rogerson, SJ 2018-03-01 Intermittent Preventive Therapy in Pregnancy and Incidence of Low Birth Weight in Malaria-Endemic Countries OBJECTIVES: To estimate the impact of hypothetical antimalarial and nutritional interventions (which reduce the prevalence of low midupper arm circumference [MUAC]) on the incidence of low birth weight (LBW). METHODS: We analyzed data from 14 633 pregnancies from 13 studies conducted across Africa and the Western Pacific from 1996 to 2015. We calculated population intervention effects for increasing intermittent preventive therapy in pregnancy (IPTp), full coverage with bed nets, reduction in malaria infection at delivery, and reductions in the prevalence of low MUAC. RESULTS: We estimated that, compared with observed IPTp use, administering 3 or more doses of IPTp to all women would decrease the incidence of LBW from 9.9% to 6.9% (risk difference = 3.0%; 95% confidence interval = 1.7%, 4.0%). The intervention effects for eliminating malaria at delivery, increasing bed net ownership, and decreasing low MUAC prevalence were all modest. CONCLUSIONS: Increasing IPTp uptake to at least 3 doses could decrease the incidence of LBW in malaria-endemic countries. The impact of IPTp on LBW was greater than the effect of prevention of malaria, consistent with a nonmalarial effect of IPTp, measurement error, or selection bias. Journal Article

Acquisition of Antibodies Against Endothelial Protein C Receptor-Binding Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 in Children with Severe Malaria

Fri, 01 Mar 2019 00:00:00 GMT

Rambhatla, JS; Turner, L; Manning, L; Laman, M; Davis, TME; Beeson, JG; Mueller, I; Warrel, J; Theander, TG; Lavstsen, T; Rogerson, SJ 2019-03-01 Acquisition of Antibodies Against Endothelial Protein C Receptor-Binding Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 in Children with Severe Malaria BACKGROUND: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates parasite sequestration in postcapillary venules in P. falciparum malaria. PfEMP1 types can be classified based on their cysteine-rich interdomain region (CIDR) domains. Antibodies to different PfEMP1 types develop gradually after repeated infections as children age, and antibodies to specific CIDR types may confer protection. METHODS: Levels of immunoglobulin G to 35 recombinant CIDR domains were measured by means of Luminex assay in acute-stage (baseline) and convalescent-stage plasma samples from Papua New Guinean children with severe or uncomplicated malaria and in healthy age-matched community controls. RESULTS: At baseline, antibody levels were similar across the 3 groups. After infection, children with severe malaria had higher antibody levels than those with uncomplicated malaria against the endothelial protein C receptor (EPCR) binding CIDRα1 domains, and this difference was largely confined to older children. Antibodies to EPCR-binding domains increased from presentation to follow-up in severe malaria, but not in uncomplicated malaria. CONCLUSIONS: The acquisition of antibodies against EPCR-binding CIDRα1 domains of PfEMP1 after a severe malaria episode suggest that EPCR-binding PfEMP1 may have a role in the pathogenesis of severe malaria in Papua New Guinea. Journal Article

Point-of-care testing and treatment of sexually transmitted infections to improve birth outcomes in high-burden, low-income settings: Study protocol for a cluster randomized crossover trial (the WANTAIM Trial, Papua New Guinea).

Tue, 01 Jan 2019 00:00:00 GMT

Vallely, AJ; Pomat, WS; Homer, C; Guy, R; Luchters, S; Mola, GDL; Kariwiga, G; Vallely, LM; Wiseman, V; Morgan, C; Wand, H; Rogerson, SJ; Tabrizi, SN; Whiley, DM; Low, N; Peeling, R; Siba, P; Riddell, M; Laman, M; Bolnga, J; Robinson, LJ; Morewaya, J; Badman, SG; Batura, N; Kelly-Hanku, A; Toliman, PJ; Peter, W; Babona, D; Peach, E; Garland, SM; Kaldor, JM 2019 Point-of-care testing and treatment of sexually transmitted infections to improve birth outcomes in high-burden, low-income settings: Study protocol for a cluster randomized crossover trial (the WANTAIM Trial, Papua New Guinea). Background: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and bacterial vaginosis have been associated with preterm birth and low birth weight, and are highly prevalent among pregnant women in many low- and middle-income settings. There is conflicting evidence on the potential benefits of screening and treating these infections in pregnancy. Newly available diagnostic technologies make it possible, for the first time, to conduct definitive field trials to fill this knowledge gap. The primary aim of this study is to evaluate whether antenatal point-of-care testing and immediate treatment of these curable sexually transmitted and genital infections (STIs) leads to reduction in preterm birth and low birth weight. Methods: The Women and Newborn Trial of Antenatal Interventions and Management (WANTAIM) is a cluster-randomised crossover trial in Papua New Guinea to compare point-of-care STI testing and immediate treatment with standard antenatal care (which includes the WHO-endorsed STI 'syndromic' management strategy based on clinical features alone without laboratory confirmation). The unit of randomisation is a primary health care facility and its catchment communities. The primary outcome is a composite measure of two events: the proportion of women and their newborns in each trial arm, who experience either preterm birth (delivery <37 completed weeks of gestation as determined by ultrasound) and/or low birth weight (<2500 g measured within 72 hours of birth). The trial will also evaluate neonatal outcomes, as well as the cost-effectiveness, acceptability and health system requirements of this strategy, compared with standard care. Conclusions: WANTAIM is the first randomised trial to evaluate the effectiveness, cost-effectiveness, acceptability and health system requirements of point-of-care STI testing and treatment to improve birth outcomes in high-burden settings. If the intervention is proven to have an impact, the trial will hasten access to these technologies and could improve maternal and neonatal health in high-burden settings worldwide. Registration: ISRCTN37134032. Journal Article

Role of IgG3 in Infectious Diseases

Fri, 01 Mar 2019 00:00:00 GMT

Damelang, T; Rogerson, SJ; Kent, SJ; Chung, AW 2019-03-01 Role of IgG3 in Infectious Diseases IgG3 comprises only a minor fraction of IgG and has remained relatively understudied until recent years. Key physiochemical characteristics of IgG3 include an elongated hinge region, greater molecular flexibility, extensive polymorphisms, and additional glycosylation sites not present on other IgG subclasses. These characteristics make IgG3 a uniquely potent immunoglobulin, with the potential for triggering effector functions including complement activation, antibody (Ab)-mediated phagocytosis, or Ab-mediated cellular cytotoxicity (ADCC). Recent studies underscore the importance of IgG3 effector functions against a range of pathogens and have provided approaches to overcome IgG3-associated limitations, such as allotype-dependent short Ab half-life, and excessive proinflammatory activation. Understanding the molecular and functional properties of IgG3 may facilitate the development of improved Ab-based immunotherapies and vaccines against infectious diseases. Journal Article

Point-of-care testing and treatment of sexually transmitted infections to improve birth outcomes in high-burden, low-income settings: Study protocol for a cluster randomized crossover trial (the WANTAIM Trial, Papua New Guinea)

Fri, 22 Mar 2019 00:00:00 GMT

Vallely, A; Pomat, W; Homer, C; Guy, R; Luchters, S; Mola, G; Kariwiga, G; Vallely, L; Wiseman, V; Morgan, C; Wand, H; Rogerson, S; Tabrizi, S; Whiley, D; Low, N; Peeling, R; Siba, P; Riddell, M; Laman, M; Bolnga, J; Robinson, L; Morewaya, J; Badman, S; Batura, N; Kelly-Hanku, A; Toliman, P; Peter, W; Babona, D; Peach, E; Garland, S; Kaldor, J 2019-03-22 Point-of-care testing and treatment of sexually transmitted infections to improve birth outcomes in high-burden, low-income settings: Study protocol for a cluster randomized crossover trial (the WANTAIM Trial, Papua New Guinea) Background: Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis and bacterial vaginosis have been associated with preterm birth and low birth weight, and are highly prevalent among pregnant women in many low- and middle-income settings. There is conflicting evidence on the potential benefits of screening and treating these infections in pregnancy. Newly available diagnostic technologies make it possible, for the first time, to conduct definitive field trials to fill this knowledge gap. The primary aim of this study is to evaluate whether antenatal point-of-care testing and immediate treatment of these curable sexually transmitted and genital infections (STIs) leads to reduction in preterm birth and low birth weight. Methods : The Women and Newborn Trial of Antenatal Interventions and Management (WANTAIM) is a cluster-randomised crossover trial in Papua New Guinea to compare point-of-care STI testing and immediate treatment with standard antenatal care (which includes the WHO-endorsed STI ‘syndromic’ management strategy based on clinical features alone without laboratory confirmation). The unit of randomisation is a primary health care facility and its catchment communities. The primary outcome is a composite measure of two events: the proportion of women and their newborns in each trial arm, who experience either preterm birth (delivery <37 completed weeks of gestation as determined by ultrasound) and/or low birth weight (<2500 g measured within 72 hours of birth). The trial will also evaluate neonatal outcomes, as well as the cost-effectiveness, acceptability and health system requirements of this strategy, compared with standard care. Conclusions: WANTAIM is the first randomised trial to evaluate the effectiveness, cost-effectiveness, acceptability and health system requirements of point-of-care STI testing and treatment to improve birth outcomes in high-burden settings. If the intervention is proven to have an impact, the trial will hasten access to these technologies and could improve maternal and neonatal health in high-burden settings worldwide. Registration: ISRCTN37134032 . Journal Article

SIRCLE: a randomised controlled cost comparison of self-administered short-course isoniazid and rifapentine for cost-effective latent tuberculosis eradication

Fri, 01 Dec 2017 00:00:00 GMT

Denholm, JT; McBryde, ES; Eisen, D; Street, A; Matchett, E; Chen, C; Shultz, T; Biggs, B; Leder, K 2017-12-01 SIRCLE: a randomised controlled cost comparison of self-administered short-course isoniazid and rifapentine for cost-effective latent tuberculosis eradication BACKGROUND: Currently, treatment of latent tuberculosis infection (LTBI) in Australia consists most commonly of a 9-month course of isoniazid (9H). A 3-month course of weekly isoniazid and rifapentine (3HP) has been shown to be as effective as 9 months of daily isoniazid, and associated with less hepatotoxicity; however, rifapentine is not currently available in Australia. Introduction of this regimen would have apparent advantages for people with LTBI in Victoria by safely shortening duration of LTBI therapy. However, the cost benefit of this new therapeutic approach is uncertain. AIM: Cost-analysis of standard and short-course therapy for LTBI in an Australian context. METHODS: Single-centre randomised controlled trial conducted between December 2013-March 2016. Participants underwent 1:1 randomisation to either a 9-month course of daily isoniazid or a 12-week course of weekly isoniazid and rifapentine. The primary outcome measure was total healthcare system costs (in Australian dollars; AUD) per completed course of LTBI therapy. Secondary cost analyses were performed to consider varying assumptions regarding commercial cost of rifapentine. RESULTS: Overall, 34 of 40 (85%) participants in the 9H group and 36/40 (90%) in the 3HR group completed therapy. One patient in the 3HP group was hospitalised for a febrile illness; no hospitalisations were recorded in the 9H group. The cost per completed course of 9H was 601 AUD, while that of 3HP was significantly lower at 511 AUD (P < 0.01). CONCLUSIONS: This study provides cost analysis evidence to support the use of 3HP for the treatment of LTBI in Australia. Journal Article

Telehealth for Hepatitis C Care in the DAA Era; Ensuring Everyone Can Access a Cure

Sun, 01 Jan 2017 00:00:00 GMT

Schulz, TR; Kanhutu, K; Sasadeusz, J; Watkinson, S; Biggs, BA 2017 Telehealth for Hepatitis C Care in the DAA Era; Ensuring Everyone Can Access a Cure Journal Article

The Australasian Society for Infectious Diseases and Refugee Health Network of Australia recommendations for health assessment for people from refugee-like backgrounds: an abridged outline

Mon, 17 Apr 2017 00:00:00 GMT

Chaves, NJ; Paxton, GA; Biggs, B-A; Thambiran, A; Gardiner, J; Williams, J; Smith, MM; Davis, JS 2017-04-17 The Australasian Society for Infectious Diseases and Refugee Health Network of Australia recommendations for health assessment for people from refugee-like backgrounds: an abridged outline INTRODUCTION: In 2009, the Australasian Society of Infectious Diseases published guidelines on the post-arrival health assessment of recently arrived refugees. Since then, the number of refugees and asylum seekers reaching Australia has increased substantially (17 555 refugees in 2015-16) and the countries of origin have changed. These groups are likely to have had poor access to health care pre-arrival and, consequently, are at risk of a range of chronic and infectious diseases. We established an advisory group that included infectious diseases physicians, general practitioners, public health specialists, paediatricians and refugee health nurses to update the 2009 guidelines.Main recommendations: All people from refugee-like backgrounds, including children, should be offered a tailored comprehensive health assessment and management plan, ideally within 1 month of arrival in Australia. This can be offered at any time if initial contact with a GP or clinic is delayed. Recommended screening depends on history, examination and previous investigations, and is tailored based on age, gender, countries of origin and transit and risk profile. The full version of the guidelines is available at http://www.asid.net.au/documents/item/1225.Changes in management as a result of this guideline: These guidelines apply to all people from refugee-like backgrounds, including asylum seekers. They provide more information about non-communicable diseases and consider Asia and the Middle East as regions of origin as well as Africa. Key changes include an emphasis on person-centred care; risk-based rather than universal screening for hepatitis C virus, malaria, schistosomiasis and sexually transmissible infections; updated immunisation guidelines; and new recommendations for other problems, such as nutritional deficiencies, women's health and mental health. Journal Article

Hepatitis B among immigrants from Myanmar: Genotypes and their clinical relevance

Thu, 01 Feb 2018 00:00:00 GMT

Schulz, TR; Edwards, R; Thurnheer, MC; Yuen, L; Littlejohn, M; Revill, P; Chu, M; Tanyeri, F; Wade, A; Biggs, B-A; Sasadeusz, J 2018-02-01 Hepatitis B among immigrants from Myanmar: Genotypes and their clinical relevance Hepatitis B virus (HBV) from 76 adult immigrants in Australia from Myanmar was characterized to determine the prevalence of different HBV genotypes and subgenotypes. A mutational analysis was then performed to determine the presence of clinically significant mutations and correlate them to clinical outcomes. Initial genotyping revealed 68 patients with genotype C (89.5%) and eight patients with genotype B (10.5%). Phylogenetic analysis revealed the large majority of the genotype C infections were of subgenotype C1 (67/68). Sequencing of the HBV polymerase gene (and overlapping surface gene) revealed no mutations associated with antiviral resistance. HBV surface gene mutations were detected in 10 patients with subgenotype C1. HBV BCP/PC sequencing was obtained for 71/76 (93%) patients. BCP and/or PC mutations were identified in 57/71 (80%) of PCR positive patients. Treatment had been commenced for 15/76 (18%) patients, a further 26 untreated patients were in a stage of disease where HBV treatment would be considered standard of care. It was identified that genotype C1 is the predominant sub-genotype in this population. Genotype C is known to be associated with increased risk of development of HCC. This highlights the need for screening for HCC given the potential for the development of liver cancer. It was also identified that people with HBV were potentially not receiving optimal therapy in a timely fashion. Journal Article

Neurological effects of iron supplementation in infancy: finding the balance between health and harm in iron-replete infants

Thu, 01 Feb 2018 00:00:00 GMT

Hare, DJ; Cardoso, BR; Szymlek-Gay, EA; Biggs, B-A 2018-02-01 Neurological effects of iron supplementation in infancy: finding the balance between health and harm in iron-replete infants Iron mediates many biochemical processes in neural networks that proliferate during brain development. Insufficient iron causes irreversible neurodevelopmental deficits, and most high-income countries recommend that infants older than 4-6 months receive additional iron via food fortification or supplementation to prevent iron-deficiency anaemia. Now that the prevalence of iron-deficiency anaemia in children has decreased to less than 10% in most developed countries, concerns that the recommended intakes far exceed those required to prevent iron-deficiency anaemia have been raised, and emerging evidence suggests that iron overexposure could be linked to adverse outcomes later in life. In this Viewpoint, we discuss the importance of iron for neurodevelopment, investigate the biochemical markers used to assess iron stores, summarise the disparity in public health policies among high-income countries, and discuss the potential association between iron overexposure and adverse neurological outcomes later in life. We present a case for new studies to establish the optimal amount of iron that both prevents deficiency and reduces the potential risk of long-term negative health outcomes. Journal Article

Co-morbid anaemia and stunting among children of pre-school age in low- and middle-income countries: a syndemic

Tue, 01 Jan 2019 00:00:00 GMT

Thach, DT; Biggs, B-A; Holton, S; Hau, TMN; Hanieh, S; Fisher, J 2019-01-01 Co-morbid anaemia and stunting among children of pre-school age in low- and middle-income countries: a syndemic OBJECTIVE: To determine the prevalence of co-morbidity of two important global health challenges, anaemia and stunting, among children aged 6-59 months in low- and middle-income countries. DESIGN: Secondary analysis of data from Demographic and Health Surveys (DHS) conducted 2005-2015. Child stunting and anaemia were defined using current WHO classifications. Sociodemographic characteristics of children with anaemia, stunting and co-morbidity of these conditions were compared with those of 'healthy' children in the sample (children who were not stunted and not anaemic) using multiple logistic models. SETTING: Low- and middle-income countries. SUBJECTS: Children aged 6-59 months. RESULTS: Data from 193 065 children from forty-three countries were included. The pooled proportion of co-morbid anaemia and stunting was 21·5 (95 % CI 21·2, 21·9) %, ranging from the lowest in Albania (2·6 %; 95 % CI 1·8, 3·7 %) to the highest in Yemen (43·3; 95 % CI 40·6, 46·1 %). Compared with the healthy group, children with co-morbidity were more likely to be living in rural areas, have mothers or main carers with lower educational levels and to live in poorer households. Inequality in children who had both anaemia and stunting was apparent in all countries. CONCLUSIONS: Co-morbid anaemia and stunting among young children is highly prevalent in low- and middle-income countries, especially among more disadvantaged children. It is suggested that they be considered under a syndemic framework, the Childhood Anaemia and Stunting (CHAS) Syndemic, which acknowledges the interacting nature of these diseases and the social and environmental factors that promote their negative interaction. Journal Article

Agreement Between Venous and Capillary Haemoglobin Concentrations in Bangladeshi Children (P10-105-19).

Sat, 01 Jun 2019 00:00:00 GMT

Larson, L; Hasan, MI; Braat, S; Baldi, A; Alam, MS; Biggs, B-A; Hamadani, J; Pasricha, S-R 2019-06 Agreement Between Venous and Capillary Haemoglobin Concentrations in Bangladeshi Children (P10-105-19). Objectives: There are concerns that capillary haemoglobin (Hb) concentrations do not agree with venous Hb, which has implications for global estimates of anaemia largely derived from capillary Hb. In children enrolled in the Benefits and Risks of Iron Supplementation in Children (BRISC) trial, we examined differences between Hb concentrations collected from venous and capillary blood samples, and predictors of these differences. Methods: Hb concentrations were measured in 3300 children at 8 months of age. Capillary Hb concentrations were measured during screening of children for inclusion in the trial. Venous Hb was measured up to 10 days after screening, during enrolment. All Hb measurements used the HemoCue® 301. In children who received both capillary and venous measurements, Hb means, standard deviations, and anaemia prevalence statistics were derived. Paired t-tests were used to compare means across groups. Pearson's correlation coefficients and a Bland-Altman plot were used to examine agreement between capillary and venous Hb. A kappa coefficient was used to examine agreement in diagnosis of anaemia between the two methods. Lastly, differences in mean venous and capillary Hb concentrations between phlebotomists were calculated using ANOVA. Results: All 3300 children will have completed baseline Hb measurements by February 2019. The current abstract presents preliminary data up to December 2018 for 2485 children. Venous and capillary Hb concentrations were moderately correlated (r = 0.62). Prevalence of anaemia using venous samples was 44.8% and using capillary samples was 69.5%. Accounting for chance, the % agreement (kappa coefficient) between the methods for diagnosis of anaemia was 34.8%. Mean Hb concentrations were significantly higher in venous than capillary samples (mean ± SD: 11.0 ± 1.0 vs 10.4 ± 1.0 g/dL, P < 0.001). This is confirmed in the Bland-Altman plot. No differences in Hb were observed between phlebotomists. Conclusions: Significant differences exist in the diagnosis of anaemia using capillary vs venous samples. Capillary Hb measurements should not be used as a surrogate for venous Hb as they may incorrectly estimate the prevalence of anaemia. Results indicated that global estimates of anaemia based on capillary Hb may be misrepresenting true estimates. Funding Sources: NHMRC. Journal Article

Using a Developmental Test and Electroencephalography to Examine Child Cognition and Its Predictors in Bangladesh (P13-024-19).

Sat, 01 Jun 2019 00:00:00 GMT

Larson, L; Hasan, MI; Feuerriegel, D; Shiraji, S; Shabnab, S; Tofail, F; Braat, S; Biggs, B-A; Pasricha, S-R; Hamadani, J; Bode, S; Johnson, K 2019-06 Using a Developmental Test and Electroencephalography to Examine Child Cognition and Its Predictors in Bangladesh (P13-024-19). Objectives: The majority of global health studies use behavioural assessments to measure early child development. Few studies have examined neural indices of cognition using electroencephalography (EEG) in low-income settings. Using data from the Benefits and Risks of Iron Supplementation in Children (BRISC) trial, we examined cognitive development and neural indices of memory and attention in 11 month-old Bangladeshi children and their environmental, socio-demographic, and biological predictors. Methods: At 8 months of age, 3300 children were randomized to iron syrup, multiple micronutrient supplementation, or placebo for 3 months. The main trial outcomes include child development measured using the Bayley Scales of Infant and Toddler Development (BSID)-III, anthropometry, haemoglobin, morbidity, and iron indices. EEG is being conducted to measure event-related brain potentials (ERPs) in a random subset of 250 children at 11 months of age. ERPs are measured in response to auditory and visual stimuli, using roving oddball and attention orienting tasks. Generalized linear mixed models estimated the predictors of BSID-derived cognitive development and EEG-derived neural indices of memory and attention. Potential predictors include psychosocial stimulation, anthropometry, haemoglobin, socio-economic status, food security, sex, and parental education. Additionally, we examined correlations between the BSID cognitive scores and EEG-derived neural indices of cognition. Results: Preliminary BSID data up to December 2018 indicates that 1749 children have completed measurements at 11 months of age. Psychosocial stimulation was significantly associated with BSID cognitive development scores. ERPs in children at 11 months of age are expected to be completed by May 2019 and relevant results will be presented. Conclusions: This study is the first to acquire ERP data in children at 11 months of age in rural Bangladesh. Our findings will identify significant predictors of cognitive functioning measured using the BSID (a well-established developmental test) and using EEG (a sensitive neurophysiological approach) in young children in this setting. Results will indicate the agreement between child cognition outcomes using the BSID and EEG. Funding Sources: NHMRC and The University of Melbourne. Journal Article

The global effect of extreme weather events on nutrient supply: a superposed epoch analysis

Tue, 01 Oct 2019 00:00:00 GMT

Park, CS; Vogel, E; Larson, LM; Myers, SS; Daniel, M; Biggs, B-A 2019-10-01 The global effect of extreme weather events on nutrient supply: a superposed epoch analysis BACKGROUND: To date, the effects of extreme weather events on nutrient supply within the population have not been quantified. In this study, we investigated micronutrient, macronutrient, and fibre supply changes during 175 extreme weather events within 87 countries in the year that a major extreme weather event occurred, with a targeted focus on low-income settings. METHODS: We collected data from the International Disasters Database and the Global Expanded Nutrient Supply model for the period 1961-2010, and applied superposed epoch analysis to calculate the percentage change in nutrient supply during the year of an extreme weather event relative to its historical context. We composited globally and by subgroup (EU, landlocked developing countries, least developed countries, low-income food deficit countries, and net food-importing developing countries). Lastly, we reported nutrient supply changes in terms of recommended dietary allowance for children aged 1-3 years. FINDINGS: Globally, all micronutrient supplies had a modest negative percentage change during the year of an extreme weather event; of these effects, those that reached an α=0·05 significance level included calcium, folate, thiamin, vitamin B6, and vitamin C, with nutrient supply changes ranging from -0·40 to -1·73% of the average supply. The effect of an extreme weather event was especially magnified among landlocked developing countries and low-income food deficit countries, with significant nutrient supply changes ranging from -1·61 to -7·57% of the average supply. Furthermore, the observed nutrient supply deficits in landlocked developing countries constituted a large percentage (ranging from 1·95 to 39·19%) of what a healthy child's sufficient average dietary intake should be. INTERPRETATION: The global effects of extreme weather events on nutrient supply found in this study are modest in isolation; however, in the context of nutrient needs for healthy child development in low-income settings, the effects observed are substantial. FUNDING: Australian-American Fulbright Commission. Journal Article

Using telehealth to improve access to hepatitis C treatment in the direct-acting antiviral therapy era

Wed, 01 Apr 2020 00:00:00 GMT

Schulz, TR; Kanhutu, K; Sasadeusz, J; Watkinson, S; Biggs, B-A 2020-04-01 Using telehealth to improve access to hepatitis C treatment in the direct-acting antiviral therapy era Introduction: One-third of the Australian population lives outside major cities and this group has worse health outcomes. Telehealth is becoming an accepted way to improve patient access to specialist healthcare. Over 200,000 Australian’s have hepatitis C virus (HCV) and new treatments are very effective and well tolerated. We aim to demonstrate that HCV treatment utilising telehealth support for care delivery has cure rates similar to onsite care in clinical trials. We also report length of consultation and calculate reductions in travel and carbon output. Methods: Patient demographic, clinical, and treatment outcome data were collected prospectively from hospital software and analysed retrospectively. This was an audit of all patients treated for HCV in one year from a single tertiary hospital that included telehealth in their care delivery. Results: Sustained virological response was achieved in 51/52 (98%) patients with completed treatment courses, and 51/58 (88%) of those who had a planned telehealth consultation as part of their management. A median of 634 km of patient travel was saved per telehealth consultation. Discussion: We found that a telehealth-supported outreach programme for patients in regional Australia with HCV produced similar outcomes to clinical trials. There was a considerable saving in time and cost for the patients and significant environmental benefit through the reduction in carbon footprint associated with travel to distant specialist health services. We conclude that telehealth facilitated outreach is a feasible and effective way to access HCV treatment and cure in regional Australia. Journal Article

Community-Based Learning Club for Women’s Health and Infant Development in Rural Vietnam

Fri, 01 Jan 2021 00:00:00 GMT

Nguyen, T; Tran, TD; Tran, H; Hanieh, S; Luchters, S; Biggs, B-A; Tran, T; Fisher, J 2021 Community-Based Learning Club for Women’s Health and Infant Development in Rural Vietnam Chapter

HTLV-I and Strongyloides in Australia: The worm lurking beneath.

Fri, 01 Jan 2021 00:00:00 GMT

Gordon, CA; Shield, JM; Bradbury, RS; Muhi, S; Page, W; Judd, JA; Lee, R; Biggs, B-A; Ross, K; Kurscheid, J; Gray, DJ; McManus, DP 2021 HTLV-I and Strongyloides in Australia: The worm lurking beneath. Strongyloidiasis and HTLV-I (human T-lymphotropic virus-1) are important infections that are endemic in many countries around the world with an estimated 370 million infected with Strongyloides stercoralis alone, and 5-10 million with HTVL-I. Co-infections with these pathogens are associated with significant morbidity and can be fatal. HTLV-I infects T-cells thus causing dysregulation of the immune system which has been linked to dissemination and hyperinfection of S. stercoralis leading to bacterial sepsis which can result in death. Both of these pathogens are endemic in Australia primarily in remote communities in Queensland, the Northern Territory, and Western Australia. Other cases in Australia have occurred in immigrants and refugees, returned travellers, and Australian Defence Force personnel. HTLV-I infection is lifelong with no known cure. Strongyloidiasis is a long-term chronic disease that can remain latent for decades, as shown by infections diagnosed in prisoners of war from World War II and the Vietnam War testing positive decades after they returned from these conflicts. This review aims to shed light on concomitant infections of HTLV-I with S. stercoralis primarily in Australia but in the global context as well. Journal Article

Benefits and Risks of Iron Interventions in Infants in Rural Bangladesh

Thu, 09 Sep 2021 00:00:00 GMT

Pasricha, S-R; Hasan, M; Braat, S; Larson, LM; Tipu, SMM-U; Hossain, SJ; Shiraji, S; Baldi, A; Bhuiyan, MSA; Tofail, F; Fisher, J; Grantham-McGregor, S; Simpson, JA; Hamadani, JD; Biggs, B-A 2021-09-09 Benefits and Risks of Iron Interventions in Infants in Rural Bangladesh BACKGROUND: Universal provision of iron supplements (drops or syrup) or multiple micronutrient powders to young children in low-to-middle-income countries where anemia is prevalent is recommended by the World Health Organization and widely implemented. The functional benefits and safety of these interventions are unclear. METHODS: We conducted a three-group, double-blind, double-dummy, individually randomized, placebo-controlled trial to assess the immediate and medium-term benefits and risks of 3 months of daily supplementation with iron syrup or iron-containing multiple micronutrient powders, as compared with placebo, in 8-month-old children in rural Bangladesh. The primary outcome was cognitive development, as assessed by the cognitive composite score on the Bayley Scales of Infant and Toddler Development, third edition, immediately after completion of the assigned 3-month regimen; scores range from 55 to 145, with higher scores indicating better cognitive performance. Secondary outcomes included the cognitive composite score at 9 months after completion of the assigned regimen; behavioral, language, and motor development, as well as growth and hematologic markers, immediately after completion and at 9 months after completion; and safety. RESULTS: We randomly assigned 3300 infants to receive iron syrup (1101 infants), multiple micronutrient powders (1099), or placebo (1100) daily. After completion of the assigned 3-month regimen, no apparent effect on the cognitive composite score was observed with iron syrup as compared with placebo (mean between-group difference in change in score from baseline, -0.30 points; 95% confidence interval [CI], -1.08 to 0.48) or with multiple micronutrient powders as compared with placebo (mean between-group difference in change in score from baseline, 0.23 points; 95% CI, -0.55 to 1.00). No apparent effect on any other developmental or growth outcome was observed immediately after completion of the assigned regimen or at 9 months after completion. At 9 months after completion of the assigned regimen, the prevalences of anemia, iron deficiency, and iron deficiency anemia increased in all three trial groups but remained lower among the children who received iron syrup or multiple micronutrient powders than among those who received placebo. The risk of serious adverse events and incidence of symptoms of infection were similar in the three trial groups. CONCLUSIONS: In this trial involving infants in Bangladesh, 3 months of daily supplementation with iron syrup or multiple micronutrient powders did not appear to have an effect on child development or other functional outcomes as compared with placebo. (Funded by the National Health and Medical Research Council of Australia; BRISC Australian New Zealand Clinical Trials Registry number, ACTRN12617000660381.). Journal Article

Australian Children Growing Up with Opportunity

Fri, 01 Sep 2017 00:00:00 GMT

Kalb, G 2017-09-01 Australian Children Growing Up with Opportunity This article focuses on the early years of children in Australia. It discusses the inequality of opportunity as reflected in the statistics and the potential impacts of this inequality. A brief literature review is provided regarding the impact of formal childcare and preschool attendance on child development, with a specific focus on the impact for children from disadvantaged families. The article concludes with a discussion of possible policy directions to counteract the inequality of opportunity. Journal Article

Introduction

Fri, 01 Sep 2017 00:00:00 GMT

Salamanca, N; Zhu, A 2017-09-01 Introduction This book builds on the burgeoning evidence-informed practice movement in social welfare that evolved from evidence-based medicine some twenty years ago. Chapter

Are Professors Worth It? The Value-added and Costs of Tutorial Instructors

Wed, 01 Jan 2020 00:00:00 GMT

Salamanca Acosta, N; Zölitz, U; Feld, J 2020 Are Professors Worth It? The Value-added and Costs of Tutorial Instructors A substantial share of university instruction happens in tutorial sessions— small group instruction given parallel to lectures. In this paper, we study whether instructors with a higher academic rank teach tutorials more effectively in a setting where students are randomly assigned to tutorial groups. We find this to be largely not the case. Academic rank is unrelated to students’ current and future performance and only weakly positively related to students’ course evaluations. Building on these results, we discuss different staffing scenarios that show that universities can substantially reduce costs by increasingly relying on lower-ranked instructors for tutorial teaching. Journal Article

Association of maternal depression and home adversities with infant hypothalamic-pituitary-adrenal (HPA) axis biomarkers in rural Pakistan

Sun, 01 Nov 2020 00:00:00 GMT

Hagaman, AK; Baranov, V; Chung, E; LeMasters, K; Andrabi, N; Bates, LM; Rahman, A; Sikander, S; Turner, E; Maselko, J 2020-11-01 Association of maternal depression and home adversities with infant hypothalamic-pituitary-adrenal (HPA) axis biomarkers in rural Pakistan Background: Each year, almost 35% of children are exposed to maternal depression and more grow up in persistent poverty, increasing the risk for stress-related disease and other socio-developmental deficits later in life. These impacts are likely related to chronic stress via the hypothalamic-pituitary-adrenal (HPA) axis. However, there is little evidence relating early windows of child HPA axis activity to multiple exposures. Methods: We investigated chronic measures of hair-derived HPA axis hormones (cortisol and dehydroepiandrosterone (DHEA)) in 104 one-year old infants from rural Pakistan and longitudinal measures of maternal depression, intimate partner violence (IPV), socio-economic status (SES), and the home environment. Results: Estimates from adjusted linear mixed effects models did not reveal consistent significant associations between infant cortisol and maternal depression or home adversities. By contrast, infants exposed to maternal depression during pregnancy had lower DHEA levels (ß= -0.18 95% confidence interval [CI]: -0.34, -0.02) as did those whose mothers experienced multiple types of IPV (ß=-4.14 95% CI: -7.42, -0.79) within one year postpartum. Higher SES had a significant positive association with infant DHEA levels (ß= 0.77 95% CI: 0.08, 1.47). Depression severity and chronicity at one year postpartum had near significant associations with infant DHEA. Measures of home environment had no observable impacts on infant HPA axis activity. Limitations: Limitations include the modest sample size and aggregation of hair samples for analysis. Conclusion: Results point to possible early HPA axis dysregulation driven by changes in DHEA activity, but not cortisol at one year of age. Findings contribute to growing research examining intergenerational transmissions of maternal depression, IPV, and household environment on infant stress-response systems. Journal Article

A review of simulation training and new 3D computer-generated synthetic organs for robotic surgery education

Fri, 03 Sep 2021 00:00:00 GMT

Costello, DM; Huntington, I; Burke, G; Farrugia, B; O'Connor, AJ; Costello, AJ; Thomas, BC; Dundee, P; Ghazi, A; Corcoran, N 2021-09-03 A review of simulation training and new 3D computer-generated synthetic organs for robotic surgery education We conducted a comprehensive review of surgical simulation models used in robotic surgery education. We present an assessment of the validity and cost-effectiveness of virtual and augmented reality simulation, animal, cadaver and synthetic organ models. Face, content, construct, concurrent and predictive validity criteria were applied to each simulation model. There are six major commercial simulation machines available for robot-assisted surgery. The validity of virtual reality (VR) simulation curricula for psychomotor assessment and skill acquisition for the early phase of robotic surgery training has been demonstrated. The widespread adoption of VR simulation has been limited by the high cost of these machines. Live animal and cadavers have been the accepted standard for robotic surgical simulation since it began in the early 2000s. Our review found that there is a lack of evidence in the literature to support the use of animal and cadaver for robotic surgery training. The effectiveness of these models as a training tool is limited by logistical, ethical, financial and infection control issues. The latest evolution in synthetic organ model training for robotic surgery has been driven by new 3D-printing technology. Validated and cost-effective high-fidelity procedural models exist for robotic surgery training in urology. The development of synthetic models for the other specialties is not as mature. Expansion into multiple surgical disciplines and the widespread adoption of synthetic organ models for robotic simulation training will require the ability to engineer scalability for mass production. This would enable a transition in robotic surgical education where digital and synthetic organ models could be used in place of live animals and cadaver training to achieve robotic surgery competency. Journal Article