Infectious Diseases - Research Publications

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    SIRCLE: a randomized controlled cost comparison of self-administered short-course isoniazid and rifapentine for cost-effective latent tuberculosis eradication (vol 47, pg 1433, 2017)
    Denholm, JT ; McBryde, ES ; Eisen, D ; Street, A ; Matchett, E ; Chen, C ; Schulz, TR ; Biggs, B ; Leder, K (WILEY, 2018-04)
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    SIRCLE: a randomised controlled cost comparison of self-administered short-course isoniazid and rifapentine for cost-effective latent tuberculosis eradication
    Denholm, JT ; McBryde, ES ; Eisen, D ; Street, A ; Matchett, E ; Chen, C ; Shultz, T ; Biggs, B ; Leder, K (WILEY, 2017-12)
    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.
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    Telehealth for Hepatitis C Care in the DAA Era; Ensuring Everyone Can Access a Cure
    Schulz, TR ; Kanhutu, K ; Sasadeusz, J ; Watkinson, S ; Biggs, BA (Oxford University Press (OUP), 2017)
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    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
    Chaves, NJ ; Paxton, GA ; Biggs, B-A ; Thambiran, A ; Gardiner, J ; Williams, J ; Smith, MM ; Davis, JS (AUSTRALASIAN MED PUBL CO LTD, 2017-04-17)
    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.
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    Hepatitis B among immigrants from Myanmar: Genotypes and their clinical relevance
    Schulz, TR ; Edwards, R ; Thurnheer, MC ; Yuen, L ; Littlejohn, M ; Revill, P ; Chu, M ; Tanyeri, F ; Wade, A ; Biggs, B-A ; Sasadeusz, J (WILEY, 2018-02)
    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.
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    Neurological effects of iron supplementation in infancy: finding the balance between health and harm in iron-replete infants
    Hare, DJ ; Cardoso, BR ; Szymlek-Gay, EA ; Biggs, B-A (ELSEVIER SCI LTD, 2018-02)
    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.
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    Co-morbid anaemia and stunting among children of pre-school age in low- and middle-income countries: a syndemic
    Thach, DT ; Biggs, B-A ; Holton, S ; Hau, TMN ; Hanieh, S ; Fisher, J (CAMBRIDGE UNIV PRESS, 2019-01)
    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.
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    Agreement Between Venous and Capillary Haemoglobin Concentrations in Bangladeshi Children (P10-105-19).
    Larson, L ; Hasan, MI ; Braat, S ; Baldi, A ; Alam, MS ; Biggs, B-A ; Hamadani, J ; Pasricha, S-R (Elsevier BV, 2019-06)
    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.
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    Using a Developmental Test and Electroencephalography to Examine Child Cognition and Its Predictors in Bangladesh (P13-024-19).
    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 (Elsevier BV, 2019-06)
    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.
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    The global effect of extreme weather events on nutrient supply: a superposed epoch analysis
    Park, CS ; Vogel, E ; Larson, LM ; Myers, SS ; Daniel, M ; Biggs, B-A (ELSEVIER SCI LTD, 2019-10)
    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.