Paediatrics (RCH) - Theses
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ItemIvermectin-based mass drug administration for the serious bacterial complications of scabies( 2022)Scabies is a skin disease caused by the mite Sarcoptes scabiei var. hominis, which is especially prevalent in populations experiencing overcrowding and poverty. Recognised as a neglected tropical disease by the World Health Organization in 2017, scabies is characterised through skin lesions and intense itch. The host is made vulnerable to secondary bacterial infection through skin breaches, scratching and inhibition of the complement system via mite secretions. Bacterial infection predominantly caused by Staphylococcus aureus and/or Group A Streptococcus most commonly manifesting as impetigo can complicate scabies. Impetigo can progress to more complicated skin and soft tissue infection, invasive bacterial infection and post streptococcal sequelae which cause significant morbidity and mortality. Previous studies in the Pacific Islands, including in Fiji, demonstrated that ivermectin-based mass drug administration substantially reduces scabies prevalence by approximately 90%, and leads to a concomitant reduction in impetigo prevalence by 60% to 70%. The focus of this thesis was to determine if ivermectin-based mass drug administration also leads to a reduction in the more serious bacterial complications of scabies. The studies and intervention described in this thesis take place in Fiji’s Northern Division (population ~131,914 in 2017). Four studies are reported in the thesis. The first study investigated the burden of hospitalisations for skin and soft tissue infections using prospective surveillance at the referral hospital of the Northern Division, and found a very high population incidence of 647 admissions per 100,000 person-years (95% CI 571-660). The second study investigated the burden of invasive infections caused by S. aureus and group A Streptococcus, using prospective surveillance also at the referral hospital, and found a high incidence at 45.2 and 12.3 per 100,000 person-years, respectively. The third study investigated the incidence of primary healthcare presentations for scabies and skin and soft tissue infections using a prospective surveillance system established at all primary healthcare facilities in the Northern Division, and found that there were 13,736 presentations over 50 weeks, equivalent to a population incidence of 108 presentations per 1000 person-years. The final major study investigated the impact of ivermectin-based mass drug administration on the bacterial complications of scabies. Ivermectin-based mass drug administration was deployed across the whole of the Northern Division. Coverage of mass drug administration was high – with the first dose achieving 97% and the second dose 87% coverage. The primary outcome measure was the annual incidence of hospitalisations for skin and soft tissue infections, with the study finding that the incidence declined significantly by 17% in the year after mass drug administration (from 467 to 388 per 100,000, incidence rate ratio 0.83 95% confidence intervals 0.74% to 0.94%). This finding was supported by a reduction in the annual incidence of primary healthcare presentations by 21%, and by a reduction in scabies and impetigo prevalence by 29% and 60% respectively. There was no decrease in the incidence of invasive infections and post streptococcal sequelae. Overall, this thesis demonstrates that scabies control through mass drug administration can lead to a reduction in the incidence of bacterial skin and soft tissue infections, measured as a fall in healthcare utilisation and community prevalence. These results are encouraging and provide further evidence of the broader benefits of scabies control via mass drug administration. In settings where scabies is endemic and where resources are limited and health priorities compete, this thesis highlights the underestimated burden of scabies and strengthens the case for policy targeting control of this neglected tropical disease.
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ItemEarly life oral exposures as risk factors for food allergy and the impact of infant feeding guidelines( 2021)Food allergy is a severe immune reaction affecting around 10% of infants. The recent rise in food allergy is a growing public health concern. Susceptibility to food allergy is affected by environmental exposures that affect infant gut immunity, including oral food and microbial exposures. Changes in infant feeding guidelines recommending introduction of allergenic foods in the first year were the first public health measure introduced specifically to prevent food allergy. I aimed to evaluate their impact on timing of allergenic food introduction and prevalence of food allergy, as well as investigating oral microbial exposure as a potential food allergy risk factor. The effect of 2016 updates to infant feeding guidelines on food allergy was evaluated using two large population-based cross-sectional studies (n=5,300 and n=1,933) that recruited 12-month-old infants in Melbourne, Australia 10-years apart (2007-2011 and 2018-2019) to study allergenic food introduction and peanut allergy. Microbial exposure was investigated in relation to food allergy using data from a cohort study (n=1,072) based in south-east Australia which measured pacifier cleaning methods in the first year of life. Data were analyzed using multivariable logistic regression models and direct standardization. Regression models were adjusted for known food allergy risk factors, depending on the exposure. An overview of systematic reviews searched systematic reviews in four databases to examine age of complementary feeding in relation to other health outcomes. These studies are the first report that peanut introduction by 12 months of age (inclusive) in the population increased (88% in 2018-2019 vs 28% in 2007-2011) following the implementation of 2016 infant feeding guidelines. Despite this massive shift, peanut allergy prevalence did not decrease as much as expected (3.1% to 2.6%). However, the increase in peanut introduction seems to have halted the rise of peanut allergy in one-year-old infants. The systematic review found 27 reviews on age of complementary or allergenic food introduction on multiple outcomes. There was no evidence of a detrimental effect on other health outcomes of the recommended introduction of solids and allergenic foods starting around 6 months of age, though solids introduced earlier than 4 months could increase the risk of overweight. Furthermore, sanitization of infant pacifier with antiseptics at 6 months of age increased the risk of food allergy at age one, possibly an effect of the chemicals on oral or gut microbiome. An increase in early introduction following 2016 guideline changes has halted the overall rise in peanut allergy. Nevertheless, peanut allergy is still high in Melbourne, thus additional prevention strategies are required. Reassuringly, other health outcomes are not risked by the recommended age of allergenic food introduction. The findings on cleaning pacifiers with antiseptics suggests that suggests microbial exposure can protect against food allergy. This warrants further interventional studies to determine if microbial exposures could prevent food allergy. Moreover, early life risk factors, prior to food introduction, need to be explored further.
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ItemImmunising the Invisible: The School-based Immunisation Program for young people with disability in specialist school in Victoria, Australia( 2020)Immunisation reduces morbidity and mortality, and affects equity in health. This is evident between countries and regions, and within them, where there may be pockets of the population vulnerable to under-immunisation that experience more barriers to preventive health care. People with disability are one such group that are largely invisible in research and immunisation policy decisions. In particular, there is a paucity of data on adolescent immunisation in young people with disability in Australia. In Australia, students receive adolescent immunisations through the School-based Immunisation Program at 12 to 13 years of age. Vaccine uptake data for the majority of young people with disability attending specialist schools are not included in aggregate immunisation reports. Therefore, there is a clear need for coverage data, as well as qualitative research to clearly identify the barriers and enablers to immunisation for young people with disability in specialist schools. The aim of this thesis was to explore and describe acceptance and delivery of immunisation in specialist schools for young people with disability in Victoria, Australia. The research was designed as a mixed methods qualitative dominant and sequential explanatory study, with a quantitative phase followed by a qualitative phase. Phase One consisted of a prospective cohort study that aimed to measure the uptake of immunisations in specialist schools for young people with disability in Victoria, Australia. Data were collected on immunisation days in the 2017 school year from specialist schools in Victoria in order to determine uptake of diphtheria-tetanus-pertussis (dTPa) and human papillomavirus (HPV) immunisations in eligible students. Demographic data, motor and intellectual function of students, and reasons for non-receipt of dTPa and HPV vaccine were recorded using REDcapTM software and were analysed using descriptive statistics. Results from this study found that of the 28 specialist schools that participated, dTPa was received by 63% (237/374) of participating students, and HPV dose 1 (HPV1) was received by 66% (76/114) of female students and 67% (174/260) of male students. Three doses of HPV were received by only 41% (100/241) of students. The main reasons for missed immunisation were absence from school, lack of consent and inability to immunise due to the student’s behaviour and/or anxiety. Comparative data during the same time period for students in mainstream schools demonstrated significantly higher uptake, at 89% for dTPa and 75% for three doses of HPV, confirming under-immunisation of students in specialist schools. Phase Two consisted of an in-depth qualitative inquiry that utilised the Socio-Ecological Model (SEM) as a framework, which aimed to determine barriers and facilitators of immunisation for young people with disability in specialist schools in Australia. Data collection included 10 observations of specialist school immunisation sessions, 40 in-depth semi-structured interviews and two focus groups with key stakeholders, including representatives from state government, local government immunisation teams, specialist schools and parents of students. Data were coded and themed using Reflexive Thematic Analysis, as described by Braun and Clarke (2006; 2019). Five main themes were identified: an invisible population, searching for support, going the extra mile, competing priorities and trust takes time. The intersection of the themes across layers of the SEM varied, demonstrating the complex nature of the issue and the need for this multilayered approach. The integrated inferences from these two phases resulted in key recommendations. These recommendations include: ongoing rigorous coverage data recorded for ungraded schools; stronger central support for immunisation teams; a review of the immunisation funding model to reflect the extra work and resources required in some schools and to provide for increased follow-up and catch-up; clear guidelines for the use of restraint during immunisation in specialist schools; and a referral pathway for students with disability who cannot be immunised in the school setting. This thesis has generated new knowledge by establishing that young people with disability in specialist schools in Australia are missing their adolescent vaccinations, and that there are unique barriers to immunisation in this school setting. Phase One provided the first Victorian figures on coverage of adolescent immunisations of young people with disability and Phase Two constitutes the first qualitative research that has been conducted internationally on immunisation in children or young people with disability. Recommendations arising from the integration of findings from both phases have the potential to be translated into policy and practice, and thereby have a significant impact on the health and health equity of young people with disability.
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ItemImproving the diagnosis of scabies in low-resource settings( 2020)Scabies is a parasitic disease and a global health problem that predominantly affects disadvantaged communities in low-resource settings. Scabies significantly impacts the health and quality of life of those with the disease. To accurately assess the global burden of disease and to compare data across regions, standardised diagnosis with consistent disease definitions is necessary. In low-resource settings, diagnosis by clinical assessment is the principal diagnostic method. In the absence of available experts, non-expert health workers are likely to play critical roles in diagnosis, including for prevalence mapping. Currently, standardised processes for clinical diagnosis for scabies do not exist. This thesis explores the diagnosis of scabies in low-resource settings and the role and utility of non-expert health workers in the diagnosis of scabies. Chapter 3 describes the evaluation of non-expert health workers in the diagnosis of scabies and impetigo using clinical criteria. The diagnosis of four briefly-trained nurses was compared to the consensus diagnosis of two experienced doctors. The sensitivity of the nurses’ diagnosis compared to the reference standard was 55.3% for scabies with a specificity of 89.9% Sensitivity for moderate to severe scabies was 93.5% with a specificity of 74%. The accuracy of diagnosis by non-expert health workers is promising and may be acceptable for scabies and impetigo disease mapping in low-resource settings. Chapter 4 describes the development and evaluation of a training protocol for the diagnosis of scabies and impetigo for non-expert health workers. The aim of this study was to measure the change in knowledge and confidence of the participants and explore their experience and perceptions of the training. Training was evaluated using a case-based test, a questionnaire and semi-structured interviews. The overall results of the case-based test were 90% for scabies and 75.5% for impetigo. The mean score for both self-reported knowledge and confidence increased from 2.5 to 4.5 following training and scores increased for all nurses (mean difference 2, 95%CI 1.1-2.9, P=0.005). The study showed that training local health staff in scabies diagnosis was enjoyable for participants and led to improvements in self-reported knowledge and confidence. Chapter 5 investigates the prevalence of scabies and impetigo using a cross-sectional study in a primary school in Gizo in the Solomon Islands. Using the International Alliance for the Control of Scabies (IACS) diagnostic criteria the classified the diagnosis of scabies. The prevalence of scabies was 54.3% and prevalence of impetigo was 32.1%. 63.5% of those with impetigo had scabies, corresponding to a population attributable risk of 11.8%. The study highlighted the extremely high burden of these diseases supporting the need for interventions for scabies in this community. Chapter 6 evaluates the methods of data collection, analysis and display for describing in detail the distribution of scabies lesions in a pilot study. The study used a novel technique of representation of dermatological lesions in the form of a choropleth map. The study found that the methods used were feasible for a larger population and would describe valuable detailed information on specific lesion location in scabies. The study will provide information on lesions at specific body sites to determine if simplified examinations are appropriate for prevalence surveys. The public health control of scabies requires identification of high-prevalence communities to target interventions, as well as methods to monitor the effectiveness of interventions. Such programs would be dependent on accurate and standardised diagnosis for population mapping. This thesis suggests methods to improve the diagnosis of scabies in low-resource settings. Modifications to training and diagnostic methods are likely to improve diagnostic accuracy. Improvements to scabies diagnosis will contribute to efficient collection methods and reliability of prevalence data.