Paediatrics (RCH) - Theses
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ItemNo Preview AvailableEffectiveness of mass drug administration regimens for the control of scabies( 2022)Scabies is a neglected tropical disease (NTD) of the skin that causes approximately 455 million cases around the world each year. It is most prevalent in low resource, crowded, tropical environments. Scabies is caused by a parasitic mite that burrows into the skin and causes intense itch, which can lead to a break in the skin barrier. Secondary bacterial infection can lead to serious invasive and immune modulated disease. Mass drug administration (MDA) has been used in the control of a number of NTDs and there is evidence that it may be an effective control strategy for scabies in populations with a high prevalence. The first part of this thesis explores the impact of scabies on the community and on individuals, providing evidence for the need for public health control. The impact of scabies on the community was assessed in a survey in Western Province in Solomon Islands. A total of 5239 participants were enrolled across 20 villages. Scabies prevalence was 15% (95% CI 11.8 – 19.1) and impetigo prevalence 5.6% (95% 4.2 – 7.3). Dermatology quality of life interviews were conducted in one-third of participants to assess the impact of scabies on individuals. This study found that scabies has a small, but measurable, impact on quality of life in children and adults, and that the impact increased with the severity of the disease. The second part of this thesis investigates the public health control of scabies. A systematic review and meta-analysis was conducted to assess the impact of MDA on both scabies and impetigo. The meta-analysis included 9 studies and found that MDA with ivermectin or permethrin led to an overall relative reduction of 79% scabies prevalence and 66% impetigo prevalence. A variety of drug and dose regimens were used across the included studies and it was not clear if one regimen was more effective than others. The major study in this thesis is the Regimens of Ivermectin for Scabies Elimination (RISE) trial. RISE was a cluster-randomised non-inferiority study of one versus two doses of ivermectin-based MDA. There were 20 villages included in the study, with 10 villages randomised to each dose group. Participating villages were scattered across 7 different island groups and neighbouring villages did not take part in MDA. The study aim was to assess the prevalence of scabies in one and two dose villages 12 months after MDA, but due to the COVID-19 global pandemic this was delayed to 21 months. At 21 months after MDA there was no change in scabies prevalence in either the one or two dose groups. There was a reduction in the severity of scabies and the prevalence of impetigo in both groups. The results were unexpected. There was considerable movement of people in and out of the study villages between baseline and 21 months which may have contributed to the finding of static scabies prevalence in both groups. Despite the lack of effect seen in the RISE trial the systematic review and meta-analysis demonstrated that MDA can have a substantial impact on scabies prevalence. The RISE trial provided important information about implementation of MDA and the need for neighbouring villages to receive treatment. The question of whether one dose of ivermectin-based MDA is non-inferior to two doses needs further research.
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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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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.