Paediatrics (RCH) - Research Publications

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    Efficacy of mass drug administration with ivermectin for control of scabies and impetigo, with coadministration of azithromycin: a single-arm community intervention trial
    Romani, L ; Marks, M ; Sokana, O ; Nasi, T ; Kamoriki, B ; Cordell, B ; Wand, H ; Whitfeld, MJ ; Engelman, D ; Solomon, AW ; Kaldor, JM ; Steer, AC (ELSEVIER SCI LTD, 2019-05)
    BACKGROUND: In small community-based trials, mass drug administration of ivermectin has been shown to substantially decrease the prevalence of both scabies and secondary impetigo; however, their effect at large scale is untested. Additionally, combined mass administration of drugs for two or more neglected diseases has potential practical advantages, but efficacy of potential combinations should be confirmed. METHODS: The azithromycin ivermectin mass drug administration (AIM) trial was a prospective, single-arm, before-and-after, community intervention study to assess the efficacy of mass drug administration of ivermectin for scabies and impetigo, with coadministration of azithromycin for trachoma. Mass drug administration was offered to the entire population of Choiseul Province, Solomon Islands, and of this population we randomly selected two sets of ten sentinel villages for monitoring, one at baseline and the other at 12 months. Participants were offered a single dose of 20 mg/kg azithromycin, using weight-based bands. Children weighing less than 12·5 kg received azithromycin oral suspension (20 mg/kg), and infants younger than 6 months received topical 1% tetracycline ointment. For ivermectin, participants were offered two doses of oral ivermectin 200 μg/kg 7-14 days apart using weight-based bands, or 5% permethrin cream 7-14 days apart if ivermectin was contraindicated. Our study had the primary outcomes of safety and feasibility of large-scale mass coadministration of oral ivermectin and azithromycin, which have been previously reported. We report here the prevalence of scabies and impetigo in residents of the ten baseline villages compared with those in the ten 12-month villages, as measured by examination of the skin, which was a secondary outcome of the trial. Further outcomes were comparison of the number of all-cause outpatient attendances at government clinics in Choiseul Province at various timepoints before and after mass drug administration. The trial was registered with the Australian and New Zealand Trials Registry (ACTRN12615001199505). FINDINGS: During September, 2015, over 4 weeks, 26 188 people (99·3% of the estimated population of Choiseul [n=26 372] as determined at the 2009 census) were treated. At baseline, 1399 (84·2%) of 1662 people living in the first ten villages had their skin examined, of whom 261 (18·7%) had scabies and 347 (24·8%) had impetigo. At 12 months after mass drug administration, 1261 (77·6%) of 1625 people in the second set of ten villages had their skin examined, of whom 29 (2·3%) had scabies (relative reduction 88%, 95% CI 76·5-99·3) and 81 (6·4%) had impetigo (relative reduction 74%, 63·4-84·7). In the 3 months after mass drug administration, 10 614 attended outpatient clinics for any reason compared with 16 602 in the 3 months before administration (decrease of 36·1%, 95% CI 34·7-37·6), and during this period attendance for skin sores, boils, and abscesses decreased by 50·9% (95% CI 48·6-53·1). INTERPRETATION: Ivermectin-based mass drug administration can be scaled to a population of over 25 000 with high efficacy and this level of efficacy can be achieved when mass drug administration for scabies is integrated with mass drug administration of azithromycin for trachoma. These findings will contribute to development of population-level control strategies. Further research is needed to assess durability and scalability of mass drug administration in larger, non-island populations, and to assess its effect on the severe bacterial complications of scabies. FUNDING: International Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, and the Wellcome Trust.
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    Systematic review of the diagnosis of scabies in therapeutic trials
    Thompson, MJ ; Engelman, D ; Gholam, K ; Fuller, LC ; Steer, AC (OXFORD UNIV PRESS, 2017-07)
    Human scabies (infestation with the mite Sarcoptes scabiei var hominis) causes a significant disease burden worldwide, yet there are no agreed diagnostic guidelines. We aimed to determine whether a consistent approach to diagnosing scabies has been used for published scabies therapeutic trials. The data sources used were the MEDLINE, Embase and Cochrane databases, from 1946 to 29 August 2013. Eligible studies were trials of therapeutic interventions against scabies in human subjects, published in English, enrolling patients with scabies, and using various therapeutic interventions. Language was a limitation of this study as some relevant trials published in languages other than English may have been excluded. Each study was reviewed by two independent authors, who assessed the clinical examination and testing approaches used for scabies diagnosis in the included studies. We found that of 71 included trials, 40 (56%) specified which clinical findings were used for diagnosis, which were predominantly rash, rash distribution, pruritus and mite burrows. Parasitological testing was used in 63% of trials (n = 45) and was used more frequently in clinic-based than in field studies. Nearly one-quarter of trials (24%, n = 17) did not define the diagnostic method used. Overall, the diagnostic approaches were poorly described, prohibiting accurate comparison of existing studies. This review further supports the need for consensus diagnostic guidelines for scabies.
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    Adherence to secondary antibiotic prophylaxis for patients with rheumatic heart disease diagnosed through screening in Fiji
    Engelman, D ; Mataika, RL ; Kado, JH ; Kee, MA ; Donath, S ; Parks, T ; Steer, AC (WILEY, 2016-12)
    OBJECTIVES: Echocardiographic screening for rheumatic heart disease (RHD) can detect subclinical cases; however, adequate adherence to secondary antibiotic prophylaxis (SAP) is required to alter disease outcomes. We aimed to investigate the adherence to SAP among young people with RHD diagnosed through echocardiographic screening in Fiji and to investigate factors associated with adherence. METHODS: Patients diagnosed with RHD through echocardiographic screening in Fiji from 2006 to 2014 were included. Dates of benzathine penicillin G injections were collected from 76 health clinics nationally from December 2011 to December 2014. Adherence was measured using the proportion of days covered (PDC). Multivariate logistic regression analysis was used to identify characteristics associated with any adherence (≥1 injection received) and adequate adherence (PDC ≥0.80). RESULTS: Of 494 patients, 268 (54%) were female and the median age was 14 years. Overall, 203 (41%) had no injections recorded and just 33 (7%) had adequate adherence. Multivariate logistic regression showed increasing age (OR 0.93 per year, 95% CI 0.87-0.99) and time since diagnosis ≥1.5 years (OR 0.53, 95% CI 0.37-0.79) to be inversely associated with any adherence. Non-iTaukei ethnicity (OR 2.58, 95%CI 1.04-6.33) and urban residence (OR 3.36, 95% CI 1.54-7.36) were associated with adequate adherence, whereas time since diagnosis ≥1.5 years (OR 0.38, 95%CI 0.17-0.83) was inversely associated with adequate adherence. CONCLUSIONS: Adherence to SAP after screening in Fiji is currently inadequate for individual patient protection or population disease control. Secondary prevention should be strengthened before further screening can be justified.
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    Toward the Global Control of Human Scabies: Introducing the International Alliance for the Control of Scabies
    Engelman, D ; Kiang, K ; Chosidow, O ; McCarthy, J ; Fuller, C ; Lammie, P ; Hay, R ; Steer, A ; Vinetz, JM (PUBLIC LIBRARY SCIENCE, 2013-08)
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    Opportunities to investigate the effects of ivermectin mass drug administration on scabies
    Engelman, D ; Martin, DL ; Hay, RJ ; Chosidow, O ; McCarthy, JS ; Fuller, LC ; Steer, AC (BIOMED CENTRAL LTD, 2013-04-17)
    The recent article by Mohammed et al. demonstrates an impressive effect of ivermectin mass drug administration for lymphatic filariasis on the burden of scabies. Partnering scabies research within the evaluation and monitoring of Neglected Tropical Disease programmes could potentially increase our understanding of the epidemiology and control of scabies and its important bacterial complications.
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    Long Term Control of Scabies Fifteen Years after an Intensive Treatment Programme
    Marks, M ; Taotao-Wini, B ; Satorara, L ; Engelman, D ; Nasi, T ; Mabey, DC ; Steer, AC ; Vinetz, JM (PUBLIC LIBRARY SCIENCE, 2015-12)
    INTRODUCTION: Scabies is a major public health problem in the Pacific and is associated with an increased risk of bacterial skin infections, glomerulonephritis and rheumatic fever. Mass drug administration with ivermectin is a promising strategy for the control of scabies. Mass treatment with ivermectin followed by active case finding was conducted in five communities in the Solomon Islands between 1997 and 2000 and resulted in a significant reduction in the prevalence of both scabies and bacterial skin infections. METHODS: We conducted a prospective follow-up study of the communities where the original scabies control programme had been undertaken. All residents underwent a standardised examination for the detection of scabies and impetigo. RESULTS: Three hundred and thirty eight residents were examined, representing 69% of the total population of the five communities. Only 1 case of scabies was found, in an adult who had recently returned from the mainland. The prevalence of active impetigo was 8.8% overall and 12.4% in children aged 12 years or less. DISCUSSION: We found an extremely low prevalence of scabies 15 years after the cessation of a scabies control programme. The prevalence of impetigo had also declined further since the end of the control programme. Our results suggest that a combination of mass treatment with ivermectin and intensive active case finding may result in long term control of scabies. Larger scale studies and integration with other neglected tropical disease control programmes should be priorities for scabies control efforts.
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    Screening for rheumatic heart disease: quality and agreement of focused cardiac ultrasound by briefly trained health workers
    Engelman, D ; Kado, JH ; Remenyi, B ; Colquhoun, SM ; Carapetis, JR ; Wilson, NJ ; Donath, S ; Steer, AC (BMC, 2016-02-01)
    BACKGROUND: Echocardiographic screening for rheumatic heart disease (RHD) has the potential to detect subclinical cases for secondary prevention, but is constrained by inadequate human resources in most settings. Training non-expert health workers to perform focused cardiac ultrasound (FoCUS) may enable screening at a population-level. We aimed to evaluate the quality and agreement of FoCUS for valvular regurgitation by briefly trained health workers. METHODS: Seven nurses participated in an eight week training program in Fiji. Nurses performed FoCUS on 2018 children aged five to 15 years, and assessed any valvular regurgitation. An experienced pediatric cardiologist assessed the quality of ultrasound images and measured any recorded regurgitation. The assessment of the presence of regurgitation and measurement of the longest jet by the nurse and cardiologist was compared, using the Bland-Altman method. RESULTS: The quality of FoCUS overall was adequate for diagnosis in 96.6%. There was substantial agreement between the cardiologist and the nurses overall on the presence of mitral regurgitation (κ = 0.75) and aortic regurgitation (κ = 0.61) seen in two views. Measurements of mitral regurgitation by nurses and the cardiologist were similar (mean bias 0.01 cm; 95% limits of agreement -0.64 to 0.66 cm). CONCLUSIONS: After brief training, health workers with no prior experience in echocardiography can obtain adequate quality images and make a reliable assessment on the presence and extent of valvular regurgitation. Further evaluation of the imaging performance and accuracy of screening by non-expert operators is warranted, as a potential population-level screening strategy in high prevalence settings.
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    The Prevalence of Scabies and Impetigo in the Solomon Islands: A Population-Based Survey
    Mason, DS ; Marks, M ; Sokana, O ; Solomon, AW ; Mabey, DC ; Romani, L ; Kaldor, J ; Steer, AC ; Engelman, D ; Vinetz, JM (PUBLIC LIBRARY SCIENCE, 2016-06)
    BACKGROUND: Scabies and impetigo are common, important and treatable skin conditions. Reports from several Pacific island countries show extremely high prevalence of these two conditions, but for many countries, including the Solomon Islands, there is a paucity of epidemiological data. METHODOLOGY: Ten rural villages in the Western Province of the Solomon Islands were included in the study, chosen so that data collection could be integrated with an existing project investigating clinical and serological markers of yaws. All residents were eligible to participate, and 1908 people were enrolled. Participants were interviewed and examined by a paediatric registrar, who recorded relevant demographic information, and made a clinical diagnosis of scabies and/or impetigo, severity and distribution. PRINCIPAL FINDINGS: The total unweighted prevalence of scabies was 19.2% (95% confidence interval [CI] 17.5-21.0), and age and gender weighted prevalence 19.2% (95%CI 16.7-21.9). The adult prevalence of scabies was 10.4% (95%CI 8.2-13.2), and the highest prevalence was found in infants < 1 year of age (34.1%, adjusted odds ratio [AOR] compared with adults: 3.6, 95%CI 2.2-6.0) and children aged 1-4 years (25.7%, AOR 2.6, 95%CI 1.7-3.9). Scabies affected two or more body regions in 80.9% of participants, and 4.4% of scabies cases were classified as severe. The total unweighted prevalence of active impetigo was 32.7% (95%CI 30.6-34.8), and age and gender weighted prevalence 26.7% (95%CI 24.2-29.5). The highest prevalence was found in children aged 1-4 years (42.6%, AOR compared with adults: 4.1, 95%CI 2.9-5.8). Scabies infestation was associated with active impetigo infection (AOR 2.0, 95%CI 1.6-2.6); with 41.1% of active impetigo cases also having scabies. CONCLUSIONS AND SIGNIFICANCE: Scabies and impetigo are very common in the rural Western Province of the Solomon Islands. Scabies infestation is strongly associated with impetigo. Community control strategies for scabies may reduce the burden of both conditions and their downstream complications.
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    Consensus criteria for the diagnosis of scabies: A Delphi study of international experts
    Engelman, D ; Fuller, LC ; Steer, AC ; Vinetz, JM (PUBLIC LIBRARY SCIENCE, 2018-05)
    BACKGROUND: Scabies was added to the WHO Neglected Tropical Diseases portfolio in 2017, and further understanding of the disease burden is now required. There are no uniformly accepted test methods or examination procedures for diagnosis, which limits the interpretation of research and epidemiological findings. The International Alliance for the Control of Scabies (IACS) designated harmonization of diagnostic procedures as a priority for the development of a global control strategy. Therefore, we aimed to develop consensus criteria for the diagnosis of scabies. METHODOLOGY / PRINCIPAL FINDINGS: We conducted an iterative, consensus (Delphi) study involving international experts in the diagnosis of scabies. Panel members were recruited through expression of interest and targeted invitation of experts. The Delphi study consisted of four rounds of anonymous surveys. Rounds 1 and 2 involved generation and ranking an extensive list of possible features. In Rounds 3 and 4, participants were presented results from previous rounds and indicated agreement with a series of draft criteria. Panel participants (n = 34, range per Round 28-30) were predominantly highly experienced clinicians, representing a range of clinical expertise and all inhabited continents. Based on initial rounds, a draft set of criteria were developed, incorporating three levels of diagnostic certainty-Confirmed Scabies, Clinical Scabies and Suspected Scabies. Consensus was reached in Round 4, with a very high level of agreement (> 89%) for all levels of criteria and subcategories. Adoption of the criteria was supported by 96% of panel members. CONCLUSIONS / SIGNIFICANCE: Consensus criteria for scabies diagnosis were established with very high agreement. The 2018 IACS Criteria for the Diagnosis of Scabies can be implemented for scabies research and mapping projects, and for surveillance after control interventions. Validation of the criteria is required.
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    Exploration of a simplified clinical examination for scabies to support public health decision-making
    Marks, M ; Engelman, D ; Romani, L ; Mason, D ; Sokana, O ; Kama, M ; Whitfeld, M ; Steer, AC ; Kaldor, J ; Murdoch, M (PUBLIC LIBRARY SCIENCE, 2018-12)
    INTRODUCTION: In most settings, the diagnosis of scabies is reliant on time-consuming and potentially intrusive clinical examination of all accesible regions of skin. With the recent recognition of scabies as a neglected tropical disease by the World Health Organization there is a need for standardised approaches to disease mapping to define populations likely to benefit from intervention, and to measure the impact of interventions. Development and validation of simplified approaches to diagnose scabies would facilitate these efforts. METHODS: We utilised data from three population-based surveys of scabies. We classified each individual as having scabies absent or present overall, based on whole body assessment, and in each of 9 regions of the body. We calculated the sensitivity of diagnosing the presence of scabies based on each individual body region compared to the reference standard based on whole body examination and identified combinations of regions which provided greater than 90% sensitivity. We assessed the sensitivity according to gender, age group, severity of scabies and the presence or absence of impetigo. RESULTS: We included 1,373 individuals with scabies. The body regions with highest yield were the hands (sensitivity compared to whole body examination 51.2%), feet (49.7%), and lower legs (48.3%). Examination of the exposed components of both limbs provided a sensitivity of 93.2% (95% CI 91.2-94.4%). The sensitivity of this more limited examination was greater than 90% regardless of scabies severity or the presence or absence of secondary impetigo. DISCUSSION: We found that examination limited to hands, feet and lower legs was close to 90% for detecting scabies compared to a full body examination. A simplified and less intrusive diagnostic process for scabies will allow expansion of mapping and improved decision-making about public health interventions. Further studies in other settings are needed to prospectively validate this simplified approach.