Effectiveness of one and two doses of ivermectin mass drug administration in reducing the prevalence and intensity of soil-transmitted helminth (STH) infections in Western Province, Solomon Islands: a cluster-randomised, before-after analysis.

Background: Ivermectin mass drug administration (MDA) is effective for controlling onchocerciasis and scabies, with evidence supporting its role in some species of soil-transmitted helminth (STH) infections. In the context of RISE, a cluster-randomised trial for scabies, this study evaluated the effectiveness of ivermectin MDA in reducing STH burden in the Western Province of Solomon Islands. Methods: Twenty villages were randomised 1:1 to receive ivermectin MDA as one dose (IVM-1) or two doses (IVM-2) for scabies. The effectiveness of one and two doses in reducing STH prevalence and intensity was evaluated before (May 2019) and 21 months after (February 2021) MDA in May 2019. All residents aged 12 months or older in the study villages were eligible to participate and provide stool specimens. Species-specific STH infection and intensity were assessed using quantitative PCR. We compared prevalence and intensity of infection between baseline and 21 months in each intervention arm individually using cluster-level analysis (adjusted for clustering) and individual-level analysis (adjusted for sex, age, and clustering). The primary outcomes were the prevalence risk difference (RD) from the cluster-level analysis, and the change in adjusted odds of infection from the individual-level analysis. Secondary outcomes included change in incident rates of mean eggs per gram (epg) of stool from baseline to 21 months, relative risk difference in prevalence and relative change in odds of infection between arms at 21 months. Sex data (male/female) were self-reported. Findings: Overall, STH infection was assessed in 830 participants from 18 villages at baseline and 1172 from 20 villages at follow-up. Females represented 58% (n = 478) of the sample at baseline and 59% (n = 690) at follow-up. We observed a reduction in Strongyloides spp. prevalence following two doses of ivermectin MDA in the cluster-level analysis from 7.0% (32/458 participants) to 1.2% (8/674 participants), corresponding to a RD of -0.07 (95% CI -0.14 to -0.01, p = 0.036), and in the individual-level analysis (OR 0.11, 95% CI 0.04-0.33, p < 0.001). T. trichiura prevalence decreased following one dose from 19.4% (74/372 participants) to 11.7% (56/505 participants) (OR 0.44, 95% CI 0.26-0.73, p = 0.0040), while egg count reduced in both arms (IVM-1: IRR 0.28, 95% CI 0.11-0.70, p = 0.0070; IVM-2: IRR 0.18, 95% CI 0.08-0.40, p < 0.001), in the individual-level analysis. We did not detect a significant difference in effect measures between the one- and two-dose arms for any species after 21 months. Interpretation: Our study highlights the long-term benefits of ivermectin MDA in reducing the burden of Strongyloides spp. and T. trichiura. STH control programs should leverage the geographical overlap of NTDs, existing drug distribution channels, and broad-spectrum agents. Funding: The National Health and Medical Research Council of Australia.

One versus two doses of ivermectin-based mass drug administration for the control of scabies: A cluster randomised non-inferiority trial.

BACKGROUND: Mass drug administration (MDA) based on two doses of ivermectin, one week apart, substantially reduces prevalence of both scabies and impetigo. The Regimens of Ivermectin for Scabies Elimination (RISE) trial assessed whether one-dose ivermectin-based MDA would be as effective. METHODS: RISE was a cluster-randomised trial in Solomon Islands. We assigned 20 villages in a 1:1 ratio to one- or two-dose ivermectin-based MDA. We planned to test whether the impact of one dose on scabies prevalence at 12 and 24 months was non-inferior to two, at a 5% non-inferiority margin. RESULTS: We deferred endpoint assessment to 21 months due to COVID-19. We enrolled 5239 participants in 20 villages at baseline and 3369 at 21 months from an estimated population of 5500. At baseline scabies prevalence was similar in the two arms (one-dose 17·2%; two-dose 13·2%). At 21 months, there was no reduction in scabies prevalence (one-dose 18·7%; two-dose 13·4%), and the confidence interval around the difference included values substantially greater than 5%. There was however a reduction in prevalence among those who had been present at the baseline assessment (one-dose 15·9%; two-dose 10·8%). Additionally, we found a reduction in both scabies severity and impetigo prevalence in both arms, to a similar degree. CONCLUSIONS: There was no indication of an overall decline in scabies prevalence in either arm. The reduction in scabies prevalence in those present at baseline suggests that the unexpectedly high influx of people into the trial villages, likely related to the COVID-19 pandemic, may have compromised the effectiveness of the MDA. Despite the lack of effect there are important lessons to be learnt from this trial about conducting MDA for scabies in high prevalence settings. TRIAL REGISTRATION: Registered with Australian New Zealand Clinical Trials Registry ACTRN12618001086257.

Using quantitative PCR to identify opportunities to strengthen soil-transmitted helminth control in Solomon Islands: A cross-sectional epidemiological survey.

BACKGROUND: The Kato-Katz microscopy technique is the global standard for assessment of soil-transmitted helminth (STH) burden. However, major limitations include its poor sensitivity, requirement for rapid sample processing, and inability to differentiate hookworm species nor detect Strongyloides spp. infections. We assessed the prevalence and intensity of STH species in Solomon Islands by conducting a province-wide survey using quantitative PCR (qPCR) for diagnosis, which can provide much better characterisation of STH burden than microscopy. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional survey in 18 villages in Western Province to detect infections with six STH species and quantify intensity with three. We used linear mixed model regression to identify potential water, sanitation, and hygiene (WASH) and environmental risk factors for infection. We collected stool specimens from 830 village residents. Overall STH prevalence was 63.3% (range 27.5 to 91.5% across villages), led by Necator americanus (54.5% [range 17.5-89.4%]), followed by Ancylostoma ceylanicum (15.5% [range 2.8-45.8%]), Trichuris trichiura (9.1% [range 0-79.2%]), and Strongyloides spp. (3.2% [range 0-29.2%]). Most infections were of light intensity for N. americanus (85.7%) and T. trichiura (90.7%). Owning a household latrine was associated with a lower risk of N. americanus infection (AOR 0.41, 95% CI 0.24-0.68) while greater precipitation was linked to more common T. trichiura infection (AOR 1.14, 95% CI 1.04-1.25). CONCLUSION/SIGNIFICANCE: In this first large-scale population survey of STH in the Pacific using qPCR, we found evidence that ivermectin should be incorporated into STH control programmes because of the presence of T. trichiura and Strongyloides spp., both of which are poorly responsive to albendazole. Furthermore, One Health strategies are needed for improved A. ceylanicum and Strongyloides spp. control, WASH access and use should be improved to complement deworming programmes, and control efforts should ideally be expanded to entire communities. TRIAL REGISTRATION: ClinicalTrials.gov Australian and New Zealand Clinical Trials Registry ACTRN12618001086257.

Health-related quality of life impact of scabies in the Solomon Islands.

BACKGROUND: Scabies causes intense itching and skin lesions. A small number of studies have shown that scabies impacts health-related quality of life (HRQoL), but no studies have been conducted in the Pacific region. We assessed the impact of scabies on HRQoL in a high-prevalence setting using the Children's Dermatology Life Quality Index (CDLQI) and Dermatology Life Quality Index (DLQI). We also assessed the validity of these tools in a Pacific Island population. METHODS: The study was conducted in the Solomon Islands. Participants with and without skin disease were randomly selected. HRQoL indices were scored on a scale of 0-30. RESULTS: We surveyed 1051 adults (91 with scabies) and 604 children (103 with scabies). Scabies had a small impact on HRQoL, with a median DLQI score of 2 (interquartile range [IQR] 0-6) and a CDLQI score of 2 (IQR 0-4). Scores increased linearly with severity. The greatest impact on QoL was due to itch, sleep disturbance and impacts on education and employment. CONCLUSIONS: Scabies has a small but measurable impact on HRQoL. The DLQI and CDLQI scores were discriminated between the skin-related QoL of patients with scabies and the control group, indicating that these tools are appropriate to measure skin-related QoL in the Solomon Islands.

Defining the need for public health control of scabies in Solomon Islands.

Pacific Island countries have a high burden of scabies and impetigo. Understanding of the epidemiology of these diseases is needed to target public health interventions such as mass drug administration (MDA). The aim of this study is to determine the prevalence of scabies and impetigo in Solomon Islands as well as the relationship between them and their distribution. We conducted a prevalence study in 20 villages in Western Province in Solomon Islands. All residents of the village were eligible to participate. Nurses conducted clinical assessments including history features and skin examination. Diagnosis of scabies was made using the 2020 International Alliance for the Control of Scabies diagnostic criteria. Assessments were completed on 5239 participants across 20 villages. Overall scabies prevalence was 15.0% (95%CI 11.8-19.1). There was considerable variation by village with a range of 3.3% to 42.6%. There was a higher prevalence of scabies in males (16.7%) than females (13.5%, adjusted relative risk 1.2, 95%CI 1.1-1.4). Children aged under two years had the highest prevalence (27%). Overall impetigo prevalence was 5.6% (95%CI 4.2-7.3), ranging from 1.4% to 19% by village. The population attributable risk of impetigo associated with scabies was 16.1% (95% CI 9.8-22.4). The prevalence of scabies in our study is comparable to previous studies in Solomon Islands, highlighting a persistent high burden of disease in the country, and the need for public health strategies for disease control.

Protocol for a cluster-randomised non-inferiority trial of one versus two doses of ivermectin for the control of scabies using a mass drug administration strategy (the RISE study).

INTRODUCTION: Scabies is a significant contributor to global morbidity, affecting approximately 200 million people at any time. Scabies is endemic in many resource-limited tropical settings. Bacterial skin infection (impetigo) frequently complicates scabies infestation in these settings. Community-wide ivermectin-based mass drug administration (MDA) is an effective control strategy for scabies in island settings, with a single round of MDA reducing population prevalence by around 90%. However, current two-dose regimens present a number of barriers to programmatic MDA implementation. We designed the Regimens of Ivermectin for Scabies Elimination (RISE) trial to investigate whether one-dose MDA may be as effective as two-dose MDA in controlling scabies in high-prevalence settings. METHODS AND ANALYSIS: RISE is a cluster-randomised non-inferiority trial. The study will be conducted in 20 isolated villages in Western Province of Solomon Islands where population prevalence of scabies is approximately 20%. Villages will be randomly allocated to receive either one dose or two doses of ivermectin-based MDA in a 1:1 ratio. The primary objective of the study is to determine if ivermectin-based MDA with one dose is as effective as MDA with two doses in reducing the prevalence of scabies after 12 months. Secondary objectives include the effect of ivermectin-based MDA on impetigo prevalence after 12 and 24 months, the prevalence of scabies at 24 months after the intervention, the impact on presentation to health facilities with scabies and impetigo, and the safety of one-dose and two-dose MDA. ETHICS AND DISSEMINATION: This trial has been approved by the ethics review committees of the Solomon Islands and the Royal Children's Hospital, Australia. Results will be disseminated in peer-reviewed publications and in meetings with the Solomon Islands Ministry of Health and Medical Services and participating communities. TRIAL REGISTRATION DETAILS: Australian New Zealand Clinical Trials Registry: ACTRN12618001086257. Date registered: 28 June 2018.