Paediatrics (RCH) - Theses

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End date: 2022 × Start date: 2020 × Type: PhD thesis × Subject: Fiji × Subject: cluster randomised trial ×

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    Fiji integrated therapy – safety and efficacy of community control strategies for lymphatic filariasis and scabies in Fiji
    Hardy, Myra ( 2022)
    Neglected tropical diseases (NTDs) are a collection of 20 diseases recognised by the World Health Organization (WHO) as causing significant harm to the health, social engagement and economic potential of billions of people living in poverty, predominantly in the tropics. Both lymphatic filariasis (LF) and scabies are NTDs. One effective approach to reduce the burden of NTDs in endemic communities is annual mass drug administration (MDA). This strategy involves providing free medication to all community members regardless of infection status at the same time. Lymphatic filariasis (LF) is a caused by the nematode Wuchereria bancrofti, transmitted between humans by mosquitoes. Chronic complications of LF include irreversible lymphoedema and hydroceles. Lymphatic filariasis remains endemic in areas of Fiji, despite regular annual MDA using diethylcarbamazine and albendazole (DA) since 2000. Experts in the field hypothesised that adding ivermectin to DA would improve the efficacy of the MDA and help accelerate towards the goal of elimination of LF as a public health problem. Scabies is a pruritic rash caused by the microscopic mite Sarcoptes scabiei variety hominis. Secondary bacterial infections from Staphylococcus aureus and Streptococcus pyogenes are common and can lead to local skin infections, sepsis and auto-immune complications including glomerulonephritis and potentially rheumatic fever. Scabies is endemic in Fiji with an estimated national prevalence of scabies of 18%. Scabies can be successfully controlled with two-dose ivermectin-based MDA. Experts in the field have highlighted evaluation of one-dose ivermectin-based MDA as a priority, because if non-inferior to a two-dose schedule it would reduce barriers to implementation of scabies control efforts. The Fiji Integrated Therapy study was initiated to evaluate the impact of MDA with ivermectin, diethylcarbamazine and albendazole, known as IDA, on 2 remote islands within the Eastern Division of Fiji where LF and scabies are co-endemic. Data arising from this cluster randomised controlled study underpins this thesis. There are 3 main components: 1) safety of IDA; 2) efficacy of IDA for LF and 3) evaluation of community control strategies for scabies. The first part of the thesis evaluates the safety of IDA MDA compared to DA. Adverse events were monitored for the first 7 days after treatment. Six hundred (16.7%) participants experienced an adverse event with no difference between treatment groups. Most (93.2%) symptoms were graded as mild with no serious events attributable to treatment. Participants with microfilaremia were more likely to experience an adverse event (43.2% versus 15.7%). The second part of the thesis reports on the efficacy of IDA compared to DA for LF. Contrary to IDA efficacy studies in other countries with different transmission profiles, we found no difference between treatment groups for clearance of microfilaremia 12 months after treatment (DA 69.2% versus IDA 62.5%). There was no difference in community prevalence of LF at 12 months. The possible reasons for this unexpected finding are discussed. The third part of the thesis addresses the effectiveness of different community control strategies for scabies. One-dose ivermectin-based MDA was non-inferior to two-dose ivermectin-based MDA for reduction in community prevalence of scabies at 12 months. Screen and treat with permethrin for individuals with scabies and their household contacts was also non-inferior, however this approach would be labour intensive and expensive and unlikely to be feasible at scale. Overall, IDA MDA was well tolerated and effective in reducing the community prevalence of LF and scabies in endemic communities in Fiji. The lack of benefit by the addition of ivermectin on LF in Fiji needs further exploration in similar transmission settings to understand the possible reasons for this finding. The success of one-dose ivermectin-based MDA for the control of scabies needs further research to determine if it can be replicated in urban and non-island settings. The findings from this thesis have informed LF and scabies control policy within Fiji, the Pacific region, and globally.