Alternative Approaches for Monitoring and Evaluation of Lymphatic Filariasis Following Mass Drug Treatment with Ivermectin, Diethylcarbamazine and Albendazole in East New Britain Province, Papua New Guinea

Abstract

AbstractBackgroundWHO recommends two annual rounds of mass drug administration (MDA) with ivermectin, diethylcarbamazine, and albendazole (IDA) for lymphatic filariasis (LF) elimination in treatment naïve areas that are not co-endemic for onchocerciasis such as Papua New Guinea (PNG). Whether two rounds of MDA are necessary or sufficient and the optimal sampling strategies and endpoints for stopping MDA remain undefined.Methods and FindingsTwo cross-sectional studies were performed, one at baseline in 2019 before MDA-IDA, and 12 months post-MDA-IDA. Pre-MDA, we selected 49 sentinel villages for LF in East New Britain Province (ENBP, PNG) and randomly sampled ∼100 individuals/village of approximately equal number of children 6-9 years (N=1,906), and those ≥10 years (N=2,346) using population proportionate and purposeful sampling. LF infection was assessed by tests for circulating filarial antigenemia (CFA) and microfilariae (Mf). Children ages 6-9, 1.9% (37/1,906, range 0-21.6%) were CFA positive at baseline, and 0.3% (5/1,906; range 0-7.8%) were Mf positive. Individuals ≥10 years, 7.5% (176/2,346, range 0-52%) were CFA positive, and 2.0% (47/2,346, range 0-36%) were Mf positive. Twenty-four of 49 clusters were CFA ≥2%, and 14 had Mf prevalence ≥1%. Post-MDA (82% coverage), 47 clusters were selected based on geospatial modeling (N=4,610), of which 38 had >2% CFA compared to 24 identified at baseline. In the 24 villages evaluated pre- and post-MDA, we stratified the impact of MDA-IDA on children 6-9 and adults ≥18 years. Children had a 34% reduction in CFA prevalence and complete Mf clearance. Adults had a 39% reduction in CFA prevalence and a 96% reduction in Mf prevalence. Post-MDAx1 showed no villages that were Mf positive in two of four districts.ConclusionsGeospatial modeling was more effective in sampling high-risk sites for LF than population-proportional sampling. The low LF prevalence in children and slight reduction of CFA prevalence limits its utility as a biomarker for LF elimination in children. A single round of MDA with IDA with high coverage was sufficient to reach elimination targets in villages with low baseline LF prevalence. Areas with higher baseline prevalence will require additional rounds of MDA, but this could be targeted to smaller evaluation units to reduce cost.Trial registrationThis study is registered atClinicaltrials.govunder the numberNCT04124250Author SummaryWhy was this study done?WHO has targeted lymphatic filariasis (LF) for global elimination as a public health problem using mass drug administration (MDA) as the primary intervention strategy.The WHO recently modified recommendations for MDA of LF with a combination of three co-administered drugs: ivermectin, diethylcarbamazine, and albendazole. This study examined the impact of one round of MDA on LF infection parameters in Papua New Guinea that had not previously received MDA for LF and examined new methodologies for monitoring and surveillance.What did the researcher do and find?Before MDA, we randomly sampled sentinel clusters (villages) using population proportional sampling of equal numbers of children 6-9 years and older children and adults using well-established LF infection parameters. Post-MDA, we selected sentinel villages using a geospatial modeling design and focused on sampling adults.Population-proportional sampling underestimated the overall LF infection because the infection was more common in less-densely populated rural areas. Sampling children 6-9 years of age was inefficient because of very low infection rates in this age group. Geospatial modeling was more effective than population proportional sampling for selecting areas at high risk for LF. One round of MDA with high coverage was highly effective for reducing microfilaremia prevalence to very low levels in most sampled villages, but CFA prevalence decreased less dramatically.What do these findings mean?Geospatial modeling and sampling adults for microfilaria are preferred methods for monitoring the impact of MDA with IDA.Results from this study suggest that one round of high-coverage MDA may be sufficient to interrupt LF transmission in areas with low baseline prevalence. Additional rounds of MDA can then be targeted to areas with higher LF prevalence, thus reducing program costs. This strategy requires high-quality baseline surveillance to capture the focality of LF infection and high-quality MDA. This approach may be especially useful in areas like Papua New Guinea, where MDA is logistically challenging.