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

Background WHO 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 Findings Two 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.   Conclusions Geospatial 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Yes ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The protocol was approved by the Medical Research Advisory Council of PNG (MRAC 19.14) and Case Western Reserve University IRB (STUDY20191141) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Detailed village specific data is included in the supplemental information