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 conducted at baseline (N = 49 clusters or villages) and 12 months after mass drug administration (MDA) with IDA (N = 47 villages) to assess lymphatic filariasis (LF) by circulating filarial antigenemia (CFA) and microfilariae (Mf). Before MDA, children aged 6–9 years (N~50) and those ≥ 10 years (N~50) in each village were randomly sampled. Before MDA, the population mean prevalence of LF in East New Britain Province (ENBP), Papua New Guinea, was estimated using population proportionate sampling (PPS, N = 30) to be 59/2,561 (2.3%) CFA positive and 14/2,561 (0.6%) Mf positive. No children were Mf positive. However, LF infection was highly heterogeneous; 8 villages (26.7%) had a CFA prevalence >2%, and 7 villages (23.3%) had an Mf prevalence >1%. To identify sentinel villages with LF in areas under-sampled by PPS, 19 additional villages suspected to have LF were sampled, with 15 (79%) having >2% CFA prevalence and 7 (38%) >1% Mf (range 1–22%). Twenty-four villages were evaluated before and after MDA in age-matched adults (≥ 18 years). Treatment reduced CFA prevalence by 34% and Mf prevalence by 90%. Post-MDA model-based geostatistics efficiently selected an additional 23 villages, of which 20 (87%) had a CFA prevalence > 2%. None of these villages had >1% Mf. Post-MDA, two of four districts had no villages with >1% Mf. Conclusions: Model-based geostatistics was more effective than PPS in sampling high-risk LF sites in a heterogeneous area. Low LF prevalence and partial reduction of CFA limit children's effectiveness as sentinels. A single round of high-coverage MDA with IDA achieved elimination targets in low-prevalence villages in PNG. Higher-prevalence areas will need additional MDA rounds, which could be targeted to smaller evaluation units to cut costs. Trial registration: Clinicaltrials.gov NCT04124250 Author summary: Why 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 for 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 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 geostatistical modeling design and focused on sampling adults. Population-proportional sampling estimated the overall LF mean prevalence. However, it led to the inappropriate conclusion that LF might be less important because PPS missed villages with high LF prevalence in less densely populated rural areas. Sampling children 6–9 years of age was inefficient because of low infection rates in this age group. One round of MDA with high coverage effectively reduced microfilaremia prevalence to very low levels in most sampled villages, but CFA prevalence decreased less dramatically. What do these findings mean?: Geostatistical modeling and sampling adults for microfilaria are preferred methods for monitoring the impact of MDA with IDA in areas heterogeneous for LF rather than PPS. Sampling children to monitor LF elimination may not be a reliable indicator for stopping MDA, because CFA declines slowly after IDA, and children have low LF infection prevalence. Results from this study suggest that one round of high-coverage MDA may be sufficient to eliminate LF in areas with low baseline prevalence. Additional rounds of MDA can then be targeted to high-risk LF locations selected by geostatistical modeling, thus reducing program costs. The accuracy of geostatistical modeling in identifying LF-infected villages improves with high-quality baseline surveillance. This approach may be especially useful in areas like Papua New Guinea, where MDA is logistically challenging and costly. [ABSTRACT FROM AUTHOR]

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