Lymphatic Filariasis Elimination in American Samoa: Evaluation of Molecular Xenomonitoring as a Surveillance Tool in the Endgame

Abstract

The Global Programme to Eliminate Lymphatic Filariasis has made significant progress toward interrupting transmission of lymphatic filariasis (LF) through mass drug administration (MDA). Operational challenges in defining endpoints of elimination programs include the need to determine appropriate post-MDA surveillance strategies. As humans are the only reservoirs of LF parasites, one such strategy is molecular xenomonitoring (MX), the detection of filarial DNA in mosquitoes using molecular methods (PCR), to provide an indirect indicator of infected persons nearby. MX could potentially be used to evaluate program success, provide support for decisions to stop MDA, and conduct post-MDA surveillance. American Samoa has successfully completed MDA and passed WHO recommended Transmission Assessment Surveys in 2011 and 2015, but recent studies using spatial analysis of antigen (Ag) and antibody (Ab) prevalence in adults (aged ≥18 years) and entomological surveys showed evidence of possible ongoing transmission. This study evaluated MX as a surveillance tool in American Samoa by linking village-level results of published human and mosquito studies. Of 32 villages, seropositive persons for Og4C3 Ag were identified in 11 (34.4%), for Wb123 Ab in 18 (56.3%) and for Bm14 Ab in 27 (84.4%) of villages. Village-level seroprevalence ranged from 0–33%, 0–67% and 0–100% for Og4C3 Ag, Wb123 Ab and Bm14 Ab respectively. PCR-positive Aedes polynesiensis mosquitoes were found in 15 (47%) villages, and their presence was significantly associated with seropositive persons for Og4C3 Ag (67% vs 6%, p<0.001) and Wb123 Ab (87% vs 29%, p = 0.001), but not Bm14 Ab. In villages with persons seropositive for Og4C3 Ag and Wb123 Ab, PCR-positive Ae. polynesiensis were found in 90.9% and 72.2% respectively. In villages without seropositive persons for Og4C3 Ag or Wb123 Ab, PCR-positive Ae. polynesiensis were also absent in 94.1% and 70.6% of villages respectively. Our study provides promising evidence to support the potential usefulness of MX in post-MDA surveillance in an Aedes transmission area in the Pacific Islands setting.

Potential strategies for strengthening surveillance of lymphatic filariasis in American Samoa after mass drug administration: targeting older age groups, hotspots, and household members of infected persons

“…Our study showed that population representative surveys of older children have the potential to reduce NNTest, and cost-effectiveness could be maintained by conducting the surveys at schools in areas where school attendance rates are high, e.g. testing age [8][9][10][11][12] year-olds in elementary schools, or age [13][14][15][16][17] year-olds at secondary school. Furthermore, testing [8][9][10][11][12] year-olds in TAS-2, TAS-3, and beyond is consistent with the rationale behind TAS, i.e targeting age groups who have lived their entire lives during and/or after MDA, so any positive cases would indicate incident infection and therefore ongoing transmission.…”

Multiplex serologic testing within a cross-sectional lymphatic filariasis sentinel site survey in coastal Kenya reveals community-level differences in IgG antibody responses to parasitic diseases and vaccines

“…S7). Results from a recent study in American Samoa demonstrated that PCR-positive pools of LF vector mosquitoes were statistically significant predictors of seropositivity for Wb123 but not Bm14, suggesting Wb123 could be an indicator of ongoing transmission [46]. Longitudinal studies in areas of intense LF transmission have shown that children acquire infections early in life [47,48].…”

Field evaluation of DNA detection of human filarial and malaria parasites using mosquito excreta/feces

“…However, since the sensitivity of parasite antigen detecting tests is reduced in low prevalence settings [10], the long term cost-effectiveness of this strategy and its ability to detect ongoing transmission has been put into question and an alternative approach may be needed. Molecular xenomonitoring has proven useful in the assessment of LF transmission or validation of elimination in many countries including Papua New Guinea [11], Ghana [12], Togo [13], Egypt [14], India [15], Sri Lanka [16] and American Samoa [17].…”