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

<div><p>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 <i>Aedes polynesiensis</i> mosquitoes were found in 15 (47%) villages, and their presence was significantly associated with seropositive persons for Og4C3 Ag (67% vs 6%, <i>p</i><0.001) and Wb123 Ab (87% vs 29%, <i>p</i> = 0.001), but not Bm14 Ab. In villages with persons seropositive for Og4C3 Ag and Wb123 Ab, PCR-positive <i>Ae</i>. <i>polynesiensis</i> were found in 90.9% and 72.2% respectively. In villages without seropositive persons for Og4C3 Ag or Wb123 Ab, PCR-positive <i>Ae</i>. <i>polynesiensis</i> 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 <i>Aedes</i> transmission area in the Pacific Islands setting.</p></div

Association between PCR-positive pools of mosquitoes and seropositive villages for Og4C3 Ag, Wb123 Ab, and Bm14 Ab.

<p>Association between PCR-positive pools of mosquitoes and seropositive villages for Og4C3 Ag, Wb123 Ab, and Bm14 Ab.</p

PCR-positive pools of mosquitoes as predictors of villages with inhabitants seropositive for Og4C3 Ag, Wb123 Ab, and Bm14 Ab.

<p>PCR-positive pools of mosquitoes as predictors of villages with inhabitants seropositive for Og4C3 Ag, Wb123 Ab, and Bm14 Ab.</p

Probabilities of identifying seropositive villages for Og4C3 Ag, Wb123 Ab and Bm14 Ab based on the presence of PCR-positive pools of a) Ae. polynesiensis, b) any mosquito species, and c) other mosquito species.

<p>Probabilities of identifying seropositive villages for Og4C3 Ag, Wb123 Ab and Bm14 Ab based on the presence of PCR-positive pools of a) Ae. polynesiensis, b) any mosquito species, and c) other mosquito species.</p

Summary of human and entomological data from the 32 villages included in this study.

<p>Summary of human and entomological data from the 32 villages included in this study.</p

Immunochromatographic test prevalence in Leogane, Haiti (2000–2007).

<p>Antigen prevalence increased from 23.2% to 31.2% in Leogane town and from 8.2% to 14.5% in Masson-Mathieu in 2007. There was no MDA in 2006. The dashed lines indicate antigen prevalence in 2007. The total number of persons surveyed each year is indicated in the legend.</p

Estimated prevalence of <i>Ae. polynesiensis</i> females containing <i>W. bancrofti</i> DNA from trap catch in each village.

<p>Prevalences were estimated by maximum likelihood and confidence intervals by the likelihood ratio method <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003087#pntd.0003087-Katholi1" target="_blank">[41]</a>. The total number of <i>Ae. polynesiensis</i> is shown above each bar. “Satala-Leloaloa Area” includes Satala, Anua, Atuu, and Leloaloa villages and “Leone Area” includes Auma, Leone, and Puapua villages.</p

Trapping and PCR results for area in and around elementary school in Iliili village

Trapping and PCR results for area in and around elementary school in Iliili villag

Household locations of individuals with positive and negative antibodies on Tutuila.

<p>A. Wb123, B. Bm14.</p

Household locations of individuals with positive and negative antigen on Tutuila.

<p>A. Og4C3>128 units, B. Og4C3>32 units.</p