Genetic epidemiology of lymphatic filariasis in American Samoa after mass drug administration.
Over 892 million people in 48 countries are at risk of infection by nematodes that cause lymphatic filariasis. As part of the Global Programme to Eliminate Lymphatic Filariasis, mass drug administration is distributed to communities until surveillance indicates infection rates are below target prevalence thresholds. In some countries, including American Samoa, lymphatic filariasis transmission persists despite years of mass drug administration and/or has resurged after cessation. Nothing is known about the population genetics of Wuchereria bancrofti worms in Polynesia, or whether local transmission is persisting and/or increasing due to inadequate mass drug administration coverage, expansion from residual hotspots, reintroduction from elsewhere, or a combination. We extracted DNA from microfilariae on blood slides collected during prevalence surveys in 2014 and 2016, comprising 31 pools of five microfilariae from 22 persons living in eight villages. We sequenced 1104 bp across three mitochondrial markers (ND4, COI, CYTB). We quantified parasite genetic differentiation using variant calls and estimated haplotypes using principal components analysis, F-statistics, and haplotype networks. Of the variants called, all but eight were shared across the main island of Tutuila, and three of those were from a previously described hotspot village, Fagali'i. Genotypic data did not support population genetic structure among regions or villages in 2016, although differences were observed between worms collected in Fagali'i in 2014 and those from 2016. Because estimated haplotype frequency varied between villages, these statistics suggested genetic differentiation, but were not consistent among villages. Finally, haplotype networks demonstrated American Samoan sequence clusters were related to previously published sequences from Papua New Guinea. These are, to our knowledge, the first reports of W. bancrofti genetic variation in Polynesia. The resurgent parasites circulating on the main island of American Samoa represent a single population. This study is the first step towards investigating how parasite population structure might inform strategies to manage resurgence and elimination of lymphatic filariasis.
Related studies
To evaluate strategies to improve the sensitivity of the TAS for detecting evidence of recent lymphatic filariasis transmission in an evaluation unit (EU). The TAS Strengthening Study in American Samoa is designed to assess additional indicators that may be added to the current TAS platform in order to strengthen the resulting stopping or surveillance decisions. A comprehensive analysis will be conducted to understand the correlation between antigen and antibody in adults and children with the mosquito data. A spatial analysis looking at microfoci of infection will also be conducted. Xenomonitoring work to assess Aedes mosquitoes is underway.
Preliminary Findings and Lessons Learned
The ultimate goal of this study is to strengthen the existing TAS platform so that the programs can be more confident with their stopping and surveillance decisions. In order to strengthen the existing TAS platform we need to better understand which target population(s) and diagnostic indicator(s) are best-suited for identifying areas with persistent transmission that is not expected to cease on its own, knowing that the answer may vary according the primary vector and stage of the program. In the selected sites a community-based TAS was conducted using the standard sampling of 6-7 year olds while a community TAS (individuals >8 years) was conducted concurrently. All samples were tested via FTS and DBS (for Wb123 ELISA). In these same communities a molecular xenomonitoring study will take place and the mosquitoes will be tested for filarial DNA to relate back to the human specimens. To date human sampling has been completed in all sites and laboratory analysis of the specimens is complete. Mosquito collection has been completed in Haiti and Tanzania and the PCR analysis has been completed in Haiti and is planned for Tanzania (pending the arrival of a new PCR machine). In American Samoa xenomonitoring has been delayed due to weather conditions and arbovirus outbreaks; work is expected to commence spring 2018.