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

Detecting and confirming residual hotspots of lymphatic filariasis transmission in American Samoa 8 years after stopping mass drug administration

The Global Programme to Eliminate Lymphatic Filariasis (LF) aims to eliminate the disease as a public health problem by 2020 by conducting mass drug administration (MDA) and controlling morbidity. Once elimination targets have been reached, surveillance is critical for ensuring that programmatic gains are sustained, and challenges include timely identification of residual areas of transmission. WHO guidelines encourage cost-efficient surveillance, such as integration with other population-based surveys. In American Samoa, where LF is caused by Wuchereria bancrofti, and Aedes polynesiensis is the main vector, the LF elimination program has made significant progress. Seven rounds of MDA (albendazole and diethycarbamazine) were completed from 2000 to 2006, and Transmission Assessment Surveys were passed in 2010/2011 and 2015. However, a seroprevalence study using an adult serum bank collected in 2010 detected two potential residual foci of transmission, with Og4C3 antigen (Ag) prevalence of 30.8% and 15.6%. We conducted a follow up study in 2014 to verify if transmission was truly occurring by comparing seroprevalence between residents of suspected hotspots and residents of other villages. In adults from non-hotspot villages (N = 602), seroprevalence of Ag (ICT or Og4C3), Bm14 antibody (Ab) and Wb123 Ab were 1.2% (95% CI 0.6–2.6%), 9.6% (95% CI 7.5%-12.3%), and 10.5% (95% CI 7.6–14.3%), respectively. Comparatively, adult residents of Fagali’i (N = 38) had significantly higher seroprevalence of Ag (26.9%, 95% CI 17.3–39.4%), Bm14 Ab (43.4%, 95% CI 32.4–55.0%), and Wb123 Ab 55.2% (95% CI 39.6–69.8%). Adult residents of Ili’ili/Vaitogi/Futiga (N = 113) also had higher prevalence of Ag and Ab, but differences were not statistically significant. The presence of transmission was demonstrated by 1.1% Ag prevalence (95% CI 0.2% to 3.1%) in 283 children aged 7–13 years who lived in one of the suspected hotspots; and microfilaraemia in four individuals, all of whom lived in the suspected hotspots, including a 9 year old child. Our results provide field evidence that integrating LF surveillance with other surveys is effective and feasible for identifying potential hotspots, and conducting surveillance at worksites provides an efficient method of sampling large populations of adults.The project was funded by grants from the Australian Institute of Tropical Health and Medicine (www.aithm.jcu.edu.au, #13122014) and the Faculty of Medicine and Biomedical Sciences at the University of Queensland (www.uq.edu.au, #2127835). CLL was supported by an Australian National Health and Medical Research Council (www.nhmrc.gov.au) Fellowship (1109035

Prevalence and risk factors associated with lymphatic filariasis in American Samoa after mass drug administration

Background: In 2000, American Samoa had 16.5% prevalence of lymphatic filariasis (LF) antigenemia. Annual mass drug administration (MDA) was conducted using single-dose albendazole plus diethylcarbamazine from 2000 to 2006. This study presents the results of a 2007 population-based PacELF C-survey in all ages and compares the adult filarial antigenemia results of this survey to those of a subsequent 2010 survey in adults with the aim of improving understanding of LF transmission after MDA. Results: The 2007 C-survey used simple random sampling of households from a geolocated list. In 2007, the overall LF antigen prevalence by immunochromatographic card test (ICT) for all ages was 2.29% (95% CI 1.66–3.07). Microfilaremia prevalence was 0.27% (95% CI 0.09–0.62). Increasing age (OR 1.04 per year, 95% CI 1.02–1.05) was significantly associated with ICT positivity on multivariate analysis, while having ever taking MDA was protective (OR 0.39, 95% CI 0.16–0.96). The 2010 survey used a similar spatial sampling design. The overall adult filarial antigenemia prevalence remained relatively stable between the surveys at 3.32% (95% CI 2.44–4.51) by ICT in 2007 and 3.23 (95% CI 2.21–4.69) by Og4C3 antigen in 2010. However, there were changes in village-level prevalence. Eight village/village groupings had antigen-positive individuals identified in 2007 but not in 2010, while three villages/village groupings that had no antigen-positive individuals identified in 2007 had positive individuals identified in 2010. Conclusions: After 7 years of MDA, with four rounds achieving effective coverage, a representative household survey in 2007 showed a decline in prevalence from 16.5 to 2.3% in all ages. However, lack of further decline in adult prevalence by 2010 and fluctuation at the village level showed that overall antigenemia prevalence at a broader scale may not provide an accurate reflection of ongoing transmission at the village level.This publication was supported by a grant from the United States Agency for International Development (USAID) through NTD SC, a program of The Task Force for Global Health, Inc. Its contents are solely the responsibility of the authors and do not necessarily represent the views of The Task Force for Global Health, Inc., NTD SC or the USAID Funding for the 2007 survey was provided by the US Centers for Disease Prevention and Control. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Funding for the 2010 serology was provided by James Cook University and Glaxo Smith Kline to the JCU WHO Collaborating Centre for Control of Lymphatic Filariasis, Soil-transmitted Helminths and other NTDs. CLL was supported by an Australian National Health and Medical Research Council (NHMRC) Fellowship (1109035). The funder had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Demographic, socioeconomic and disease knowledge factors, but not population mobility, associated with lymphatic filariasis infection in adult workers in American Samoa in 2014

Background: Prevalence of lymphatic flariasis (LF) antigen in American Samoa was 16.5% in 1999. Seven rounds of mass drug administration (MDA) programmes between 2000 and 2006 reduced antigen prevalence to 2.3%. The most efcient methods of surveillance after MDA are not clear, but testing specifc at-risk groups such as adults may provide earlier warning of resurgence. The role of migration from LF endemic countries in maintaining transmission also needs investigation. Few studies have investigated knowledge about LF and how that relates to infection risk. This study aims to investigate associations between socio-demographics, population mobility, disease knowledge and LF infection risk. Methods: In 2014, we surveyed 670 adults aged 16–68 years (62% female) at two worksites in American Samoa. Sera were tested for LF antigen and antibodies (Bm14 and Wb123) by rapid test and/or ELISA. Multivariate logistic regression was used to assess association between seromarkers and demographic factors, household socioeconomic status (SES), residence, travel history, and knowledge of LF. Results: Overall, 1.8% of participants were positive for antigen, 11.8% for Bm14, 11.3% for Wb123 and 17.3% for at least one antibody. Recent travel outside American Samoa was not associated with positivity for any seromarker. Men had higher seroprevalence than women for all outcomes (any antibody: adjusted odds ratio (aOR)=3.49 (95% CI: 2.21–5.49). Those aged over 35 years (compared to 15–24 years) had higher prevalence of Bm14 antibody (aOR=3.75, 3.76 and 4.17 for ages 35–44, 45–54 and ≥55 years, respectively, P<0.05). Lower SES was associated with seropositivity (antigen: aOR=2.89, 95% CI: 1.09–7.69; either antibody: aOR=1.51, 95% CI: 1.12–2.05). Those who knew that mosquitoes transmitted LF had lower Wb123 antibody prevalence (aOR=0.55, 95% CI: 0.32–0.95). Conclusions: Opportunistic sampling of adults at worksites provided an efcient and representative way to assess prevalence and risk factors for LF in American Samoa and in hindsight, foreshadowed the resurgence of transmission. Risk of LF infection, detected by one or more serological markers, was not related to recent travel history, but was strongly associated with male gender, older age, lower SES, and lack of knowledge about mosquito transmission. These results could guide future eforts to increase MDA participation. Keywords: Lymphatic flariasis, American Samoa, Population mobility, Socioeconomic status, Disease knowledge, Sero-epidemiology, Surveillance, MosquitoThe project was funded by grants from the Australian Institute of Tropical Health and Medicine (www.aithm.jcu.edu.au, #13122014) and the Faculty of Medicine and Biomedical Sciences at the University of Queensland (www. uq.edu.au, #2127835). CLL was supported by an Australian National Health and Medical Research Council (www.nhmrc.gov.au) Fellowship (1109035)

Leptospirosis in American Samoa 2010: Epidemiology, environmental drivers, and the management of emergence

Leptospirosis has recently been reported as an emerging disease worldwide, and a seroprevalence study was undertaken in American Samoa to better understand the drivers of transmission. Antibodies indicative of previous exposure to leptospirosis were found in 15.5% of 807 participants, predominantly against three serovars that were not previously known to occur in American Samoa. Questionnaires and geographic information systems data were used to assess behavioral factors and environmental determinants of disease transmission, and logistic regression was used to identify factors associated with infection. Many statistically significant factors were consistent with previous studies, but we also showed a significant association with living at lower altitudes (odds ratio [OR] = 1.53, 95% confidence interval [CI]: 1.03-2.28), and having higher numbers of piggeries around the home (OR = 2.63, 95% CI: 1.52-4.40). Our findings support a multifaceted approach to combating the emergence of leptospirosis, including modification of individual behavior, but importantly also managing the evolving environmental drivers of risk

Prevalence and risk factors associated with lymphatic filariasis in American Samoa after mass drug administration

Abstract Background In 2000, American Samoa had 16.5% prevalence of lymphatic filariasis (LF) antigenemia. Annual mass drug administration (MDA) was conducted using single-dose albendazole plus diethylcarbamazine from 2000 to 2006. This study presents the results of a 2007 population-based PacELF C-survey in all ages and compares the adult filarial antigenemia results of this survey to those of a subsequent 2010 survey in adults with the aim of improving understanding of LF transmission after MDA. Results The 2007 C-survey used simple random sampling of households from a geolocated list. In 2007, the overall LF antigen prevalence by immunochromatographic card test (ICT) for all ages was 2.29% (95% CI 1.66–3.07). Microfilaremia prevalence was 0.27% (95% CI 0.09–0.62). Increasing age (OR 1.04 per year, 95% CI 1.02–1.05) was significantly associated with ICT positivity on multivariate analysis, while having ever taking MDA was protective (OR 0.39, 95% CI 0.16–0.96). The 2010 survey used a similar spatial sampling design. The overall adult filarial antigenemia prevalence remained relatively stable between the surveys at 3.32% (95% CI 2.44–4.51) by ICT in 2007 and 3.23 (95% CI 2.21–4.69) by Og4C3 antigen in 2010. However, there were changes in village-level prevalence. Eight village/village groupings had antigen-positive individuals identified in 2007 but not in 2010, while three villages/village groupings that had no antigen-positive individuals identified in 2007 had positive individuals identified in 2010. Conclusions After 7 years of MDA, with four rounds achieving effective coverage, a representative household survey in 2007 showed a decline in prevalence from 16.5 to 2.3% in all ages. However, lack of further decline in adult prevalence by 2010 and fluctuation at the village level showed that overall antigenemia prevalence at a broader scale may not provide an accurate reflection of ongoing transmission at the village level