Lymphatic Filariasis in 2016 in American Samoa: Identifying Clustering and Hotspots Using Non-Spatial and Three Spatial Analytical Methods

Background: American Samoa completed seven rounds of mass drug administration from 2000–2006 as part of the Global Programme to Eliminate Lymphatic Filariasis (LF). However, resurgence was confirmed in 2016 through WHO-recommended school-based transmission assessment survey and a community-based survey. This paper uses data from the 2016 community survey to compare different spatial and non-spatial methods to characterise clustering and hotspots of LF. Method: Non-spatial clustering of infection markers (antigen [Ag], microfilaraemia [Mf], and antibodies (Ab [Wb123, Bm14, Bm33]) was assessed using intra-cluster correlation coefficients (ICC) at household and village levels. Spatial dependence, clustering and hotspots were examined using semivariograms, Kulldorf’s scan statistic and Getis-Ord Gi* statistics based on locations of surveyed households. Results: The survey included 2671 persons (750 households, 730 unique locations in 30 villages). ICCs were higher at household (0.20–0.69) than village levels (0.10–0.30) for all infection markers. Semivariograms identified significant spatial dependency for all markers (range 207–562 metres). Using Kulldorff’s scan statistic, significant spatial clustering was observed in two previously known locations of ongoing transmission: for all markers in Fagali’i and all Abs in Vaitogi. Getis-Ord Gi* statistic identified hotspots of all markers in Fagali’i, Vaitogi, and Pago Pago-Anua areas. A hotspot of Ag and Wb123 Ab was identified around the villages of Nua-Seetaga-Asili. Bm14 and Bm33 Ab hotspots were seen in Maleimi and Vaitogi-Ili’ili-Tafuna. Conclusion: Our study demonstrated the utility of different non-spatial and spatial methods for investigating clustering and hotspots, the benefits of using multiple infection markers, and the value of triangulating results between method

Comparison of immunochromatographic test (ICT) and filariasis test strip (FTS) for detecting lymphatic filariasis antigen in American Samoa, 2016

Circulating filarial antigen (Ag) prevalence, measured using rapid point-of-care tests, is the standard indicator used for monitoring and surveillance in the Global Program to Eliminate Lymphatic Filariasis. In 2015, the immunochromatographic test (ICT) was replaced with the filariasis test strip (FTS), which has higher reported sensitivity. Despite differences in sensitivity, no changes in recommended surveillance targets were made when the FTS was introduced. In 2016, we conducted lymphatic filariasis surveys in American Samoa using FTS, which found higher Ag prevalence than previous surveys that used ICT. To determine whether the increase was real, we assessed the concordance between FTS and ICT results by paired testing of heparinised blood from 179 individuals (63% FTS-positive). ICT had 93.8% sensitivity and 100% specificity for identifying FTS-positive persons, and sensitivity was not associated with age, gender, or presence of microfilariae. Based on these findings, if ICT had been used in the 2016 surveys, the results and interpretation would have been similar to those reported using FTS. American Samoa would have failed Transmission Assessment Survey (TAS) of Grade 1 and 2 children with either test, and community prevalence would not have been significantly different (4.1%, 95% CI, 3.3–4.9% with FTS vs. predicted 3.8%, 95%, CI: 3.1–4.6% with ICT)

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 administrations (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 Wb 123 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 hotspost, 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 hostpots, and conducting surveillance at worksites provides an efficient method of sampling large populations of adults

Potential strategies for strengthening surveillance of lymphatic filariasis in American Samoa after mass drug administration: reducing ‘number needed to test’ by targeting older age groups, hotspots, and household members of infected persons

Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000–2006. Despite passing Transmission Assessment Surveys (TAS) in 2011/2012 and 2015, American Samoa failed TAS-3 in 2016, with antigen (Ag) prevalence of 0.7% (95%CI 0.3–1.8%) in 6–7 year-olds. A 2016 community survey (Ag prevalence 6.2% (95%CI 4.4–8.5%) in age ≥8 years) confirmed resurgence. Using data from the 2016 survey, this study aims to i) investigate antibody prevalence in TAS-3 and the community survey, ii) identify risk factors associated with being seropositive for Ag and anti-filarial antibodies, and iii) compare the efficiency of different sampling strategies for identifying seropositive persons in the post-MDA setting. Antibody prevalence in TAS-3 (n = 1143) were 1.6% for Bm14 (95%CI 0.9–2.9%), 7.9% for Wb123 (95%CI 6.4–9.6%), and 20.2% for Bm33 (95%CI 16.7–24.3%); and in the community survey (n = 2507), 13.9% for Bm14 (95%CI 11.2–17.2%), 27.9% for Wb123 (95%CI 24.6–31.4%), and 47.3% for Bm33 (95%CI 42.1–52.6%). Multivariable logistic regression was used to identify risk factors for being seropositive for Ag and antibodies. Higher Ag prevalence was found in males (adjusted odds ratio [aOR] 3.01), age ≥18 years (aOR 2.18), residents of Fagali’i (aOR 15.81), and outdoor workers (aOR 2.61). Ag prevalence was 20.7% (95%CI 9.7–53.5%) in households of Ag-positive children identified in TAS-3. We used NNTestav (average number needed to test to identify one positive) to compare the efficiency of the following strategies for identifying persons who were seropositive for Ag and each antibody: i) TAS of 6–7 year-old children, ii) population representative surveys of older age groups, and iii) targeted surveillance of subpopulations at higher risk of being seropositive (older ages, householders of Ag-positive TAS children, and known hotspots). For Ag, NNTestav ranged from 142.5 for TAS, to <5 for households of index children. NNTestav was lower in older ages, and highest for Ag, followed by Bm14, Wb123 and Bm33 antibodies. We propose a multi-stage surveillance strategy, starting with population-representative sampling (e.g. TAS or population representative survey of older ages), followed by strategies that target subpopulations and/or locations with low NNTestav. This approach could potentially improve the efficiency of identifying remaining infected persons and residual hotspots. Surveillance programs should also explore the utility of antibodies as indicators of transmission

Potential use of antibodies to provide an earlier indication of lymphatic filariasis resurgence in post–mass drug ad ministration surveillance in American Samoa

Background: Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted 7 rounds of mass drug administration (MDA) between 2000 and 2006. The territory passed transmission assessment surveys (TASs) in 2011 (TAS-1) and 2015 (TAS-2). In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Abs) may have provided a timelier indication of LF resurgence in American Samoa. Methods: We examined school-level antigen (Ag) and Ab status (presence/absence of Ag- and Ab-positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, and Bm33 Ags at each TAS. Pearson chi-square test and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3. Results: Schools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% confidence interval [CI] 1.2–512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33, or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0–24.5). Conclusion: Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in surveillance after MDA and decision making should be further investigated in other settings

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)

Cost-effectiveness analysis of a cluster-randomized, culturally tailored, community health worker home-visiting diabetes intervention versus standard care in American Samoa

Abstract Background Type 2 diabetes mellitus (T2DM) is highly prevalent in American Samoa. Community health worker (CHW) interventions may improve T2DM care and be cost-effective. Current cost-effectiveness analyses (CEA) of CHW interventions have either overlooked important cost considerations or not been based on randomized clinical trials (RCTs). The Diabetes Care in American Samoa (DCAS) intervention which occurred in 2009–2010 was a cluster-randomized, culturally tailored, home-visiting CHW intervention and improved HbA1c levels. Objective To analyze the cost-effectiveness of the DCAS intervention against standard care using a RCT in a low-resource setting. Methods We collected clinical, utilization, and cost data over 2 years and modeled quality-adjusted life years (QALYs) gained based on the RCT glycated hemoglobin (HbA1c) improvements. We calculated an incremental cost-effectiveness ratio (ICER) from the societal perspective over a 2-year time horizon and reported all costs in 2012 USD ($). Results Two hundred sixty-eight American Samoans diagnosed with T2DM were cluster randomized into the CHW (n = 104) or standard care control (n = 164) arms. The CHW arm had a mean reduction of 0.53$594 in cost, and an increase of 0.05 QALYs. The ICER for the CHW arm compared to the control arm was $1121 per percentage point HbA1c reduced and$13 191 per QALY gained. Conclusions Compared to a variety of willingness-to-pay thresholds from $39 000 to$154 353 per QALY gained, this ICER shows that the CHW intervention is highly cost-effective. Future studies of the cost-effectiveness of CHW T2DM interventions in similar settings should model lifetime costs and QALYs gained to better assess long-term cost-effectiveness. Trial registration ClinicalTrials.gov, ID NCT00850824. Registered 9 February 2009, https://clinicaltrials.gov/ct2/show/NCT00850824