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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.

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.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.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).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.

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 a community-based survey and a WHO-recommended school-based transmission assessment survey (TAS). 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 explored using semivariograms, Kulldorf’s scan statistic and Getis-Ord Gi* statistics at 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 Kuldorff’s scan statistic, significant 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-Afao. 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 methods.Funding Statement: This work received financial support from the Coalition for Operational Research on Neglected Tropical Diseases (COR-NTD), which is funded at The Task Force for Global Health primarily by the Bill & Melinda Gates Foundation, by UK aid from the British government, and by the United States Agency for International Development through its Neglected Tropical Diseases Program. CLL was funded by an Australian National Health and Medical Research Council Fellowship (1109035). The funders had no role in interpretation of results, decision to publish, or preparation of the manuscript. MS is funded by a fellowship from the Westpac Scholars Trust.Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: This study was approved by the American Samoa Institutional Review Board and the Human Research Ethics Committee at the Australian National University (protocol number 2016/482).

Additional file 1: Figure S1. Distribution of the male and female population by age group (denominator is the total population aged 15 years and over, 2010 census). Figure S2. Frequency of households by asset index. Figure S3. Asset index by income category. Figure S4. Number of participants by county vs population size of county. Figure S5. Antigen and antibody prevalence by county. Figure S6. Antigen and antibody positivity, by short-term travel from and to American Samoa, last 12 months. Figure S7. Prevalence of antigen and antibody by whether or not MDA was taken. Table S1. Reported symptoms of LF. Table S2. Reported causes of LF. Table S3. MODEL B: multivariate logistic regression of risk factors affecting LF antigen and antibody positivity: sociodemographic and residence variables only (n = 639–642). Table S4. MODEL C: multivariate logistic regression of risk factors affecting LF antigen and antibody positivity: sociodemographic, residence and knowledge covariates, only participants who stated they had heard of LF (n = 537–540).

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% in HbA1c, an increase of $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. Electronic supplementary material The online version of this article (10.1186/s12960-019-0356-6) contains supplementary material, which is available to authorized users.

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, Author summary Lymphatic filariasis (LF) is a parasitic infection transmitted by mosquito bites. Globally, tens of millions are infected, with many disfigured and disabled by severe damage to their lymphatic systems, such as severe swelling of the legs (elephantiasis) or scrotum (hydrocele). The Global Programme to Eliminate LF (GPELF) aims to interrupt disease transmission through mass drug administration (MDA), and to control illness and suffering in affected persons. The World Health Organization recommends conducting Transmission Assessment Surveys (TAS) in school children aged 6 to 7 years to determine if infection rates have dropped to levels where disease transmission is no longer sustainable. From 2000–2006, American Samoa conducted MDA and made significant progress towards eliminating LF. However, despite passing TAS in 2011/2012 and 2015, surveys in 2016 showed evidence of resurgence. This study aimed to investigate the prevalence of anti-filarial antibodies in American Samoa in 2016; identify risk factors for testing positive for antigen, microfilaria and antibodies; and compare the efficiency of different sampling strategies for identifying persons who test positive. The sampling strategies that we compared included testing of 6–7 year-old children, population representative surveys of older age groups, and targeted surveys of high-risk groups such as older people, household members of infected children identified through TAS, and known hotspots. Based on our findings, we recommended that in addition to TAS, strategies that target high-risk populations and hotspots would strengthen surveillance and help countries achieve their goals of LF elimination.

Population mobility has been demonstrated to contribute to the persistent transmission and global diffusion of epidemics. In the Pacific Islands, population mobility is particularly important for emerging infectious diseases, disease elimination programs, and diseases spread by close contact. The extent of population mobility between American Samoa villages, Samoa districts and other countries was investigated based on travel data collected during community surveys in American Samoa in 2010 and 2014. Within American Samoa, workers commuted daily across the whole of the main island of Tutuila, with work hubs drawing from villages across the island. Of the 670 adult workers surveyed, 37% had traveled overseas in the past year, with 68% of trips to Samoa. Of children aged 8–13 years (n = 337), 57% had traveled overseas, with 55% of trips to Samoa. An extensive network of connections between American Samoa villages and Samoa districts was demonstrated, with most trips lasting one week to one month. Our study showed that populations in the Samoan islands are highly mobile, and quantified the extent and destinations of their travels. Our findings offer insight into the impact of population mobility on the transmission of infectious diseases and data to refine existing models of disease transmission in the Pacific islands.

Background Current WHO recommendations for lymphatic filariasis (LF) surveillance advise programs to implement activities to monitor for new foci of transmission after stopping mass drug administration (MDA). A current need in the global effort to eliminate LF is to standardize diagnostic tools and surveillance activities beyond the recommended transmission assessment survey (TAS). Methodology TAS was first conducted in American Samoa in 2011 (TAS 1) and a repeat TAS was carried out in 2015 (TAS 2). Circulating filarial antigen (CFA) and serologic results from both surveys were analyzed to determine whether interruption of LF transmission has been achieved in American Samoa. Principal findings A total of 1,134 and 864 children (5–10 years old) were enrolled in TAS 1 and TAS 2, respectively. Two CFA-positive children were identified in TAS 1, and one CFA-positive child was identified in TAS 2. Results of both surveys were below the threshold for which MDA was warranted. Additionally, 1,112 and 836 dried blood spots from TAS 1 and TAS 2, respectively were tested for antibodies to Wb123, Bm14 and Bm33 by luciferase immunoprecipitation system (LIPS) assay and multiplex bead assay. In 2011, overall prevalence of responses to Wb123, Bm14, and Bm33 was 1.0%, 6.8% and 12.0%, respectively. In 2015, overall prevalence of positive Bm14 and Bm33 responses declined significantly to 3.0% (p, Author summary Lymphatic filariasis (LF), endemic in 72 countries, is a debilitating mosquito-transmitted parasitic disease caused by filarial worms. The Global Program to Eliminate Lymphatic Filariasis (GPELF) aims to interrupt transmission through mass drug administration (MDA) and to reduce suffering caused by the disease. At the start of GPELF in 2000 it was estimated that approximately 1.4 billion people were at risk for infection. By the end of 2016, primarily through successful MDA programs, the global number of people requiring interventions was reduced to 856.4 million. Current recommendations by the World Health Organization for LF surveillance advise programs to implement activities to monitor for new foci of transmission after stopping MDA. A current need in the global effort to eliminate LF is to standardize diagnostic tools and surveillance activities beyond the recommended transmission assessment survey (TAS). Two TAS were conducted in American Samoa; first in 2011 (TAS 1) and repeated in 2015 (TAS 2). In our evaluation, circulating filarial antigen and serologic results from both surveys were analyzed to determine whether interruption of LF transmission has been achieved in American Samoa. Despite passing TAS 1 and TAS 2, clustering and persistence of positive antibody responses in schools may be an indication of ongoing transmission. Results from our evaluation suggest that serologic tools can have a role in guiding programmatic decision-making.

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.

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. Refereed/Peer-reviewed

Background As part of the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000–2006, and passed transmission assessment surveys in 2011–2012. We examined the seroprevalence and spatial epidemiology of LF post-MDA to inform strategies for ongoing surveillance and to reduce resurgence risk. Methods ELISA for LF antigen (Og4C3) and antibodies (Wb123, Bm14) were performed on a geo-referenced serum bank of 807 adults collected in 2010. Risk factors assessed for association with sero-positivity included age, sex, years lived in American Samoa, and occupation. Geographic clustering of serological indicators was investigated to identify spatial dependence and household-level clustering. Results Og4C3 antigen of >128 units (positive) were found in 0.75% (95% CI 0.3–1.6%) of participants, and >32 units (equivocal plus positive) in 3.2% (95% CI 0.6–4.7%). Seroprevalence of Wb123 and Bm14 antibodies were 8.1% (95% CI 6.3–10.2%) and 17.9% (95% CI 15.3–20.7%) respectively. Antigen-positive individuals were identified in all ages, and antibody prevalence higher in older ages. Prevalence was higher in males, and inversely associated with years lived in American Samoa. Spatial distribution of individuals varied significantly with positive and equivocal levels of Og4C3 antigen, but not with antibodies. Using Og4C3 cutoff points of >128 units and >32 units, average cluster sizes were 1,242 m and 1,498 m, and geographical proximity of households explained 85% and 62% of the spatial variation respectively. Conclusions High-risk populations for LF in American Samoa include adult males and recent migrants. We identified locations and estimated the size of possible residual foci of antigen-positive adults, demonstrating the value of spatial analysis in post-MDA surveillance. Strategies to monitor cluster residents and high-risk groups are needed to reduce resurgence risk. Further research is required to quantify factors contributing to LF transmission at the last stages of elimination to ensure that programme achievements are sustained., Author Summary Lymphatic filariasis (LF) is caused by infection with filarial worms that are transmitted by mosquito bites. Globally, 120 million people are affected, and 40 million are disfigured and disabled by complications such as severe swelling of the legs (elephantiasis). The Global Programme to Eliminate LF (GPELF) aims to interrupt disease transmission through mass drug administration (MDA), and to control illness and suffering in affected persons. In American Samoa, significant progress has been made towards LF elimination, and antigen prevalence has dropped from 16.5% in 1999 to