National University of Samoa

Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally scalable analytical pipeline for functionally informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits in 61,838 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered and replicated new associations with lipid traits missed by single-trait analysis.

Background Sensitive diagnostic tools that signal lymphatic filariasis (LF) transmission are needed to monitor the progress of LF elimination programs. Anti-filarial antibody (Ab) markers could be more sensitive than antigen (Ag) point-of-care tests for monitoring LF transmission in some settings. This study aimed to investigate the sensitivity of anti-filarial Abs for detecting signals of LF transmission in Samoa by i) investigating the sensitivity and specificity of Ab to identify Ag-positives; ii) estimating the average number needed to test (NNTest av ) to identify LF-seropositives (seropositive for Ag and/or any Ab), and iii) compare the efficiency of the different serological indicators by target age group and sampling design. Methods A community-based serological survey of participants aged ≥5 years was conducted 1.5-3.5 months following the first round of triple-drug mass drug administration in Samoa in 2018, covering 35 primary sampling units (PSUs) (30 randomly selected and five purposively selected ‘suspected hotspots’). Ag-positivity was detected using Alere Filariasis Test Strips, and Ab-seropositivity ( Bm14 , Wb123 , Bm33 Abs) were measured using multiplex bead assays. Seroprevalence was adjusted for study design and standardised for age and gender. NNTest av was calculated using the formula 1/p, where p was the adjusted seroprevalence for each subgroup. Results Of 3795 participants (mean age: 20.7; 51.2% female), 1892 (49.9%) were LF-seropositive. If Ag alone was used to identify LF-seropositives, only 5% (117/1892) would be identified. Of the three Ab seromarkers, Bm14 Ab had the highest area under the Receiver-Operating Characteristic Curve ([ROC]=0.88) to classify participants as Ag-positive, followed by Wb123 Ab (ROC=0.83) and Bm33 Ab (ROC=0.76). Participants aged ≥10 years had lower NNTest av compared to participants aged 5-9 years for all seromarkers. NNTest av was lower in purposively versus randomly selected PSUs. Conclusions All Ab seromarkers had high ROC values to classify patients as Ag-positive and may be useful tools for LF surveillance in some settings. However, further research is required to fully understand how best Ab serosurveillance can be incorporated into LF elimination programmes.

Background There is growing evidence that climate-related disasters increase rates of intimate partner violence (IPV) against women. However, there are only limited understandings of the size and nature of such associations needed to inform appropriate programming. Gaps in evidence are particularly pronounced in the Pacific—one of the regions most at risk of increased disasters from climate change. Methods We analysed data from 450 men and 707 women collected as part of cross-sectional study of IPV experience, risk and protective factors in rural Samoan villages. Data were analysed using multivariable logistic regression models to assess associations between (1) men’s and women’s exposure to climate-related disasters and their mental health and (2) women’s exposure to climate-related disasters and their risk of IPV in the previous 12 months. Findings Reported symptoms of depression and anxiety were associated with having experienced a disaster. Those who reported experiencing a disaster 2–3 times had 61% greater odds of reporting depression (OR 1.61; 95% CI 1.00 to 2.58) and 88% greater odds of reporting anxiety (OR 1.88; 95% CI 1.01 to 3.49), in comparison to those who reported never experiencing a disaster. Women who reported experiencing 2–3 disasters had more than twice the odds of experiencing recent IPV (adjusted OR, aOR 2.37, 95% CI 1.77 to 3.19), while those who reported experiencing 4+ disasters had over 8 times the odds (aOR 8.12; 95% CI 2.02 to 32.61). Interpretation This is one of the first studies in the Pacific region to provide quantitative evidence of associations between exposure to climate-related events and women’s experiences of IPV. We identify a clear dose–response relationship between higher exposure to climate-related events and an increased risk of IPV for women. This points to the role of cumulative stress from experiencing repeat disasters in driving higher rates of IPV in climate-affected regions.

As we navigate the complex landscape of global public health in 2024, this article provides a comprehensive exploration of challenges, ranging from infectious diseases, mental health, and substance use to environmental sustainability and emerging technologies. The aftermath of the COVID‐19 pandemic underscores the critical need to strengthen health systems, increase public financing, and foster effective international collaboration. The intricacies of global geopolitics, diplomacy, and public health highlight the importance of countries that do not address shared challenges through enhanced cooperative mechanisms and joint initiatives. From the imperative of global health security to the persistence of non‐communicable diseases and health disparities, this study delves into multifaceted issues, advocating for collective action, targeted interventions, and a commitment to prioritizing public health on a global scale. Focusing on addressing root causes and fostering equity, this study emphasizes the role of sustainable practices, community engagement, and intersectionality of research in building a resilient global health landscape. In this dynamic environment, 2024 calls for a unified global vision that encourages nations to collaborate more effectively to build a healthier and more resilient global community, ultimately paving the way for a future characterized by a shared commitment to public health challenges.

Introduction Lymphatic filariasis (LF) is a neglected tropical disease caused by parasitic worms, transmitted via mosquito bites. Significant global efforts have led to the interruption of LF transmission, with eight of the 16 previously endemic Pacific Island countries and territories (PICTs) validated by WHO as having eliminated the disease as a public health problem. Post-validation surveillance (PVS) is recommended to verify the absence of a resurgence in transmission; however, there are no guidelines on how to implement such surveillance effectively. Aim This protocol outlines a research study that aims to explore, synthesise, and prioritise the perspectives of LF program staff from LF-eliminated PICTs. The study will focus on identifying the challenges faced in implementing PVS in the PICT settings and determining corresponding context-relevant operational research priorities. Method The study will employ a nominal group technique (NGT) involving representatives from LF-eliminated PICTs. The NGT will adhere to a structured process for generating, ranking, and prioritising ideas, followed by group discussions, debates, and the collation of shared views. Discussion The research will provide insights into the most significant challenges faced in implementing PVS in the PICTs. It will also identify priority areas where operational research is required to inform policy and practice. To our knowledge, this study is the first to apply a rigorous consensus group method to distil challenges and research priorities for LF PVS in PICTs. We expect that this research will inform the development of national and regional LF guidelines.

Women are globally underrepresented as political leaders; as of January 2023, only 17 countries had a woman head of government. Included in this small group is Samoa, which elected Fiame Naomi Mata’afa as its first woman prime minister in 2021 after a fiercely contested election and subsequent protracted legal disputes centered around interpretations of Samoa’s 10% gender quota. Drawing on data from the Pacific Attitudes Survey, the first large-scale, nationally representative popular political attitudes survey conducted in the Pacific region, this article examines how the political environment in Samoa shapes opportunities for women’s political participation and leadership. Using the theoretical framework of cohabitation, it finds that although there is an enabling environment for women’s participation and leadership in formal politics, women’s access to decision-making spaces more broadly is still constrained by norms of traditional leadership. This speaks to traditional and nontraditional political norms and practices that coexist, at times uneasily, alongside one another.

The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P < 6×10−10$6\times {10}^{-10}$ after conditioning on previously reported variants, with effect sizes ranging from −7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based associations proximal to HMGA1 containing variants associated with a 5 cm taller height and of highly-conserved variants in MIR497HG on chromosome 17. We have developed an approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data associated with complex traits.

The impact of climate change on human societies is now well recognised. However, little is known about how climate change alters health conditions over time. National level data around climate shocks and subsequent rates of intimate partner violence (IPV) could have relevance for resilience policy and programming. We hypothesise that climate shocks are associated with a higher national prevalence of IPV two years following a shock, and that this relationship persists for countries with different levels of economic development. We compiled national data for the prevalence of IPV from 363 nationally representative surveys from 1993 to 2019. These representative data from ever-partnered women defined IPV incidence as any past-year act of physical and/or sexual violence. We also compiled data from the Emergency Events Database (EM DAT) on the national frequency of eight climate shocks from 1920 to 2022 within 190 countries. Using exploratory factor analysis, we fit a three-factor latent variable composed of climate shock variables. We then fit a structural equation model from climate shocks (lagged by two years) and IPV incidence, controlling for (log) national gross domestic product (GDP). National data representing 156 countries suggest a significant relationship between IPV and a climate factor (Hydro-meteorological) composed of storms, landslides and floods (standardised estimate = 0·32; SE = 0·128; p = 0·012). GDP has a moderately large cross-sectional association with IPV (estimate = -0·529; SE = 0·047; p = 0·0001). Other climate shocks (Geological: earthquakes/volcanos; Atmospheric: wildfire/droughts/extreme temperature) had no measurable association with IPV. Model fit overall was satisfactory (RMSEA = 0·064 (95%CI: 0·044–0·084); CFI = 0·91; SRMR = 0·063). Climate shocks have a longitudinal association with IPV incidence in global population-based data. This suggests an urgent need to address the higher prevalence of IPV likely to come about through climate shocks due to climate change. Our analysis offers one way policy makers could track national progress using existing data.

Sleep apnea is a global public health concern, but little research has examined this issue in low- and middle-income countries, including Samoa. The purpose of this study was to examine the sample prevalence and characteristics of sleep apnea using a validated home sleep apnea device (WatchPAT, Itamar) and explore factors that may influence sleep health in the Samoan setting. This study used data collected through the Soifua Manuia (“Good Health”) study, which investigated the impact of the body mass index (BMI)-associated genetic variant rs373863828 in CREBRF on metabolic traits in Samoan adults (sampled to overrepresent the obesity-risk allele of interest). A total of 330 participants had sleep data available. Participants (53.3 % female) had a mean (SD) age of 52.0 (9.9) years and BMI of 35.5 (7.5) kg/m², and 36.3 % of the sample had type 2 diabetes. Based on the 3 % and 4 % apnea hypopnea indices (AHI) and the 4 % oxygen desaturation index (ODI), descriptive analyses revealed moderate to severe sleep apnea (defined as ≥15 events/hr) in 54.9 %, 31.5 %, and 34.5 % of the sample, respectively. Sleep apnea was more severe in men (e.g., AHI 3 % ≥15 in 61.7 % of men and 48.9 % of women). Correction for non-representational sampling related to the CREBRF obesity-risk allele resulted in only slightly lower estimates. Multiple linear regression linked a higher number of events/hr to higher age, male sex, higher BMI, higher abdominal-hip circumference ratio, and geographic region of residence. Further research and an increased focus on equitable and affordable diagnosis and access to treatment are crucial to addressing sleep apnea in Samoa and globally.

Background To monitor the progress of lymphatic filariasis (LF) elimination programmes, field surveys to assess filarial antigen (Ag) prevalence require access to reliable, user-friendly rapid diagnostic tests. We aimed to evaluate the performance of the new Q Filariasis Antigen Test (QFAT) with the currently recommended Filariasis Test Strip (FTS) for detecting the Ag of Wuchereria bancrofti, the causative agent of LF, under field laboratory conditions. Methodology/Principal findings During an LF survey in Samoa, 344 finger-prick blood samples were tested using FTS and QFAT. Microfilariae (Mf) status was determined from blood slides prepared from any sample that reported Ag-positive by either Ag-test. Each test was re-read at 1 hour and the next day to determine the stability of results over time. Overall Ag-positivity by FTS was 29.0% and 30.2% by QFAT. Concordance between the two tests was 93.6% (kappa = 0.85). Of the 101 Mf slides available, 39.6% were Mf-positive, and all were Ag-positive by both tests. Darker test line intensities from Ag-positive FTS were found to predict Mf-positivity (compared to same/lighter line intensities). QFAT had significantly higher reported test result changes than FTS, mostly reported the next day, but fewer changes were reported between 10 minutes to 1hour. The field laboratory team preferred QFAT over FTS due to the smaller blood volume required, better usability, and easier readability. Conclusion/Significance QFAT could be a suitable and user-friendly diagnostic alternative for use in the monitoring and surveillance of LF in field surveys based on its similar performance to FTS under field laboratory conditions.

To investigate the palliative care experiences of Samoan patients with cancer and the impact these experiences have on their quality of life. Methods This qualitative interview study was part of a larger study that interviewed19 participants recruited among patients with cancer registered with Samoa Cancer Society, or patients recently discharged from the main tertiary hospital in Samoa. Interview transcripts were reviewed, and the research team identified the key palliative-care-related themes. Results Analysis led to the generation of the following key themes: living with pain; resource constraints; support from family and faith; and interactions with healthcare professionals. Most participants were experiencing unresolved pain as a result of poor health knowledge, lack of access to medications and practical issues, such as financial limitations and lack of transport. Participants also reported a lack of resources, including financial constraints, as a significant barrier to effective healthcare. Sources of support for patients with cancer were most commonly strong family relationships and religious faith. Although it was difficult for the participants to access care from healthcare professionals, they found that honest communication about their condition was comforting. However, they were frustrated if they felt communication was unsatisfactory. Conclusion This study provides much needed evidence on the issues that affect the quality of life patients with cancer receiving palliative care and their families in Samoa. It also highlights the intersectionality of these issues and how this compounds the patient experience. Practical recommendations for improving palliative care lie in a few key areas, including a need for improved access to opioids and support for family caregivers. However, from a systemic perspective, the way forward should lie in harnessing the strengths of Samoan culture, including the strong sense of family and the role of religion, to provide support and care for palliative patients.

Objectives Circulating filarial antigen (Ag) is used by elimination programs to monitor lymphatic filariasis (LF) transmission; however, antifilarial antibodies (Ab) may be more sensitive than Ag for detecting LF. Our objectives were to describe Ab seroprevalence, identify risk factors for Ab seropositivity, investigate age-specific associations between Ag and Ab, and evaluate geographic clustering of seropositivity. Methods Community-based serosurveys of participants aged ≥5 years were conducted in 35 primary sampling units (PSUs). Ag-positivity was detected using Alere™ Filariasis Test Strips and Ab-seropositivity using multiplex bead assays. Seroprevalence was adjusted for study design. Results Of 3795 participants (range:5-90 years), adjusted prevalence for Ag, Bm14 Ab, Wb123 Ab, and Bm33 Ab were 3.7% (n=117), 20.3% (n=583), 32.2% (n=987), and 51.0% (n=1659), respectively. Male sex, older age, and residents of suspected hotspots had higher odds of seropositivity to all seromarkers. Seroprevalence was lower in 5-9-year-olds vs ≥10-year-olds (P<0.001). Clustering was significantly higher in households (intra-cluster correlation for Ag:0.45; Bm14 Ab:0.32; Bm33 Ab:0.31; Wb123 Ab:0.29) compared to PSUs or region. Conclusions Abs enabled identification of risk factors for seropositivity and geographical clustering to inform targeted interventions for LF programmes. Further research is needed to define Ab thresholds for active versus past infection and elimination targets.

Background Lymphatic filariasis (LF) remains a significant global issue. To eliminate LF as a public health problem, the World Health Organization (WHO) recommends multiple rounds of mass drug administration (MDA). In certain scenarios, including when elimination targets have not been met with two-drug MDA, triple-drug MDA (using ivermectin, diethylcarbamazine and albendazole) is recommended. In this study, we report on antigen (Ag) and microfilaria (Mf) prevalence in eight primary sampling units (PSUs) in Samoa 4.5 years after one round of triple-drug MDA. Methodology In 2023, community surveys were conducted in eight PSUs that had been surveyed previously in 2018 (between 1.5 and 3.5 months post triple-drug MDA) and 2019 (six to eight-months post triple-drug MDA). Fifteen houses were randomly selected in each PSU with household members aged ≥ 5 years invited to participate. Blood samples were tested for Ag and Mf. Principal findings Ag-positive participants were observed in six of the eight PSUs, and Ag prevalence was significantly above the 1% threshold in four PSUs. The presence of Mf-positive participants in five PSUs confirms the presence of residual active infections. Conclusions/Significance This study provides evidence of persistent LF transmission in Samoa 4.5 years after one round of triple-drug MDA, confirming that one round was insufficient for interruption of transmission in this setting. Our findings highlight the negative impact of delaying MDA rounds, for example, due to public health emergencies.

This chapter is about the role of mutual mental health in sustaining wellbeing during back-to-back public health crises—the measles outbreak and the COVID-19 pandemic—in Samoa. We write this chapter as an exercise in mutual narrative creation, which we approached through a combination of Zoom-based conversations, individual reflections, informal conversations, and writing and rewriting together. We draw out the ways that wellbeing is created through mutual commitment to family, co-workers, and church as various, often overlapping spheres of community. Ultimately, our exploration together revealed something long known by Pacific scholars and practitioners—biomedical notions of wellbeing at the intersection of mental health tend to be individualised, which negates the role of family and community that are so crucial in terms of what shapes and constrains wellbeing in Samoa. We refer to this as mutual mental health.

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.

We examined whether the A allele of CREBRF rs373863828, which is common in Samoans but rare in non-Pacific Islanders, predicts better cognition. Samoan interviewers interviewed participants who were 60 years and older, lived in the Independent State of Samoa, and had four Samoan grandparents. The AA genotype significantly predicted older Samoans’ better subjective and objective cognition; it also contributed 5.9 times more than APOE to subjective cognition and 12.3 times more than APOE to objective cognition, in effect-size analyses. Since CREBRF operates in the universal CREB system, the findings could inform general aging-cognition resilience.

Background Current research suggests that energy transfer through human milk influences infant nutritional development and initiates metabolic programming, influencing eating patterns into adulthood. To date, this research has predominantly been conducted among women in high income settings and/or among undernourished women. We will investigate the relationship between maternal body composition, metabolic hormones in human milk, and infant satiety to explore mechanisms of developmental satiety programming and implications for early infant growth and body composition in Samoans; a population at high risk and prevalence for overweight and obesity. Our aims are (1) to examine how maternal body composition influences metabolic hormone transfer from mother to infant through human milk, and (2) to examine the influences of maternal metabolic hormone transfer and infant feeding patterns on early infant growth and satiety. Methods We will examine temporal changes in hormone transfers to infants through human milk in a prospective longitudinal cohort of n = 80 Samoan mother-infant dyads. Data will be collected at three time points (1, 3, & 4 months postpartum). At each study visit we will collect human milk and fingerpick blood samples from breastfeeding mother-infant dyads to measure the hormones leptin, ghrelin, and adiponectin. Additionally, we will obtain body composition measurements from the dyad, observe breastfeeding behavior, conduct semi-structured interviews, and use questionnaires to document infant hunger and feeding cues and satiety responsiveness. Descriptive statistics, univariate and multivariate analyses will be conducted to address each aim. Discussion This research is designed to advance our understanding of variation in the developmental programming of satiety and implications for early infant growth and body composition. The use of a prospective longitudinal cohort alongside data collection that utilizes a mixed methods approach will allow us to capture a more accurate representation on both biological and cultural variables at play in a population at high risk of overweight and obesity.

Background : The prevalence of obesity-related cardiometabolic disease in Samoa is among the highest globally. While physical activity is a modifiable risk factor for obesity-related disease, little is known about physical activity levels among adult Samoans. Using wrist-worn accelerometer-based devices, this study aimed to characterize physical activity among Samoan adults. Methods : Samoan adults (n = 385; 55% female, mean [SD] age 52 [10] y) wore Actigraph GT3X+ devices for 7 to 10 days. General linear models were used to examine mean daily minutes of sedentary time, light physical activity, and moderate to vigorous physical activity by various participant characteristics. Results : Time spent in moderate to vigorous physical activity did not differ statistically between men (88 [5] min; 95% confidence interval [CI], 80–97) and women (78 [4] min; 95% CI, 70–86; P = .08). Women, however, spent more time than men in light physical activity: 380 (7) minutes (95% CI, 367–393) versus 344 (7) minutes (95% CI, 329–358; P < .001). While there were no differences in physical activity by census region, education, or occupation among women, men in urban areas spent significantly less time in moderate to vigorous physical activity than those in peri-urban and rural areas ( P = .015). Women with class II/III obesity spent more time in sedentary activities than those with healthy weight or overweight/class I obesity ( P = .048). Conclusions : This study characterizes physical activity among Samoan adults and highlights variation by sex, urbanicity, and weight status. In providing initial device-measured estimates of physical activity in Samoa, this analysis establishes a baseline from which the success of future attempts to intervene on physical activity may be assessed.