Drug resistance profiling of asymptomatic and low-density Plasmodium falciparum malaria infections on Ngodhe island, Kenya, using custom dual-indexing next-generation sequencing.

Malaria control initiatives require rapid and reliable methods for the detection and monitoring of molecular markers associated with antimalarial drug resistance in Plasmodium falciparum parasites. Ngodhe island, Kenya, presents a unique malaria profile, with lower P. falciparum incidence rates than the surrounding region, and a high proportion of sub-microscopic and low-density infections. Here, using custom dual-indexing and Illumina next generation sequencing, we generate resistance profiles on seventy asymptomatic and low-density P. falciparum infections from a mass drug administration program implemented on Ngodhe island between 2015 and 2016. Our assay encompasses established molecular markers on the Pfcrt, Pfmdr1, Pfdhps, Pfdhfr, and Pfk13 genes. Resistance markers for sulfadoxine-pyrimethamine were identified at high frequencies, including a quintuple mutant haplotype (Pfdhfr/Pfdhps: N51I, C59R, S108N/A437G, K540E) identified in 62.2% of isolates. The Pfdhps K540E biomarker, used to inform decision making for intermittent preventative treatment in pregnancy, was identified in 79.2% of isolates. Several variants on Pfmdr1, associated with reduced susceptibility to quinolones and lumefantrine, were also identified (Y184F 47.1%; D1246Y 16.0%; N86 98%). Overall, we have presented a low-cost and extendable approach that can provide timely genetic profiles to inform clinical and surveillance activities, especially in settings with abundant low-density infections, seeking malaria elimination.

Challenges and opportunities in rapid disaster research: lessons from the field in New Mexico and Vanuatu.

Rapid research is essential to assess impacts in communities affected by disasters, particularly those communities made "hard-to-reach" due to their active marginalization across history and in contemporary practices. In this article, we describe two rapid research projects developed to assess needs for and experiences of communities hard-hit by disasters. The first is a project on the COVID-19 pandemic in southern New Mexico (USA) that was developed to provide information to local agencies that are deploying programs to rebuild and revitalize marginalized communities. The second is a project on population displacement due to a volcanic eruption in Vanuatu, a lower-middle income country in the South Pacific, with mental and physical health outcomes data shared with the Vanuatu Ministry of Health. We describe the similar and unique challenges that arose doing rapid research in these two different contexts, the potential broader impacts of the research, and a synthesis of lessons learned. We discuss the challenges of rapidly changing rules and regulations, lack of baseline data, lack of survey instruments validated for specific populations and in local languages, limited availability of community partners, finding funding for rapid deployment of projects, rapidly training and working with research assistants, health and safety concerns of researchers and participants, and communicating with local and international partners. We also specifically discuss how we addressed our own personal challenges while also conducting time-intensive rapid research. In both studies, researchers shared results with governmental and non-governmental partners who may use the data to inform the design of their own relief programs. While different in context, type of disaster, and research strategy, our discussion of these projects provides insights into common lessons learned for working with communities at elevated risk for the worst outcomes during disasters, such as the need for flexibility, compromise, and good working relationships with community partners.

Evaluation of the protective efficacy of Olyset®Plus ceiling net on reducing malaria prevalence in children in Lake Victoria Basin, Kenya: study protocol for a cluster-randomized controlled trial.

BACKGROUND: In the Lake Victoria Basin of western Kenya, malaria remains highly endemic despite high coverage of interventions such as insecticide-impregnated long-lasting insecticidal nets (LLIN). The malaria-protective effect of LLINs is hampered by insecticide resistance in Anopheles vectors and its repurposing by the community. Ceiling nets and LLIN with synergist piperonyl butoxide (PBO-LLIN) are novel tools that can overcome the problems of behavioral variation of net use and metabolic resistance to insecticide, respectively. The two have been shown to reduce malaria prevalence when used independently. Integration of these two tools (i.e., ceiling nets made with PBO-LLIN or Olyset®Plus ceiling nets) appears promising in further reducing the malaria burden. METHODS: A cluster-randomized controlled trial is designed to assess the effect of Olyset®Plus ceiling nets on reducing malaria prevalence in children on Mfangano Island in Homa Bay County, where malaria transmission is moderate. Olyset®Plus ceiling nets will be installed in 1315 residential structures. Malaria parasitological, entomological, and serological indicators will be measured for 12 months to compare the effectiveness of this new intervention against conventional LLIN in the control arm. DISCUSSION: Wider adoption of Olyset®Plus ceiling nets to complement existing interventions may benefit other malaria-endemic counties and be incorporated as part of Kenya's national malaria elimination strategy. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000045079. Registered on 4 August 2021.

Patterns of distress and psychosocial support 2 years post-displacement following a natural disaster in a lower middle income country.

Background: Displacement due to natural disaster exposure is a major source of distress, and disproportionately affects people in low- and middle-income countries (LMICs). Public mental health resources following natural disasters and displacement are often limited in LMICs. In 2017, the population of one island in Vanuatu, a lower-middle income country, was displaced due to volcanic activity. Following the launch of a public mental health policy in 2009, psychosocial support interventions are increasingly available, providing an opportunity to assess relationships with distress following displacement. Methods: 440 people contributed data. We assessed distress using a local adaptation of the Impact of Event Scale-Revised, and types of psychosocial support available and received, including from health professionals, support groups, and traditional networks such as chiefs, traditional healers, and church leaders. We analyzed relationships between distress and psychosocial support, controlling for sociodemographic covariates. Results: Professional and group support was reported available by 86.8-95.1% of participants. Traditional support networks were widely used, especially by men. Availability of professional support predicted lower distress among men (p < 0.001) and women (p = 0.015) ( η p 2 = 0.026-0.083). Consulting church leaders for psychosocial support was associated with higher distress among men (p = 0.026) and women (p = 0.023) ( η p 2 = 0.024-0.031). Use of professional and group support was lower than reported availability. Discussion: Increased collaboration between professional and traditional support networks could help respond to mental health needs following natural disasters in LMICs with limited infrastructure. Providing training and resources to church leaders might be a specific target for improvement. Promoting use of available services represents a continued public health need.

Potential application of the haematology analyser XN-31 prototype for field malaria surveillance in Kenya.

BACKGROUND: Simple and accurate diagnosis is a key component of malaria control programmes. Microscopy is the current gold standard, however it requires extensive training and the results largely rely on the skill of the microscopists. Malaria rapid diagnostic tests (RDT) can be performed with minimal training and offer timely diagnosis, but results are not quantitative. Moreover, some Plasmodium falciparum parasites have evolved and can no longer be detected by existing RDT. Developed by the Sysmex Corporation, the XN-31 prototype (XN-31p) is an automated haematology analyser capable of detecting Plasmodium-infected erythrocytes and providing species differentiation and stage specific parasite counts in venous blood samples without any preparation in approximately one minute. However, factors such as stable electricity supply in a temperature-controlled room, cost of the instrument and its initial set-up, and need for proprietary reagents limit the utility of the XN-31p across rural settings. To overcome some of these limitations, a hub and spoke diagnosis model was designed, in which peripheral health facilities were linked to a central hospital where detection of Plasmodium infections by the XN-31p would take place. To explore the feasibility of this concept, the applicability of capillary blood samples with the XN-31p was evaluated with respect to the effect of sample storage time and temperature on the stability of results. METHODS: Paired capillary and venous blood samples were collected from 169 malaria-suspected outpatients in Homa Bay County Referral Hospital, Kenya. Malaria infections were diagnosed with the XN-31p, microscopy, RDT, and PCR. Capillary blood samples were remeasured on the XN-31p after 24 h of storage at either room (15-25 °C) or chilled temperatures (2-8 °C). RESULTS: Identical results in malaria diagnosis were observed between venous and capillary blood samples processed immediately after collection with the XN-31p. Relative to PCR, the sensitivity and specificity of the XN-31p with capillary blood samples were 0.857 and 1.000, respectively. Short-term storage of capillary blood samples at chilled temperatures had no adverse impact on parasitaemia and complete blood counts (CBC) measured by the XN-31p. CONCLUSION: These results demonstrate the potential of the XN-31p to improve routine malaria diagnosis across remote settings using a hub and spoke model.

ROR2 regulates self-renewal and maintenance of hair follicle stem cells.

Hair follicles undergo cycles of regeneration fueled by hair follicle stem cells (HFSCs). While ß-catenin-dependent canonical Wnt signaling has been extensively studied and implicated in HFSC activation and fate determination, very little is known about the function of ß-catenin-independent Wnt signaling in HFSCs. In this study, we investigate the functional role of ROR2, a Wnt receptor, in HFSCs. By analyzing Ror2-depleted HFSCs, we uncover that ROR2 is not only essential to regulate Wnt-activated signaling that is responsible for HFSC activation and self-renewal, but it is also required to maintain proper ATM/ATR-dependent DNA damage response, which is indispensable for the long-term maintenance of HFSCs. In analyzing HFSCs lacking ß-catenin, we identify a compensatory role of ROR2-PKC signaling in protecting ß-catenin-null HFSCs from the loss of stem cell pool. Collectively, our study unveils a previously unrecognized role of ROR2 in regulation of stem cell self-renewal and maintenance.

Characterizing the genomic variation and population dynamics of Plasmodium falciparum malaria parasites in and around Lake Victoria, Kenya.

Characterising the genomic variation and population dynamics of Plasmodium falciparum parasites in high transmission regions of Sub-Saharan Africa is crucial to the long-term efficacy of regional malaria elimination campaigns and eradication. Whole-genome sequencing (WGS) technologies can contribute towards understanding the epidemiology and structural variation landscape of P. falciparum populations, including those within the Lake Victoria basin, a region of intense transmission. Here we provide a baseline assessment of the genomic diversity of P. falciparum isolates in the Lake region of Kenya, which has sparse genetic data. Lake region isolates are placed within the context of African-wide populations using Illumina WGS data and population genomic analyses. Our analysis revealed that P. falciparum isolates from Lake Victoria form a cluster within the East African parasite population. These isolates also appear to have distinct ancestral origins, containing genome-wide signatures from both Central and East African lineages. Known drug resistance biomarkers were observed at similar frequencies to those of East African parasite populations, including the S160N/T mutation in the pfap2mu gene, which has been associated with delayed clearance by artemisinin-based combination therapy. Overall, our work provides a first assessment of P. falciparum genetic diversity within the Lake Victoria basin, a region targeting malaria elimination.

Relationships between mental health and diet during pregnancy and birth outcomes in a lower-middle income country: "Healthy mothers, healthy communities" study in Vanuatu.

Poor maternal mental health during pregnancy is associated with adverse birth outcomes, including lower birthweight and gestational age. However, few studies assess both mental health and diet, which might have interactive effects. Furthermore, most studies are in high-income countries, though patterns might differ in low- and middle-income countries (LMICs). OBJECTIVES: To analyze relationships between mental health and diet during pregnancy with birth outcomes in Vanuatu, a lower-middle income country. METHODS: We assessed negative emotional symptoms of depression, anxiety, and stress (referred to as "distress") and dietary diversity during pregnancy, and infant weight and gestational age at birth, among 187 women. We used multivariate linear regression to analyze independent and interactive relationships between distress, dietary diversity, and birth outcomes, controlling for sociodemographic and maternal health covariates. RESULTS: There were no direct linear relationships between dietary diversity or distress with infant birthweight or gestational age, and no curvilinear relationships between distress and infant outcomes. We observed interactive relationships between distress and dietary diversity on birthweight, explaining 2.1% of unique variance (P = .024). High levels of distress predicted lower birthweights among women with low dietary diversity. These relationships were not evident among women with moderate or high dietary diversity. CONCLUSIONS: Relationships between mental health and diet might underlie inconsistencies in past studies of prenatal mental health and birthweight. Results highlight the importance of maternal mental health on birthweight in LMICs. Interactive relationships between mental health and diet might ultimately point to new intervention pathways to address the persistent problem of low birthweight in LMICs.

Relationships between Prenatal Distress and Infant Body Mass Index in the First Year of Life in a Lower-Middle Income Country.

Prenatal stress affects body composition in childhood and later in life. However, few studies assess body composition in infancy. Furthermore, most are in high-income countries and do not consider interactive or curvilinear relationships. We assessed distress and diet during pregnancy via questionnaires among 310 women in Vanuatu, a lower-middle income country. We measured body mass index (BMI) among 54 infants at 4-12 months of age. We analyzed interactive relationships between prenatal distress and diet with BMI Z-scores, and curvilinear relationships between distress and BMI Z-scores. There were no direct linear or interactive relationships between prenatal distress or diet with BMI Z-scores. We observed curvilinear relationships between prenatal distress and BMI Z-scores (p = 0.008), explaining 13.3 percent of unique variance. Results highlight that relationships between prenatal stress and body composition are evident in infancy but might not be detected if only linear relationships are assessed. Analyses in more diverse samples might help to explain inconsistencies in past studies.

CYP2D6 genotyping analysis and functional characterization of novel allelic variants in a Ni-Vanuatu and Kenyan population by assessing dextromethorphan O-demethylation activity.

While CYP2D6 allele and phenotype frequencies have been extensively studied, currently, very little ethnically specific data is available regarding the East African and South Pacific region, including Kenya and Vanuatu. The absence of information regarding gene polymorphisms and their resulting clinical effects in these populations may hinder treatment strategies and patient outcome. Given the scarceness of CYP2D6 related data in these populations, the purpose of this study was to perform a pharmacogenomic analysis of the Kenyan and Ni-Vanuatu population and ultimately characterize the enzymatic properties of eight novel CYP2D6 variant proteins expressed in 293FT cells in vitro using dextromethorphan as a substrate. Our study revealed a prevalence of functional alleles in both populations a low frequency for decreased function defining genotypes in the Ni-Vanuatu population, with approximately 36% of our Kenyan subjects presenting substrate-dependent decreased function alleles. Additionally, 6 variants (P171L, G306R, V402L, K1, K2, and K3) showed significantly reduced intrinsic clearance compared to wild-type CYP2D6.1. Our findings aid in efforts to bridge the gap between pharmacogenomic analysis and clinical application, by providing useful information in the development of ethnic-specific strategies as well as stressing the importance of population-specific genotyping when conducting multi-regional clinical trials and designing therapeutic strategies.

Deoxyelephantopin induces ROS-mediated autophagy and apoptosis in human colorectal cancer in vitro and in vivo

Objective: To systematically map the stepwise events leading to deoxyelephantopin-induced cell death of HCT116 human colorectal cancer cells and evaluate the effectiveness of deoxyelephantopin in vivo. Methods: HCT116 cells were treated with deoxyelephantopin at various concentrations and time points. Autophagy was confirmed by the detection of autophagosomes and autophagosomal proteins by electron microscopy and Western blotting assays, respectively, and then validated by siRNA knockdown. In addition, apoptosis was confirmed by the detection of apoptosis-related proteins. The intracellular reactive oxygen species (ROS) level was measured using flow cytometry. The growth inhibitory effect of deoxyelephantopin was further evaluated in vivo using a mouse xenograft model. Results: Deoxyelephantopin firstly elevated ROS production, which then triggered autophagic flux with the accumulation of autophagosomal proteins including LC3A/B, ATG5, and ATG7, followed by the induction of apoptosis via the intrinsic and extrinsic pathways. Pre-treatment with N-acetyl-L-cysteine, a ROS inhibitor, reversed both apoptosis and autophagy. The knockdown of LC3 prevented apoptosis induction which confirmed that deoxyelephantopin induced autophagy-dependent apoptosis in HCT116 cells. Accumulation of ROS also activated apoptosis via the mitogen-activated protein kinases signaling pathway. Furthermore, deoxyelephantopin also inhibited the PI3K/AKT/mTOR pathway, which then released the inhibition of autophagy. In vivo study further showed that deoxyelephantopin significantly suppressed the growth of HCT116 subcutaneous xenograft in nude mice. Conclusions: Our findings revealed that deoxyelephantopin elevates oxidative stress and induces ROS-dependent autophagy followed by apoptosis in HCT116 cells via the concerted modulation of multiple signaling pathways. These findings further support the development of deoxyelephantopin as a therapeutic agent for colorectal cancer.

Malaria resurgence after significant reduction by mass drug administration on Ngodhe Island, Kenya.

Although WHO recommends mass drug administration (MDA) for malaria elimination, further evidence is required for understanding the obstacles for the optimum implementation of MDA. Just before the long rain in 2016, two rounds of MDA with artemisinin/piperaquine (Artequick) and low-dose primaquine were conducted with a 35-day interval for the entire population of Ngodhe Island (~500 inhabitants) in Lake Victoria, Kenya, which is surrounded by areas with moderate and high transmission. With approximately 90% compliance, Plasmodium prevalence decreased from 3% to 0% by microscopy and from 10% to 2% by PCR. However, prevalence rebounded to 9% by PCR two months after conclusion of MDA. Besides the remained local transmission, parasite importation caused by human movement likely contributed to the resurgence. Analyses of 419 arrivals to Ngodhe between July 2016 and September 2017 revealed Plasmodium prevalence of 4.6% and 16.0% by microscopy and PCR, respectively. Risk factors for infection among arrivals included age (0 to 5 and 11 to 15 years), and travelers from Siaya County, located to the north of Ngodhe Island. Parasite importation caused by human movement is one of major obstacles to sustain malaria elimination, suggesting the importance of cross-regional initiatives together with local vector control.

Streptomyces sp. MUM256: A Source for Apoptosis Inducing and Cell Cycle-Arresting Bioactive Compounds against Colon Cancer Cells.

New and effective anticancer compounds are much needed as the incidence of cancer continues to rise. Microorganisms from a variety of environments are promising sources of new drugs; Streptomyces sp. MUM256, which was isolated from mangrove soil in Malaysia as part of our ongoing efforts to study mangrove resources, was shown to produce bioactive metabolites with chemopreventive potential. This present study is a continuation of our previous efforts and aimed to investigate the underlying mechanisms of the ethyl acetate fraction of MUM256 crude extract (MUM256 EA) in inhibiting the proliferation of HCT116 cells. Our data showed that MUM256 EA reduced proliferation of HCT116 cells via induction of cell-cycle arrest. Molecular studies revealed that MUM256 EA regulated the expression level of several important cell-cycle regulatory proteins. The results also demonstrated that MUM256 EA induced apoptosis in HCT116 cells mediated through the intrinsic pathway. Gas chromatography-mass spectrometry (GC-MS) analysis detected several chemical compounds present in MUM256 EA, including cyclic dipeptides which previous literature has reported to demonstrate various pharmacological properties. The cyclic dipeptides were further shown to inhibit HCT116 cells while exerting little to no toxicity on normal colon cells in this study. Taken together, the findings of this project highlight the important role of exploring the mangrove microorganisms as a bioresource which hold tremendous promise for the development of chemopreventive drugs against colorectal cancer.

Formononetin: A Review of Its Anticancer Potentials and Mechanisms.

Cancer, a complex yet common disease, is caused by uncontrolled cell division and abnormal cell growth due to a variety of gene mutations. Seeking effective treatments for cancer is a major research focus, as the incidence of cancer is on the rise and drug resistance to existing anti-cancer drugs is major concern. Natural products have the potential to yield unique molecules and combinations of substances that may be effective against cancer with relatively low toxicity/better side effect profile compared to standard anticancer therapy. Drug discovery work with natural products has demonstrated that natural compounds display a wide range of biological activities correlating to anticancer effects. In this review, we discuss formononetin (C16H12O4), which originates mainly from red clovers and the Chinese herb Astragalus membranaceus. The compound comes from a class of 7-hydroisoflavones with a substitution of methoxy group at position 4. Formononetin elicits antitumorigenic properties in vitro and in vivo by modulating numerous signaling pathways to induce cell apoptosis (by intrinsic pathway involving Bax, Bcl-2, and caspase-3 proteins) and cell cycle arrest (by regulating mediators like cyclin A, cyclin B1, and cyclin D1), suppress cell proliferation [by signal transducer and activator of transcription (STAT) activation, phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT), and mitogen-activated protein kinase (MAPK) signaling pathway], and inhibit cell invasion [by regulating growth factors vascular endothelial growth factor (VEGF) and Fibroblast growth factor 2 (FGF2), and matrix metalloproteinase (MMP)-2 and MMP-9 proteins]. Co-treatment with other chemotherapy drugs such as bortezomib, LY2940002, U0126, sunitinib, epirubicin, doxorubicin, temozolomide, and metformin enhances the anticancer potential of both formononetin and the respective drugs through synergistic effect. Compiling the evidence thus far highlights the potential of formononetin to be a promising candidate for chemoprevention and chemotherapy.

Wnt Signaling Pathways in Keratinocyte Carcinomas.

The skin functions as a barrier between the organism and the surrounding environment. Direct exposure to external stimuli and the accumulation of genetic mutations may lead to abnormal cell growth, irreversible tissue damage and potentially favor skin malignancy. Skin homeostasis is coordinated by an intricate signaling network, and its dysregulation has been implicated in the development of skin cancers. Wnt signaling is one such regulatory pathway orchestrating skin development, homeostasis, and stem cell activation. Aberrant regulation of Wnt signaling cascades not only gives rise to tumor initiation, progression and invasion, but also maintains cancer stem cells which contribute to tumor recurrence. In this review, we summarize recent studies highlighting functional evidence of Wnt-related oncology in keratinocyte carcinomas, as well as discussing preclinical and clinical approaches that target oncogenic Wnt signaling to treat cancers. Our review provides valuable insight into the significance of Wnt signaling for future interventions against keratinocyte carcinomas.

Psychosocial distress among women following a natural disaster in a low- to middle-income country: "healthy mothers, healthy communities" study in Vanuatu.

Natural disasters have major consequences for mental health in low- and middle-income countries. Symptoms are often more pronounced among women. We analyzed patterns and predictors of distress among pregnant and non-pregnant women 3-4 and 15-16 months after a cyclone in Vanuatu, a low- to middle-income country. Distress levels were high among both pregnant and non-pregnant women, although pregnant women showed lower longer-term symptoms. Low dietary diversity predicted greater distress, which could affect women even in villages with little cyclone damage.

Using multiple correspondence analysis to identify behaviour patterns associated with overweight and obesity in Vanuatu adults.

OBJECTIVE: The present study evaluates the use of multiple correspondence analysis (MCA), a type of exploratory factor analysis designed to reduce the dimensionality of large categorical data sets, in identifying behaviours associated with measures of overweight/obesity in Vanuatu, a rapidly modernizing Pacific Island country. DESIGN: Starting with seventy-three true/false questions regarding a variety of behaviours, MCA identified twelve most significantly associated with modernization status and transformed the aggregate binary responses of participants to these twelve questions into a linear scale. Using this scale, individuals were separated into three modernization groups (tertiles) among which measures of body fat were compared and OR for overweight/obesity were computed. SETTING: Vanuatu.ParticipantsNi-Vanuatu adults (n 810) aged 20-85 years. RESULTS: Among individuals in the tertile characterized by positive responses to most of or all the twelve modernization questions, weight and measures of body fat and the likelihood that measures of body fat were above the US 75th percentile were significantly greater compared with individuals in the tertiles characterized by mostly or partly negative responses. CONCLUSIONS: The study indicates that MCA can be used to identify individuals or groups at risk for overweight/obesity, based on answers to simply-put questions. MCA therefore may be useful in areas where obtaining detailed information about modernization status is constrained by time, money or manpower.

Psychosocial support during displacement due to a natural disaster: relationships with distress in a lower-middle income country.

BACKGROUND: Past studies show relationships between disaster-related displacement and adverse psychosocial health outcomes. The development of psychosocial interventions following displacement is thus increasingly prioritized. However, data from low- and middle-income countries (LMICs) are lacking. In October 2017, the population of Ambae Island in Vanuatu, a lower-middle income country, was temporarily displaced due to volcanic activity. We analyzed distress among adults displaced due to the event and differences based on the psychosocial support they received. METHODS: Data on experiences during displacement, distress and psychosocial support were collected from 443 adults 2-3 wk after repatriation to Ambae Island. Four support categories were identified: Healthcare professional, Traditional/community, Not available and Not wanted. We analyzed differences in distress by sex and group using one-way ANOVA and generalized linear models. RESULTS: Mean distress scores were higher among women (1.90, SD=0.97) than men (1.64, SD=0.98) (p<0.004). In multivariate models, psychosocial support group was associated with distress among women (p=0.033), with higher scores among women who reported no available support compared with every other group. Both healthcare professional and traditional support networks were widely used. CONCLUSIONS: Women might be particularly vulnerable to distress during disaster-related displacement in LMICs, and those who report a lack of support might be at greater risk. Both healthcare professional and traditional networks provide important sources of support that are widely used and might help to ameliorate symptoms.

Coming to grips with economic development: Variation in adult hand grip strength during health transition in Vanuatu.

OBJECTIVES: To determine whether (1) maximal handgrip strength (HGS) is associated with inter-island level of economic development in Vanuatu, (2) how associations between island of residence and HGS are mediated by age, sex, body size/composition, and individual sociodeomographic variation, and (3) whether HGS is predictive of hypertension. MATERIAL AND METHODS: HGS was collected from 833 adult (aged 18 and older) men and women on five islands representing a continuum of economic development in Vanuatu. HGS was measured using a handheld dynamometer. Participants were administered in an extensive sociobehavioral questionnaire and were also assessed for height, weight, percent body fat, forearm skinfold thickness, forearm circumference, and blood pressure. RESULTS: HGS was significantly greater in men than in women regardless of island of residence. HGS was also significantly positively associated with inter-island level of economic development. Grip strength-to-weight ratio was not different across islands except in older individuals, where age-related decline occurred primarily on islands with greater economic development. HGS significantly declined with age in both men and women. CONCLUSION: HGS is positively associated with modernization in Vanuatu, but the relationship between HGS and modernization is largely due to an association of both variables with increased body size on more modernized islands. Further research on the role of individual variation in diet and physical activity are necessary to clarify the relationship between HGS and modernization.