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In high-income countries, one's relative socio-economic position and economic inequality may affect health and well-being, arguably via psychosocial stress. We tested this in a small-scale subsistence society, the Tsimane, by associating relative household wealth (n = 871) and community-level wealth inequality (n = 40, Gini = 0.15-0.53) with a range of psychological variables, stressors, and health outcomes (depressive symptoms [n = 670], social conflicts [n = 401], non-social problems [n = 398], social support [n = 399], cortisol [n = 811], body mass index [n = 9,926], blood pressure [n = 3,195], self-rated health [n = 2523], morbidities [n = 1542]) controlling for community-average wealth, age, sex, household size, community size, and distance to markets. Wealthier people largely had better outcomes while inequality associated with more respiratory disease, a leading cause of mortality. Greater inequality and lower wealth were associated with higher blood pressure. Psychosocial factors did not mediate wealth-health associations. Thus, relative socio-economic position and inequality may affect health across diverse societies, though this is likely exacerbated in high-income countries.

BackgroundSoil-transmitted helminths (STHs) and humans share long co-evolutionary histories over which STHs have evolved strategies to permit their persistence by downregulating host immunity. Understanding the interactions between STHs and other pathogens can inform our understanding of human evolution and contemporary disease patterns.MethodologyWe worked with Tsimane forager-horticulturalists in the Bolivian Amazon, where STHs are prevalent. We tested whether STHs and eosinophil levels-likely indicative of infection in this population-are associated with dampened immune responses to in vitro stimulation with H1N1 and lipopolysaccharide (LPS) antigens. Whole blood samples (n = 179) were treated with H1N1 vaccine and LPS and assayed for 13 cytokines (INF-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, GM-CSF and TNF-ɑ). We evaluated how STHs and eosinophil levels affected cytokine responses and T helper (Th) 1 and Th2-cytokine suite responses to stimulation.ResultsInfection with Ascaris lumbricoides was significantly (P ≤ 0.05) associated with lower response of some cytokines to H1N1 and LPS in women. Eosinophils were significantly negatively associated with some cytokine responses to H1N1 and LPS, with the strongest effects in women, and associated with a reduced Th1- and Th2-cytokine response to H1N1 and LPS in women and men.Conclusions and implicationsConsistent with the 'old friends' and hygiene hypotheses, we find that STHs were associated with dampened cytokine responses to certain viral and bacterial antigens. This suggests that STH infections may play an essential role in immune response regulation and that the lack of STH immune priming in industrialized populations may increase the risk of over-reactive immunity. Lay Summary: Indicators of helminth infection were associated with dampened cytokine immune responses to in vitro stimulation with viral and bacterial antigens in Tsimane forager-horticulturalists in the Bolivian Amazon, consistent with the 'old friends' and hygiene hypotheses.

The intensifying pace of research based on cross-cultural studies in the social sciences necessitates a discussion of the unique challenges of multi-sited research. Given an increasing demand for social scientists to expand their data collection beyond WEIRD (Western, educated, industrialized, rich and democratic) populations, there is an urgent need for transdisciplinary conversations on the logistical, scientific and ethical considerations inherent to this type of scholarship. As a group of social scientists engaged in cross-cultural research in psychology and anthropology, we hope to guide prospective cross-cultural researchers through some of the complex scientific and ethical challenges involved in such work: (a) study site selection, (b) community involvement and (c) culturally appropriate research methods. We aim to shed light on some of the difficult ethical quandaries of this type of research. Our recommendation emphasizes a community-centred approach, in which the desires of the community regarding research approach and methodology, community involvement, results communication and distribution, and data sharing are held in the highest regard by the researchers. We argue that such considerations are central to scientific rigour and the foundation of the study of human behaviour.

High social status is often associated with greater mating opportunities and fertility for men, but do women also obtain fitness benefits of high status? Greater resource access and child survivorship may be principal pathways through which social status increases women's fitness. Here, we examine whether peer-rankings of women's social status (indicated by political influence, project leadership, and respect) positively covaries with child nutritional status and health in a community of Amazonian horticulturalists. We find that maternal political influence is associated with improved child health outcomes in models adjusting for maternal age, parental height and weight, level of schooling, household income, family size, and number of kin in the community. Children of politically influential women have higher weight-for-age (B = 0.33; 95% CI = 0.12-0.54), height-for-age (B = 0.32; 95% CI = 0.10-0.54), and weight-for-height (B = 0.24; 95% CI = 0.04-0.44), and they are less likely to be diagnosed with common illnesses (OR = 0.48; 95% CI = 0.31-0.76). These results are consistent with women leveraging their social status to enhance reproductive success through improvements in child health. We discuss these results in light of parental investment theory and the implications for the evolution of female social status in humans.

BackgroundIn an energy-limited environment, caloric investments in one characteristic should trade-off with investments in other characteristics. In high pathogen ecologies, biasing energy allocation towards immune function over growth would be predicted, given strong selective pressures against early-life mortality.MethodologyIn the present study, we use flow cytometry to examine trade-offs between adaptive immune function (T cell subsets, B cells), innate immune function (natural killer cells), adaptive to innate ratio and height-for-age z scores (HAZ) among young children (N = 344; aged 2 months-8 years) in the Bolivian Amazon, using maternal BMI and child weight-for-height z scores (WHZ) as proxies for energetic status.ResultsMarkers of adaptive immune function negatively associate with child HAZ, a pattern most significant in preadolescents (3+ years). In children under three, maternal BMI appears to buffer immune and HAZ associations, while child energetic status (WHZ) moderates relationships in an unexpected direction: HAZ and immune associations are greater in preadolescents with higher WHZ. Children with low WHZ maintain similar levels of adaptive immune function, but are shorter compared to high WHZ peers.ConclusionsReduced investment in growth in favor of immunity may be necessary for survival in high pathogen contexts, even under energetic constraints. Further, genetic and environmental factors are important considerations for understanding variation in height within this population. These findings prompt consideration of whether there may be a threshold of investment into adaptive immunity required for survival in high pathogen environments, and thus question the universal relevance of height as a marker of health.Lay summaryAdaptive immune function is negatively associated with child height in this high pathogen environment. Further, low weight-for-height children are shorter but maintain similar immune levels. Findings question the relevance of height as a universal health marker, given that costs and benefits of height versus immunity may be calibrated to local ecology.

The Tsimane Health and Life History Project, an integrated bio-behavioral study of the human life course, is designed to test competing hypotheses of human life-history evolution. One aim is to understand the bidirectional connections between life history and social behavior in a high-fertility, kin-based context lacking amenities of modern urban life (e.g. sanitation, banks, electricity). Another aim is to understand how a high pathogen burden influences health and well-being during development and adulthood. A third aim addresses how modernization shapes human life histories and sociality. Here we outline the project's goals, history, and main findings since its inception in 2002. We reflect on the implications of current findings and highlight the need for more coordinated ethnographic and biomedical study of contemporary nonindustrial populations to address broad questions that can situate evolutionary anthropology in a key position within the social and life sciences.

ObjectivesResting metabolic rate (RMR) reflects energetic costs of homeostasis and accounts for 60 to 75% of total energy expenditure (TEE). Lean mass and physical activity account for much RMR variability, but the impact of prolonged immune activation from infection on human RMR is unclear in naturalistic settings. We evaluate the effects of infection on mass-corrected RMR among Bolivian forager-horticulturalists, and assess whether RMR declines more slowly with age than in hygienic sedentary populations, as might be expected if older adults experience high pathogen burden.Materials and methodsRMR was measured by indirect calorimetry (Fitmate MED, Cosmed) in 1,300 adults aged 20 to 90 and TEE was measured using doubly labeled water (n = 40). Immune biomarkers, clinical diagnoses, and anthropometrics were collected by the Tsimane Health and Life History Project.ResultsTsimane have higher RMR and TEE than people in sedentary industrialized populations. Tsimane RMR is 18 to 47% (women) and 22 to 40% (men) higher than expected using six standard prediction equations. Tsimane mass-corrected TEE is similarly elevated compared to Westerners. Elevated leukocytes and helminths are associated with excess RMR in multivariate regressions, and jointly result in a predicted excess RMR of 10 to 15%. After age 40, RMR declines by 69 kcal/decade (p

ObjectivesDespite well-known fitness advantages to males who produce and maintain high endogenous testosterone levels, such phenotypes may be costly if testosterone-mediated investment in reproductive effort trade-off against investment in somatic maintenance. Previous studies of androgen-mediated trade-offs in human immune function find mixed results, in part because most studies either focus on a few indicators of immunity, are confounded by phenotypic correlation, or are observational. Here the association between male endogenous testosterone and 13 circulating cytokines are examined before and after ex vivo antigen stimulation with phytohemagglutinin (PHA) and lipopolysaccharides (LPS) in a high pathogen population of Bolivian forager-horticulturalists.Materials and methodsA Milliplex 13-plex cytokine panel measured cytokine concentration in whole blood samples from 109 Tsimane men aged 40-89 (median = 50 years) before and after antigen stimulation with PHA and LPS. Urinary testosterone was measured via enzyme immunoassay, demographic, and anthropometric data were collected as part of the Tsimane Health and Life History Project.ResultsHigher endogenous testosterone was associated with down-regulated responses in all cytokines after PHA stimulation (but significantly in only 2/13 cytokines), controlling for age and body mass index. In contrast, testosterone was not significantly associated with down-regulation of cytokines after LPS stimulation. MANOVAs indicate that men with higher testosterone showed reduced cytokine responses to PHA compared with LPS (p = 0.0098).DiscussionEndogenous testosterone appears to be immunomodulatory rather than immunosuppressive. Potentially costlier forms of immune activation like those induced by PHA (largely T-cell biased immune activation) are down-regulated in men with higher testosterone, but testosterone has less impact on potentially less costly immune activation following LPS stimulation (largely B-cell mediated immunity).

BackgroundAmazonian populations are exposed to diverse parasites and pathogens, including protozoal, bacterial, fungal and helminthic infections. Yet much knowledge of the immune system is based on industrialised populations where these infections are relatively rare.AimThis study examines distributions and age-related differences in 22 measures of immune function for Bolivian forager-horticulturalists and US and European populations.Subjects and methodsSubjects were 6338 Tsimane aged 0-90 years. Blood samples collected between 2004-2014 were analysed for 5-part blood differentials, C-reactive protein, erythrocyte sedimentation rate (ESR) and total immunoglobulins E, G, A and M. Flow cytometry was used to quantify naïve and non-naïve CD4 and CD8 T cells, natural killer cells, and B cells.ResultsCompared to reference populations, Tsimane have elevated levels of most immunological parameters, particularly immunoglobulins, eosinophils, ESR, B cells, and natural killer cells. However, monocytes and basophils are reduced and naïve CD4 cells depleted in older age groups.ConclusionTsimane ecology leads to lymphocyte repertoires and immunoglobulin profiles that differ from those observed in industrialised populations. These differences have consequences for disease susceptibility and co-vary with patterns of other life history traits, such as growth and reproduction.

BackgroundMarket integration (MI)-increasing production for and consumption from a market-based economy-is drastically altering traditional ways of life and environmental conditions among indigenous Amazonian peoples. The effects of MI on the biology and health of Amazonian children and adolescents, however, remain unclear.AimThis study examines the impact of MI on sub-adult body size and nutritional status at the population, regional and household levels among the Shuar of Amazonian Ecuador.Subjects and methodsAnthropometric data were collected between 2005-2014 from 2164 Shuar (aged 2-19 years) living in two geographic regions differing in general degree of MI. High-resolution household economic, lifestyle and dietary data were collected from a sub-sample of 631 participants. Analyses were performed to investigate relationships between body size and year of data collection, region and specific aspects of household MI.ResultsResults from temporal and regional analyses suggest that MI has a significant and overall positive impact on Shuar body size and nutritional status. However, household-level results exhibit nuanced and heterogeneous specific effects of MI underlying these overarching relationships.ConclusionThis study provides novel insight into the complex socio-ecological pathways linking MI, physical growth and health among the Shuar and other indigenous Amazonian populations.

ObjectivesInformation concerning physical growth among small-scale populations remains limited, yet such data are critical to local health efforts and to foster basic understandings of human life history and variation in childhood development. Using a large dataset and robust modeling methods, this study aims to describe growth from birth to adulthood among the indigenous Shuar of Amazonian Ecuador.MethodsMixed-longitudinal measures of height, weight, and body mass index (BMI) were collected from Shuar participants (n = 2,463; age: 0-29 years). Centile growth curves and tables were created for each anthropometric variable of interest using Generalized Additive Models for Location, Scale, and Shape (GAMLSS). Pseudo-velocity and Lambda-Mu-Sigma curves were generated to further investigate Shuar patterns of growth and to facilitate comparison with United States Center for Disease Control and Prevention and multinational World Health Organization growth references.ResultsThe Shuar are small throughout life and exhibit complex patterns of growth that differ substantially from those of international references. Similar to other Amazonians, Shuar growth in weight compares more favorably to references than growth in height, resulting in BMI curves that approximate international medians. Several additional characteristics of Shuar development are noteworthy, including large observed variation in body size early in life, significant infant growth faltering, extended male growth into adulthood, and a markedly early female pubertal growth spurt in height. Phenotypic plasticity and genetic selection in response to local environmental factors may explain many of these patterns.ConclusionsProviding a detailed reference of growth for the Shuar and other Amazonian populations, this study possesses direct clinical application and affords valuable insight into childhood health and the ecology of human growth.

Heart disease and type 2 diabetes are commonly believed to be rare among contemporary subsistence-level human populations, and by extension prehistoric populations. Although some caveats remain, evidence shows these diseases to be unusual among well-studied hunter-gatherers and other subsistence populations with minimal access to healthcare. Here we expand on a relatively new proposal for why these and other populations may not show major signs of these diseases. Chronic infections, especially helminths, may offer protection against heart disease and diabetes through direct and indirect pathways. As part of a strategy to insure their own survival and reproduction, helminths exert multiple cardio-protective effects on their host through their effects on immune function and blood lipid metabolism. Helminths consume blood lipids and glucose, alter lipid metabolism, and modulate immune function towards Th-2 polarization - which combined can lower blood cholesterol, reduce obesity, increase insulin sensitivity, decrease atheroma progression, and reduce likelihood of atherosclerotic plaque rupture. Traditional cardiometabolic risk factors, coupled with the mismatch between our evolved immune systems and modern, hygienic environments may interact in complex ways. In this review, we survey existing studies in the non-human animal and human literature, highlight unresolved questions and suggest future directions to explore the role of helminths in the etiology of cardio-metabolic disease.

Infection with intestinal helminths results in immunological changes that influence co-infections, and might influence fecundity by inducing immunological states affecting conception and pregnancy. We investigated associations between intestinal helminths and fertility in women, using 9 years of longitudinal data from 986 Bolivian forager-horticulturalists, experiencing natural fertility and 70% helminth prevalence. We found that different species of helminth are associated with contrasting effects on fecundity. Infection with roundworm (Ascaris lumbricoides) is associated with earlier first births and shortened interbirth intervals, whereas infection with hookworm is associated with delayed first pregnancy and extended interbirth intervals. Thus, helminths may have important effects on human fertility that reflect physiological and immunological consequences of infection.

Sadness is an emotion universally recognized across cultures, suggesting it plays an important functional role in regulating human behavior. Numerous adaptive explanations of persistent sadness interfering with daily functioning (hereafter "depression") have been proposed, but most do not explain frequent bidirectional associations between depression and greater immune activation. Here we test several predictions of the host defense hypothesis, which posits that depression is part of a broader coordinated evolved response to infection or tissue injury (i.e. "sickness behavior") that promotes energy conservation and reallocation to facilitate immune activation. In a high pathogen population of lean and relatively egalitarian Bolivian forager-horticulturalists, we test whether depression and its symptoms are associated with greater baseline concentration of immune biomarkers reliably associated with depression in Western populations (i.e. tumor necrosis factor alpha [TNF-α], interleukin-1 beta [IL-1β], interleukin-6 [IL-6], and C-reactive protein [CRP]). We also test whether greater pro-inflammatory cytokine responses to ex vivo antigen stimulation are associated with depression and its symptoms, which is expected if depression facilitates immune activation. These predictions are largely supported in a sample of older adult Tsimane (mean±SD age=53.2±11.0, range=34-85, n=649) after adjusting for potential confounders. Emotional, cognitive and somatic symptoms of depression are each associated with greater immune activation, both at baseline and in response to ex vivo stimulation. The association between depression and greater immune activation is therefore not unique to Western populations. While our findings are not predicted by other adaptive hypotheses of depression, they are not incompatible with those hypotheses and future research is necessary to isolate and test competing predictions.

Background and objectivesLow social status increases risk of disease due, in part, to the psychosocial stress that accompanies feeling subordinate or poor. Previous studies report that chronic stress and chronically elevated cortisol can impair cardiovascular and immune function. We test whether lower status is more benign in small-scale, relatively egalitarian societies, where leaders lack coercive authority and there is minimal material wealth to contest.MethodologyAmong Tsimane' forager-horticulturalists of lowland Bolivia, we compare informal political influence among men with urinary cortisol, immune activation (innate and acquired), and morbidity as assessed during routine medical exams.ResultsAfter controlling for potential confounds, we find that politically influential men have lower cortisol, and that this association is partly attributable to access to social support. Cortisol is positively associated with men's income, which may reflect chronic psychosocial stress from market involvement. Greater influence is also associated with lower probability of respiratory infection, which is a frequent source of morbidity among Tsimane'. Among men who lost influence over a 4-year period, cortisol and probability of respiratory infection were higher the greater the decline in influence.Conclusions and implicationsDeleterious effects of low status on health are not merely 'diseases of civilization' but may result from how (even subtle) status differences structure human behavior.

ObjectivesThis study explores whether cardiovascular fitness levels and senescent decline are similar in the Tsimane of Bolivia and Canadians, as well as other subsistence and industrialized populations. Among Tsimane, we examine whether morbidity predicts lower levels and faster decline of cardiovascular fitness, or whether their lifestyle (e.g., high physical activity) promotes high levels and slow decline. Alternatively, high activity levels and morbidity might counterbalance such that Tsimane fitness levels and decline are similar to those in industrialized populations.MethodsMaximal oxygen uptake (VO2 max) was estimated using a step test heart rate method for 701 participants. We compared these estimates to the Canadian Health Measures Survey and previous studies in industrialized and subsistence populations. We evaluated whether health indicators and proxies for market integration were associated with VO2 max levels and rate of decline for the Tsimane.ResultsThe Tsimane have significantly higher levels of VO2 max and slower rates of decline than Canadians; initial evidence suggests differences in VO2 max levels between other subsistence and industrialized populations. Low hemoglobin predicts low VO2 max for Tsimane women while helminth infection predicts high VO2 max for Tsimane men, though results might be specific to the VO2 max scaling parameter used. No variables tested interact with age to moderate decline.ConclusionsThe Tsimane demonstrate higher levels of cardiovascular fitness than industrialized populations, but levels similar to other subsistence populations. The high VO2 max of Tsimane is consistent with their high physical activity and few indicators of cardiovascular disease, measured in previous studies.

ObjectivesThis study explores whether cardiovascular fitness levels and senescent decline are similar in the Tsimane of Bolivia and Canadians, as well as other subsistence and industrialized populations. Among Tsimane, we examine whether morbidity predicts lower levels and faster decline of cardiovascular fitness, or whether their lifestyle (e.g., high physical activity) promotes high levels and slow decline. Alternatively, high activity levels and morbidity might counterbalance such that Tsimane fitness levels and decline are similar to those in industrialized populations.MethodsMaximal oxygen uptake (VO2 max) was estimated using a step test heart rate method for 701 participants. We compared these estimates to the Canadian Health Measures Survey and previous studies in industrialized and subsistence populations. We evaluated whether health indicators and proxies for market integration were associated with VO2 max levels and rate of decline for the Tsimane.ResultsThe Tsimane have significantly higher levels of VO2 max and slower rates of decline than Canadians; initial evidence suggests differences in VO2 max levels between other subsistence and industrialized populations. Low hemoglobin predicts low VO2 max for Tsimane women while helminth infection predicts high VO2 max for Tsimane men, though results might be specific to the VO2 max scaling parameter used. No variables tested interact with age to moderate decline.ConclusionsThe Tsimane demonstrate higher levels of cardiovascular fitness than industrialized populations, but levels similar to other subsistence populations. The high VO2 max of Tsimane is consistent with their high physical activity and few indicators of cardiovascular disease, measured in previous studies.

Co-infection may affect transmission and recovery from infection, but remains an understudied element of disease ecology, particularly with regard to antagonism between parasites sharing a host. Helminth and giardia infections are often endemic in the same populations and both occupy the small intestine; yet few studies have examined interactions between these parasites. We report on helminth-giardia co-infections in a panel study of forager-horticulturalists in the Bolivian lowlands. Parasites were identified in faecal samples from 3275 participants, collected during 5235 medical exams over 6 years. Longitudinal co-infection patterns were examined using logistic mixed and multi-state Markov models. The most prevalent infections were hookworm (56%), Giardia lamblia (30%) and Ascaris lumbricoides (15%). Cross-sectionally, hookworm and A. lumbricoides were negatively associated with G. lamblia (OR = 0.60; OR = 0.65, respectively). Longitudinally, giardia infection was less likely in helminth-infected individuals (HR: 0.46). Infection with helminths was also less likely for individuals infected with giardia (HR: 0.71). Finally, treatment with mebendazole reduced subsequent hookworm infections, but resulted in a marginal increase in the odds of G. lamblia infection. Our results provide evidence for an antagonistic relationship between helminths and giardia, and suggest that co-infection should be considered in disease transmission models and treatment decisions.

BackgroundMarket integration (MI), the suite of social and cultural changes that occur with economic development, has been associated with negative health outcomes such as cardiovascular disease; however, key questions remain about how this transition manifests at the local level.AimThe present paper investigates the effects of MI on health among Shuar, an indigenous lowland Ecuadorian population, with the goal of better understanding the mechanisms responsible for this health transition.Subjects and methodsThis study examines associations between measures of MI and several dimensions of cardiovascular and metabolic health (fasting glucose, lipids [LDL, HDL and total cholesterol; triglycerides] and blood pressure) among 348 adults.ResultsOverall, Shuar males and females have relatively favourable cardiovascular and metabolic health. Shuar who live closer to town have higher total (p < 0.001) and HDL cholesterol (p < 0.001), while Shuar in more remote regions have higher diastolic blood pressure (p = 0.007). HDL cholesterol is positively associated with consumption of market foods (r = 0.140; p = 0.045) and ownership of consumer products (r = 0.184; p = 0.029).ConclusionsThis study provides evidence that MI among Shuar is not a uniformly negative process but instead produces complex cardiovascular and metabolic health outcomes.

The rise in blood pressure with age is a major risk factor for cardiovascular and renal disease, stroke, and type 2 diabetes mellitus. Age-related increases in blood pressure have been observed in almost every population, except among hunter-gatherers, farmers, and pastoralists. Here we tested for age-related increases in blood pressure among Tsimane forager-farmers. We also test whether lifestyle changes associated with modernization lead to higher blood pressure and a greater rate of age-related increase in blood pressure. We measured blood pressure longitudinally on 2248 adults age ≥ 20 years (n=6468 observations over 8 years). Prevalence of hypertension was 3.9% for women and 5.2% for men, although diagnosis of persistent hypertension based on multiple observations reduced prevalence to 2.9% for both sexes. Mixed-effects models revealed systolic, diastolic, and pulse blood pressure increases of 2.86 (P

Sexual risk-taking and reproductive morbidity are common among rapidly modernizing populations with little material wealth, limited schooling, minimal access to modern contraception and healthcare, and gendered inequalities in resource access that limit female autonomy in cohabiting relationships. Few studies have examined how modernization influences sexual risk-taking and reproductive health early in demographic transition. Tsimane are a natural fertility population of Bolivian forager-farmers; they are not urbanized, reside in small-scale villages, and lack public health infrastructure. We test whether modernization is associated with greater sexual risk-taking, report prevalence of gynecological morbidity (GM), and test whether modernization, sexual risk-taking and parity are associated with greater risk of GM. Data were collected from 2002-2010 using interviews, clinical exams, and laboratory analysis of cervical cells. We find opposing effects of modernization on both sexual risk-taking and risk of GM. Residential proximity to town and Spanish fluency are associated with greater likelihood of men's infidelity, and with number of lifetime sexual partners for men and women. However, for women, literacy is associated with delayed sexual debut after controlling for town proximity. Fifty-five percent of women present at least one clinical indicator of GM (n = 377); 48% present inflammation of cervical cells, and in 11% the inflammation results from sexually transmitted infection (trichomoniasis). Despite having easier access to modern healthcare, women residing near town experience greater likelihood of cervical inflammation and trichomoniasis relative to women in remote villages; women who are fluent in Spanish are also more likely to present trichomoniasis relative to women with moderate or no fluency. However, literate women experience lower likelihood of trichomoniasis. Parity has no effect on risk of GM. Our results suggest a net increase in risk of reproductive morbidity among rapidly modernizing, resource-stressed populations.

UnlabelledMinimal data on bone mineral density changes are available from populations in developing countries. Using calcaneal quantitative ultrasound (QUS) techniques, the current study contributes to remedying this gap in the literature by establishing a normative data set on the indigenous Shuar and non-Shuar Colonos of the Ecuadorian Amazon.PurposeThe paucity of bone mineral density (BMD) data from populations in developing countries partially reflects the lack of diagnostic resources in these areas. Portable QUS techniques now enable researchers to collect bone health data in remote field-based settings and to contribute normative data from developing regions. The main objective of this study is to establish normative QUS data for two Ecuadorian Amazonian populations-the indigenous Shuar and non-Shuar Colonos. The effects of ethnic group, sex, age, and body size on QUS parameters are also considered.MethodsA study cohort consisting of 227 Shuar and 261 Colonos (15-91 years old) were recruited from several small rural Ecuadorian communities in the Upano River Valley. Calcaneal QUS parameters were collected on the right heel of each participant using a Sahara bone sonometer. Three ultrasound generated parameters were employed: broadband ultrasound attenuation (BUA), speed of sound (SOS), and calculated heel BMD (hBMD).ResultsIn both populations and sexes, all QUS values were progressively lower with advancing age. Shuar have significantly higher QUS values than Colonos, with most pronounced differences found between pre-menopausal Shuar and Colono females. Multiple regression analyses show that age is a key predictor of QUS while weight alone is a less consistent determinant. Both Shuar males and females display comparatively greater QUS parameters than other reference populations.ConclusionsThese normative data for three calcaneal QUS parameters will be useful for predicting fracture risk and determining diagnostic QUS criteria of osteoporosis in non-industrialized populations in South America and elsewhere.

ObjectiveMinimal information on physical activity is available for non-Western populations undergoing the transition to a market economy. This is unfortunate given the importance of these data for understanding health issues such as the global obesity epidemic. We consider the utility of using accelerometry technology to examine activity patterns and energy use regulation among indigenous Shuar, an Ecuadorian forager-horticulturalist population undergoing economic and lifestyle change. We investigate sex differences in Shuar activity patterns and the effects of reproductive status on activity. Finally, we discuss the potential of accelerometry use in human biology research.MethodsPhysical activity levels were measured using Actical accelerometers in 49 indigenous Shuar adults (23 males, 26 females) from a rural Ecuadorian community. Female participants were in various reproductive states including pregnant, lactating, and nonpregnant/nonlactating.ResultsActivity counts (AC), activity energy expenditure (AEE), and physical activity levels (PAL) were significantly higher (P < 0.05) in males than females. Significant differences in energy expenditure were found among pregnant or lactating females and males with pregnant or lactating partners (P < 0.001). Males with pregnant or lactating partners also had significantly higher activity levels than did other men (P < 0.01).ConclusionsShuar activity levels are relatively low compared to other non-Western populations. Despite increasing market integration, pregnant and lactating females seem to be adopting a strategy noted in other subsistence populations where male participation in subsistence activities increases to compensate for their partners' elevated reproductive costs. Despite certain limitations, use of accelerometry in human biology research shows promise.

BackgroundThe peak shift model predicts that the age-profile of a pathogen's prevalence depends upon its transmission rate, peaking earlier in populations with higher transmission and declining as partial immunity is acquired. Helminth infections are associated with increased immunoglobulin E (IgE), which may convey partial immunity and influence the peak shift. Although studies have noted peak shifts in helminths, corresponding peak shifts in total IgE have not been investigated, nor has the age-patterning been carefully examined across populations. We test for differences in the age-patterning of IgE between two South American forager-horticulturalist populations and the United States: the Tsimane of Bolivia (n=832), the Shuar of Ecuador (n=289), and the U.S. NHANES (n=8,336). We then examine the relationship between total IgE and helminth prevalences in the Tsimane.Methodology/principal findingsTotal IgE levels were assessed in serum and dried blood spots and age-patterns examined with non-linear regression models. Tsimane had the highest IgE (geometric mean =8,182 IU/ml), followed by Shuar (1,252 IU/ml), and NHANES (52 IU/ml). Consistent with predictions, higher population IgE was associated with steeper increases at early ages and earlier peaks: Tsimane IgE peaked at 7 years, Shuar at 10 years, and NHANES at 17 years. For Tsimane, the age-pattern was compared with fecal helminth prevalences. Overall, 57% had detectable eggs or larva, with hookworm (45.4%) and Ascaris lumbricoides (19.9%) the most prevalent. The peak in total IgE occurred around the peak in A. lumbricoides, which was associated with higher IgE in children

ObjectivesInfection with helminths is associated with shifts in host immunity, including increased production of immunoglobulin E (IgE) and reduced inflammation. Given limited energy budgets, these shifts may involve changes in energy allocation toward competing demands. Here we test for potential trade-offs between growth, IgE, and the inflammatory marker C-reactive protein (CRP).MethodsDried blood spots and anthropometrics were collected from 162 Shuar forager-horticulturalists from a village in southeastern Ecuador. Enzyme-linked immunosorbent assays (ELISAs) were used to measure IgE and CRP. Relationships among IgE, CRP, and anthropometrics were examined in three groups: children aged 2-7 years (n = 63), children aged 8-15 (n = 61), and adults over age 18 (n = 37).ResultsGeometric mean IgE was 1,196 IU ml⁻¹ while geometric mean CRP was 1.33 mg l⁻¹. In children, IgE and CRP were negatively correlated (r = -0.21, P = 0.02, df = 122). Controlling for fat stores and age, IgE was associated with lower stature in children (t = -2.04, P = 0.04, df = 109), and adults (t = -3.29, P < 0.01, df = 33). In children there was a significant interaction between age and CRP, such that in younger children CRP was associated with shorter stature, but in older children was associated with greater stature (t = 2.15, P = 0.04, df = 109).ConclusionsThese results suggest that infection with helminths may have hidden costs associated with immunological changes, and that these costs may ultimately affect growth and other life history parameters.

We describe and compare the growth of three groups of juveniles, aged 0-18, who experience different degrees of market integration and acculturation in the Ecuadorian Amazon. These include 1,384 indigenous Shuar from the Upano Valley of Ecuador and surrounding areas, 570 nonindigenous colono (or colonist) children from the same area, and 42 Shiwiar from the interior of Ecuador. We use differences between these populations in National Health and Nutrition Examination Survey (NHANES) z-scores to assess the effects of changing subsistence patterns on Shuar growth and nutrition. Although, for all three groups, mean height-for-age z-scores were negative, Shuar z-scores were significantly lower than either colono or Shiwiar z-scores. Mean weight-for-age z-scores were also negative for Shuar and colono juveniles, while mean BMI-for-age and weight-for-height z-scores were greater than zero for all three groups. Using NHANES standards, 41% of male and 38% of female Shuar were classified as stunted, versus 16% of male and 20% of female colonos. Compared to Shuar, colonos were three times less likely to be stunted (OR = 0.33, P < 0.01) and Shiwiar were eight times less likely to be stunted (OR = 0.13, P = 0.01). These differences suggest that changes in diet have negatively affected Shuar growth and nutrition.

ObjectivesTo determine and compare hepatitis C (HCV) screening and testing rates among four groups: those with (i) bipolar disorder [BD group (history of BD but no substance use disorder)]; (ii) substance use disorders [SUD group (history of SUD but no BD)]; (iii) co-occurring disorders [DD group (history of both BD and an SUD)]; and (iv) a control group (no history of either bipolar disorder or substance use disorder). Our hypothesis was that HCV antibody testing rates and HCV prevalence would be higher in the BD, SUD, and DD groups than the control group.MethodsData were retrospectively collected on 325,410 patients seen between 1998 and 2004 within facilities and clinics of the Veterans Integrated Service Network (VISN) 20 Northwest Veterans Health Care Administration from electronic medical records. HCV screening and prevalence rates were compared between the BD, SUD, DD, and control groups. Odds ratios and relative risks were determined and compared between groups.ResultsPatients in the BD, SUD, and DD groups had been tested at a higher rate than controls and were at increased risk for HCV infection compared with controls. These high-risk groups had a 1.31-fold, 4.86-fold, and 5.46-fold increase in the relative risk of HCV infection, respectively. Overall, compared to the control group, the relative risk of a patient having HCV if he or she had BD (with or without an SUD) was 3.6.ConclusionsPatients with BD and comorbid SUD had an over fourfold increase in relative risk for HCV than our control group and a similar risk as patients in our SUD group. Furthermore, even if bipolar patients did not have a comorbid SUD (the BD group), their relative risk of HCV was significantly higher than that of the control group. This suggests that patients with BD, particularly those with a comorbid SUD, should be screened and tested for HCV.

BackgroundIndividuals with substance use disorders (SUDs) are at increased risk for hepatitis C viral infection (HCV), and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN) completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20) of the Veterans Healthcare Administration (VHA) between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN) or combination therapy (IFN and ribavirin) who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group) and patients without a history of SUD (SUD- Group).ResultsOdds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%), and if they had genotypes 1 and 4 (39.5% vs. 39.9%). Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8%) and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%).ConclusionIndividuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy.

This paper reviews the preclinical and clinical evidence regarding the use of the dietary supplement 5-hydroxytryptophan (5-HTP) for the treatment of depression. In the absence of supplementation with exogenous 5-HTP, the amount of endogenous 5-HTP available for serotonin synthesis depends on the availability of tryptophan and on the activity of various enzymes, especially tryptophan hydroxylase, indoleamine 2,3-dioxygenase, and tryptophan 2,3-dioxygenase (TDO). Factors affecting each of these are reviewed. The amount of 5-HTP reaching the central nervous system (CNS) is affected by the extent to which 5-HTP is converted to serotonin in the periphery. This conversion is controlled by the enzyme amino acid decarboxylase, which, in the periphery, can be blocked by peripheral decarboxylase inhibitors (PDIs) such as carbidopa. Preclinical and clinical evidence for the efficacy of 5-HTP for depression is reviewed, with emphasis on double-blind, placebo-controlled (DB-PC) trials. Safety issues with 5-HTP are also reviewed, with emphasis on eosinophilia myalgia syndrome (EMS) and serotonin syndrome.

Interferon-alpha (IFN) is widely used in the treatment of certain cancers and viral infections, including hepatitis C (HCV). Unfortunately, depression is a common side effect of IFN therapy, affecting approximately a third of HCV patients receiving IFN therapy. Studies have shown that selective serotonin reuptake inhibitors (SSRIs) can effectively treat IFN-induced depression in only 63-75% of cases. For the remaining percentage, depression often necessitates dose reduction of or discontinuation from IFN therapy. Emerging evidence indicates that IFN may cause depression by affecting brain serotonin. IFN has been shown to increase serotonin reuptake and to decrease serotonin synthesis. We hypothesize that SSRIs are not fully effective because they affect only serotonin reuptake, not serotonin synthesis, and that effective treatment must address both uptake and synthesis. 5-Hydroxytryptophan (5-HTP) effectively increases central nervous system synthesis of serotonin. It is the immediate precursor of serotonin and is widely available as a dietary supplement, which is well absorbed after an oral dose. Several double-blind studies have shown 5-HTP to be effective in the treatment of nondrug-induced depression. We hypothesize that patients who become depressed on IFN will respond to the synergistic combination of SSRIs plus 5-HTP.

Cellular iron uptake in most tissues occurs via endocytosis of diferric transferrin (Tf) bound to the transferrin receptor (TfR). Recently, a second transferrin receptor, transferrin receptor 2 (TfR2), has been identified and shown to play a critical role in iron metabolism. TfR2 is capable of Tf-mediated iron uptake and mutations in this gene result in a rare form of hereditary hemochromatosis unrelated to the hereditary hemochromatosis protein, HFE. Unlike TfR, TfR2 expression is not controlled by cellular iron concentrations and little information is currently available regarding the role of TfR2 in cellular iron homeostasis. To investigate the relationship between TfR and TfR2, we performed a series of in vivo and in vitro experiments using antibodies generated to each receptor. Western blots demonstrate that TfR2 protein is expressed strongest in erythroid/myeloid cell lines. Metabolic labeling studies indicate that TfR2 protein levels are approximately 20-fold lower than TfR in these cells. TfR and TfR2 have similar cellular localizations in K562 cells and coimmunoprecipitate to only a very limited extent. Western analysis of the receptors under nonreducing conditions reveals that they can form heterodimers.

Objective: Cytomegalovirus (CMV) infection is associated with age‐related chronic disease, and co‐infection with Epstein‐Barr virus (EBV) may compound disease risk. We aimed to assess the frequency of CMV infection and its relationship with age among EBV seropositive individuals in an Indigenous Amazonian population. Methods: We report concentrations of CMV and EBV antibodies in dried blood spot samples collected from 157 EBV positive Shuar participants aged 15–86 years (60.5% female) to assess CMV infection rate. We used logistic and linear regression models to examine associations among CMV, EBV, and age, adjusting for sex, geographic region, and body mass index. Results: Nearly two‐thirds (63.1%) of EBV seropositive participants were also CMV seropositive. A 1‐year increase in age was associated with 3.4% higher odds of CMV infection (OR [95% CI]: 1.034 [1.009–1.064], p =.012), but CMV antibody concentration was not significantly associated with age or EBV antibody concentration among co‐infected individuals. Conclusions: Herpesvirus‐related immunosenescence may be important to understanding chronic disease risk among Shuar. Future studies should further explore the role of co‐infection in shaping age‐related changes in immune function. [ABSTRACT FROM AUTHOR]