Metapopulation dynamics of SARS-CoV-2 transmission in a small-scale Amazonian society.

The severity of infectious disease outbreaks is governed by patterns of human contact, which vary by geography, social organization, mobility, access to technology and healthcare, economic development, and culture. Whereas globalized societies and urban centers exhibit characteristics that can heighten vulnerability to pandemics, small-scale subsistence societies occupying remote, rural areas may be buffered. Accordingly, voluntary collective isolation has been proposed as one strategy to mitigate the impacts of COVID-19 and other pandemics on small-scale Indigenous populations with minimal access to healthcare infrastructure. To assess the vulnerability of such populations and the viability of interventions such as voluntary collective isolation, we simulate and analyze the dynamics of SARS-CoV-2 infection among Amazonian forager-horticulturalists in Bolivia using a stochastic network metapopulation model parameterized with high-resolution empirical data on population structure, mobility, and contact networks. Our model suggests that relative isolation offers little protection at the population level (expected approximately 80% cumulative incidence), and more remote communities are not conferred protection via greater distance from outside sources of infection, due to common features of small-scale societies that promote rapid disease transmission such as high rates of travel and dense social networks. Neighborhood density, central household location in villages, and household size greatly increase the individual risk of infection. Simulated interventions further demonstrate that without implausibly high levels of centralized control, collective isolation is unlikely to be effective, especially if it is difficult to restrict visitation between communities as well as travel to outside areas. Finally, comparison of model results to empirical COVID-19 outcomes measured via seroassay suggest that our theoretical model is successful at predicting outbreak severity at both the population and community levels. Taken together, these findings suggest that the social organization and relative isolation from urban centers of many rural Indigenous communities offer little protection from pandemics and that standard control measures, including vaccination, are required to counteract effects of tight-knit social structures characteristic of small-scale populations.

Applying an evolutionary mismatch framework to understand disease susceptibility.

Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of "lifestyle" diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be "mismatched" and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions, with different health effects in "ancestral" versus "modern" environments. To identify such loci, we advocate for combining genomic tools in partnership with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the "matched" to "mismatched" spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.

Natural selection of immune and metabolic genes associated with health in two lowland Bolivian populations.

A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype-phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands. We focused most intensively on the Tsimane, because long-term anthropological work with this group has shown that they have a high burden of both macro and microparasites, as well as minimal cardiometabolic disease or dementia. We therefore generated genome-wide genotype data for Tsimane individuals to study natural selection, and paired this with blood mRNA-seq as well as cardiometabolic and immune biomarker data generated from a larger sample that included both populations. In the Tsimane, we identified 21 regions that are candidates for selective sweeps, as well as 5 immune traits that show evidence for polygenic selection (e.g., C-reactive protein levels and the response to coronaviruses). Genes overlapping candidate regions were strongly enriched for known involvement in immune-related traits, such as abundance of lymphocytes and eosinophils. Importantly, we were also able to draw on extensive phenotype information for the Tsimane and Moseten and link five regions (containing PSD4, MUC21 and MUC22, TOX2, ANXA6, and ABCA1) with biomarkers of immune and metabolic function. Together, our work highlights the utility of pairing evolutionary analyses with anthropological and biomedical data to gain insight into the genetic basis of health-related traits.

Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations.

Little is known about brain aging or dementia in nonindustrialized environments that are similar to how humans lived throughout evolutionary history. This paper examines brain volume (BV) in middle and old age among two indigenous South American populations, the Tsimane and Moseten, whose lifestyles and environments diverge from those in high-income nations. With a sample of 1,165 individuals aged 40 to 94, we analyze population differences in cross-sectional rates of decline in BV with age. We also assess the relationships of BV with energy biomarkers and arterial disease and compare them against findings in industrialized contexts. The analyses test three hypotheses derived from an evolutionary model of brain health, which we call the embarrassment of riches (EOR). The model hypothesizes that food energy was positively associated with late life BV in the physically active, food-limited past, but excess body mass and adiposity are now associated with reduced BV in industrialized societies in middle and older ages. We find that the relationship of BV with both non-HDL cholesterol and body mass index is curvilinear, positive from the lowest values to 1.4 to 1.6 SDs above the mean, and negative from that value to the highest values. The more acculturated Moseten exhibit a steeper decrease in BV with age than Tsimane, but still shallower than US and European populations. Lastly, aortic arteriosclerosis is associated with lower BV. Complemented by findings from the United States and Europe, our results are consistent with the EOR model, with implications for interventions to improve brain health.

Labour's pain: strenuous subsistence work, mechanical wear-and-tear and musculoskeletal pain in a non-industrialized population.

Musculoskeletal pain is the most debilitating human health condition. Neurophysiological pain mechanisms are highly conserved and promote somatic maintenance and learning to avoid future harm. However, some chronic pain might be more common owing to mismatches between modern lifestyles and traits that originally evolved under distinct premodern conditions. To inform assumptions about factors affecting chronic pain vulnerability prior to industrialization, we assess pain prevalence, perceived causes, and predictors among Tsimane forager-horticulturalists. Habitual subsistence work is the primary reported cause of pain throughout life for both sexes, and pain is more common with age, especially in the back, and for those with more musculoskeletal problems. Sex differences in pain are relatively weak, and we find no association between women's reproductive history and pain, contrary to the hypothesis that reproduction causes women's greater pain susceptibility. Age-standardized current pain prevalence is 1.7-8.2 times higher for Tsimane than other select populations, and Tsimane chronic pain prevalence is within the range of variation observed elsewhere. Chronic low back pain is not a 'mismatch disease' limited to post-industrialized populations. Hominin musculoskeletal changes supporting bipedalism probably imposed health costs, which, after millions of years of evolution, remain an epidemiological burden that may be exacerbated by modern conditions.

Adolescence is characterized by more sedentary behaviour and less physical activity even among highly active forager-farmers.

Over 80% of adolescents worldwide are insufficiently active, posing massive public health and economic challenges. Declining physical activity (PA) and sex differences in PA consistently accompany transitions from childhood to adulthood in post-industrialized populations and are attributed to psychosocial and environmental factors. An overarching evolutionary theoretical framework and data from pre-industrialized populations are lacking. This cross-sectional study tests hypotheses from life history theory, that adolescent PA is inversely related to age, but this association is mediated by Tanner stage, reflecting higher and sex-specific energetic demands for growth and reproductive maturation. Detailed measures of PA and pubertal maturation are assessed among Tsimane forager-farmers (age: 7-22 years; 50% female, n = 110). Most Tsimane sampled (71%) meet World Health Organization PA guidelines (greater than or equal to 60 min/day of moderate-to-vigorous PA). Like post-industrialized populations, sex differences and inverse age-activity associations were observed. Tanner stage significantly mediated age-activity associations. Adolescence presents difficulties to PA engagement that warrant further consideration in PA intervention approaches to improve public health.

Energetic costs of testosterone in two subsistence populations.

OBJECTIVE: Testosterone plays a role in mediating energetic trade-offs between growth, maintenance, and reproduction. Investments in a high testosterone phenotype trade-off against other functions, particularly survival-enhancing immune function and cellular repair; thus only individuals in good condition can maintain both a high testosterone phenotype and somatic maintenance. While these effects are observed in experimental manipulations, they are difficult to demonstrate in free-living animals, particularly in humans. We hypothesize that individuals with higher testosterone will have higher energetic expenditures than those with lower testosterone. METHODS: Total energetic expenditure (TEE) was quantified using doubly labeled water in n = 40 Tsimane forager-horticulturalists (50% male, 18-87 years) and n = 11 Hadza hunter-gatherers (100% male, 18-65 years), two populations living subsistence lifestyles, high levels of physical activity, and high infectious burden. Urinary testosterone, TEE, body composition, and physical activity were measured to assess potential physical and behavioral costs associated with a high testosterone phenotype. RESULTS: Endogenous male testosterone was significantly associated with energetic expenditure, controlling for fat free mass; a one standard deviation increase in testosterone is associated with the expenditure of an additional 96-240 calories per day. DISCUSSION: These results suggest that a high testosterone phenotype, while beneficial for male reproduction, is also energetically expensive and likely only possible to maintain in healthy males in robust condition.

Prevalence of dementia and mild cognitive impairment in indigenous Bolivian forager-horticulturalists.

INTRODUCTION: We evaluated the prevalence of dementia and mild cognitive impairment (MCI) in indigenous Tsimane and Moseten, who lead a subsistence lifestyle. METHODS: Participants from population-based samples ≥ 60 years of age (n = 623) were assessed using adapted versions of the Modified Mini-Mental State Examination, informant interview, longitudinal cognitive testing and brain computed tomography (CT) scans. RESULTS: Tsimane exhibited five cases of dementia (among n = 435; crude prevalence = 1.2%, 95% confidence interval [CI]: 0.4, 2.7); Moseten exhibited one case (among n = 169; crude prevalence = 0.6%, 95% CI: 0.0, 3.2), all age ≥ 80 years. Age-standardized MCI prevalence was 7.7% (95% CI: 5.2, 10.3) in Tsimane and 9.8% (95% CI: 4.9, 14.6) in Moseten. Cognitive impairment was associated with visuospatial impairments, parkinsonian symptoms, and vascular calcification in the basal ganglia. DISCUSSION: The prevalence of dementia in this cohort is among the lowest in the world. Widespread intracranial medial arterial calcifications suggest a previously unrecognized, non-Alzheimer's disease (AD) dementia phenotype.

The Pregnancy Pickle: Evolved Immune Compensation Due to Pregnancy Underlies Sex Differences in Human Diseases.

We hypothesize that, ancestrally, sex-specific immune modulation evolved to facilitate survival of the pregnant person in the presence of an invasive placenta and an immunologically challenging pregnancy - an idea we term the 'pregnancy compensation hypothesis' (PCH). Further, we propose that sex differences in immune function are mediated, at least in part, by the evolution of gene content and dosage on the sex chromosomes, and are regulated by reproductive hormones. Finally, we propose that changes in reproductive ecology in industrialized environments exacerbate these evolved sex differences, resulting in the increasing risk of autoimmune disease observed in females, and a counteracting reduction in diseases such as cancer that can be combated by heightened immune surveillance. The PCH generates a series of expectations that can be tested empirically and that may help to identify the mechanisms underlying sex differences in modern human diseases.

There and back again: The biosocial dynamics of returning from the field.

BACKGROUND: Leaving "home" to pursue fieldwork is a necessity but also a rite of passage for many biological anthropology/human biology scholars. Field-based scientists prepare for the potential changes to activity patterns, sleep schedules, social interactions, and more that come with going to the field. However, returning from extended fieldwork and the reverse-culture shock, discomforts, and mental shifts that are part of the return process can be jarring, sometimes traumatic experiences. A failure to acknowledge and address such experiences can compromise the health and wellbeing of those returning. AIMS: We argue for an engaged awareness of the difficult nature of returning from the field and offer suggestions for individuals and programs to better train and prepare PhD students pursuing fieldwork. MATERIALS & METHODS: Here, we offer personal stories of "coming back" and give professional insights on how to best ready students and scholars for returning from fieldwork. DISCUSSION/CONCLUSION: By bringing forward and normalizing the difficulty of the fieldwork-return process, we hope that this reflection acts as a tool for future scholars to prepare to come home as successfully and consciously as possible.

Voluntary collective isolation as a best response to COVID-19 for indigenous populations? A case study and protocol from the Bolivian Amazon.

Indigenous communities worldwide share common features that make them especially vulnerable to the complications of and mortality from COVID-19. They also possess resilient attributes that can be leveraged to promote prevention efforts. How can indigenous communities best mitigate potential devastating effects of COVID-19? In Bolivia, where nearly half of all citizens claim indigenous origins, no specific guidelines have been outlined for indigenous communities inhabiting native communal territories. In this Public Health article, we describe collaborative efforts, as anthropologists, physicians, tribal leaders, and local officials, to develop and implement a multiphase COVID-19 prevention and containment plan focused on voluntary collective isolation and contact-tracing among Tsimane forager-horticulturalists in the Bolivian Amazon. Phase 1 involves education, outreach, and preparation, and phase 2 focuses on containment, patient management, and quarantine. Features of this plan might be exported and adapted to local circumstances elsewhere to prevent widespread mortality in indigenous communities.

Fathers' oxytocin responses to first holding their newborns: Interactions with testosterone reactivity to predict later parenting behavior and father-infant bonds.

Little is known about human fathers' physiology near infants' births. This may represent a period during which paternal psychobiological axes are sensitive to fathers' new experiences of interacting with their newborns and that can provide insights on how individual differences in fathers' biology relate to post-partum parenting. Drawing on a sample of men in South Bend, IN (U.S.), we report results from a longitudinal study of fathers' oxytocin, cortisol, and testosterone (N = 211) responses to their first holding of their infants on the day of birth and men's reported caregiving and father-infant bonding at 2-4 months post-partum (N = 114). First-time fathers' oxytocin was higher following first holding of their newborns, compared to their pre-holding levels. Contrasting with prior results, fathers' percentage change in oxytocin did not differ based on skin-to-skin or standard holding. Drawing on psychobiological frameworks, we modeled the interactions for oxytocin reactivity with testosterone and cortisol reactivity, respectively, in predicting father-infant outcomes months later. We found significant cross-over interactions for (oxytocin × testosterone) in predicting fathers' later post-partum involvement and bonding. Specifically, we found that fathers whose testosterone declined during holding reported greater post-partum play if their oxytocin increased, compared to fathers who experienced increases in both hormones. We also observed a similar non-significant interaction for (oxytocin × cortisol) in predicting fathers' post-partum play. Fathers whose testosterone declined during holding also reported less involvement in direct caregiving and lower father-infant bonding if their oxytocin decreased but greater direct care and bonding if their testosterone increased and oxytocin decreased. The results inform our understanding of the developmental time course of men's physiological responsiveness to father-infant interaction and its relevance to later fathering behavior and family relationships.

Relationship of sanitation, water boiling, and mosquito nets to health biomarkers in a rural subsistence population.

OBJECTIVES: Throughout human evolutionary history, parasites and pathogens were a major cause of mortality-modern urban life with public health infrastructure has changed disease exposure. We examine associations between boiling water, using latrines, mosquito net usage, and biomarkers among the Tsimane, a nonindustrial subsistence population with little public health infrastructure. METHODS: We conducted cross sectional surveys on water, latrines, and bed nets among 507 heads of households (aged 18-92 years, median age 41 years). Regression models estimated associations between behaviors and health biomarkers (ie, white blood cell count [WBC], hemoglobin, eosinophil count, and erythrocyte sedimentation rate) adjusting for age, sex, body mass index, wealth, schooling, and distance to the nearby market town. RESULTS: Latrine use is associated with 6.5% lower WBC count (ß = -679.6, P = .031, SE = 314.1), 17.4% lower eosinophil counts (ß = -244.7, P = .023, SE = 107.2), and reduced odds of eosinophilia (adjusted OR = 0.40, P < .019, 95% CI = 0.18-0.86). Boiling water and mosquito net use are not significantly associated with any biomarkers measured. CONCLUSIONS: In a subsistence population currently undergoing epidemiological transition, we find that latrine use was associated with several objective measures of health. This suggests that relatively low cost and low maintenance public health interventions may wish to focus on latrine use, as there is unmet need and potential health benefits for those who use latrines. Additionally, while the cost is higher, public health organizations aimed at improving sanitation may be able to use minimally invasive field-collected biomarkers as a diagnostic to objectively test the efficacy of interventions with greater specificity than anthropometric measurements.

Old friends and friendly fire: Pregnancy, hookworm infection, and anemia among tropical horticulturalists.

OBJECTIVES: Despite public health concerns about hookworm infection in pregnancy, little is known about immune profiles associated with hookworm (Necator americanus and Ancylostoma duodenale) infection during pregnancy. Fetal tolerance requirements may constrain maternal immune response to hookworm, thereby increasing susceptibility to new infections or increasing hemoglobin loss. To explore this possibility, we study systemic immune response and hemoglobin levels in a natural fertility population with endemic helminthic infection. METHODS: We used Bayesian multilevel models to analyze mixed longitudinal data on hemoglobin, hookworm infection, reproductive state, eosinophils, and erythrocyte sedimentation rate (ESR) to examine the effects of pregnancy and hookworm infection on nonspecific inflammation, cellular parasite response, and hemoglobin among 612 Tsimane women aged 15-45 (1016 observations). RESULTS: Pregnancy is associated with lower eosinophil counts and lower eosinophil response to hookworm, particularly during the second and third trimesters. Both hookworm and pregnancy are associated with higher ESR, with evidence for an interaction between the two causing further increases in the first trimester. Pregnancy is moderately associated with higher odds of hookworm infection (OR: 1.23, 95% CI: 0.83 to 1.83). Pregnancy and hookworm both decrease hemoglobin and may interact to accentuate this effect in the first-trimester of pregnancy (Interaction: ß: -0.30 g/dL; CI: -0.870 to 0.24). CONCLUSIONS: Our findings are consistent with a possible trade-off between hookworm immunity and successful pregnancy, and with the suggestion that hookworm and pregnancy may have synergistic effects, particularly in the first trimester.

Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study.

BACKGROUND: Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. METHODS: We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. FINDINGS: Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1-100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants. INTERPRETATION: Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. FUNDING: National Institute on Aging, National Institutes of Health; St Luke's Hospital of Kansas City; and Paleocardiology Foundation.

Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden.

The apolipoprotein E4 (E4) allele is present worldwide, despite its associations with higher risk of cardiovascular morbidity, accelerated cognitive decline during aging, and Alzheimer's disease (AD). The E4 allele is especially prevalent in some tropical regions with a high parasite burden. Equatorial populations also face a potential dual burden of high E4 prevalence combined with parasitic infections that can also reduce cognitive performance. We examined the interactions of E4, parasite burden, and cognitive performance in a traditional, nonindustrialized population of Amazonian forager-horticulturalists (N = 372) to test whether E4 protects against cognitive decline in environments with a heavy pathogen burden. Contrary to observations in industrial populations, older adult E4 carriers with high parasite burdens either maintained or showed slight improvements in cognitive performance, whereas non-E4 carriers with a high parasite burden showed reduced cognitive performance. Being an E4 carrier is the strongest risk factor to date of AD and cognitive decline in industrial populations; it is associated with greater cognitive performance in individuals facing a high parasite and pathogen load, suggesting advantages to the E4 allele under certain environmental conditions. The current mismatch between postindustrial hygienic lifestyles and active parasite-rich environs may be critical for understanding genetic risk for cognitive aging.-Trumble, B. C., Stieglitz, J., Blackwell, A. D., Allayee, H., Beheim, B., Finch, C. E., Gurven, M., Kaplan, H. Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden.

Group-level competition influences urinary steroid hormones among wild red-tailed monkeys, indicating energetic costs.

Various theories emphasize that intergroup competition should affect intragroup cooperation and social relationships, especially if the cost of intergroup competition outweighs that of intragroup competition. This cost of intergroup competition may be quantified by changes in physiological status, such as in the steroid hormones cortisol (C) and testosterone (T), which rise or are depressed during periods of energetic stress, respectively. Here we tested for changes in urinary C and T after intergroup encounters (IGEs) among wild red-tailed monkeys (Cercopithecus ascanius), a species that experiences frequent intergroup feeding competition, at the Ngogo station in Kibale National Park, Uganda. We assayed 108 urine samples, of which 36 were collected after IGEs, from 23 individuals in four social groups. Bayesian multilevel models controlling for various confounds revealed that IGEs increased C and decreased T relative to baseline, consistent with an energetic cost to IGEs. The C change was more apparent in samples collected early after IGEs, suggesting an anticipatory increase, whereas the T change was stronger in later samples, suggesting sustained energetic trade-offs. Hormone responses were not affected by the IGE outcome. This cost to intergroup competition, together with little evidence for intragroup competition in redtails and other guenons, establishes an interesting test case for theories emphasizing the effect of intergroup competition on intragroup cooperation.

Child nutritional status among births exceeding ideal family size in a high fertility population.

Ideal family size (IFS) is measured in social surveys to indicate unmet need for contraception and impending shifts in fertility behaviour. Whether exceeding IFS affects parental behaviour in ways that result in lower investments in child nutrition, well-being, and educational attainment is not known. This study examines parental IFS and the association between exceeding stated ideals and child nutritional status in a high-fertility, high-mortality population in the Bolivian Amazon. Height-for-age z-scores, weight-for-age z-scores, weight-for-height z-scores, stunting, haemoglobin, and anaemia status in 638 children aged 0-5 years are predicted as a function of birth order in relation to parental IFS, adjusting for household characteristics and mother and child random effects. Children of birth orders above paternal IFS experience higher weight-for-age z-scores when living further away from the market town of San Borja, consistent with underlying motivations for higher IFS and lower human capital investment in children in more remote areas (ß = .009, p = .027). Overall, we find no statistical evidence that birth orders in excess of parental ideals are associated with compromised child nutrition below age 2, a period of intensive breastfeeding in this population. Despite a vulnerability to nutritional deficiencies postweaning for children age 2-5, there was no association between birth order in excess of parental ideals and lower nutritional status. Further studies examining this association at various stages of the fertility transition will elucidate whether reported ideal or optimal family sizes are flexible as trade-offs between quality and quantity of children shift during the transition to lower fertility.