Severe drought exposure in utero associates to children's epigenetic age acceleration in a global climate change hot spot.

The goal of this study is to examine the association between in utero drought exposure and epigenetic age acceleration (EAA) in a global climate change hot spot. Calculations of EAA in adults using DNA methylation have been found to accurately predict chronic disease and longevity. However, fewer studies have examined EAA in children, and drought exposure in utero has not been investigated. Additionally, studies of EAA in low-income countries with diverse populations are rare. We assess EAA using epigenetic clocks and two DNAm-based pace-of-aging measurements from whole saliva samples in 104 drought-exposed children and 109 same-sex sibling controls in northern Kenya. We find a positive association between in utero drought exposure and EAA in two epigenetic clocks (Hannum's and GrimAge) and a negative association in the DNAm based telomere length (DNAmTL) clock. The combined impact of drought's multiple deleterious stressors may reduce overall life expectancy through accelerated epigenetic aging.

Mineral Nutrition of Samburu Adolescents: A Comparative Study of Pastoralist Communities in Kenya.

Objectives: This study aimed to characterize mineral nutrition (copper, magnesium, selenium, and zinc) in Samburu pastoralist youth, in the context of differential cultural transitions due to uneven changes in educational access, herding intensity, polygyny, and access to wild, domesticated, and market-sourced foods. Materials and Methods: Whole dried blood spots were collected in a total of 161 youth (highlands, n = 97; lowlands, n = 64) to assess concentrations of: cadmium, copper, lead, magnesium, mercury, selenium, and zinc. Concentrations were determined through Inductively Coupled Mass Spectrometry. Dietary intakes were assessed by 24-hour recall method and calculation of probability of inadequate intakes. WHO protocols were applied to collect anthropometric measures in the youth. Results: Nearly half of the adolescents (47.8%) fell below the reference range for zinc status, and 88.2% had low zinc-to-copper ratios. High probability of nutrient inadequacies were evident for protein, fat, vitamins A, B12, C, and E. In generalized linear modeling, lowland residence was negatively associated with zinc status and the zinc-to-copper ratio, and positively correlated with selenium and copper status. Other significant correlates were: dairy livestock ownership; wife number of the youth's mother; meat consumption; vegetable consumption; protein intake; infectious disease morbidities; BMI; and hemoglobin concentrations. Discussion: In recent decades, Samburu pastoralists of northern Kenya have experienced marked dietary changes in the context of market integration, extreme drought, diminishing pasture availability, and violent civil conflict. Some children (particularly boys) successfully supplement their diets by foraging for wild foods, while others (particularly actively herding girls) may be more vulnerable.

Epigenetic mechanisms underlying the association between maternal climate stress and child growth: characterizing severe drought and its impact on a Kenyan community engaging in a climate change-sensitive livelihood.

Pastoralists in East Africa are among the world's most vulnerable communities to climate change, already living near their upper thermal limits and engaging in a climate-sensitive livelihood in a climate change global hot spot. Pregnant women and children are even more at risk. Here, we report the findings of a study characterizing Samburu pastoralist women's experiences of severe drought and outcomes in their children (N = 213, 1.8-9.6 y). First, we examined potential DNA methylation (DNAm) differences between children exposed to severe drought in utero and same-sex unexposed siblings. Next, we performed a high-dimensional mediation analysis to test whether DNAm mediated associations of exposure to severe drought with body weight and adiposity. DNAm was measured using the Infinium MethylationEPIC BeadChip array. After quality control; batch, chip, and genomic inflation corrections; covariate adjustment; and multiple testing correction, 16 CpG sites were differentially methylated between exposed and unexposed children, predominantly in metabolism and immune function pathways. We found a significant indirect effect of drought exposure on child body weight through cg03771070. Our results are the first to identify biological mediators linking severe drought to child growth in a low-income global hot spot for climate change. A better understanding of the mechanisms underlying the association between drought exposure and child growth is important to increasing climate change resilience by identifying targets for intervention.

For pregnant women in populations engaging in climate-sensitive livelihoods, severe drought is characterized by multiple stressors, including intense, sometimes hazardous labour, food and water insecurity, and other stressors. This study found differential methylation between children exposed to severe drought in utero versus their unexposed same-sex siblings in 16 CpG sites in pathways relevant to the immune system and metabolism. Cg03771070 was found to mediate the association between severe drought exposure and child body weight. The necessary next step includes context-nuanced prospective studies to further refine our understanding of biological mechanisms for climate-associated child outcomes. This is necessary for targeted interventions to improve climate change resilience in these communities.

Heavy metal blood concentrations in association with sociocultural characteristics, anthropometry and anemia among Kenyan adolescents.

OBJECTIVES: To measure heavy metal concentrations among Kenyan youth and quantify associations with sociocultural, demographic, and health factors as well as anthropometry. METHODS: Using data from a study of semi-nomadic pastoralists in Samburu County, Kenya, we measured blood concentrations of lead (Pb), mercury (Hg), and cadmium (Cd) in 161 adolescents. We identified sociocultural, demographic and health characteristics associated with each metal and quantified the association between metals and adolescent anthropometry. RESULTS: Median blood concentrations of Pb, Cd, and Hg were 1.82 µg/dL, 0.24 µg/L and 0.16 µg/L, respectively. Place of residence (highlands vs lowlands) was a determinant of metal concentrations. Hg was inversely related to anemia, and metals were not associated with anthropometry. CONCLUSIONS: In this population of Samburu adolescents, median Pb and Cd blood concentrations were higher than other North American or European biomonitoring studies. These findings motivate further investigation into the environmental sources of metals in this community.

Family socioeconomic status and child telomere length among the Samburu of Kenya.

Previous research in high-income countries suggests that children from families with lower socioeconomic status (SES) tend to have shorter telomere length - a biomarker of stress and cell aging - than children from families with greater social and economic resources. However, little is known about predictors of child telomere length in low-income settings. Data for the current study are from a sample of 214 Samburu children aged 1-9 years. The Samburu are semi-nomadic pastoralists who live in the Rift Valley of north-central Kenya. Samburu livelihood is based primarily on livestock, and polygynous marriage is common. Drawing on prior ethnographic research, we measured 14 culturally relevant indicators of family SES, including mother's education, head of household's education, whether the child is currently attending school, household spending, mother's employment history, head of household's employment history, mother's perceived wealth, whether the child lives in a modern house, livestock holdings (total, cows, sheep/goats, and camels), mother's wife number, and whether the child lives in a polygynous household. Telomere length was measured in salivary DNA by the quantitative polymerase chain reaction (qPCR) method. Using latent class analysis, we identified four groups of children that are similar based on the 14 indicators of family SES: Lower SES; Middle SES, Traditional; Middle SES, Modern; and Higher SES. SES classes were not significantly associated with child telomere length. In models examining individual indicators of SES, we found that telomere length was 0.57 standard deviations greater for children who lived in families in the lowest quartile of total livestock holdings compared to those in the highest quartile (b = 0.57, p = 0.03). While additional research is needed to identify the mechanisms underlying this counterintuitive finding, the current study highlights the importance of cultural context in shaping the social gradient in health.

Lifetime stress and war exposure timing may predict methylation changes at NR3C1 based on a pilot study in a warrior cohort in a small-scale society in Kenya.

OBJECTIVES: Candidate gene methylation studies of NR3C1 have identified associations with psychosocial adversity, including war trauma. This pilot study (sample sizes from 22 to 45 for primary analyses) examined NR3C1 methylation in a group of Kenyan pastoralist young men in relation to culturally relevant traumatic experiences, including participation in coalitional lethal gun violence. METHODS: Adolescent and young adult Samburu men ("warriors") were recruited for participation. DNA was obtained from whole saliva and methylation analyses performed using mass spectrometry. We performed a data reduction of variables from a standardized instrument of lifetime stress using a factor analysis and we assessed the association between the extracted factors with culturally relevant and cross-culturally comparative experiences. RESULTS: Cumulative lifetime trauma exposure and forms of violence to which warriors are particularly susceptible were associated with DNA methylation changes in the NR3C1 1F promoter region but not in the NR3C1 1D promoter region. However, sensitivity analyses revealed significant associations between individual CpG sites in both regions and cumulative stress exposures, war exposure timing, and war fatalities. CONCLUSIONS: This study supports the importance of NR3C1 methylation changes in response to challenging life circumstances, including in a global south cultural context that contrasts in notable ways from global north contexts and from the starkly tragic examples of the Rwandan genocide and war-associated rape explored in recent studies. Timing of traumatic exposure and culturally salient means to measure enduring symptoms of trauma remain important considerations for DNA methylation studies.

Prosocial Emotion, Adolescence, and Warfare : DNA Methylation Associates with Culturally Salient Combat Variables.

Examining the costs and motivations of warfare is key to conundrums concerning the relevance of this troubling phenomenon to the evolution of social attachment and cooperation, particularly during adolescence and young adulthood-the developmental time period during which many participants are first recruited for warfare. The study focuses on Samburu, a pastoralist society of approximately 200,000 people occupying northern Kenya's semi-arid and arid lands, asking what role the emotionally sensitized, peer-driven adolescent life stage may have played in the cultural and genetic coevolution of coalitional lethal aggression. Research in small-scale societies provides unparalleled opportunities for sharply defined variables, particularly in age generation societies in which all young men are initiated into "warriorhood." Proposing an epigenetic and component behavior approach, we examine whether raiding activities such as number of raids, killing, and sparing enemy lives associate with DNA methylation in two candidate genes: MAOA, linked to mood and arousal, and NR3C1, linked to stress and immune response. We report statistically significant associations between the epigenetic variables and the combat (exposure) variables of overall raiding activity and reportedly showing mercy to enemies. In contrast, epigenetic variables did not associate with post-traumatic stress disorder (PTSD) symptom scores (a potential outcome measure), and the only combat variable associated with PTSD (but not DNA methylation) was losing one's own livestock in a raid. These findings raise important questions concerning the mechanisms driving warfare's paradoxical mix of violent and altruistic behaviors.

Health-seeking pathway and factors leading to delays in tuberculosis diagnosis in West Pokot County, Kenya: A grounded theory study.

BACKGROUND: Patients' health-seeking behaviour can lead to delays in tuberculosis (TB) diagnosis, however little is known about the experiences and treatment pathways of patients diagnosed with TB in Kenya. The aim of this study is to explore the health seeking practices and factors contributing to delay in TB diagnosis. METHODS: This study was based on explorative qualitative research using a constructivist grounded theory approach. A total of 61 TB patients in the intensive phase of treatment were recruited as informants in the study. Six focus group discussions and 15 in-depth interviews were used to collect data. Data were analysed through three step coding using the grounded theory approach. RESULTS: Participants adopted different treatment pathways as they sought care from a pluralistic health care system involving traditional healers, herbalists, private clinic, drug shops and the public health sector. The study revealed an explanatory model of factors leading to delay illustrated by the participant's expression "I suffered for a long time." The model is comprised of three categories that lead to delays, namely individual, social-cultural and structural factors. CONCLUSION: There is a need to improve timely diagnosis of TB through innovative approaches such as intensive case finding. Similarly, the health-care system should decentralize TB services as much as possible and offer free diagnostic services to increase accessibility.

Knowledge and perceptions of tuberculosis among patients in a pastoralist community in Kenya: a qualitative study.

INTRODUCTION: Tuberculosis awareness is crucial to the success of control and prevention of tuberculosis. However, the knowledge and perceptions of tuberculosis patients in rural Kenya is not well documented. The study sought to explore the knowledge and perceptions of TB patients in West Pokot County Kenya. METHODS: This was a qualitative descriptive study conducted between January-March 2016. A total of 61 pulmonary tuberculosis patients took part in the study which comprised 6 focus group discussion and 15 in-depth interviews. Thematic analysis was used to analyse the data. RESULTS: Participants perceived TB as a serious contagious disease that is hard to diagnose and treat. They attributed tuberculosis to smoking, drinking alcohol, dust, cold air, witchcraft, trauma to the chest, contact with livestock and genetic factors. They believed that TB was transmitted through casual contact with TB patients and sharing of utensils. CONCLUSION: The study showed a lot of misperceptions among tuberculosis patients. The tuberculosis program should heighten patient education to improve patient knowledge and put more effort to dispel misinformation about the cause and mode of transmission of the disease.