scholarly journals Individual-level variations in malaria susceptibility and acquisition of clinical protection

2021 ◽  
Vol 6 ◽  
pp. 22
Author(s):  
John Joseph Valletta ◽  
John W.G. Addy ◽  
Adam J. Reid ◽  
Francis M. Ndungu ◽  
Yaw Bediako ◽  
...  

After decades of research, our understanding of when and why individuals infected with Plasmodium falciparum develop clinical malaria is still limited. Correlates of immune protection are often sought through prospective cohort studies, where measured host factors are correlated against the incidence of clinical disease over a set period of time. However, robustly inferring individual-level protection from these population-level findings has proved difficult due to small effect sizes and high levels of variance underlying such data. In order to better understand the nature of these inter-individual variations, we analysed the long-term malaria epidemiology of children ≤12 years old growing up under seasonal exposure to the parasite in the sub-location of Junju, Kenya. Despite the cohort’s limited geographic expanse (ca. 3km x 10km), our data reveal a high degree of spatial and temporal variability in malaria prevalence and incidence rates, causing individuals to experience varying levels of exposure to the parasite at different times during their life. Analysing individual-level infection histories further reveal an unexpectedly high variability in the rate at which children experience clinical malaria episodes. Besides exposure to the parasite, measured as disease prevalence in the surrounding area, we find that the birth time of year has an independent effect on the individual’s risk of experiencing a clinical episode. Furthermore, our analyses reveal that those children with a history of an above average number of episodes are more likely to experience further episodes during the upcoming transmission season. These findings are indicative of phenotypic differences in the rates by which children acquire clinical protection to malaria and offer important insights into the natural variability underlying malaria epidemiology.

2021 ◽  
Vol 6 ◽  
pp. 22
Author(s):  
John Joseph Valletta ◽  
John W.G. Addy ◽  
Adam J. Reid ◽  
Francis M. Ndungu ◽  
Yaw Bediako ◽  
...  

After decades of research, our understanding of when and why individuals infected with Plasmodium falciparum develop clinical malaria is still limited. Correlates of immune protection are often sought through prospective cohort studies, where measured host factors are correlated against the incidence of clinical disease over a set period of time. However, robustly inferring individual-level protection from these population-level findings has proved difficult due to small effect sizes and high levels of variance underlying such data. In order to better understand the nature of these inter-individual variations, we analysed the long-term malaria epidemiology of children ≤12 years old growing up under seasonal exposure to the parasite in the sub-location of Junju, Kenya. Despite the cohort’s limited geographic expanse (ca. 3km x 10km), our data reveal a high degree of spatial and temporal variability in malaria prevalence and incidence rates, causing individuals to experience varying levels of exposure to the parasite at different times during their life. Analysing individual-level infection histories further reveal an unexpectedly high variability in the rate at which children experience clinical malaria episodes. Besides exposure to the parasite, measured as disease prevalence in the surrounding area, we find that the birth time of year has an independent effect on the individual’s risk of experiencing a clinical episode. Furthermore, our analyses reveal that those children with a history of an above average number of episodes are more likely to experience further episodes during the upcoming transmission season. These findings are indicative of phenotypic differences in the rates by which children acquire clinical protection to malaria and offer important insights into the natural variability underlying malaria epidemiology.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Natalie E Hofmann ◽  
Stephan Karl ◽  
Rahel Wampfler ◽  
Benson Kiniboro ◽  
Albina Teliki ◽  
...  

The molecular force of blood-stage infection (molFOB) is a quantitative surrogate metric for malaria transmission at population level and for exposure at individual level. Relationships between molFOB, parasite prevalence and clinical incidence were assessed in a treatment-to-reinfection cohort, where P.vivax (Pv) hypnozoites were eliminated in half the children by primaquine (PQ). Discounting relapses, children acquired equal numbers of new P. falciparum (Pf) and Pv blood-stage infections/year (Pf-molFOB = 0–18, Pv-molFOB = 0–23) resulting in comparable spatial and temporal patterns in incidence and prevalence of infections. Including relapses, Pv-molFOB increased >3 fold (relative to PQ-treated children) showing greater heterogeneity at individual (Pv-molFOB = 0–36) and village levels. Pf- and Pv-molFOB were strongly associated with clinical episode risk. Yearly Pf clinical incidence rate (IR = 0.28) was higher than for Pv (IR = 0.12) despite lower Pf-molFOB. These relationships between molFOB, clinical incidence and parasite prevalence reveal a comparable decline in Pf and Pv transmission that is normally hidden by the high burden of Pv relapses.Clinical trial registration: ClinicalTrials.gov NCT02143934


Author(s):  
Joshua D. Bundy ◽  
Zhengbao Zhu ◽  
Hongyan Ning ◽  
Victor W. Zhong ◽  
Amanda E. Paluch ◽  
...  

Background Better cardiovascular health (CVH) scores are associated with lower risk of cardiovascular disease (CVD). However, estimates of the potential population‐level impact of improving CVH on US CVD event rates are not currently available. Methods and Results Using data from the National Health and Nutrition Examination Survey 2011 to 2016 (n=11 696), we estimated the proportions of US adults in CVH groups. Levels of 7 American Heart Association CVH metrics were scored as ideal (2 points), intermediate (1 point), or poor (0 points), and summed to define overall CVH (low, 0–8 points; moderate, 9–11 points; or high, 12–14 points). Using individual‐level data from 7 US community‐based cohort studies (n=30 447), we estimated annual incidence rates of major CVD events by levels of CVH. Using the combined data sources, we estimated population attributable fractions of CVD and the number of CVD events that could be prevented annually if all US adults achieved high CVH. High CVH was identified in 7.3% (95% CI, 6.3%–8.3%) of US adults. We estimated that 70.0% (95% CI, 56.5%–79.9%) of CVD events were attributable to low and moderate CVH. If all US adults attained high CVH, we estimated that 2.0 (95% CI, 1.6–2.3) million CVD events could be prevented annually. If all US adults with low CVH attained moderate CVH, we estimated that 1.2 (95% CI, 1.0–1.4) million CVD events could be prevented annually. Conclusions The potential benefits of achieving high CVH in all US adults are considerable, and even a partial improvement in CVH scores would be highly beneficial.


2021 ◽  
Vol 34 (3) ◽  
pp. 234-241
Author(s):  
Norrina B Allen ◽  
Sadiya S Khan

Abstract High blood pressure (BP) is a strong modifiable risk factor for cardiovascular disease (CVD). Longitudinal BP patterns themselves may reflect the burden of risk and vascular damage due to prolonged cumulative exposure to high BP levels. Current studies have begun to characterize BP patterns as a trajectory over an individual’s lifetime. These BP trajectories take into account the absolute BP levels as well as the slope of BP changes throughout the lifetime thus incorporating longitudinal BP patterns into a single metric. Methodologic issues that need to be considered when examining BP trajectories include individual-level vs. population-level group-based modeling, use of distinct but complementary BP metrics (systolic, diastolic, mean arterial, mid, and pulse pressure), and potential for measurement errors related to varied settings, devices, and number of readings utilized. There appear to be very specific developmental periods during which divergent BP trajectories may emerge, specifically adolescence, the pregnancy period, and older adulthood. Lifetime BP trajectories are impacted by both individual-level and community-level factors and have been associated with incident hypertension, multimorbidity (CVD, renal disease, cognitive impairment), and overall life expectancy. Key unanswered questions remain around the additive predictive value of BP trajectories, intergenerational contributions to BP patterns (in utero BP exposure), and potential genetic drivers of BP patterns. The next phase in understanding BP trajectories needs to focus on how best to incorporate this knowledge into clinical care to reduce the burden of hypertensive-related outcomes and improve health equity.


2021 ◽  
Vol 13 (1) ◽  
pp. 368
Author(s):  
Dillon T. Fitch ◽  
Hossain Mohiuddin ◽  
Susan L. Handy

One way cities are looking to promote bicycling is by providing publicly or privately operated bike-share services, which enable individuals to rent bicycles for one-way trips. Although many studies have examined the use of bike-share services, little is known about how these services influence individual-level travel behavior more generally. In this study, we examine the behavior of users and non-users of a dockless, electric-assisted bike-share service in the Sacramento region of California. This service, operated by Jump until suspended due to the coronavirus pandemic, was one of the largest of its kind in the U.S., and spanned three California cities: Sacramento, West Sacramento, and Davis. We combine data from a repeat cross-sectional before-and-after survey of residents and a longitudinal panel survey of bike-share users with the goal of examining how the service influenced individual-level bicycling and driving. Results from multilevel regression models suggest that the effect of bike-share on average bicycling and driving at the population level is likely small. However, our results indicate that people who have used-bike share are likely to have increased their bicycling because of bike-share.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Kirstine Wodschow ◽  
Kristine Bihrmann ◽  
Mogens Lytken Larsen ◽  
Gunnar Gislason ◽  
Annette Kjær Ersbøll

Abstract Background The prevalence and incidence rate of atrial fibrillation (AF) increase worldwide and AF is a risk factor for more adverse cardiovascular diseases including stroke. Approximately 44% of AF cases cannot be explained by common individual risk factors and risk might therefore also be related to the environment. By studying geographical variation and clustering in risk of incident AF adjusted for socioeconomic position at an individual level, potential neighbourhood risk factors could be revealed. Methods Initially, yearly AF incidence rates 1987–2015 were estimated overall and stratified by income in a register-based cohort study. To examine geographical variation and clustering in AF, we used both spatial scan statistics and a hierarchical Bayesian Poisson regression analysis of AF incidence rates with random effect of municipalities (n = 98) in Denmark in 2011–2015. Results The 1987–2015 cohort included 5,453,639 individuals whereof 369,800 were diagnosed with an incident AF. AF incidence rate increased from 174 to 576 per 100,000 person-years from 1987 to 2015. Inequality in AF incidence rate ratio between highest and lowest income groups increased from 23% in 1987 to 38% in 2015. We found clustering and geographical variation in AF incidence rates, with incidence rates at municipality level being up to 34% higher than the country mean after adjusting for socioeconomic position. Conclusions Geographical variations and clustering in AF incidence rates exist. Compared to previous studies from Alberta, Canada and the United States, we show that geographical variations exist in a country with free access to healthcare and even when accounting for socioeconomic differences at an individual level. An increasing social inequality in AF was seen from 1987 to 2015. Therefore, when planning prevention strategies, attention to individuals with low income should be given. Further studies focusing on identification of neighbourhood risk factors for AF are needed.


Author(s):  
Marie Krousel-Wood ◽  
Leslie S Craig ◽  
Erin Peacock ◽  
Emily Zlotnick ◽  
Samantha O’Connell ◽  
...  

Abstract Interventions targeting traditional barriers to antihypertensive medication adherence (AHMA) have been developed and evaluated, with evidence of modest improvements in adherence. Translation of these interventions into population-level improvements in adherence and clinical outcomes among older adults remains suboptimal. From the Cohort Study of Medication Adherence among Older adults (CoSMO), we evaluated traditional barriers to AHMA among older adults with established hypertension (N=1544; mean age=76.2 years, 59.5% women, 27.9% Black, 24.1% and 38.9% low adherence by proportion of days covered (i.e., PDC<0.80) and the 4-item Krousel-Wood Medication Adherence Scale (i.e., K-Wood-MAS-4≥1), respectively), finding that they explained 6.4% and 14.8% of variance in pharmacy refill and self-reported adherence, respectively. Persistent low adherence rates, coupled with low explanatory power of traditional barriers, suggest that other factors warrant attention. Prior research has investigated explicit attitudes toward medications as a driver of adherence; the roles of implicit attitudes and time preferences (e.g., immediate versus delayed gratification) as mechanisms underlying adherence behavior are emerging. Similarly, while associations of individual-level social determinants of health (SDOH) and medication adherence are well-reported, there is growing evidence about structural SDOH and specific pathways of effect. Building on published conceptual models and recent evidence, we propose an expanded conceptual framework that incorporates implicit attitudes, time preferences and structural SDOH, as emerging determinants that may explain additional variation in objectively and subjectively measured adherence. This model provides guidance for design, implementation and assessment of interventions targeting sustained improvement in implementation medication adherence and clinical outcomes among older women and men with hypertension.


2018 ◽  
Vol 148 (12) ◽  
pp. 1946-1953 ◽  
Author(s):  
Magali Rios-Leyvraz ◽  
Pascal Bovet ◽  
René Tabin ◽  
Bernard Genin ◽  
Michel Russo ◽  
...  

ABSTRACT Background The gold standard to assess salt intake is 24-h urine collections. Use of a urine spot sample can be a simpler alternative, especially when the goal is to assess sodium intake at the population level. Several equations to estimate 24-h urinary sodium excretion from urine spot samples have been tested in adults, but not in children. Objective The objective of this study was to assess the ability of several equations and urine spot samples to estimate 24-h urinary sodium excretion in children. Methods A cross-sectional study of children between 6 and 16 y of age was conducted. Each child collected one 24-h urine sample and 3 timed urine spot samples, i.e., evening (last void before going to bed), overnight (first void in the morning), and morning (second void in the morning). Eight equations (i.e., Kawasaki, Tanaka, Remer, Mage, Brown with and without potassium, Toft, and Meng) were used to estimate 24-h urinary sodium excretion. The estimates from the different spot samples and equations were compared with the measured excretion through the use of several statistics. Results Among the 101 children recruited, 86 had a complete 24-h urine collection and were included in the analysis (mean age: 10.5 y). The mean measured 24-h urinary sodium excretion was 2.5 g (range: 0.8–6.4 g). The different spot samples and equations provided highly heterogeneous estimates of the 24-h urinary sodium excretion. The overnight spot samples with the Tanaka and Brown equations provided the most accurate estimates (mean bias: −0.20 to −0.12 g; correlation: 0.48–0.53; precision: 69.7–76.5%; sensitivity: 76.9–81.6%; specificity: 66.7%; and misclassification: 23.0–27.7%). The other equations, irrespective of the timing of the spot, provided less accurate estimates. Conclusions Urine spot samples, with selected equations, might provide accurate estimates of the 24-h sodium excretion in children at a population level. At an individual level, they could be used to identify children with high sodium excretion. This study was registered at clinicaltrials.gov as NCT02900261.


2017 ◽  
Author(s):  
Alex Mesoudi

AbstractHow do migration and acculturation (i.e. psychological or behavioral change resulting from migration) affect within- and between-group cultural variation? Here I answer this question by drawing analogies between genetic and cultural evolution. Population genetic models show that migration rapidly breaks down between-group genetic structure. In cultural evolution, however, migrants or their descendants can acculturate to local behaviors via social learning processes such as conformity, potentially preventing migration from eliminating between-group cultural variation. An analysis of the empirical literature on migration suggests that acculturation is common, with second and subsequent migrant generations shifting, sometimes substantially, towards the cultural values of the adopted society. Yet there is little understanding of the individual-level dynamics that underlie these population-level shifts. To explore this formally, I present models quantifying the effect of migration and acculturation on between-group cultural variation, for both neutral and costly cooperative traits. In the models, between-group cultural variation, measured using F statistics, is eliminated by migration and maintained by conformist acculturation. The extent of acculturation is determined by the strength of conformist bias and the number of demonstrators from whom individuals learn. Acculturation is countered by assortation, the tendency for individuals to preferentially interact with culturally-similar others. Unlike neutral traits, cooperative traits can additionally be maintained by payoff-biased social learning, but only in the presence of strong sanctioning institutions. Overall, the models show that surprisingly little conformist acculturation is required to maintain realistic amounts of between-group cultural diversity. While these models provide insight into the potential dynamics of acculturation and migration in cultural evolution, they also highlight the need for more empirical research into the individual-level learning biases that underlie migrant acculturation.


2022 ◽  
Vol 15 ◽  
Author(s):  
Andrzej Z. Wasilczuk ◽  
Qing Cheng Meng ◽  
Andrew R. McKinstry-Wu

Previous studies have demonstrated that the brain has an intrinsic resistance to changes in arousal state. This resistance is most easily measured at the population level in the setting of general anesthesia and has been termed neural inertia. To date, no study has attempted to determine neural inertia in individuals. We hypothesize that individuals with markedly increased or decreased neural inertia might be at increased risk for complications related to state transitions, from awareness under anesthesia, to delayed emergence or confusion/impairment after emergence. Hence, an improved theoretical and practical understanding of neural inertia may have the potential to identify individuals at increased risk for these complications. This study was designed to explicitly measure neural inertia in individuals and empirically test the stochastic model of neural inertia using spectral analysis of the murine EEG. EEG was measured after induction of and emergence from isoflurane administered near the EC50 dose for loss of righting in genetically inbred mice on a timescale that minimizes pharmacokinetic confounds. Neural inertia was assessed by employing classifiers constructed using linear discriminant or supervised machine learning methods to determine if features of EEG spectra reliably demonstrate path dependence at steady-state anesthesia. We also report the existence of neural inertia at the individual level, as well as the population level, and that neural inertia decreases over time, providing direct empirical evidence supporting the predictions of the stochastic model of neural inertia.


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