scholarly journals Genetic Variation of G6PD and CYP2D6: Clinical Implications on the Use of Primaquine for Elimination of Plasmodium vivax

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexandra G. A. Stewart ◽  
Peter A. Zimmerman ◽  
James S. McCarthy

Primaquine, an 8-aminoquinoline, is the only medication approved by the World Health Organization to treat the hypnozoite stage of Plasmodium vivax and P. ovale malaria. Relapse, triggered by activation of dormant hypnozoites in the liver, can occur weeks to years after primary infection, and provides the predominant source of transmission in endemic settings. Hence, primaquine is essential for individual treatment and P. vivax elimination efforts. However, primaquine use is limited by the risk of life-threatening acute hemolytic anemia in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. More recently, studies have demonstrated decreased efficacy of primaquine due to cytochrome P450 2D6 (CYP2D6) polymorphisms conferring an impaired metabolizer phenotype. Failure of standard primaquine therapy has occurred in individuals with decreased or absent CYP2D6 activity. Both G6PD and CYP2D6 are highly polymorphic genes, with considerable geographic and interethnic variability, adding complexity to primaquine use. Innovative strategies are required to overcome the dual challenge of G6PD deficiency and impaired primaquine metabolism. Further understanding of the pharmacogenetics of primaquine is key to utilizing its full potential. Accurate CYP2D6 genotype-phenotype translation may optimize primaquine dosing strategies for impaired metabolizers and expand its use in a safe, efficacious manner. At an individual level the current challenges with G6PD diagnostics and CYP2D6 testing limit clinical implementation of pharmacogenetics. However, further characterisation of the overlap and spectrum of G6PD and CYP2D6 activity may optimize primaquine use at a population level and facilitate region-specific dosing strategies for mass drug administration. This precision public health approach merits further investigation for P. vivax elimination.

2011 ◽  
Vol 8 (63) ◽  
pp. 1510-1520 ◽  
Author(s):  
H. L. Mills ◽  
T. Cohen ◽  
C. Colijn

Individuals living with HIV experience a much higher risk of progression from latent M. tuberculosis infection to active tuberculosis (TB) disease relative to individuals with intact immune systems. A several-month daily course of a single drug during latent infection (i.e. isoniazid preventive therapy (IPT)) has proved in clinical trials to substantially reduce an HIV-infected individual's risk of TB disease. As a result of these findings and ongoing studies, the World Health Organization has produced strong guidelines for implementing IPT on a community-wide scale for individuals with HIV at risk of TB disease. To date, there has been limited use of IPT at a community-wide level. In this paper, we present a new co-network model for HIV and TB co-epidemics to address questions about how the population-level impact of community-wide IPT may differ from the individual-level impact of IPT offered to selected individuals. In particular, we examine how the effect of clustering of contacts within high-TB incidence communities may affect the rates of re-infection with TB and how this clustering modifies the expected population-level effects of IPT. We find that populations with clustering of respiratory contacts experience aggregation of TB cases and high numbers of re-infection events. While, encouragingly, the overall population-level effects of community-wide IPT appear to be sustained regardless of network structure, we find that in populations where these contacts are highly clustered, there is dramatic heterogeneity in the impact of IPT: in some sub-regions of these populations, TB is nearly eliminated, while in others, repeated re-infection almost completely undermines the effect of IPT. Our findings imply that as IPT programmes are brought to scale, we should expect local heterogeneity of effectiveness as a result of the complex patterns of disease transmission within communities.


Author(s):  
Kirti Sundar Sahu ◽  
Arlene Oetomo ◽  
Niloofar Jalali ◽  
Plinio P. Morita

The World Health Organization declared the coronavirus outbreak as a pandemic on March 11, 2020. To inhibit the spread of COVID-19, governments around the globe, including Canada, have implemented physical distancing and lockdown measures, including a work-from-home policy. Canada in 2020 has developed a 24-Hour Movement Guideline for all ages laying guidance on the ideal amount of physical activity, sedentary behaviour, and sleep (PASS) for an individual in a day. The purpose of this study was to investigate changes on the household and population-level in lifestyle behaviours (PASS) and time spent indoors at the household level, following the implementation of physical distancing protocols and stay-at-home guidelines. For this study, we used 2019 and 2020 data from ecobee, a Canadian smart Wi-Fi thermostat company, through the Donate Your Data (DYD) program. Using motion sensors data, we quantified the amount of sleep by using the absence of movement, and similarly, increased sensor activation to show a longer duration of household occupancy. The key findings of this study were; during the COVID-19 pandemic, overall household-level activity increased significantly compared to pre-pandemic times, there was no significant difference between household-level behaviours between weekdays and weekends during the pandemic, average sleep duration has not changed, but the pattern of sleep behaviour significantly changed, specifically, bedtime and wake up time delayed, indoor time spent has been increased and outdoor time significantly reduced. Our data analysis shows the feasibility of using big data to monitor the impact of the COVID-19 pandemic on the household and population-level behaviours and patterns of change.


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.


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.


2015 ◽  
Vol 36 (10) ◽  
pp. 2036-2060 ◽  
Author(s):  
JULIA MENICHETTI ◽  
PIETRO CIPRESSO ◽  
DARIO BUSSOLIN ◽  
GUENDALINA GRAFFIGNA

ABSTRACTIn 2002, the World Health Organization emphasised the concept of active ageing to manage and increase the last third of life. Although many efforts have been made to optimise treatment management, less attention has been paid to health promotion initiatives. To date, few shared guidelines exist that promote an active life in healthy older targets. To fill this gap, we conducted a systematic review to map health promotion interventions that targeted an active and healthy ageing among older citizens. Articles containing the key term active ageing and seven synonyms were searched for in the electronic databases. Because we were interested in actions aimed to promote healthier lifestyles, we connected the string with the term health. A total of 3,918 titles were retrieved and 20 articles were extracted. Twelve of the 20 studies used group interventions, five interventions targeted the individual level and three interventions targeted the community level. Interventions differed for the health focus of the programmes, which ranged from physical activity interventions to social participation or cognitive functioning. Most of the studies aimed to act on psychological components. The review suggests that different interventions promoted for active ageing are effective in improving specific healthy and active lifestyles; however, no studies were concerned directly with a holistic process of citizen health engagement to improve long-term outcomes.


Author(s):  
S. Rochford ◽  
P. Dodd ◽  
C. Austin

Abstract This article provides an overview of the public health approach to suicide in Ireland. The authors provide detail on the current suicide prevention strategy in Ireland, Connecting for Life, which is a whole-of-government, systemic, multicomponent national strategy. As the strategy enters its final extended phase of implementation over the period 2020–2024, the public health elements of Connecting for Life are presented, including the population level and more targeted approaches. The findings of an interim review of the strategy are discussed, in addition to the local and national implementation structures which are in place to assist implementation and monitoring of the strategy.


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.


Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4028
Author(s):  
Theodosia Adom ◽  
Anniza De Villiers ◽  
Thandi Puoane ◽  
André Pascal Kengne

To address the issue of obesity, the World Health Organization (WHO) recommends a set of comprehensive programmes aimed at changing the obesogenic environments to provide opportunities for healthy food options and increased physical activity in the school, home, and at the population level. The objectives of this study were to examine the nature and range of policies related to overweight and obesity prevention in Africa, and to assess how they align with international guidelines. An existing methodological framework was adapted for this scoping review. A search of publicly available national documents on overweight/obesity, general health, and non-communicable diseases (NCDs) was undertaken from relevant websites, including WHO, ministries, and Google Scholar. Additional requests were sent to key contacts at relevant ministries about existing policy documents. The documents were reviewed, and the policies were categorised, using the Analysis Grid for Environments Linked to Obesity (ANGELO) framework. The framework categorises the environmental drivers of obesity into four domains (physical, economic, legislative, and socio-cultural) and two scales: macro (national, regional, sectors, food industries, media, etc.) and micro (household, institutional, and community). This review included documents from 41 African countries. The policy initiatives to prevent overweight/obesity target the school, family and community settings, and macro environments, and broadly align with global recommendations. The NCD documents were in the majority, with only two on obesity. The majority of the documents detailed strategies and key interventions on unhealthy diets and physical inactivity. The physical, legislative, and sociocultural domains were largely featured, with less emphasis on the economic domain. Additionally, nutrition- and diet-related policies were in the majority. Overlaps and interactions of policies were observed in the application of the ANGELO framework. This study has provided information on national policies and programmes in Africa and can be useful as a first point of call for policymakers. The overlapping and interaction in the initiatives demonstrate the importance of multi-sectoral partnerships in providing supportive environments for healthy behaviours.


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.


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