Complex interactions between malaria and malnutrition: a systematic literature review

Abstract Background Despite substantial improvement in the control of malaria and decreased prevalence of malnutrition over the past two decades, both conditions remain heavy burdens that cause hundreds of thousands of deaths in children in resource-poor countries every year. Better understanding of the complex interactions between malaria and malnutrition is crucial for optimally targeting interventions where both conditions co-exist. This systematic review aimed to assess the evidence of the interplay between malaria and malnutrition. Methods Database searches were conducted in PubMed, Global Health and Cochrane Libraries and articles published in English, French or Spanish between Jan 1980 and Feb 2018 were accessed and screened. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale and the risk of bias across studies was assessed using the GRADE approach. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline were followed. Results Of 2945 articles screened from databases, a total of 33 articles were identified looking at the association between malnutrition and risk of malaria and/or the impact of malnutrition in antimalarial treatment efficacy. Large methodological heterogeneity of studies precluded conducting meaningful aggregated data meta-analysis. Divergent results were reported on the effect of malnutrition on malaria risk. While no consistent association between risk of malaria and acute malnutrition was found, chronic malnutrition was relatively consistently associated with severity of malaria such as high-density parasitemia and anaemia. Furthermore, there is little information on the effect of malnutrition on therapeutic responses to artemisinin combination therapies (ACTs) and their pharmacokinetic properties in malnourished children in published literature. Conclusions The evidence on the effect of malnutrition on malaria risk remains inconclusive. Further analyses using individual patient data could provide an important opportunity to better understand the variability observed in publications by standardising both malaria and nutritional metrics. Our findings highlight the need to improve our understanding of the pharmacodynamics and pharmacokinetics of ACTs in malnourished children. Further clarification on malaria-malnutrition interactions would also serve as a basis for designing future trials and provide an opportunity to optimise antimalarial treatment for this large, vulnerable and neglected population. Trial registration PROSPERO CRD42017056934

Noncoding RNAs in neurodegeneration

The emerging complexity of the transcriptional landscape poses great challenges to our conventional preconceptions of how the genome regulates brain function and dysfunction. Non-protein-coding RNAs (ncRNAs) confer a high level of intricate and dynamic regulation of various molecular processes in the CNS and they have been implicated in neurodevelopment and brain ageing, as well as in synapse function and cognitive performance, in both health and disease. ncRNA-mediated processes may be involved in various aspects of the pathogenesis of neurodegenerative disorders. Understanding these events may help to develop novel diagnostic and therapeutic tools. Here, we provide an overview of the complex mechanisms that are affected by the diverse ncRNA classes that have been implicated in neurodegeneration

The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Funding Bill & Melinda Gates Foundation