Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing

Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)’s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance

The biospheric emergency calls for scientists to change tactics

Our current economic and political structures have an increasingly devastating impact on the Earth’s climate and ecosystems: we are facing a biospheric emergency, with catastrophic consequences for both humans and the natural world on which we depend. Life scientists – including biologists, medical scientists, psychologists and public health experts – have had a crucial role in documenting the impacts of this emergency, but they have failed to drive governments to take action in order to prevent the situation from getting worse. Here we, as members of the movement Scientist Rebellion, call on life scientists to re-embrace advocacy and activism – which were once hallmarks of academia – in order to highlight the urgency and necessity of systemic change across our societies. We particularly emphasise the need for scientists to engage in nonviolent civil resistance, a form of public engagement which has proven to be highly effective in social struggles throughout history

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Climate change increases risk of fusarium ear blight on wheat in central China

In this work, a logistic weather-based regression model for estimating incidence of wheat fusarium ear blight in central China was developed, using up to 10 years of disease, anthesis date and weather data available for 10 locations in Anhui and Hubei provinces. In the model, the weather variables were defined with respect to the anthesis date for each location in each year. The model suggested that incidence of fusarium ear blight is related to number of days of rainfall in a 30-day period after anthesis and that high temperatures before anthesis increase the incidence of disease. Validation was done to test whether this relationship was satisfied for another five locations in Anhui province with fusarium ear blight data but no nearby weather data, using weather data generated by the regional climate modelling system PRECIS. How climate change may affect wheat anthesis date and fusarium ear blight in central China was investigated for period 2020-2050 using wheat growth model Sirius and climate data generated by PRECIS. The projection suggested that wheat anthesis dates will generally be earlier and fusarium ear blight incidence will increase substantially for most locations.Non peer reviewe

Commonly administered drug regimens from the 129 studies collecting data on the efficacy of drugs for treating ascariasis, trichuriasis and hookworm.

<p>These regimens account for the majority (89%) of IPD suitable for efficacy estimation. Other miscellaneous drugs or regimens administered include variations on the common mebendazole regimens, levamisole, diethylcarbamazine (DEC), and plant extracts tested for their anthelmintic effect. There are also some treatments which were not reported in enough detail to characterise.</p

Geographical coverage of studies collecting data on the efficacy of drugs for treating ascariasis, trichuriasis and hookworm.

<p>The 39 countries with studies generating individual participant data (IPD) suitable for estimating drug efficacy are shaded blue, with darker shades corresponding to higher estimated abundance of IPD. Five of these, with a red border, do not require preventive chemotherapy and transmission control (PCT) for soil-transmitted helminthiases [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006053#pntd.0006053.ref024" target="_blank">24</a>] (infection prevalence <20%). while the other 34 require PCT. The 69 countries shaded in yellow had no studies identified here, and have been designated by the World Health Organization as requiring PCT. The map was created using freely available country outline data from Natural Earth (naturalearthdata.com).</p

Number of cohorts and estimated number of individual participant data by key age groups from 128 of the 129 studies on the efficacy of drugs for treating ascariasis, trichuriasis and hookworm.

<p>Age groups are assigned according to reporting of the study, which does not always coincide with World Health Organization definitions.</p

Histogram and box plot showing the right-skewed distribution of the estimated number of individual participant data (IPD) per cohort from 129 studies collecting data on the efficacy of drugs for treating ascariasis, trichuriasis and hookworm.

<p>The median estimated cohort size is 146 with a range from 3 to 1,835, with 15 cohorts having no estimate calculated.</p

Summary of main diagnostic methods used to detect and count eggs in the feces of participants in 129 studies collecting data on the efficacy of drugs for treating ascariasis, trichuriasis and hookworm.

<p>Summary of main diagnostic methods used to detect and count eggs in the feces of participants in 129 studies collecting data on the efficacy of drugs for treating ascariasis, trichuriasis and hookworm.</p

Variation in samples and repeats used with the Kato-Katz technique.

<p>Number of cohorts (and number of estimated individual participant data in parentheses) from the subset comprising 91 studies collecting data on the efficacy of drugs for treating the soil-transmitted helminthiases ascariasis, trichuriasis and hookworm in which infection was diagnosed, primarily using a Kato-Katz method, before (a) or after (b) treatment by performing <i>X</i> × <i>Y</i> (samples × replicates) egg counts.</p