Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases

Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination 'as a public health problem' when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models' predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020

Microbial and plant ecology of a long-term TNT-contaminated site

The contamination of the environment with explosive residues presents a serious ecological problem at sites across the world, with the highly toxic compound trinitrotoluene (TNT) the most widespread contaminant. This study examines the soil microbial community composition across a long-term TNT-contaminated site. It also investigates the extent of nitroaromatic contamination and its effect on vegetation. Concentrations of TNT and its metabolites varied across the site and this was observed to dramatically impact on the extent and diversity of the vegetation, with the most heavily contaminated area completely devoid of vegetation. Bryophytes were seen to be particularly sensitive to TNT contamination. The microbial population experienced both a reduction in culturable bacterial numbers and a shift in composition at the high concentrations of TNT. DGGE and community-level physiological profiling (CLPP) revealed a clear change in both the genetic and functional diversity of the soil when soil was contaminated with TNT. Long-term contamination of soil with TNT reduces the extent and diversity of vegetation, decreases culturable bacterial numbers and shifts the microbial community composition

Exocytotic release from individual granules exhibits similar properties at mast and chromaffin cells

The effects of temperature on granular secretion were studied in individual bovine adrenal chromaffin and rat peritoneal mast cells. It was found that more molecules are released from individual granules at physiological temperature than at room temperature, where such experiments are normally performed. In mast cells, there is also a dramatic decrease in the time required for exocytosis to be complete at 37 degrees C compared to room temperature. In the presence of some cations, the amount released from individual granules at room temperature from both types of cells could be altered. The amount of secretion decreased with the divalent cation zinc but increased with the monovalent cation cesium. These experiments used two electrochemical techniques: cyclic voltammetry and amperometry. With amperometry, the concentration gradient created by the electrode near the cell further increased the amount of release. Similar responses to changes in the extracellular environment in chromaffin and mast cells suggest that the mechanism of extrusion of the granule contents is similar in both cell types

LAMBDR: Long-range amplification and Nanopore sequencing of the<i>Mycobacterium bovis direct-repeat region</i>. A novel method for in-silico spoligotyping of<i>M. bovis</i>directly from badger faeces

AbstractThe environment is an overlooked source ofMycobacterium bovis, the causative agent of bovine TB. Long read, end to end sequencing of variable repeat regions across theM. bovisgenome was evaluated as a method of acquiring rapid strain level resolution directly from environmental samples. Eight samples ofM. bovis, two BCG strains (Danish and Pasteur), and a singleM. tuberculosistype culture (NCTC 13144) were used to generate data for this method. Long range PCR amplification of the direct repeat region was used to synthesize ∼5kb template DNA for onward sequence analysis. This has permitted culture independent identification ofM. bovisspoligotypes present in the environment. Sequence level analysis of the direct repeat region showed that spoligotyping may underestimate strain diversity due to the inability to identify both SNPs and primer binding mutations using a biotinylated hybridisation approach.</jats:p