Integrated Surveys of Neglected Tropical Diseases in Southern Sudan: How Much Do They Cost and Can They Be Refined?

Background

Increasing emphasis on integrated control of neglected tropical diseases (NTDs) requires identification of co-endemic areas. Integrated surveys for lymphatic filariasis (LF), schistosomiasis and soil-transmitted helminth (STH) infection have been recommended for this purpose. Integrated survey designs inevitably involve balancing the costs of surveys against accuracy of classifying areas for treatment, so-called implementation units (IUs). This requires an understanding of the main cost drivers and of how operating procedures may affect both cost and accuracy of surveys. Here we report a detailed cost analysis of the first round of integrated NTD surveys in Southern Sudan.

Methods and Findings

Financial and economic costs were estimated from financial expenditure records and interviews with survey staff using an ingredients approach. The main outcome was cost per IU surveyed. Uncertain variables were subjected to univariate sensitivity analysis and the effects of modifying standard operating procedures were explored. The average economic cost per IU surveyed was USD 40,206 or USD 9,573, depending on the size of the IU. The major cost drivers were two key categories of recurrent costs: i) survey consumables, and ii) personnel.

Conclusion

The cost of integrated surveys in Southern Sudan could be reduced by surveying larger administrative areas for LF. If this approach was taken, the estimated economic cost of completing LF, schistosomiasis and STH mapping in Southern Sudan would amount to USD 1.6 million. The methodological detail and costing template provided here could be used to generate cost estimates in other settings and readily compare these to the present study, and may help budget for integrated and single NTDs surveys elsewhere.     

Development and Validation of a Quantitative,High-Throughput,Fluorescent-Based Bioassay to Detect Schistosoma Viability

Background

Schistosomiasis, caused by infection with the blood fluke Schistosoma, is responsible for greater than 200,000 human deaths per annum. Objective high-throughput screens for detecting novel anti-schistosomal targets will drive ‘genome to drug’ lead translational science at an unprecedented rate. Current methods for detecting schistosome viability rely on qualitative microscopic criteria, which require an understanding of parasite morphology, and most importantly, must be subjectively interpreted. These limitations, in the current state of the art, have significantly impeded progress into whole schistosome screening for next generation chemotherapies.

Methodology/Principal Findings

We present here a microtiter plate-based method for reproducibly detecting schistosomula viability that takes advantage of the differential uptake of fluorophores (propidium iodide and fluorescein diacetate) by living organisms. We validate this high-throughput system in detecting schistosomula viability using auranofin (a known inhibitor of thioredoxin glutathione reductase), praziquantel and a range of small compounds with previously-described (gambogic acid, sodium salinomycin, ethinyl estradiol, fluoxetidine hydrochloride, miconazole nitrate, chlorpromazine hydrochloride, amphotericin b, niclosamide) or suggested (bepridil, ciclopirox, rescinnamine, flucytosine, vinblastine and carbidopa) anti-schistosomal activities. This developed method is sensitive (200 schistosomula/well can be assayed), relevant to industrial (384-well microtiter plate compatibility) and academic (96-well microtiter plate compatibility) settings, translatable to functional genomics screens and drug assays, does not require a priori knowledge of schistosome biology and is quantitative.

Conclusions/Significance

The wide-scale application of this fluorescence-based bioassay will greatly accelerate the objective identification of novel therapeutic lead targets/compounds to combat schistosomiasis. Adapting this bioassay for use with other parasitic worm species further offers an opportunity for great strides to be made against additional neglected tropical diseases of biomedical and veterinary importance.     

Modelling the Canada lynx and snowshoe hare population cycle: the role of specialist predators

Mathematical models of the snowshoe hare (Lepus americanus) and Canada lynx (Lynx canadensis) population cycles in the boreal forest have largely focused on the interaction between a single specialist predator and its prey. Here, we consider the role that other hare predators play in shaping the cycles, using a predator–prey model for up to three separate specialist predators. We consider the Canada lynx, coyote (Canis latrans) and great horned owl (Bubo virginianus). Our model improves on past modelling efforts in two ways: (1) our model solutions more closely represent the boreal hare and predator cycles with respect to the cycle period, maximum and minimum hare densities and maximum and minimum predator densities for each predator, and (2) our model sheds light on the role each specialist plays in regulation of the hare cycle, in particular, the dynamics of the raptor appear to be crucial for characterising the low hare densities correctly.     

Fibroblast growth factor-10 promotes cardiomyocyte differentiation from embryonic and induced pluripotent stem cells

Background

The fibroblast growth factor (FGF) family is essential to normal heart development. Yet, its contribution to cardiomyocyte differentiation from stem cells has not been systemically studied. In this study, we examined the mechanisms and characters of cardiomyocyte differentiation from FGF family protein treated embryonic stem (ES) cells and induced pluripotent stem (iPS) cells.

Methodology/Principal Findings

We used mouse ES cells stably transfected with a cardiac-specific α-myosin heavy chain (αMHC) promoter-driven enhanced green fluorescent protein (EGFP) and mouse iPS cells to investigate cardiomyocyte differentiation. During cardiomyocyte differentiation from mouse ES cells, FGF-3, -8, -10, -11, -13 and -15 showed an expression pattern similar to the mesodermal marker Brachyury and the cardiovascular progenitor marker Flk-1. Among them, FGF-10 induced cardiomyocyte differentiation in a time- and concentration-dependent manner. FGF-10 neutralizing antibody, small molecule FGF receptor antagonist PD173074 and FGF-10 and FGF receptor-2 short hairpin RNAs inhibited cardiomyocyte differentiation. FGF-10 also increased mouse iPS cell differentiation into cardiomyocyte lineage, and this effect was abolished by FGF-10 neutralizing antibody or PD173074. Following Gene Ontology analysis, microarray data indicated that genes involved in cardiac development were upregulated after FGF-10 treatment. In vivo, intramyocardial co-administration of FGF-10 and ES cells demonstrated that FGF-10 also promoted cardiomyocyte differentiation.

Conclusion/Significance

FGF-10 induced cardiomyocyte differentiation from ES cells and iPS cells, which may have potential for translation into clinical applications.     

Cluster of Nipah virus infection, Kushtia District, Bangladesh, 2007

Objective

In March 2007, we investigated a cluster of Nipah encephalitis to identify risk factors for Nipah infection in Bangladesh.

Methods

We defined confirmed Nipah cases by the presence of IgM and IgG antibodies against Nipah virus in serum. Case-patients, who resided in the same village during the outbreak period but died before serum could be collected, were classified as probable cases.

Results

We identified three confirmed and five probable Nipah cases. There was a single index case. Five of the secondary cases came in close physical contact to the index case when she was ill. Case-patients were more likely to have physical contact with the index case (71% cases versus 0% controls, p = <0.001). The index case, on her third day of illness, and all the subsequent cases attended the same religious gathering. For three probable cases including the index case, we could not identify any known risk factors for Nipah infection such as physical contact with Nipah case-patients, consumption of raw date palm juice, or contact with sick animals or fruit bats.

Conclusion

Though person-to-person transmission remains an important mode of transmission for Nipah infection, we could not confirm the source of infection for three of the probable Nipah case-patients. Continued surveillance and outbreak investigations will help better understand the transmission of Nipah virus and develop preventive strategies.     

Transitions between central and peripheral vision create spatial/temporal distortions: a hypothesis concerning the perceived break of the curveball

Background

The human visual system does not treat all parts of an image equally: the central segments of an image, which fall on the fovea, are processed with a higher resolution than the segments that fall in the visual periphery. Even though the differences between foveal and peripheral resolution are large, these differences do not usually disrupt our perception of seamless visual space. Here we examine a motion stimulus in which the shift from foveal to peripheral viewing creates a dramatic spatial/temporal discontinuity.

Methodology/Principal Findings

The stimulus consists of a descending disk (global motion) with an internal moving grating (local motion). When observers view the disk centrally, they perceive both global and local motion (i.e., observers see the disk''s vertical descent and the internal spinning). When observers view the disk peripherally, the internal portion appears stationary, and the disk appears to descend at an angle. The angle of perceived descent increases as the observer views the stimulus from further in the periphery. We examine the first- and second-order information content in the display with the use of a three-dimensional Fourier analysis and show how our results can be used to describe perceived spatial/temporal discontinuities in real-world situations.

Conclusions/Significance

The perceived shift of the disk''s direction in the periphery is consistent with a model in which foveal processing separates first- and second-order motion information while peripheral processing integrates first- and second-order motion information. We argue that the perceived distortion may influence real-world visual observations. To this end, we present a hypothesis and analysis of the perception of the curveball and rising fastball in the sport of baseball. The curveball is a physically measurable phenomenon: the imbalance of forces created by the ball''s spin causes the ball to deviate from a straight line and to follow a smooth parabolic path. However, the curveball is also a perceptual puzzle because batters often report that the flight of the ball undergoes a dramatic and nearly discontinuous shift in position as the ball nears home plate. We suggest that the perception of a discontinuous shift in position results from differences between foveal and peripheral processing.     

Impacts of forest fragmentation on orchid bee (Hymenoptera: Apidae: Euglossini) communities in the Chocó biodiversity hotspot of northwest Ecuador

Habitat loss is a major driver of bee declines worldwide, and is of key relevance in the tropics given high deforestation rates, but we continue to have a poor understanding of the impact of land-cover change on tropical bee communities. Orchid bees (Apidae: Euglossini) are critical long-distance pollinators and may be highly susceptible to forest fragmentation given their reliance on forest habitat. Previous studies on the impact of forest fragmentation on euglossines have been geographically limited, have largely ignored β-diversity, and have not compared fragments with continuous forest. To contribute to addressing these gaps, we sampled male euglossine bees in 18 forest fragments (area range: 2.5–33 ha) and at eight locations within a large (3500 ha) continuous forest in the Chocó biodiversity hotspot of Ecuador during the dry season in 2014. We assessed how euglossine abundance, richness, and evenness related to fragment area, isolation, and edge:area ratio. We also compared fragments to continuous forest, in terms of α- and β-diversity. In fragments, a single species (Euglossa tridentata) comprised 78% of captures, and we found no significant effect of fragment area, isolation, or edge on abundance, richness, or evenness among fragments. Forest fragments and continuous forest differed in both community composition and evenness, but not in abundance or species richness. Spatial turnover (β-diversity) showed a non-significant trend toward changing more rapidly in continuous forest relative to fragments. These results underscore the conservation value of continuous forest for orchid bee diversity.     

Effects of landscape features on gene flow of valley oaks (<Emphasis Type="Italic">Quercus lobata</Emphasis>)

Landscape features affect habitat connectivity and patterns of gene flow and hence influence genetic structure among populations. We studied valley oak (Quercus lobata), a threatened species of California (USA) savannas and oak woodlands, with a distribution forming a ring around the Central Valley grasslands. Our main goal was to determine the role of topography and land cover on patterns of gene flow and to test whether elevation or land cover forms stronger barriers to gene flow among valley oak populations. We sampled valley oaks in 12 populations across the range of this species, genotyped each tree at eight nuclear microsatellite loci, and created a series of resistance surfaces by assigning different resistance values to land cover type and elevation. We also estimated recent migration rates and evaluated them with regard to landscape features. There was a significant but weak relationship between Euclidian distance and genetic distance. There was no relationship between genetic distances and land cover, but a significant relationship between genetic distances and elevation resistance. We conclude that gene flow is restricted by high elevations in the northern part of the valley oak range and by high elevations and the Central Valley further south. Migration rate analysis indicated some gene flow occurring east–west but we suggest that the high connectivity in the northern Central Valley is facilitating the formation of these links. We predict that southern populations may become more differentiated in the future through genetic isolation and local adaptation taking place in the face of climate change.