Safety and efficacy of three trypanocides in confirmed field cases of trypanosomiasis in working equines in The Gambia: a prospective, randomised, non-inferiority trial

Background: Globally, working equines have a continued and growing socioeconomic role in supporting the livelihoods of between 300–600 million people in low income countries which is rarely recognised at a national or international level. Infectious diseases have significant impact on welfare and productivity in this population and equine trypanosomiasis is a priority disease due to its severity and prevalence. Strategies are required to improve the prevention, diagnosis, management and treatment of trypanosomiasis in equines and more data are required on the efficacy and safety of current trypanocidal drugs. Methods: A prospective randomised, open-label non-inferiority trial was performed in The Gambia on horses and donkeys that fulfilled 2/5 clinical inclusion criteria (anaemia, poor body condition, pyrexia, history of abortion, oedema). Following randomised trypanocidal treatment (diminazene diaceturate, melarsomine dihydrochloride or isometamidium chloride), animals were observed for immediate adverse drug reactions and follow-up assessment was performed at 1 and 2 weeks. Blood samples underwent PCR analysis with specific Trypanosoma sp. primers. Treatment efficacy was assessed by measuring changes in clinical parameters, clinicopathological results and PCR-status post-treatment after evaluating for bias. Using PCR status as the outcome variable, non-inferiority of isometamidium treatment was determined if the upper bound limit of a 2-sided 95% CI was less than 10%. Results: There was a significant beneficial effect upon the Trypanosoma sp. PCR positive population following trypanocidal treatment for all groups. The findings of clinical evaluation and PCR status supported a superior treatment effect for isometamidium. Melarsomine dihydrochloride efficacy was inferior to isometamidium. There were immediate, self-limiting side effects to isometamidium in donkeys (26%). Diminazene had the longest duration of action as judged by PCR status. Conclusions: The data support the continued use of isometamidium following careful dose titration in donkeys and diminazene for trypanosomiasis in equines using the doses and routes of administration reported

Variation in disease phenotype is marked in equine trypanosomiasis

Background: Equine trypanosomiasis is a severe and prevalent disease that has the greatest impact globally upon working equids due to its distribution across lower income countries. Morbidity and mortality rates are high; disease management strategies in endemic regions are ineffective and cost prohibitive. Individual variation in disease phenotype in other species suggests host factors could reveal novel treatment and control targets but has not been investigated in equids. Methods: A prospective clinical evaluation of equines presenting for a free veterinary examination was performed in hyperendemic villages in The Gambia. Age, body condition score and body weight were estimated by validated methods, and haematocrit and total protein concentration measured. Animals fulfilling 2 out of 5 clinical inclusion criteria (anaemia, poor body condition, pyrexia, history of abortion, oedema) for a diagnosis of trypanosomiasis received trypanocidal treatment with follow-up at 1 and 2 weeks. Blood samples underwent PCR analysis with specific Trypanosoma spp. primers and results were compared to the subject’s clinical and clinicopathological features. A mixed effects generalised linear model was generated to evaluate the association of infection status with degree of pyrexia and anaemia. Results: Morbidity was high within examined (n = 641) and selected (n = 247) study populations. PCR status was not associated with a defined disease phenotype; there was intra- and inter-species variability. Donkeys were more frequently Trypanosoma spp.-positive (P < 0.001) and febrile (P < 0.001) than horses, but infected horses were more anaemic (P < 0.001), and in poorer body condition (P < 0.001) than donkeys. Sex was correlated to disease phenotype: males were more anaemic (P = 0.03) and febrile (P < 0.001). Haemoparasite co-infections were more common than a single infection. Conclusions: There was evidence of diversity in trypanosomiasis clinical signs plus variable disease phenotypes within equid subpopulations that warrant further investigation. The complex co-infection profile of field cases requires greater consideration to optimise disease management

Comparison of loop-mediated isothermal amplification (LAMP) and PCR for the diagnosis of infection with Trypanosoma brucei ssp. in equids in The Gambia

Introduction: Infection of equids with Trypanosoma brucei (T. brucei) ssp. is of socioeconomic importance across sub-Saharan Africa as the disease often progresses to cause fatal meningoencephalitis. Loop-mediated isothermal amplification (LAMP) has been developed as a cost-effective molecular diagnostic test and is potentially applicable for use in field-based laboratories. Part I: Threshold levels for T. brucei ssp. detection by LAMP were determined using whole equine blood specimens spiked with known concentrations of parasites. Results were compared to OIE antemortem gold standard of T. brucei-PCR (TBR-PCR). Results I: Threshold for detection of T. brucei ssp. on extracted DNA from whole blood was 1 parasite/ml blood for LAMP and TBR-PCR, and there was excellent agreement (14/15) between tests at high (1 x 103/ml) concentrations of parasites. Detection threshold was 100 parasites/ml using LAMP on whole blood (LWB). Threshold for LWB improved to 10 parasites/ml with detergent included. Performance was excellent for LAMP at high (1 x 103/ml) concentrations of parasites (15/15, 100%) but was variable at lower concentrations. Agreement between tests was weak to moderate, with the highest for TBR-PCR and LAMP on DNA extracted from whole blood (Cohen’s kappa 0.95, 95% CI 0.64–1.00). Part II: A prospective cross-sectional study of working equids meeting clinical criteria for trypanosomiasis was undertaken in The Gambia. LAMP was evaluated against subsequent TBR-PCR. Results II: Whole blood samples from 321 equids in The Gambia were processed under field conditions. There was weak agreement between LWB and TBR-PCR (Cohen’s kappa 0.34, 95% CI 0.19–0.49) but excellent agreement when testing CSF (100% agreement on 6 samples). Conclusions: Findings support that LAMP is comparable to PCR when used on CSF samples in the field, an important tool for clinical decision making. Results suggest repeatability is low in animals with low parasitaemia. Negative samples should be interpreted in the context of clinical presentation

Prediction of pH Change in Processed Acidified Turnips

The acetic acid uptake by turnips was studied during an acidification process in containers. The process was successfully described by a Fickian diffusion, using a correlation for the buffer effect. Diffusion coefficients (0.629 to 3.99 × 10-9 m2/sec) and partition coefficients (0.8 to 1.1) were obtained by optimization of the fit between experimental and theoretical values, using the simplex method. The partition coefficient did not show an evident dependence on temperature, while diffusivity followed an Arrhenius type behavior. The relationship between acid concentration and pH was described using a cubic model with parameters independent of temperature. Results showed that the combination of these models describing the acid diffusion into the food and the buffering effects of the food allowed accurate prediction of pH evolution in the acidification process

Spin glass overlap barriers in three and four dimensions

For the Edwards-Anderson Ising spin-glass model in three and four dimensions (3d and 4d) we have performed high statistics Monte Carlo calculations of those free-energy barriers $F^q_B$ which are visible in the probability density $P_J(q)$ of the Parisi overlap parameter $q$. The calculations rely on the recently introduced multi-overlap algorithm. In both dimensions, within the limits of lattice sizes investigated, these barriers are found to be non-self-averaging and the same is true for the autocorrelation times of our algorithm. Further, we present evidence that barriers hidden in $q$ dominate the canonical autocorrelation times.Comment: 20 pages, Latex, 12 Postscript figures, revised version to appear in Phys. Rev.

Understanding Volumetric Water Storage in Monsoonal Wetlands of Northeastern Bangladesh

The volume of water stored in seasonal wetlands is a fundamental but difficult to measure variable for developing a physical understanding of wetland behavior. For seasonal wetlands that are a major source of water for rice and fish production, this physical understanding is key to planning for water-food security and ecosystem services. This study quantified variations in volumetric storage for the numerous seasonal wetlands of northeastern Bangladesh, locally known as “haors.” These haors receive transboundary runoff from densely vegetated and mountainous terrain in India and face persistent monsoonal cloud cover as they become full. We estimated volumetric storage for 13 haors by using extensive remote sensing data on water surface extent and elevation that was complemented with citizen-contributed gauge data. Assuming a trapezoidal bathymetry, an area-volume relationship was developed for selected haors. This relationship was assumed to be valid for extrapolating volumetric estimations over all the haors in the region. Results suggested that as haors get filled with the onset of monsoon rains, total estimated storage relative to the lowest observable level varied from 6.5 (±0.4) km3 in May to 30.9 (±2.0) km3 in July (peak of monsoon). Choosing a rectangular bathymetry can lead to 47% higher estimates compared to trapezoidal cross section. Estimating this intra-annual/interannual increase in storage is important for the region to plan water management policies that balance the human and ecosystem needs. Our analytical approach has potential for application to wetlands worldwide in light of the upcoming Surface Water and Ocean Topography (SWOT) mission

Monitoring variations in lake water storage with satellite imagery and citizen science

Despite lakes being a key part of the global water cycle and a crucial water resource, there is limited understanding of whether regional or lake‐specific factors control water storage variations in small lakes. Here, we study groups of small, unregulated lakes in North Carolina, Washington, Illinois, and Wisconsin, USA using lake level measurements gathered by citizen scientists and lake surface area measurements from optical satellite imagery. We show the lake level measurements to be highly accurate when compared to automated gauges (mean absolute error = 1.6 cm). We compare variations in lake water storage between pairs of lakes within these four states. On average, water storage variations in lake pairs across all study regions are moderately positively correlated (ρ = 0.49) with substantial spread in the degree of correlation. The distance between lake pairs and the extent to which their changes in volume are correlated show a weak but statistically significant negative relationship. Our results indicate that, on regional scales, distance is not a primary factor governing lake water storage patterns, which suggests that other, perhaps lakes‐specific, factors must also play important roles

Research of working area development parameters in conditions of deep steep deposit finalizing

Отримано формули розрахунку об’єму запасів корисних копалин в приконтурній та глибинній зоні. Встановлено характер впливу параметрів доробки глибоких крутоспадних родовищ відкритим способом на доцільне положення поточних та проектних контурів кар’єру. Встановлено, що найменший середній коефіцієнт розкриву досягається при мінімальному значенні суми обсягів корисної копалини приконтурної зони лежачого і висячого боків покладу в проектному положенні. Найменший поточний коефіцієнт розкриву досягається при мінімальному значенні суми обсягів корисної копалини приконтурної зони лежачого і висячого боків покладу, а також робочого борту кар'єру в поточному положенні

Effects of Intermittent IL-2 Alone or with Peri-Cycle Antiretroviral Therapy in Early HIV Infection: The STALWART Study

The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy