The Dispersal Ecology of Rhodesian Sleeping Sickness Following Its Introduction to a New Area

Tsetse-transmitted human and animal trypanosomiasis are constraints to both human and animal health in sub-Saharan Africa, and although these diseases have been known for over a century, there is little recent evidence demonstrating how the parasites circulate in natural hosts and ecosystems. The spread of Rhodesian sleeping sickness (caused by Trypanosoma brucei rhodesiense) within Uganda over the past 15 years has been linked to the movement of infected, untreated livestock (the predominant reservoir) from endemic areas. However, despite an understanding of the environmental dependencies of sleeping sickness, little research has focused on the environmental factors controlling transmission establishment or the spatially heterogeneous dispersal of disease following a new introduction. In the current study, an annually stratified case-control study of Rhodesian sleeping sickness cases from Serere District, Uganda was used to allow the temporal assessment of correlations between the spatial distribution of sleeping sickness and landscape factors. Significant relationships were detected between Rhodesian sleeping sickness and selected factors, including elevation and the proportion of land which was “seasonally flooding grassland” or “woodlands and dense savannah.” Temporal trends in these relationships were detected, illustrating the dispersal of Rhodesian sleeping sickness into more ‘suitable’ areas over time, with diminishing dependence on the point of introduction in concurrence with an increasing dependence on environmental and landscape factors. These results provide a novel insight into the ecology of Rhodesian sleeping sickness dispersal and may contribute towards the implementation of evidence-based control measures to prevent its further spread

Improvements on Restricted Insecticide Application Protocol for Control of Human and Animal African Trypanosomiasis in Eastern Uganda

African trypanosomes constrain livestock and human health in Sub-Saharan Africa, and aggravate poverty and hunger of these otherwise largely livestock-keeping communities. To solve this, there is need to develop and use effective and cheap tsetse control methods. To this end, we aimed at determining the smallest proportion of a cattle herd that needs to be sprayed on the legs, bellies and ears (RAP) for effective Human and Animal African Trypanosomiasis (HAT/AAT) control.; Cattle in 20 villages were ear-tagged and injected with two doses of diminazene diaceturate (DA) forty days apart, and randomly allocated to one of five treatment regimens namely; no treatment, 25%, 50%, 75% monthly RAP and every 3 month Albendazole drench. Cattle trypanosome re-infection rate was determined by molecular techniques. ArcMap V10.3 was used to map apparent tsetse density (FTD) from trap catches. The effect of graded RAP on incidence risk ratios and trypanosome prevalence was determined using Poisson and logistic random effect models in R and STATA V12.1 respectively. Incidence was estimated at 9.8/100 years in RAP regimens, significantly lower compared to 25.7/100 years in the non-RAP regimens (incidence rate ratio: 0.37; 95% CI: 0.22-0.65; P>0.001). Likewise, trypanosome prevalence after one year of follow up was significantly lower in RAP animals than in non-RAP animals (4% vs 15%, OR: 0.20, 95% CI: 0.08-0.44; P>0.001). Contrary to our expectation, level of protection did not increase with increasing proportion of animals treated.; Reduction in RAP coverage did not significantly affect efficacy of treatment. This is envisaged to improve RAP adaptability to low income livestock keepers but needs further evaluation in different tsetse challenge, HAT/AAT transmission rates and management systems before adopting it for routine tsetse control programs

The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor

The DEAD box RNA helicase, p68, has been implicated in various cellular processes and has been shown to possess transcriptional coactivator function. Here, we show that p68 potently synergises with the p53 tumour suppressor protein to stimulate transcription from p53-dependent promoters and that endogenous p68 and p53 co-immunoprecipitate from nuclear extracts. Strikingly, RNAi suppression of p68 inhibits p53 target gene expression in response to DNA damage, as well as p53-dependent apoptosis, but does not influence p53 stabilisation or expression of non-p53-responsive genes. We also show, by chromatin immunoprecipitation, that p68 is recruited to the p21 promoter in a p53-dependent manner, consistent with a role in promoting transcriptional initiation. Interestingly, p68 knock-down does not significantly affect NF-κB activation, suggesting that the stimulation of p53 transcriptional activity is not due to a general transcription effect. This study represents the first report of the involvement of an RNA helicase in the p53 response, and highlights a novel mechanism by which p68 may act as a tumour cosuppressor in governing p53 transcriptional activity

Common Negative Thoughts in Early Motherhood and Their Relationship to Guilt, Shame and Depression

New mothers in Western societies report being influenced by ideologies which suggest mothering comes naturally to women and is joyful and fulfilling. However, research reveals motherhood-related negative thoughts are common even among non-depressed new mothers, and it has been suggested experiencing such thoughts may be related to guilt and shame. This study updates and extends Hall and Wittkowski’s (2006) prevalence survey of motherhood-related negative thoughts by assessing new mothers’ perceptions of the social acceptability of negative thoughts, and by exploring relationships with guilt, shame and psychological distress. A cross-sectional survey design was used. A self-selected sample of non-clinical new mothers (N = 395) from the United Kingdom and Ireland completed online questionnaires including measures of the frequency and social acceptability of motherhood-related negative thoughts, shame and guilt proneness, depression and motherhood experience. Hierarchical regression analyses were used to explore relationships between variables. The frequency of negative thoughts was much higher than reported by Hall and Wittkowski. After controlling for demographic variables and social support, frequency of negative thoughts significantly predicted shame and guilt, whereas social acceptability of negative thoughts significantly predicted guilt. Negative thoughts, shame, guilt and motherhood experience relative to expectations significantly predicted depression score. These results suggest that negative thoughts are more common in early motherhood than previously reported, are considered socially unacceptable, and are related to guilt, shame and depression scores. The findings increase our understanding of postnatal distress in non-clinical populations. Future research should explore information and/or interventions aimed at “normalising” negative thoughts in early motherhood