Combined Spatial Prediction of Schistosomiasis and Soil-Transmitted Helminthiasis in Sierra Leone: A Tool for Integrated Disease Control

Two forms of schistosomiasis or bilharzia (intestinal and urogenital) exist in Sierra Leone. The main control strategy for this disease currently is through mass drug administration (MDA) according to the World Health Organization recommended anthelminthic chemotherapy guidelines, and others include snail control, behavior change, and safe water, sanitation and hygiene. Survey on distribution and prevalence of the disease is vital to the planning of MDA in each district. The distribution of intestinal schistosomiasis in the country has been reported previously. The current national survey showed that urogenital schistosomiasis has a specific focal distribution particularly in the central and eastern regions of the country, most prevalent in Bo (24.6%), Koinadugu (20.4%) and Kono (25.3%) districts. Using a simple probabilistic model, this map was combined with the previously reported maps on intestinal schistosomiasis and the combined schistosomiasis prevalence was estimated. The combined schistosomiasis map highlights the presence of high-risk communities in an extensive area in the northeastern half of the country, which provides a tool for planning the national MDA activities

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Improved mapping strategy to better inform policy on the control of schistosomiasis and soil-transmitted helminthiasis in Sierra Leone

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis and soil-transmitted helminthiasis (STH) are endemic in Sierra Leone confirmed by national mapping in 2008. To better inform planning of preventive chemotherapy strategy, another survey was conducted before mass drug administration (MDA) in seven districts according to the mapping results or local knowledge. Fifty-nine chiefdoms and one school in every chiefdom were selected. Thirty school children aged 9-14 years from each school (total: 1760) were examined by parasitological methods for infection with <it>Schistosoma mansoni </it>and STHs.</p> <p>Results</p> <p>The overall prevalence of <it>S. mansoni </it>was 40.2% (95% confidence interval (CI): 37.9-42.5%), particularly in Kailahun (63.3%), Kenema (46.7%), Koinadugu (41.9%) and Kono (71.7%). The results demonstrated the focal distribution of <it>S. mansoni </it>in Bo, Tonkolili and Bombali districts with prevalence ranging from 0.0-63.3%, 3.3-90.0% and 0.0-67.9% respectively. The arithmetic mean intensity of <it>S. mansoni </it>infection was 95.4 epg (95% CI: 61.4-129.5 epg), Heavy mean intensity of infection was found in Kailahun (120.2 epg), Kenema (104.5 epg), Koinadugu (112.3 epg) and Kono (250.3 epg). Heavy or moderate infection with <it>S. mansoni </it>occurred in 20.7% of children examined. Hookworm prevalence was moderate: 31.2% (95% CI: 29.1-33.4%), but high in Bo (50.0%) and Tonkolili (56.7%). Hookworm intensity of infection was light with a mean epg of 53.0 (95% CI: 38.4-67.7 epg). Prevalence and intensity of <it>Ascaris lumbricoides </it>(1.5%, 17.8 epg) and <it>Trichuris trichiura </it>(2.5%, 20.3 epg) was low.</p> <p>Conclusions</p> <p>The prediction by previous spatial analysis that <it>S. mansoni </it>was highly endemic across north-eastern Sierra Leone was confirmed with a significant proportion of children heavily or moderately infected. The distribution of <it>S. mansoni </it>in Bo, Tonkolili and Bombali districts ranged widely, highlighting the importance of considering the nature of focal transmission in national mapping exercises. These results were used to refine the MDA for schistosomiasis control to chiefdom implementation units rather than the entire district in these 3 districts. The survey demonstrated that sufficient number of survey sites for schistosomiasis mapping in each district should be used to provide a better national planning of MDA activities, and that it is affordable with the contributions from all parties involved and national resources mobilized.</p

The Prospects for Payment for Ecosystem Services (PES) in Vietnam: A Look at Three Payment Schemes

Global conservation discourses and practices increasingly rely on market-based solutions to fulfill the dual objective of forest conservation and economic development. Although varied, these interventions are premised on the assumption that natural resources are most effectively managed and preserved while benefiting livelihoods if the market-incentives of a liberalised economy are correctly in place. By examining three nationally supported payment for ecosystem service (PES) schemes in Vietnam we show how insecure land tenure, high transaction costs and high opportunity costs can undermine the long-term benefits of PES programmes for local households and, hence, potentially threaten their livelihood viability. In many cases, the income from PES programmes does not reach the poor because of political and economic constraints. Local elite capture of PES benefits through the monopolization of access to forestland and existing state forestry management are identified as key problems. We argue that as PES schemes create a market for ecosystem services, such markets must be understood not simply as bald economic exchanges between ‘rational actors’ but rather as exchanges embedded in particular socio-political and historical contexts to support the sustainable use of forest resources and local livelihoods in Vietnam

Heterochronic faecal transplantation boosts gut germinal centres in aged mice

Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system, however it is not clear if there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer’s patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli

Prediction of uncomplicated pregnancies in obese women: A prospective multicentre study

BACKGROUND: All obese pregnant women are considered at equal high risk with respect to complications in pregnancy and birth, and are commonly managed through resource-intensive care pathways. However, the identification of maternal characteristics associated with normal pregnancy outcomes could assist in the management of these pregnancies. The present study aims to identify the factors associated with uncomplicated pregnancy and birth in obese women, and to assess their predictive performance. METHODS: Data form obese women (BMI ≥ 30 kg/m 2 ) with singleton pregnancies included in the UPBEAT trial were used in this analysis. Multivariable logistic regression was used to identify sociodemographic, clinical and biochemical factors at 15 +0 to 18 +6 weeks' gestation associated with uncomplicated pregnancy and birth, defined as delivery of a term live-born infant without antenatal or labour complications. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). Internal validation and calibration were also performed. Women were divided into fifths of risk and pregnancy outcomes were compared between groups. Sensitivity, specificity, and positive and negative predictive values were calculated using the upper fifth as the positive screening group. RESULTS: Amongst 1409 participants (BMI 36.4, SD 4.8 kg/m 2 ), the prevalence of uncomplicated pregnancy and birth was 36% (505/1409). Multiparity and increased plasma adiponectin, maternal age, systolic blood pressure and HbA1c were independently associated with uncomplicated pregnancy and birth. These factors achieved an AUROC of 0.72 (0.68-0.76) and the model was well calibrated. Prevalence of gestational diabetes, preeclampsia and other hypertensive disorders, preterm birth, and postpartum haemorrhage decreased whereas spontaneous vaginal delivery increased across the fifths of increasing predicted risk of uncomplicated pregnancy and birth. Sensitivity, specificity, and positive and negative predictive values were 38%, 89%, 63% and 74%, respectively. A simpler model including clinical factors only (no biomarkers) achieved an AUROC of 0.68 (0.65-0.71), with sensitivity, specificity, and positive and negative predictive values of 31%, 86%, 56% and 69%, respectively. CONCLUSION: Clinical factors and biomarkers can be used to help stratify pregnancy and delivery risk amongst obese pregnant women. Further studies are needed to explore alternative pathways of care for obese women demonstrating different risk profiles for uncomplicated pregnancy and birth

Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8(+) T cell response.

Adaptive immune responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct serotypes can precipitate life-threatening clinical disease. We found that clonotypes expressing the T cell antigen receptor (TCR) β-chain variable region 11 (TRBV11-2) were 'preferentially' activated and mobilized within immunodominant human-leukocyte-antigen-(HLA)-A*11:01-restricted CD8(+) T cell populations specific for variants of the nonstructural protein epitope NS3133 that characterize the serotypes DENV1, DENV3 and DENV4. In contrast, the NS3133-DENV2-specific repertoire was largely devoid of such TCRs. Structural analysis of a representative TRBV11-2(+) TCR demonstrated that cross-serotype reactivity was governed by unique interplay between the variable antigenic determinant and germline-encoded residues in the second β-chain complementarity-determining region (CDR2β). Extensive mutagenesis studies of three distinct TRBV11-2(+) TCRs further confirmed that antigen recognition was dependent on key contacts between the serotype-defined peptide and discrete residues in the CDR2β loop. Collectively, these data reveal an innate-like mode of epitope recognition with potential implications for the outcome of sequential exposure to heterologous DENVs

Characterisation of a Peripheral Neuropathic Component of the Rat Monoiodoacetate Model of Osteoarthritis

Joint degeneration observed in the rat monoiodoacetate (MIA) model of osteoarthritis shares many histological features with the clinical condition. The accompanying pain phenotype has seen the model widely used to investigate the pathophysiology of osteoarthritis pain, and for preclinical screening of analgesic compounds. We have investigated the pathophysiological sequellae of MIA used at low (1 mg) or high (2 mg) dose. Intra-articular 2 mg MIA induced expression of ATF-3, a sensitive marker for peripheral neuron stress/injury, in small and large diameter DRG cell profiles principally at levels L4 and 5 (levels predominated by neurones innervating the hindpaw) rather than L3. At the 7 day timepoint, ATF-3 signal was significantly smaller in 1 mg MIA treated animals than in the 2 mg treated group. 2 mg, but not 1 mg, intra-articular MIA was also associated with a significant reduction in intra-epidermal nerve fibre density in plantar hindpaw skin, and produced spinal cord dorsal and ventral horn microgliosis. The 2 mg treatment evoked mechanical pain-related hypersensitivity of the hindpaw that was significantly greater than the 1 mg treatment. MIA treatment produced weight bearing asymmetry and cold hypersensitivity which was similar at both doses. Additionally, while pregabalin significantly reduced deep dorsal horn evoked neuronal responses in animals treated with 2 mg MIA, this effect was much reduced or absent in the 1 mg or sham treated groups. These data demonstrate that intra-articular 2 mg MIA not only produces joint degeneration, but also evokes significant axonal injury to DRG cells including those innervating targets outside of the knee joint such as hindpaw skin. This significant neuropathic component needs to be taken into account when interpreting studies using this model, particularly at doses greater than 1 mg MIA

Lifestyle intervention in obese pregnancy and cardiac remodelling in 3-year olds: children of the UPBEAT RCT

Background/Objectives: Obesity in pregnancy has been associated with increased childhood cardiometabolic risk and reduced life expectancy. The UK UPBEAT multicentre randomised control trial was a lifestyle intervention of diet and physical activity in pregnant women with obesity. We hypothesised that the 3-year-old children of women with obesity would have heightened cardiovascular risk compared to children of normal BMI women, and that the UPBEAT intervention would mitigate this risk. Subjects/Methods: Children were recruited from one UPBEAT trial centre. Cardiovascular measures included blood pressure, echocardiographic assessment of cardiac function and dimensions, carotid intima-media thickness and heart rate variability (HRV) by electrocardiogram. Results: Compared to offspring of normal BMI women (n = 51), children of women with obesity from the trial standard care arm (n = 39) had evidence of cardiac remodelling including increased interventricular septum (IVS; mean difference 0.04 cm; 95% CI: 0.018 to 0.067), posterior wall (PW; 0.03 cm; 0.006 to 0.062) and relative wall thicknesses (RWT; 0.03 cm; 0.01 to 0.05) following adjustment. Randomisation of women with obesity to the intervention arm (n = 31) prevented this cardiac remodelling (intervention effect; mean difference IVS −0.03 cm (−0.05 to −0.008); PW −0.03 cm (−0.05 to −0.01); RWT −0.02 cm (−0.04 to −0.005)). Children of women with obesity (standard care arm) compared to women of normal BMI also had elevated minimum heart rate (7 bpm; 1.41 to 13.34) evidence of early diastolic dysfunction (e prime) and increased sympathetic nerve activity index by HRV analysis. Conclusions: Maternal obesity was associated with left ventricular concentric remodelling in 3-year-old offspring. Absence of remodelling following the maternal intervention infers in utero origins of cardiac remodelling. Clinical trial registry name and registration number: The UPBEAT trial is registered with Current Controlled Trials, ISRCTN89971375