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The onchocerciasis transmission models EPIONCHO and ONCHOSIM have been independently developed and used to explore the feasibility of eliminating onchocerciasis from Africa with mass (annual or biannual) distribution of ivermectin within the timeframes proposed by the World Health Organization (WHO) and endorsed by the 2012 London Declaration on Neglected Tropical Diseases (i.e. by 2020/2025). Based on the findings of our previous model comparison, we implemented technical refinements and tested the projections of EPIONCHO and ONCHOSIM against long-term epidemiological data from two West African transmission foci in Mali and Senegal where the observed prevalence of infection was brought to zero circa 2007–2009 after 15–17 years of mass ivermectin treatment. We simulated these interventions using programmatic information on the frequency and coverage of mass treatments and trained the model projections using longitudinal parasitological data from 27 communities, evaluating the projected outcome of elimination (local parasite extinction) or resurgence. We found that EPIONCHO and ONCHOSIM captured adequately the epidemiological trends during mass treatment but that resurgence, while never predicted by ONCHOSIM, was predicted by EPIONCHO in some communities with the highest (inferred) vector biting rates and associated pre-intervention endemicities. Resurgence can be extremely protracted such that low (microfilarial) prevalence between 1% and 5% can be maintained for 3–5 years before manifesting more prominently. We highlight that post-treatment and post-elimination surveillance protocols must be implemented for long enough and with high enough sensitivity to detect possible residual latent infections potentially indicative of resurgence. We also discuss uncertainty and differences between EPIONCHO and ONCHOSIM projections, the potential importance of vector control in high-transmission settings as a complementary intervention strategy, and the short remaining timeline for African countries to be ready to stop treatment safely and begin surveillance in order to meet the impending 2020/2025 elimination targets. [ABSTRACT FROM AUTHOR]

The predictions of two mathematical models of the transmission dynamics of Ascaris lumbricoides and hookworm infection and the impact of mass drug administration (MDA) are compared, using data from India. One model has an age structured partial differential equation (PDE) deterministic framework for the distribution of parasite numbers per host and sexual mating. The second model is an individual-based stochastic model. Baseline data acquired prior to treatment are used to estimate key transmission parameters, and forward projections are made, given the known MDA population coverage. Predictions are compared with observed post-treatment epidemiological patterns. The two models could equally well predict the short-term impact of deworming on A. lumbricoides and hookworm infection levels, despite being fitted to different subsets and/or summary statistics of the data. As such, the outcomes give confidence in their use as aids to policy formulation for the use of PCT to control A. lumbricoides and hookworm infection. The models further largely agree in a qualitative sense on the added benefit of semi-annual vs. annual deworming and targeting of the entire population vs. only children, as well as the potential for interruption of transmission. Further, this study also illustrates that long-term predictions are sensitive to modelling assumptions about which age groups contribute most to transmission, which depends on human demography and age-patterns in exposure and contribution to the environmental reservoir of infection, the latter being notoriously difficult to empirically quantify. [ABSTRACT FROM AUTHOR]

Background Brazil has the second highest annual number of new leprosy cases. The aim of this study is to formally compare predictions of future new case detection rate (NCDR) trends and the annual probability of NCDR falling below 10/100,000 of four different modelling approaches in four states of Brazil: Rio Grande do Norte, Amazonas, Ceará, Tocantins. Methods A linear mixed model, a back-calculation approach, a deterministic compartmental model and an individual-based model were used. All models were fitted to leprosy data obtained from the Brazilian national database (SINAN). First, models were fitted to the data up to 2011, and predictions were made for NCDR for 2012–2014. Second, data up to 2014 were considered and forecasts of NCDR were generated for each year from 2015 to 2040. The resulting distributions of NCDR and the probability of NCDR being below 10/100,000 of the population for each year were then compared between approaches. Results Each model performed well in model fitting and the short-term forecasting of future NCDR. Long-term forecasting of NCDR and the probability of NCDR falling below 10/100,000 differed between models. All agree that the trend of NCDR will continue to decrease in all states until 2040. Reaching a NCDR of less than 10/100,000 by 2020 was only likely in Rio Grande do Norte. Prediction until 2040 showed that the target was also achieved in Amazonas, while in Ceará and Tocantins the NCDR most likely remain (far) above 10/100,000. Conclusions All models agree that, while incidence is likely to decline, achieving a NCDR below 10/100,000 by 2020 is unlikely in some states. Long-term prediction showed a downward trend with more variation between models, but highlights the need for further control measures to reduce the incidence of new infections if leprosy is to be eliminated. [ABSTRACT FROM AUTHOR]

We present three transmission models of visceral leishmaniasis (VL) in the Indian subcontinent (ISC) with structural differences regarding the disease stage that provides the main contribution to transmission, including models with a prominent role of asymptomatic infection, and fit them to recent case data from 8 endemic districts in Bihar, India. Following a geographical cross-validation of the models, we compare their predictions for achieving the WHO VL elimination targets with ongoing treatment and vector control strategies. All the transmission models suggest that the WHO elimination target (<1 new VL case per 10,000 capita per year at sub-district level) is likely to be met in Bihar, India, before or close to 2020 in sub-districts with a pre-control incidence of 10 VL cases per 10,000 people per year or less, when current intervention levels (60% coverage of indoor residual spraying (IRS) of insecticide and a delay of 40 days from onset of symptoms to treatment (OT)) are maintained, given the accuracy and generalizability of the existing data regarding incidence and IRS coverage. In settings with a pre-control endemicity level of 5/10,000, increasing the effective IRS coverage from 60 to 80% is predicted to lead to elimination of VL 1–3 years earlier (depending on the particular model), and decreasing OT from 40 to 20 days to bring elimination forward by approximately 1 year. However, in all instances the models suggest that L. donovani transmission will continue after 2020 and thus that surveillance and control measures need to remain in place until the longer-term aim of breaking transmission is achieved. [ABSTRACT FROM AUTHOR]

Background: A diagnosis of Hymenoptera venom allergy is based on clinical history and the results of skin tests and/or laboratory methods. Objective: To analyze the utility of available laboratory tests in diagnosing Hymenoptera venom allergy. Methods: Ninety-five patients with Hymenoptera venom allergy with a history of bee (35) or wasp (60) anaphylactic sting reaction and positive skin test with bee or wasp venom were included in this analysis. Specific immunoglobulin E (to bee venom extract, wasp venom extract, available recombinant molecules, and a basophil activation test with venom extracts were assessed in all the patients. Test sensitivity and specificity were calculated by using standard threshold values; then, receiver operating characteristic curve analysis was performed to compute optimal threshold values. Also, statistical analysis of the utility of different combinations of laboratory tests was performed. Results: The optimal threshold values were revealed to be the following: 1.0 kIU/L for bee venom extract (sensitivity, 97.14%; specificity, 100%), 0.35 kIU/L for rApi m 1 (sensitivity, 68.57%; specificity, 100%), 1.22 kIU/L for wasp venom extract (sensitivity, 88.33%; specificity, 95.45%), 0.7 kIU/L for rVes v 5 (sensitivity, 86.67%; specificity, 95.45%), 1.0 kIU/L for rVes v 1 (sensitivity, 56.67%; specificity, 95.45%), 6.5% for basophil activation test with bee venom extract (sensitivity, 80%; specificity, 95.45%), and 4.5% for basophil activation test with wasp venom extract (sensitivity, 91.53%; specificity, 95.45%). The best test combinations were found to be the following: bee venom extract plus rApi m 1 (sensitivity, 97.14%; specificity, 95.45%) in bee and either wasp venom extract plus rVes v 5, or rVes v 5 plus rVes v 1 (both sensitivity, 98.33%; specificity, 95.45%) in patients with wasp venom allergy. Conclusion: Our analysis confirmed that currently used laboratory tests represent effective tools in diagnosing Hymenoptera venom allergy. Moreover, our probabilistic approach offered another way to interpret concrete values of laboratory test results and opened possible direction on how to optimize the laboratory diagnostic procedure. [ABSTRACT FROM AUTHOR]

Unlabelled: Background Female sex workers (FSWs) are highly vulnerable to HIV but make little use of HIV-related intervention services provided by the Chinese government. Determinants of the low uptake of HIV services by FSWs in Shenzhen, Guangdong province were investigated.Methods: FSWs were recruited by venue-based sampling; 1656 FSWs were interviewed about sociodemographics, behaviours and uptake of HIV-related intervention services. Determinants of no uptake of HIV testing, condom promotion, and peer education were determined through logistic regression. The association between uptake of HIV-related services, condom use and HIV-related knowledge was also assessed.Results: The overall uptake of HIV testing, condom promotion, and peer education by FSWs was 21.5%, 47.8% and 28.0%, respectively. Young age and shorter duration of working in Shenzhen were statistically significantly correlated with no uptake of all three interventions. Uptake of these services was positively associated with consistent condom use and good HIV-related knowledge.Conclusions: The uptake of HIV-related intervention services by FSWs is low in Shenzhen. As their uptake is positively associated with condom use and HIV-related knowledge, it is necessary to intensify promotion of these, focusing on young and recently started FSWs. [ABSTRACT FROM AUTHOR]

Aims. Mesenchymal stromal cells (MSC) derived from adult bone marrow or adipose tissue offer the potential to open a new frontier in medicine. MSC are involved in modulating immune response and tissue repair in vitro and in vivo. Experimental evidence and preliminary clinical studies have demonstrated that MSC exhibit an important immunomodulatory function in patients with graft versus host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. The immunosuppressive properties of MSC have already been exploited in the clinical setting. However the precise mechanisms are being still investigated. Methods. We examined the immunosuppressive function of MSC by coculturing them with stimulated HLA incompatible allogeneic lymphocytes in a mixed lymphocyte culture test. The metabolic and proliferative activity of lymphocytes was determined by MTT test. Results. After stimulation with alloantigens the presence of MSC caused significant decrease of absorbance levels by 62% (P<0.01), 26% (P<0.01) and 6% (P=0.0437) in comparison to positive control depending on the MSC/lymphocyte ratio (1:5, 1:50, 1:500). The mitogenic stimulation of lymphocytes with fMLP or PHA was also significantly reduced during MSC cocultivation. The absorbance was reduced by 42% (P<0.001) and 67% (P<0.001). Conclusions. Allogeneic bone marrow is an ideal source of MSC for clinical application. The experiments confirmed the dose-dependent inhibitory effect of MSC on lymphocyte proliferation triggered by cellular or mitogenic stimulation. The mixed lymphocyte culture test offers a simple method for characterization and verification of the immunosuppressive potential of MSC, being prepared for clinical use. [ABSTRACT FROM AUTHOR]

The present article aims to explore the complex relation between global and European Pentecostalism and politics. The self-evident scarcity of studies on this particular topic, despite the global prominence and the dynamic growth of Pentecostalism, and the tendency to collapse strikingly opposing tendencies under a generic terminology call for a serious examination of the approaches Pentecostalism adopts in relation to political involvement. Throughout the three main sections of this paper, political, historical, cultural and theological concepts will be employed in order to: firstly, provide a qualitative and quantitative overview of global Pentecostalism; secondly, explore worldwide different political preferences of Pentecostal churches and denominations that range from apolitism, to full-fledged political involvement, or to the preference for an alternative polis; thirdly, to analyse European Pentecostalism and the particularities of its relation with politics. [ABSTRACT FROM AUTHOR]

This paper aims to analyze the place of religion in the Romanian society and politics, by focusing specifically on the process of readjusting religious freedom in Romania after 1990. Although the regulation of religious life in accordance with international human rights principles was considered one of the cornerstones of the Romanian democracy, the replacement of the communist legal framework with a new one took more than 17 years and was accompanied by numerous tensions among the religious actors themselves, state institutions and civil society organizations. The analysis of the state of religious freedom two decades after the fall of the communism in Romania reveals ambivalent developments. Despite some undeniable signs of progress, there are still significant areas that require improvement. The most problematic aspects are the maintenance of the two-tier system and the financial dependence of the culte on the state. [ABSTRACT FROM AUTHOR]

Unlike other Post-Communist countries, Romania displays three clear individual-level trends related to political and religious institutions. The Romanians are the most supportive for the EU and Church, and the most critical towards national political institutions in the region. By conducting an empirical longitudinal study on the Romanian population, we aim to understand the linkages between these two trends and to identify what can explain the high level of trust vested by the Romanian citizens in the Orthodox Church in the post-Communist period. In doing so, we test two alternative explanations and we employ bivariate and multivariate statistics. The results indicate that there is weak evidence for the relationship between trust in political and religious institutions, with a stronger emphasis on the EU aspect. Whenever the attitudes are linked, they are consistent: positive attitudes towards the national government and Parliament trigger positive attitudes towards the Church. [ABSTRACT FROM AUTHOR]

Background: Intrathoracic hilar or mediastinal lymph node metastases (HMLNMs) of extrathoracic carcinomas are infrequent. Their treatment strategy is not established and their prognosis poorly known. We reviewed the place of surgical intervention in their management. Methods: Among 565 patients with mediastinal lymph node enlargement, 37 had a history of extrathoracic carcinoma. The enlargement consisted in HMLNMs in 26 (15 men, 11 women), with a mean age of 57.6 (range 19-78) years. Surgical procedures were reviewed. Results: Diagnostic procedures, comprising mediastinoscopy in 9, anterior mediastinotomy in 2, and video-assisted thoracic surgery (VATS) in 4, were performed mainly because of unresectability due to diffuse and bilateral HMLNMs. Cancer location was breast in 6, kidney or prostate in 2 each, and bladder, rectum, testis, melanoma, and larynx in 1 each. Median survival was 21 months. Resection was performed in 11 patients, comprising posterolateral thoracotomy in 6, muscle sparing thoracotomy in 2, and VATS in 3. Seventeen involved LN stations were removed; of these, primary were kidney in 3, testis or thyroid in 2 each, and larynx, nasopharynx, and intestinum in 1 each. Five-year survival was 41.6% (median, 45 months). Conclusions: HMLNMs of extrathoracic carcinoma may be isolated, probably in the context of a particular lymphatic mode of spread. Our experience demonstrates that operation is mainly diagnostic but resection may safely achieve local control of the disease and deserves being advocated in patients with isolated and resectable HMLNMs. [Copyright &y& Elsevier]

Summary: The precise mechanisms of protective immunity and pathogenesis of tuberculosis (TB) are poorly understood. Yet, many efforts are underway to develop new, more effective vaccines against Mycobacterium tuberculosis. This development appears to be predicated upon the assumption that natural acquired immunity to TB exists. In this paper we review the evidence for such immunity, explore the hypothesis that disease progression is due to some, often transient, immunological dysfunction, and discuss its relevance for vaccine development. Several mechanisms for such an immune dysfunction are proposed, including the recently suggested involvement of viral co-infections. Developing vaccines for such co-infections may be a new challenge for TB control. [Copyright &y& Elsevier]

Methicillin resistant Staphylococcus aureus (MRSA) bacteria cause serious, often healthcare-associated infections and are frequently highly resistant to diverse antibiotics. Multiple MRSA clonal complexes (CCs) have evolved independently and countries have different prevalent CCs. It is unclear when and why the dominant CC in a region may switch. We developed a mathematical deterministic model of MRSA CC competing for limited resource. The model distinguishes 'standard MRSA' and multidrug resistant sub-populations within each CC, allowing for resistance loss and transfer between same CC bacteria. We first analysed how dynamics of this system depend on growth-rate and resistance-potential differences between CCs, and on their resistance gene accumulation. We then fit the model to capture the longitudinal CC dynamics observed at a single UK hospital, which exemplified the UK-wide switch from mainly CC30 to mainly CC22. We find that within a CC, gain and loss of resistance can allow for co-existence of sensitive and resistant sub-populations. Due to more efficient transfer of resistance at higher CC density, more drug resistance can accumulate in the population of a more prevalent CC. We show how this process of density dependent competition, together with prevalence disruption, could explain the relatively sudden switch from mainly CC30 to mainly CC22 in the UK hospital setting. Alternatively, the observed hospital dynamics could be reproduced by assuming that multidrug resistant CC22 evolved only around 2004. We showed how higher prevalence may advantage a CC by allowing it to acquire antimicrobial resistances more easily. Due to this density dependence in competition, dominance in an area can depend on historic contingencies; the MRSA CC that happened to be first could stay dominant because of its high prevalence advantage. This then could help explain the stability, despite frequent stochastic introductions across borders, of geographic differences in MRSA CC. • More frequent transfer of resistance elements may advantage prevalent MRSA clones. • MRSA clonal complex competition could be a density dependent process. • Average length of hospital stay may influence which clones dominate in a hospital. • Shorter hospital stay perhaps triggered the UK switch from mainly CC30 to CC22. • Abruptness of this UK clonal switch is consistent with advantage from density. [ABSTRACT FROM AUTHOR]

We recruited 510 male sex workers (also referred as 'money boys' (MBs) and 533 other men who have sex with men (MSM) to investigate determinants of recent (last year) HIV testing in Shenzhen, China. Overall, 43% of MBs and 48% of other MSM reported having been tested for HIV in the last year. The most important determinant of testing among MBs was having multiple anal sex partners; among other MSM, the most important determinants were having a homosexual orientation and having a history of sexually transmissible infection. For MBs, education programs are needed to increase their awareness of actual HIV risk. For other MSM, destigmatising programs are needed. [ABSTRACT FROM AUTHOR]