Allergen-specific desensitization is the only disease-modifying therapy currently available for the treatment of allergies. These therapies require application of allergen over several years and some ...may induce life-threatening anaphylactic reactions. An ideal vaccine for desensitization should be highly immunogenic and should alleviate allergic symptoms upon few injections while being nonreactogenic. We describe such a vaccine for the treatment of cat allergy, consisting of the major cat allergen Fel d1 coupled to bacteriophage Qbeta-derived virus-like particles (Qbeta-Fel d1). Qbeta-Fel d1 was highly immunogenic, and a single vaccination was sufficient to induce protection against type I allergic reactions. Allergen-specific immunoglobulin G antibodies were shown to be the critical effector molecules and alleviated symptoms by two distinct mechanisms. Although allergen-induced systemic basophil degranulation was inhibited in an FcgammaRIIb-dependent manner, inhibition of local mast cell degranulation in tissues occurred independently of FcgammaRIIb. In addition, treatment with Qbeta-Fel d1 abolished IgE memory responses upon antigen recall. Despite high immunogenicity, the vaccine was essentially nonreactogenic and vaccination induced neither local nor systemic anaphylactic reactions in sensitized mice. Moreover, Qbeta-Fel d1 did not induce degranulation of basophils derived from human volunteers with cat allergies. These data suggest that vaccination with Qbeta-Fel d1 may be a safe and effective treatment for cat allergy.
BACKGROUND: Schistosomiasis is a water-based disease that affects an estimated 250 million people, mainly in sub-Saharan Africa. The transmission of schistosomiasis is spatially and temporally ...restricted to freshwater bodies that contain schistosome cercariae released from specific snails that act as intermediate hosts. Our objective was to assess the contribution of remote sensing applications and to identify remaining challenges in its optimal application for schistosomiasis risk profiling in order to support public health authorities to better target control interventions. METHODS: We reviewed the literature (i) to deepen our understanding of the ecology and epidemiology of schistosomiasis, placing particular emphasis on remote sensing; and (ii) to fill an identified gap, namely interdisciplinary research that bridges different strands of scientific inquiry to enhance spatially explicit risk profiling. As a first step, we reviewed key factors that govern schistosomiasis risk. Secondly, we examined remote sensing data and variables that have been used for risk profiling of schistosomiasis. Thirdly, the linkage between the ecological consequence of environmental conditions and the respective measure of remote sensing data were synthesised. RESULTS: We found that the potential of remote sensing data for spatial risk profiling of schistosomiasis is – in principle – far greater than explored thus far. Importantly though, the application of remote sensing data requires a tailored approach that must be optimised by selecting specific remote sensing variables, considering the appropriate scale of observation and modelling within ecozones. Interestingly, prior studies that linked prevalence of Schistosoma infection to remotely sensed data did not reflect that there is a spatial gap between the parasite and intermediate host snail habitats where disease transmission occurs, and the location (community or school) where prevalence measures are usually derived from. CONCLUSIONS: Our findings imply that the potential of remote sensing data for risk profiling of schistosomiasis and other neglected tropical diseases has yet to be fully exploited.
Schistosomiasis is the most widespread water-based disease in sub-Saharan Africa. Transmission is governed by the spatial distribution of specific freshwater snails that act as intermediate hosts and ...human water contact patterns. Remote sensing data have been utilized for spatially explicit risk profiling of schistosomiasis. We investigated the potential of remote sensing to characterize habitat conditions of parasite and intermediate host snails and discuss the relevance for public health.
We employed high-resolution remote sensing data, environmental field measurements, and ecological data to model environmental suitability for schistosomiasis-related parasite and snail species. The model was developed for Burkina Faso using a habitat suitability index (HSI). The plausibility of remote sensing habitat variables was validated using field measurements. The established model was transferred to different ecological settings in Côte d'Ivoire and validated against readily available survey data from school-aged children.
Environmental suitability for schistosomiasis transmission was spatially delineated and quantified by seven habitat variables derived from remote sensing data. The strengths and weaknesses highlighted by the plausibility analysis showed that temporal dynamic water and vegetation measures were particularly useful to model parasite and snail habitat suitability, whereas the measurement of water surface temperature and topographic variables did not perform appropriately. The transferability of the model showed significant relations between the HSI and infection prevalence in study sites of Côte d'Ivoire.
A predictive map of environmental suitability for schistosomiasis transmission can support measures to gain and sustain control. This is particularly relevant as emphasis is shifting from morbidity control to interrupting transmission. Further validation of our mechanistic model needs to be complemented by field data of parasite- and snail-related fitness. Our model provides a useful tool to monitor the development of new hotspots of potential schistosomiasis transmission based on regularly updated remote sensing data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite considerable progress made over the past 20 years in reducing the global burden of malaria, the disease remains a major public health problem and there is concern that climate change might ...expand suitable areas for transmission. This study investigated the relative effect of climate variability on malaria incidence after scale-up of interventions in western Kenya.
Bayesian negative binomial models were fitted to monthly malaria incidence data, extracted from records of patients with febrile illnesses visiting the Lwak Mission Hospital between 2008 and 2019. Data pertaining to bed net use and socio-economic status (SES) were obtained from household surveys. Climatic proxy variables obtained from remote sensing were included as covariates in the models. Bayesian variable selection was used to determine the elapsing time between climate suitability and malaria incidence.
Malaria incidence increased by 50% from 2008 to 2010, then declined by 73% until 2015. There was a resurgence of cases after 2016, despite high bed net use. Increase in daytime land surface temperature was associated with a decline in malaria incidence (incidence rate ratio IRR = 0.70, 95% Bayesian credible interval BCI: 0.59–0.82), while rainfall was associated with increased incidence (IRR = 1.27, 95% BCI: 1.10–1.44). Bed net use was associated with a decline in malaria incidence in children aged 6–59 months (IRR = 0.78, 95% BCI: 0.70–0.87) but not in older age groups, whereas SES was not associated with malaria incidence in this population.
Variability in climatic factors showed a stronger effect on malaria incidence than bed net use. Bed net use was, however, associated with a reduction in malaria incidence, especially among children aged 6–59 months after adjusting for climate effects. To sustain the downward trend in malaria incidence, this study recommends continued distribution and use of bed nets and consideration of climate-based malaria early warning systems when planning for future control interventions.
Liberal PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to contain the coronavirus disease 2019 (COVID-19) pandemic. Combined multi-sample testing in pools instead ...of single tests might enhance laboratory capacity and reduce costs, especially in low- and middle-income countries.
The purpose of our study was to assess the value of a simple questionnaire to guide and further improve pooling strategies for SARS-CoV-2 laboratory testing.
Pharyngeal swabs for SARS-CoV-2 testing were obtained from healthcare and police staff, hospital inpatients, and nursing home residents in the southwestern part of Germany. We designed a simple questionnaire, which included questions pertaining to a suggestive clinical symptomatology, recent travel history, and contact with confirmed cases to stratify an individual's pre-test probability of having contracted COVID-19. The questionnaire was adapted repeatedly in face of the unfolding pandemic in response to the evolving epidemiology and observed clinical symptomatology. Based on the response patterns, samples were either tested individually or in multi-sample pools. We compared the pool positivity rate and the number of total PCR tests required to obtain individual results between this questionnaire-based pooling strategy and randomly assembled pools.
Between March 11 and July 5, 2020, we processed 25,978 samples using random pooling (n = 6,012; 23.1%) or questionnaire-based pooling (n = 19,966; 76.9%). The overall prevalence of SARS-CoV-2 was 0.9% (n = 238). Pool positivity (14.6% vs. 1.2%) and individual SARS-CoV-2 prevalence (3.4% vs. 0.1%) were higher in the random pooling group than in the questionnaire group. The average number of PCR tests needed to obtain the individual result for one participant was 0.27 tests in the random pooling group, as compared to 0.09 in the questionnaire-based pooling group, leading to a laboratory capacity increase of 73% and 91%, respectively, as compared to single PCR testing.
Strategies that combine pool testing with a questionnaire-based risk stratification can increase laboratory testing capacities for COVID-19 and might be important tools, particularly in resource-constrained settings.
Ga-prostate-specific membrane antigen (PSMA) PET/CT is a promising diagnostic tool for patients with prostate cancer. Our study evaluates SUVs in benign prostate tissue and malignant, intraprostatic ...tumor lesions and correlates results with several clinical parameters.
One hundred four men with newly diagnosed prostate carcinoma and no previous therapy were included in this study. SUV
was measured and correlated with biopsy findings and MRI. Afterward, data were compared with current prostate-specific antigen (PSA) values, Gleason score (GS), and d'Amico risk classification.
In this investigation a mean SUV
of 1.88 ± 0.44 in healthy prostate tissue compared with 10.77 ± 8.45 in malignant prostate lesions (
< 0.001) was observed. Patients with higher PSA, higher GS, and higher d'Amico risk score had statistically significant higher PSMA uptake on PET/CT (
< 0.001 each).
PSMA PET/CT is well suited for detecting the intraprostatic malignant lesion in patients with newly diagnosed prostate cancer. Our findings indicate a significant correlation of PSMA uptake with PSA, GS, and risk classification according to the d'Amico scale.
Schistosomiasis is a widespread water-based disease that puts close to 800 million people at risk of infection with more than 250 million infected, mainly in sub-Saharan Africa. Transmission is ...governed by the spatial distribution of specific freshwater snails that act as intermediate hosts and the frequency, duration and extent of human bodies exposed to infested water sources during human water contact. Remote sensing data have been utilized for spatially explicit risk profiling of schistosomiasis. Since schistosomiasis risk profiling based on remote sensing data inherits a conceptual drawback if school-based disease prevalence data are directly related to the remote sensing measurements extracted at the location of the school, because the disease transmission usually does not exactly occur at the school, we took the local environment around the schools into account by explicitly linking ecologically relevant environmental information of potential disease transmission sites to survey measurements of disease prevalence. Our models were validated at two sites with different landscapes in Côte d'Ivoire using high- and moderate-resolution remote sensing data based on random forest and partial least squares regression. We found that the ecologically relevant modelling approach explained up to 70% of the variation in Schistosoma infection prevalence and performed better compared to a purely pixel-based modelling approach. Furthermore, our study showed that model performance increased as a function of enlarging the school catchment area, confirming the hypothesis that suitable environments for schistosomiasis transmission rarely occur at the location of survey measurements.
Objectives: 68Ga-PSMA11-PET/CT is a promising diagnostic tool for patients in recurrent prostate cancer (PCa). However, only limited investigations are available about the impact of the loco-regional ...tumor T-Staging using PSMA-ligands. Our study evaluates standardized uptake values (SUV) in benign prostate tissue and malignant, intraprostatic tumor lesions and its correlations to several clinical parameters (PSA, Gleason Score). Methods: 104 men with prostate carcinoma and therapeutic naiv to any anti-androgen deprivation or other therapeutic management were included into this study. SUV-valsues (SUVmax) were measured with reference to histopathological findings or magnetic resonance imaging (mpMRI). Afterwards, data was compared with current prostate specific antigen (PSA) values, Gleason Score (GS) and d'Amico risk classification. Results: We identified a mean SUVmax=1.89 ± 0.45 in healthy prostate parecnyhma compared to SUVmax=10.95 ± 8.47 in malignant, intraprostatic tumor segments (p < 0.001). Patients with higher PSA, higher GS and higher risk score according to d'Amico showed a statistically significant higher tracer uptake in PSMA-PET/CT (p < 0.001/ p = 0.002, respectively). Conclusion: 68Ga-PSMA11-PET/CT is well suited for detecting dominant intraprostatic tumor lesion of patients with newly diagnosed prostate cancer. Our findings from a large cohort suggest a correlation of PMSA uptake with PSA, GS and risk classification according to d'Amico. These findings might impact into biospie guidance, radio-oncological management and further treatment stratification.
68Ga-prostate-specific membrane antigen (PSMA) PET/CT is a promising diagnostic tool for patients with prostate cancer. Our study evaluates SUVs in benign prostate tissue and malignant, ...intraprostatic tumor lesions and correlates results with several clinical parameters. Methods: One hundred four men with newly diagnosed prostate carcinoma and no previous therapy were included in this study. SUVmax was measured and correlated with biopsy findings and MRI. Afterward, data were compared with current prostate-specific antigen (PSA) values, Gleason score (GS), and d'Amico risk classification. Results: In this investigation a mean SUVmax of 1.88 ± 0.44 in healthy prostate tissue compared with 10.77 ± 8.45 in malignant prostate lesions (P < 0.001) was observed. Patients with higher PSA, higher GS, and higher d'Amico risk score had statistically significant higher PSMA uptake on PET/CT (P < 0.001 each). Conclusion: PSMA PET/CT is well suited for detecting the intraprostatic malignant lesion in patients with newly diagnosed prostate cancer. Our findings indicate a significant correlation of PSMA uptake with PSA, GS, and risk classification according to the d'Amico scale.
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