Modeling the risk of malaria for travelers to areas with stable malaria transmission

BACKGROUND: Malaria is an important threat to travelers visiting endemic regions. The risk of acquiring malaria is complex and a number of factors including transmission intensity, duration of exposure, season of the year and use of chemoprophylaxis have to be taken into account estimating risk. MATERIALS AND METHODS: A mathematical model was developed to estimate the risk of non-immune individual acquiring falciparum malaria when traveling to the Amazon region of Brazil. The risk of malaria infection to travelers was calculated as a function of duration of exposure and season of arrival. RESULTS: The results suggest significant variation of risk for non-immune travelers depending on arrival season, duration of the visit and transmission intensity. The calculated risk for visitors staying longer than 4 months during peak transmission was 0.5% per visit. CONCLUSIONS: Risk estimates based on mathematical modeling based on accurate data can be a valuable tool in assessing risk/benefits and cost/benefits when deciding on the value of interventions for travelers to malaria endemic regions

Scavenger receptors and β-glucan receptors participate in the recognition of yeasts by murine macrophages

Objectives: Numerous receptors have been implicated in recognition of pathogenic fungi by macrophages, including the $\beta$-glucan receptor dectin-1. The role of scavenger receptors (SRs) in anti-fungal immunity is not well characterized. Methods: We studied uptake of unopsonized Saccharomycetes cerevisiae (zymosan) and live Candida albicans yeasts as well as zymosan-stimulated $H_2O_2$ production in J774 macrophage-like cells and peritoneal exudate macrophages (PEMs). The role of different receptors was assessed with the use of competitive ligands, transfected cells and receptor-deficient macrophages. Results: The uptake of zymosan by untreated J774 cells was mediated approximately half by SRs and half by a $\beta$-glucan receptor which was distinct from dectin-1 and not linked to stimulation of $H_2O_2$ production. Ligands of $\beta$-glucan receptors and of SRs also inhibited uptake of C. albicans by macrophages (J774 cells and PEMs). In macrophages pretreated with a CpG motif-containing oligodeoxynucleotide (CpG-ODN) the relative contribution of SRs to yeast uptake increased and that of $\beta$-glucan receptors decreased. Whereas the class A SR MARCO participated in the uptake of both zymosan and C. albicans by CpG-ODN-pretreated, but not untreated macrophages, the related receptor SR-A/CD204 was involved in the uptake of zymosan, but not of C. albicans. The reduction of zymosan-stimulated $H_2O_2$ production observed in DS-pretreated J774 cells and in class A SRs-deficient PEMs suggest that class A SRs mediate part of this process. Conclusions: Our results revealed that SRs belong to a redundant system of receptors for yeasts. Binding of yeasts to different receptors in resting versus CpG-ODN-pre-exposed macrophages may differentially affect polarization of adaptive immune responses

Podoconiosis, trachomatous trichiasis and cataract in northern Ethiopia: a comparative cross-sectional study

Background: Rural populations in low-income countries commonly suffer from the co-morbidity of neglected tropical diseases (NTDs). Podoconiosis, trachomatous trichiasis (both NTDs) and cataract are common causes of morbidity among subsistence farmers in the highlands of northern Ethiopia. We explored whether podoconiosis was associated with cataract or trachomatous trichiasis (TT) among this population. Methods: A comparative cross-sectional study was conducted in East Gojam region, Amhara, Ethiopia in May 2016 . Data were collected from patients previously identified as having podoconiosis and from matched healthy neighbourhood controls. Information on socio- demographic factors, clinical factors and past medical history were collected by an interview-administered questionnaire. Clinical examination involved grading of podoconiosis by examination of both legs, measurement of visual acuity, direct ophthalmoscopy of dilated pupils to grade cataract, and eyelid and corneal examination to grade trachoma. Multiple logistic regression was conducted to estimate independent association and correlates of podoconiosis, TT and cataract. Findings: A total of 700 participants were included in this study; 350 podoconiosis patients and 350 healthy neighbourhood controls. The prevalence of TT was higher among podoconiosis patients than controls (65 (18.6%) vs 43 (12.3%)) with an adjusted odds ratio (OR) 1.55 (95% Confidence Interval (CI) 1.12 - 2.11), p=0.05. There was no significant difference in 3 prevalence of cataract between the two populations with an adjusted OR 0.83 (95% CI 0.55-1.38), p=0.37. Mean best visual acuity was 0.59 (SD +/- 0.06) in podoconiosis cases compared to 0.44 (SD +/- 0.04) in controls, p=< 0.001. The proportion of patients classified as blind was higher in podoconiosis cases compared with healthy controls; 5.6% vs 2.0%; adjusted OR 2.63 (1.08-6.39), P = 0.03. Conclusions Individuals with podoconiosis have a higher burden of TT and worse visual acuity than their matched healthy neighbourhood controls. Further research into the environmental and biological reasons for this co-morbidity is required. A shared approach to managing these two NTDs within the same population could be beneficial

Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation

Wear particles from automotive friction brake pads of various sizes, morphology, and chemical composition are significant contributors towards particulate matter. Knowledge concerning the potential adverse effects following inhalation exposure to brake wear debris is limited. Our aim was, therefore, to generate brake wear particles released from commercial low-metallic and non-asbestos organic automotive brake pads used in mid-size passenger cars by a full-scale brake dynamometer with an environmental chamber simulating urban driving and to deduce their potential hazard in vitro. The collected fractions were analysed using scanning electron microscopy via energy-dispersive X-ray spectroscopy (SEM-EDS) and Raman microspectroscopy. The biological impact of the samples was investigated using a human 3D multicellular model consisting of human epithelial cells (A549) and human primary immune cells (macrophages and dendritic cells) mimicking the human epithelial tissue barrier. The viability, morphology, oxidative stress, and (pro-)inflammatory response of the cells were assessed following 24 h exposure to similar to 12, similar to 24, and similar to 48 A mu g/cm(2) of non-airborne samples and to similar to 3.7 A mu g/cm(2) of different brake wear size fractions (2-4, 1-2, and 0.25-1 A mu m) applying a pseudo-air-liquid interface approach. Brake wear debris with low-metallic formula does not induce any adverse biological effects to the in vitro lung multicellular model. Brake wear particles from non-asbestos organic formulated pads, however, induced increased (pro-)inflammatory mediator release from the same in vitro system. The latter finding can be attributed to the different particle compositions, specifically the presence of anatase.Web of Science9272351233