Rapid Host Defense against Aspergillus fumigatus Involves Alveolar Macrophages with a Predominance of Alternatively Activated Phenotype

The ubiquitous fungus Aspergillus fumigatus is associated with chronic diseases such as invasive pulmonary aspergillosis in immunosuppressed patients and allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis or severe asthma. Because of constant exposure to this fungus, it is critical for the host to exercise an immediate and decisive immune response to clear fungal spores to ward off disease. In this study, we observed that rapidly after infection by A. fumigatus, alveolar macrophages predominantly express Arginase 1 (Arg1), a key marker of alternatively activated macrophages (AAMs). The macrophages were also found to express Ym1 and CD206 that are also expressed by AAMs but not NOS2, which is expressed by classically activated macrophages. The expression of Arg1 was reduced in the absence of the known signaling axis, IL-4Rα/STAT6, for AAM development. While both Dectin-1 and TLR expressed on the cell surface have been shown to sense A. fumigatus, fungus-induced Arg1 expression in CD11c+ alveolar macrophages was not dependent on either Dectin-1 or the adaptor MyD88 that mediates intracellular signaling by most TLRs. Alveolar macrophages from WT mice efficiently phagocytosed fungal conidia, but those from mice deficient in Dectin-1 showed impaired fungal uptake. Depletion of macrophages with clodronate-filled liposomes increased fungal burden in infected mice. Collectively, our studies suggest that alveolar macrophages, which predominantly acquire an AAM phenotype following A. fumigatus infection, have a protective role in defense against this fungus

A Quantitative and Qualitative Evaluation of Mass Drug Administration (MDA) program in three districts of Madhya Pradesh (India)

Introduction: Lymphatic filariasis (LF) is the world's second leading cause of long-term disability. According to the World Health Organization, India, Indonesia, Nigeria and Bangladesh alone contribute about 70% of the infection worldwide. Mass drug administration of one annual dose of diethylcarbamazine citrate and albendazole is currently advocated by WHO for control of lymphatic filariasis. The state of Madhya Pradesh (MP), India adopted MDA for elimination of LF in 2004. The aim of this study was to assess the effective coverage of MDA and to determine the causes of coverage compliance gap. Methodology: It was a cross-sectional survey in which both quantitative and qualitative data was collected from the study clusters by house-to-house surveys. Multistage random sampling method was used to select the clusters. 30 household were covered in each cluster, covering 4 clusters per district; so in each district 120 households were surveyed. Results: The present study was conducted in three filariasis endemic districts of Madhya Pradesh. The study covered a target population of 1863 from twelve clusters of which 94.09% (1753) were eligible for drug consumption. The overall drug distribution rate (coverage) was 84.59% and the coverage compliance gap was 16.82%. Overall drug ingestion compliance was 80.10%. The overall effective coverage was 67.77% (Z Score=3.6338, p=0.00014). The drug distribution rate (coverage) was much better in urban areas (92.55%) as compared to rural areas (82.45%) and therefore the effective coverage was much better in urban areas (75.53%) as against 65.65% in the rural areas. The most important reason of noncompliance was lack of awareness about the disease (47.45%). Understaffing was also reported in all the districts and impact assessment data was not collected in any of the three districts. Conclusion: There is need of intensive health education campaigns to increase the level of scientific information about the disease. The coverage activities should be prioritized equally with Behavior Change Communication (BCC) activities. The timings of drug distribution should be properly thought out