Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): A patient from Sri Lanka

We report the first patient from Sri Lanka (the third patient from the Indian subcontinent) with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The patient experienced a young onset familial stroke with an 856T>G missense mutation in exon 5 of the NOTCH3 gene resulting in a C260G mutation in the sixth epidermal growth factor-like repeat. We believe this is the first reported Sri Lankan patient. CADASIL is probably underdiagnosed in the region.     

Dengue outbreak in Hadramout, Yemen, 2010: an epidemiological perspective

We analyzed surveillance data of a dengue outbreak (2010) reported to the Hadramout Health Office (Yemen) and retrospectively analyzed dengue-related epidemiological and entomological events reported in Hadramout from 2005 to 2009. A total of 630 immunoglobulin M (IgM) -confirmed dengue cases of 982 febrile cases was reported during the period from February to June of 2010; 12 cases died, giving case fatality a rate of 1.9%. Among febrile cases, the highest proportion of dengue cases (37.3%) was reported in the 15- to 24-year-old age group. The overall attack rate was 0.89/1,000. The average number of cases reported by month over the preceding 5-year period compared with the 2010 data is consistent with endemicity of dengue in the region and supports epidemic designation for the dengue activity in 2010. Recognition of endemic dengue transmission and potential for substantial dengue epidemics highlight the need for consistent laboratory-based surveillance that can support prevention and control activities accordingly.     

Exposure of Salmonella enterica Serovar Typhimurium to a Protective Monoclonal IgA Triggers Exopolysaccharide Production via a Diguanylate Cyclase-Dependent Pathway

Sal4 is a monoclonal polymeric IgA antibody directed against the O antigen (O-Ag) of Salmonella enterica serovar Typhimurium (S. Typhimurium), which is sufficient to protect mice against intestinal infections from S. Typhimurium. We recently reported that the exposure of S. Typhimurium to Sal4 results in the immediate loss of flagellum-based motility, in alterations to the outer membrane (OM) integrity, and in the concomitant appearance of a mucoid phenotype that is reminiscent of cells in the earliest stages of biofilm formation. We demonstrate here that prolonged (>4 h) exposure of S. Typhimurium to Sal4 at 37°C (but not at ambient temperature [25°C]) results in measurable exopolysaccharide (EPS) accumulation and biofilm formation on both borosilicate glass surfaces and polystyrene microtiter plates. The polysaccharide produced by S. Typhimurium in response to Sal4 contains cellulose, in addition to O-Ag capsule and colanic acid. EPS production was dependent on YeaJ, a proposed inner membrane-localized diguanylate cyclase (DGC) and a known regulator of cellulose biosynthesis. An S. Typhimurium ΔyeaJ strain was unable to produce cellulose or form a biofilm in response to Sal4. Conversely, the overexpression of yeaJ in S. Typhimurium enhanced Sal4-induced biofilm formation and resulted in increased intracellular levels of cyclic dimeric guanosine monophosphate (c-di-GMP) compared to that of a wild-type control; this strongly suggests that YeaJ is indeed a functional DGC. Based on these data, we speculate that Sal4, by virtue of its ability to associate with the O-Ag and to induce OM stress, renders S. Typhimurium avirulent by triggering a c-di-GMP-dependent signaling pathway via YeaJ that leads to the suppression of bacterial motility while simultaneously stimulating EPS production.