Signaling from the transmembrane receptor Toll to Rel-related transcription factors regulates dorsoventral patterning of the Drosophila embryo, as well as larval and adult immunity. To identify additional pathway components, we have used double-stranded RNA interference to investigate Drosophila counterparts of genes that regulate the mammalian Rel family member NF-B. Experiments in cultured cells reveal that the fly orthologue of the adaptor protein MyD88 is essential for signal transduction from Toll to a second adaptor protein, Tube. By using coimmunoprecipitation studies, we find a heterotrimeric association of the death domains of MyD88, Tube, and the protein kinase Pelle. Site-directed mutational analyses of interaction sites defined by crystallographic studies demonstrate that Tube recruits MyD88 and Pelle into the heterotrimer by two distinct binding surfaces on the Tube death domain. Furthermore, functional assays confirm that the formation of this heterotrimer is critical for signal transduction by the Toll pathway.

Coccidioidomycosis is a fungal disease that occurs throughout the Americas. It is contracted by inhaling spores, which are carried in dust. Therefore, it occurs most commonly in dry areas and in persons who work in dusty conditions (such as agricultural workers, construction workers, military personnel, and archeological site workers). A substantial number of people die of this disease each year, so researchers examined what other factors increase the risk for death. They found that risk for death was highest among men, elderly persons (>65 years), Hispanics, Native Americans, residents of California and Arizona, and those who also had HIV or other immune-suppressive conditions. Physicians should be aware of which patients are at increased risk and should ask patients about their travel history or occupation to determine possible sources of exposure.

BackgroundCongenital cytomegalovirus (CMV) infection is the most common intrauterine infection in the United States disproportionately affecting minority races and those of lower socio-economic class. Despite its importance there is little information on the burden of congenital CMV-related mortality in the US. To measure congenital CMV-associated mortality in the US and assess possible racial/ethnic disparities, we reviewed national death certificate data for a 17-year period.MethodsCongenital CMV-associated deaths from 1990 through 2006 were identified from multiple-cause-coded death records and were combined with US census data to calculate mortality rates.ResultsA total of 777 congenital CMV-associated deaths occurred over the 17-year study period resulting in 56,355 years of age-adjusted years of potential life lost. 71.7% (557) of congenital CMV-associated deaths occurred in infants (age less than 1 year). Age-adjusted mortality rates stratified by race/ethnicity revealed mortality disparities. Age-adjusted rate ratios were calculated for each racial/ethnic group using whites as the reference. Native Americans and African Americans were 2.34 (95% CI, 2.11–2.59) and 1.89 (95% CI, 1.70–2.11) times respectively, more likely to die from congenital CMV than whites. Asians and Hispanics were 0.54 (95% CI, 0.44–0.66) and 0.96 (95% CI, 0.83–1.10) times respectively, less likely to die from congenital CMV than whites.Conclusions/SignificanceCongenital CMV infection causes appreciable mortality in the US exacting a particular burden among African Americans and Native Americans. Enhanced surveillance and increased screening are necessary to better understand the epidemiology of congenital CMV infection in addition to acceleration of vaccine development efforts.

Few data are available on the burden of malaria hospitalization in the United States. Study of malaria using hospital-based data can better define the impact of malaria and help inform prevention efforts. U.S. malaria cases identified from hospitalization discharge records in the 2000-2014 Nationwide Inpatient Sample were examined. Frequencies and population rates were reported by demographics, infecting species, clinical, financial, institutional, geographic, and seasonal characteristics, and disparities were identified. Time trends in malaria cases were assessed using negative binomial regression. From 2000 to 2014, there were an estimated 22,029 malaria-related hospitalizations (4.88 per 1 million population) in the United States, including 182 in-hospital deaths and 4,823 severe malaria cases. The rate of malaria-related hospitalizations did not change significantly over the study period. The largest number of malaria-related hospitalizations occurred in August. Malaria-related hospitalizations occurred disproportionately among patients who were male, black, or 25-44 years of age. accounted for the majority of malaria-related hospitalizations. On average, malaria patients were hospitalized for 4.36 days with charges of $25,789. Patients with a malaria diagnosis were more often hospitalized in the Middle Atlantic and South Atlantic census divisions, urban teaching, private not-for-profit, and large-bed-size hospitals. Malaria imposes a substantial disease burden in the United States. Enhanced primaryand secondary prevention measures, including strategies to increase the use of pretravel consultations and prompt diagnosis and treatment are needed.