Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011.

IMPORTANCE: Clostridium difficile infection (CDI) has been increasingly reported among healthy individuals in the community. Recent data suggest that community-associated CDI represents one-third of all C difficile cases. The epidemiology and potential sources of C difficile in the community are not fully understood. OBJECTIVES: To determine epidemiological and clinical characteristics of community-associated CDI and to explore potential sources of C difficile acquisition in the community. DESIGN AND SETTING: Active population-based and laboratory-based CDI surveillance in 8 US states. PARTICIPANTS: Medical records were reviewed and interviews performed to assess outpatient, household, and food exposures among patients with community-associated CDI (ie, toxin or molecular assay positive for C difficile and no overnight stay in a health care facility within 12 weeks). Molecular characterization of C difficile isolates was performed. Outpatient health care exposure in the prior 12 weeks among patients with community-associated CDI was a priori categorized into the following 3 levels: no exposure, low-level exposure (ie, outpatient visit with physician or dentist), or high-level exposure (ie, surgery, dialysis, emergency or urgent care visit, inpatient care with no overnight stay, or health care personnel with direct patient care). MAIN OUTCOMES AND MEASURES: Prevalence of outpatient health care exposure among patients with community-associated CDI and identification of potential sources of C difficile by level of outpatient health care exposure. RESULTS: Of 984 patients with community-associated CDI, 353 (35.9%) did not receive antibiotics, 177 (18.0%) had no outpatient health care exposure, and 400 (40.7%) had low-level outpatient health care exposure. Thirty-one percent of patients without antibiotic exposure received proton pump inhibitors. Patients having CDI with no or low-level outpatient health care exposure were more likely to be exposed to infants younger than 1 year (P = .04) and to household members with active CDI (P = .05) compared with those having high-level outpatient health care exposure. No association between food exposure or animal exposure and level of outpatient health care exposure was observed. North American pulsed-field gel electrophoresis (NAP) 1 was the most common (21.7%) strain isolated; NAP7 and NAP8 were uncommon (6.7%). CONCLUSIONS AND RELEVANCE: Most patients with community-associated CDI had recent outpatient health care exposure, and up to 36% would not be prevented by reduction of antibiotic use only. Our data support evaluation of additional strategies, including further examination of C difficile transmission in outpatient and household settings and reduction of proton pump inhibitor use.

Skin disorders among construction workers following Hurricane Katrina and Hurricane Rita: an outbreak investigation in New Orleans, Louisiana.

OBJECTIVES: To determine the extent and scope of the outbreak of skin eruptions, to identify the causes of the acute skin diseases, to identify risk factors for the conditions, and to reduce the dermatologic morbidity among workers repairing buildings damaged by Hurricane Katrina and Hurricane Rita. DESIGN: Retrospective cohort study. SETTING: Military base in New Orleans, Louisiana. PARTICIPANTS: Civilian construction workers living and working at a New Orleans military base between August 30, 2005, and October 3, 2005. Living conditions were mainly wooden huts and tents with limited sanitation facilities. MAIN OUTCOME MEASURES: Survey of risk factors, physical examination, skin biopsy specimens, and environmental investigation of the occupational and domiciliary exposures. RESULTS: Of 136 workers, 58 reported rash, yielding an attack rate of 42.6%. The following 4 clinical entities were diagnosed among 41 workers who had a physical examination (some had >1 diagnosis): 27 (65.9%) having papular urticaria, 8 (19.5%) having bacterial folliculitis, 6 (14.6%) having fiberglass dermatitis, and 2 (4.9%) having brachioradial photodermatitis. All diagnoses except brachioradial photodermatitis were confirmed by histopathologic examination. After adjusting for race/ethnicity and occupation, sleeping in previously flooded huts was statistically significantly (adjusted odds ratio, 20.4; 95% confidence interval, 5.9-70.2) associated with developing papular urticaria, the most common cause of rash in this cluster. CONCLUSIONS: We identified 4 distinct clinical entities, although most workers were diagnosed as having papular urticaria. Huts previously flooded as a result of the hurricanes and used for sleeping may have harbored mites, a likely source of papular urticaria. To reduce the morbidity of hurricane-related skin diseases, we suggest avoiding flooded areas, fumigating with an acaricide, and wearing protective clothing.

Antibodies targeting linear determinants of the envelope protein protect mice against West Nile virus.

The flavivirus envelope (E) protein mediates cellular attachment and fusion with host cell membranes and is recognized by virus-neutralizing antibodies. We raised antibodies against a broad range of epitopes by immunizing a horse with recombinant West Nile virus (WNV) E protein. To define epitopes recognized by protective antibodies, we selected, by affinity chromatography, immunoglobulins against immobilized linear peptides derived from parts of the E protein. Immunoglobulins binding 9 different peptides from domains I, II, and III of the E protein neutralized WNV in vitro. This indicates that multiple protective epitopes can be found in the E protein. Immunoglobulins recognizing 3 peptides derived from domains I and II of E protein protected mice against a lethal challenge with WNV. These immunoglobulins recognized the E proteins of related flaviviruses, demonstrating that antibodies targeting specific E protein epitopes could be developed for prevention and treatment of multiple flavivirus infections.

Crystal structure of west nile virus envelope glycoprotein reveals viral surface epitopes.

West Nile virus, a member of the Flavivirus genus, causes fever that can progress to life-threatening encephalitis. The major envelope glycoprotein, E, of these viruses mediates viral attachment and entry by membrane fusion. We have determined the crystal structure of a soluble fragment of West Nile virus E. The structure adopts the same overall fold as that of the E proteins from dengue and tick-borne encephalitis viruses. The conformation of domain II is different from that in other prefusion E structures, however, and resembles the conformation of domain II in postfusion E structures. The epitopes of neutralizing West Nile virus-specific antibodies map to a region of domain III that is exposed on the viral surface and has been implicated in receptor binding. In contrast, we show that certain recombinant therapeutic antibodies, which cross-neutralize West Nile and dengue viruses, bind a peptide from domain I that is exposed only during the membrane fusion transition. By revealing the details of the molecular landscape of the West Nile virus surface, our structure will assist the design of antiviral vaccines and therapeutics.

A recombinant envelope protein-based enzyme-linked immunosorbent assay for West Nile virus serodiagnosis.

Recombinant West Nile virus envelope (E) protein was examined in enzyme-linked immunosorbent assay (ELISA) to detect antibodies elicited during West Nile virus infection. Horses (nine of 10) and humans (six of six) with confirmed West Nile virus infection had IgG and/or IgM antibodies to the E protein. Antibodies to the recombinant West Nile virus membrane and nonstructural 1 proteins were not detected in any of these sera. An E protein-based ELISA may aid in the serological diagnosis of West Nile virus infection.