Rats! Infection prevention's journey during a hospital kitchen infestation.

Infection Prevention and Control programs have the inherent authority to institute extreme measures when an infection is a threat to wellness. This report describes an Infection Prevention and Control program's collaborative approach when a hospital kitchen was closed due to rodents, how infection risks were mitigated, and practice revisions were made to avoid future infestations. Learnings from this report can be adopted across health care settings to encourage reporting vectors and promote transparency.

Francisella tularensis Exposure Among National Park Service Employees During an Epizootic: Devils Tower National Monument, Wyoming, 2015.

Introduction: Tularemia is a zoonotic infection caused by the highly infectious bacterium Francisella tularensis. Persons having outdoor professions are more likely than others to be exposed to F. tularensis through increased contact with arthropods, infected animals, and contaminated aerosols. Materials and Methods: After a tularemia epizootic during July and August 2015 at Devils Tower National Monument and an associated tularemia infection in a park employee, we assessed seroprevalence of F. tularensis antibodies, risk factors for F. tularensis seropositivity, and use of protective measures among park employees. Results: Seroprevalence among participating employees was 13% (3/23). Seropositive employees reported multiple risk factors for F. tularensis exposure through both job-related and recreational activities. Activities reported by more seropositive than seronegative employees included using a power blower (67% vs. 5%, p = 0.03), collecting animal carcasses (100% vs. 30%, p = 0.047), and hunting prairie dogs recreationally (67% vs. 5%, p = 0.03). Seropositive employees reported exposure to more ticks (median 30, range 25-35) than seronegative employees (median 6, range 0-25, p = 0.001). Most employees used protective measures (e.g., insect repellent) inconsistently but increased use after receiving educational materials. Conclusions: Educating and enabling at-risk employees to use protective measures consistently, both at work and during recreational activities, can reduce exposure during epizootics.

Defects in recombination activity caused by somatic and germline mutations in the multimerization/BRCA2 binding region of human RAD51 protein.

The human RAD51 recombinase possesses DNA pairing and strand exchange activities that are essential for the error-free, homology-directed repair of DNA double-strand breaks. The recombination activities of RAD51 are activated upon its assembly into presynaptic filaments on single-stranded DNA at resected DSB ends. Defects in filament assembly caused by mutations in RAD51 or its regulators such as BRCA2 are associated with human cancer. Here we describe two novel RAD51 missense variants located in the multimerization/BRCA2 binding region of RAD51. F86L is a breast tumor-derived somatic variant that affects the interface between adjacent RAD51 protomers in the presynaptic filament. E258A is a germline variant that maps to the interface region between the N-terminal and RecA homology domains of RAD51. Both variants exhibit abnormal biochemistry including altered DNA strand exchange activity. Both variants inhibit the DNA strand exchange activity of wild-type RAD51, suggesting a mechanism for negative dominance. The inhibitory effect of F86L on wild-type RAD51 is surprising since F86L alone exhibits robust DNA strand exchange activity. Our findings indicate that even DNA strand exchange-proficient variants can have negative functional interactions with wild-type RAD51. Thus heterozygous F86L or E258 mutations in RAD51 could promote genomic instability, and thereby contribute to tumor progression.

RAD51 variant proteins from human lung and kidney tumors exhibit DNA strand exchange defects.

In human cells, error-free repair of DNA double-strand breaks requires the DNA pairing and strand exchange activities of RAD51 recombinase. Activation of RAD51 recombination activities requires the assembly of RAD51 presynaptic filaments on the single-stranded DNA that forms at resected DSB ends. Mutations in proteins that control presynaptic filament assembly, such as BRCA2, and in RAD51 itself, are associated with human breast cancer. Here we describe the properties of two mutations in RAD51 protein that derive from human lung and kidney tumors, respectively. Sequence variants Q268P and Q272L both map to the DNA binding loop 2 (L2) region of RAD51, a motif that is involved in DNA binding and in the allosteric activation of ATP hydrolysis and DNA strand exchange activities. Both mutations alter the thermal stability, DNA binding, and ATPase properties of RAD51, however both variants retain intrinsic DNA strand exchange activity towards oligonucleotide substrates under optimized conditions. In contrast, both Q268P and Q272L variants exhibit drastically reduced DNA strand exchange activity in reaction mixtures containing long homologous ssDNA and dsDNA substrates and human RPA protein. Mixtures of wild-type and variant proteins also exhibit reduced DNA strand exchange activity, suggesting that heterozygous mutations could negatively affect DNA recombination and repair processes in vivo. Together, the findings of this study suggest that hypomorphic missense mutations in RAD51 protein could be drivers of genomic instability in cancer cells, and thereby contribute to the etiology of metastatic disease.

Notes from the Field: Increase in Human Cases of Tularemia--Colorado, Nebraska, South Dakota, and Wyoming, January-September 2015.

Tularemia is a rare, often serious disease caused by a gram-negative coccobacillus, Francisella tularensis, which infects humans and animals in the Northern Hemisphere. Approximately 125 cases have been reported annually in the United States during the last two decades. As of September 30, a total of 100 tularemia cases were reported in 2015 among residents of Colorado (n = 43), Nebraska (n = 21), South Dakota (n = 20), and Wyoming (n = 16) (Figure). This represents a substantial increase in the annual mean number of four (975% increase), seven (200%), seven (186%) and two (70%) cases, respectively, reported in each state during 2004-2014.

Assessment of vaccine exemptions among Wyoming school children, 2009 and 2011.

During 2010-2011, varicella vaccination was an added requirement for school entrance in Wyoming. Vaccination exemption rates were compared during the 2009-2010 and 2011-2012 school years, and impacts of implementing a new childhood vaccine requirement were evaluated. All public schools, grades K-12, were required to report vaccination status of enrolled children for the 2009-2010 and 2011-2012 school years to the Wyoming Department of Health. Exemption data were analyzed by exemption category, vaccine, county, grade, and rurality. The proportion of children exempt for ≥ 1 vaccine increased from 1.2% (1,035/87,398) during the 2009-2010 school year to 1.9% (1,678/89,476) during 2011-2012. In 2011, exemptions were lowest (1.5%) in urban areas and highest (2.6%) in the most rural areas, and varicella vaccine exemptions represented 67.1% (294/438) of single vaccination exemptions. Implementation of a new vaccination requirement for school admission led to an increased exemption rate across Wyoming.