Early Supported Discharge for patients with febrile neutropenia - Experience at a large district hospital in the UK.

Neutropenic sepsis can be life threatening, with mortality 2-21%. The heterogeneity of patients referred with "suspected neutropenic sepsis" has led to strategies being developed to risk-stratify patients and identify those with a low risk of septic complications that could be managed in the outpatient setting, such as The Multinational Association for Supportive Care in Cancer score (MASCC). Outcomes for patients referred with suspected neutropenic sepsis were assessed before and after use of MASCC guided early-supported discharge. 50/123 (41%) patients over 24 months were eligible for early-supported discharge. 26/50 patients had same-day discharge, 14 had overnight admission, 8 stayed 2 nights and 2 stayed 3 nights. Patients received on average 2 follow-up telephone consultations. There were 5 readmissions (10%) and no adverse events. In comparison group; 8 patients over 3-months would have been suitable, potentially saving 40 bed-days. This shows MASCC guided early-supported discharge is safe and cost-effective.

A simple intervention to improve antibiotic treatment times for neutropenic sepsis.

OBJECTIVES: Patients with suspected Neutropenic sepsis require rapid antibiotic administration, but despite extensive education, only 67% of patients received antibiotics within 60 minutes . METHODS: A Neutropenic Sepsis Alert Card was created, as a Patient Specific Directive - this allows nurses to administer antibiotics to specific patients without prior medical review. RESULTS: Since the intervention, 301 patients presented with suspected neutropenic sepsis. 277 patients (92%) received their first dose of intravenous antibiotics within 1 hour of arrival into hospital, compared to 95 out of 143 patients (67%) presenting between January and June of 2014 (p=0.036). CONCLUSION: The Neutropenic Sepsis Alert Card can significantly improve door to antibiotic needle time for chemotherapy patients with suspected neutropenic sepsis. This intervention is inexpensive and easily replicable in other health care organisations.

Establishment of a deer mouse (Peromyscus maniculatus rufinus) breeding colony from wild-caught founders: comparison of reproductive performance of wild-caught and laboratory-reared pairs.

The deer mouse (Peromyscus maniculatus) is a natural reservoir for several human pathogens, but little is known about the mechanisms by which such pathogens are maintained in nature. As a first step toward developing a colony of deer mice that were permissive for infection with Sin Nombre (SN) hantavirus, we collected 68 wild P. maniculatus rufinus from central New Mexico. Mice from this cohort were used to establish 26 breeding pairs, of which 85% were fertile. In subsequent generations, fertility decreased slightly to 73% (N = 59) in laboratory-reared F1 and F2 pairs. Wild-caught females delivered 7.2 litters on average (range, 1 to 18), whereas laboratory-reared pairs delivered 5.5 (range, 1 to 13). The average time between pairing and first litter was 106 days for wild-caught animals, whereas that for laboratory-reared pairs was 71 days. None of the pairs displayed a seasonal breeding preference. Cannibalistic behavior increased from 5% in founders to 26% in laboratory-reared pairs. Mean litter size for wild-caught females was 4.3, whereas that for laboratory-reared dams was 4. Founding animals have been maintained in captivity for longer than 2 years, with only 2 deaths (4.8%). Our colony is competent for infection with SN virus. Thus, it should be useful for testing of models for maintenance of SN virus in wild rodents, and other aspects of the virus-host relationship.

Experimental infection model for Sin Nombre hantavirus in the deer mouse (Peromyscus maniculatus).

The relationship between hantaviruses and their reservoir hosts is not well understood. We successfully passaged a mouse-adapted strain of Sin Nombre virus from deer mice (Peromyscus maniculatus) by i.m. inoculation of 4- to 6-wk-old deer mouse pups. After inoculation with 5 ID(50), antibodies to the nucleocapsid (N) antigen first became detectable at 14 d whereas neutralizing antibodies were detectable by 7 d. Viral N antigen first began to appear in heart, lung, liver, spleen, and/or kidney by 7 d, whereas viral RNA was present in those tissues as well as in thymus, salivary gland, intestine, white fat, and brown fat. By 14 d nearly all tissues examined displayed both viral RNA and N antigen. We noted no consistent histopathologic changes associated with infection, even when RNA load was high. Viral RNA titers peaked on 21 d in most tissues, then began to decline by 28 d. Infection persisted for at least 90 d. The RNA titers were highest in heart, lung, and brown fat. Deer mice can be experimentally infected with Sin Nombre virus, which now allows provocative examination of the virus-host relationship. The prominent involvement of heart, lung, and brown fat suggests that these sites may be important tissues for early virus replication or for maintenance of the virus in nature.

Characterization of age- and dose-related outcomes of duck hepatitis B virus infection.

Experimental inoculation of naive ducks with duck hepatitis B virus (DHBV) can lead to one of three outcomes, namely, persistent viremia, transient infection with or without viremia, or no evidence of infection. The ability of individual ducks to resolve DHBV infection was found to be linked to the age of the duck at the time of inoculation and the dose of inoculated virus. (1) In recently hatched ducks inoculated intravenously (i.v.) with 4 x 10(4) DHBV DNA genomes, a switch from persistent viremia to transient antibody appearance was seen at an age of inoculation between 7 and 14 days. A 25-fold increase in the dose of virus (1 x 10(6) DHBV genomes) delayed this switch by 7 days. (2) When 4-month-old ducks were inoculated i.v. with different doses of virus, only those receiving the highest dose (2 x 10(11) DHBV genomes) showed viremia and extensive viral replication and histological changes in the liver; 2/3 ducks in this group had a transient infection, while the third duck had viral replication and histological changes in the liver that were still present at day 120 postinoculation (p.i.). In all ducks receiving lower doses (1 x 10(3), 1 x 10(6), 1 x 10(9) DHBV genomes) antibodies to viral surface and core antigens developed without detectable viral replication in the liver on days 6, 9, or 12 p.i. (3) When 10- to 16-month-old ducks were inoculated i.v. with 2 x 10(11) DHBV genomes, all showed extensive viral replication in hepatocytes and mild to moderate histological changes in the liver on days 4 or 6 p.i. In 4/5 ducks viremia was not detected, anti-surface antibodies were first detected on day 8 p.i., and viral DNA and antigen were cleared from the liver by days 35-47 p.i. The remaining duck became viremic with persistence of virus in the liver until at least day 46 p.i. The findings of the study are consistent with a model for noncytopathic viruses (R. M. Zinkernagel (1996) Science 271, 173-178).

Rio Mamore virus: genetic characterization of a newly recognized hantavirus of the pygmy rice rat, Oligoryzomys microtis, from Bolivia.

Human hantavirus disease occurs throughout much of South America. The rodent hosts and the specific etiologic agent(s) are largely unknown, but many reported cases occurred within the habitation ranges of oryzomine rodents (rice rats). We have identified a genetically novel hantavirus (Rio Mamore virus [RM]) of the pygmy rice rat Oligoryzomys microtis in Bolivia. The complete sequence of the small (S) genome and the partial sequence of the medium (M) genome are described. This virus is closely related to the newly identified human pathogen Andes virus from Patagonia. To facilitate improved diagnosis of hantavirus infections in South America, we have expressed the complete nucleocapsid protein of RM in Escherichia coli and affinity-purified it for use in an ELISA and Western blot assays for antibodies to RM.

Characterization of a class II pilin expression locus from Neisseria meningitidis: evidence for increased diversity among pilin genes in pathogenic Neisseria species.

Strains of Neisseria meningitidis elaborate one of two classes of pili. Meningococcal class I pili have many features in common with pili produced by N. gonorrhoeae, including the ability to bind monoclonal antibody SM1 and a common gene and protein structure consisting of conserved, semivariable, and hypervariable regions. Class II pili are SM1 nonreactive and display smaller subunit molecular weights than do gonococcal or meningococcal class I pili. In this study, we have determined the N-terminal amino acid sequence for class II pilin and isolated the expression locus encoding class II pilin from N. meningitidis FAM18. Meningococcal class II pilin displays features typical of type IV pili and shares extensive amino acid identity with the N-terminal conserved regions of other neisserial pilin proteins. However, the deduced class II pilin sequence displays several unique features compared with previously reported meningococcal class I and gonococcal pilin sequences. Class II pilin lacks several conserved peptide regions found within the semivariable and hypervariable regions of other neisserial pilins and displays a large deletion in a hypervariable region of the protein believed to be exposed on the pilus face in gonococcal pili. DNA sequence comparisons within all three regions of the coding sequence also suggest that the meningococcal class II pilin gene is the most dissimilar of the three types of neisserial pilE loci. Additionally, the class II locus fails to display flanking-sequence homology to class I and gonococcal genes and lacks a downstream Sma/Cla repeat sequence, a feature present in all other neisserial pilin genes examined to date. These data indicate meningococcal class II pili represent a structurally distinct class of pili and suggest that relationships among pilin genes in pathogenic Neisseria do not necessarily follow species boundaries.