Cryptococcus gattii infection in solid organ transplant recipients: description of Oregon outbreak cases

Cryptococcus gattii was recognized as an emerging infection in the Pacific Northwest in 2004. Out of 62 total infections in Oregon since the outbreak, 11 were in solid organ transplant (SOT) recipients. SOT recipients were more likely to have disseminated disease and higher mortality than normal hosts, who mostly had isolated mass lesions. The median time from transplantation to C. gattii diagnosis was 17.8 months. The primary sites of infection were lung (n = 4), central nervous system (n = 3), or both (n = 4). The Oregon‐endemic strain, VGII (subtypes IIa and IIc) was present in 10 of 11 patients; the median fluconazole minimum inhibitory concentration (MIC) was 12 μg/mL (range 2–32 μg/mL) for this strain. We found C. gattii infection among organ transplant recipients was disseminated at diagnosis, had low cerebrospinal fluid cryptococcal antigen titers, and was associated with an elevated fluconazole MIC and high attributable mortality.     

Protection of gerbils from amebic liver abscess by immunization with a recombinant Entamoeba histolytica antigen.

Amebiasis, infection by the intestinal protozoan parasite Entamoeba histolytica, is a leading parasitic cause of death. As a step in the development of a recombinant antigen vaccine to prevent E. histolytica infection, we looked at the ability of a recombinant version of the serine-rich E. histolytica protein (SREHP) to elicit a protective immune response against invasive amebic disease. Gerbils, a standard model for amebic liver abscess, were immunized with either a recombinant SREHP/maltose-binding protein (MBP) fusion, recombinant MBP alone, or phosphate-buffered saline (PBS), all combined with complete Freund's adjuvant. In the first trial (group 1), gerbils received a primary and two booster immunizations intraperitoneally; in the second trial (group 2), gerbils were immunized by a single intradermal injection. SREHP/MBP-immunized gerbils in both groups produced antibody to native SHEHP and developed delayed-type hypersensitivity responses to recombinant SREHP. All gerbils were challenged by an intrahepatic injection with 5 x 10(4) virulent E. histolytica HM1-IMSS trophozoites. Complete protection from amebic liver abscess was seen in 64% of the SHEHP/MBP-immunized gerbils in group 1 and in 100% of the SREHP/MBP-immunized gerbils in group 2. There was no protection observed in MBP- or PBS-immunized gerbils in either group. Our results indicate that the SREHP molecule has potential as a vaccine to prevent amebic infection and demonstrate that successful vaccination of animals with recombinant E. histolytica antigen vaccines is possible.     

Medical management of the suspected victim of bioterrorism: an algorithmic approach to the undifferentiated patient

We have purposely expanded on the well-known ATLS paradigm to aid EHCPs in their approach to a potential bioterrorism event. By building on a process that is already familiar, we hope this will aid the EHCP to remember a systematic approach to such an incident. By following this ten-step process, we believe that all EHCPs, and especially those practicing at the first echelons of care in urgent care clinics and EDs, can approach the daunting problem of biological defense with a good deal more confidence. This same model advocated for bioterrorism also may apply to natural infectious disease epidemics, particularly of emerging or re-emerging diseases, that might not be optimally managed by reliance on the conventional public health strategy that requires physician-dependent definitive diagnosis and active reporting mechanisms. The authors hope the acquired knowledge and skills one might gain will rarely be needed, but if the events surrounding the dispersal of anthrax-contaminated mail in the fall of 2001 are any indication of the future, such competencies will be invaluable.     

Local termination pattern analysis: a tool for comparing white matter morphology

Disconnections between structures in the brain have long been hypothesized to be the mechanism behind numerous disease states and pathological behavioral phenotypes. Advances in diffusion weighted imaging (DWI) provide an opportunity to study white matter, and therefore brain connectivity, in great detail. DWI-based research assesses white matter at two different scales: voxelwise indexes of anisotropy such as fractional anisotropy (FA) are used to compare small units of tissue and network-based methods compare tractography-based models of whole-brain connectivity. We propose a method called local termination pattern analysis (LTPA) that considers information about both local and global brain connectivity simultaneously. LTPA itemizes the subset of streamlines that pass through a small set of white matter voxels. The “local termination pattern” is a vector defined by counts of these streamlines terminating in pairs of cortical regions. To assess the reliability of our method we applied LTPA exhaustively over white matter voxels to produce complete maps of local termination pattern similarity, based on diffusion spectrum imaging (DSI) data from 11 individuals in triplicate. Here we show that local termination patterns from an individual are highly reproducible across the entire brain. We discuss how LTPA can be deployed into a clinical database and used to characterize white matter morphology differences due to disease, developmental or genetic factors.     

Conversion and non-conversion approach to preimplantation diagnosis for chromosomal rearrangements in 475 cycles

Due to the limitations of preimplantation genetic diagnosis (PGD) for chromosomal rearrangements by interphase fluorescent in-situ hybridization (FISH) analysis, a method for obtaining chromosomes from single blastomeres was introduced by their fusion with enucleated or intact mouse zygotes, followed by FISH analysis of the resulting heterokaryons. Although this allowed a significant improvement in the accuracy of testing of both maternally and paternally derived translocations, it is still labour intensive and requires the availability of fertilized mouse oocytes, also creating ethical issues related to the formation of interspecies heterokaryons. This method was modified with a chemical conversion procedure that has now been clinically applied for the first time on 877 embryos from PGD cycles for chromosomal rearrangements and has become the method of choice for performing PGD for structural rearrangements. This is presented within the context of overall experience of 475 PGD cycles for translocations with pre-selection and transfer of balanced or normal embryos in 342 (72%) of these cycles, which resulted in 131 clinical pregnancies (38%), with healthy deliveries of 113 unaffected children. The spontaneous abortion rate in these cycles was as low as 17%, which confirms an almost five-fold reduction of spontaneous abortion rate following PGD for chromosomal rearrangements.