Two herpesviruses associated with disease in wild Atlantic loggerhead sea turtles (Caretta caretta).

Herpesviruses are associated with lung-eye-trachea disease and gray patch disease in maricultured green turtles (Chelonia mydas) and with fibropapillomatosis in wild sea turtles of several species. With the exception fibropapillomatosis, no other diseases of wild sea turtles of any species have been associated with herpesviral infection. In the present study, six necropsied Atlantic loggerhead sea turtles (Caretta caretta) had gross and histological evidence of viral infection, including oral, respiratory, cutaneous, and genital lesions characterized by necrosis, ulceration, syncytial cell formation, and intranuclear inclusion bodies. Nested polymerase chain reaction targeting a conserved region of the herpesvirus DNA-dependent-DNA polymerase gene yielded two unique herpesviral sequences referred to as loggerhead genital-respiratory herpesvirus and loggerhead orocutaneous herpesvirus. Phylogenetic analyses indicate that these viruses are related to and are monophyletic with other chelonian herpesviruses within the subfamily alpha-herpesvirinae. We propose the genus Chelonivirus for this monophyletic group of chelonian herpesviruses.

Increased adherence to cardiac standards of care during participation in cardiac disease management programs.

Adherence to cardiovascular disease standards of care is critically important for minimizing the risk of mortality and morbidity for individuals with coronary heart disease (CHD) and heart failure (HF). The purpose of this study was to assess the ability of cardiac disease management (DM) programs to assist members with their adherence to evidence-based medicine for cardiovascular diseases. A total of 20,202 members with CHD and/or HF were evaluated 12 months prior to the start of DM programs and during their first 12 months of participation in the programs. Members were assessed for their adherence to appropriate cardiac medications. In addition, low-density lipoprotein (LDL) testing rates and clinical control of LDL values (defined as <100 mg/dL) were measured. The association between LDL control and use of lipid-lowering statins also was assessed. During participation in the cardiac programs, members achieved significant improvement in their adherence to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and beta-blockers (P < 0.0001). The cardiac population also achieved a significant increase in LDL testing rates and statin use (P < 0.0001). More members attained appropriate LDL control in year 1 compared to baseline (36% relative increase), and this improvement was associated with a 40% relative increase in statin use. In summary, participation in these cardiac DM programs assisted members to improve their adherence to cardiac medications and standards of care guidelines. Such improvements in cardiovascular disease care are likely associated with improved quality of life and reduced risk for mortality.

Effectiveness of disease management programs on improving diabetes care for individuals in health-disparate areas.

In addition to race and ethnicity, specific geographic regions are associated with poorer outcomes of care. Individuals with diabetes experiencing health disparities typically have worse long-term outcomes, such as increased diabetes complications and mortality. Zip code mapping, or geocoding, was utilized in this study to identify regions of the United States with high diabetes prevalence rates and to identify areas with high densities of minority populations. Use of this methodology to examine the effect of disease management on a large, diverse diabetes population revealed greater improvement in clinical testing rates in health disparity zones compared with members living outside of these areas. In particular, significant improvement was achieved by members living in minority zip codes and by members aged 65 years or older. These findings demonstrate that members living in areas of health disparity obtain even greater benefit from diabetes disease management program participation, helping to reduce gaps in care.

Association between frequency of telephonic contact and clinical testing for a large, geographically diverse diabetes disease management population.

Diabetes disease management (DM) programs strive to promote healthy behaviors, including obtaining hemoglobin A1c (A1c) and low-density lipoprotein (LDL) tests as part of standards of care. The purpose of this study was to examine the relationship between frequency of telephonic contact and A1c and LDL testing rates. A total of 245,668 members continuously enrolled in diabetes DM programs were evaluated for performance of an A1c or LDL test during their first 12 months in the programs. The association between the number of calls a member received and clinical testing rates was examined. Members who received four calls demonstrated a 24.1% and 21.5% relative increase in A1c and LDL testing rates, respectively, compared to members who received DM mailings alone. Response to the telephonic intervention as part of the diabetes DM programs was influenced by member characteristics including gender, age, and disease burden. For example, females who received four calls achieved a 27.7% and 23.6% increase in A1c and LDL testing, respectively, compared to females who received mailings alone; by comparison, males who were called achieved 21.2% and 19.9% relative increase in A1c and LDL testing, respectively, compared to those who received mailings alone. This study demonstrates a positive association between frequency of telephonic contact and increased performance of an A1c or LDL test in a large, diverse diabetes population participating in DM programs. The impact of member characteristics on the responsiveness to these programs provides DM program designers with knowledge for developing strategies to promote healthy behaviors and improve diabetes outcomes.

Neurological disease in wild loggerhead sea turtles Caretta caretta.

Beginning in October 2000, subadult loggerhead sea turtles Caretta caretta showing clinical signs of a neurological disorder were found in waters off south Florida, USA. Histopathology indicated generalized and neurologic spirorchiidiasis. In loggerhead sea turtles (LST) with neurospirorchiidiasis, adult trematodes were found in the meninges of the brain and spinal cord of 7 and 3 affected turtles respectively, and multiple encephalic intravascular or perivascular eggs were associated with granulomatous or mixed leukocytic inflammation, vasculitis, edema, axonal degeneration and occasional necrosis. Adult spirorchiids were dissected from meningeal vessels of 2 of 11 LST brains and 1 of 10 spinal cords and were identified as Neospirorchis sp. Affected LST were evaluated for brevetoxins, ciguatoxins, saxitoxins, domoic acid and palytoxin. While tissues from 7 of 20 LST tested positive for brevetoxins, the levels were not considered to be in a range causing acute toxicosis. No known natural (algal blooms) or anthropogenic (pollutant spills) stressors co-occurred with the turtle mortality. While heavy metal toxicosis and organophosphate toxicosis were also investigated as possible causes, there was no evidence for their involvement. We speculate that the clinical signs and pathologic changes seen in the affected LST resulted from combined heavy spirorchiid parasitism and possible chronic exposure to a novel toxin present in the diet of LST.

Improvement of LDL-C laboratory values achieved by participation in a cardiac or diabetes disease management program.

Poor lipid control is a risk factor for cardiovascular diseases and diabetes complications. Frequently, however, patients with these diseases do not achieve blood lipid levels recommended by current standards of care. A retrospective study of 67,244 members eligible for disease management (DM) was initiated to evaluate the ability of interventions to promote improvement in low-density lipoprotein cholesterol (LDL-C) laboratory values for people with cardiovascular diseases or diabetes. The baseline trend in improving LDL-C values in the absence of DM was established. A two-year period prior to the start of the DM intervention was examined to measure the mean percent change in LDL-C values that was occurring in the population. The mean percent change observed for this pre-intervention group was then compared to the change in LDL-C values observed during the DM study period. A significant reduction in elevated LDL-C values (F-test; p < 0.0001) was observed for members who participated in the DM interventions, even when elevated LDL-C was defined as low as > or =70 mg/dL. Members with LDL-C values within threshold limits maintained these levels during the DM program. The significant reduction in elevated LDL-C values and maintenance of optimal values (< 100 mg/dL) was observed over the course of 3 years of participation in a DM program. A subset of the population also was examined to assess the impact of telephone intervention on reducing elevated LDL-C values. A significant relationship between receiving care calls and reduction in elevated LDL-C levels was observed; members who received calls achieved up to a 32.5% relative reduction in elevated LDL-C values compared to members who did not receive calls. In conclusion, these findings demonstrate the ability of DM interventions to assist a large, geographically diverse member population in reducing a clinical laboratory value.

A focused telephonic nursing intervention delivers improved adherence to A1c testing.

Compliance with hemoglobin A1c (A1c) testing is suboptimal despite the clear national recommendations and guidelines established for care of patients with diabetes. Recent studies have demonstrated a relationship between participation in a diabetes disease management (DM) program and improved adherence to A1c testing. A focused intervention study was initiated to investigate the ability of a DM program to drive improvement in A1c testing. A cohort of 36,327 members experienced a statistically significant increase (29%) in A1c testing while participating in the 6-month focused intervention. This finding demonstrated that a focused DM intervention is able to deliver improvement in a clinical process metric critical for managing patients with diabetes, thereby reducing their risk of disease exacerbation.

Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses.

BACKGROUND: Virus-like particle (VLP)-based vaccines have the advantage of being morphologically and antigenically similar to the live virus from which they are derived. Expression of the glycoprotein and VP40 matrix protein from Lake Victoria marburgvirus (MARV) results in spontaneous production of VLPs in mammalian cells. Guinea pigs vaccinated with Marburg virus VLPs (mVLPs) or inactivated MARV (iMARV) develop homologous humoral and T-cell responses and are completely protected from a lethal homologous MARV challenge. AIMS & METHODS: To determine whether mVLPs based on the Musoke (aka Lake Victoria) isolate of MARV could broadly protect against diverse isolates of MARV, guinea pigs were vaccinated with mVLPs or iMARV-Musoke and challenged with MARV-Musoke, -Ravn or -Ci67. RESULTS: Prior to challenge, the mVLP- and iMARV-vaccinated guinea pigs had high levels of homologous MARV-Musoke and heterologous MARV-Ravn and -Ci67 antibodies. The Musoke-based mVLPs and iMARV vaccines provided complete protection in guinea pigs against viremia, viral replication and pathological changes in tissues, and lethal disease following challenge with MARV-Musoke, -Ravn or -Ci67. Guinea pigs vaccinated with RIBI adjuvant alone and infected with guinea pig-adapted MARV-Musoke, -Ravn or -Ci67 had histopathologic findings similar to those seen in the nonhuman primate model for MARV infection. Based on the strong protection observed in guinea pigs, we next vaccinated cynomolgus macaques with Musoke-based mVLPs and showed the VLP-vaccinated monkeys were broadly protected against three isolates of MARV (Musoke, Ravn and Ci67). CONCLUSION: Musoke mVLPs are effective at inducing broad heterologous immunity and protection against multiple MARV isolates.

Impact of telephonic interventions on glycosylated hemoglobin and low-density lipoprotein cholesterol testing.

OBJECTIVES: To determine whether diabetes disease management (DM) programs are able to improve adherence to glycosylated hemoglobin (A1C) and low-density lipoprotein cholesterol (LDL-C) clinical testing in a nonadherent population and to quantify the efficacy of telephonic interventions in improving clinical testing rates. STUDY DESIGN: Retrospective, observational cohort study before and after DM program implementation. METHODS: A baseline cohort of members with diabetes (n = 5640) was identified from among large-scale diabetes DM programs administered for 13 geographically diverse health plans. Members were defined by nonadherence at baseline to A1C and/or LDL-C testing, grouped together based on how long they had participated in the program, divided retrospectively into telephonically contacted and uncontacted groups, and analyzed in the subsequent 12-month implementation period for testing rates. Subgroups defined by disease burden at baseline and frequency of telephonic interactions were analyzed to determine achievement of guideline-based A1C and LDL-C testing rates. RESULTS: Participation in diabetes DM programs was associated with improved A1C and LDL-C testing rates in previously nonadherent members. Calling nonadherent members improved A1C testing by 30.2% and LDL-C testing by 10.9% compared with testing rates for members who were not called. Members with high disease burden benefited even more from the diabetes intervention. Frequency of telephonic contacts with nonadherent individuals demonstrated a linear relationship with improved rates of adherence to A1C and LDL-C testing guidelines, and markedly improved testing rates compared with a not-called group. CONCLUSION: Telephonic interventions as part of comprehensive DM programs are associated with improved disease-monitoring testing.

Activation of triggering receptor expressed on myeloid cells-1 on human neutrophils by marburg and ebola viruses.

Marburg virus (MARV) and Ebola virus (EBOV), members of the viral family Filoviridae, cause fatal hemorrhagic fevers in humans and nonhuman primates. High viral burden is coincident with inadequate adaptive immune responses and robust inflammatory responses, and virus-mediated dysregulation of early host defenses has been proposed. Recently, a novel class of innate receptors called the triggering receptors expressed in myeloid cells (TREM) has been discovered and shown to play an important role in innate inflammatory responses and sepsis. Here, we report that MARV and EBOV activate TREM-1 on human neutrophils, resulting in DAP12 phosphorylation, TREM-1 shedding, mobilization of intracellular calcium, secretion of proinflammatory cytokines, and phenotypic changes. A peptide specific to TREM-1 diminished the release of tumor necrosis factor alpha by filovirus-activated human neutrophils in vitro, and a soluble recombinant TREM-1 competitively inhibited the loss of cell surface TREM-1 that otherwise occurred on neutrophils exposed to filoviruses. These data imply direct activation of TREM-1 by filoviruses and also indicate that neutrophils may play a prominent role in the immune and inflammatory responses to filovirus infections.

Identification and expression of immunogenic proteins of a disease-associated marine turtle herpesvirus.

Herpesviruses are associated with several diseases of marine turtles, including lung-eye-trachea disease (LETD) and fibropapillomatosis. Two approaches were used to identify immunodominant antigens of LETV, the LETD-associated herpesvirus. The first approach targeted glycoprotein B, which is known to be immunogenic and neutralizing in other species. The second strategy identified LETV proteins recognized on Western blots by antibodies in immune green turtle plasma. A 38-kDa protein was resolved by two-dimensional gel electrophoresis, sequenced, and identified as a scaffolding protein encoded by the overlapping open reading frames of UL26 and UL26.5. Glycoprotein B and the scaffolding protein were cloned and expressed in Escherichia coli. The expressed proteins were recognized on Western blots by antibodies in immune green turtle plasma. Phylogenetic studies based on UL26, DNA polymerase, and glycoprotein B revealed that LETV clusters with the alphaherpesviruses.