Detection of BK virus and simian virus 40 in the urine of healthy children

Seroprevalence studies indicate that most primary infections with BK virus (BKV) and JC virus (JCV) occur in the first and second decades of life, respectively. Relatively little is known about the transmission of these agents, including the primary source of human exposure, the portal of entry, and the pathophysiology of life-long viral persistence. We sought to determine if simian virus 40 (SV40) excretion could be detected in the urine of healthy children and to define the age-related prevalence of polyomavirus shedding in this population. A point prevalence study of polyomavirus shedding was conducted in healthy children using rigorous enrollment criteria. Urine samples were collected from healthy children, age from 3 to 18 years, during routine evaluation at two urban pediatric clinics. Qualitative PCR analysis was performed using primers that detect a conserved region of the T-antigen gene of BKV, JCV, and SV40. The identity of polyomaviruses detected was determined by DNA sequence analysis and/or PCR amplification of other regions of the viral genomes. Seven of 72 (9.7%) urine samples were positive for polyomaviruses: three with BKV (ages 4, 6, 13), two with SV40 (ages 6, 16), two with BKV and SV40 co-excretion (ages 6, 15), and none with JCV. DNA sequence analysis confirmed the identity of viruses detected. These results suggest that the timing of SV40 infections in humans may be similar to that of BKV and that urine from healthy children could contribute to the ubiquity of BKV infection early in life.     

Human parvovirus B19 infections: Routine diagnosis by a new nested polymerase chain reaction assay

A nested primer PCR assay was developed to detect human parvovirus B19 in various clinical specimens in a routine diagnostic laboratory. Under optimized conditions the highly specific assay had a sensitivity of less than 10 genome units. For practical reasons, however, this sensitivity was adjusted to 10–100 virus genomes in diagnostic applications. Using clinical specimens from 200 patients with suspected B19 infection, nested PCR was shown to have important diagnostic advantages over the detection of B19 specific antibodies. The data suggest that on the basis of serological data as obtained with currently available test systems a considerable proportion of B19 infections would be misdiagnosed. Examples for the usefulness of the PCR assay in routine diagnosis are given. © 1993 Wiley-Liss, Inc.     

From the Cover: Changing central Pacific El Ni?os reduce stability of North American salmon survival rates

Pacific salmon are a dominant component of the northeast Pacific ecosystem. Their status is of concern because salmon abundance is highly variable—including protected stocks, a recently closed fishery, and actively managed fisheries that provide substantial ecosystem services. Variable ocean conditions, such as the Pacific Decadal Oscillation (PDO), have influenced these fisheries, while diminished diversity of freshwater habitats have increased variability via the portfolio effect. We address the question of how recent changes in ocean conditions will affect populations of two salmon species. Since the 1980s, El Niño Southern Oscillation (ENSO) events have been more frequently associated with central tropical Pacific warming (CPW) rather than the canonical eastern Pacific warming ENSO (EPW). CPW is linked to the North Pacific Gyre Oscillation (NPGO), whereas EPW is linked to the PDO, different indicators of northeast Pacific Ocean ecosystem productivity. Here we show that both coho and Chinook salmon survival rates along western North America indicate that the NPGO, rather than the PDO, explains salmon survival since the 1980s. The observed increase in NPGO variance in recent decades was accompanied by an increase in coherence of local survival rates of these two species, increasing salmon variability via the portfolio effect. Such increases in coherence among salmon stocks are usually attributed to controllable freshwater influences such as hatcheries and habitat degradation, but the unknown mechanism underlying the ocean climate effect identified here is not directly subject to management actions.Understanding the influence of nonstationary climatic shifts on the productivity and persistence of populations is a key challenge to successful management of harvested marine and anadromous resources (1). Management of Pacific salmon fisheries in the United States and Canada exemplifies the challenges posed by climatic shifts; managers must set harvests for some stocks while protecting stocks at risk. The influence of variable survival of juvenile salmon after ocean entry complicates decision making, with increasing variability generally increasing population risk. As an example of this variability, poor ocean productivity was largely responsible for an unprecedented complete closure of the Chinook salmon fisheries in California and southern Oregon when extremely low numbers returned to spawn in 2008 and 2009 (2).Salmon management is unique in that it focuses on stocks comprising identifiable separate populations in individual spawning streams. Recent studies show that increased covariability in abundance among separate populations of Chinook salmon has increased coherence of salmon stocks, thus increasing aggregate variability of the stocks through the portfolio effect (3–5). These effects of declining diversity among salmon subpopulations are an example of the general global concern for the loss of biodiversity in many forms (e.g., loss of genes, species, within-species variability) and its effects on ecosystem services (6–10). The portfolio effect has been a useful way of quantifying the effects on aggregate population variability in salmon stocks in terms of the loss of diversity among populations spawning in different streams (3, 4, 11). The recently detected increased coherence of salmon populations, and associated increases in aggregate population variability, and, thus, increased risk, have generally been attributed to declining biocomplexity of freshwater habitats due to the increase in hatcheries, dams, and stream habitat homogenization (3–5, 12, 13). However, the extent to which responses to physical oceanographic conditions in the marine phase of salmon life limit the scope for reducing population variability through the portfolio effect has not been considered. We analyzed early ocean survival of hatchery coho salmon from 72 hatcheries and Chinook salmon from 104 hatcheries along western North America from central California to southeast Alaska between 1980 and 2006 using coded wire tag (CWT) data (14, 15) to show how a climatic shift has influenced the coherence in survival rates of two important salmon species in the northeast Pacific Ocean (Fig. S1).Open in a separate windowFig. S1.Locations of the 72 coho (Oncorhynchus kisutch, red diamonds) and 104 Chinook salmon (O. tshawytscha, blue circles) hatcheries and the geographical regions used in this study; note that some hatcheries release both species (black squares). Geographic regions with survival time series data used in this study: A, northern southeast Alaska; B, southern southeast Alaska; C, west coast of Vancouver Island; D, Strait of Georgia and Puget Sound; E, north coastal Washington; F, south coastal Washington; G, Columbia River; H, north coastal Oregon; I, south coastal Oregon; J, north coastal California; K, central California. Geographic regions with insufficient time series data to include in this study: L, northern British Columbia; M, Fraser River.In recent decades, El Niño events have been characterized by central Pacific warming (CPW) events more frequently than eastern Pacific warming (EPW) events typically associated with El Niño (16, 17). El Niño events drive a large fraction of both interannual and decadal variability in the northern Pacific Ocean (18), but CPW and EPW events excite different teleconnections to the northern Pacific Ocean. EPW events drive fluctuations in the North Pacific Ocean by intensifying the variance of the wintertime Aleutian Low pressure cell (19), which, in turn, drives the Pacific Decadal Oscillation (PDO). CPW events, however, influence northern Pacific Ocean climate differently by influencing the North Pacific Oscillation (NPO), which, in turn, modulates the strength of the North Pacific Current indexed by the North Pacific Gyre Oscillation (NPGO) (17). This shift in El Niño signals influences teleconnections to the northern Pacific Ocean, with less variability ascribed to PDO, which is the dominant mode of northern Pacific Ocean low-frequency variability, and an increasing fraction to the second mode of low-frequency variability, the NPGO (17, 20, 21). Because the PDO explained important shifts in salmon productivity in the past (22), the increased variability related to the NPGO raises the question of how it affects salmon productivity.     

Using the Nonhuman Primate Model of HCMV to Guide Vaccine Development

The natural history of human cytomegalovirus (HCMV) is inextricably associated with mucosal surfaces. The vast preponderance of primary infections occur following mucosal exposure to infectious virions, and the high seroprevalence of HCMV throughout the world is due to long-term excretion of HCMV in bodily fluids from multiple mucosal sites. Accumulating evidence presents a model where the earliest virus-host interactions following infection dictate the long-term pattern of infection, alter innate immune responses that skew adaptive responses to enable persistence within an immune host, and are essential for reinfection of a host with prior immunity. HCMV has evolved a complex repertoire of viral functions fine-tuned to manipulate the immune environment both locally at the sites of infection and systemically within an infected host. Collectively, viral immune modulation represents a significant impediment for an HCMV vaccine. As HCMV can disseminate beyond mucosal surfaces to reinfect immune hosts, it may not matter whether prior immunity results from prior infection or immunization. A better understanding of the earliest virus-hosts interactions at mucosal surfaces may identify elements of the viral proteome that are especially susceptible to vaccine-mediated disruption and prevent challenge virus from disseminating to distal sites, particularly the maternal-fetal interface.     

Antibody persistence and booster responses 24–36 months after different 4CMenB vaccination schedules in infants and children: A randomised trial

Objectives

This phase IIIb, open-label, multicentre, extension study (NCT01894919) evaluated long-term antibody persistence and booster responses in participants who received a reduced 2 + 1 or licensed 3 + 1 meningococcal serogroup B vaccine (4CMenB)-schedule (infants), or 2-dose catch-up schedule (2–10-year-olds) in parent study NCT01339923.

Poorly cemented coral reefs of the eastern tropical Pacific: possible insights into reef development in a high-CO2 world

Ocean acidification describes the progressive, global reduction in seawater pH that is currently underway because of the accelerating oceanic uptake of atmospheric CO₂. Acidification is expected to reduce coral reef calcification and increase reef dissolution. Inorganic cementation in reefs describes the precipitation of CaCO₃ that acts to bind framework components and occlude porosity. Little is known about the effects of ocean acidification on reef cementation and whether changes in cementation rates will affect reef resistance to erosion. Coral reefs of the eastern tropical Pacific (ETP) are poorly developed and subject to rapid bioerosion. Upwelling processes mix cool, subthermocline waters with elevated pCO₂ (the partial pressure of CO₂) and nutrients into the surface layers throughout the ETP. Concerns about ocean acidification have led to the suggestion that this region of naturally low pH waters may serve as a model of coral reef development in a high-CO₂ world. We analyzed seawater chemistry and reef framework samples from multiple reef sites in the ETP and found that a low carbonate saturation state (Ω) and trace abundances of cement are characteristic of these reefs. These low cement abundances may be a factor in the high bioerosion rates previously reported for ETP reefs, although elevated nutrients in upwelled waters may also be limiting cementation and/or stimulating bioerosion. ETP reefs represent a real-world example of coral reef growth in low-Ω waters that provide insights into how the biological–geological interface of coral reef ecosystems will change in a high-CO₂ world.     

Adherence to Premixed Insulin in a Prefilled Pen Compared With a Vial/Syringe in People With Diabetes in Singapore

Background

The real-world clinical effectiveness of exogenous insulin is limited by nonadherence. Various insulin delivery systems have been developed to help improve adherence, with prefilled pens gaining popularity among adult Singaporeans with diabetes. However, adherence to insulin in people with diabetes in Singapore and most of Asia has not been studied.

Objectives

This study aimed to compare adherence to premixed insulin formulated in a prefilled pen versus a vial/syringe and to identify predictors of adherence in 955 patients managed at the outpatient clinics of the largest acute care hospital in Singapore.

Methods

In this retrospective longitudinal study, electronic medical and pharmacy refill records were used to determine adherence to insulin over 24 months, measured in terms of compliance and persistence. Compliance is expressed as the medication possession ratio (used as continuous and categorical variables), and persistence is reported as a dichotomous variable with a permissible refill gap of 30 days before discontinuation of therapy is considered. Multivariate linear or logistic regression analysis was used to identify predictors of adherence.

Results

Compared with prefilled pen users, vial/syringe users were older (mean [SD] age, 64.1 [10.6] vs 62.4 [11.9] years; P = 0.032), and more were undergoing polypharmacy (69.6% vs 54.1%; P < 0.001). The mean (SD) medication possession ratio was comparable in vial/syringe versus prefilled pen users (83.8% [26.9%] vs 86.0% [23.2%]; P = 0.266). Prefilled pen users were more persistent with therapy compared with vial/syringe users (odds ratio = 1.36; 95% CI, 1.01–1.86) after adjusting for sociodemographic and clinical covariates. Median time to discontinuation of therapy was comparable (vial/syringe vs prefilled pen: 409 vs 532 days; P = 0.076). Being managed by an endocrinologist and not receiving government subsidies were significant predictors of persistence.

Conclusions

Compared with other studies that found strong associations between adherence and insulin devices, the findings of this study suggest that persistence but not compliance varies by insulin device. The willingness to pay for health care, in addition to affordability, may affect insulin therapy adherence. Patients with uncontrolled diabetes due to suspected nonadherence may benefit from referral to a multidisciplinary care team comprising endocrinologists, diabetes nurse educators, dietitians, and allied health professionals. These findings are applicable to outpatients with similar demographic features managed at other acute care hospitals in Singapore. The impact of insulin devices on glycemic control needs to be investigated in future larger studies.