Tuberculosis Infection in the United States: Prevalence Estimates from the National Health and Nutrition Examination Survey, 2011-2012

Background

Reexamining the prevalence of persons infected with tuberculosis (TB) is important to determine trends over time. In 2011–2012 a TB component was included in the National Health and Nutrition Examination Survey (NHANES) to estimate the reservoir of persons infected with TB.

Methods

Civilian, noninstitutionalized U.S. population survey participants aged 6 years and older were interviewed regarding their TB history and eligibility for the tuberculin skin test (TST) and interferon gamma release assay (IGRA) blood test. Once eligibility was confirmed, both tests were conducted. Prevalence and numbers of TST positive (10 mm or greater), IGRA positive, and both TST and IGRA positive were calculated by adjusting for the complex survey design after applying corrections for item nonresponse and digit preference in TST induration measurements. To examine TST positivity over time, data from NHANES 1999–2000 were reanalyzed using the same statistical methods. The TST was performed using Tubersol, a commercially available purified protein derivative (PPD), rather than PPD-S, which was the antigen used in NHANES 1999–2000. Prior patient history of TB vaccination was not collected in this study nor were patients examined for the presence of a Bacillus of Calmette and Guerin (BCG) vaccine scar.

Results

For NHANES 2011–2012, TST and IGRA results were available for 6,128 (78.4%) and 7,107 (90.9%) eligible participants, respectively. There was no significant difference between the percentage of the U.S. population that was TST positive in 2011–2012 (4.7% [95% CI 3.4–6.3]; 13,276,000 persons) compared with 1999–2000 (4.3%; 3.5–5.3). In 2011–2012 the percentage that was IGRA positive was 5.0% (4.2–5.8) and double TST and IGRA positivity was 2.1% (1.5–2.8). The point estimate of IGRA positivity prevalence in foreign-born persons (15.9%; 13.5–18.7) was lower than for TST (20.5%; 16.1–25.8) in 2011–2012. The point estimate of IGRA positivity prevalence in U.S.-born persons (2.8%; 2.0–3.8) was higher than for TST (1.5%; 0.9–2.6).

Conclusions

No statistically significant decline in the overall estimated prevalence of TST positivity was detected from 1999–2000 to 2011–2012. The prevalence of TB infection, whether measured by TST or IGRA, remains lower among persons born in the United States compared with foreign-born persons.     

In Vivo Assessment of NS1-Truncated Influenza Virus with a Novel SLSYSINWRH Motif as a Self-Adjuvanting Live Attenuated Vaccine

Mutants of influenza virus that encode C-terminally truncated NS1 proteins (NS1-truncated mutants) characteristically induce high interferon responses. The dual activity of interferon in blocking virus replication and enhancing the development of adaptive immune responses makes these mutants promising as self-adjuvanting live-attenuated influenza vaccine (LAIV) candidates. Yet, among the NS1-truncated mutants, the length of NS1 is not directly correlated with the interferon-inducing efficiency, the level of attenuation, or effectiveness as LAIV. Using quantitative in vitro biologically active particle subpopulation analysis as a tool to identify potential LAIV candidates from a pool of NS1-truncated mutants, we previously predicted that a NS1-truncated mutant pc2, which was less effective as a LAIV in chickens, would be sufficiently effective as a LAIV in mammalian hosts. In this study, we confirmed that pc2 protected mice and pigs against heterologous virus challenge in terms of preventing clinical signs and reducing virus shedding. pc2 expresses a unique SLSYSINWRH motif at the C-terminus of its truncated NS1. Deletion of the SLSYSINWRH motif led to ~821-fold reduction in the peak yield of type I interferon induced in murine cells. Furthermore, replacement of the SLSYSINWRH motif with the wildtype MVKMDQAIMD sequence did not restore the interferon-inducing efficiency. The diminished interferon induction capacity in the absence of the SLSYSINWRH motif was similar to that observed in other mutants which are less effective LAIV candidates. Remarkably, pc2 induced 16-fold or more interferon in human lung and monkey kidney cells compared to the temperature-sensitive, cold-adapted Ann Arbor virus that is currently used as a master backbone for LAIVs such as FluMist. Although the mechanism by which the SLSYSINWRH motif regulates the vaccine properties of pc2 has not been elucidated, this motif has potential use in engineering self-adjuvanting NS1-truncated-based LAIVs.     

Metabolic Plasticity in Resting and Thrombin Activated Platelets

Platelet thrombus formation includes several integrated processes involving aggregation, secretion of granules, release of arachidonic acid and clot retraction, but it is not clear which metabolic fuels are required to support these events. We hypothesized that there is flexibility in the fuels that can be utilized to serve the energetic and metabolic needs for resting and thrombin-dependent platelet aggregation. Using platelets from healthy human donors, we found that there was a rapid thrombin-dependent increase in oxidative phosphorylation which required both glutamine and fatty acids but not glucose. Inhibition of fatty acid oxidation or glutamine utilization could be compensated for by increased glycolytic flux. No evidence for significant mitochondrial dysfunction was found, and ATP/ADP ratios were maintained following the addition of thrombin, indicating the presence of functional and active mitochondrial oxidative phosphorylation during the early stages of aggregation. Interestingly, inhibition of fatty acid oxidation and glutaminolysis alone or in combination is not sufficient to prevent platelet aggregation, due to compensation from glycolysis, whereas inhibitors of glycolysis inhibited aggregation approximately 50%. The combined effects of inhibitors of glycolysis and oxidative phosphorylation were synergistic in the inhibition of platelet aggregation. In summary, both glycolysis and oxidative phosphorylation contribute to platelet metabolism in the resting and activated state, with fatty acid oxidation and to a smaller extent glutaminolysis contributing to the increased energy demand.     

Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru

Introduction

The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear.

Materials and Methods

We conducted a prospective, household-based cohort study of children aged <3 years living in remote rural highland communities in San Marcos, Cajamarca, Peru. Acute respiratory illnesses (ARI), including lower respiratory tract infection (LRTI), were monitored through weekly household visits from March 2009 through September 2011. Nasal swabs collected during ARI/LRTI were tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. Incidence rates and rate ratios were calculated using mixed effects Poisson regression.

Results

Among 892 enrolled children, incidence rates of RSV and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. The proportions of RSV and MPV ARI that presented as LRTI were 12.5% and 8.9%, respectively. Clinic visits for ARI and hospitalizations were significantly more frequent (all p values <0.05) among children with RSV (clinic 41% and hospital 5.3%) and MPV ARI (38% and 3.5%) when compared with other viral infections (23% and 0.7%) and infections without virus detected (24% and 0.6%). In multivariable analysis, risk factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2^nd compared to 1^st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3^rd compared to 1^st quartile residents). Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01).

Conclusion

In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional studies to control infections by these viruses among young children from developing countries.     

Strain,biochemistry, and cultivation-dependent measurement variability of algal biomass composition

Accurate compositional analysis in biofuel feedstocks is imperative; the yields of individual components can define the economics of an entire process. In the nascent industry of algal biofuels and bioproducts, analytical methods that have been deemed acceptable for decades are suddenly critical for commercialization. We tackled the question of how the strain and biochemical makeup of algal cells affect chemical measurements. We selected a set of six procedures (two each for lipids, protein, and carbohydrates): three rapid fingerprinting methods and three advanced chromatography-based methods. All methods were used to measure the composition of 100 samples from three strains: Scenedesmus sp., Chlorella sp., and Nannochloropsis sp. The data presented point not only to species-specific discrepancies but also to cell biochemistry-related discrepancies. There are cases where two respective methods agree but the differences are often significant with over- or underestimation of up to 90%, likely due to chemical interferences with the rapid spectrophotometric measurements. We provide background on the chemistry of interfering reactions for the fingerprinting methods and conclude that for accurate compositional analysis of algae and process and mass balance closure, emphasis should be placed on unambiguous characterization using methods where individual components are measured independently.     

Enhancing single-molecule fluorescence with nanophotonics

Single-molecule fluorescence spectroscopy has become an important research tool in the life sciences but a number of limitations hinder the widespread use as a standard technique. The limited dynamic concentration range is one of the major hurdles. Recent developments in the nanophotonic field promise to alleviate these restrictions to an extent that even low affinity biomolecular interactions can be studied. After motivating the need for nanophotonics we introduce the basic concepts of nanophotonic devices such as zero mode waveguides and nanoantennas. We highlight current applications and the future potential of nanophotonic approaches when combined with biological systems and single-molecule spectroscopy.     

Alleviating social avoidance: Effects of single dose testosterone administration on approach–avoidance action

Testosterone is an important regulator of social–motivational behavior and is known for its dominance-enhancing and social-anxiolytic properties. However, to date no studies have systematically investigated the causal effect of testosterone on actual social approach–avoidance behavior in humans. The present study sets out to test the effects of testosterone administration in healthy female volunteers using an objective implicit measure of social motivational behavior: the social Approach–Avoidance Task, a reaction time task requiring participants to approach or avoid visually presented emotional (happy, angry, and neutral) faces. Participants showed significantly diminished avoidance tendencies to angry faces after testosterone administration. Testosterone did not affect approach–avoidance tendencies to social affiliation (happy) faces. Thus, a single dose testosterone administration reduces automatic avoidance of social threat and promotes relative increase of threat approach tendencies in healthy females. These findings further the understanding of the neuroendocrine regulation of social motivational behavior and may have direct treatment implications for social anxiety, characterized by persistent social avoidance.     

Do birds of a feather flock together? Comparing habitat preferences of piscivorous waterbirds in a lowland river catchment

The aim of the present study was to use the analysis of surface water chemistry to understand vegetation succession pathways in terrestrializing polyhumic lakes. We hypothesized that Sphagnum mire development was accompanied by a decrease in the mineral content in water. A total of 111 vegetation plots along 23 transects were analysed in 11 lakes and adjacent peat lands in the Wigry National Park (NE Poland). The vegetation of the lake-mire systems forms distinct zones: (1) nymphaeid-, bladderwort- and bryophyte-dominated aquatic vegetation; (2) sedge-dominated edge of the Sphagnumcarpet; (3) quaking, extremely poor fen with various Cyperaceae; (4) non-quaking, Eriophorum vaginatum-dominated bog-like vegetation and (5) pine woodland. Surface water corrected conductivity (EC_corr.), pH, COD-KMnO₄ and Ca²⁺, Mg²⁺, Fetot. and SiO₂ were measured along the transects. The environmental gradients best explaining the observed pattern were pH (with the highest values in the lake and the lowest in the bog-like vegetation) and COD-KMnO₄ (showing an inverse direction). At least in some Sphagnum-mires conditions were more minerotrophic than in the lakes. The process of humic lake overgrowing by Sphagnum-mires in NE Poland results in pine woodlands on mineralised peat. The climate conditions in NE Poland, combined with evapotranspiration accelerated by encroaching trees, do not seem to support the development of ombrotrophic bogs.     

Adjustment of pre‐moult foraging strategies in Macaroni Penguins Eudyptes chrysolophus according to locality,sex and breeding status

The annual moult creates the highest physiological stress during a penguin's breeding‐cycle and is preceded by a period of hyperphagia at sea. Although crucial to individual survival, foraging strategies before moult have been little investigated in keystone marine consumers in the Southern Ocean. The Macaroni Penguin Eudyptes chrysolophus demonstrates how individuals may adjust their foraging strategies during this period in line with constraints such as potential intraspecific competition between localities, foraging ability between dimorphic sexes and timing at sea between breeding and non‐breeding population components. We recorded pre‐moult behaviour at sea for 22 Macaroni Penguins from Crozet and Kerguelen Islands (southern Indian Ocean) during 2009 and 2011, using light‐based geolocation and stable isotope analysis. Penguins were distributed in population‐specific oceanic areas with similar surface temperatures (3.5 °C) south of the archipelagos, where they foraged at comparable trophic levels based on stable isotopes of their blood. Bayesian ‘broken stick’ modelling with concurrent analysis of seawater temperature records from the animal‐borne devices showed that within each population, females remained 6 days longer than males in the colder waters before heading back towards their colonies. Finally, 17 other non‐breeding individuals that moulted earlier had a higher mean blood δ¹⁵N value than did post‐breeding birds, meaning that early moulters probably fed more on fish than did late moulters. Our findings of such adjustments in foraging strategies developed across locality, sex and breeding status help understanding of the species' contrasted pre‐moult biology across its range and its ecology in the non‐breeding period.     

CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.