Antimicrobial resistance surveillance systems: Are potential biases taken into account?

BACKGROUND:

The validity of surveillance systems has rarely been a topic of investigation.

OBJECTIVE:

To assess potential biases that may influence the validity of contemporary antimicrobial-resistant (AMR) pathogen surveillance systems.

METHODS:

In 2008, reports of laboratory-based AMR surveillance systems were identified by searching Medline. Surveillance systems were appraised for six different types of bias. Scores were assigned as ‘2’ (good), ‘1’ (fair) and ‘0’ (poor) for each bias.

RESULTS:

A total of 22 surveillance systems were included. All studies used appropriate denominator data and case definitions (score of 2). Most (n=18) studies adequately protected against case ascertainment bias (score = 2), with three studies and one study scoring 1 and 0, respectively. Only four studies were deemed to be free of significant sampling bias (score = 2), with 17 studies classified as fair, and one as poor. Eight studies had explicitly removed duplicates (score = 2). Seven studies removed duplicates, but lacked adequate definitions (score = 1). Seven studies did not report duplicate removal (score = 0). Eighteen of the studies were considered to have good laboratory methodology, three had some concerns (score = 1), and one was considered to be poor (score = 0).

CONCLUSION:

Contemporary AMR surveillance systems commonly have methodological limitations with respect to sampling and multiple counting and, to a lesser degree, case ascertainment and laboratory practices. The potential for bias should be considered in the interpretation of surveillance data.     

Absence of hepatitis B virus DNA detected by polymerase chain reaction in blood donors who are hepatitis B surface antigen negative and antibody to hepatitis B core antigen positive from a United States population with a low prevalence of hepatitis B serologic markers

A recent study in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive blood donors from a population with a high prevalence of hepatitis B serologic markers showed the presence of hepatitis B virus DNA (HBV DNA) as detected by polymerase chain reaction (PCR) in 4 percent of these donors. A sensitive, nested PCR assay was used to assess the prevalence of HBV DNA in a population of HBsAg-negative, anti-HBc-positive blood donors from a United States population with a low prevalence of hepatitis B serologic markers. The lower limit for detection by the PCR assay was 10(-5) pg per mL of HBV DNA. There was a review of 26,492 consecutive blood donations in a 12-month period. During this time, only 1 unit (0.004%) was HBsAg positive. An additional 158 units (0.6%) were repeatably reactive for anti-HBc. These 158 HBsAg-negative, anti- HBc-positive units were given by 119 donors of blood for allogeneic and autologous use. HBV DNA was not detected by PCR in blood from 83 allogeneic blood donors (93 samples) or 36 autologous blood donors (65 samples). Anti-HBc testing is an inefficient means of screening for potential hepatitis B infectivity and is associated with low test specificity in populations with a low prevalence of hepatitis B serologic markers.     

Variable expression of coxsackie-adenovirus receptor in thyroid tumors: implications for adenoviral gene therapy.

Adenoviral gene therapy represents a novel approach for the treatment of aggressive thyroid carcinomas. Both coxsackie-adenovirus receptor (CAR) and integrins have been shown to be the major determinants for adenoviral infectivity in many types of cancer cells, yet conflicting results have been reported. In this report we examine these factors mediating adenoviral infection in thyroid cells and to evaluate CAR expression in various types of thyroid cancer. We found that neither expression levels of CAR nor integrins are solely predictive of adenoviral infectivity in thyroid cells. However, the absence of CAR was associated with poor adenoviral infectivity in immortalized rat FRTL-5 cells. Moreover, preincubation with alpha-CAR antibody decreased infectivity in FTC 238 cells, a human thyroid tumor line. These results indicate that CAR does play a role in adenoviral infection of thyroid cells. Immunohistochemical analysis revealed that CAR is expressed at the cell surface in the majority of malignant thyroid tumors. We further show that adenoviral infectivity in some thyroid cancer cells can be improved by poly-L-lysine. Our study warrants a functional method to evaluate adenoviral infectivity should be developed and instituted prior to clinical trials of adenoviral gene therapy in patients with advanced thyroid cancer.     

Percutaneous angioscopy. Work in progress

The cardiovascular applications of flexible fiber-optic technology are imminent because of recent advances in miniaturization. In the work described here, angioscopy, or vascular endoscopy, was performed in the cadaveric aorta and in the systemic and pulmonary circulations of the canine model and selected human patients. Subsequent to our development of percutaneous techniques, clinical trials have ranged from lower-extremity venoscopy to aortic-root arterioscopy. Angioscopy could be clinically useful because of relative or absolute contraindications to iodinated contrast material. The ability to see in color and three dimensions may afford some other advantages to angioscopy over conventional angiography.     

Toxicity induced by nanoparticles

Nanoparticle research is currently an area of intense scientific interest due to a wide variety of potential applications. Human beings have been exposed to airborne nanosized particles throughout their evolutionary stages, and such exposures have increased dramatically over the last century. Nanoparticle can modify the physicochemical properties of the material as well as create the opportunity for increased uptake and interaction with biological tissues through inhalation, ingestion, and injection. This combination of effects can generate adverse biological effects in living cells. Nanoparticles have proved toxic to human once in the blood stream, nanoparticles, spleen, bone marrow and nervous system can be transported around the body and be taken up by organs tissue and cell cultures, resulting in increased oxidative stress, inflammatory cytokine production and cell death. Unlike larger particles, nanoparticles may be taken up by cell mitochondria and the cell nucleus studies demonstrate the potential for nanoparticles to cause DNA mutation and induce major structural damage to mitochondria, even resulting in cell death. Size is therefore a key factor in determining the potential toxicity of a particle. How these nanoparticles behave inside the body is still a major question that needs to be resolved. There is a responsibility to test and optimize these new nanomaterials early during the development process to eliminate or ameliorate identified toxic characteristics.     

Cross-linking of the beta-glucan receptor on human monocytes results in interleukin-1 receptor antagonist but not interleukin-1 production

The beta-glucan receptor, found on monocytes and neutrophils, binds glucose polymers derived from fungi. Ligands for the receptor have various immunomodulatory effects, including increased microbicidal killing activity. We have investigated the effect of beta-glucans on the production of interleukin-1 (IL-1) and its naturally occurring inhibitor, the IL-1 receptor antagonist (IL-1Ra). Particulate beta- glucan induced IL-1Ra production from human peripheral blood mononuclear cells (PBMC) but did not stimulate IL-1 beta synthesis or gene expression in these same cells. Monomeric (soluble) beta-glucan did not induce IL-1Ra production. However, when preincubated with PBMC, monomeric beta-glucan significantly (P < .01) reduced particulate beta- glucan induction of IL-1Ra by 40%, suggesting that crosslinking of beta- glucan receptors is required for induction of IL-1Ra. In support of this, monomeric beta-glucan immobilized on plastic surfaces stimulated IL-1Ra production. Vitamin D3, which increases the functional capacity of beta-glucan receptors, increased IL-1Ra production induced by particulate beta-glucan, whereas dexamethasone suppressed IL-1Ra synthesis. Because of their differential effects on cytokine production, beta-glucans may be used to therapeutic advantage in the diseases in which IL-1 is implicated.