Package Inserts Overstate Diagnostic TB Tests' Accuracy
Clinicians and laboratory professionals often rely on manufacturers' package inserts to assess the accuracy of diagnostic medical tests. However, package inserts frequently greatly overstate such tests' accuracy, according to a case study of package inserts for tuberculosis (TB), which is published in the July 2012 Journal of Clinical Microbiology.
"It is likely that these issues are not restricted to TB, and they should be explored for diagnostics for other diseases as well," says first author Claudia M. Denkinger of Beth Israel Deaconess Medical Center, Boston, MA.
The study grew out of an understanding that the market for TB tests includes many diagnostics which have not been recommended by independent organizations such as the World Health Organization (WHO) and the US Food and Drug Administration (FDA).
"These diagnostics have significant market share in much of the world where the market is not regulated, notably in developing nations, despite questionable performance," says Denkinger. "Given that oftentimes end-users have only the package insert to assess a test, we wondered how well package inserts actually reflected a tests performance."
In the study, Denkinger et al. compared package inserts' evaluations to systematic reviews of 19 diagnostic tests. The package inserts tended to overrate tests' accuracies by 20-30 percent as compared with systematic reviews of their performance, although within the package inserts, tests that were recommended by independent organizations were likely to report more realistic performance. "Our study suggests that independent assessments of diagnostic tests are helpful to provide reliable data to decision-makers and clinicians on the performance of diagnostic tests," says Denkinger.
"We propose that countries create systems for in-country validation of TB tests or that international organizations such as the WHO expand their evaluation programs in order to help countries procure quality-assured TB tests."
Such studies "must go beyond accuracy and assess clinical impact of tests on decision-making and patient outcomes and collect operational and cost-effectiveness data in programmatic settings," conclude the investigators, who were led by Madhukar Pai of McGill University, Montreal, Canada.
(C.M. Denkinger, J. Grenier, J. Minion, and M. Pai, 2012. Promise versus reality: optimism bias in package inserts for tuberculosis diagnostics. J. Clin. Microbiol. 50:2455-2461.)
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UVC Light Kills Wound Bacteria
Ultraviolet (UVC) light can eradicate wound-infecting bacteria on mice increasing both survival and healing rates, according to a paper in the July 2012 issue of Antimicrobial Agents and Chemotherapy. The light did not damage the animals' skin or delay wound healing, says principal investigator Michael R. Hamblin, of the Massachusetts General Hospital, and the Harvard Medical School, Boston, MA.
Skin infections range from the superficial, to the life threatening, which are rare except among immunocompromised patients. However, "…these infections are becoming worrisome due to bacterial resistance to conventional antibiotics," the researchers write.
Unlike with antibiotics, bacteria probably cannot develop complete resistance to UVC light, "although it is possible that variants with enhanced DNA repair systems may emerge," the investigators note, adding that only four times more radiation would be needed to decimate Deinococcus radiodurans, a species that is famous for its radiation resistance, than in the case of E. coli.
In the study, the investigators infected the mice with bioluminescent strains of gram-negative Pseudomonas aeruginosa, and Staphylococcus aureus, the former "noted for its invasive properties in mouse wound models," according to the report. The dimming of the bioluminescence—down to near zero—indicated the fate of the infective bacteria. The mice were exposed to UVC light 30 minutes after inoculation.
For both bacteria UVC treatment reduced bacterial contamination of wounds by 10-fold compared to untreated mice. In addition, treatment increased the survival rate of mice infected with P. aeruginosa and the wound healing rate in mice infected with S. aureus.
"These results suggested that UVC light may be used for the prophylaxis of cutaneous wound infections," write the researchers.
(T. Dai, B. Garcia, C.K. Murray, M.S. Vrahas, and M.R. Hamblin, 2012. UVC light prophylaxis for cutaneous wound infections in mice. Antim. Agents Chemother. 56:3841-3848.)
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Copper Surfaces Could Reduce Hospital Acquired Infections
Research from the Medical University of South Carolina suggests that adding copper to hospital surfaces which are commonly touched by medical personnel and patients could help reduce the risk of hospital-acquired infections. The findings appear in the July 2012 issue of the Journal of Clinical Microbiology.
Hospital-acquired infections kill around 100,000 people annually in the United States—equivalent to a wide-body jet crash every day of the year. About five percent of patients admitted to US hospitals—nearly 5,500 daily, or two million annually—get sick from the hospital, adding $45 billion ($45,000,000,000) to the annual cost of healthcare.
In this study, the microbial burden on commonly touched surfaces in the medical intensive care units of three hospitals was determined, first to assess the risk from those surfaces, and second, to determine whether or not copper surfacing would lower that burden, and those risks. The study was divided into two phases, pre- and post-copper, and lasted for 43 months.
During the pre-copper phase, "We learned that the average microbial burden found on six commonly touched objects was 28 times higher than levels considered benign, and thus represented a risk to the patient," says Michael Schmidt, a researcher on the study. Installing copper surfaces, he says, resulted in an 83 percent reduction of that microbial burden, leading the team to conclude that copper surfaces on commonly touched objects could provide a substantially safer environment.
"Given that the average hospital acquired infection in the United States conservatively adds an additional 19 days of hospitalization and $43,000 in costs the use of antimicrobial copper surfaces warrants further study and optimization," says Schmidt, adding that this is the fourth leading cause of death, after cancer, heart disease, and strokes. He notes that "Copper has been used by humans for millennia, first as tools and then as a tool to fight the spread of infectious agents."
(M.G. Schmidt, H.H. Attaway, P.A. Sharpe, J. John, Jr., K.A. Sepkowitz, A. Morgan, S.E. Fairey, S. Singh, L.L. Steed, J.R. Cantey, K.D. Freeman, H.T. Michels, and C.D. Salgado, 2012. Sustained reduction of microbial burden on common hospital surfaces through induction of copper. J. Clin. Microbiol. 50:2217-2223.)
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Penile Foreskin Is Immunologically Complete: Raises New Vaccine Possibilities For HIV Vaccine
Rhesus macaque monkeys infected with simian immunodeficiency virus (SIV) harbor immunoglobulin G (IgG) and SIV-specific antibodies and T cells in the foreskin of the penis, according to a study in the July 2012 Journal of Virology. This is the first time antibody secreting cells, antiviral antibodies or antiviral T cells have been reported in the foreskin of any primate.
Although "it has been known for some time that there was a population of immune cells in the surfaces of the human penis, and in all skin, for that matter, the potential functions of these cells, especially with regard to anti-HIV activity, had never been determined," says principal investigator Christopher J. Miller of the University of California, Davis. The new finding, he says, could lead to vaccine strategies designed to elicit HIV-specific immunity in the foreskin.
Cells which are targets of HIV are present in multiple epithelial tissues of the penis, and the foreskin—the skin of the penis that is lost during circumcision—is thought to be an especially important route of HIV transmission. "…the presence of an intact foreskin is associated with an approximately 50 percent increased risk of HIV acquisition," the researchers write, citing seven studies. Although HIV-specific antibodies and T cells are present in semen of HIV-infected humans, very little research has investigated mucosal immune responses of the surface of the penis, says Miller.
Male rhesus macaques are good models for the human reproductive system immunity. "…based on histology, there is no difference in the numbers or locations of CD4+ cells in the inner and outer foreskin of adult [rhesus macaques] or men," according to the report. "In addition to CD4+ T cells, the foreskin and glans of the human penis have a complete population of immune cells, but antigen-specific immune responses in these tissues have not been described [until now]," says Miller.
Miller's lab was also the first to report antiviral T cells in the female genital tract, research which led to efforts to develop vaccines that could elicit anti-HIV immunity in the female reproductive tract.
(K. Rothaeusler, Z.-M. Ma, H. Qureshi, T.D. Carroll, T. Rourke, M.B. McChesney, and C.J. Miller, 2012. Antiviral antibodies and T cells are present in the foreskin of simian immunodeficiency virus-infected rhesus macaques. Journal of Virology 86:7098-7106.)
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