MALDI-TOF MS 'Revolutionizing' Diagnosis of Mold Infections

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) can better identify mold species, compared to traditional microscopic-based techniques, according to a study published in the December issue of Clinical Microbiology and Infection. The combination of continued adoption of MS platforms and the extension of MALDI-TOF MS technology into diagnosis of mold infections will further challenge traditional techniques, as has been seen with microbiological identification of bacterial infections. As with most infections in hospitalized patients, prognosis with mold infections is largely dependent on rapid and accurate diagnosis and the resulting initiation of appropriate therapy. Current diagnosis of mold infections involves error-prone, species identification based on microscopic examination by highly skilled mycologists, followed by DNA sequencing, when necessary. In the present study, the French researchers developed an extensive, in-house reference library (2,832 reference spectra with 708 strains from 347 species), which they incorporated into a routine laboratory analyses for mold identification. The accuracy of MALDI-TOF MS (Bruker) was compared with both traditional morphology-based identification and DNA sequencing both during a 4-month period in 2013 and using preserved samples from the same 4-month period in 2011. The researchers found that implementation of MALDI-TOF MS resulted in a "dramatic" improvement in identification of mold species over the 4-month assessment period. Mold isolates were cultured in 262 of the 6,531 samples received from January through April 2014. Species-level identification using morphological features was achieved for 205 isolates (78.2 percent), compared to identification in 257 isolates (98.1 percent) using MALDI-TOF MS (243 after one run and an additional 14 after two runs). The five isolates not identified with MALDI-TOF MS or morphology could only be identified with DNA sequencing. The misidentification rate fell from 9.8 percent using morphology to 1.2 percent using MALDI-TOF MS. When comparing pre- and post- MALDI-TOF MS initiation, species-level identification improved from 64.6 percent in 2011 (a rate the authors call "far from satisfactory") to 100 percent in 2013. Reassessment of 247 of the 2011-period isolates using MALDI-TOF MS yielded an increase in species diversity from 16 to 42 species. In addition to the improved accuracy of species identification, the authors say that employment of MALDI-TOF MS for mold infections is "rapid and rather simple to perform," taking approximately 95 minutes for analysis for a series of 24 isolates. An added benefit, the authors say, is the ability to identify young colonies, even before the appearance of characteristics necessary for morphological identification. "The current study demonstrates that use of an appropriate reference spectral library plays a major role in enhancing mold identification," writes co-author Renaud Piarroux, Ph.D., from Aix-Marseille University. "The increased proportion of successful MALDI-TOF MS-based identifications has enabled us to devote more resources to identifying the remaining unidentified specimens by increasing the number of analyzed DNA targets for DNA sequence-based identification. ... The clinical significance of these emerging fungal species, which have rarely been reported in Europe, must be examined further." Takeaway: The increasing employment of MALDI-TOF MS technology in routine laboratory practice could transform diagnosis of mold infections, potentially rapidly replacing the need for traditional microscope-based techniques. Personalized Cancer Screening Could Combat Overscreening With President Barak Obama's call for expanded investment in precision medicine, the promise of personalized medicine has once again made national headlines, yet, much of the attention has been focused on personalized treatment of disease. In an era of cost containment, experts say that employing personalized screening strategies can increase the benefits yielded from screening while improving stewardship of health care resources. "Maximizing benefits while minimizing the harms of screening requires moving from a '1-size-fits-all' guideline paradigm to more personalized strategies," says Tracy Onega, Ph.D., from Dartmouth University (Lebanon, N.H.) in a paper on personalized breast cancer screening strategies, published in Cancer in October 2014. "There is indeed a tension between personalized medicine and population-wide guidelines. ... A refined conceptual model for breast cancer screening is needed to align women's risks and preferences with screening regimens." With improvements in the sensitivity of screening technology, it is acknowledged that the more we search for cancer, the more we will find. Yet, emerging evidence shows that for many manifestations of the disease, these additional cancer cases are often cases of overdiagnosis and would not negatively impact the patient had they been left undetected. Yet detection provokes costly workups and unnecessary invasive biopsies and treatment. One often cited example is the "epidemic" of thyroid cancer diagnosis. Thanks to a free/low-cost screening program in South Korea the incidence of the disease has risen 15-fold over the past 20 years, but death rates have remained consistently low. Effective screening programs, experts say, should lead to a decrease in cancer deaths through initiation of treatment. But, in South Korea as in the United States, treatment for these additional thyroid cancer cases has not altered the death rate. While molecular diagnostics are improving in their ability to assess the pathogenic risk posed by certain mutations for some cancers, like prostate cancer, it remains imperfect at differentiating aggressive from slow-growing cancers. Experts say that personalizing recommendations for cancer screening can be implemented that incorporate individual cancer risk as well as expected benefit to be derived from screening based on the patient's age, health status, and anticipated life expectancy. There is substantial emerging evidence that overscreening with PSA tests, colonoscopies and mammograms in elderly patients or those with terminal illnesses remains a costly problem. Researchers from the University of North Carolina at Chapel Hill found that between 31 percent and 55 percent of study participants in patients aged 65 years or older with less than nine years to live were still receiving screenings for four common cancers (prostate, breast, cervical and colon cancer), according to a study published Aug. 18, 2014 in JAMA Internal Medicine. Current screening guidelines are often age-based and fail to address the issue of current health status. "Even though validated simulation models are available for a variety of screen- detectable cancers, the capability of these models to provide personalized recommendations for screening has not been fully exploited," writes coauthor Sameer D. Saini, M.D., from University of Michigan, Ann Arbor in a Dec. 3, 2014 Viewpoint published in the Journal of the American Medical Association (JAMA). “Although no physician has the intention to overtreat or overdiagnose cancer, screening and patient awareness have increased the chance of identifying a spectrum of cancers, some of which are not life threatening,” writes Laura Esserman, M.D., from University of California, San Francisco, in a July 2013 JAMA Viewpoint. “The goal going forward is to personalize screening strategies, and focus screening policies on the conditions that are most likely to result in aggressive illness and death.” Such a shift in strategy will ultimately require patient education, shifts in physicians' habits, and some system-wide changes to quality measures. Experts recommend improved communication to ease patients’ and physicians’ discomfort at curtailing routine screening in low-risk individuals or in those unlikely to achieve benefit, including candid communication of the risk-benefit of screening and life expectancy. To facilitate these discussions physicians need accessible, personalized estimates of benefit (ideally integrated in electronic health record systems). System-wide, clinically sensitive, personalized measures of quality will need to be developed that may recognize effective care is not employing screening. The flip side of personalized screening is that in certain high-risk populations, like those at risk for Lynch Syndrome, personalized strategies can triage those needing higher intensity screening. Key to implementing risk-based screening strategies rather than those guided strictly by age is the use of genomic data. Experts are hopeful that risk-stratified personalized screening has the potential to detect all relevant cancer, including in younger but higher-risk patients, while achieving greater cost-effectiveness by minimizing overdiagnosis, and overtreatment in low-risk patients. Takeaway: While the preponderance of attention for precision medicine has been on targeting treatments more effectively, applying personalized strategies to cancer screening can better target health care resources to those most likely to yield benefits from such testing. Personalized screening strategies based on risk can identify patients most likely to benefit from recommended or even aggressive screening, as well as those likely to only face harm from screening.