The Observatory

Feb. 22, 2018
The Toll of Tuberculosis Tuberculosis (TB) remains a global scourge. Every day, as many people die of TB as would die in 15 jetliner crashes.

33%
Is the proportion of the people in the world infected with the TB bacterium; only a small number become sick with the disease.

10.4 million
Is the estimated number of new cases of TB that occurred worldwide in 2016.

6.3 million
Is the number of 2016 new cases who were detected and notified.

7
Is the number of countries that account for nearly two-thirds of total TB cases: India, Indonesia, China, the Philippines, Nigeria, Pakistan, and South Africa.

61%
Is the proportion of total TB cases that occur in Asia.

26%
Is the proportion of total TB cases that occur in Africa.

1.7 million
Is the number of people who died of TB in 2016.

1 million
Is the number of children who became ill with TB in 2016.

210,000
Is the number of children who died of the disease in 2016.

400,000
Is the number of people with HIV who died of TB in 2016.

490,000
Is the number of people who developed multidrug-resistant TB in 2016.

37%
Is the decrease in TB deaths between 2000 and 2016; WHO efforts to diagnose and treat TB are having an effect.

53 million
Is the number of lives saved by TB treatment between 2000 and 2016.

83%
Is the treatment success rate achieved in 2016.

Sources: http://www.who.int/features/factfiles/tuberculosis/en/ and http://www.stoptb.org/resources/factsheets/fastfacts.asp

Infectious Diseases

New research suggests immune system can protect against MRSA. Researchers at Johns Hopkins, the University of California, Davis, and NIAID have discovered how the immune system might protect a person from recurrent bacterial skin infections caused by staph. The findings, published online in The Journal of Clinical Investigation, open new doors to developing vaccines to prevent staph skin infections, which account for 14 million outpatient visits, nearly 500,000 hospital admissions, and $3 to $4 billion in inpatient healthcare costs in the U.S. annually.

Multidrug-resistant strains, such as MRSA, are causing severe skin infections in healthy people outside of hospitals. And subsequent to infection, the recurrence rate is 50 percent within six months.

Using mice with defective immune systems, a research team found that after an initial exposure of the skin to staph, they were protected against a second skin exposure with the same bacteria. After testing for antibodies and other “usual suspects” of the immune system against this infection, it was not clear what immune response was protecting the mice. The researchers then tested a drug that is FDA-approved for treatment of multiple sclerosis, which acts by preventing certain immune cells from leaving lymph nodes for sites of inflammation.

Genetic sequencing data revealed that specific cells substantially multiplied after the initial infection, then moved to the infection site and provided protection against the second infection. These so-called gamma delta T cells account for less than one percent of all the cells in the lymph node prior to infection. After infection, they accounted for more than 20 percent.

To see whether the findings were applicable to people, researchers tested blood from healthy individuals and people with a rare immune disorder that makes them highly susceptible to staph skin infections. Patient blood samples presented an increase in percentage of gamma delta T cells, similar to what they observed in mice, which remained stable over years.

Researchers hope gamma delta T cells may be targeted for developing new therapies or even a vaccine against staph skin infections. This, they say, could alleviate the burden of staph skin infections, prevent invasive complications, and reduce healthcare costs.

Rapid Testing

A roadside test for marijuana intoxication? It isn’t as easy as it sounds. As the movement to legalize marijuana in the U.S. gains momentum, researchers worry about public safety, particularly on the roads. Recent studies in which marijuana users took controlled doses of cannabis in the lab have identified new biomarkers that can be used to estimate a person’s recent cannabinoid intake. But using those markers to judge cognitive and behavioral impairment is complex, say toxicologists in a commentary published in the journal Trends in Molecular Medicine on biomarkers of substance abuse.

“There is no one blood or oral fluid concentration that can differentiate impaired and not impaired,” says Marilyn Huestis, who spent over 20 years leading cannabinoid-related research projects at the National Institute on Drug Abuse.

Alcohol can impair a user more than cannabis, and the risk of an accident while driving increases in proportion with blood alcohol concentrations. But marijuana is different: many variables can affect how impaired someone is at any given concentration of THC, the primary psychoactive agent in cannabinoids. Whether it is inhaled or consumed, and whether the user titrates the dose, can affect the level of impairment.

Another problem is that THC quickly leaves the bloodstream. Previous research by Huestis has shown that blood THC concentrations can be effectively zero after 2.5 hours. And on average in the U.S., it takes 1.4 to four hours after a crash or traffic stop to administer a blood test.

Long-term users, such as those who use marijuana for medical reasons, also present a challenge for developing roadside protocols. THC accumulates in body tissues and then slowly releases over time, so chronic users can test positive for cannabis even after 30 days of abstinence. Psychomotor impairment can be observed three weeks after the last dose.

Huestis advocates for well-trained police officers who can identify the behavioral signs of impairment and less invasive biological marker tests, which could be immediately performed at the roadside to confirm the presence of a cannabinoid. To that end, recent research has identified new blood and urine markers, and tests using breath and saliva markers are being developed. These new markers and tests could also be used to assist in treating drug dependence, in determining appropriate therapeutic levels of medical marijuana, and in monitoring women who want to stop using cannabinoids during pregnancy.

Phlebotomy

Study demonstrates reduction in blood culture contamination rates. A Medical University of South Carolina (MUSC) research study found that use of a mechanical initial specimen diversion device (ISDD) and staff education led to a four-fold decrease in contaminated blood cultures that was sustained over 20 months.

Results of the Emergency Department (ED) research were presented at the Institute for Healthcare Improvement (IHI) National Forum by lead study author Lisa Steed, PhD, MUSC Department of Pathology and Laboratory Medicine professor.

Blood cultures help physicians determine whether patients have serious and potentially life-threatening blood infections such as sepsis. These blood draws may become contaminated with bacteria-containing fragments of a patient’s skin that enter the needle during the blood collection process. Studies have shown that conventional techniques can lead to false positives, which in turn may lead to patients receiving more blood draws, extended length of stay, increased exposure to HAIs, and unnecessary antibiotic treatment.

The mechanical ISDD used in the study, called Steripath (Magnolia Medical Technologies), is a sterile, closed blood culture collection system that diverts, sequesters, and isolates the first 1.5 to 2 milliliters of blood—the portion that is known to contain contaminants—during the blood draw.

The study also showed that use of the mechanical ISDD could reduce costs and use staff time more efficiently. Researchers suggested that MUSC would have saved $744,955 if the ISDD had been used for every blood draw in the ED during the study, based on an estimate of $4,850 for the cost of a contaminated culture.

Molecular Diagnostics

Medical organizations update guideline for molecular testing and targeted therapies in lung cancer. Rapid advancements in the molecular diagnostic testing of lung cancer have led to new treatments for patients battling the disease, the most common cause of cancer death worldwide. To ensure that clinicians stay apace and provide optimal patient care, three leading medical societies—the College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and International Association for the Study of Lung Cancer (IASLC)—have updated their 2013 evidence-based guideline.

Published online, the “Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment with Targeted Tyrosine Kinase Inhibitors” continues to set standards for the molecular analysis of lung cancers for test results that effectively guide targeted therapy and treatment.

Targeted cancer therapies are drugs or other treatments that block the spread of cancer by interfering with specific molecules that spur that specific cancer’s growth and progression. Patients whose tumors harbor certain, specific molecular alterations may be candidates for targeted tyrosine kinase inhibitor (TKI) therapy, which may improve survival and quality of life.

The updated guideline strengthens the majority of the 2013 recommendations for patients with lung adenocarcinoma, and also recommends testing for some new genes.

The complete guideline is available online at the Archives of Pathology & Laboratory Medicine, Journal of Thoracic Oncology, and Journal of Molecular Diagnostics. Additionally, the three societies developed resources to help pathologists and oncologists review and implement the guideline, including a summary of recommendations, a teaching presentation, and frequently asked questions.

Industry News

FDA extends comment period to March 30, 2018, for two draft guidances. The U.S. Food and Drug Administration (FDA) is extending the comment period to March 30, 2018, for these two draft guidances:

  • Select Updates for Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices – Draft Guidance for Industry and Food and Drug Administration Staff; and
  • Recommendations for Dual 510(k) and CLIA Waiver by Application Studies – Draft Guidance for Industry and Food and Drug Administration Staff.

Instructions for submitting comments are available in the Federal Register under docket numbers FDA-2017-D-5570 and FDA-2017-D-5625.

The FDA published these two draft guidance documents on November 29, 2017, to help manufacturers of IVD devices apply for and receive CLIA waivers.

“Select Updates…” is issued in accordance with section 3057 of the 21st Century Cures Act [P.L. 114-255]. When finalized, this will represent FDA’s thinking regarding the appropriate use of comparable performance between a user in a waived facility and a user in a moderately complex laboratory to demonstrate accuracy. When final, this content will revise “Section V. Demonstrating Insignificant Risk of an Erroneous Result — Accuracy” of the guidance Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices (2008).

“Recommendations for Dual 510(k)…,” when finalized, will describe the agency’s expectations regarding study designs for generating data that supports both 510(k) clearance and CLIA Waiver by Application. The FDA believes that increased use of this pathway will speed up the process of bringing simple and accurate IVD devices to CLIA waived settings, which will better serve patients and providers.