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05/20 10:00 PM ET; 05/24 5:00 AM ET; 05/25 2:00 PM ET

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IMAGE: An Anopheles stephensi mosquito is obtaining a blood meal from a human host through its pointed proboscis. Note the droplet of blood being expelled from the abdomen after having engorged... view more 

Credit: Jim Gathany / CDC

Typhoid Mary may have infected a hundred or more people, but asymptomatic carriers of malaria infect far more people every year. An international team of researchers is working toward a way to identify malaria patients including infected individuals who show no malaria symptoms.

People who have malaria but are not symptomatic abound in the heaviest areas of malaria infestation. Even blood tests do not necessarily pick up infection with the plasmodium parasite, especially at low parasite densities. DNA tests for the parasite usually show infection, but they are far from rapid.

"Our previous work in a mouse model found that malaria infection altered the odors of infected mice in ways that made them more attractive to mosquitoes, particularly at a stage of infection where the transmissible stage of the parasite was present at high levels," said Consuelo De Moraes, adjunct professor of biology, Penn State, and professor of environmental systems science, ETH Zurich. "We also found long-term changes in the odor profiles of infected mice."

The researchers wanted to see if they could identify changes in human odors associated with malaria infection that might be useful for diagnosing infected individuals. They were particularly interested in identifying those who were infected, but had no symptoms. The researchers initially used microscopy and an SD Bioline Rapid Diagnostic Test to identify patients with malaria. Because these methods have limited sensitivity, particularly when parasite loads are low, infections were confirmed by DNA tests. They identified 333 people who unambiguously were either infected with malaria or were not infected with malaria.

Only if both microscopy and DNA studies were negative were subjects considered malaria-free. Infected patients for the initial studies were both microscopy and DNA positive for malaria. In some later analyses, the researchers included 77 people who were positive for malaria according to DNA, but showed no parasites in the microscopic tests.Malaria infection does not create new volatile chemicals in the body, but alters the amounts -- up or down -- of volatile chemicals that are already present in the odors of healthy people.

"It is interesting that the symptomatic and asymptomatic infections were different from each other as well as from healthy people," said Mark C. Mescher, adjunct professor of biology, Penn State, and professor of environmental systems science, ETH Zurich.

This difference among infected, infected asymptomatic, and healthy individuals may eventually lead to tests capable of rapidly and accurately identifying infected people, even those without symptoms.

The researchers report in today's (May 14) issue of Proceedings of the National Academy of Sciences that predictive models using machine learning reliably identify infection status based on volatile biomarkers. They state "our models identified asymptomatic infections with 100 percent sensitivity, even in the case of low-level infections not detectable by microscopy." These results far exceed any currently available rapid diagnostic tests.

"But, we should emphasize that we are a long way away from developing a practical diagnostic assay based on odor cues," said De Moraes.

For a test to succeed it would need to be rapidly and cheaply deployable under field conditions, but still detect infections with high sensitivity.

"In the near term, our goal is to refine the current findings to find the most reliable and effective biomarkers we can," said Mescher. "This is really basic science to identify the biomarkers of malaria. There is still a lot more work to be done to develop a practical diagnostic assay."

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Also working on this research from Penn State are Andrew Read, Evan Pugh Professor of Biology and Entomology and Eberly Professor of Biotechnology; and Heike Betz, research technologist in biology.

Caroline Wanjiku and Baldwyn Torto of the International Centre of Insect Physiology and Ecology; and Nina Stanczyk, Hannier Pulido and James Sims of ETH Zurich were also part of the project.

The Bill and Melinda Gates Foundation, David and Lucile Packard Foundation and ETH Zurich funded this research.

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The number of employees who tested positive for prescription opioid use declined 17 percent from 2016 to 2017, according to data from Quest Diagnostics. (AP Photo/Toby Talbot, File)

The number of U.S. workers who tested positive for cocaine and methamphetamine use skyrocketed last year, while fewer employees are using prescription opioids, according to data released by Quest Diagnostics.

According to an analysis of more than 10 million drug tests, 4.2 percent of workers who were screened for drug use in the United States last year tested positive. The rate remains unchanged since 2016, but it still remains significantly higher than in 2012, when 3.5 percent of employees tested positive for drugs.

Not only have declines appeared to have bottomed out, but also in some drug classes and areas of the country, drug positivity rates are increasing, said Barry Sample, senior director of science and technology at Quest Diagnostics.

Positive testing for methamphetamine has skyrocketed in the South and Midwest in the past five years. Between 2013 and 2017, positive drug tests for methamphetamine increased by 167 percent in the region that includes Illinois, Indiana, Michigan, Ohio and Wisconsin and 160 percent in Alabama, Kentucky, Mississippi and Tennessee. Rates were also high in the Northeast and South Atlantic regions.

There also has been a surge in positive tests for cocaine. In Nebraska, there was a 91 percent increase in positive cocaine tests from 2016 to 2017, and an 88 percent increase in Idaho.

Quest also reported spikes for positive marijuana tests in states that have made recreational use of the drug legal. There was a 43 percent increase in Nevada, 14 percent in Massachusetts and 11 percent in California. The states also saw increases in positive marijuana tests among safety-sensitive workers, which include pilots and truck drivers, who are regularly drug tested by the U.S. Department of Transportation.

These changing patterns and geographical variations may challenge the ability of employers to anticipate the drug of choice for their workforce or where to best focus their drug prevention efforts to ensure a safe and healthy work environment, Sample said.

The increases come as the number of workers testing positive for prescription opioids and heroin have declined, even though the opioid crisis continues to ravage the United States. The rate of drug tests that were positive for a prescription painkiller declined by 17 percent from 2016 to 2017. Tests for a metabolite that is in heroin dropped by 11 percent from 2016 to 2017, a three-year low.

According to the Centers for Disease Control and Prevention, the opioid prescribing rate fell to a 10-year low in 2016.

The depth of our large-scale analysis supports the possibility that efforts by policymakers, employers, and the medical community to decrease the availability of opioid prescriptions and curtail the opioid crisis is working to reduce their use, at least among the working public, said Kim Samano, scientific director at Quest Diagnostics.

Quest said it does not test for synthetic opioids such as fentanyl, a powerful drug that has been involved in the rise of the nations overdose death rate.

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