A Look into Advanced Molecular Tools Used by the CDC to Advance Public Health

Cutting-edge technologies help public health professionals detect and respond to infectious disease outbreaks more rapidly and effectively than traditional methods. The Centers for Disease Control and Prevention’s Epidemic Intelligence Service (EIS) officers presented a few of their resources to their colleagues in a special session on May 3, Using Advanced Molecular Tools to Direct Public Health Action, at the 65th Annual EIS Conference in Atlanta, Georgia.

“Being in genomics in 2016 is like being in PCs in the 1980s. We’re using DOS as our operating system, we’re using WordStar as our word processor, and ten years from now, this is all going to look very different. There is a lot of opportunity here, especially for incoming epidemiologists who have a talent for data, are interested in working with big data and who have a passion for public health science,” Greg Armstrong, MD, director of the Office of Advanced Molecular Detection (AMD) at the Centers for Disease Control and Prevention, said in his introduction.

“In 2007, a new generation of nanotechnologies became available that could sequence DNA on a scale previously unimaginable,” Dr. Armstrong said, adding that under the AMD initiative, Congress is allocating funds to modernize CDC’s program. “Its objective is to bring next-generation sequencing bioinformatics and related technologies to bear against public health threats, starting here at CDC and soon thereafter in the broader public health system. Based on industry projections, we’re going to continue to see an increase in throughput in automation and a decrease in costs, all of which will increase the applicability of these technologies.”

Alexa Oster, MD, described how she and her colleagues use molecular sequence data to identify and respond to HIV transmission clusters.

“This is an exciting time for using molecular surveillance data for HIV prevention. Identifying and interrupting transmission is clearly what we’re aiming to do in public health. Effective prevention tools, such as medical care, antiretroviral therapy, and pre-exposure prophylaxis are available, but it’s critical to know where to focus efforts for maximum impact. Identifying growing clusters of active transmission can help target interventions to interrupt transmission,” she said in her talk.

Dr. Oster explained that drug resistance testing is recommended for all HIV-infected persons in the United States as the standard of care. A person with HIV who visits their HIV care provider and is tested for HIV drug resistance is automatically entered into the national HIV surveillance system. Their specimen is sent to a lab and the genetic sequence generated is electronically reported to the local or state health department, which forwards the de-identified data, including demographics, to the CDC.

Because HIV mutates over time, people with genetically similar HIV strains may be more closely related in transmission, so researchers can compare sequences and use their degree of similarity to examine epidemiologic relationships. They can infer potential transmission partners, clusters of related sequences and the extent of outbreaks so they can monitor them and tailor prevention strategies to individual patients.

“The short-term investigation of a tuberculosis outbreak can overwhelm state and local TB control program capacity; however, opportunities to interrupt ongoing transmission in vulnerable populations are important,” Benjamin Silk, PhD, said about his group’s work with molecular surveillance for recent TB transmission.

Since the LOTUS national surveillance program to detect large TB outbreaks in the US began as a pilot program in 2014, Dr. Silk and his colleagues have been stopping transmissions before they become outbreaks by using molecular surveillance and statistical methods that analyze the geospatial concentration of genotype-matched clusters.

While routine genotyping methods for outbreak control examine about 1% of the TB genome, Dr. Silk and his team are increasingly using whole genome sequencing (WGS), which analyzes around 90% of the genome and reveals how isolates are genetically related.

“Food production and distribution has really changed substantially over the last couple of decades in the United States. There are fewer food producers and they have wider distribution. So on average, the means our food is coming from farther away. There are also more ready-to-eat and industrially produced foods and we’re seeing more highly disseminated outbreaks where there are illnesses all over the country that may not be readily detectable at the local level and require national, state and federal coordination,” said Matthew Wise, PhD, MPH, in his talk about the impact of WGS on multistate enteric disease outbreak investigations.

The PulseNet national laboratory network that detects foodborne illness outbreaks uses pulsed-field gel electrophoresis (PFGE) DNA fingerprinting to identify bacteria that make people ill. But PFGE results, based on genetic information available at the cut sites of genome fragments, are not always correct, so PulseNet has begun testing organisms by WGS, which contains information from many more positions in the genome.

In one of several outbreaks Dr. Wise described, Listeria isolated from a sprout facility was closely related to five clinical isolates from listeriosis cases, and based on WGS with only limited epidemiologic data, the sprouts were removed from the market and the firm shut down.

“We’re detecting more clusters of listeriosis, we’re detecting them sooner; the number of outbreaks that have a food source identified has been going up; the median number of cases in this outbreak has actually been going down; and the number of cases that we are actually able to link to a specific food item is going up,” Dr. Wise said.

Scott D. Holmberg, MD, MPH, described the AMD his research team uses to fight viral hepatitis, GHOST (Global Health, Outbreak, and Surveillance Technology)

“We have the largest infectious disease outbreak in the United States. Our hepatitis C cases number over 3 million people, and the mortality rate that now supersedes all other reportable infectious diseases to CDC combined. Even with our imprecise surveillance, we have observed a 2.6-fold increase in acute cases between 2010 and 2014. We see the greatest increase in rural areas of Appalachia and the Midwest and in rural New England as well, mainly among young white persons who inject drugs after they transition from oral prescriptions to opioid abuse,” Dr. Holmberg said.

After infection, multiple quasi species of HCV develop in the host and increase in number and complexity over time. AMD generates data from the many sequences and fragments created that describes the transmission links among people.

Traditional epidemiologic contact tracing in HIV cases gives researchers good information about relationships between people, but analyzing the specimens with GHOST gives a much richer picture of the interactions between them, Dr. Holmberg said. This is important because we have curative therapies for hepatitis C now and can try to prevent future cases and help people receive care for HCV HIV, drug addiction and other conditions. AMD sequencing can also provide information about virulence and resistance, which is developing to some newer drugs.

Lorraine L. Janeczko, MPH, is a medical science writer who creates news, continuing medical education and feature content in a wide range of specialties for clinicians, researchers and other readers. She has completed a Master of Public Health degree through the Department of Epidemiology of the Johns Hopkins Bloomberg School of Public Health and a Dana Postdoctoral Fellowship in Preventive Public Health Ophthalmology from the Wilmer Eye Institute, the Johns Hopkins University School of Medicine and the Bloomberg School.

SOURCE: EIS 2016 Conference Program, p 52: Using Advanced Molecular Tools to Direct Public Health Action

Studies Presented:

Greg Armstrong, EIS officer, The National Center for Emerging and Zoonotic Infectious Diseases, Advanced Molecular Detection at CDC and the Impact on Public Health

Alexa Oster, MD, EIS officer, Division of HIV/AIDS Prevention, Using Molecular Sequence Data to Identify and Respond to HIV Transmission Clusters

Benjamin Silk, PhD, EIS officer, Division of Tuberculosis Monitoring, Molecular Surveillance for Recent TB Transmission

Matthew Wise, PhD, MPH, EIS officer, Division of Foodborne, Waterborne, and Environmental Diseases, The Practical Impact of Whole-Genome Sequencing on Multistate Enteric Disease Outbreak

Scott D. Holmberg, MD, MPH, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Global Health, Outbreak, and Surveillance Technology (GHOST): Advanced Molecular Detection in Viral Hepatitis