Research Roundup: What we’re reading this week

In this guest post, Dr. Martin Schriefer, chief of the Diagnostic and Reference Activity in the Bacterial Diseases Branch of the Division of Vector-Borne Diseases (DVBD) in Fort Collins, Colo., writes about his laboratory’s development of a new diagnostic tool, the plague dipstick. DVBD is one of seven divisions in the Centers for Disease Control and Prevention’s (CDC) National Center for Emerging and Zoonotic Infectious Diseases (NCEZID). His blog is the second in a four-part series from experts at NCEZID. Uganda is considered a “hot zone” for emerging infectious diseases that have the potential for far- ranging impact. These diseases include Ebola and Marburg hemorrhagic fevers, yellow fever, chikungunya, West Nile virus disease, and plague. The NCEZID has a number of field programs in Uganda to study this unique ecological environment. I have traveled there several times, learning about the health infrastructure and a critical gap in plague diagnostics that was putting people's lives at risk. Plague is an acute and potentially fatal febrile illness that is harbored in rodents and transmitted by fleas. In its pneumonic form, plague can be transmitted by aerosol from person to person, resulting in local outbreaks and the risk for global spread. Now rare in the United States, plague remains a real threat to human health in sub-Saharan Africa and Madagascar. These regions account for more than 95 percent of the world’s reported plague cases. Fatality rates for untreated infections range from 50 percent to 60 percent for bubonic plague to nearly 100 percent for pneumonic infections. A convalescing plague patient in Uganda. Photo Credit: NCEZID In my laboratory, a team of CDC researchers has developed, manufactured, and field-tested a rapid, affordable diagnostic tool—the plague dipstick. The point-of-care plague dipstick, which works like a pregnancy test, brings the laboratory to the bedside. In September 2012, we delivered a supply of dipsticks to Uganda in anticipation of the 2012-2013 plague season. At the plague field station and several local health clinics, the plague dipsticks are providing significant improvements in terms of time, ease of use, storage, and handling. Healthcare workers have been trained in the collection of blood, lymph node aspirate, or sputum from suspected plague patients and the application of these samples to the dipstick. Results are visualized in 15 minutes. During a recent outbreak involving four patients and three deaths, the dipstick successfully diagnosed a pneumonic plague patient, allowing rapid prevention measures to 130 contacts—as a result, no further cases occurred. Before the dipstick was introduced, early clinical diagnosis of plague was difficult and could delay life-saving treatment. Sending samples away for laboratory verification took weeks. Overcoming barriers to effective diagnosis and timely treatment is a priority for CDC laboratory technicians. Plague dipsticks do not require electricity or refrigeration—a critical issue in an environment where electricity is sporadic. And each test costs less than $1.00 to produce. However, better diagnostics are not useful in Uganda unless people can access and use them with confidence. Many Ugandans living in more rural, remote areas are unable to trek long distances to find a health clinic and visit “traditional healers” instead. CDC has been working with field staff to train local healers to recognize plague symptoms and its effects on rats and to refer cases of plague to local clinics as necessary. Healthcare workers can be quickly trained to apply blood or lymph node aspirate to the dipstick, which yields results in 15 minutes. The dipsticks do not require electricity or refrigeration— important in an environment where electricity is sporadic. Photo Credit: NCEZID By educating healers in plague recognition, CDC is helping them to better protect their villages from this deadly disease. NCEZID’s highly innovative programs in Uganda are saving lives with early detection and response. They serve as an important source to strengthen the country’s public health capacity and better prepare for potential bioterrorism events in the United States. The plague dipstick is now being submitted to the US Food and Drug Administration for 510(k) clearance, which is the next step in showing the dipstick to be a clinically validated, sensitive, and specific test.

In this guest post, Dr. Beth P. Bell, director of the National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) at the Centers for Disease Control and Prevention (CDC), describes some of her center’s active engagement in global health work. She also highlights an important technology initiative called Advanced Molecular Detection that is proposed in the President’s fiscal year (FY) 2014 budget. This is the first in a four-part series about NCEZID’s global activities focused on the prevention of illnesses and death from infectious diseases. I am pleased to write this inaugural blog from NCEZID for the Global Health Technologies Coalition. We work closely with other CDC centers, federal agencies, and domestic and international partners to protect people from infectious diseases and enhance global health security.We’re excited to have the opportunity to showcase our portfolio of global activities that evidence NCEZID’s research, technology, and program priorities. One example is our work in Uganda, where we helped build laboratories and train staff at the Uganda Virus Research Institute (UVRI). The main UVRI facility is based in Entebbe in central Uganda, and it has a satellite laboratory about 320 miles northwest in the town of Arua, near the border with the Democratic Republic of the Congo (DRC). NCEZID staff based at UVRI in Entebbe collaborates with other UVRI scientists to deliver in-country expertise in diagnosing and preventing viral hemorrhagic fevers, plague, and other infectious diseases.For instance, UVRI staff last year used modern diagnostic technologies while working closely with Atlanta-based CDC response teams, local public health authorities, and other experts to contain four near-simultaneous outbreaks of filovirus disease (caused by Ebola and Marburg viruses) in Uganda and the DRC. Separately, I learned first-hand about the benefit of building local diagnostic capacity in Uganda when I traveled there last fall and spoke with scientists and residents about the successful use of a new plague dipstick test (more on this in our next guest blog).In October 2012, Dr. Bell (far right) visited Uganda and met a farmer (third from left) who had developed symptoms of plague. He was promptly tested with the plague dipstick test and learned within 15 minutes that he had tested positive for plague. He was treated with antibiotics,fully recovered, and was back working in 3 days. Also pictured is Ugandan clinical coordinator Dr. Titus Apangu (center, wearing a tie).  Photo credit: NCEZIDOther examples of NCEZID’s commitment to using innovative technology in response to infectious diseases on the global front include our efforts to develop vaccines for dengue and Rift Valley fever, and to establish safe water projects in places like Malawi and Haiti. And in just the past few months, we’ve helped with a Japanese encephalitis immunization campaign in western Cambodia (with support from the Bill & Melinda Gates Foundation) and assisted India in the development of a pilot outbreak investigation and surveillance for enteric diseases in several states.But as we anticipate new and evolving global challenges in infectious disease, we also recognize the need to strengthen our capacity in using next-generation public health tools. This step is crucial if we are to successfully confront what CDC Director Dr. Tom Frieden calls the “perfect storm of vulnerability: emerging microbes, resistant microbes that outsmart the drugs used to treat them, globalization of travel and trade, and the greater ease of making deadly organisms in a laboratory.”Of particular importance is the need to implement new approaches for strengthening our expertise and capacity in molecular-based sequencing and bioinformatics and applying these advances to public health—both domestically and internationally. Real-time genomic sequencing of pathogens rapidly generates massive amounts of information, and bioinformatics helps us interpret these data and apply the results to public health. To be sure, CDC and its public health partners have had some success with the global application of genetic sequencing and molecular epidemiology—the global polio eradication effort being one example. But much more remains to be done. Advances in these evolving areas will help us to more rapidly and accurately diagnose infectious diseases, investigate and control outbreaks, understand transmission patterns, determine antimicrobial resistance, and develop and target prevention measures, including vaccines.The President’s FY 2014 budget contains an initiative called the “Advanced Molecular Detection (AMD) and Response to Infectious Disease Outbreaks,” which would provide CDC an unprecedented opportunity to build our expertise across all infectious diseases. This initiative can help us move beyond older methods of detecting a microbe and determining its threat to human health. Strengthening our detection and response capabilities with these technologies will help us take bold new steps in protecting the public’s health, both here and abroad. You can read more about the AMD initiative on CDC’s website (see link below).In our next three guest blog posts for Breakthroughs, we intend to show you how technology enables us to extend our reach of work around the globe. For example, one of our scientists who developed the plague dipstick will give a first-hand account of creating this tool that diagnoses plague easily, rapidly, and inexpensively. Other blogs will detail recent efforts to combat rabies in Haiti and the ever-growing challenge of controlling the spread of dengue. I hope you enjoy reading them.For more information about the AMD initiative, click hereTo learn more about NCEZID, click here